Patent ID: 12194274

DETAILED DESCRIPTION

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

In combination with a specific medicament, the presently described devices may also be customized in order to operate within required specifications. For example, the device may be customized to inject a medicament within a certain time period (e.g., about 3 to about 20 seconds for auto-injectors, and about 10 minutes to about 60 minutes for a large volume device). Other specifications can include a low or minimal level of discomfort, or to certain conditions related to human factors, shelf-life, expiry, biocompatibility, environmental considerations, etc. Such variations can arise due to various factors, such as, for example, a drug ranging in viscosity from about 3 cP to about 50 cP. Consequently, a drug delivery device will often include a hollow needle ranging from about 25 to about 31 Gauge in size. Common sizes are 27 and 29 Gauge.

FIGS.1to10show a medicament delivery device10, which in the exemplary embodiment comprises a bolus injector device, according to a first embodiment. The medicament delivery device10may be in the form of a large volume device.

The medicament delivery device10comprises a housing11, a needle12and a medicament delivery mechanism comprising a needle actuating mechanism13and a dispensing mechanism14. The medicament delivery device10further comprises an actuator15that is moveable relative to the housing11.

The housing11comprises a distal portion16and a proximal portion17. The term “distal” refers to a location that is relatively closer to a site of injection and the term “proximal” refers to a location that is relatively further away from the injection site.

The distal portion16of the housing11comprises a cylindrical peripheral wall18and an end wall19that together have a generally U-shaped cross-section. The distal portion16of the housing11further comprises a cylindrical internal wall16A that is arranged concentrically with the cylindrical peripheral wall18of the distal portion16. The proximal portion17of the housing11comprises a cylindrical peripheral wall20and an end wall21that together have a generally U-shaped cross-section. The proximal portion17of the housing11comprises a cylindrical internal wall17A that is arranged concentrically with the cylindrical peripheral wall20of the proximal portion17.

The peripheral wall18of the distal portion16of the housing11is slidably received in the peripheral wall20of the proximal portion17such that the end wall19of the distal portion16is spaced from the end wall21of the proximal portion17and a recess22is formed therebetween. The distal and proximal portions16,17of the housing11together form a generally cylindrical shape that has a central axis (see the dashed line A-A inFIGS.2and7).

The end wall19of the distal portion16has an outer surface19A and an inner surface19B and the end wall21of the proximal portion17has an outer surface21A and an inner surface21B. One or both of the outer surfaces19A,21A of the end walls19,21of the distal and proximal portions16,17may be substantially flat.

The outer surface19A of the end wall19of the distal portion16comprises an adhesive layer (not shown) that is initially covered by a label (not shown). In use, the label is removed from the adhesive layer and then the adhesive layer is stuck to the patient's skin at the injection site of the patient such that the end wall19of the distal portion16is adhered to the injection site.

The dispensing mechanism14comprises a medicament reservoir23, a dispensing member24, a dispensing biasing member25and a dispensing lock (not shown).

The medicament reservoir23is in the form of a flexible bag23. The flexible bag23is disposed in the recess22in the housing11and abuts the inner surface19B of the end wall19of the distal portion16.

The flexible bag23has a first end23A and a second end23B. The wall26of the flexible bag23is deformable. The flexible bag23extends at least partially about the central axis A-A of the housing11. The flexible bag23may, for example, be C-shaped or U-shaped.

The flexible bag23is fluidly connected to an aperture18A in the peripheral wall18of the distal portion16. The aperture18A forms a filling port18A that allows for the flexible bag23to be filled with medicament through the peripheral wall18of the distal portion16. The flexible bag23and/or the aperture18A may comprise a one-way valve (not shown) that is configured to prevent medicament from flowing out of the flexible bag23via the aperture18A. Alternatively, or additionally, a bung (not shown) may be provided that is inserted into the aperture18A to seal the aperture18A after the flexible bag23has been filled with medicament.

