Drug delivery device

Abstract

A drug delivery device (20) is provided. The drug delivery device (20) comprises: a housing (22) for accommodating a drug container (24); a partition wall (38) in an initial position in an initial state of the drug delivery device (20), the partition wall being movable relative to the housing (22) for a dispensing operation, and the partition wall sealingly separating a first chamber (42) within the housing (22) from a second chamber (44) within the housing (22); a pressure source for providing a predetermined gas pressure, the pressure source configured for communicating with the first chamber (42) for driving the partition wall (38) to an operating position of the partition wall (38) for the dispensing operation, and for communicating with the second chamber (44) after completion of the dispensing operation for driving the partition wall (38) to an operating position of the partition wall (38) for the dispensing operation, and a drive to drive the partition wall (38) from the operating position to a final position of the partition wall (38).

Description

BACKGROUND

[0001] The present disclosure relates to a drug delivery device.

[0002] In drug delivery devices, a drug is typically delivered to a user, e.g. a patient, via a needle that pierces the skin of the user. The drug can be contained within a drug container of the drug delivery device, e.g. within a syringe arranged or to be arranged within the drug delivery device. Conventional drug delivery devices comprising a syringe and an associated drive mechanism have a shape that substantially corresponds to the shape of the syringe. In particular, conventional drug delivery devices comprising a syringe have an elongated cylindrical shape, wherein an axis of the drug delivery device can correspond to an axis of the needle. Such drug delivery devices can generally be referred to as pen-type devices. The needle of the syringe can be protected by a needle sleeve, a needle shield and / or a cap of the drug delivery device.

[0003] In many conventional drug delivery devices, the force required for a dispensing operation is introduced mechanically. However, when a drug delivery device shall inject a relatively large amount of drug, a corresponding high force has to be applied in order to dispense the drug, and in this case mechanical approaches are limited. Alternative drive concepts can be advantageous for delivering larger amounts of drug. Further, for mechanical solutions, the installation space required within the drug delivery device is typically relatively large. Moreover, with increasing degree of digitalization, new forms of controllable drives for drug delivery devices can be required. SUMMARY

[0004] It is an object of the present disclosure to facilitate improvements associated with drug delivery devices, in particular improvements in size and operability.

[0005] This object is achieved by the disclosed subject matter, e.g. by the subject matter defined in the independent claims. Advantageous improvements and refinements are in accordance with the dependent claims and / or set out in the following description.

[0006] One aspect of the present disclosure relates to a drug delivery device comprising a housing for accommodating a drug container, a partition wall in an initial position in an initial state of the drug delivery device, the partition wall being movable relative to the housing, e.g. towards a distal end of the housing or away from a proximal end of the housing for a dispensing operation, and sealingly separating a first chamber within the housing from a second chamber within the housing, a pressure source for providing a predetermined gas pressure, the pressure source being configured for communication with the first chamber for driving the partition wall to an operating position of the partition wall for the dispensing operation and for communication with the second chamber for driving the partition wall from the operating position to a final position of the partition wall after completion of the dispensing operation. The partition wall can be configured to sealingly separate the first chamber within the housing from the second chamber within the housing in the initial position and / or in the operating position of the partition wall. The partition wall can also be configured to sealingly separate the first chamber within the housing from the second chamber within the housing in the initial position, in the final position and / or in the operating position of the partition wall.

[0007] The housing can have a distal end facing an injection site during the dispensing operation and can have a proximal end facing away from the distal end, e.g. in case the drug delivery device is a pen-type drug delivery device. The partition wall can be movable towards the distal end of the housing or away from the proximal end for the dispensing operation. The housing can have an elongated shape. The first chamber can be arranged between the partition wall and the proximal end of the housing and the second chamber can be arranged between the partition wall and the distal end of the housing. The pressure source can be configured for communication with the first chamber for driving the partition wall to the operating position of the partition wall towards the distal end of the housing or away from the proximal end of the housing for the dispensing operation and for communication with the second chamber for driving the partition wall to the final position of the partition wall from the operating position towards the proximal end of the housing or away from the distal end of the housing after completion of the dispensing operation. The drug container can be arranged within the housing. If the drug container is arranged within the housing, a distal end of the drug container can face the distal end of the housing and / or a proximal end of the drug container can face the proximal end of the housing. The drug container can accommodate a drug. The drug can be a medicament.

[0008] The drug delivery device can be referred to as an auto-operated syringe and / or an auto-injector. The drug delivery device can be a fully functional drug delivery device. The described drug delivery device can be driven by a gas. In an auto-injector, the energy for the drug delivery operation can be pre-stored in an energy storage means. That is, a user does not have to provide the energy for the drug delivery operation, e.g. when preparing the drug delivery device for use. Rather, the energy can be pre-loaded into the system by the manufacturer. For example, a gas cartridge comprising a gas, e.g. a propellant gas, under high pressure or a battery for driving a pump to generate a gas pressure can be used as the energy storage means to provide the energy for the drug delivery operation.

[0009] The drug delivery device enables first to bring the injection member of the drug delivery device into contact with the injection site by moving the partition wall from its initial position to its operational position. For example, in case of a needle as injection member, the needle can pierce the skin of the user when the partition wall is moved from its initial position to its operational position. In other embodiments, in case of a nozzle as injection member, the nozzle can come into contact with the injection site when the drug container is moved from its initial position to its operational position. Then, the drug within the drug chamber of the drug container can be injected into the injection site via the injection member and by the gas pressure within the first chamber (e.g. only due to the energy transferred with the drug onto the skin; in other words, the drug delivery device can be a needle-free jet injector).

[0010] The partition wall and / or the pressure source can be configured for injecting the drug into the injection site when the partition wall is in its operational position. Further, the drug delivery device can enable to protect or retract the injection member after injecting the drug, thus by retracting the partition wall from its operational position to its final position without the risk of injuring the user. The sequence of movements of the partition wall can be realized with gas only (e.g. compressed air), which sequence of movements can first enable to move the injection member to the injection site, second to enable to inject the drug, and third to enable to retract the partition wall to its final position. Each position of the partition wall can only be reached after the partition wall has taken the preceding position.

[0011] In one embodiment, the partition wall can be formed by or can be the partition member. Thus, features described in connection with the partition wall also apply to the partition member and vice versa.

[0012] In one embodiment, the partition wall is configured to hold the drug container such that the drug container moves together with the partition wall, for example when the partition wall is moved from its initial position to its operational position and / or when the partition wall is moved from its operational position to its final position. If the drug container is arranged within the housing, the partition wall can be coupled to the drug container in order to hold the drug container and to move it relative to the housing. Thus, the drug container can move together with the partition wall relative to the housing. When the partition wall is in its initial position, the drug container can also be in its initial position. When the partition wall is in its operational position, the drug container can also be in its operational position. When the partition wall is in its final position, the drug container can also be in its final position.

[0013] In an embodiment, the drug delivery device comprises a fluid channel within the housing. The fluid channel can be in communication with the pressure source. The fluid channel can be configured for enabling communication between the pressure source and / or the first chamber. The fluid channel can be configured for preventing (fluid) communication between the pressure source and the second chamber in the initial state. The fluid channel can be configured for preventing (fluid) communication between the first chamber and the pressure source and / or for enabling communication of the second chamber with the pressure source after completion of the dispensing operation. The fluid channel can enable distribution of gas and thereby gas pressure to the area of the drug delivery device that currently needs gas and gas pressure. The fluid channel can extend from the pressure source to the first chamber and the second chamber. For example, the fluid channel can have three branches. A first branch of the fluid channel can extend to the first chamber, a second branch of the fluid channel can extend to the second chamber, and a third branch of the fluid channel extends to the pressure source. Which branch of the fluid channel is currently in (fluid) communication with the pressure source can depend on the position of the partition wall.

