CN121240902A

CN121240902A - Self-propelled pharmaceutical containers and pharmaceutical delivery devices

Info

Publication number: CN121240902A
Application number: CN202480036962.4A
Authority: CN
Inventors: U·达斯巴赫; T·格拉瑟; M·拉乌; S·温德兰
Original assignee: Sanofi Aventis France
Current assignee: Sanofi Aventis France
Priority date: 2023-06-05
Filing date: 2024-06-05
Publication date: 2025-12-30
Also published as: EP4719532A1; WO2024251799A1

Abstract

A self-driven medicament container (10, 10 ') is provided for storing and expelling a medicament in response to a user interaction, the self-driven medicament container (10, 10') comprising a reservoir body (2), a holder (3), a plug (4) configured to divide an interior of the reservoir body (2) into a drive compartment (21) and a medicament compartment (22), the medicament compartment (22) containing the medicament and comprising an outlet (23) through which the medicament can be expelled in a dispensing operation. The self-driven medicament container (10, 10) further comprises a drive element (5), a plunger having a shaft (61,6T) with a locking element (62, 62 ') configured to engage the holder (3) to prevent distal movement of the plunger relative to the reservoir body (2), and a contact element (63) configured to contact the bung (4), and a release mechanism configured to disengage the locking element (62, 62') from the holder (3) in response to the user interaction, thereby enabling distal movement of the plunger relative to the reservoir body (2). The medicament compartment (22) is distal to the drive compartment (21). The plug (4) is further configured to seal the medicament compartment (22) from the drive compartment (21). The drive element (5) is positioned in the drive compartment (21) before and after the locking element (62, 62') is disengaged from the holder (3). The drive element (5) is configured to provide an axial force to the plunger when the locking element (62, 62') is disengaged from the holder (3) in order to move the plunger distally relative to the reservoir body (2), thereby moving the bung (4) relative to the reservoir body (2) and expelling the medicament. Further, a medicament delivery device (100, 100') is provided, comprising the self-driven medicament container.

Description

Self-driven medicament container and medicament delivery device

Background

The present disclosure relates to a self-driven medicament container for storing a medicament and expelling the medicament in a dispensing operation in response to user interaction. The present disclosure further relates to a medicament delivery device comprising a self-driven medicament container.

Medicament containers storing medicaments are commonly used in medicament delivery devices. A conventional medicament container comprises a medicament compartment containing a medicament and a stopper axially movable relative to the medicament compartment for expelling medicament therefrom. The force for moving the stopper is typically provided by a drive mechanism, such as a pretensioned compression spring and plunger of the medicament delivery device. In an initial state, the medicament delivery device is blocked such that the plunger cannot move relative to the medicament container. In response to one or more user interactions, the medicament delivery device is activated via the activation element to unlock the plunger and enable the plunger to move relative to the medicament container. This relative movement is typically transferred to the bung of the medicament container such that medicament is expelled from the medicament compartment.

Disadvantageously, conventional medicament containers require a medicament delivery device for expelling medicament because those containers do not themselves have a drive mechanism capable of expelling medicament in response to user interaction. The drive mechanism needs to be adapted to the specific situation of the medicament container to be used. This typically requires redesigning several parts of the medicament delivery device, which is expensive. Therefore, a medicament container with an integrated drive mechanism would be advantageous, which allows it to be used in less complex medicament delivery devices.

Disclosure of Invention

Hereinafter, the term "distal" refers to the direction of expelling a medicament from a medicament container or medicament delivery device. Accordingly, the term "proximal" refers to the opposite direction. With respect to pen-shaped medicament delivery devices, the term "distal" refers to a direction towards the injection site and/or the tip of the injection needle of the device. Accordingly, the term "proximal" refers to a direction pointing away from the injection site and/or the tip of the injection needle of the device.

It is an object of the present disclosure to provide an improved medicament container.

This object is achieved by the subject matter disclosed herein, for example by the subject matter defined in the appended independent claims. Advantageous refinements and developments are set forth in the dependent claims and/or in the following description.

One aspect of the present disclosure relates to a (self-driven) medicament container for storing and expelling a medicament in response to a user interaction. The medicament container comprises a reservoir body, a retainer, a stopper, a drive element, a plunger and a release mechanism. The stopper is configured to divide the interior of the reservoir body into a drive compartment and a medicament compartment. The medicament compartment is configured to contain a medicament. The plug may be configured to seal the medicament compartment from the drive compartment. The medicament compartment comprises an outlet through which medicament may be expelled during a dispensing operation. The medicament compartment may be distal to the drive compartment.

The plunger has a shaft with a locking element configured to engage the retainer to prevent distal movement of the plunger relative to the reservoir body. For example, the locking element may abut a proximal surface of the retainer when engaged with the retainer. The locking element may be formed at a proximal portion of the shaft. The shaft of the plunger may extend along the longitudinal axis of the reservoir body such that the longitudinal axis of the shaft may be parallel to the longitudinal axis of the reservoir body. For example, the longitudinal axis of the shaft may be parallel to the longitudinal axis of the reservoir body before, during and/or after disengagement of the locking element from the holder.

The release mechanism is configured to disengage the locking element from the retainer in response to a user interaction (e.g., an activation movement). Disengagement enables distal movement of the plunger relative to the reservoir body. The holder may have an opening through which the shaft extends into the drive compartment, e.g. through the holder.

The drive element is positioned in the drive compartment before and after the locking element is disengaged from the retainer. The drive element is configured to provide an axial force to the plunger, for example when the locking element is disengaged from the retainer, in order to move the plunger distally relative to the reservoir body, thereby moving the stopper relative to the reservoir body and expelling the medicament. The drive element may be part of the medicament container, e.g. be wholly or at least partly accommodated in the medicament container, e.g. in a drive compartment of the reservoir body. In particular, the drive element may be at least partially housed in the medicament container before, during and/or after the dispensing operation. Since the drive element is part of the medicament container, the medicament container may be referred to as "self-driven" in that it comprises a drive element and no external drive element is required.

In one embodiment, the distal end of the shaft may be arranged to contact the stopper and transmit movement of the plunger to the stopper.

In one embodiment, the shaft may further have a contact element configured to contact the stopper and transmit movement of the plunger to the stopper. The contact element may have a larger cross section than the shaft. The contact element may be formed at the distal end of the shaft.

In one embodiment, the contact element may have a plate-like shape, for example such that the extension of the contact element in the radial direction is longer than the extension of the contact element in the longitudinal direction, preferably at least twice as long as the latter. The contact element may have a constant cross section along its longitudinal axis. The cross section of the contact element may be circular. The longitudinal axis of the contact element may be parallel to the longitudinal axis of the reservoir body. The contact element may be integrally formed with the shaft. Alternatively, the contact element may be connected to the shaft. The connection between the contact element and the shaft may be such that the shaft may not be rotatable relative to the contact element. The angle formed between the longitudinal axis of the shaft and the proximal surface of the contact element may be 90 degrees. The contact element may be formed from a complete material.

The distally facing end surface of the contact element may be configured to contact the plug. The distally facing end surface may be a closed surface. The distally facing end surface may be configured to contact the stopper throughout its cross-section. The distally facing end surface may be a planar surface. The cross-section of the distally facing end surface may correspond to the cross-section of the contact element, which may be circular. The diameter of the distally facing end surface may almost correspond to the diameter of the stopper. Thus, the contact interface between the contact element and the plug may be maximized. This may improve the force transfer to the plug and may enable a uniform distribution of the force over the entire cross-section of the plug. However, the cross-section of the contact element may be smaller than the cross-section of the stopper, such that the contact element does not contact the inner wall of the reservoir body.