The dispensing member24is in the form of a roller24. The roller24may be cylindrical. The roller24is disposed in the recess22in the housing11such that the flexible bag23is located between the roller24and the inner surface19B of the end wall19of the distal portion16. The roller24is configured to move about a first rotational axis in an arcuate path (shown by arrow ‘X’ inFIG.9) from the first end23A to the second end23B of the flexible bag23. The first rotational axis may be common with the central axis A-A of the housing11.

The roller24is rotatably coupled to an axle24A configured such that the roller24is able to roll about a second rotational axis (shown by the dashed line B-B inFIGS.2,7and8). The second rotational axis B-B is at an angle to the central axis A-A. The roller24may be configured to roll about a second rotational axis B-B that is perpendicular to the central axis A-A.

In one embodiment, the axle24A is moveably mounted to the housing11. For example, the peripheral wall18of the distal portion16of the housing11may comprise a rail (not shown) and an end of the axle24A may be mounted to the rail to slide along the rail when the roller24rolls about the second rotational axis B-B. In another embodiment (not shown), the axle24A is coupled to the internal wall16A of the distal portion16or the internal wall17A of the proximal portion17via a bearing. In yet another embodiment, the axle24A is not mounted to the housing11.

The dispensing biasing member25is in the form of a dispensing spring25. In the present embodiment, the dispensing spring25is a spiral spring25. In an alternative embodiment (not shown), the dispensing member25comprises a different type of spring, for example, a torsion spring. In another embodiment (not shown), the dispensing biasing member25comprises a portion of resilient material that is twisted to exert a biasing force on the dispensing member24.

The spiral spring25is disposed in the recess22in the housing11and extends about the central axis A-A of the housing11. The spiral spring25is positioned between the internal wall17A of the proximal portion17and the peripheral wall18of the distal portion16.

A first end51of the spiral spring25is fixed to the internal wall17A of the proximal portion17via a connecting member52. A second end53of the spiral spring25is coupled to the axle24A of the roller24. In the present embodiment, the second end of the spiral spring25is coupled to the axle24A of the roller24A by a connecting member27. However, in an alternative embodiment the connecting member27is omitted and instead the second end of the spiral spring25is connected directly to the axle24A of the roller24.

The medicament delivery device10further comprises a coupling28between the distal and proximal portions16,17of the housing11. The coupling28comprises first and second screw threads29,30. The first screw thread29is formed in the inner surface of the peripheral wall20of the proximal portion17. The second screw thread30is formed in the outer surface of the peripheral wall18of the distal portion16.

The first and second screw threads29,30are configured to engage to couple the distal and proximal portions16,17of the housing11such that the proximal portion17can be screwed to the distal portion16of the housing11. Therefore, the proximal portion17is moveable from an initial position (shown inFIGS.2and3), wherein the proximal portion17is coupled to the distal portion16such that the end walls19,21of the distal and proximal portions16,17are spaced apart, to a primed position (shown inFIGS.4,6,7and10), wherein the proximal portion17is twisted relative to the distal portion16such that the screw threads29,30engage and thus the end walls19,21of the distal and proximal portions16,17are moved closer together.

When the proximal portion17is in the initial position, the spiral spring25is in a natural state such that substantially no biasing force is exerted on the roller24by the spiral spring25.

When the proximal portion17is moved to the primed position, the internal wall17A of the proximal portion17, and thus the first end of the spiral spring25attached thereto, is rotated relative to the distal portion16. The dispensing lock (not shown) is initially in a locked state to retain the roller24in position relative to the distal portion16when the proximal portion17is moved from the initial position to the primed position. Thus, the second end of the spiral spring25, which is coupled to the roller24by the connecting member27, is retained in position relative to the distal portion16by the dispensing lock. Therefore, when the proximal portion17is moved from the initial position to the proximal position, the first end of the spiral spring25is rotated relative to the second end of the spiral spring25such that the spiral spring25is coiled to exert a biasing force on the roller24. The biasing force urges the roller24to move along the arcuate path X relative to the housing11. However, the dispensing lock initially prevents movement of the roller24along the arcuate path X.

