Needle arrangement, drug delivery device comprising the needle arrangement and method for operating the drug delivery device

Abstract

Needle arrangement for a drug delivery device, the needle arrangement comprising a needle shield and a needle, wherein the needle shield is configured to interact with the needle in at least two different orientations relative to the needle, wherein the two different orientations comprise a first orientation in which the needle shield is configured to interact with the needle before use of the drug delivery device, and a second orientation in which the needle shield is configured to interact with the needle after use of the drug delivery device.

Description

[0001] Title

[0002] Needle Arrangement, drug delivery device comprising the needle arrangement and method for operating the drug delivery device.

[0003] Technical field

[0004] The disclosure generally relates to a needle arrangement for a drug delivery device, such as an injection device, in particular an autoinjector, e.g. a reusable autoinjector, and to the drug delivery device comprising the needle arrangement. The disclosure further relates to a method for operating the drug delivery device.

[0005] Background

[0006] Needle arrangements having a distal needle tip for piercing an injection site and a needle shield configured to interact with the needle are known in the art.

[0007] There remains, however, a need for an improved needle arrangement.

[0008] Summary

[0009] An object of the present disclosure is to provide an improved needle arrangement for a drug delivery device.

[0010] The object is achieved by a needle arrangement according to claim 1. Exemplary embodiments are provided in the dependent claims.

[0011] According to one aspect of the present disclosure, the needle arrangement for a drug delivery device may comprise a needle shield. The needle arrangement may further comprise a needle. The needle shield may be configured to interact with the needle in at least two orientations relative to the needle. The at least two orientations may be different to each other. The at least two orientations may comprise a first orientation in which the needle shield is configured to interact with the needle before use of the drug delivery device. The at least two orientations may comprise a second orientation in which the needle shield is configured to interact with the needle after use of the drug delivery device.

[0012] The needle shield may be a soft needle shield (SNS), e.g. a rubber needle shield, or a rigid needle shield (RNS) which may be composed of an inner rubber material and a full or partial harder shell, e.g. a plastic shell.

[0013] The needle shield may extend along a longitudinal axis. The longitudinal axis may be the main extension axis of the needle shield. A radial direction of the needle shield may be a direction perpendicular to the longitudinal axis and intersecting with the longitudinal axis. An azimuthal direction of the needle shield, also referred to as angular direction, may be a direction perpendicular to the radial direction and to the longitudinal axis. The same definition of the directions may hold for the drug delivery device comprising the needle arrangement described later on.

[0014] The orientation of the needle shield in the present sense may be considered the orientation of the needle shield with respect to the needle. As such, phrases like "in its second orientation, the needle shield..." may be understood as "in its second orientation with respect to the needle, the needle shield...", if not explicitly stated otherwise.

[0015] In other words, the needle shield of the present application may have at least two orientations in which it may face the needle and in which it may be configured to interact with the needle. These at least two orientations may be the first orientation and the second orientation.

[0016] The first orientation of the needle shield may be different from the second orientation of the needle shield. The difference may lie in that, in the first orientation, more surfaces of the needle shield, less surfaces of the needle shield or a different surface of the needle shield may be facing the needle compared to the second orientation of the needle shield.

[0017] According to one embodiment the first orientation may differ from the second orientation in that the needle shield may be rotated relative to its azimuthal direction or relative to its radial direction with respect to the needle between the first and the second orientation.

[0018] The at least two different orientations of the needle shield may allow the needle shield to be used in at least two different situations, e.g. before and / or after use of the drug delivery device. According to at least one embodiment when interacting with the needle in its second orientation, the needle shield may be configured to cover and protect at least a needle tip of the needle. The needle shield may also be configured to cover and protect a portion of the needle adjacent to the needle tip. The needle shield in its second orientation may allow, for example, covering and protecting a contaminated needle after an injection occurred, e.g. after use of the drug delivery device. This can minimize potential injuries when handling the used and, optionally, contaminated needle.

[0019] According to at least one embodiment, the first orientation may be opposite to the second orientation.

[0020] According to one embodiment the first orientation may be opposite to the second orientation in that the needle shield is rotated by 180 degree (180°) relative to its azimuthal direction with respect to the needle. Alternatively, the first orientation may be opposite to the second orientation in that the needle shield is rotated by 180 degree relative to its radial direction with respect to the needle.

[0021] According to at least one embodiment the needle shield may comprise a first portion. The first portion may be configured to interact with the needle when the needle shield interacts with the needle in its first orientation. The first portion may be configured to interact with the needle when the needle shield interacts with the needle in its second orientation. The first portion may be configured to receive the needle. The first portion may interact with the needle when the first portion receives the needle.

[0022] According to a at least one embodiment the needle shield may comprise a second portion. The second portion may be configured to interact with the needle when the needle shield interacts with the needle in its second orientation. The second portion may interact with the needle when the second portion receives the needle.

[0023] When the needle shield comprises the first portion and the second portion, the first portion may be configured to interact with, e.g. receive, the needle when the needle shield interacts with the needle in its first orientation and the second portion may be configured to interact with, e.g. receive, the needle when the needle shield interacts with the needle in its second orientation.

[0024] The first portion may comprise a first end of the needle shield. The second portion may comprise a second end of the needle shield. The second end may be opposite to the first end along the longitudinal axis of the needle shield. According to at least one embodiment, the first end of the needle shield may be configured to interact with the needle when the needle shield, e.g. when the first portion of the needle shield, interacts with the needle in its first orientation. The first end may be configured to receive the needle in the first orientation of the needle shield.

[0025] According to at least one embodiment, the second end of the needle shield may be configured to interact with the needle when the needle shield, e.g. when the second portion of the needle shield, interacts with the needle in its second orientation. The second end may be configured to receive the needle in the second orientation of the needle shield.

[0026] According to at least one embodiment, the first portion of the needle shield may be configured to be detachable from the second portion. The first portion may be detachable from the second portion, when the needle shield interacts with the needle in its second orientation, e.g. when the second portion interacts with the needle. This may be after use of the drug delivery device.

[0027] Detachment of the first portion from the second portion may occur in many different ways. The first portion may be configured to detach from the second portion, when a rotation is applied to the first portion, e.g. a rotation around the longitudinal axis.

[0028] Additionally, or alternatively a force applied to the first portion in a longitudinal direction of the needle shield, away from the second portion, may suffice to detach the first portion of the needle shield from the second portion of the needle shield, e.g. when the second portion of the needle shield interacts with the needle.

[0029] According to at least one embodiment, the interaction force of the second portion of the needle shield with the needle, when the needle shield is interacting with the needle in its second orientation may be greater than a force required to detach the first portion of the needle shield from the second portion of the needle shield.

[0030] In other words, the needle shield may be configured such that, once the needle shield, e.g. the second portion of the needle shield, interacts with the needle in the second orientation, the first portion of the needle shield may be detached from the second portion of the needle shield without detaching, e.g. removing, the second portion of the needle shield from the needle.

[0031] According to one embodiment, the first and section portions may comprise or consist of different materials. The first portion, may comprise or consist of a first material. The first material may for example be a rubber material. The first material may be configured to keep the needle under sterile conditions. The second portion may comprise or consist of a second material. The second material may be a material being stronger and / or harder than the first material. The second material may for example comprise one of, ore of, or all of steel, Aluminium, Polycarbonate (PC), Cycloolefin-Copolymere (COC).

[0032] The second portion may be configured to border the first portion. The second portion may be configured to border the first portion when no additional carrier component is provided.

[0033] According to at least one embodiment, the needle shield may comprise at least one engagement feature. The at least one engagement feature may be configured to engage the needle when the needle shield interacts with the needle in the first and / or in the second orientation.

[0034] The at least one engagement feature may be configured to be an inner structure of the needle shield. When the needle shield interacts with, e.g. receives, the needle, the engagement feature may engage, e.g. receive, the needle.

[0035] The at least one engagement feature may be configured such that a rotation of the needle shield causes a disengagement of at least a portion of the needle from the drug delivery device. Disengaging at least a portion of the needle from the drug delivery device may comprise breaking at least a portion of the needle from the drug delivery device.

[0036] The at least one engagement feature may be configured to retain the disengaged portion of the needle.

[0037] According to at least one embodiment, the at least one engagement feature may be configured to induce a deformation to at least a portion of the needle. According to at least one embodiment the at least one engagement feature may provide a needle path for the needle.

[0038] The second portion of the needle shield may comprise one engagement feature. The engagement feature of the second portion of the needle shield may be configured as a needle path. The needle path may be configured to receive the needle when the second portion of the needle shield interacts, e.g. receives, the needle.

[0039] The needle path may be configured to induce a deformation to at least a portion of the needle being received in the needle path.

[0040] Inducing a deformation to at least a portion of the needle may comprise inducing at least one kink, e.g. two kinks, to the portion of the needle. The at least one kink may define a breaking point. The breaking point may be the location at which the needle breaks, when rotating the needle shield and when the needle is engaged to the engagement feature, e.g. the needle path, of the second portion of the needle shield.

[0041] According to at least one embodiment the needle shield may further comprise at least one retention feature. The retention feature may be operable to at least partially prevent removal of the needle shield from the needle when the needle shield interacts with the needle, e.g. in its second orientation.

[0042] The at least one retention feature may be configured to interact with the needle shield to prevent the removal of the needle shield from the needle. Additionally, or alternatively, the at least one retention feature may directly interact with the needle to prevent the removal of the needle shield from the needle. A direct interaction may occur when the at least one retention feature directly contacts the needle.

[0043] The at least one retention feature may be configured as part of the needle shield, e.g. the needle shield may be shaped such as to prevent removal of the needle shield from the needle, in its second orientation. Additionally, or alternatively, the at least one retention feature may be an individual element being comprised in the needle shield and acting on the needle, e.g. directly interacting with the needle, to prevent removal of the needle shield from the needle, e.g. in its second orientation.