The reservoir body has an interior wall surface that is in contact with the medicament at least along the length of its medicament compartment. The interior wall surface may define an interior cross-section of the reservoir body. In one embodiment, the interior cross-section of the reservoir body may be constant along the length of the reservoir body along which the stopper moves during a dispensing operation. In one embodiment, the interior cross-section of the reservoir body may be constant along its entire length. The (shape of the) inner cross section may be defined by the (shape of the) inner wall surface. The cross-section may be taken perpendicularly with respect to the longitudinal axis of the reservoir body. The longitudinal axis may extend between the proximal and distal ends of the container. The interior wall surface of the reservoir body may be configured to be continuously connected to an exterior surface of the self-driven medicament container. Thus, there may be only a single wall separating the interior of the reservoir body from the exterior of the reservoir body. In other words, there may be no void, only the walls of the reservoir body, when travelling from the interior of the reservoir body to the exterior of the reservoir body or the medicament container.

The drive element may be or may comprise a spring, preferably a compression spring. The drive element may surround the shaft. In other embodiments, the drive element may be disposed in the interior of the shaft. The drive element may be formed by more than one spring. The drive element may contact a distal surface of the holder. The drive element may be positioned between the holder and the contact element, for example between a distal surface of the holder and a proximal surface of the contact element.

The release mechanism may comprise an activating element, for example by activating the movement. The activation movement may comprise an axial and/or rotational movement of the activation element relative to the reservoir body. The axial movement of the activation element may be a distal movement relative to the reservoir body. The activation movement that the user can perform can be converted into a movement of the locking element relative to the holder by an interaction between the locking element and the activation element. The self-driven medicament container may be activated due to, for example, a relative movement between the locking element and the holder.

In one embodiment, the activation element is a push button. The push button may have at least one guide groove. The holder may have at least one guiding element configured to interact with a guiding groove of the push button when the push button is pushed in distal direction with respect to the reservoir body and/or the holder and/or the locking element. Due to the interaction of the guide element with the guide groove, the push button may be supported by the holder in the radial direction.

The opening of the holder may be configured such that the locking element may pass through the holder in a distal direction when the locking element is disengaged from the holder.

After the dispensing operation, the proximal end of the plunger, shaft and/or locking element may be inside the drive compartment.

In one embodiment, the locking element may be formed by two or more flexible arms configured to deflect radially, preferably in a radially inward direction, in response to movement of the activation element relative to the reservoir body, e.g. in response to an activation movement. The flexible arms of the locking element may be evenly distributed in the circumferential direction such that the angular offset between all flexible arms is the same. Each flexible arm may, for example, include radial protrusions at the free end that are configured to engage with the retainer. The free end may be a proximal end of the arm. Preferably, the protrusion protrudes in a radially outward direction such that the flexible arm is configured to deflect radially inward in response to movement of the activation element relative to the reservoir body.

In one embodiment, the retainer includes two additional openings. These openings may have a similar cross-section as the free ends of the flexible arms, such that the free ends of the flexible arms may pass through the holder when the flexible arms are deflected radially outwards due to the movement of the activation element relative to the reservoir body.

In one embodiment, the self-driven medicament container may include a dock that may be established between the engagement feature and the sloped surface. The engagement feature may be formed on one of the locking element and the activation element, and the sloped surface may be provided on the other of the locking element and the activation element. The locking element may disengage from the retainer when the abutment is established and the engagement feature moves relative to the inclined surface. In other words, the locking element may disengage from the holder when movement of the activation element is converted into movement of the locking element via such abutment. Preferably, the engagement feature slides along the inclined surface to disengage the locking element from the keeper.

In one embodiment, the flexible arm deflects as the engagement feature slides along the sloped surface. Preferably, the flexible arms deflect in a radially inward direction.

In one embodiment, the engagement feature may be a distal surface of the activation element. The inclined surface may be formed on the flexible arm such that the inclined surface is inclined in a radially inward direction as seen from the distal end of the medicament container.

In one embodiment, the engagement feature may be a proximal surface of the flexible arm and the angled surface may be formed at an inner wall surface of the activation element. The inclined surface may be inclined in a radially inward direction as seen from the distal end of the medicament container.

In one embodiment, the engagement feature may be a sloped surface having a different angle of slope than a sloped surface configured to interact with the engagement feature.

In one embodiment, the locking element may be formed by a stop bar, which may be configured to abut a proximal surface of the retainer prior to user interaction. The locking element may be configured to rotate relative to the retainer in response to user interaction so as to align with the opening of the retainer. The opening is configured to allow the locking element to pass through the opening when the locking element is aligned with the opening, for example after user interaction.

In one embodiment, the opening may have a cross-section similar to that of the locking element, such that the locking element may pass through the opening in a distal direction after user interaction. In one embodiment, the opening may have a larger cross section than the locking element.

The reservoir body may have a circular internal cross-section. The diameter of the circular cross section may be constant, for example along the length of the medicament compartment. The outer surface of the reservoir body may form the outer surface of the self-driving medicament container. The outer surface of the reservoir body may define an outer dimension, such as an outer diameter, of the self-driving medicament container.

The holder may be fixed relative to the reservoir body in an axial direction and/or in a rotational direction. In one embodiment, the retainer may be mounted to the proximal end of the drive compartment. In another embodiment, the retainer may be mounted to an inner wall of the drive compartment. The holder may be directly connected to the reservoir body, e.g. to a proximal surface of the reservoir body or to an inner wall of the reservoir body. Thus, the holder may form the proximal end of the reservoir body. The connection between the holder and the reservoir body may be configured to counteract the driving force provided by the driving element.

The self-driven medicament container may be configured for use in a syringe housing having an activation mechanism.

The self-driven medicament container may comprise a needle. The needle may be connected to the outlet such that the medicament may be expelled through the needle. The self-driven medicament container may further comprise a needle shield attachable to the self-driven medicament container, preferably to the distal end of the self-driven medicament container. The needle shield may enclose the needle so that the needle may be protected from mechanical shock and remain sterile.

The self-driven medicament container with the needle may comprise a grip enabling a user to perform medicament injection without using an external device into which the self-driven medicament container is inserted, e.g. without inserting the self-driven medicament container into a medicament delivery device such as an auto-injector.

Another aspect of the present disclosure relates to a medicament delivery device. The medicament delivery device comprises a self-driven medicament container with a needle according to one of the preceding embodiments. The medicament delivery device is configured to enable a user to inject a medicament stored in a self-driven medicament container through a needle into the body of the user. The medicament delivery device further comprises an elongated housing and optionally an external button. The self-driven medicament container abuts the elongate housing. The elongate housing has a distal wall.

The self-driven medicament container may abut the distal wall. The distal wall may provide a distal stop for the container. The distal wall may have an opening through which the needle and/or the outlet may protrude distally beyond the housing. In other embodiments, the distal stop may be proximally offset from the distal wall of the device. An external button may be connected to the proximal portion of the housing. Such connection may be achieved via a snap fit.

The external button may be configured to interact with a release mechanism of the self-driven medicament container in order to disengage the locking element from the retainer. The external button may interact with an activation element of the release mechanism.

In one embodiment, the external button may be connected to the release mechanism such that (e.g., any) movement of the external button may be directly translated into a corresponding movement of the activation element. In another embodiment, the external button may be connected to the release mechanism such that movement of the external button translates into movement of the activation element in a different spatial direction. For example, the helical movement (i.e., axial and rotational movement) of the external button may be translated into an axial movement of the release mechanism, or vice versa.

In one embodiment, the connection of the external button to the release mechanism may be achieved by friction between the proximal surface of the activation element and the distal surface of the external button.

In one embodiment, the connection of the external button and the release mechanism may be achieved by interaction of engagement elements on the external button and/or the release mechanism.

In one embodiment, disengagement of the locking element from the retainer may be caused by axial movement of the external button relative to the housing.

In one embodiment, disengagement of the locking element from the retainer may be caused by rotational movement of the external button relative to the housing.