The dispensing lock comprises a dispensing locking member (not shown) that is connected to the distal portion16of the housing11by a pivotal coupling. The dispensing locking member comprises an elongate member and a projection that is integrally formed with the elongate member.

The elongate member has first and second ends. The elongate member is attached to the pivotal coupling towards the first end of the elongate member. The second end of the elongate member is spaced from the pivotal coupling such that the second end is pivotable about the pivotal coupling. The pivotal coupling couples the locking member to the internal wall16A of the distal portion16.

The projection extends at an angle from the elongate member and is located proximate to the first end of the elongate member. The elongate member and projection may be arranged such that the dispensing locking member is generally L-shaped or V-shaped.

The dispensing locking member is moveable from a locked state to an unlocked state. In the locked state, the dispensing locking member is positioned such that the elongate member extends radially outwardly, in the direction away from the central axis A-A of the housing11, to abut the roller24such that the roller24is prevented from moving along the arcuate path X.

Moreover, in the locked state, the dispensing locking member is positioned such that the projection extends towards the end wall21of the proximal portion17at an angle towards the central axis A-A of the housing11.

The dispensing locking member is moveable to the unlocked state, wherein the dispensing locking member is rotated such that the second end of the elongate member and the projection pivot about the pivotal couplings to move radially inwardly towards the central axis A-A of the housing11. When the dispensing locking member is in the unlocked state, the second end of the elongate member is spaced from the roller24such that the dispensing locking member does not abut the roller24. Therefore, the roller24is not restricted from moving relative to the housing11along the arcuate path X by the dispensing locking member.

The actuator15is in the form of a button15that has a peripheral wall15A and an end wall15B. The button15is received in the proximal portion17of the housing11such that the peripheral wall15A of the button15is located on the inside of the internal wall17A of the proximal portion17and is concentrically aligned therewith. The button15is slidable within the internal wall17A of the proximal portion17in the direction of the central axis A-A of the housing11.

The needle12is moveable relative to the distal portion16of the housing11between a retracted position (shown inFIGS.2to4, and10) and an extended position (shown inFIGS.6and7). When the needle12is in the retracted position, the needle12is fully received in the recess22in the housing11such that the needle12is shielded to prevent damage to the needle12and to protect the patient from being accidentally injured by the needle12.

When the needle12is moved from the retracted position to the extended position, the needle12is moved linearly in the direction of the central axis A-A of the housing11such that the end of the needle12projects out of an aperture19C in the end wall19of the distal portion16. Thus, when the adhesive layer of the distal portion16is adhered to the injection site of a patient, the needle12pierces the patient's skin to extend into the injection site to deliver medicament thereto.

The medicament delivery device10further comprises a septum31that is fixed to the inner surface19B of the end wall19of the distal portion16. The septum31is located over the aperture19C in the end wall19of the distal portion16. The needle12, which is initially in the retracted position, is protected by the septum31. More specifically, the septum31prevents the ingress of contaminants through the aperture19C in the end wall19of the distal portion16and into contact with the sterile needle12. When the needle12is moved to the extended position, the needle12pierces the septum31and the end of the needle12passes through the septum31to project from the end wall19. The septum31may be manufactured from an impermeable material such as plastic, rubber or metal foil. In alternative embodiments, the septum31is fixed to the outer surface19A of the end wall19of the distal portion16or is located in the aperture19C in the end wall19.

The needle actuating mechanism13comprises needle extension and retraction biasing members32,33, extension and retraction holding elements34,35, a needle extension lock36and a needle retraction lock (not shown).

The needle extension biasing member32is in the form of a needle extension spring32. The needle extension spring32may be a helical spring. The needle extension spring32is located inside the peripheral wall15A of the button15and extends about the central axis A-A of the housing11. The needle extension spring32is disposed between a base12A of the needle12and the extension holding element34.