[0044] The at least one retention feature may at least partially prevent the needle shield from being removed from the needle, e.g. when the needle shield interacts with the needle in its second orientation, e.g. after use of the drug delivery device. This may be particularly advantageous as it may prevent unintentional or intentional removal of the needle shield after use of the drug delivery device, for example the removal of the needle shield from a contaminated needle. Such a safety mechanism, e.g. the provision of at least one retention feature, may reduce the occurrence of infections and / or injuries caused by unintentional use of a used, e.g. contaminated needle

[0045] According to at least one embodiment, the engagement feature may comprise the retention features. According to at least one embodiment the engagement feature may serve as retention feature. The engagement feature may be the retention feature.

[0046] According to at least one embodiment, the needle arrangement may comprise at least one connection feature configured to releasably connect the needle shield with a cap of the drug delivery device. The needle shield may comprise the connection feature.

[0047] According to at least one embodiment the connection feature may be configured such that a rotation of the cap causes a rotation of the needle shield.

[0048] According to at least one embodiment the connection feature may be configured to releasably connect the needle shield to the cap in the first orientation of the needle shield. Additionally, or alternatively, the connection feature may be configured to releasably connect the needle shield to the cap in the second orientation of the needle shield.

[0049] The cap may be configured to receive the needle shield in its first orientation. Additionally, or alternatively, the cap may be configured to receive the needle shield in its second orientation. When receiving the needle shield, the cap and the needle shield may be releasably connected via the connection feature.

[0050] According to at least one embodiment the needle arrangement, e.g. the needle shield, may comprise at least one identifier configured to identify the first orientation and / or the second orientation. The at least one identifier may be configured to be identifiable by a user of the drug delivery device, e.g. by a patient using the drug delivery device.

[0051] The at least one identifier may additionally or alternatively be configured to be identified by an automatic imaging system, e.g. an optical system, and / or an add-on device and / or any automatic device capable of identifying an identifier. The identifier may comprise any one or more of a color scheme on the needle shield, e.g. a color ring coding, a QR code, an NFC Chip.

[0052] Additionally, or alternatively, the identifier may be configured as a magnet or plastic magnetized material arranged on a portion of the needle shield. Additionally, or alternatively the identifier may be configured as an inductive coil or wire for an inductive sensor request.

[0053] According to at least one embodiment, the needle shield may comprise one identifier arranged on one portion, e.g. the first portion or the second portion, of the needle shield. The identifier may be arranged on an outer surface of the needle shield.

[0054] According to a second aspect of the disclosure, a drug delivery device may comprise the needle arrangement according to the first aspect.

[0055] The drug delivery device may be a reusable drug delivery device. The drug delivery device may be an autoinjector, e.g. a reusable autoinjector. The drug delivery device may be electronically controlled.

[0056] The drug delivery device may be provided to receive a medicament container. The medicament container may contain a medicament. The drug delivery may comprise the medicament container. The medicament container may be fluidly connected or fluidly connectable to the needle. The medicament container may be a pre-filled syringe. The medicament container may be replaceable after use of the drug delivery device.

[0057] According to at least one embodiment the needle arrangement, e.g. the needle shield, may further comprise at least one resetting feature. The resetting feature may be configured to interact with the drug delivery device when the needle shield interacts with the needle in its second orientation. The resetting feature may be configured to assist in bringing the drug delivery device into a condition that allows it to be operated again after an operation occurred.

[0058] The resetting feature may for example be configured to reset a needle shroud of the drug delivery device. The resetting feature may bring the needle shroud of the drug delivery device into a ready-to-use state. The resetting feature may be configured such that, when the needle shield interacts with the needle in its second orientation, the resetting feature interacts with the drug delivery device, e.g. with the needle shroud, to reset the needle shroud, e.g. to bring the needle cover into a ready-to-use state.

[0059] The resetting feature may be configured to allow removal of a used medicament container, e.g. by interacting with, e.g. unlocking, a lock mechanism of the drug delivery device locking the medicament container to the drug delivery device. The needle shield may comprise a dedication feature, e.g. a coding feature. The type of dedication feature of the needle shield may be dependent on the type of medicament comprised in a medicament container to which the needle arrangement is attached. For each medicament a different dedication feature may be used.

[0060] A drug delivery device may be configured, e.g. through a dedication interface, to only allow insertion of medicament containers comprising the needle arrangement comprising the corresponding dedication feature.

[0061] As such it may be avoided that a medicament container comprising one medicament is inserted into a drug delivery device configured for a different medicament.

[0062] The dedication feature may be a mechanical feature, an optical feature and / or a magnetic or inductive feature. A needle shield may comprise more than one dedication features, which may be of a different type, e.g. a mechanical feature, an optical feature and / or a magnetic or inductive feature.

[0063] The dedication feature of the needle shield may be configured to interact with the dedication interface of the drug delivery device, e.g. in such a way that insertion of the medicament container comprising the needle arrangement into the drug delivery device is possible, e.g. only possible, when the needle shield interacts with the needle in its first orientation.

[0064] Additionally, or alternatively, the dedication feature of the needle shield may be configured to interact with the dedication interface of the drug delivery device in such a way that extraction of the medicament container comprising the needle arrangement from the drug delivery device is possible, e.g. is only possible, when the needle shield interacts with the needle in its second orientation.

[0065] The dedication feature may be configured as one or more or all of the following: a toothing pattern on the needle shield, e.g. on the outer surface of the needle shield, at least one rip arranged on the needle shield, e.g. on the outer surface of the needle shield, at least one groove arranged on the needle shield, e.g. on the outer surface of the needle shield, at least one pocket arranged on the needle shield, e.g. on the outer surface of the needle shield.

[0066] The dedication feature may comprise the resetting feature. The dedication feature may be the resetting feature. The dedication feature may comprise or may be the identifier. The dedication interface of a drug delivery device may for example be an automatic imaging identification system configured to identify the dedication feature, e.g. a QR code, of the needle shield.

[0067] According to a further aspect of the present disclosure a method for operating a drug delivery device according to the second aspect is provided.

[0068] The method may comprise the step of removing the needle shield from the needle of the drug delivery device, the needle shield interacting with the needle in its first orientation before removal.

[0069] The method may optionally comprise the step of dispensing a medicament dose from the drug delivery device.

[0070] The method may further comprise the step of arranging the needle shield in its second orientation onto the used needle of the drug delivery device in order to cover and protect at least a needle tip and / or a piercing portion of the needle. The step may comprise bringing the needle shield and the needle into interaction.

[0071] According to at least one embodiment the method may further comprise the step of rotating the needle shield around its radial axis to its second orientation to cause the disengagement of at least a part of the needle from the drug delivery device.

[0072] According to an aspect, the present disclosure relates to method for dispensing or delivering a medicament from a drug delivery device or a system by using the drug delivery device. The drug delivery device may be a drug delivery device as described in the foregoing.

[0073] According to a further aspect, a method of delivering a drug from a drug delivery device is provided, the method comprising using the drug delivery device according to the present disclosure, e.g. according to any one of the above-mentioned embodiments.

[0074] According to a further aspect, a drug for use in a method of treating a patient is provided, wherein the method comprises delivering the drug to the patient using the drug delivery device according to the present disclosure, e.g. according to any one of the above-mentioned embodiments.

[0075] We note that features described above and below in conjunction with different embodiments or aspects can be combined with one another, even if such a combination is not explicitly disclosed herein above or below. Further features, advantages and expediencies of the disclosure and, particularly, of the proposed concepts will become apparent from the following description of the exemplary embodiments in conjunction with the drawings.

[0076] Further scope of applicability of the present disclosure will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating exemplary embodiments of the disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure will become apparent to those skilled in the art from this detailed description.

[0077] Brief Description of the Drawings

[0078] The present disclosure will become more fully understood from the detailed description given below and the accompanying drawings, which are given by way of illustration only, and do not limit the present disclosure, and wherein:

[0079] Figures 1A to 1B are schematic views of an exemplary drug delivery devices according to the present disclosure.

[0080] Figures 2a and 2B are schematic views of an exemplary embodiment of a needle arrangement according to the present disclosure.

[0081] Figures 3A and 3B are schematic views of a further exemplary embodiment of a needle arrangement according to the present disclosure.

[0082] Figures 3C and 3D are schematic views of certain states of the needle arrangement of Figures 3A and 3B.

[0083] Figures 4A to 4B are schematic views of another exemplary embodiment of a needle arrangement according to the present disclosure.

[0084] Figures 4C and 4D are schematic views of certain states of the needle arrangement of Figures 4A and 4B.

[0085] Figure 5 shows exemplary states of a drug delivery device, when operated according to a method according to the present disclosure. Figure 6 shows further exemplary states of a drug delivery device, when operated according to a method according to the present disclosure.

[0086] Figures 7A and 7B show different exemplary embodiments of needle shields.

[0087] Figure 8 shows a schematic view of another exemplary embodiment of a needle arrangement according to the present disclosure.

[0088] Figure 9 shows an expanded structural formula, molecular formula, and molecular weight of fitusiran, e.g. sodium form.

[0089] According to some embodiments of the present disclosure, an exemplary drug delivery device 10 is shown in Figures 1A and 1B.

[0090] Device 10, as described above, may be configured to inject a drug or medicament into a patient’s body.

[0091] Device 10 may include a housing 11 which typically may contain a reservoir or cartridge or medicament container 24 containing the medicament to be injected (e.g., a syringe or a container) and the components required to facilitate one or more steps of the delivery process.

[0092] Device 10 may also include a cap assembly 12 that may be detachably mounted to the housing 11, in particular on a distal or front end D of the device 10. Typically, a user must remove cap assembly or cap 12 from housing 11 before device 10 can be operated.