In one embodiment, disengagement of the locking element from the retainer may be caused by a combination of movements of the external button relative to the housing, such as a combination of axial movements and rotational movements (so-called screw movements).

The medicament delivery device may comprise a needle cannula movably connected to the housing. When the needle cannula is in the first position, the needle cannula protrudes beyond the tip of the needle. The needle cannula may be in the first position after the medicament has been expelled from the self-driven medicament container and the medicament delivery device is moved away from the injection site. The needle cannula may be in the first position before activation of the medicament delivery device and/or before the needle pierces the skin of the user. The first position may be an extended position of the needle cannula.

The needle cannula is movable proximally relative to the housing to a second position. During the proximal relative movement, the outer wall surface of the needle cannula or at least the proximal end of the needle cannula may slide along the inner wall surface of the housing. In the second position, the tip of the needle protrudes distally beyond the needle cannula. In the second position, the distal end of the needle cannula may be more proximal than the distal end of the housing. Alternatively, in the second position, the distal end of the needle cannula may be at the same level as the distal end of the housing or more distal than the distal end of the housing. The second position may be a retracted position of the needle cannula.

In one embodiment, the needle cannula may be configured to activate the medicament delivery device when the needle cannula is moved to its second position. In one embodiment, the needle cannula may activate the medicament delivery device via interaction with an external button when the needle cannula is moved to its second position.

The needle cannula may have an opening through which the needle may pass when the needle cannula is moved proximally relative to the housing from its first position to its second position.

The medicament delivery device may comprise a needle cannula spring. The needle cannula spring may be configured to provide an axial force to the needle cannula. Due to this axial force, the needle cannula may be moved from its second position to its first position in which the needle cannula extends distally beyond the tip of the needle in order to avoid injuries caused by the needle after a dispensing operation.

The medicament delivery device may comprise a distal cap configured to be detachably attached to the housing or the needle cannula. The distal cap may be configured to be detached from the housing or needle cannula by distal movement relative to the housing or needle cannula, respectively.

In one embodiment, the distal cap may be configured to engage with a needle shield of the self-driven drug device when the distal cap is attached to the drug delivery device. The distal cap may comprise an engagement groove which fits onto the needle shield, thereby supporting the needle shield in a radially outward direction. The distal cap may engage with the needle shield such that, due to such engagement, the needle shield may be removed from the self-driven medicament container when the distal cap is removed from the medicament delivery device, e.g. by distal movement of the distal cap relative to the housing.

The housing may include a button lock configured to engage an external button (e.g., a locking protrusion thereof) when the needle cannula is in its first position so as to block distal movement of the external button relative to the housing. The button lock is configured to disengage from the external button due to interaction with the needle cannula when the needle cannula is moved proximally relative to the housing to its second position.

In one embodiment, the button lock may include at least two blocking arms. The blocking arm may be configured to deflect radially outwardly due to interaction with the needle cannula as the needle cannula moves proximally relative to the housing. For example, as the needle cannula moves proximally relative to the housing, the proximal end of the needle cannula may slide along the blocking arm, thereby deflecting the free end of the blocking arm in a radial direction. Due to the radial deflection, the blocking arm may disengage from the external button. This enables the external button to move distally relative to the housing. The blocking arms may deflect radially outwardly or radially inwardly depending on whether the proximal end of the needle cannula is inside or outside the blocking arms in the radial direction.

A needle cannula spring may be positioned between the housing and the needle cannula. Preferably, a needle cannula spring may be positioned between the distal wall of the housing and the needle cannula. More preferably, the needle cannula spring may be positioned between the distal surface of the distal wall of the housing and the proximal inner surface of the needle cannula.

The housing may include a protrusion at its distal end that extends the housing in a distal direction. The protrusion may be configured to connect the distal cap to the housing and/or to axially guide movement of the distal cap during attachment to or detachment from the housing.

The housing may have a circular interior cross-section along at least a portion of its length. In the case of a housing having a circular internal cross section, the diameter of the housing may be constant.

In one embodiment, the medicament delivery device may be an automatic injector.

In one embodiment, the medicament delivery device may comprise a guiding unit, which guiding unit is preferably attached to the housing. The needle cannula may include a guide pin, a torsion guard, and/or a flexible rod. The guide pin may protrude outwardly from the outer wall of the needle cannula. The flexible rod may be separated by a through recess extending through the wall of the needle cannula. The flexible rod and the body of the needle cannula may be made of one piece. The torsion guard may comprise a rod extending preferably in the axial direction of the needle cannula.

The guide unit may include a first channel and a second channel. The first channel may first extend against the axial direction with a sliding ramp and then extend substantially in the axial direction towards a bend of the first channel and then return towards a dead end of the first channel. The extension towards the dead end may comprise a sliding incline against the axial direction and/or may be parallel to the axial direction. The dead end may be separated from the remainder of the first channel by a barb.

In the first state of the needle cannula, the guide pin may be arranged in a portion of the first channel below the dead end and at the beginning of the bevel of the first channel.

A torsion guard of the needle cannula may be disposed within the second passageway. The torsion guard may be guided by the second channel during movement of the needle cannula relative to the guide unit. The second channel may be straight and parallel to the direction of movement of the needle cannula. The torsion guard in the second channel may act as a guard protecting the needle cannula from rotation.

In the second state of the needle cannula, the needle cannula may be arranged partly within the guiding unit, e.g. due to the medicament delivery device being arranged partly on the skin of the user. In the second state of the needle cannula, the guide pin is movable within the first channel towards the bend. When the guide pin passes the inclined portion of the first channel, the upper portion of the needle cannula may move perpendicular to the direction of movement of the needle cannula and the flexible rod may flex as the remaining portion of the needle cannula is secured against any rotation by the torsion guard in the second channel. The flexible rod is then biased.

In the third state of the needle cannula, the needle cannula may be fully pressed into the guiding unit, e.g. due to the user arranging the medicament delivery device on his/her skin. Thus, in the third state of the needle cannula, the needle may be exposed by the needle cannula. In this case, the guide pin has reached the bend of the first channel and can move within the bend perpendicular to the direction of movement of the needle cannula. In a third state of the needle cannula, the biased flexible rod may force the guide pin through the bend.

In a fourth state of the needle cannula, the flexible rod may be released and the guide pin may move within the bend perpendicular to the direction of movement of the needle cannula.

In a fifth state of the needle cannula, the medicament delivery device may be partially removed from the skin of the user. The guide pin may be forced past the barb of the first channel so that the flexible rod may be biased again. When the medicament delivery device is removed from the skin of the user, the needle cannula may be pushed out of the housing in a distal direction, e.g. by a needle cannula spring, so that the guide pin may be forced over the barb.

In the sixth state of the needle cannula, the medicament delivery device may be completely removed from the skin of the user. The needle cannula may completely cover the needle. The guide pin may snap into the dead end of the first channel such that the needle cannula may be fixedly engaged to the guide unit.

It should be noted that features described above and below in connection with different embodiments or aspects may be combined with each other even if such a combination is not explicitly disclosed herein above or below. Further features, advantages and convenience of the present disclosure, in particular of the proposed concept, will become apparent from the following description of exemplary embodiments with reference to the accompanying drawings.

A self-driven medicament container according to the present disclosure provides the advantage that the medicament stored therein may be expelled without the need for an external drive element or delivery device. Thus, the self-driven medicament container may be used as a stand-alone device.

When used in a medicament delivery device (e.g. an auto injector), the self-driven medicament container provides the advantage that the structure of the medicament delivery device may be simpler than conventional medicament delivery devices. For example, the medicament delivery device does not require a drive mechanism or drive element. Thus, the medicament delivery device may be less complex and have less risk of malfunction. In addition, the medicament delivery device may be used with self-driven medicament containers of the same or different lengths without structural adjustment. Therefore, costs can be saved and waste can be reduced. Nevertheless, if structural adjustment is necessary, fewer parts of the medicament delivery device need to be adjusted, which simplifies the redesign process and reduces costs.