[0014] In an embodiment, the drug delivery device comprises a first valve configured for coupling the pressure source to the first chamber via the fluid channel in the initial state of the drug delivery device and / or for decoupling the first chamber from the pressure source after completion of the dispensing operation. The drug delivery device can further comprise a second valve configured for decoupling the second chamber from the pressure source in the initial state and / or for coupling the second chamber with the pressure source after completion of the dispensing operation. For example, the first valve can be arranged at the first branch of the fluid channel and / or the second valve can be arranged at the second branch of the fluid channel. The first valve and the second valve enable a simple way of coupling the pressure source to the first chamber via the fluid channel in the initial state of the drug delivery device and decoupling the first chamber from the pressure source after completion of the dispensing operation, and correspondingly decoupling the second chamber from the pressure source in the initial state and coupling the second chamber with the pressure source after completion of the dispensing operation.

[0015] In an embodiment, the first valve is configured for coupling the pressure source to the first chamber via the fluid channel, for example, when the gas pressure within the first chamber is below a predetermined first pressure threshold, and / or for decoupling the first chamber from the pressure source, for example, when the gas pressure within the first chamber corresponds to or exceeds the predetermined first pressure threshold. In other embodiments, for example, alternatively or additionally, the second valve can be configured for decoupling the second chamber from the pressure source, for example, when the gas pressure in the fluid channel is below a predetermined second pressure threshold, and / or for coupling the second chamber with the pressure source, for example, when the gas pressure within the fluid channel corresponds to or exceeds the predetermined second pressure threshold. The first pressure threshold can be smaller than the second pressure threshold. In other embodiments, the first pressure threshold can correspond to the second pressure threshold, for example, the thresholds can be equal.

[0016] In one embodiment, the drug delivery device comprises a flexible gas tube. The flexible gas tube can be coupled or couplable to the drug container and the flexible gas tube is configured for expelling the drug out of the drug container when pressurized such that the drug is dispensed from the drug delivery device. The gas tube can be pressurized by filling the gas tube with gas. When the gas tube is filled with gas, the gas tube inflates and the volume occupied by the gas tube and thereby the length of the gas tube can increase, e.g. compared to an "empty" (e.g. unpressurized) gas tube.

[0017] The drug container can comprise a reservoir for containing the drug. The gas tube can act on the drug container such that the drug can be expelled from the reservoir by the gas tube. For example, the gas tube can act on a pressure member such that the pressure member can expel the drug from the reservoir. For example, due to the increase in length of the pressurized gas tube, the gas tube can push the pressure member in a dispensing direction (e.g. towards the distal end of the housing or away from the proximal end) when pressurized. The pressure member can be a stopper which can be movably arranged within the drug container and / or which can sealingly close the reservoir, e.g. in case the drug container is a syringe or a cartridge. In other embodiments, the pressure member can be a plunger for moving the stopper in the dispensing direction. The stopper can sealingly close the reservoir of the drug container on the proximal side. The drug can be enclosed by the inner wall of the drug container and the stopper. In other embodiments, e.g. if the drug container is a bag, the pressure member can be a plunger and can press against the outside of the flexible wall of the bag to squeeze the bag and expel the drug out of the bag. The gas tube can be in communication with the first chamber, e.g. at the proximal end of the gas tube. The gas tube, e.g. pressurized and / or unpressurized, can have a spiral form. The plunger can be arranged between the gas tube and the stopper. Thus, the plunger can be coupled or couplable to the stopper and / or the gas tube. The plunger can be configured for being pushed by the gas tube and for pushing the stopper in the dispensing direction. Thus, the plunger can act as a pressure transfer element and / or can be regarded as a pressure member.

[0018] In one embodiment, the gas tube is configured for being in communication with the first chamber, e.g. when the partition wall is in its operational position, and / or for being decoupled from the first chamber, e.g. when the partition wall is in its initial and / or final position.

[0019] In one embodiment, the partition wall comprises a gas conduit. The gas conduit can be provided to couple the first chamber in communication with the gas tube, e.g. when the partition wall is in its operational position. The gas conduit can be closed and / or not in communication with the pressure source when the partition wall is not in its operational position. Thus, the gas tube can not be pressurized when the partition wall (and thereby the drug container) is not in the operational position.

[0020] In one embodiment, the gas tube comprises an opening for receiving gas, e.g. when the partition wall is in its operational position. The opening can be closed when the partition wall is not in its operational position. For example, the opening can be closed when the partition wall (and thereby the medicament container) is in the initial position. The opening for receiving gas can be formed at a proximal end of the gas tube, which proximal end faces the proximal end of the housing.

[0021] In one embodiment, the gas conduit and the opening of the gas tube can be formed and arranged such that the gas conduit and / or the opening is closed when the partition wall is in its initial position and / or in its final position. In other embodiments, e.g. alternatively or additionally, the gas conduit and the opening of the gas tube can be formed and arranged such that the gas conduit and / or the opening is open, e.g. when the partition wall is in its operational position, such that the interior of the gas tube can be in communication with the first chamber via the opening and the gas conduit.

[0022] In one embodiment, the medicament delivery device comprises a closure body, e.g. for closing the gas conduit of the partition wall and the opening of the gas tube. The closure body can be arranged at the housing. The closure body can be arranged to cover the gas conduit of the partition wall and / or the opening of the gas tube, e.g. when the partition wall is in its initial position and / or in its final position, and / or to uncover the gas conduit and / or the opening, e.g. when the partition wall is in its operational position.

[0023] In one embodiment, the pressure source comprises or forms the closure body. This can contribute to a simple design of the medicament delivery device, as a separate closure body does not have to be arranged. This can contribute to an easy, fast and / or cost-effective medicament delivery device.

[0024] In one embodiment, the medicament delivery device comprises at least one first engagement element. The at least one first engagement element can be arranged at the partition wall. In other embodiments, e.g. alternatively or additionally, the medicament delivery device comprises at least one second engagement element. The at least one second engagement element can be arranged at the housing. The first engagement element and the second engagement element can be configured for engaging with each other, e.g. when the partition wall (and optionally the medicament container thereby) reaches its final position. This can prevent the medicament container from moving proximally and / or distally after the dispensing operation of the device has been completed and / or after the injection member has been retracted from the injection site.

[0025] In one embodiment, the drug delivery device comprises an end stop which is coupled, e.g. fixed, to the housing and which is configured to prevent further movement of the partition wall, e.g. when the partition wall reaches its operational position. The end stop can define the operational position of the partition wall. The end stop can be arranged at a distal side of the partition wall, wherein the distal side can face the distal end of the housing and / or be directed away from the proximal end of the housing. The end stop can block further movement of the partition wall in a distal direction or dispensing direction. The end stop can be configured to prevent further movement of the partition wall towards the distal end of the housing or further away from the proximal end of the housing, e.g. when the partition wall reaches or is in its operational position.

[0026] The drug delivery device can comprise a needle as an injection member for injecting the drug into the injection site, wherein the needle can be communicatively coupled to the drug container at an outlet of the drug container. The needle can be configured to pierce the skin of the user. The needle can extend in a direction parallel to an axis of the drug delivery device and / or parallel to the dispensing direction, e.g. along an axis extending from the proximal end to the distal end of the housing. A tip of the needle which is arranged to pierce the skin of the user can be furthest away from the proximal end of the housing and / or define a distal end of the needle. The needle can be in fluid communication with the interior of the drug container, or can be brought into fluid communication with the interior of the drug container, in particular with the reservoir. The needle can be integrated into the drug container. The drug, e.g. a liquid medicament, can be suitably arranged in the interior of the drug container. The drug container can be a syringe, e.g. with a pre-mounted needle such as a staked needle. Alternatively, the drug container can be a cartridge which can have to be brought into fluid communication with the needle, e.g. by piercing a cartridge septum with the needle. Optionally, the drug delivery device can comprise a second needle. The second needle can be used to pierce a container, e.g. a cartridge septum. The first needle, e.g. the needle used to pierce the skin and / or to inject the drug into the injection site, can be in communication with the second needle, e.g. via a (flexible) drug conduit, to guide the drug from the drug container through the second needle towards the first needle.