[0093] As shown, housing 11 may be substantially cylindrical and may have a substantially constant diameter along the longitudinal axis X. The housing 11 may have a distal region 20 and a proximal region 21. The term “distal” may refer to a direction that is relatively closer to a site of injection, and the term "proximal" may refer to a direction that is relatively further away from the injection site.

[0094] Device 10 may also include a needle shroud 13 coupled to the housing 11 to permit movement of the shroud 13 relative to the housing 11. For example, the shroud 13 may move in a longitudinal direction parallel to longitudinal axis X. Specifically, movement of the shroud 13 in a proximal direction may permit a needle 17 to extend beyond distal region 20 of housing 11 in the distal direction D. Insertion of the needle 17 may occur via several mechanisms. For example, the needle 17 may be fixedly located relative to housing 11 and initially be located within an extended needle shroud 13. Proximal movement of the shroud 13 by placing a distal end of shroud 13 against a patient’s body and moving housing 11 in a distal direction will uncover the distal end of needle 17. Such relative movement may allow the distal end of needle 17 to extend into the patient’s body. Such insertion may be termed “manual” insertion as the needle 17 is manually inserted via the patient’s manual movement of the housing 11 relative to the shroud 13.

[0095] Another form of insertion may be “automated” whereby the needle 17 moves relative to housing 11. Such insertion may be triggered by movement of shroud 13 or by another form of activation, such as, for example, a button 22. As shown in Figures 1A & 1 B, button 22 may located at a proximal or back end P of the housing 11. However, in other embodiments, button 22 could be located on a side of housing 11. In further embodiments, the button 22 may be replaced, for instance, by a shroud trigger mechanism, e.g. provided by pushing the needle shroud 13 inside the housing when the drug delivery device is put onto an injection site.

[0096] Other manual or automated features may include drug injection or needle retraction, or both. Injection may be the process by which a bung or piston 23 is moved from a proximal location within a container or cartridge or drug container 24 to a more distal location within the cartridge 24 in order to force a medicament from the cartridge 24 to be discharged through needle 17 into the patient’s body.

[0097] In some embodiments, an energy source, e.g. a drive spring 30, may be arranged, e.g. in a plunger 40, and may be under compression before device 10 is activated. A proximal end of the drive spring 30 may be fixed within proximal region 21 of housing 11, and a distal end of the drive spring 30 can be configured to apply a compressive force to a proximal surface of piston 23. Following activation, at least part of the energy stored in the drive spring 30 may be applied to the proximal surface of piston 23. This compressive force may act on piston 23 to move it in a distal direction. Such distal movement may act to compress the liquid medicament within the cartridge 24, forcing it out of needle 17.

[0098] In some embodiments, the housing 11 may comprise a window 11a through which the cartridge 24 can be monitored.

[0099] Figures 2A and 2B are schematic views of an exemplary embodiment of a needle arrangement 200 for a drug delivery device according to the present disclosure. The needle arrangement 200 may comprise a needle 217 and a needle shield 250. For a better understanding the needle shield 250 is shown not interacting with the needle 217. The needle shield 250 in this embodiment is a rigid needle shield, but it may also be a soft needle shield. The needle 217 may be fluidly connected to a medicament container 224, which in the following embodiment is shown as a pre-filled syringe 224. The medicament container 224 however is not limited to pre-filled syringes.

[0100] The needle shield 250 may be configured to interact with the needle in at least two different orientations. In this exemplary embodiment, there are two orientations of the needle shield 250 in which it can interact with the needle 217, namely a first orientation 01 and a second orientation 02. The first orientation 01 may be different than the second orientation 02.

[0101] In the first orientation 01 of the needle shield 250, the needle shield 250 may be configured to interact with the needle 217 before use of the drug delivery device (not shown).

[0102] The needle shield 250 may comprise a first portion 250a and a second portion 250b. The first portion 250a may be opposite to the second portion 250b along the longitudinal axis X. The longitudinal axis X may be the axis of extension of the needle shield 250. The needle shield 250, e.g. the first portion 250a, may comprise a first end 252. The needle shield 250, e.g. the second portion 250b, may comprise a second end 254. The first end 252 and the second end 254 may be arranged opposite to each other along the longitudinal axis X.

[0103] The first end 252 may be configured to interact with the needle 217 when the needle shield 250 is in its first orientation 01. Before use of the drug delivery device, the needle shield 250, in its first orientation 01 , may interact with, e.g. receive, the needle 217. In particular the first portion 250a, e.g. the first end 252, may receive the needle 217 when the needle shield 250 is interacting with the needle 217, in its first orientation 01.

[0104] In its first orientation 01 the second end 254 may be arranged at a distal end of the needle shield 250. The first end 252 may face the needle 217.

[0105] When interacting with the needle 217 in its first orientation 01, e.g. before use of the drug delivery device, the needle shield 250 covers and protects a portion of the needle 217 and in particular the needle tip.

[0106] The needle 217 may be arranged at a distal end of a medicament container such as a pre-filled syringe 224. The pre-filled syringe may 224 be a 1.0 ml pre-filled syringe. Other volumes are possible as well. Usually, the pre-filled syringe 224 and the needle shield 250 may have variations in dimensions, e.g. in length and / or in diameter

[0107] Figure 2A shows a state before use of the pre-filled syringe 224 and optionally before the prefilled syringe 224 may be arranged inside a drug delivery device, such as an autoinjector, for example a reusable autoinjector.

[0108] Before use, the needle shield 250 may receive the needle 217 of the pre-filled syringe 224. The pre-filled syringe 224 may be usually arranged inside a drug delivery with the needle shield 250 receiving, e.g. covering and protecting, the needle 217, e.g. in an assembled state.

[0109] The needle shield 250a may comprise a first engagement feature 256 and a second engagement feature 258. The first engagement feature 256 may be configured to engage the needle 217 when the needle shield 250 is interacting with the needle 217, e.g. in the first orientation 01.

[0110] The needle shield 250 may for example be prevented, by the engagement of the needle 217 with the first engagement feature 256, from falling off the needle 217, when the needle shield in the first orientation 01 interacts with the needle 217.

[0111] The needle shield 250 may for example be prevented, by the engagement of the needle 217 with the second engagement feature 258, from falling off the needle 217, when the needle shield 250 in the second orientation 02 interacts with the needle 217.

[0112] The first portion 250a of the needle shield 250 may comprise the first engagement feature 256. The first engagement feature 256 in this example may be configured as an inner structure of the first portion 250a of the needle shield 250. The engagement feature 256 may be configured to receive the needle 217 before use of the drug delivery device and to cover and protect the needle 217. The engagement feature 256 may also seal the needle 217.

[0113] The first and / or second engagement features 256 / 258 in this embodiment have a droplet shape. The droplet shape may vary between the first engagement feature and the second engagement feature, for example relative to their respective size.

[0114] The first and / or second engagement features 256, 258 may however also have shapes different than the droplet shape. The first and / or second engagement features 256, 258 in this or in any other embodiment may also have different shapes with respect to each other. Figure 2B shows a state after use of drug delivery device, e.g. of the pre-filled syringe 224. The image is a schematic representation. The pre-filled syringe 224 may be arranged in a drug delivery device. In an after-use state the needle 217 was used and may be contaminated and therefore represent a health hazard. The needle 217 after use may be a danger for the user or other persons around him.

[0115] The needle shield 250 in its second orientation 02 may be configured to interact with the needle 217 after use of the drug delivery device. For a better understanding the needle shield 250 is shown not interacting with the needle 217.

[0116] The needle shield 250 may comprise the second portion 250b. The second portion 250b may comprise the second end 254 of the needle shield 250. In the second orientation 02 of the needle shield 250, the second portion 250b may be configured to interact with the needle 217, e.g. receive the needle 217, when the needle shield 250 interacts with the needle 217.

[0117] The second end 254 of the needle shield 250 may be configured to receive the needle 217 when the needle shield 250 is interacting with the needle 217 in its second orientation 02.

[0118] In its second orientation 02, the first end 252 of the needle shield 250 may be arranged on a distal end of the needle shield 250 with respect to the pre-filled syringe 224. The second end 254 instead may be arranged on a proximal end with respect to the pre-filled syringe 224.

[0119] When interacting with the needle 217 in its second orientation 02 the needle shield 250, e.g. the second portion 250b of the needle shield 250, may be configured to cover and protect at least the needle tip of the needle. It may also cover at least a portion of the needle 217 adjacent to the needle tip.

[0120] As such, when in its second orientation 02, the needle shield 250 interacts with the needle 217, the needle 217 may be protected from environmental influence. A user, e.g. a patient, and other persons are therefore not at risk of getting injured by a free standing needle. Furthermore, contamination by the used needle may be prevented.

[0121] The needle shield 250 can be configured such that when it interacts with the needle in its second orientation 02, the needle shield 250 may be at least partially restricted, e.g. hindered, from being removed from the needle 217. This may be achieved by a second engagement feature 258. This represents a further safety mechanism as it makes it difficult for a user, that may have confused a used drug delivery device with a new drug delivery device, to remove the needle shield 250 from the used needle 217.

[0122] The resistance in removing the needle shield 250 from the needle 217, when the needle shield 250 interacts with the needle 217 in its second orientation 02, also serves as early alert to the user, that the needle shield 250 he / she is trying to remove may be arranged on a used needle 217.

[0123] In any embodiment, the force required by a user to remove the needle shield 250 from the needle 217, when the needle shield 250 is interacting with the needle 217 in its first orientation 01 , may be less than the force required by a user to remove the needle shield 250 from the needle 217, when the needle shield 250 is interacting with the needle 217 in its second orientation 02.

[0124] The difference between the first orientation 01 of the needle shield 250 (Figure 2A) and the second orientation 02 of the needle shield 250 (Figure 2B), lies in a 180 degrees rotation of the needle shield around the radial axis. The rotation is shown by the arrow.