The medicament delivery device according to the present disclosure provides the advantage that it has a simpler structure than conventional medicament delivery devices, as it does not require a drive mechanism or drive element. Accordingly, a redesign may not always be necessary even when self-driven medicament containers having different geometries are to be used therein. Nevertheless, if redesign becomes necessary, fewer parts of the medicament delivery device need to be adjusted, which simplifies the redesign process and reduces costs.

Drawings

Fig. 1 illustrates an embodiment of a self-driven medicament container prior to a dispensing operation.

Fig. 2 illustrates an embodiment of a self-driven medicament container at the beginning of a dispensing operation after having been activated by a user interaction.

Fig. 3 illustrates an embodiment of a self-driven medicament container at the end of a dispensing operation.

Fig. 4 illustrates another embodiment of a self-driven medicament container prior to a dispensing operation.

Fig. 5A and 5B illustrate an embodiment of a locking element of a self-driven medicament container.

Fig. 6A and 6B illustrate the embodiment of the self-driven medicament container of fig. 1-3 and 4-5, respectively, including a needle.

Fig. 7 illustrates an embodiment of a medicament delivery device prior to activation by a user.

Fig. 8A-8E illustrate different states of the medicament delivery device of fig. 7 during a dispensing operation.

Fig. 9 shows an exemplary embodiment of the needle cannula and the guiding unit in a first state.

Fig. 10 shows the needle cannula and guiding unit of fig. 9 in a second state.

Fig. 11 shows the needle cannula and guiding unit of fig. 9 in a third state.

Fig. 12 shows the needle cannula and guiding unit of fig. 9 in a fourth state.

Fig. 13 shows the needle cannula and guiding unit of fig. 9 in a fifth state.

Fig. 14 shows the needle cannula and guiding unit of fig. 9 in a sixth state.

Figure 15 shows the developed structural formula, molecular formula and molecular weight of cetuximab.

Detailed Description

In the drawings, identical elements, elements of the same kind and elements that function identically or similarly may bear the same reference numerals.

Fig. 1 illustrates an embodiment of a self-driven medicament container 10 according to an aspect of the present disclosure. The self-driven medicament container 10 comprises a reservoir body 2, a holder 3, a stopper 4, a drive element 5, a plunger and a release mechanism. The plug 4 divides the interior of the reservoir body 2 into a drive compartment 21 and a medicament compartment 22. The medicament compartment 22 contains a medicament. The medicament compartment 22 comprises an outlet 23 through which medicament may be expelled during a dispensing operation. The plug 4 seals the medicament compartment 22 towards the drive compartment 21.

The holder 3 is attached to the proximal end of the drive compartment 22 and forms a proximal end wall of said drive compartment 22. The holder 3 has an opening 31.

The plunger has a shaft 61 with a locking element at its proximal end. The locking element is formed by two flexible arms 62 each having a radial projection at their free ends. The protrusion of each flexible arm 62 engages the proximal surface of the holder 3, thereby preventing distal movement of the plunger relative to the reservoir body 2.

A contact element 63 is provided at the distal end of the shaft 61 in order to contact the stopper 4 and transfer the movement of the plunger to the stopper 4. The contact element 63 has a larger diameter than the shaft 61.

The drive element 5 is entirely inside the drive compartment 21 and extends between the distal surface of the holder 3 and the proximal surface of the contact element 63. The drive element surrounds the shaft 61.

The release mechanism comprises an activation element formed as a push button 7. The push button 7 has an engagement feature, in particular an inclined surface 71, which interacts with the inclined surface 64 of the flexible arm 62 when the push button 7 is moved in distal direction with respect to the reservoir body 2, the holder 3 and/or the plunger. The push button 7 further has guide grooves 72 which interact with the guide elements 32 of the holder 3, thereby radially supporting the push button 7 during its distal movement. The inclined surface 71 has a different inclination angle from the inclined surface 64.

As shown in fig. 2, due to the interaction of the inclined surface 71 with the inclined surface 64, the flexible arms 62 deflect radially inwards such that the free ends of the flexible arms 62 disengage from the proximal surface of the holder 3. This enables the plunger to move distally relative to the reservoir body 2.

Due to the force provided by the drive element 5, the plunger moves distally and the free end of the flexible arm 62 passes through the opening 31 (not shown in fig. 2) of the holder 3. The distal movement of the plunger is transferred to the stopper 4, which is moved distally relative to the reservoir body 2, thereby dispensing the medicament stored in the medicament compartment 22 through the outlet 23.

Fig. 3 illustrates the self-driven medicament container 10 at the end of a dispensing operation. The bung 4 has reached a final distal position at the distal end of the reservoir body 2 and all medicament stored in the medicament compartment 22 has been expelled through the outlet 23. The free end of the flexible arm 62 is completely inside the drive compartment 21 after having passed through the opening 31 of the holder 3.

Fig. 4 illustrates another embodiment of a self-driven medicament container 10'. The shaft 61 'of the plunger has a locking element formed as a stop bar 62'. The stop bar 62' abuts the proximal surface of the holder 3, thereby preventing distal movement of the plunger relative to the reservoir body 2. Correspondingly, the release mechanism has an activation element 7 'adapted to cause the stop bar 62' to rotate relative to the holder 3. The activation element 7' may be connected to the stopper rod 62' in a rotationally fixed manner or in a manner adapted to cause a rotational movement of the stopper rod 62' relative to the holder 3 in response to user interaction. Due to the rotational movement of the stopper rod 62' relative to the holder 3, the cross section of the stopper rod 62' may be aligned with the opening 31' (not shown) of the holder 3, as described below, thereby allowing movement of the plunger relative to the reservoir body 2.

The structure and other components of the self-driven medicament container of fig. 4 (even if not all of them are labeled in detail) correspond to the structure and components of the self-driven medicament container as illustrated in fig. 1-3.

As shown in fig. 5A, the shape of the opening 31 'of the holder 3 is adapted to the shape of the stopper rod 62'. Due to the rotation of the stop bar 62' relative to the holder 3, the stop bar 62' is aligned with the opening 31' as exemplarily indicated by the arrow. This causes the stop bar 62' to disengage from the retainer 3. Fig. 5B shows the stopper rod 62 'aligned with the opening 31'. In this position, the stopper rod 62 'may pass through the opening 31', thereby enabling the plunger to move distally relative to the reservoir body 2 (not shown).

After disengagement of the stop bar 62' from the proximal surface of the holder 3, the dispensing operation and interaction of the components is similar to the dispensing operation described in relation to fig. 1-3. At the end of the dispensing operation, the stop bar 62' is completely inside the actuation compartment 21.

Fig. 6A and 6B show an embodiment of a self-driven medicament container according to the illustrations in fig. 1 to 3 and 4 to 5, respectively. The self-driven medicament container of fig. 6a and 6B additionally comprises a needle 8 so that a user can inject and dispense medicament from the self-driven medicament container without additional injection means. The needle is protected and kept sterile by a needle shield 24 (not shown) attachable to the distal end of the reservoir body 2.

Fig. 7 illustrates an embodiment of a medicament delivery device 100 according to an aspect of the present disclosure. The medicament delivery device 100 comprises a self-driven medicament container 10 as illustrated in fig. 1 to 3 and 6A. The medicament delivery device 100 comprises an elongated housing 200 and an external button 300. The elongate housing 200 has a distal wall 210 against which the self-driven medicament container 10 abuts. Distal wall 210 has an opening 211 through which needle 8 protrudes distally beyond housing 200. An external button 300 is connected to a proximal portion of the housing 200. The distal inner surface of the external button 300 abuts the proximal surface of the activation button 7 such that the distal movement of the external button 300 is transferred to the activation button 7.