[0027] In one embodiment, the drug container is a syringe. Alternatively, the drug container can be a cartridge. The drug container can comprise a needle, e.g. the first needle or the second needle, or can be coupled with a needle, e.g. the first needle or the second needle, manually before use of the drug delivery device or automatically when the drug delivery device is used.

[0028] In one embodiment, the drug delivery device comprises a drug container, wherein the drug container comprises a reservoir in which a drug is contained.

[0029] It should be noted that features described above and below in connection with different embodiments or aspects can be combined with each other, even if such combinations are not explicitly disclosed herein above or below. Further features, advantages and particulars of the present disclosure, in particular of the proposed concept, will become clear from the following description of exemplary embodiments in connection with the drawings. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 A side sectional view of an exemplary embodiment of a drug delivery device is shown in an initial state of the drug delivery device.

[0031] Figure 2 A side sectional view of the drug delivery device is shown in an operational state of the drug delivery device. Figure 1

[0032] Figure 3 A side sectional view of an exemplary embodiment of a drug delivery device is shown in an initial state of the drug delivery device. The drug delivery device 20 can be referred to as an auto-operated syringe and / or an auto-injector. The drug delivery device 20 can be a fully functional drug delivery device 20. The drug delivery device 20 can be a single-shot device, i.e. it can be arranged to dispense a dose only once. The drug delivery device 20 can be a disposable drug delivery device 20, that is to say a drug delivery device 20 which is discarded after its use. The drug delivery device 20 can be driven by a gas. In other embodiments, the drug delivery device 20 can be reusable and / or refillable.

[0033] In the drawings, identical elements, identical kinds of elements, and elements acting identically or similarly can bear the same reference signs.

[0034] Figure 1 A side sectional view of an exemplary embodiment of a drug delivery device is shown in an initial state of the drug delivery device. The drug delivery device 20 can be referred to as an auto-operated syringe and / or an auto-injector. The drug delivery device 20 can be a fully functional drug delivery device 20. The drug delivery device 20 can be a single-shot device, i.e. it can be arranged to dispense a dose only once. The drug delivery device 20 can be a disposable drug delivery device 20, that is to say a drug delivery device 20 which is discarded after its use. The drug delivery device 20 can be driven by a gas. In other embodiments, the drug delivery device 20 can be reusable and / or refillable.

[0035] The drug delivery device 20 comprises a housing 22, a pressure arrangement and a plunger arrangement. The housing 22 comprises a distal end 21 and a proximal end 23 facing away from the distal end 21. The distal end 21 can be configured to face towards an injection site during use of the drug delivery device 20. For example, during a dispensing operation of the drug delivery device 20, the distal end 21 of the housing 22 can be arranged on a user’s skin. In this context, the distal end 21 of the housing 22 can be referred to as a support surface. The housing 22 holds and / or can be arranged to hold a drug container 24 inside thereof. If the drug container 24 is arranged within the housing 22, a distal end of the drug container 24 can face towards the distal end 21 of the housing 22 and a proximal end of the drug container 24 can face towards the proximal end 23 of the housing 22.

[0036] ​​The drug container 24 comprises an outlet 28 at or near the dispensing end, i.e. the distal end, of the drug container 24. A needle 30 can be arranged at the distal end of the drug container 24. The needle 30 can open into the outlet 28 and / or can be in communication with the outlet 28. The drug container 24 can comprise a reservoir 26. A drug, i.e. a medicament, e.g. a liquid medicament, can be arranged within the reservoir 26. The reservoir 26 can be fluid-tightly closed by a stopper 32. Thus, the drug can be enclosed by the inner wall of the drug container 24 and the stopper 32. The stopper 32 can be displaceably held in the drug container 24 and can proximally seal the drug container 24. The stopper 32 can be displaced by a pressure member of the pressure arrangement towards the outlet 28 of the drug container 24 to dispense the drug held within the reservoir 26 through the outlet 28 and the needle 30. In particular, the stopper 32 can be movable in a dispensing direction 40 towards the outlet 28. When the stopper 32 is moved by the pressure member in the dispensing direction 40, the drug is dispensed through the outlet 28 and the needle 30. The dispensing direction 40 can be parallel to an axis 41 of the drug delivery device 20. In other embodiments, the drug container 24 can be a bag. In the latter case, the pressure member can press against the outside of a flexible wall of the bag to squeeze the bag and thereby squeeze the drug out of the bag.

[0037] The needle 30 can be an integral part of the drug container 24, e.g. (permanently or releasably) connected to a drug container body of the drug container 24, or separate from the drug container 24. In the first case, the drug container 24 can be a syringe. In the second case, the drug container 24 can be a cartridge. In case a cartridge is used as the drug container 24, initially, the drug container 24 and the needle 30 can be fluidically separated and only during operation of the drug delivery device 20, fluid communication between the reservoir 26 and the needle 30 can be established, e.g. by the needle 30 piercing a septum of the cartridge. Further, instead of only one single needle, two separate needles can be arranged. In this context, the needle 30 for piercing the skin of a user can be referred to as a first needle 30 and a second needle (not shown) can be used for piercing the septum of the cartridge, wherein the first needle 30 and the second needle can be in communication with each other via a drug conduit (not shown).

[0038] The pressure arrangement can comprise a first chamber 42, a second chamber 44, a partition wall 38 sealingly separating the first chamber 42 from the second chamber 44, and a pressure source for providing a predetermined gas pressure. Further, the pressure arrangement can comprise an end stop 46, an enclosure 48 and a fluid passage 50.

[0039] The partition wall 38 can be in its initial position in an initial state of the drug delivery device 20, as Figure 1The partition wall 38 can be movable towards the distal end 21 of the housing 22 for a dispensing operation. The partition wall 38 hermetically separates a first chamber 42 from a second chamber 44. The first chamber 42 and the second chamber 44 are arranged within the housing 22. The first chamber 42 can be arranged between the partition wall 38 and the proximal end 23 of the housing 22. The second chamber 44 can be arranged between the partition wall 38 and the distal end 21 of the housing 22. The partition wall 38 can be configured to hold the drug container 24 so that the drug container 24 can be moved with the partition wall 38 when the partition wall 38 is moved from its initial position to its operational position and when the partition wall 38 is moved from its operational position to its final position. The partition wall 38 can be coupled to the drug container 24 in order to hold the drug container 24 and move it relative to the housing 22. The drug container 24 can also be in its initial position when the partition wall 38 is in its initial position. The drug container 24 can also be in its operational position when the partition wall 38 is in its operational position. The drug container 24 can also be in its final position when the partition wall 38 is in its final position.

[0040] The pressure source can comprise a gas cartridge. The gas cartridge can be pre-filled, for example by the manufacturer of the drug delivery device, with a gas, for example a propellant gas, under high pressure. In other embodiments, the drug delivery device 20 can comprise an electrically driven pump and a battery for driving the pump to generate gas pressure within the gas cartridge. The electrically driven pump can be controlled by a controller (not shown) of the drug delivery device 20. The pressure source can comprise or can form the enclosure 48. In other words, the pressure source can act and / or can be used as the enclosure 48 and / or the pressure source and the enclosure 48 can be embodied by the same entity. In other embodiments, the pressure source can be arranged separate from the enclosure 48. The pressure source can be configured for communication with the first chamber 42 to drive the partition wall 38 towards the distal end 21 of the housing 22 to the operational position of the partition wall 38 for a dispensing operation (see Figure 2 ). The pressure source can be configured for communication with the second chamber 44 after completion of the dispensing operation (not shown) to drive the partition wall 38 from the operational position (see Figure 2 ) towards the proximal end 23 of the housing 22 to the final position of the partition wall 38. The partition wall 38 is configured to hermetically separate the first chamber 42 within the housing 22 from the second chamber 44 within the housing 22 in the initial position, the final position and / or the operational position of the partition wall (38).