[0125] In other words, a rotation of 180 degrees of the needle shield 250 around either of these directions, e.g. radial or azimuthal, when the needle shield 250 is in its first orientation 01 , moves the needle shield 250 to its second orientation 02 with respect to the needle 217.

[0126] When the needle shield 250 interacts with the needle 217 in the first orientation 01, the second end 254 may be arranged more distally than the first end 252. When the needle shield 250 interacts with the needle 217 in the second orientation 02, the first end 252 may be arranged more distally than the second end 254.

[0127] This means that after use of the drug delivery device the needle shield 250 can be rotated 180 degrees around the radial or azimuthal direction compared to its first orientation 01, such as to be usable (e.g. for its intended use) with the needle 217 in its second orientation 02.

[0128] The needle shield 250 may be configured to be used in both orientations, one before use of the drug delivery device, e.g. the first orientation 01 , and one after use of the drug delivery device, e.g. the second orientation 02. As such a needle shield 250 may be provided configured to have more than one intended use. Such a needle shield 250 minimizes unnecessary waste compared to single use needle shield, e.g. needle shield which can only be removed from the needle 217 before use and may have to be thrown away after that.

[0129] Figures 3A and 3B are schematic views of a further exemplary embodiment of a needle arrangement.

[0130] This embodiment is similar to the one of Figures 2A and 2B. In particular, the needle shield 350 may be similar to the needle shield 250 of figure 2A, 2B. To avoid repetition, only the differences between the embodiments are described below. As regards the other elements and features, reference is made to the explanations given in the context of Figures 2A and 2B.

[0131] In this embodiment, the needle shield 350 may comprise in its second portion 350b a second engagement feature 358. The second engagement feature 358 may be configured to receive the needle 317 when the needle shield 350 interacts with the needle 317 in its second orientation 02.

[0132] The engagement feature 358 may be configured as a needle path. In other words, the engagement feature may be configured such that when the needle 317 is received by the needle shield 350 in its second orientation 02, the needle 317 is guided through the needle path. The needle path may be straight or comprise edges (as may be the case here). The needle path may engage the needle 317.

[0133] The needle path in this embodiment may comprise two kinks or bends which are configured to kink or bend the needle 317 once the needle 317 may be received in the needle path.

[0134] The shape of the needle 317 assumes the shape of the needle path, once received in the needle path of the needle shield 350 in its second orientation 02, as shown in Figure 3C.

[0135] In Figure 3C the needle shield 350 was removed from the figure to show more clearly the shape of the needle 317 after being deformed by the needle path.

[0136] As shown in Figure 3C the needle 317 was deformed by the engagement feature 358 configured as a needle path. The deformation may be such that the needle 317 may comprise two kinks 319 and 320. The two kinks may form two angles. A portion of the needle most proximate to the pre-filled syringe may also be bent / kinked such as to form an angle denoted with the letter alpha with respect to the longitudinal axis x of the pre-filled syringe 324.

[0137] The angle alpha may be more than or equal to 25°, 30°, 35°, 40°, 45°, 50°, 55°, 60°, 65°.

[0138] The angle alpha may be less than or equal to 65°, 60°, 55°, 50°, 45°, 40°, 35°, 30°, 25°.

[0139] The angle alpha may for example be 45°.

[0140] The angle alpha may be configured depending on the needle gauge. A larger angle alpha may result into a lower needle insertion force. A larger angle alpha result in more revolutions (e.g. turns) required to separate the needle. A larger angle alpha may result in sharper fracture sites of the needle.

[0141] A lower angle alpha may result into higher needle insertion force. A lower angle alpha result in less revolutions (e.g. turns) required to separate the needle. A lower angle alpha may result in less sharp fracture sites of the needle.

[0142] The engagement feature 358 of the needle shield 350 engages and deforms the needle 317. Specifically, the deformation of the needle 317 inside the needle shield 350 may be such that the needle shield 350 cannot be removed from the needle 317, e.g. the needle shield 350 and the needle 317 are fixedly engaged to each other.

[0143] The second engagement feature 358 may be further configured such that a rotation of the needle shield 350 around the longitudinal axis, when the needle shield 350 is interacting with the needle 317 in its second orientation 02, causes a disengagement of at least a portion of the needle 317 from the drug delivery device, e.g. from the pre-filled syringe 324.

[0144] The disengagement may occur when the needle shield 350 is rotated 180 degrees, or up to and including 270 degrees around the longitudinal axis.

[0145] The disengagement may be caused by a breakage of the needle 317. The breaking point of the needle 317 depends on the angle denoted with the letter alpha between the most proximate portion of the needle with respect to the longitudinal axis X. The needle arrangement according to Figure 3A and 3B may be hence configured to allow removal of the needle 317, e.g. a distal portion thereof, by breakage of the needle 317, from the pre-filed syringe.

[0146] As shown in Figure 3D, after removal, e.g. breakage, of the needle 317 from the pre-filled syringe 324, the needle 317 may remain inside the needle shield 350, e.g. it does not fall off the needle shield 350. In particular, the broken-off portion of the needle 317 may remain engaged to the second engagement feature 358.

[0147] As such, a user of the drug delivery device, after use of the drug delivery device and after breakage of the used needle 317 from the drug delivery device, e.g. from the pre-filled syringe 324, through rotation around the longitudinal axis X of the needle shield 350 interacting with the needle 317 in its second orientation 02, may be left with a needle shield 350 comprising the broken-off portion of the needle 317 and the drug delivery device comprising the medicament container, e.g. the pre-filled syringe 324, without the broken-off portion of the needle 317.

[0148] At that point, the user may be able to dispose of the needle shield 350 including the broken off needle 317 and, for example, replace the used pre-filled syringe 324 in the reusable drug delivery device.

[0149] Figures 4A and 4B are schematic views of a further exemplary embodiment of a needle arrangement.

[0150] This embodiment may be similar to the one of Figure 2A and 2B and / or Figure 3A and 3B. To avoid repetition, only the differences between the embodiments are described below. As regards the other elements, reference is made to the foregoing explanations.

[0151] In this embodiment, the needle shield 450 may comprise a first portion 450a and a second portion 450b. According to this exemplary embodiment, the first portion 450a may be detachable from the second portion 450b when the second portion 450b interacts with the needle 417, as shown schematically in Figure 4C.

[0152] The interaction force of the second portion 450b of the needle shield 450 with the needle 417, when the needle shield 450 may be interacting with the needle 417 in its second orientation 02 may be greater than a force required to detach the first portion 450a from the second portion 450b, when the second portion 450b may be interacting with the needle 417 in the second orientation 02 of the needle shield 450. On the other hand, when a user tries to remove the needle shield 450 from the needle 417, when the needle shield is interacting with the needle 417 in its first orientation 01 , e.g. before use of the drug delivery device, the needle shield 450 can be removed in its entirety, e.g. with both the first portion 450a and second portion 450b attached to each other.

[0153] When a user tries to remove the needle shield 450 from the needle 417, when the needle shield is interacting with the needle 417 in its second orientation 02, e.g. after use of the drug delivery device, the first portion 450a of the needle shield 450 may be detached from the second portion 450b of the needle shield 450. The second portion 450b of the needle shield 450 remains engaged to the needle 417.

[0154] The detachability properties of the first portion 450a and second portion 450b of the needle shield 450 (as described here above) may be configured through a respective configuration of the engagement features, e.g. of the first engagement 456 and / or the second engagement feature 458.

[0155] The second portion 405b of the needle shield 450 may comprise a second engagement feature 458 which may be similarly shaped as the second engagement feature 258 of Figure 2A.

[0156] In particular, the second engagement feature 458 may be configured such as to engage the needle 417 with an increased engagement force than the first engagement feature 456. As such, it may be easier to remove the needle shield 450 from the needle 417 when the first engagement feature 456 interacts with the needle 417.

[0157] The second engagement feature 458 may be configured so that the engagement force of the second engagement feature 458 engaging the needle 417, when the needle shield 450 is interacting with the needle 417 in its second orientation 02, may be greater than a force required to detach the first portion 450a from the second portion 450b.

[0158] The needle shield 450 may comprise at least one retention feature 460 operable to further prevent removal of the needle shield 450 from the needle 417 when the needle shield 450 interacts with the needle 417 in its second orientation 02, as shown for example in Figure 4D.

[0159] The retention feature 460 in Figure 4D directly interacts with the needle 417 by contacting the needle 417 In this embodiment, the retention feature 460 further restricts the possibility of a removal of the needle shield 450 from the needle 417. In this embodiment the retention feature 460 may be an independent element arrangeable or arrange inside the second portion 450b of the needle shield 450 and configured to retain the needle 417 in the second potion 450b of the needle shield 450.

[0160] The retention feature 460 may not require an engagement feature 458 and may be the sole element retaining the second portion 450b of the needle to the needle 417.

[0161] In such an embodiment, the retention feature 460 may be configured so that the retention force of the retention feature 460 retaining the needle 417, when the needle shield 450 is interacting with the needle 417 in its second orientation 02, may be greater than a force required to detach the first portion 450a from the second portion 450b.

[0162] The provision of a retention feature 460 may be not limited to embodiments in which the first portion 450a and second portion 450b of the needle shield 450 are detachable to each other. The retention feature 460 may for example be provided in any of the previous embodiments and independent on the number of portions of the needle shield 450.

[0163] Figure 5 shows a schematic exemplary embodiment of a needle arrangement, a drug delivery device and a method for operating the drug delivery device.

[0164] As can be seen from the figure, a drug delivery device 510 may be provided in the form of a reusable drug delivery device 510, in particular a reusable autoinjector. The drug delivery device 510 is shown schematically.

[0165] A pre-filled syringe 524 may be configured to be inserted into the drug delivery device 510. The drug delivery device 510 further may comprise a cap 512. The cap 512 may be arranged at a distal end of the drug delivery device 510 and may be configured to cover the needle shield 550 of the pre-filled syringe 524, once the pre-filled syringe 524 may be arranged inside the drug delivery device 510.