The medicament delivery device 100 further comprises a needle cannula 400 movably connected to the housing 200. When the needle cannula 400 is in the first position (i.e. a position prior to activation of the medicament delivery device 100 and prior to penetration of the skin of the user), the needle cannula 400 protrudes beyond the distal end of the housing 200 and the tip of the needle 8. Needle cannula 400 has an opening 410 through which needle 8 passes when needle cannula 400 is moved proximally relative to housing 200.

The medicament delivery device 100 comprises a needle cannula spring 500 positioned between the distal end wall 210 and the proximal inner surface 420 of the needle cannula 400. When needle cannula spring 500 is compressed due to proximal movement of needle cannula 400 relative to housing 200, the needle cannula spring provides a distal force to needle cannula 400.

The medicament delivery device 100 comprises a distal cap 600 configured to be detachably attached to the housing 200. The distal cap 600 includes an engagement groove that fits over the needle shield 24, thereby supporting the needle shield 24 in a radially outward direction. By moving distally relative to the housing 200, the distal cap 600 may be removed from the housing 200 by a user. Due to engagement with the distal cap 600, the needle shield 24 may be removed from the reservoir body 2 when the distal cap 600 is removed from the housing 200.

The housing 200 further includes a button lock. The button lock comprises two blocking arms 221 configured to engage the locking protrusion 310 of the external button 300 when the needle cannula 400 is in its first position, thereby blocking distal movement of the external button 300 relative to the housing 200. The blocking arm 221 is flexible and is configured to deflect radially outwardly due to interaction with the proximal end 430 of the needle cannula 400 as the needle cannula 400 moves proximally relative to the housing 200. The blocking arm 221 is disengaged from the locking protrusion 310 due to the radially outward deflection. This enables the external button 300 to move distally relative to the housing 200.

The housing 200 includes a protrusion 212 at its distal end that extends the housing in a distal direction. The protrusion 212 is configured to connect the distal cap 600 to the housing and axially guide movement of the distal cap when the distal cap 600 is attached to or detached from the housing 200.

Fig. 8A-8E illustrate different states of the medicament delivery device 100 during a dispensing operation. In fig. 8A, the medicament delivery device is in an initial position. The self-driven medicament container is inserted into the housing of the medicament delivery device. The end cap remains attached to the housing and the needle cannula is in the first position. Fig. 8B illustrates the start of a dispense operation. The cap has been removed and the user may press the distal end of the needle cannula against the desired injection site so that the needle cannula may be moved proximally inside the housing to its second position and the needle may pierce the user's skin (not shown). The needle cannula spring is compressed as the needle cannula moves proximally relative to the housing.

As illustrated in fig. 8C, the user may then activate the medicament delivery device by pushing the external button distally relative to the housing. This disengages the locking element of the self-driven medicament container from the retainer. The plunger and stopper are urged distally relative to the reservoir body due to the force of the drive element in the drive compartment. As the stopper is moved distally relative to the reservoir body, the medicament stored in the medicament compartment is expelled through the outlet and the needle. In other words, the medicament is injected into the body of the user.

Fig. 8D illustrates the end of the dispense operation. The stopper has reached the distal wall of the reservoir body. Thus, the medicament compartment has been emptied and all medicament has been injected into the body of the user.

As shown in fig. 8E, when the user removes the medicament delivery device from the injection site, the force of the needle cannula spring pushes the needle cannula distally relative to the housing and the needle such that the tip of the needle is covered by the needle cannula.

Any invention described herein is not limited by the description in connection with the exemplary embodiments. Rather, the invention and the associated disclosure include any novel feature and any combination of features, in particular including any combination of features in the patent claims, even if said feature or said combination itself is not explicitly stated in the patent claims or in the exemplary embodiments.

Fig. 9 shows a cut-away side view of an exemplary embodiment of a needle cannula 400 and a guiding unit 700 in a first state. In the first state of the needle cannula 400, the medicament delivery device 100 has not been arranged on the skin of the user and the needle cannula 400 protects the needle 8.

Needle cannula 400 includes guide pin 90, torsion guard 92, and flexible rod 94. The guide pin 90 protrudes outwardly from the outer wall of the needle cannula 400. These flexible rods 94 are separated by through recesses extending through the wall of the needle cannula 400. Thus, the flexible rod 94 and the body of the needle cannula 400 may be made of one piece. The torsion guard 92 may comprise a rod extending in the axial direction of the needle cannula (i.e., in the vertical direction in fig. 9).

The guide unit 700 includes a first passage 96 and a second passage 97. The first channel 96 extends first against the axial direction with a sliding incline and then extends substantially in the axial direction towards a bend 98 of the first channel 96 and then returns towards a dead end 99 of the first channel 96. Dead end 99 is separated from the remainder of first channel 96 by barb 102. In the first state of needle cannula 400, guide pin 90 is disposed in a portion of first channel 96 below dead end 99 and at the beginning of the bevel of first channel 96.

The torsion guard 92 of the needle cannula 400 is arranged in the second channel 97 and guided by the second channel 97 during movement of the needle cannula 400 relative to the guiding unit 700. The second channel 97 is straight and parallel to the direction of movement of the needle cannula 400. The torsion guard 92 in the second channel 97 acts as a guard that protects the needle cannula 400 from rotation of the needle cannula 400.

Fig. 10 shows the needle cannula 400 and the guiding unit 700 of fig. 9 in a second state. In the second state of the needle cannula 400, the needle cannula 400 may be partially arranged within the guiding unit 700, e.g. due to the medicament delivery device 100 being partially arranged on the skin of the user. In the second state of needle cannula 400, guide pin 90 moves within first channel 96 toward bend 98. When the guide pin 90 passes the inclined portion of the first channel 96, the upper portion of the needle cannula 400 moves perpendicular to the direction of movement of the needle cannula 400 and the flexible rod 94 flexes because the remaining portion of the needle cannula 400 is secured against rotation by the torsion guard 92 within the second channel 97. Thus, the flexible rod 94 is biased.

Fig. 11 shows the needle cannula 400 and the guiding unit 700 of fig. 9 in a third state. In the third state of the needle cannula 400, the needle cannula 400 is fully pressed into the guiding unit 700, e.g. due to the user arranging the medicament delivery device 100 on his/her skin. Thus, in the third state of needle cannula 400, needle 8 is exposed by needle cannula 400. In this case, guide pin 90 has reached bend 98 of first channel 96 and can move within bend 98 perpendicular to the direction of movement of needle cannula 400. In the third state of needle cannula 400, biased flexible rod 94 forces guide pin 90 past bend 98.

Fig. 12 shows the needle cannula 400 and the guiding unit 700 of fig. 9 in a fourth state. In the fourth state of the needle cannula 400, the flexible rod 94 is released and the guide pin 90 has moved within the bend 98 perpendicular to the direction of movement of the needle cannula 400.

Fig. 13 shows the needle cannula 400 and the guiding unit 700 of fig. 9 in a fifth state. In a fifth state of the needle cannula 400, the medicament delivery device 100 may be partially removed from the skin of the user. The guide pin 90 is forced past the barb 102 of the first channel 100 so that the flexible rod 94 is again biased. When the medicament delivery device 100 is removed from the skin of the user, the needle cannula 400 may be pushed out of the housing 200, for example by a conventional needle cannula spring (not shown), such that the guide pin 90 is forced over the barb 102.

Fig. 14 shows the needle cannula 400 and the guiding unit 700 of fig. 9 in a sixth state. In the sixth state of the needle cannula 400, the medicament delivery device 100 may be completely removed from the skin of the user. Needle cannula 400 may completely cover needle 8. The guide pin 90 snaps into the dead end 99 of the first channel 96 such that the needle cannula 400 is fixedly engaged to the guide unit 700.