[0041] The fluid channel 50 can be formed within and / or by the housing 22, e.g. by a recess within the housing 22. The fluid channel 50 can be in communication with the pressure source. The fluid channel 50 can be configured to enable communication between the pressure source and the first chamber 42 in the initial state of the drug delivery device 20 and to prevent communication between the pressure source and the second chamber 44. The fluid channel 50 can be configured to prevent communication between the first chamber 42 and the pressure source after completion of the dispensing operation and to enable communication of the second chamber 44 with the pressure source. The fluid channel 50 can be configured to distribute gas and thereby gas pressure from the pressure source to areas of the drug delivery device 20 that currently require gas and gas pressure, e.g. the first chamber 42, the second chamber 44 and / or the gas conduit 36. The fluid channel 50 can extend from the pressure source to the first chamber 42 and the second chamber 44. For example, the fluid channel 50 can have three branches. A first branch 52 of the fluid channel 50 can extend to the first chamber 42, a second branch 54 of the fluid channel 50 can extend to the second chamber 44 and a third branch 56 of the fluid channel 60 can extend to the pressure source, e.g. the closure body 48.

[0042] The pressure arrangement can further comprise a first valve 62. The first valve 62 can be arranged at the inlet of the first chamber 42. For example, the first valve 62 can be arranged at the first branch 52 of the fluid channel 50. The first valve 62 can be configured to couple the pressure source to the first chamber 42 via the fluid channel 50, in particular via the first branch 52 of the fluid channel 50, in the initial state of the drug delivery device 20. In particular, the first valve 62 can be configured to couple the pressure source to the first chamber 42 via the fluid channel 50 when the gas pressure within the first chamber 42 is below a predetermined first pressure threshold. The first valve 62 can be a pressure relief valve that closes as soon as the overpressure within the first chamber 42 reaches the first pressure threshold. At the same time, the first valve 62 can allow the overpressure in the first chamber 42 to escape to the atmosphere through the vent opening 58 within the housing 22. The first valve 62 can further be configured to decouple the first chamber 42 from the pressure source after completion of the dispensing operation. Thus, the first valve 62 can be configured to decouple the first chamber 42 from the pressure source when the gas pressure within the first chamber 42 corresponds to or exceeds the first pressure threshold.

[0043] The pressure arrangement can further comprise a second valve 64. The second valve 64 can be arranged at the second branch 54 of the fluid channel 50. The second valve 64 can be configured for decoupling the second chamber 44 from the pressure source in an initial state of the drug delivery device 20. In particular, the second valve 64 can be configured for decoupling the second chamber 44 from the pressure source when the pressure in the fluid channel 50 is below a second predetermined pressure threshold. Additionally, the second valve 64 can be configured for coupling the second chamber 44 to the pressure source when the gas pressure within the fluid channel 50 corresponds to or exceeds the second pressure threshold. The second valve 64 can further be configured for coupling the second chamber 44 to the pressure source after completion of a dispensing operation. The first predetermined pressure threshold can be smaller than the second predetermined pressure threshold or can be identical to the second predetermined pressure threshold.

[0044] The plunger arrangement can comprise a plunger 34 and a gas tube 36, in particular a flexible and / or inflatable gas tube. The plunger 34 can be referred to as a pressure member. The plunger 34 can be arranged between the gas tube 36 of the plunger arrangement and the stopper 32. The plunger 34 can be coupled to or couplable to the stopper 32 and / or the gas tube 36. The plunger 34 can be configured for being pushed by the gas tube 36 and for pushing the stopper 32 towards the distal end 21 of the housing 22. Thus, the plunger 34 can act as a pressure transfer element.

[0045] The flexible gas tube 36 can be inflatable. The gas tube 36 can be coupled to or couplable to the drug container 24. The flexible gas tube 36 can be configured for expelling the drug out of the drug container 24 when pressurized, such that the drug is dispensed from the drug delivery device 20. The gas tube 36 can be pressurized by, for example, filling the gas tube 36 with a gas, e.g. air, from the pressure source. When the gas tube 36 is filled with the gas, the gas tube 36 is inflated and the volume occupied by the gas tube 36 and the length of the gas tube 36 increase. The pressurized gas tube 36 can have the form of a spiral. The gas tube 36 can comprise an opening 78 (see Figure 2 ) at the proximal end 74 of the drug container 24 for receiving the gas. The opening 78 can be closed when the partition wall 38 is not in its operational position, e.g. when the partition wall 38 is in its initial position as shown in Figure 1 .

[0046] The gas tube 36 can be configured for being in communication with the first chamber 42 when the partition wall 38 is in its operational position and for being decoupled from the first chamber 42 when the partition wall 38 is in its initial or final position. For example, the partition wall 38 can comprise a gas conduit 60 which is in communication with the first chamber 42 when the partition wall 38 is in its operational position (see Figure 2The gas conduit 60 couples the first chamber 42 in communication with the gas tube 36 when the partition wall 38 is in its operational position. The gas conduit 60 can be closed when the partition wall 38 is not in its operational position. Thus, the gas tube 36 can not be pressurized when the partition wall 38 and, thus, the drug container 24 are not in their operational position. In particular, the gas conduit 60 and the opening 78 of the gas tube 36 can be formed and arranged such that the gas conduit 60 and / or the opening 78 are closed when the partition wall 38 is in its initial position and / or final position and open when the partition wall 38 is in its operational position such that the interior of the gas tube 36 can be in communication with the first chamber 42 via the opening 78 and the gas conduit 60. For example, a closure body 48 can be configured for closing the gas conduit 60 and the opening 78 of the gas tube 36 of the partition wall 38 when the partition wall 38 and the drug container 24 are in their initial position and / or final position. The closure body 48 can be arranged at the housing 22. The closure body 48 can cover the gas conduit 60 and the opening 78 of the gas tube 36 of the partition wall 38 when the partition wall 38 is in its initial position and / or final position and can uncover the gas conduit 60 and the opening 78 when the partition wall 38 is in its operational position.

[0047] The gas tube 36 can act on the drug container 24 such that the drug can be expelled from the drug container 24 by the gas tube. For example, the gas tube 36 can act on a pressure member such that the pressure member can expel the drug from the reservoir 26. For example, the gas tube 36 can push the pressure member in the dispensing direction 40 towards the distal end 21 of the housing 22 when pressurized. The pressure member can be the stopper 32 or the plunger 34 or can comprise the stopper 32 and / or the plunger 34.

[0048] The drug delivery device 20 can comprise a first engagement element 70 arranged at the partition wall 38 and a second engagement element 72 arranged at the housing 22. The first engagement element 70 and the second engagement element 72 are configured for engaging with each other in case the partition wall 38 and, thus, the drug container 24 reach their final position (not shown).

[0049] The drug delivery device 20 can comprise an end stop 46 coupled to the housing 22. The end stop 46 can be arranged at a distal side of the partition wall 38. The end stop 46 can be configured for preventing the partition wall 38 from moving further towards the distal end 21 of the housing 22 when the partition wall 38 reaches its operational position. Thus, the end stop 46 can define the operational position of the partition wall 38.

[0050] The drug delivery device 20 can comprise a cap (not shown). The cap can be arranged at the dispensing end of the needle 30. The cap can be detachably connected to the rest of the drug delivery device 20, for example to the housing 22. The cap can cover the tip of the needle 30.