[0166] The pre-filled syringe 524 may comprise the needle arrangement according to one of the previous embodiments, for example according to the exemplary embodiment of Figure 2A and 2B. The needle shield 550 interacts with the needle (not shown) of the pre-filled syringe 524 in its first orientation 01. The pre-filled syringe 524 with the needle shield 550 may be so ready to be inserted into the drug delivery device 510 as shown by the arrow in step 501.

[0167] The drug delivery device 510 with the pre-filled syringe 524 inserted is shown in step 502. At this stage the cap 512 may be still attached to the drug delivery device 510. The second end of the needle shield 550 may be arranged distally and may be received by the cap 512 (not shown).

[0168] The needle arrangement in this embodiment may comprise at least one connection feature configured to releasably connect the needle shield 550 with the cap 512 of the drug delivery device 510. The connection feature may be configured to releasably connect the needle shield 550 to the cap 512 in the first orientation 01 of the needle shield 550 and / or in the second orientation 02 of the needle shield 550 relative to the needle 517.

[0169] The connection feature in this embodiment may be represented by the outer surface of the needle shield 550 being toothed, so that the needle shield 550 can interact with corresponding recesses in the cap 512.

[0170] The connection features in this embodiment may be configured such that a rotation of the cap 512 causes a rotation of the needle shield 550.

[0171] The connection feature in this embodiment, also acts as a dedication feature. In other words, the drug delivery device 510 may have a dedication interface which allows only pre-filled syringes 524 comprising that specific embodiment of a needle arrangement, e.g. the needle shield 550 comprising a toothed outer surface, to be inserted into the drug delivery device 510.

[0172] The toothed outer surface therefore acts both as connection feature and dedication feature

[0173] As can be seen in step 503, rotating the cap 512 around the longitudinal axis causes a rotation of the needle shield 550 connected to the cap 512 by the connection feature around the longitudinal axis. The rotation of the cap 512 along the longitudinal axis X causes the removal of the cap 512 from the drug delivery device 510 and a respective removal of the needle shield 550 from the needle of the pre-filled syringe (not shown).

[0174] The removal of the cap 512 from the drug delivery device 510, however, is not limited to a rotational movement around the longitudinal axis X. The removal may, for example, occur through an axial movement of the cap 512 with respect to the drug delivery device along the longitudinal axis X. The needle shield 550 may be rotationally and / or axially connected to the cap 512 via the connection feature.

[0175] The cap 512 may be removed from the drug delivery device, in this embodiment, through a rotation around the longitudinal axis X, as shown in step 503. The rotation around the longitudinal axis X and respective removal of the cap 512 causes the rotation around the longitudinal axis X and removal of the needle shield 550. The needle shield 550 may at this step still be connected to the cap 512 via the connection feature.

[0176] The drug delivery device 510 may be now ready to be used, for example, optionally, for dispensing a dose of a medicament. At this stage a needle shroud 513 may be still covering the needle in order to prevent unintentional piercing.

[0177] Step 504 shows the drug delivery device 510 after use. The needle shroud 513 extends distally and covers the used, e.g. contaminated, needle.

[0178] The cap 512 and the needle shield 550 are not arranged on the drug delivery device 510 and needle, respectively.

[0179] In step 504 the needle shield 550 may be released from the cap 512. The orientation of the needle shield 550 with respect to the needle 517 may be changed, e.g. from its first orientation 01 to its second orientation 02. The change of orientation occurs through a 180° rotation around the azimuthal or radial direction, as shown by the two arrows.

[0180] The needle shield 550 in its new orientation, e.g. its second orientation 02, may be then releasably connected to the cap 512, for example through the connection feature. The first end of the needle shield 550 may be now received inside the cap 512 and the second end of the needle shield faces the needle.

[0181] In step 505 the cap 512 may be pushed onto the drug delivery device 510 and rotated around the longitudinal axis X (as shown by the arrows) in order to connect, e.g. fix the cap to the drug delivery device. The needle shield 550 in its second orientation 02 now interacts with the used needle of the pre-filled syringe.

[0182] The needle arrangement, e.g. the needle shield, may further comprise at least one resetting feature configured to interact with the drug delivery device 512, e.g. with the needle shroud, when the needle shield 550 interacts with the needle in its second orientation 02. The resetting feature may be configured to assist in bringing the drug delivery device 512 into a condition that allows it to be operated again after an operation occurred.

[0183] The resetting feature may for example bring the needle shroud 513 in a locked or in an unlocked position. The resetting feature may for example also be configured to unlock the prefilled syringe 524 from the drug delivery device 510, such that the used pre-filled syringe 524 may be removed from the drug delivery device 510 as shown in step 506.

[0184] The resetting feature may comprise or may be the connection feature. The toothing of the outer surface of the needle shield 550 may for example be configured to reset the needle shroud when the needle shield 550 is arranged in its second orientation 02 on the needle.

[0185] In this exemplary embodiment the cap 512 may comprise a closed surface on its distal end. Other cap arrangements may however be envisaged, as will become clear for example from Figure 6

[0186] Figure 6 shows a schematic exemplary embodiment of a needle arrangement, a drug delivery device and a method for operating the drug delivery device.

[0187] The drug delivery device 610 in this embodiment may be similar to the drug delivery device 510 of Figure 5, e.g. it may be a reusable autoinjector in which a pre-filled syringe 624 can be inserted.

[0188] The cap 612 of the drug delivery device 610 however differs with respect to the cap 512 shown in the embodiment of Figure 5. The cap 612 of the drug delivery device 610 may be configured to interact with the drug delivery device 610 in at least two different cap orientations, e.g. a first cap orientation and a second cap orientation. The first cap orientation and the second cap orientation may substantially correspond to the first orientation 01 and second orientation 02 of the needle shield 650.

[0189] As can be seen in step 601 of Figure 6, the needle shield 650, in its first orientation 01, is interacting with the needle (not visible) of the pre-filled syringe 624. In other words the pre-filled syringe may comprise the needle shield arranged on the pre-filled syringe in its first orientation. The cap 612 may be arranged on the drug delivery device in its first cap orientation.

[0190] In step 602 the pre-filled syringe (not visible anymore) was inserted into the drug delivery device 610. The cap 612 may be configured to permit the needle shield 650 to pass at least partially through the cap 612. As can be seen in step 602 the needle shield 650 extends at least partially from the distal end of the cap 612 in the distal direction, when connected to the cap 612.

[0191] The needle arrangement may comprise at least one connection feature configured to releasably connect the needle shield 650 with the cap 612 of the drug delivery device 610. The connection feature may be configured to releasably connect the needle shield 650 to the cap 612 in the first orientation 01 of the needle shield 650 and / or in the second orientation 02 of the needle shield 650.

[0192] The connection feature in this embodiment may be represented by the outer surface of the needle shield 650 being toothed. Similarly, to the embodiment of Figure 5 the connection feature also acts as dedication feature.

[0193] The connection features in this embodiment may be configured such that a rotation in any direction of the cap 612 causes a respective rotation of the needle shield 650.

[0194] As can be seen in step 603, rotating the cap 612 around the longitudinal axis causes a rotation of the needle shield 650 connected to the cap 612 caused by the connection feature interacting with the cap 612. The rotation of the cap 612 around the longitudinal axis X causes the removal of the cap 612 from the drug delivery device 610 and a respective removal of the needle shield 650 from the needle 617 of the pre-filled syringe (not visible).

[0195] The needle shield 650 may remain connected to the cap 612 as can be seen in step 603. This may be achieved through the connection feature. In particular, the needle shield 650 may have a portion extending distally from the cap 612 and a portion extending proximally from the cap 612.

[0196] In particular, a first end 652 of the needle shield 650 extends proximally from the cap 612 and faces the needle 617. A second end 654 of the needle shield 650 extends distally from the cap 612.

[0197] The drug delivery device 610 may be now ready to be used, for example, optionally, for dispensing a dose of a medicament. At this stage a needle shroud 613 may be still covering the needle 617 in order to prevent unintentional piercing.

[0198] Step 604 shows the drug delivery device 610 after use. The needle shroud 613 extends distally and covers the used, e.g. contaminated, needle 617. The cap 612 and the needle shield 650 are not arranged on the drug delivery device and needle, respectively. The needle shield 650, however may be still connected to the cap 612.

[0199] In step 604 the cap 612 and the needle shield 650 are rotated around the radial axis. The rotation around the radial axis causes a change in orientation for both the cap 612 with respect to the drug delivery device 610 and the needle shield 650 with respect to the needle 617. The cap 612 may be rotated around the radial axis from its first cap orientation to its second cap orientation. The needle shield 650 may be rotated around the radial axis from its first orientation to its second orientation. The rotation may be a 180° rotation.

[0200] After rotation around the radial axis of the cap 612 and the needle shield 650, the second end 654 of the needle shield 650 faces the needle 617.

[0201] In step 605 the cap 612 may be pushed onto the drug delivery device 610 and rotated around the longitudinal axis (as shown by the arrows) in order to connect, e.g. fix, the cap 612 in its second cap orientation to the drug delivery device 610. The needle shield 650 in its second orientation now interacts with the used needle (not visible) of the pre-filled syringe.

[0202] The needle arrangement, e.g. the needle shield 650, may further comprise at least one resetting feature configured to interact with the drug delivery device 610 when the needle shield 650 interacts with the needle 617 in its second orientation 02. The resetting feature may be configured to assist in bringing the drug delivery device 610 into a condition that allows it to be operated again after an operation occurred.

[0203] The resetting feature may for example reset the needle shroud 613 as for example explained with reference to Figure 5. The resetting feature may for example also unlock the pre-filled syringe from drug delivery device 612, such that the used pre-filled syringe may be removed from the drug delivery device 612, as shown in step 606.