The terms "drug" or "medicament" are used synonymously herein and describe a pharmaceutical formulation comprising one or more active pharmaceutical ingredients or a pharmaceutically acceptable salt or solvate thereof, and optionally a pharmaceutically acceptable carrier. In the broadest sense, an active pharmaceutical ingredient ("API") is a chemical structure that has a biological effect on humans or animals. In pharmacology, drugs or agents are used to treat, cure, prevent or diagnose diseases or to otherwise enhance physical or mental well-being. The medicament or agent may be used for a limited duration or periodically for chronic disorders.

As described below, the drug or medicament may include at least one API in different types of pharmaceutical formulations or combinations thereof for treating one or more diseases. Examples of APIs may include small molecules (having a molecular weight of 500 Da or less), polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments and enzymes), carbohydrates and polysaccharides, as well as nucleic acids, double-or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids (such as antisense DNA and RNA), small interfering RNAs (sirnas), ribozymes, genes and oligonucleotides. The nucleic acid may be incorporated into a molecular delivery system (such as a vector, plasmid, or liposome). Mixtures of one or more drugs are also contemplated.

The medicament or agent may be contained in a primary package or "medicament reservoir" suitable for use with a medicament delivery device. The drug reservoir 101a may be, for example, a cartridge, syringe, reservoir, or other sturdy or flexible vessel (bag) configured to provide a suitable chamber for storing (e.g., short-term or long-term storage) one or more drugs. For example, in some cases, the chamber may be designed to store the drug for at least one day (e.g., 1 day to at least 30 days). In some cases, the chamber may be designed to store the drug for about 1 month to about 2 years. Storage may be at room temperature (e.g., about 20 ℃) or at refrigeration temperatures (e.g., about-4 ℃ to about 4 ℃). In some cases, the drug reservoir may be or include a dual chamber cartridge configured to separately store two or more components of the 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 may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., through a conduit between the two chambers) and allow a user to mix the two components as desired prior to dispensing. Alternatively or additionally, the two chambers may be configured to allow mixing when the components are dispensed into a human or animal body.

The drugs or agents contained in the drug delivery devices as described herein may be used to treat and/or prevent many different types of medical disorders. Examples of disorders include, for example, diabetes or complications associated with diabetes (such as diabetic retinopathy), thromboembolic disorders (such as deep vein or pulmonary thromboembolism). Further examples of disorders are Acute Coronary Syndrome (ACS), angina pectoris, myocardial infarction, tumors, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in the manual such as Rote list 2014 (e.g., without limitation, main group 12 (antidiabetic drugs) or 86 (oncology drugs)) and Merck Index (Merck Index) version 15.

Examples of APIs for the treatment and/or prevention of type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin (e.g., human insulin, or a human insulin analog or derivative), glucagon-like peptide (GLP-1), GLP-1 analog or GLP-1 receptor agonist, or an analog or derivative thereof, dipeptidyl peptidase-4 (DPP 4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms "analog" and "derivative" refer to polypeptides having a molecular structure that may be formally derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin) by deletion and/or exchange of at least one amino acid residue present in the naturally occurring peptide and/or by addition of at least one amino acid residue. The amino acid residues added and/or exchanged may be encodable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogs are also known as "insulin receptor ligands". In particular, the term "derivative" refers to a polypeptide having a molecular structure that may be formally derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin) in which one or more organic substituents (e.g., fatty acids) are bound to one or more amino acids. Alternatively, one or more amino acids present in a naturally occurring peptide may have been deleted and/or replaced with other amino acids (including non-encodable amino acids), or amino acids (including non-encodable amino acids) have been added to a naturally occurring peptide.

Examples of insulin analogues are Gly (A21), arg (B31), arg (B32) human insulin (insulin glargine), lys (B3), glu (B29) human insulin (insulin glulisine), lys (B28), pro (B29) human insulin (insulin lispro), asp (B28) human insulin (insulin aspart), human insulin wherein the proline at position B28 is replaced by Asp, lys, leu, val or Ala and wherein the Lys at position B29 may be replaced by Pro, ala (B26) human insulin, des (B28-B30) human insulin, des (B27) human insulin and Des (B30) human insulin.

Examples of insulin derivatives are, for example, B29-N-myristoyl-des (B30) human insulin, lys (B29) (N-myristoyl) -des (B30) human insulin (Det insulin, levemir) B29-N-palmitoyl-des (B30) human insulin, B29-N-myristoyl human insulin, B29-N-palmitoyl human insulin, B28-N-myristoyl LysB28ProB29 human insulin, B28-N-palmitoyl-LysB 28ProB29 human insulin, B30-N-myristoyl-ThrB 29LysB30 human insulin, B30-N-palmitoyl-ThrB 29LysB30 human insulin, B29-N- (N-palmitoyl-gamma-glutamyl) -des (B30) human insulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des (B30) human insulin (De insulin, tresiba) B29-N- (N-palmitoyl-gamma-glutamyl) -des (B30) human insulin and B29-carboxyglutamyl-des (B30) human insulin.

Examples of GLP-1, GLP-1 analogs and GLP-1 receptor agonists are, for example, lixiviapeptide (Lyxumia), exenatide (Exendin-4, byetta, bydureon, 39 amino acid peptides produced by the salivary glands of Ji Ladu Exendin (Gila monster), liraglutide (Victoza), cable Ma Lutai, tasraglutide, abirstupeptide (Syncria), dolraglutide (Trulicity), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, lanraglatin (LANGLENATIDE)/HM-11260C (Ai Pi-peptide （Efpeglenatide））、HM-15211、CM-3、GLP-1 Eligen、ORMD-0901、NN-9423、NN-9709、NN-9924、NN-9926、NN-9927、Nodexen、Viador-GLP-1、CVX-096、ZYOG-1、ZYD-1、GSK-2374697、DA-3091、MAR-701、MAR709、ZP-2929、ZP-3022、ZP-DI-70、TT-401（Pegapamodtide）、BHM-034.MOD-6030、CAM-2036、DA-15864、ARI-2651、ARI-2255、 tenipotene (LY 3298176), bamadutide (SAR 425899), exenatide-XTEN and glucagon-Xten.

Examples of oligonucleotides are, for example, sodium milbemex (Kynamro x), cholesterol-reducing antisense therapeutic agents for the treatment of familial hypercholesterolemia, or RG012 for the treatment of Alport syndrome.

Examples of DPP4 inhibitors are linagliptin, vildagliptin, sitagliptin, duloxetine, saxagliptin, berberine.

Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists such as gonadotrophin (follitropin, luteinizing hormone, chorionic gonadotrophin, fertility promoter), somatotropin (growth hormone), desmopressin, terlipressin, gonadorelin, triptorelin, leuprolide, buserelin, nafarelin and goserelin.

Examples of polysaccharides include glycosaminoglycans, 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-F20 (Synvisc), a sodium hyaluronate.

As used herein, the term "antibody" refers to an immunoglobulin molecule or 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 may be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or 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 to an Fc receptor. For example, an antibody may be an isotype or subtype, an antibody fragment or mutant that does not support binding to Fc receptors, e.g., its Fc receptor binding region has been mutagenized or deleted. The term "antibody" also includes Tetravalent Bispecific Tandem Immunoglobulin (TBTI) -based antigen binding molecules and/or double variable region antibody-like binding proteins with cross-binding region orientation (CODV).

The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., an antibody heavy and/or light chain polypeptide) derived from an antibody polypeptide molecule that does not comprise a full-length antibody polypeptide, but still comprises at least a portion of a full-length antibody polypeptide capable of binding an antigen. An antibody fragment may comprise a cleavage portion of a full-length antibody polypeptide, although the term is not limited to such a cleavage fragment. Antibody fragments useful in the present invention include, for example, fab fragments, F (ab') 2 fragments, scFv (single chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, triabodies or diabodies, intracellular antibodies, nanobodies, minibodies, modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies and antibodies comprising VHH. Additional examples of antigen-binding antibody fragments are known in the art.