[0051] Figure 1 An initial state of the drug delivery device 20 is shown before the needle 30 is inserted into the injection site and before the drug is injected into the injection site. When the drug delivery device 20 is activated, compressed gas (e.g. air) flows through the fluid path 50 and fills the first chamber 42. Due to the corresponding overpressure in the first chamber 42, the partition wall 38 can be moved in the dispensing direction 40 and thus move the drug container 24 into its operating position (see Figure 2 ). When the partition wall 38 and the drug container 24 are moved from their initial position to their operating position, the injection member is brought into contact with the injection site. For example, in case the needle 30 is the injection member, the needle 30 can pierce the skin of the user when the partition wall 38 and the drug container 24 are moved from their initial position to their operating position.

[0052] Figure 2 A side sectional view of the drug delivery device is shown in an operating state of the drug delivery device 20 Figure 1 . In the operating state, the needle 30 is inserted into the injection site and the drug is injected into the injection site.

[0053] When the partition wall 38 and the drug container 24 are moved from their initial position (see Figure 1 ) to Figure 2As soon as the plunger 34 reaches its distal position (which can be its end position), the overpressure in the first chamber 42 continues to build up. When the overpressure within the first chamber 42 reaches a predetermined first pressure threshold, the first valve 62 closes the first branch 52. The closing of the first valve 62 and the first branch 52 can cause an overpressure to build up in the fluid channel 50 upstream of the second valve 64. When the overpressure in the fluid channel 50 reaches a second predetermined pressure threshold, the second valve 64 can open, so that the second chamber 44 can be filled with gas. If only atmospheric pressure is present in the first chamber 42 and if the vent opening 58 is permanently open, the gas pressure in the second chamber 44 can be sufficient to press the partition walls 38 together with the drug container 24 in a direction opposite to the dispensing direction 40 into their final positions, which can exceed their initial positions (in other words: the final positions can be offset proximally from the initial positions). During this movement, the needle 30 can be withdrawn from the skin. In the final positions, the partition walls 38 can be locked by the engagement elements 70, 72 engaging each other. For example, the first engagement element 70 can snap behind the second engagement element 72 when the partition walls 38 reach their final positions. The partition walls 38 and the drug container 24 can be locked (e.g., to prevent movement distally and / or proximally) and thereby fixed in their final positions to permanently protect the needle after use of the needle 30.

[0054] The proposed automatic injector can be gas-driven with automatic needle insertion and / or automatic needle retraction. However, it should be noted that the proposed movability of the partition walls also provides other options and is not limited to automatic injectors with needle injection and / or needle withdrawal. Rather, the partition walls can be used to selectively couple the needle cannula to a pressure source to deploy the needle cannula to cover the needle in its final position.

[0055] 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. In the broadest sense, an active pharmaceutical ingredient ("API") is a chemical structure intended for 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. The drug or medicament can be used for a limited duration, or on a regular basis for chronic disorders.

[0056] As described below, the drug or medicament can include at least one API, or combinations thereof, in different types of pharmaceutical formulations, for the treatment of one or more diseases. Examples of APIs can 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 can be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0057] The drug or medicament can be contained in a primary package or "drug reservoir" suitable for use with a drug delivery device. The drug reservoir 101a can be, for example, a cartridge, syringe, reservoir, or other rigid or flexible vessel (bag) configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. For example, in some cases, the chamber can be designed to store a drug for at least one day (e.g., 1 day to at least 30 days). In some cases, the chamber can be designed to store a drug for about 1 month to about 2 years. Storage can occur at room temperature (e.g., about 20°C) or refrigerated temperatures (e.g., about - 4°C to about 4°C). In some cases, the drug reservoir can be or can include a dual-chamber cartridge configured to separately store two or more components of a pharmaceutical formulation to be administered (e.g., an API and a diluent, or two different drugs), one in each chamber. In such cases, the two chambers of the dual-chamber cartridge can 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 can be configured such that they are in fluid communication with each other (e.g., by a conduit between the two chambers) and allow the user to mix the two components when desired prior to dispensing. Alternatively, or additionally, the two chambers can be configured to allow mixing as the components are being dispensed into the human or animal body.

[0058] 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), thromboembolic disorders (such as deep vein or pulmonary thromboembolism). Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, tumour, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those described in, e.g., the

[0059] 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 1 (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” refer to a polypeptide which has a molecular structure which can formally be derived by deleting and / or exchanging at least one amino acid residue occurring in a naturally occurring peptide, and / or by adding at least one amino acid residue, from the structure of the naturally occurring peptide (e.g., the structure of human insulin). The added and / or exchanged amino acid residue can be a codable amino acid residue or other naturally occurring residue or a purely synthetic amino acid residue. 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 can formally be derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin), wherein one or more organic substituent (e.g., a fatty acid) is bound to one or more amino acids. Alternatively, one or more amino acids occurring in the naturally occurring peptide can have been deleted and / or replaced by other amino acids, including non-codable amino acids, or amino acids, including non-codable amino acids, have been added to the naturally occurring peptide.

[0060] Examples of insulin analogues are Gly(A21 ), Arg(B25), Arg(B26) 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, Val or Ala and wherein in position B29 Lys can be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0061] 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 Lys B28Pro B29 human insulin; B28-N-palmitoyl-Lys B28Pro B29 human insulin; B30-N-myristoyl-Thr B29Lys B30 insulin; B30-N-palmitoyl-Thr B29Lys B30 insulin; B29-N- (N-palmitoyl-Y-glutamyl)-des(B30) human insulin, B29-N-ooxocarboxypentadecanoyl-Y- glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N- (N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(ooxocarboxyheptadecanoyl)-des(B30) and B29-N-(ooxocarboxyheptadecanoyl) human insulin.

[0062] Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lyxumia®, Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide produced in the salivary gland of the Gila monster, Liraglutide (Victoza®), Solabegron, 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, MAR 709, 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.

[0063] Examples of oligonucleotides are, for example: Kynamro®, a cholesteryl-reducing antisense therapeutic for the treatment of familial hypercholesterolemia, or RG012 for the treatment of Alport syndrome.

[0064] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Teneligliptin, Saxagliptin, Berberine.

[0065] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and antagonists thereof, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, menotropin), somatotropin (growth hormone), desmopressin, terlipressin, goserelin, triptorelin, leuprolide, buserelin, nafarelin and goserelin.

[0066] Examples of polysaccharides include glucosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or ultra-low molecular weight heparin or derivatives thereof, or sulfated polysaccharides (e.g. polysulfated forms of the above polysaccharides), and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.

[0067] The term "antibody", as used herein, refers to an immunoglobulin molecule or an antigen binding 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 a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a de-immunized antibody or a humanized antibody, a fully human antibody, a non-human, e.g., murine, antibody, or a 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 the Fc receptor. For example, the antibody can be of an isotype or subtype that 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 antigen binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or dual variable region antibody-like binding proteins with cross-over binding region orientation (CODV).

[0068] The term "fragment" or "antibody fragment" refers to polypeptides derived from an antibody polypeptide molecule (e.g., an antibody heavy and / or light chain polypeptide) that do not comprise a full-length antibody polypeptide, but that still comprise 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 application 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.

[0069] The term "complementarity determining region" or "CDR" refers 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 framework regions by 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 participate directly in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with an antigen.

[0070] 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).

[0071] Further examples of APIs for preventing hemophilia A or B (with or without inhibitors) include siRNAs targeting antithrombin. An example of an siRNA targeting antithrombin is Fitusiran. The terms "preventing" and "prophylactic treatment" are used interchangeably herein.

[0072] It is also contemplated to use a pharmaceutically acceptable salt of any of the APIs described herein for use in a medicament or pharmaceutical agent in a drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts.