The extension holding element34is fixed relative to the distal portion16of the housing11and is located on the opposite side of the base12A of the needle12to the septum31. The extension holding element34is configured to act as a stop against which the proximal end of the needle extension spring32abuts such that the proximal end of the needle extension spring32is prevented from moving towards the end wall21of the proximal portion17in the direction of the central axis A-A of the housing11. When the needle12is in the initial retracted position, the needle extension spring32is compressed between the base12A of the needle12and the extension holding element34such that the needle extension spring32urges the needle12away from the extension holding element34in the direction of the central axis A-A of the housing11such that the needle12is biased to move into the extended position.

The needle extension lock36comprises an extension locking member38that is connected to the distal portion16of the housing11by a pivotal coupling39. The extension locking member38comprises an elongate member38A and first and second projections40,41that are integrally formed with the elongate member38A. The first projection40is located at the distal end of the elongate member38A and the second projection41is located towards the proximal end of the elongate member38A.

The elongate member38A is attached to the pivotal coupling39at a point between the proximal and distal ends of the elongate member38A such that the first and second projections40,41are pivotable about the pivotal coupling39.

The extension locking member38is moveable from a locked state to an unlocked state (as shown inFIG.5). In the locked state, the extension locking member38is positioned such that the elongate member38A extends substantially parallel to the central axis A-A of the housing11and the first projection40of the extension locking member38is located nearer to the end wall21of the proximal portion17of the housing11than the second projection41.

The first projection40of the extension locking member38extends radially inwardly towards the central axis A-A of the housing11when the extension locking member38is in the locked state. The first projection40comprises a proximal-facing surface40A that abuts the base12A of the needle12when the extension locking member38is in the locked state such that movement of the needle12in the direction of the central axis A-A of the housing11towards the end wall19of the distal portion16is prevented. Thus, when the extension locking member38is in the locked state, the extension locking member38retains the needle12in the retracted position against the force of the needle extension spring32, which is held in a compressed state between the base12A of the needle12and the extension holding element34.

The second projection41of the extension locking member38extends radially outwardly away from the central axis A-A of the housing11when the extension locking member38is in the locked state. The second projection41comprises an angled surface41A that faces at an angle away from the central axis A-A of the housing11and towards the end wall21of the proximal portion17.

The button15comprises a lip15C that extends radially inwardly from the inside of the peripheral wall15A of the button15in the direction towards the central axis A-A of the housing11. The lip15C may be generally annular.

The lip15C of the button15is configured to abut the angled surface41A of the extension locking member38when the button15is moved within the housing11towards the end wall19of the distal portion16. This causes the second projection41of the extension locking member38to be urged radially inwardly towards the central axis A-A such that the extension locking member38is rotated from the locked state to the unlocked state (in the direction of arrow ‘C’ inFIG.5). In the unlocked state, the first projection40is moved radially outwardly such that it no longer abuts the base12A of the needle12and therefore the base12A of the needle12is able to move away from the extension holding element34under the force of the needle extension spring32. Thus, when the extension locking member38is in the unlocked state, the needle12moves from the retracted position to the extended position under the force of the needle extension spring32.

The needle retraction biasing member33is in the form of a needle retraction spring33. The needle retraction spring33may be a helical spring. The needle retraction spring33is located inside the distal portion16of the housing11and extends about the central axis A-A thereof. The needle retraction spring33is disposed between the retraction holding element35and the septum31. The septum31is fixed relative to the distal portion16of the housing11and therefore acts as a stop against which the distal end of the needle retraction spring33abuts. Alternatively, the needle retraction spring33may abut the end wall19of the distal portion16.

The retraction holding element35is slidably received in the internal wall16A of the distal portion16of the housing11. The needle retraction spring33is initially compressed between the septum31and the retraction holding element35such that the needle retraction spring33urges the retraction holding element35away from the septum31in the direction of the central axis A-A of the housing11. The needle retraction lock (not shown) initially retains the retraction holding element35in position against the force of the needle retraction spring33such that the needle retraction spring33is compressed.

The needle retraction lock comprises a retraction locking member (not shown) that is connected to the distal portion16of the housing11by a pivotal coupling (not shown). The retraction locking member comprises first and second elongate members and a projection. The first and second elongate members are integrally formed at one end. The first and second elongate members extend at an angle to each other. The first and second elongate members may extend substantially perpendicular to each other.