[0204] The resetting feature may comprise or may be the connection feature. The toothing of the outer surface of the needle shield 650 may for example be configured to reset the needle shroud 613, when the needle shield 650 may be arranged in its second orientation on the needle.

[0205] The cap 612 in step 606 may be connected to the drug delivery device in its second cap orientation. The cap 612 may be configured the same with respect to its interaction with the drug delivery device in both the first cap orientation and the second cap orientation. In other words, the first cap orientation and the second cap orientation may correspond to a 180° rotation with respect to each other around the radial axis, but the cap 612 may be configured substantially equal in both cap orientations.

[0206] Figure 7A shows different exemplary embodiments of needle shields 750a to 750f. The needle shields according to these exemplary embodiments all comprise different dedication features 751a to 751f.

[0207] The dedication feature 751a to 751 f may be configured to allow the extraction of a medicament container from and / or the insertion of the medicament container into the drug delivery device. The dedication feature may be configured to interact with a dedication interface of the drug delivery device. A drug delivery device may be configured to allow insertion of a pre-filled syringe only if the dedication feature of the needle arrangement, e.g. of the needle shield, corresponds to a corresponding dedication interface of the drug delivery device.

[0208] Correspondence may be given when the dedication feature of the needle shield can interact with the dedication feature of the drug delivery device.

[0209] Medicament containers, such as pre-filled syringes comprising a needle arrangement with one type of dedication feature may all comprise the same medicament. For each type of medicament, a different dedication feature may be used. A drug delivery device may be configured, e.g. through a dedication interface, to allow insertion only of medicament containers, e.g. of pre-filled syringes, comprising a needle arrangement with a corresponding dedication feature. A such, it may be avoided that a medicament container with one drug, may be inserted into a drug delivery device aimed at dispensing another drug.

[0210] Needle shield 750a may comprise as dedication feature 751a one or more teeth extending longitudinally along substantially the entire longitudinal length of the needle shield 750a and arranged radially around substantially the entire outer surface of the needle shield 750a.

[0211] Needle shield 750b may comprise as dedication feature 751b one or more teeth extending longitudinally along only a portion of the entire longitudinal length of the needle shield, e.g. along the first portion or the second portion of the needle shield 750b (see previous figures).

[0212] The teeth may be arranged radially around substantially the entire outer surface of the portion of the needle shield 750b. Needle shield 750c may comprise as dedication feature 751c at least one rip extending longitudinally along a portion of the needle shield, e.g. along the first portion of the needle shield 750c or along the second portion of the needle shield 750c (see previous figures).

[0213] Needle shield 750d may comprise as dedication feature 751 d a collar arranged on the outer surface of the needle shield 750d.

[0214] Needle shields 750e and 750f comprise as dedication feature 751 e, 751f pockets arranged on the outer surface of the respective needle shields. Needle shield 750e may comprise a pocket extending longitudinally from one end of the needle shield towards the second end of the needle shield. Needle shield 750f may comprise a pocket arranged on the outer surface of a portion of the outer surface of the needle shield.

[0215] Figure 7B shows different exemplary embodiments of needle shields 750g to 750k. The needle shields according to these exemplary embodiments comprise optical or magnetic or inductive dedication features.

[0216] Needle shield 750g may comprise as dedication feature 751g a QR code arranged on the outer surface of the needle shield 750g, e.g. on one portion of the needle shield.

[0217] Needle shield 750h may comprise as dedication feature 751 h a color ring coding arranged on the outer surface of the needle shield 750h, e.g. on one portion of the needle shield.

[0218] Needle shield 750i may comprise as dedication feature 751 i one magnet or plastic magnetized material area arranged on the outer surface of the needle shield 750i, e.g. on one portion of the needle shield.

[0219] Needle shield 750j may comprise as dedication feature 75j an NFC chip arranged on the outer surface of the needle shield 750j, e.g. on one portion of the needle shield.

[0220] Needle shield 750k may comprise as dedication feature 751k an inductive coil or wire arranged on the outer surface of the needle shield 750k, e.g. on one portion of the needle shield.

[0221] The drug delivery device may comprise electronical switches configured to allow the use of the drug delivery device and / or the insertion of the medicament container, e.g. the pre-filled syringe, only if the dedication feature corresponds to the dedication interface of the drug delivery device. The dedication interface of the drug delivery device may comprise (automatic) optical elements, magnetic elements, (automatic) inductive elements or mechanical elements depending on the type of dedication feature intended to be used.

[0222] The dedication feature described in the previous embodiment may also act as identifier. A user of the drug delivery device may for example be able to identify if the needle shield may be interacting with the needle in its first or second orientation depending on where the dedication feature may be arranged with respect to the needle and / or the medicament container, e.g. the pre-filled syringe.

[0223] Figures 8A to 8C show schematic views of a further exemplary embodiment of a needle arrangement.

[0224] The needle arrangement may comprise a needle 817 and a needle shield 850. For a better understanding the needle shield 850 is shown in Figure 8A as not interacting with the needle 817.

[0225] The needle shield 850 of the needle arrangement of this embodiment may comprise only one portion 850a. The one portion may comprise a first end 852a and a second end 852b. The needle shield 850 may further comprise only one engagement feature 856. The engagement feature 856 in this embodiment may be configured to interact with the needle 817 of a pre-filled syringe 824 in the first orientation 01 of the needle shield 850 and in the second orientation 02 of the needle shield 850 (as can be seen in Figure 8B).

[0226] The needle shield 850 further may comprise at least partially a plastic shell 870 which may at least partially surround the needle shield.

[0227] When the needle shield 850 interacts with the needle 817 in its first orientation 01, the plastic shell 870 may be attached to the needle shield 850 (see Figure 8A).

[0228] The plastic shell 870 may be configured to be detachable or detached from the needle shield 850, when the needle shield 850 interacts with the needle 817 in the second orientation 02 (as can be seen in Figure 8C).

[0229] As such, the plastic shell may be thrown away separately from the pre-filled syringe with the attached needle shield. This is advantageous for recycling reasons and is an important contribution to the fight against unsorted waste disposal. The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.

[0230] As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0231] The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., shorter long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20°C), or refrigerated temperatures (e.g., from about - 4°C to about 4°C). In some instances, the drug container may be or may include a dualchamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and / or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively, or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body. The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and / or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (antidiabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.

[0232] Examples of APIs for the treatment and / or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and / or exchanging at least one amino acid residue occurring in the naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term ..derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and / or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide. Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Vai or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin. Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N- palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega- carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(w- carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(w-carboxyheptadecanoyl) human insulin.

[0233] Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC- 1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211 , CM-3, GLP-1 Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1 , GSK-2374697, DA-3091 , MAR-701 , MAR709, ZP- 2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA- 15864, ARI-2651 , ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide- XTEN and Glucagon-Xten.

[0234] An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom.

[0235] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0236] Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

[0237] Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and / or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.

[0238] The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigenbinding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).

[0239] The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and / or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full- length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0240] The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.

[0241] Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

[0242] Further examples of APIs for the prophylaxis of hemophilia A or B, with or without inhibitors, include an siRNA targeting antithrombin. An example of an siRNA targeting antithrombin is fitusiran. The term “prophylaxis” and “prophylactic treatment” are used interchangeably herein.

[0243] Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.

[0244] Those of skill in the art will understand that modifications (additions and / or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

[0245] An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1 :2014(E). As described in ISO 11608-1 :2014(E), needlebased injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container.

[0246] As further described in ISO 11608-1 :2014(E), a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).

[0247] As further described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with a replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation). As also described in ISO 11608-1:2014(E), a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).

[0248] Fitusiran as the API for the medicament in the device

[0249] Fitusiran is a synthetic, chemically modified double-stranded small interfering RNA (siRNA) oligonucleotide covalently linked to a tri-antennary N-acetyl-galactosamine (GalNAc) ligand targeting AT3 mRNA in the liver, thereby suppressing the synthesis of antithrombin. See, e.g., Pasi et al., N Engl J Med. (2017) 377(9):819-28. The nucleosides in each strand of fitusiran are connected through either 3’-5’ phosphodiester or phosphorothioate linkages, thus forming the sugar-phosphate backbone of the oligonucleotide.

[0250] The sense strand and the antisense strand contain 21 and 23 nucleotides, respectively. The 3’ end of the sense strand is conjugated to the GalNAc containing moiety (referred to herein as L96) through a phosphodiester linkage. The sense strand contains two consecutive phosphorothioate linkages at its 5’ end. The antisense strand contains four phosphorothioate linkages, two at the 3’ end and two at the 5’ end. The 21 nucleotides of the sense strand hybridize with the complementary 21 nucleotides of the antisense strand, thus forming 21 nucleotide base pairs and a two-base overhang at the 3’-end of the antisense strand. See also U.S. Pat. 9,127,274, U.S. Pat. 11,091,759, US2020 / 0163987A1, and WO 2019 / 014187, the entire contents each of which are expressly incorporated herein by reference.

[0251] The two nucleotide strands of fitusiran are shown below: sense strand: 5’Gf-ps-Gm-ps-Uf-Um-Af-Am-Cf-Am-Cf-Cf-Af-Um-Uf-Um-Af-Cm-Uf-Um- Cf-Am-Af-L96 3’ (SEQ ID NO:1), and antisense strand: 5’ Um-ps-Uf-ps-Gm-Af-Am-Gf-Um-Af-Am-Af-Um-Gm-Gm-Uf-Gm-Uf- Um-Af-Am-Cf-Cm-ps-Am-ps-Gm 3’ (SEQ ID NO:2), wherein

[0252] Af = 2’ -deoxy- 2’-fluoroadenosine Cf = 2’ -deoxy- 2’-fluorocytidine Gf = 2’ -deoxy- 2’-fluoroguanosine Uf = 2’ -deoxy- 2’-fluorouridine Am = 2’-O-methyladenosine

[0253] Cm = 2’-0-methylcytidine

[0254] Gm = 2’-O-methylguanosine

[0255] Um = 2’-0-methyluridine

[0256] (hyphen) = 3’-5’ phosphodiester linkage sodium salt “-ps-” = 3’-5’ phosphorothioate linkage sodium salt and wherein L96 has the following formula:

[0257] As used herein, the terms 2’ -deoxy- 2’-fluoroadenosine and 2’-fluoroadenosine may be used interchangeably.