[0073] Those skilled in the art will appreciate that modifications (additions and / or removals) can be made to the different components of the APIs, pharmaceutical formulations, apparatuses, methods, systems and embodiments described herein without departing from the entire scope and spirit of the present application, which encompass such modifications and any and all equivalents thereof.

[0074] Example drug delivery devices can involve needle-based injection systems as described in Table 1 of Section 5.2 of ISO 11608-1 :2014(E). As described in ISO 11608-1 :2014(E), needle-based injection systems can be broadly classified into multi-dose container systems and single-dose (partial or complete emptying) container systems. The container can be a replaceable container or an integrated non-replaceable container.

[0075] As further described in ISO 11608-1 :2014(E), a multi-dose container system can involve a needle-based injection device with replaceable containers. In such a system, each container holds multiple doses, which can be of fixed or variable size (pre-set by the user). Another multi-dose container system can involve a needle-based injection device with integrated non-replaceable containers. In such a system, each container holds multiple doses, which can be of fixed or variable size (pre-set by the user).

[0076] As further described in ISO 11608-1 :2014(E), a single-dose container system can involve a needle-based injection device with replaceable containers. In one example of such a system, each container holds a single dose, where the entire deliverable volume is expelled (full emptying). In another example, each container holds a single dose, where a portion of the deliverable volume is expelled (partial emptying). As also described in ISO 11608-1 :2014(E), a single-dose container system can involve a needle-based injection device with integrated non-replaceable containers. In one example of such a system, each container holds a single dose, where the entire deliverable volume is expelled (full emptying). In another example, each container holds a single dose, where a portion of the deliverable volume is expelled (partial emptying).

[0077] Fomivirsen as an API of the medicament in the device

[0078] Fomivirsen is a synthetic, chemically modified double-stranded small interfering RNA (siRNA) oligonucleotide covalently linked to a triantennary N-acetyl-galactosamine (GalNAc) ligand targeting AT3 mRNA in the liver, thereby inhibiting 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 fomivirsen are linked by 3’-5’ phosphodiester or phosphorothioate linkages, forming a sugar-phosphate backbone of the oligonucleotide.

[0079] The sense and antisense strands contain 21 and 23 nucleotides, respectively. The 3’ end of the sense strand is conjugated via a phosphodiester linkage to a GalNAc-containing moiety (referred to herein as L96). 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 are hybridized to 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. Patent 9,127,274, U.S. Patent 11,091,759, US2020 / 0163987 Al, and WO 2019 / 014187, the entire contents of each of which are expressly incorporated herein by reference.

[0080] The two nucleotide strands of Fomivirsen are shown below:

[0081] 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

[0082] 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),

[0083] wherein

[0084] Af = 2’ -deoxy- 2’-fluoroadenosine

[0085] Cf = 2’ -deoxy- 2’-fluorocytidine

[0086] Gf = 2’ -deoxy- 2’-fluoroguanosine

[0087] Uf = 2’ -deoxy- 2’-fluorouridine

[0088] Am = 2’-O-methyladenosine

[0089] Cm = 2’-O-methylcytidine

[0090] Gm = 2’-O-methylguanosine

[0091] Um = 2’-O-methyluridine

[0092] “-” (hyphen) = 3’-5’ phosphodiester linkage sodium salt

[0093] " -ps- " = 3'-5' phosphorothioate linkage sodium salt

[0094] and wherein L96 has the following formula:

[0095] (I).

[0096] As used herein, the terms "2' -deoxy- 2' -fluoro-adenosine" and "2' -fluoro- adenosine" can be used interchangeably.

[0097] As used herein, the terms "2' -deoxy- 2' -fluoro-cytidine" and "2' -fluoro- cytidine" can be used interchangeably.

[0098] As used herein, the terms "2' -deoxy- 2' -fluoro-guanosine" and "2' -fluoro- guanosine" can be used interchangeably.

[0099] As used herein, the terms "2' -deoxy- 2' -fluoro-uridine" and "2' -fluoro- uridine" can be used interchangeably.

[0100] The expanded structural formula, molecular formula, and molecular weight of FeneXylan are shown in Figure 3 .

[0101] The structure of FeneXylan can also be described with the following figure, where X is O:

[0102] .

[0103] FeneXylan is shown in Figure 3 as a sodium salt.

[0104] In some embodiments, the device delivers FeneXylan in an aqueous solution, wherein the concentration of FeneXylan is 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 the recited ranges and values are intended to be part of this disclosure. In addition, ranges using any of the stated values as endpoints are intended to be included in the disclosure. In further embodiments, the pharmaceutical formulation comprises FeneXylan 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, FeneXylan is provided in an aqueous solution at a concentration of about 100 mg / mL.

[0105] The term "delivering" is intended to mean "administering."

[0106] Unless specifically stated or otherwise evident from context, as used herein, the term "about" or "approximately" means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined. For example, "about" or "approximately" can mean within 10% (i.e., ±10%). Thus, "about" or "approximately" 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 the disclosure, the meaning of "about" or "approximately" should be assumed to be within an acceptable error range of the specific value, unless otherwise stated.

[0107] While the nonotuximab dose weights described herein refer to the weight of nonotuximab free acid (the active moiety), the administration of nonotuximab to a patient herein refers to the administration of nonotuximab sodium (drug substance) provided in a pharmaceutically suitable aqueous solution (e.g., phosphate buffered saline at physiological pH). For example, about 100 mg / mL nonotuximab means that each mL contains about 100 mg nonotuximab free acid (equivalent to about 106 mg nonotuximab sodium, drug substance). Unless otherwise stated, the nonotuximab weights listed in the disclosure are the weights of nonotuximab free acid (the active moiety).

[0108] In some embodiments, the pharmaceutical formulation in the device comprises nonotuximab in phosphate buffered saline. The phosphate concentration in the solution can 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) at a pH of about 6.0-8.0. The pharmaceutical formulation herein can include a stabilizer, such as EDTA. The pharmaceutical formulation can be preservative-free. In some embodiments, the nonotuximab pharmaceutical formulation in the device is preservative-free and comprises, consists of, or consists essentially of about 100 mg nonotuximab per mL of about 5 mM phosphate buffered saline (PBS) solution. In some embodiments, the nonotuximab pharmaceutical formulation in the device is preservative-free and comprises, consists of, or consists essentially of nonotuximab in about 5 mM phosphate buffered saline (PBS) solution. The PBS solution consists of sodium chloride, sodium phosphate dibasic (heptahydrate), and sodium phosphate monobasic (monohydrate). The pH of the pharmaceutical formulation can be adjusted to about 7.0 or about 7.1 using sodium hydroxide solution and dilute phosphoric acid.

[0109] In some embodiments, the nonacoxib pharmaceutical formulation in a device for subcutaneous delivery contains nonacoxib in 5 mM phosphate buffered saline at pH 7.0 with 0.64 mM NaH2PO4, 4.36 mM Na2HPO4, and 84 mM NaCl. In certain embodiments, the nonacoxib solution pharmaceutical formulation for subcutaneous delivery is shown in Table 1 below:

[0110] Table 1. Exemplary nonacoxib pharmaceutical formulations

[0111]

[0112] q.s.: q.s.

[0113] In some embodiments, a nonacoxib solution pharmaceutical formulation for subcutaneous delivery with a device can be described as shown in Table 2 below.

[0114] Table 2. Exemplary nonacoxib pharmaceutical formulations

[0115]

[0116] In some embodiments, the device can be used to deliver a single dose of nonacoxib, wherein the single dose comprises about 20 to about 80 mg of nonacoxib (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 can be used to deliver a single dose of nonacoxib, wherein the single dose comprises about 1 to about 30 mg of nonacoxib (e.g., about 1.25 mg, about 2.5 mg, about 5 mg, about 10 mg, about 20 mg, or about 30 mg).