The term "complementarity determining region" or "CDR" refers to a short polypeptide sequence within the variable regions of both heavy and light chain polypeptides, which is primarily responsible for mediating specific antigen recognition. The term "framework region" refers to an amino acid sequence within the variable region of both a heavy chain polypeptide and a light chain polypeptide that is not a CDR sequence and is primarily responsible for maintaining the correct positioning of the CDR sequences to allow antigen binding. Although the framework regions are not themselves typically directly involved in antigen binding, as known in the art, certain residues within the framework regions of certain antibodies may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDRs to interact with an antigen.

Examples of antibodies are anti-PCSK-9 mAb (e.g., ash Li Xiyou mab), anti-IL-6 mAb (e.g., sha Lilu mab), and anti-IL-4 mAb (e.g., dupumab).

Additional 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 cetuximab. The terms "prevention" and "prophylactic treatment" are used interchangeably herein

It is also contemplated that pharmaceutically acceptable salts of any of the APIs described herein are used in medicaments or medicaments in a drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts.

It will be appreciated by those skilled in the art that modifications (additions and/or deletions) may be made to the different components, pharmaceutical formulations, devices, methods, systems and embodiments of the API described herein without departing from the full scope and spirit of the invention, and that the invention encompasses such modifications and any and all equivalents thereof.

An example drug delivery device may involve a needle-based injection system as described in table 1 of section 5.2 of ISO 11608-1:2014 (E). Needle-based injection systems can be broadly divided into multi-dose container systems and single-dose (partially or fully empty) container systems, as described in ISO 11608-1:2014 (E). The container may be a replaceable container or an integrated non-replaceable container.

As further described in ISO 11608-1:2014 (E), multi-dose container systems may involve needle-based injection devices with replaceable containers. In such a system, each container contains a number of doses, which may be of fixed or variable size (preset by the user). Another multi-dose container system may involve a needle-based injection device with an integral non-replaceable container. In such a system, each container contains a number of doses, which may be of fixed or variable size (preset by the user).

As further described in ISO 11608-1:2014 (E), single dose container systems may involve needle-based injection devices with replaceable containers. In one example of such a system, each container contains a single dose, wherein the entire deliverable volume is expelled (completely emptied). In further examples, each container contains a single dose, wherein a portion of the deliverable volume is expelled (partially emptied). Also as described in ISO 11608-1:2014 (E), single dose container systems may involve needle-based injection devices with integrated non-exchangeable containers. In one example of such a system, each container contains a single dose, wherein the entire deliverable volume is expelled (completely emptied). In further examples, each container contains a single dose, wherein a portion of the deliverable volume is expelled (partially emptied).

API for use of non-toxilan as a medicament in devices

The non-toxilan is a synthetic chemically modified double-stranded small interfering RNA (siRNA) oligonucleotide that is covalently linked to a tri-antennal N-acetyl-galactosamine (GalNAc) ligand that targets AT3 mRNA in the liver, thereby inhibiting the synthesis of antithrombin. See, e.g., pasi et al, N Engl J Med. [ J.New England medical ] (2017) 377 (9): 819-28. The nucleosides in each strand of the non-toxilan are linked by 3'-5' phosphodiester or phosphorothioate linkages, thereby forming the sugar-phosphate backbone of the oligonucleotide.

The sense and antisense strands contain 21 and 23 nucleotides, respectively. The 3' end of the sense strand is conjugated to a GalNAc-containing moiety (referred to herein as L96) via a phosphodiester linkage. The sense strand contains two consecutive phosphorothioate linkages at its 5' end. The antisense strand contains four phosphorothioate linkages, two at the 3 'end and two at the 5' end. The 21 nucleotides of the sense strand hybridize 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 (two-base overhang). See also U.S. patent 9,127,274, U.S. patent 11,091,759, U.S. patent 2020/0163987 A1 and WO 2019/014187, each of which is expressly incorporated herein by reference in its entirety.

The two nucleotide chains of the non-toxilan are shown below:

Sense strand 5 'gf-ps-Gm-ps-Uf-Um-Af-Am-Cf-Cf-Af-Um-Uf-Um-Af-Cm-Uf-Um-Cf-Cf-Cf-Am-Af-L96' (SEQ ID NO: 1), and

Antisense strand ：5' Um-ps-Uf-ps-Gm-Af-Am-Gf-Um-Af-Am-Af-Um-Gm-Gm-Uf-Gm-Uf-Um-Af-Am-Cf-Cm-ps-Am-ps-Gm 3'（SEQ ID NO:2）,

Wherein, the

Af=2 '-deoxy-2' -fluoroadenosine

Cf=2 '-deoxy-2' -fluorocytidine

Gf=2 '-deoxy-2' -fluoroguanosine

Uf=2 '-deoxy-2' -fluorouridine

Am=2' -O-methyladenosine

Cm=2' -O-methylcytidine

Gm=2' -O-methylguanosine

Um = 2' -O-methyluridine

"-" (Hyphen) =3 '-5' phosphodiester linkage sodium salt

"-Ps" = 3'-5' phosphorothioate linkage sodium salt

And wherein L96 has the formula:

(I)。

As used herein, the terms "2' -deoxy-2 ' -fluoroadenosine" and "2' -fluoroadenosine" are used interchangeably.

As used herein, the terms "2' -deoxy-2 ' -fluorocytidine" and "2' -fluorocytidine" are used interchangeably.

As used herein, the terms "2' -deoxy-2 ' -fluoroguanosine" and "2' -fluoroguanosine" are used interchangeably.

As used herein, the terms "2' -deoxy-2 ' -fluorouridine" and "2' -fluorouridine" are used interchangeably.

The developed structural formula, molecular formula and molecular weight of the etoposide are shown in fig. 15.

The structure of the non-toxilan can also be described by the following diagram, wherein X is O:

。

the etoposide is shown in fig. 15 as the sodium salt.

In some embodiments, the device delivers the cetuximab in an aqueous solution, wherein the concentration of the cetuximab 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 between the ranges and values are also intended to be part of the present disclosure. Further, it is intended to include ranges of values using any combination of the recited values as upper and/or lower limits. In further embodiments, the pharmaceutical formulation comprises cetuximab at a concentration of about 40, about 50, about 75, about 100, about 125, about 150, or about 200 mg/mL in aqueous solution. In certain embodiments, a concentration of about 100 mg/mL of cetuximab in an aqueous solution is provided.

The term "delivery" is intended to mean "administration".

Unless specifically stated or otherwise apparent from the context, as used herein, the term "about" or "approximately" refers to a value that is within an acceptable error range for the particular value determined by one of ordinary skill, a portion of which will depend on how the measurement or determination is made. For example, "about" or "approximately" may mean a range of up to 10% (i.e., ±10%). Thus, "about" or "approximately" may be understood to be 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 particular value is provided in this disclosure, unless otherwise indicated, the meaning of "about" or "approximately" should be assumed to be within an acceptable error range for the particular value.

Although the weight of the dosage of the cetuximab described herein refers to the weight of the free acid (active moiety) of the cetuximab, the administration of the cetuximab to a patient herein refers to the administration of the sodium (bulk drug) of the cetuximab provided in a pharmaceutically suitable aqueous solution (e.g., phosphate buffered saline at physiological pH). For example, about 100 mg/mL of cetuximab means that about 100 mg cetuximab free acid (equivalent to about 106 mg cetuximab sodium, bulk drug) is contained per mL. Unless otherwise indicated, the weight of the non-tragacanth recited in the present disclosure is the weight of the non-tragacanth free acid (active moiety).