[0258] As used herein, the terms 2’ -deoxy- 2’-fluorocytidine and 2’-fluorocytidine may be used interchangeably.

[0259] As used herein, the terms 2’ -deoxy- 2’-fluoroguanosine and 2’-fluoroguanosine may be used interchangeably.

[0260] As used herein, the terms 2’ -deoxy- 2’-fluorouridine and 2’-fluorouridine may be used interchangeably.

[0261] The expanded structural formula, molecular formula, and molecular weight of fitusiran, e.g. sodium form, are shown in Figure 9.

[0262] The structure of fitusiran can also be described using the following diagram, wherein the X is O:

[0263]

[0264] Fitusiran is shown in Figure 9 in sodium salt form.

[0265] In some embodiments, the device delivers fitusiran in an aqueous solution, wherein fitusiran is at a concentration of about 40 to about 200 mg / mL (e.g., about 50 to about 150 mg / mL, about 80 to about 110 mg / mL, or about 90 to about 110 mg / mL). As used herein, values intermediate to recited ranges and values are also intended to be part of this disclosure. In addition, ranges of values using a combination of any of recited values as upper and / or lower limits are intended to be included. In further embodiments, the pharmaceutical formulation comprises fitusiran in an aqueous solution at a concentration of about 40, about 50, about 75, about 100, about 125, about 150, or about 200 mg / mL. In certain embodiments, fitusiran is provided in an aqueous solution at a concentration of about 100 mg / mL.

[0266] The term “deliver,” “delivers,” or “delivering” is intended to mean “administer,” “administers,” or “administering.”

[0267] Unless specifically stated or otherwise evident from the context, as used herein, the term “approximately” or "about" refers to a value that is within an acceptable error range for a particular value determined by a person of ordinary skill, a portion of which will depend on how the measurement or determination is made. For example, “approximately” or "about" may mean a range of up to 10% (ie, ±10%). Therefore, “approximately” or "about" can be understood as greater than or less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1 %, 0.05%, 0.01%, or 0.001%. When a specific value is provided in this disclosure, unless otherwise stated, the meaning of “approximately” or "about" should be assumed to be within an acceptable error range for that specific value.

[0268] While the fitusiran dosage weight described herein refers to the weight of fitusiran free acid (active moiety), administration of fitusiran to patients herein refers to administration of fitusiran sodium (drug substance) provided in a pharmaceutically suitable aqueous solution (e.g., a phosphate-buffered saline at a physiological pH). For example, about 100 mg / mL fitusiran means about 100 mg of fitusiran free acid (equivalent to about 106 mg fitusiran sodium, the drug substance) per mL. Unless otherwise indicated, a fitusiran weight recited in the present disclosure is the weight of fitusiran free acid (the active moiety).

[0269] In some embodiments, a pharmaceutical formulation in the device comprises fitusiran in a phosphate-buffered saline. The phosphate concentration in the solution may be about 1 to about 10 mM (e.g., about 2, about 3, about 4, about 5, about 6, about 7, about 8, or about 9 mM), with a pH of about 6.0-8.0. The pharmaceutical formulations herein may include a stabilizing agent such as EDTA. The pharmaceutical formulations may be preservative-free. In some embodiments, the fitusiran pharmaceutical formulation in the device is preservative-free and comprises, consists of, or consists essentially of about 100 mg of fitusiran per mL of an approximately 5 mM phosphate buffered saline (PBS) solution. In some embodiments, the fitusiran pharmaceutical formulation in the device is preservative-free and comprises, consists of, or consists essentially of fitusiran in an approximately 5 mM phosphate buffered saline (PBS) solution. The PBS solution is composed of sodium chloride, dibasic sodium phosphate (heptahydrate), and monobasic sodium phosphate (monohydrate). Sodium hydroxide solution and diluted phosphoric acid may be used to adjust the pH of the formulation to about 7.0 or about 7.1.

[0270] In some embodiments, the fitusiran formulation in the device for subcutaneous delivery contains fitusiran in a 5 mM phosphate buffered saline having 0.64 mM Na^PCL, 4.36 mM Na2HPC>4, and 84 mM NaCI at pH 7.0. In certain embodiments, the formulation of fitusiran solution for subcutaneous delivery is shown in Table 1 below:

[0271] Table 1. Exemplary Fitusiran Formulation

[0272] *q.s.: quantum satis

[0273] In some embodiments, the formulation of fitusiran solution for subcutaneous delivery with the device can be described as shown in Table 2 below.

[0274] Table 2. Exemplary Fitusiran Formulation

[0275] In some embodiments, the device may be used to deliver a single dose of fitusiran wherein the single dose comprises about 20 to about 80 mg of fitusiran (e.g., about 20 mg, about 25 mg, about 30 mg, about 40 mg, about 50 mg, or about 80 mg). In some embodiments, the device may be used to deliver single dose of fitusiran, wherein the single dose comprises about 1 to about 30 mg of fitusiran (e.g., about 1.25 mg, about 2.5 mg, about 5 mg, about 10 mg, about 20 mg, or about 30 mg).

[0276] In one embodiment, the device may be used to deliver a single dose of about 80 mg of fitusiran.

[0277] In one embodiment, the device may be used to deliver a single dose of about 50 mg of fitusiran.

[0278] In one embodiment, the device may be used to deliver a single dose of about 20 mg of fitusiran.

[0279] In one embodiment, the device may be used to deliver a single dose of about 30 mg of fitusiran.

[0280] In one embodiment, the device may be used to deliver a single dose of about 10 mg of fitusiran.

[0281] In one embodiment, the device may be used to deliver a single dose of about 5 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 2.5 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 1.25 mg of fitusiran. In some embodiments, the single dose of fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL). Other delivery volumes described herein may also be used.

[0282] In one embodiment, the device may be used to deliver a single dose of about 80 mg of fitusiran in about 0.8 mL (about 100 mg fitusiran / mL). In one embodiment, the device may be used to deliver a single dose of about 50 mg of fitusiran in about 0.5 mL (about 100 mg fitusiran / mL). In one embodiment, the device may be used to deliver a single dose of about 20 mg of fitusiran in about 0.5 mL (about 40 mg fitusiran / mL). In one embodiment, the device may be used to deliver a single dose of about 30 mg of fitusiran in about 0.5 mL (about 60 mg fitusiran / mL). In one embodiment, the device may be used to deliver a single dose of about 10 mg of fitusiran in about 0.5 mL (about 20 mg fitusiran / mL). In one embodiment, the device may be used to deliver a single dose of about 5 mg of fitusiran in about 0.5 mL (about 10 mg fitusiran / mL). In one embodiment, the device may be used to deliver a single dose of about 2.5 mg of fitusiran in about 0.5 mL (about 5 mg fitusiran / mL). In one embodiment, the device may be used to deliver a single dose of about 1.25 mg of fitusiran in about 0.5 mL (about 2.5 mg fitusiran / mL).

[0283] In one embodiment, the device delivers fitusiran at a prophylactically effective amount to prophylactically treat hemophilia (e.g., hemophilia A or B, in a patient with or without inhibitors) in a patient in need thereof (e.g., a hemophilia A or B patient, with or without inhibitors). “Prophylactically effective amount” refers to the amount of fitusiran that helps the patient with hemophilia A or B, with or without inhibitors to achieve a desired clinical endpoint such as reducing the Annualized Bleeding Rate (ABR), Annualized Joint Bleeding Rate (AjBR), Annualized Spontaneous Bleeding Rate (AsBR), or the frequency of bleeding episodes. As used herein in the context of fitusiran, the term “treat” “treating,” or “treatment” includes prophylactic treatment of the disease and refers to achievement of a desired clinical endpoint.

[0284] A hemophilia A or B patient with inhibitors refers to a patient who has developed alloantibodies to the factor he / she has previously received (e.g., factor VIII for hemophilia A patients or factor IX for hemophilia B patients). A hemophilia A or B patient with inhibitors may become refractory to replacement coagulation factor therapies. A patient without inhibitors refers to a patient who does not have such alloantibodies. The present treatment methods may be beneficial for hemophilia A patients with inhibitors, as well as for hemophilia B patients with inhibitors.

[0285] As used herein, a patient with “hemophilia A or B, with or without inhibitors,” or refers to 1) a hemophilia A patient with inhibitors, or 2) a hemophilia B patient with inhibitors, 3) a hemophilia A patient without inhibitors, or 4) a hemophilia B patient without inhibitors. As used herein, a patient refers to a human patient. A patient can also refer to a human subject.

[0286] In some embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 50 mg of fitusiran once every two months (or every eight weeks). In other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 50 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 80 mg of fitusiran every two months (or every eight weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 80 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 20 mg of fitusiran every two months (or every eight weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 20 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 10 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 30 mg every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 5 mg every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 2.5 mg every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 1.25 mg every month (or every four weeks).

[0287] Accordingly, provided herein is a method of prophylactic treatment of a patient with hemophilia A or hemophilia B, with or without inhibitors, comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof. The prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg. The prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks). Fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

[0288] As an example, a method of prophylactic treatment of a patient with hemophilia A or hemophilia B, with or without inhibitors, may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks). The about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran / mL).