[0117] In one embodiment, the device can be used to deliver a single dose of about 80 mg of nonacoxib. In one embodiment, the device can be used to deliver a single dose of about 50 mg of nonacoxib. In one embodiment, the device can be used to deliver a single dose of about 20 mg of nonacoxib. In one embodiment, the device can be used to deliver a single dose of about 30 mg of nonacoxib. In one embodiment, the device can be used to deliver a single dose of about 10 mg of nonacoxib. In one embodiment, the device can be used to deliver a single dose of about 5 mg of nonacoxib. In one embodiment, the device can be used to deliver a single dose of about 2.5 mg of nonacoxib. In one embodiment, the device can be used to deliver a single dose of about 1.25 mg of nonacoxib.

[0118] In some embodiments, a single dose of nonaciximab can be delivered in a delivery volume of about 0.5 mL to about 1 mL (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 can also be used.

[0119] In one embodiment, the device can be used to deliver a single dose of about 80 mg of nonaciximab in about 0.8 mL (about 100 mg nonaciximab / mL). In one embodiment, the device can be used to deliver a single dose of about 50 mg of nonaciximab in about 0.5 mL (about 100 mg nonaciximab / mL). In one embodiment, the device can be used to deliver a single dose of about 20 mg of nonaciximab in about 0.5 mL (about 40 mg nonaciximab / mL). In one embodiment, the device can be used to deliver a single dose of about 30 mg of nonaciximab in about 0.5 mL (about 60 mg nonaciximab / mL). In one embodiment, the device can be used to deliver a single dose of about 10 mg of nonaciximab in about 0.5 mL (about 20 mg nonaciximab / mL). In one embodiment, the device can be used to deliver a single dose of about 5 mg of nonaciximab in about 0.5 mL (about 10 mg nonaciximab / mL). In one embodiment, the device can be used to deliver a single dose of about 2.5 mg of nonaciximab in about 0.5 mL (about 5 mg nonaciximab / mL). In one embodiment, the device can be used to deliver a single dose of about 1.25 mg of nonaciximab in about 0.5 mL (about 2.5 mg nonaciximab / mL).

[0120] In one embodiment, the device delivers nonaciximab in a prophylactically effective amount to provide prophylactic treatment of hemophilia (e.g., hemophilia A or B with or without inhibitors) in a patient in need thereof (e.g., a patient with or without inhibitors of hemophilia A or B). A "prophylactically effective amount" refers to an amount of nonaciximab that helps a patient with hemophilia A or B (with or without inhibitors) achieve a desired clinical endpoint, such as a reduction in annualized bleeding rate (ABR), annualized joint bleeding rate (AjBR), annualized spontaneous bleeding rate (AsBR), or frequency of bleeding episodes. As used herein, in the context of nonaciximab, the term "treatment" includes prophylactic treatment of a disease and refers to achieving a desired clinical endpoint.

[0121] An inhibitor A or B patient with hemophilia refers to a patient who has developed alloantibodies against a factor they have previously received (e.g., Factor VIII for hemophilia A patients or Factor IX for hemophilia B patients). Inhibitor A or B patients with hemophilia can be difficult to treat with replacement clotting factor therapy. A non-inhibitor patient refers to a patient who does not have such alloantibodies. The present methods of treatment can be beneficial for inhibitor A patients with hemophilia as well as inhibitor B patients with hemophilia.

[0122] As used herein, a patient with "hemophilia A or B (with or without inhibitors)" refers to either 1) an inhibitor A patient with hemophilia, or 2) an inhibitor B patient with hemophilia, 3) a non-inhibitor A patient with hemophilia, or 4) a non-inhibitor B patient with hemophilia. As used herein, a patient refers to a human patient. A patient can also refer to a human subject.

[0123] In some embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 50 mg once every two months (or every eight weeks). In other embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 50 mg once a month (or every four weeks). In yet other embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 80 mg once every two months (or every eight weeks). In yet other embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 80 mg once a month (or every four weeks). In yet other embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 20 mg once every two months (or every eight weeks). In yet other embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 20 mg once a month (or every four weeks). In yet other embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 10 mg once a month (or every four weeks). In yet other embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 30 mg once a month (or every four weeks). In yet other embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 5 mg once a month (or every four weeks). In yet other embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 2.5 mg once a month (or every four weeks). In yet other embodiments, the device can be used for prophylactic treatment of a patient with hemophilia A or B (with or without inhibitors) with nonacog alfa at a subcutaneous dose of about 1.25 mg once a month (or every four weeks).

[0124] Accordingly, provided herein is a method of prophylactically treating a patient having hemophilia A or B (with or without an inhibitor) comprising subcutaneously delivering to the patient in need thereof a prophylactically effective amount of fitusiran using the device. The prophylactically effective amount of fitusiran can be any of the doses 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 can 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 can be delivered monthly (or every four weeks) or every two months (or every eight weeks). The fitusiran can be delivered in a delivery volume of about 0.5 mL to about 1 mL (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).

[0125] As an example, the method of prophylactically treating a patient having hemophilia A or B (with or without an inhibitor) can comprise subcutaneously delivering to the patient in need thereof about 50 mg of fitusiran monthly (or every four weeks) or every two months (or every eight weeks) using the device. The about 50 mg of fitusiran can be delivered in about 0.5 mL PBS (concentration of about 100 mg fitusiran / mL).

[0126] Further, provided herein is a method of reducing the frequency of bleeding episodes in a patient having hemophilia A or B (with or without an inhibitor) comprising subcutaneously delivering to the patient in need thereof a prophylactically effective amount of fitusiran using the device. The prophylactically effective amount of fitusiran can be any of the doses 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 can 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 can be delivered monthly (or every four weeks) or every two months (or every eight weeks). The fitusiran can be delivered in a delivery volume of about 0.5 mL to about 1 mL (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).

[0127] As an example, the method of reducing the frequency of bleeding episodes in a patient having hemophilia A or B (with or without an inhibitor) can comprise subcutaneously delivering to the patient in need thereof about 50 mg of fitusiran monthly (or every four weeks) or every two months (or every eight weeks) using the device. The about 50 mg of fitusiran can be delivered in about 0.5 mL PBS (concentration of about 100 mg fitusiran / mL).

[0128] Further provided herein is a method of reducing ABR in a patient having hemophilia A or B, with or without an inhibitor, comprising subcutaneously delivering to the patient in need thereof a prophylactically effective amount of emicizumab using the device. The prophylactically effective amount of emicizumab can be any of the doses 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 emicizumab can 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 emicizumab can be delivered once monthly (or every four weeks) or once every two months (or every eight weeks). The emicizumab can be delivered in a delivery volume of about 0.5 mL to about 1 mL (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).

[0129] As an example, the method of reducing ABR in a patient having hemophilia A or B, with or without an inhibitor, can comprise subcutaneously delivering to the patient in need thereof about 50 mg of emicizumab once monthly (or every four weeks) or once every two months (or every eight weeks) using the device. The about 50 mg of emicizumab can be delivered in about 0.5 mL PBS (concentration of about 100 mg emicizumab / mL).

[0130] Further provided herein is a method of reducing AjBR in a patient having hemophilia A or B, with or without an inhibitor, comprising subcutaneously delivering to the patient in need thereof a prophylactically effective amount of emicizumab using the device. The prophylactically effective amount of emicizumab can be any of the doses 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 emicizumab can 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 emicizumab can be delivered once monthly (or every four weeks) or once every two months (or every eight weeks). The emicizumab can be delivered in a delivery volume of about 0.5 mL to about 1 mL (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).

[0131] As an example, the method of reducing AjBR in a patient having hemophilia A or B, with or without an inhibitor, can comprise subcutaneously delivering to the patient in need thereof about 50 mg of emicizumab once monthly (or every four weeks) or once every two months (or every eight weeks) using the device. The about 50 mg of emicizumab can be delivered in about 0.5 mL PBS (concentration of about 100 mg emicizumab / mL).