The first and second elongate members comprise respective free ends that are remote to the pivotal coupling. The projection is located at the free end of the second elongate member.

The retraction locking member is pivotable from a locked state to an unlocked state. In the locked state, the retraction locking member is positioned such that the first elongate member extends radially outwardly away from the central axis A-A of the housing11and, in one embodiment, is substantially perpendicular to the central axis A-A of the housing11. The free end of the first elongate member is located at, or near to, the second end23B of the flexible bag23. Moreover, in the locked state, the retraction locking member is positioned such that the second elongate member extends towards the end wall21of the proximal portion17from the pivotal coupling and, in one embodiment, is substantially parallel to the central axis A-A of the housing11.

When the retraction locking member is in the locked state, the projection of the retraction locking member extends radially inwardly towards the central axis A-A of the housing11to abut a proximal-facing surface of the retraction holding element35. Thus, the retraction holding element35is prevented from moving towards the end wall21of the proximal portion17and thus the needle retraction spring33is held in a compressed state between the septum31and the retraction holding element35.

Movement of the roller24along the arcuate path X within the housing11to the second end23B of the flexible bag23causes the roller24to be urged against the free end of the first elongate member. Thus, movement of the roller24to the second end23B of the flexible bag23results in a force being exerted on the free end of the first elongate member. This force causes the free end of the first elongate member to be urged towards the end wall19of the distal portion16such that the retraction locking member is urged to rotate about the pivotal coupling from the locked state to the unlocked state.

When the retraction locking member is rotated to the unlocked state, the projection at the free end of the second elongate member is moved radially outwardly away from the central axis A-A of the housing11such that the projection is spaced from the retraction holding element35. Thus, the projection no longer hold the retraction holding element35in place against the force of the needle retraction spring33and so the retraction holding element35is moved towards the end wall21of the proximal end17by the needle retraction spring33.

The needle12extends through an aperture35A in the retraction holding element35such that when the needle12is in the extended position and the retraction locking member is in the locked state the base12A of the needle12is located in proximity to the retraction holding element35. Thus, when the retraction locking member is subsequently moved to the unlocked state, the retraction holding element35is released such that the needle retraction spring33urges the retraction holding element35against the base12A of the needle12to move the needle12towards the end wall21of the proximal portion17and into the retracted position.

A clearance gap (not shown) may be provided between the retraction locking member and the septum31and end wall19of the distal portion16to facilitate movement of the retraction locking member between the locked and unlocked states. Alternatively, the septum31may be manufactured from a flexible material that facilitates movement of the retraction locking member.

An exemplary operation of the medicament delivery device10will now be described. The medicament delivery device10is typically stored in a sterile packaging (not shown). The patient first removes the medicament delivery device10from the sterile packaging. When the medicament delivery device10is removed from the sterile packaging the proximal portion17of the housing11is in the initial position, the needle12is in the retracted position, and the button15is retracted into the proximal portion17(as shown inFIG.2) such that the patient is not able to access the button15to actuate the button15. For example, the inner dimension of the internal wall17A of the proximal portion17may be sufficiently small that the patient is not able to insert a finger into the internal wall17A to access the button15. Thus, the patient is not able to depress the button15to operate the dispensing mechanism14to dispense medicament from the flexible bag23and thus the dispensing mechanism14is rendered inoperable. Moreover, the patient is not able to operate the needle actuating mechanism13to move the needle12to the extended position.

The patient then supplies medicament to the dispensing mechanism14of the medicament delivery device10. More specifically, the patient supplies medicament to the flexible bag23via the filling port18A in the peripheral wall18of the distal portion16of the housing11such that the flexible bag23is filled with medicament (as shown inFIG.3). The medicament may be supplied from, for example, a syringe, container, or pressurised canister. In an alternative embodiment, the medicament reservoir23is pre-filled with medicament, in which case the filling port18A may be omitted.

Next, the label (not shown) is removed from the adhesive layer (not shown) on the outer surface19A of the end wall19of the distal portion16. The adhesive layer is then adhered to the patient's skin at the injection site such that the end wall19of the distal portion16is secured to the injection site.