[0289] Further provided herein is a method of reducing the frequency of bleeding episodes in a patient with hemophilia A or B, with or without inhibitors, comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof. The prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg. The prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks). Fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

[0290] As an example, a method of reducing the frequency of bleeding episodes in a patient with hemophilia A or B, with or without inhibitors, may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks). The about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran / mL).

[0291] Also, provided herein is a method of reducing the ABR in a patient with hemophilia A or B, with or without inhibitors, comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof. The prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg. The prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks). Fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

[0292] As an example, a method of reducing the ABR in a patient with hemophilia A or B, with or without inhibitors, may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks). The about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran / mL).

[0293] Also, provided herein is a method of reducing the AjBR in a patient with hemophilia A or B, with or without inhibitors, comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof. The prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg. The prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks). The fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

[0294] As an example, a method of reducing the AjBR in a patient with hemophilia A or B, with or without inhibitors, may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks). The about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran / mL).

[0295] Also, provided herein is a method of reducing the AsBR in a patient with hemophilia A or B, with or without inhibitors, comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof. The prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg. The prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks). Fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL). As an example, a method of reducing the AsBR in a patient with hemophilia A or B, with or without inhibitors, may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks). The about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran / mL).

[0296] Similar drug delivery devices as the ones discussed above are described in WO2015 / 004049 A1 , WO 2015 / 004052 A1, WO2015 / 144870 A1 , WO2016 / 193374 A1, WO2016 / 193343 A1, WO2016 / 193375 A1, WO2016 / 193346 A1 , WO2016 / 193348 A1 , WO2016 / 193352 A1, WO2016 / 193353 A1, WO2016 / 193355 A1 , WO2019 / 086561 A 1 , WO2019 / 086562 A1, WO2019 / 086575 A1 , WO2019 / 086563 A1 , WO2019 / 086564 A1 , WO2019 / 086576 A1, W02019 / 101613 A1, W02020 / 069994 A1 , W02020 / 200995 A1 , W02020 / 245206 A1, W02020 / 074570 A1 , W02022 / 003093 A1 , WO2022 / 106504 A1 , WO2017 / 089263 A1 , WO2016 / 193344 A1, WO2016 / 193356 A1 , W02019 / 101689 A1, WO2020 / 239844 A1 , EP1743666B1, US20050101919, US7955304, US7442185, US8308695, and US8529510, the entire disclosure content of each of which is included by reference for all purposes into the present disclosure.

[0297] Although embodiments of the present disclosure and their advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made therein without departing from the spirit and scope of the disclosure as defined by the appended claims. For example, it will be readily understood by those skilled in the art that many of the features, functions, processes and methods described herein may be varied while remaining within the scope of the present disclosure. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the system, process, manufacture, method or steps described in the present disclosure. As one of ordinary skill in the art will readily appreciate from the disclosure of the present disclosure, systems, processes, manufacture, methods or steps presently existing or to be developed later that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present disclosure. Accordingly, the appended claims are intended to include within their scope such systems, processes, methods or steps. The embodiments mentioned in the first part of the description may be combined with each other. The embodiments of the description of figures may also be combined with each other. Further, it is possible to combine embodiments mentioned in the first part of the description with examples of the second part of the description which relates to Figures 1 to 9. Reference numerals

[0298] 10 Drug delivery device

[0299] 11 housing

[0300] 11a window

[0301] 12 Cam assembly

[0302] 13 shroud

[0303] 17, needle

[0304] 22 button

[0305] 24 medicament container

[0306] 20 distal region

[0307] 21 proximal region

[0308] 23 piston

[0309] 30 drive spring

[0310] 40 plunger

[0311] 217 needle

[0312] 224 medicament container

[0313] 250 needle shield

[0314] 250a first portion

[0315] 250b second portion

[0316] 252 first end

[0317] 254 second end

[0318] 256 first engagement feature

[0319] 258 second engagement feature

[0320] 317 needle

[0321] 319 first kink

[0322] 320 second kink

[0323] 324 medicament container

[0324] 350 needle shield

[0325] 350a first portion

[0326] 350b second portion

[0327] 352 first end

[0328] 354 second end

[0329] 356 first engagement feature

[0330] 358 second engagement feature

[0331] 450 needle shield

[0332] 450a first portion

[0333] 450b second portion 452 first end

[0334] 454 second end

[0335] 456 first engagement feature

[0336] 458 second engagement feature

[0337] 460 retention feature 501-506 Steps 510 drug delivery device

[0338] 512 cap

[0339] 513 needle shroud

[0340] 517 needle

[0341] 524 medicament container

[0342] 550 needle shield 601-606 Steps 610 drug delivery device

[0343] 612 cap

[0344] 613 needle shroud

[0345] 617 needle

[0346] 624 medicament container

[0347] 650 needle shield 750a-750k needle shields 751a-751k dedication feature

[0348] 850 needle shield

[0349] 850a first portion

[0350] 852a first end

[0351] 852b second end

[0352] 856 first engagement feature

[0353] 870 plastic shell

[0354] 01 first orientation

[0355] 02 second orientation x longitudinal axis y radial axis z azimutal axis

[0356] D distal

[0357] P proximal

Claims

Claims1. Needle arrangement for a drug delivery device, the needle arrangement comprising a needle shield and a needle, wherein the needle shield is configured to interact with the needle in at least two different orientations relative to the needle, wherein the two different orientations comprise a first orientation in which the needle shield is configured to interact with the needle before use of the drug delivery device, and a second orientation in which the needle shield is configured to interact with the needle after use of the drug delivery device.

2. Needle arrangement according to claim 1, wherein, when interacting with the needle in its second orientation, the needle shield is configured to cover and protect at least a needle tip and a portion of the needle adjacent to the needle tip.

3. Needle arrangement according to claim 2, wherein the needle shield further comprises at least one retention feature operable to prevent removal of the needle shield from the needle when the needle shield interacts with the needle in its second orientation.

4. Needle arrangement according to any one of the preceding claims wherein the first orientation is opposite to the second orientation.

5. Needle arrangement according to any one of the preceding claims, wherein the needle shield comprises a first portion and a second portion, wherein the first portion is configured to receive the needle when the needle shield interacts with the needle in its first orientation and the second portion is configured to receive the needle when the needle shield interacts with the needle in its second orientation, wherein the needle shield is configured such that the first portion is detachable from the second portion when the second portion interacts with the needle.

6. Needle arrangement according to any one of the preceding claims, the needle shield comprising at least one engagement feature configured to engage the needle when the needle shield interacts with the needle in its second orientation, the engagement feature being further configured such that a rotation of the needle shield causes a disengagement of at least a portion of the needle from the drug delivery device.

7. Needle arrangement according to claim 6, wherein the engagement feature is configured to induce a deformation to at least a portion of the needle.

8. Needle arrangement according to any one of the preceding claims, comprising at least one connection feature configured to releasably connect the needle shield with a cap of the drug delivery device.

9. Needle arrangement according to claim 8, wherein the connection feature is configured such that a rotation of the cap causes a rotation of the needle shield.

10. Needle arrangement according to claim 8 or 9, wherein the connection feature is configured to releasably connect the needle shield to the cap in the first orientation of the needle shield and / or in the second orientation of the needle shield relative to the needle.

11. Needle arrangement according to any one of the preceding claims comprising at least one identifier configured to identify the first orientation and / or the second orientation.

12. Drug delivery device comprising the needle arrangement of any one of the preceding claims, the drug delivery device being provided to receive a medicament container which contains a medicament or comprising the medicament container, wherein the medicament container is fluidly connected or fluidly connectable to the needle, wherein the drug delivery device is an autoinjector, e.g. a reusable autoinjector.

13. Drug delivery device according to claim 12, the needle arrangement, e.g. the needle shield, further comprising at least one resetting feature configured to interact with the drug delivery device when the needle shield interacts with the needle in its second orientation, wherein the resetting feature is configured to assist in bringing the drug delivery device into a condition that allows it to be operated again after an operation occurred.

14. Method for operating a drug delivery device according to any one of the claims 12 or 13, the method comprising the steps of:Removing the needle shield from the needle of the drug delivery device, the needle shield interacting with the needle in its first orientation before removal;Optionally dispensing a medicament dose; andArranging the needle shield in its second orientation onto the used needle of the drug delivery device in order to cover and protect at least a needle tip and / or a piercing portion of the needle.

15. The method of claim 14, further comprising the step of rotating the needle shield when interacting with the needle in its second orientation to cause the disengagement of at least a portion of the needle from the drug delivery device.

16. Needle arrangement for a drug delivery device, the needle arrangement comprising a needle shield and a needle, wherein the needle shield is configured to interact with the needle in at least two different orientations relative to the needle, wherein the two different orientations comprise a first orientation in which the needle shield is configured to interact with the needle before use of the drug delivery device, and a second orientation in which the needle shield is configured to interact with the needle after use of the drug delivery device, wherein the needle shield comprises a first portion and a second portion, wherein the first portion is configured to receive the needle when the needle shield interacts with the needle in its first orientation and the second portion is configured to receive the needle when the needle shield interacts with the needle in its second orientation, wherien the first portion is opposite to the second portion along a longitudinal axis X, wherein the longitudinal axis X is an axis of extension of the needle shield, and wherein the needle shield is configured such that the first portion is detachable from the second portion when the second portion interacts with the needle.

17. Needle arrangement for a drug delivery device, the needle arrangement comprising a needle shield and a needle, wherein the needle shield is configured to interact with the needle in at least two different orientations relative to the needle, wherein the two different orientations comprise a first orientation in which the needle shield is configured to interact with the needle before use of the drug delivery device, and a second orientation in which the needle shield is configured to interact with the needle after use of the drug delivery device, the needle shield comprising an engagement feature configured to engage the needle when the needle shield interacts with the needle in its second orientation, wherein the engagement feature is configured to deform the needle inside the needle shield such that the needle shield cannot be removed from the needle.

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