[0132] Further, provided herein is a method of reducing AsBR in a patient having hemophilia A or B, with or without an inhibitor, comprising subcutaneously delivering to the patient in need thereof a prophylactically effective amount of fitusiran with the device. The prophylactically effective amount of fitusiran can 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 can 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 can be delivered once a month (or every four weeks) or once every two months (or every eight weeks). The fitusiran can be delivered in a delivery volume of about 0.5 mL to about 1 mL (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).

[0133] As an example, the method of reducing AsBR in a patient having hemophilia A or B, with or without an inhibitor, can comprise subcutaneously delivering to the patient in need thereof about 50 mg of fitusiran once a month (or every four weeks) or once every two months (or every eight weeks) with the device. The about 50 mg of fitusiran can be delivered in about 0.5 mL PBS (concentration of about 100 mg fitusiran / mL).

[0134] Any of the applications described herein are not limited by the description of the exemplary embodiments. Rather, the applications, and associated disclosures, include any novel feature or any combination of features, particularly in view of the patent claims, and include any and all equivalents thereof. The applications are not limited to the examples described, but rather, the full scope of the applications should be determined from the patent claims.

[0135] Reference numerals

[0136] 20 drug delivery device

[0137] 21 distal end of housing

[0138] 22 housing

[0139] 23 proximal end of housing

[0140] 24 drug container

[0141] 26 reservoir

[0142] 28 outlet

[0143] 30 needle

[0144] 32 stopper

[0145] 34 plunger

[0146] 36 gas tube

[0147] 38 partition wall

[0148] 40 dispensing direction

[0149] 41 axis

[0150] 42 first chamber

[0151] 44 second chamber

[0152] 46 end stop

[0153] 48 closure body

[0154] 50 fluid channel

[0155] 52 first branch

[0156] 54 second branch

[0157] 56 third branch

[0158] 58 vent opening

[0159] 60 gas conduit

[0160] 62 first valve

[0161] 64 second valve

[0162] 70 first engagement element

[0163] 72 second engagement element

[0164] 74 proximal end of the medicament container

[0165] 76 distal end of the medicament container

[0166] 78 opening.

Claims

1. A drug delivery device (20), comprising: A housing (22) for containing a drug container (24); A partition wall (38) is in an initial position in the initial state of the drug delivery device (20), the partition wall (38) is movable relative to the housing (22) for dispensing operations, and the partition wall (38) sealably separates the first chamber (42) in the housing (22) from the second chamber (44) in the housing (22); as well as A pressure source is configured to provide a predetermined gas pressure and to communicate with the first chamber (42) to drive the partition wall (38) to the operating position of the partition wall (38) for the dispensing operation, and to communicate with the second chamber (44) after the dispensing operation is completed to drive the partition wall (38) from the operating position to the final position of the partition wall (38).

2. The drug delivery device as claimed in claim 1, wherein, The partition wall (38) is configured to hold the drug container (24) such that the drug container (24) moves together with the partition wall (38) when the partition wall (38) moves from its initial position to its operating position and when the partition wall (38) moves from its operating position to its final position.

3. The drug delivery device (20) as claimed in any one of claims 1 or 2, comprising a fluid channel (50) within the housing (22), the fluid channel (50) being in communication with the pressure source and configured for use with respect to the pressure source. In this initial state, communication between the pressure source and the first chamber (42) is established, and communication between the pressure source and the second chamber (44) is prevented; and After the distribution operation is completed, the connection between the first chamber (42) and the pressure source is prevented and the connection between the second chamber (44) and the pressure source is realized.

4. The drug delivery device (20) as claimed in claim 3, comprising: A first valve (62) is configured to connect the pressure source to the first chamber (42) via the fluid passage (50) in the initial state of the drug delivery device (20), and to disconnect the first chamber (42) from the pressure source after the dispensing operation is completed; as well as A second valve (64) is configured to disconnect the second chamber (44) from the pressure source in the initial state and to reconnect the second chamber (44) to the pressure source after the dispensing operation is completed.

5. The drug delivery device (20) as claimed in claim 4, wherein, The first valve (62) is configured to connect the pressure source to the first chamber (42) via the fluid passage (50) when the gas pressure in the first chamber (42) is lower than a predetermined first pressure threshold, and to disconnect the first chamber (42) from the pressure source when the gas pressure in the first chamber (42) corresponds to or exceeds the first pressure threshold; and / or The second valve (64) is configured to disconnect the second chamber (44) from the pressure source when the pressure in the fluid passage (50) is lower than a predetermined second pressure threshold, and to connect the second chamber (44) to the pressure source when the gas pressure in the fluid passage (50) corresponds to or exceeds the second pressure threshold.

6. The drug delivery device (20) as described in any of the preceding claims, comprising: A flexible gas tube (36) is connected to or can be connected to the drug container (24) and is configured to expel the drug from the drug container (24) when pressurized, so that the drug is dispensed from the drug delivery device (20).

7. The drug delivery device (20) as claimed in claim 6, wherein, The gas tube (36) is configured to communicate with the first chamber (42) when the partition wall (38) is in its operating position, and to disconnect from the first chamber (42) when the partition wall (38) is in its initial and / or final position.

8. The drug delivery device (20) as claimed in claim 7, wherein, The partition wall (38) includes a gas conduit (60) that connects the first chamber (42) in communication with the gas tube (36) when the partition wall (38) is in its operating position.

9. The drug delivery device (20) as claimed in any one of claims 7 or 8, wherein, The gas pipe (36) includes an opening (78) for receiving gas when the partition wall (38) is in its operating position.

10. The drug delivery device (20) as claimed in claims 8 and 9, wherein, The opening (78) of the gas conduit (60) and the gas tube (36) can be formed and arranged such that when the partition wall (38) is in its initial and / or final position, the gas conduit (60) and / or the opening (78) are closed, and when the partition wall (38) is in its operating position, the gas conduit (60) and the opening (78) are open, so that the interior of the gas tube (36) can communicate with the first chamber (42) via the opening (78) and the gas conduit (60).

11. The drug delivery device (20) of claim 10, comprising a closure (48) for closing the opening (78) of the gas conduit (60) and the gas tube (36) of the partition wall (38), the closure (48) being disposed in the housing (22) and covering the opening (78) of the gas conduit (60) and the gas tube (36) of the partition wall (38) when the partition wall (38) is in its initial and / or final position, and exposing the gas conduit (60) and the opening (78) when the partition wall (38) is in its operating position.

12. The drug delivery device (20) as claimed in claim 11, wherein, The pressure source includes or forms the enclosure (48).

13. The drug delivery device (20) as claimed in any of the preceding claims, comprising: At least one first engaging element (70) is disposed at the partition wall (38); as well as At least one second engaging element (72) is disposed at the housing (22). The first and second engaging elements (70, 72) are configured to engage with each other when the partition wall (38) and thus the drug container (24) reach their final positions.

14. The drug delivery device (20) as claimed in any of the preceding claims includes an end stop (46) coupled to the housing (22) and configured to prevent further movement of the partition wall (38) when the partition wall (38) reaches its operating position.

15. The drug delivery device (20) as claimed in any of the preceding claims, comprising the drug container (24), wherein, The drug container (24) includes a reservoir (26) in which the drug is contained.

16. The drug delivery device (20) as described in any of the preceding claims, wherein, The first chamber (42) is disposed between the partition wall (38) and the proximal end of the housing (22), and the second chamber (44) is disposed between the partition wall (38) and the distal end of the housing (22).

17. The drug delivery device (20) as claimed in any of the preceding claims, wherein, The partition wall (38) is configured to sealably separate the first chamber (42) within the housing (22) from the second chamber (44) within the housing (22) in the initial position, final position and operating position of the partition wall (38).

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