The patient then rotates the proximal portion17relative to the distal portion16such that the engagement of the first and second screw threads62,63causes the proximal portion17to move from the initial position to the primed position (as shown inFIG.4). For example, the patient may use one hand to apply a force to the proximal portion17to twist the proximal portion17relative to the distal portion16. The rotation of the proximal portion17relative to the distal portion16causes the proximal portion17to move relative to the distal portion16in the direction of the central axis A-A of the housing11such that the end wall21of the proximal portion17moves towards the end wall19of the distal portion16.

As the proximal portion17is moved to the primed position, the first end of the spiral spring25, which is attached to the internal wall17A of the proximal portion17, is moved relative to the second end of the spiral spring24, which is attached to the initially stationary roller24, such that the spiral spring25is coiled to exert a biasing force on the roller24. The biasing force urges the roller24to move along the arcuate path X relative to the housing11. The dispensing locking member of the dispensing mechanism14is initially in the locked state to hold the roller24in position against the force of the spiral spring25.

When the proximal portion17reaches the primed position, the proximal portion17is retained in the primed position by the engagement of the first and second screw threads29,30. The coiled spiral spring25urges the proximal portion17to rotate relative to the distal portion16, in the opposite direction to which the proximal portion17was rotated from the initial position to the proximal position, such that the proximal portion17is biased away from the primed position by the force of the spiral spring25. However, the configuration of the first and second screw threads29,30is such to prevent the proximal portion17from moving away from the primed position under the force of the spiral spring25. This may be achieved, for example, due to the pitch of the first and second screw threads29,30or alternatively by a latch or locking members that engage to hold the proximal portion17in position relative to the distal portion16. Therefore, once the patient has moved the proximal portion17to the primed position the patient no longer needs to apply a force to the proximal portion17to retain the proximal portion17in the primed position.

The button15is received in the internal wall17A of the proximal portion17of the housing11such that when the proximal portion17is moved to the primed position, and thus the end wall21of the proximal portion17is moved towards the end wall19of the distal portion16, the proximal portion17slides relative to the button15. This causes the button15to project from the proximal portion17(as shown inFIG.4). Therefore, the button15may be actuated by the patient. The button15projects from the end wall21of the proximal portion17when the proximal portion17is in the primed position.

With the proximal portion17in the primed position, the medicament delivery device10is primed for supplying medicament to the injection site of the patient. The patient depresses the end wall15B of the button15such that the button15is slid into the proximal portion17of the housing11. This causes the button15to engage with the needle extension lock36such that the needle extension spring32is released to move the needle12to the extended position. In more detail, the button15is slid towards the end wall19of the distal portion16until the projection15C of the button15is urged against the angled surface41A of the second projection41of the extension locking member38, resulting in the extension locking member38rotating from the locked state to the unlocked state (as shown inFIG.5). As discussed above, this allows the base12A of the needle12to move away from the extension holding element34under the force of the needle extension spring32such that the needle12moves axially to pass through the septum31to extend out of the aperture19C in the end wall19of the distal portion16. Thus, the needle12is moved to the extended position (as shown inFIG.6). The end wall19of the distal portion16is adhered to the patient's skin and therefore when the needle12is moved to the extended position the needle12enters the injection site of the patient.

When the needle12is moved to the extended position the needle12is fluidly communicated with the inside of the flexible bag23. In one embodiment, a conduit (not shown) is provided that is fluidly communicated with the inside of the flexible bag23. The needle12comprises an aperture (not shown) that aligns with the conduit to fluidly communicate therewith when the needle12is moved to the extended position such that medicament is able to flow out of the flexible bag23, through the conduit, and into the aperture of the needle12to be dispensed from the needle12. The conduit may fluidly communicate with an outlet (not shown) provided towards the second end23B of the flexible bag23.

The patient continues to push the button15into the housing11to then engage the button15with the dispensing lock such that, after the needle12has been moved to the extended position, the spiral spring25is released to urge the roller24along the arcuate path X relative to the distal portion16of the housing11(as shown inFIGS.7and9). This causes the roller24to move over the wall26of the flexible bag23from the first end23A to the second end23B of the flexible bag23such that the wall26deforms to increase the pressure of the medicament in the flexible bag23. This causes medicament to be dispensed from the flexible bag23. More specifically, the distal end of the button15is urged against the projection of the dispensing locking member, resulting in the dispensing locking member rotating from the locked state to the unlocked state such that the dispensing locking member is moved away from the roller24. As discussed above, this allows the roller24to move across the wall26of the flexible bag23under the force of the spiral spring25. Therefore, the flexible bag23is compressed between the roller24and the end wall19of the distal portion16such that the pressure of the medicament in the flexible bag23is increased to cause the medicament to flow towards the second end23B of the flexible bag23. The medicament flows out of the flexible bag23and through the needle12to enter the injection site of the patient.

Once the button15has been depressed to the extent that the dispensing locking member is moved to the unlocked state to commence medicament delivery, the patient may stop pressing the button15. The roller24will continue to move towards the second end23B of the flexible bag23such that medicament is delivered to the injection site of the patient via the needle12. Therefore, the medicament delivery device10may be used to deliver medicament to the injection site of the patient over an extended time period, for example, several hours, without requiring the patient to continuously apply a force to the button15.

Medicament will continue to be delivered to the injection site until the roller24reaches the second end23B of the flexible bag23and engages with the needle retraction lock such that the needle retraction spring33is released to move the needle12to the retracted position. In more detail, the roller24is moved towards the second end23B of the flexible bag23by the force of the spiral spring25until the roller24is urged against the free end of the first elongate member of the retraction locking member42, resulting in the retraction locking member rotating from the locked state to the unlocked state. As discussed above, this allows the retraction holding element35to move away from the end wall19of the distal portion16under the force of the needle retraction spring33such that the retraction holding element35is urged against the base12A of the needle12to move the needle12into the housing11to the retracted position (as shown inFIG.10). The patient may then remove the medicament delivery device10from the injection site.

In an alternative embodiment, one of the first and second screw threads62,63is omitted and is replaced by a protrusion (not shown) that engages with the other one of the first and second screw threads62,63.

In one embodiment (not shown), an actuator lock may be provided to lock the button15in position when the proximal portion17is in the initial positon. The actuator lock may comprise a actuator locking member that is in a locked state when the proximal portion17is in the initial position to prevent movement of the button15relative to the housing11. The actuator locking member is moved to an unlocked state when the proximal portion17is moved to the primed position such that the button15can be moved relative to the housing11.

In the above described embodiment, the proximal portion17is rotated relative to the distal portion16of the housing11to coil the spiral spring25such that a biasing force is exerted on the dispensing member24. However, in an alternative embodiment (not shown), the spiral spring25is pre-coiled and therefore the patient does not need to rotate the proximal portion17relative to the distal portion16to exert a biasing force on the dispensing member24. In one such embodiment, the distal and proximal portions16,17of the housing11are fixed relative to each other, and may be integrally formed.

In the above described embodiment, the flexible bag23extends approximately 180 degrees about the central axis A-A of the housing11. However, it should be recognised that the flexible bag23may extend a different angle about the central axis A-A of the housing11, for example, 45 degrees or 360 degrees.

Although in the above described embodiment the reservoir23comprises a flexible bag23, in alternative embodiments (not shown) the reservoir23may have a different configuration. For example, the reservoir may instead comprise a rigid container with a flexible wall at one end, wherein the dispensing member is arranged to move across the flexible wall to deform the flexible wall such that medicament is dispensed from the reservoir. In another embodiment, the edges of a flexible wall of material are secured to the inner surface19B of the end wall19of the distal portion16such that a space is formed between the flexible wall and the inner surface19B. The space forms a reservoir for medicament. The dispensing member is moved across the flexible wall to increase the pressure in the reservoir such that medicament is dispensed from the reservoir.

In the above described embodiment the dispensing member24comprises a roller24. However, it should be recognised that the roller24may be omitted such that the dispensing member24does not roll about a second central axis B-B relative to the housing11. In one such embodiment (not shown), the dispensing member is instead fixed relative to the connecting member27such that the dispensing member instead slides across the wall26of the flexible bag23under the force of the dispensing biasing member25.

In the above described embodiment, the needle12is moveable relative to the housing11between the retracted and extended positions. However, in an alternative embodiment the needle12is fixed in the extended position such that the needle12permanently projects from the housing11. Thus, when the end wall19of the distal portion16is secured to the patient's skin the needle12pierces the skin to enter the injection site of the patient.

In the above described embodiment, the dispensing lock is mechanically operated, the end of the button15being urged against the dispensing locking member to rotate the dispensing locking member from the locked state to the unlocked state. However, in an alternative embodiment the dispensing lock is electrically operated. For example, the dispensing lock may comprise an electromagnetic latch (not shown) that holds the roller24in position relative to the distal portion16of the housing11. When the button15is depressed by the patient the electromagnetic latch changes state such that the roller24is released to move along an arcuate path X relative to the housing11. Similarly, the needle actuating mechanism may instead be electrically operated, for example comprising a motor (not shown) that moves the needle12between the retracted and extended positions.

The terms “drug” or “medicament” are used herein to describe one or more pharmaceutically active compounds. As described below, a drug or medicament can include at least one small or large molecule, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Exemplary pharmaceutically active compounds may include small molecules; 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 of these drugs are also contemplated.

The term “drug delivery device” shall encompass any type of device or system configured to dispense a drug into a human or animal body. Without limitation, a drug delivery device may be an injection device (e.g., syringe, pen injector, auto injector, large-volume device, pump, perfusion system, or other device configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), skin patch (e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal or pulmonary), implantable (e.g., coated stent, capsule), or feeding systems for the gastro-intestinal tract. The presently described drugs may be particularly useful with injection devices that include a needle, e.g., a small gauge needle.

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 vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more pharmaceutically active compounds. 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 dual-chamber cartridge configured to store two or more components of a drug formulation (e.g., a drug and a diluent, or two different types of 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 of the drug or medicament 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 drug delivery devices and drugs described herein can be used for the treatment and/or prophylaxis of many different types of disorders. Exemplary 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 exemplary disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.

Exemplary drugs for the treatment and/or prophylaxis of diabetes mellitus or complications associated with 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 term “derivative” refers to any substance which is sufficiently structurally similar to the original substance so as to have substantially similar functionality or activity (e.g., therapeutic effectiveness).

Exemplary insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val 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.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin; 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-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(w-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyhepta¬decanoyl) human insulin. Exemplary GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example: Lixisenatide/AVE0010/ZP10/Lyxumia, Exenatide/Exendin-4/Byetta/Bydureon/ITCA 650/AC-2993 (a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide/Victoza, Semaglutide, Taspoglutide, Syncria/Albiglutide, Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, 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, TT-401, BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten.

An exemplary oligonucleotide is, for example: mipomersen/Kynamro, a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia.

Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

Exemplary 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.

Exemplary 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.

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 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 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 embodiments discussed herein 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, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), 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.

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.

Exemplary antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

The compounds described herein may be used in pharmaceutical formulations comprising (a) the compound(s) or pharmaceutically acceptable salts thereof, and (b) a pharmaceutically acceptable carrier. The compounds may also be used in pharmaceutical formulations that include one or more other active pharmaceutical ingredients or in pharmaceutical formulations in which the present compound or a pharmaceutically acceptable salt thereof is the only active ingredient. Accordingly, the pharmaceutical formulations of the present disclosure encompass any formulation made by admixing a compound described herein and a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any drug described herein are also contemplated for use in drug delivery devices. Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g. salts having a cation selected from an alkali or alkaline earth metal, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharmaceutically acceptable salts are known to those of skill in the arts.

Pharmaceutically acceptable solvates are for example hydrates or alkanolates such as methanolates or ethanolates.

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