In some embodiments, the pharmaceutical formulation in the device comprises etoposide in phosphate buffered saline. The phosphate concentration in the solution may be from about 1 to about 10mM (e.g., about 2, about 3, about 4, about 5, about 6, about 7, about 8, or about 9 mM), and the pH is from about 6.0 to 8.0. The pharmaceutical formulations herein may include a stabilizer, such as EDTA. The pharmaceutical formulation may be preservative-free. In some embodiments, the pharmaceutical formulations of cetuximab in the device are preservative-free and comprise, consist of, or consist essentially of about 100 mg cetuximab in about 100 mg cetuximab per mL of about 5mM Phosphate Buffered Saline (PBS) solution. In some embodiments, the pharmaceutical formulation of cetuximab in the device is preservative-free and comprises, consists of, or consists essentially of cetuximab in approximately 5mM Phosphate Buffered Saline (PBS) solution. The PBS solution consisted of sodium chloride, disodium hydrogen phosphate (heptahydrate) and sodium dihydrogen phosphate (monohydrate). The pH of the pharmaceutical formulation may be adjusted to about 7.0 or about 7.1 using sodium hydroxide solution and diluted phosphoric acid.

In some embodiments, the pharmaceutical formulation of cetuximab in the device for subcutaneous delivery contains cetuximab in 5mM phosphate buffered saline at pH 7.0, the phosphate buffered saline having 0.64 mM NaH ₂PO₄、4.36 mM Na₂HPO₄ and 84 mM NaCl. In certain embodiments, pharmaceutical formulations of the cetuximab solution for subcutaneous delivery are shown in table 1 below:

TABLE 1 exemplary pharmaceutical formulations of cetuximab

Proper amount of

In some embodiments, pharmaceutical formulations of a solution of cetuximab for subcutaneous delivery with a device may be described, as shown in table 2 below.

TABLE 2 exemplary pharmaceutical formulations of cetuximab

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

In one embodiment, the device may be used to deliver a single dose of approximately 80 mg of cetuximab. In one embodiment, the device may be used to deliver a single dose of approximately 50 mg of cetuximab. In one embodiment, the device may be used to deliver a single dose of approximately 20mg of cetuximab. In one embodiment, the device may be used to deliver a single dose of approximately 30 mg of cetuximab. In one embodiment, the device may be used to deliver a single dose of approximately 10 mg of cetuximab. In one embodiment, the device may be used to deliver a single dose of approximately 5 mg of cetuximab. In one embodiment, the device may be used to deliver a single dose of approximately 2.5 mg of cetuximab. In one embodiment, the device may be used to deliver a single dose of approximately 1.25 mg of cetuximab.

In some embodiments, a single dose of cetuximab may be delivered in a delivery volume of about 0.5 mL to about 1mL (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL). Other delivery volumes described herein may also be used.

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

In one embodiment, the device delivers the etoriclan in a prophylactically effective amount to prophylactically treat hemophilia (e.g., hemophilia a or B patients with or without inhibitors) in a patient in need thereof (e.g., hemophilia a or B patients with or without inhibitors). "prophylactically effective amount" refers to an amount of atoxin that aids a patient with hemophilia a or B (with or without inhibitors) to reach a desired clinical endpoint, such as a reduction in Annual Bleeding Rate (ABR), annual joint bleeding rate (AjBR), annual spontaneous bleeding rate (AsBR), or frequency of bleeding episodes. As used herein, the term "treatment" in the context of atosiban includes prophylactic treatment of a disease and refers to reaching a desired clinical endpoint.

Hemophilia a or B patients with inhibitors refer to patients who have produced alloantibodies to their previously accepted factors (e.g., factor VIII for hemophilia a patients or factor IX for hemophilia B patients). Hemophilia a or B patients with inhibitors can be refractory to alternative clotting factor therapies. Patients without inhibitors are patients without such alloantibodies. The present methods of treatment may be beneficial to hemophilia a patients with inhibitors and hemophilia B patients with inhibitors.

As used herein, a patient with "hemophilia a or B (with or without inhibitor)" refers to either 1) a hemophilia a patient with an inhibitor, or 2) a hemophilia B patient with an inhibitor, 3) a hemophilia a patient without an inhibitor, or 4) a hemophilia B patient without an inhibitor. As used herein, a patient refers to a human patient. A patient may also refer to a human subject.

In some embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of about 50 mg of non-tussilagin once every two months (or every eight weeks). In other embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of approximately 50 mg a month (or four weeks) of atosiban. In still other embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of about 80 mg of non-tussilagin every two months (or every eight weeks). In still other embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of approximately 80 mg a month (or four weeks) of atosiban. In still other embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of approximately 20 mg of non-tussilagin every two months (or every eight weeks). In still other embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of approximately 20 mg a month (or four weeks) of atosiban. In still other embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of approximately 10 mg a month (or four weeks) of atosiban. In still other embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of approximately 30 mg a month (or four weeks) of atosiban. In still other embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of approximately 5 mg a per month (or four weeks) of atosiban. In still other embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of approximately 2.5 mg per month (or four weeks) of atosiban. In still other embodiments, the device may be used for prophylactic treatment of patients with hemophilia a or B (with or without inhibitors) with a subcutaneous dose of approximately 1.25 mg per month (or four weeks) of atosiban.

Accordingly, provided herein is a method of prophylactic treatment of a patient suffering from hemophilia a or hemophilia B (with or without inhibitors), the method comprising subcutaneously delivering to the patient in need thereof a prophylactically effective amount of atoxin using the device. A prophylactically effective amount of cetuximab may be any of the dosages provided herein, such as from about 1mg to about 80 mg, from about 1mg to about 30 mg, or from about 20 mg to about 80 mg. A prophylactically effective amount of cetuximab may be, for example, about 1.25 mg, about 2.5 mg, about 5mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. A prophylactically effective amount of cetuximab may be delivered monthly (or every four weeks) or every two months (or every eight weeks). The non-toxilan may 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).

As an example, a method of prophylactic treatment of a patient suffering from hemophilia a or hemophilia B (with or without inhibitors) may comprise subcutaneously delivering about 50 mg of the non-tussilags with the device once a month (or four weeks) or once every two months (or eight weeks) to a patient in need thereof. About 50 mg of the non-trastulan may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg non-trastulan/mL).

Further provided herein is a method of reducing the frequency of bleeding episodes in a patient suffering from hemophilia a or B (with or without inhibitors), the method comprising subcutaneously delivering a prophylactically effective amount of cetuximab to a patient in need thereof with the device. A prophylactically effective amount of cetuximab may be any of the dosages provided herein, such as from about 1mg to about 80 mg, from about 1mg to about 30 mg, or from about 20 mg to about 80 mg. A prophylactically effective amount of cetuximab may be, for example, about 1.25 mg, about 2.5 mg, about 5mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. A prophylactically effective amount of cetuximab may be delivered monthly (or every four weeks) or every two months (or every eight weeks). The non-toxilan may 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).

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

Further, provided herein is a method of reducing ABR in a patient suffering from hemophilia a or B (with or without inhibitors), the method comprising subcutaneously delivering a prophylactically effective amount of cetuximab to a patient in need thereof with the device. A prophylactically effective amount of cetuximab may be any of the dosages provided herein, such as from about 1 mg to about 80 mg, from about 1 mg to about 30 mg, or from about 20 mg to about 80 mg. A prophylactically effective amount of cetuximab may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. A prophylactically effective amount of cetuximab may be delivered monthly (or every four weeks) or every two months (or every eight weeks). The non-toxilan may 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).

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

Further, provided herein is a method of reducing AjBR in a patient having hemophilia a or B (with or without an inhibitor), the method comprising subcutaneously delivering a prophylactically effective amount of cetuximab to a patient in need thereof with the device. A prophylactically effective amount of cetuximab may be any of the dosages provided herein, such as from about 1 mg to about 80 mg, from about 1 mg to about 30 mg, or from about 20 mg to about 80 mg. A prophylactically effective amount of cetuximab may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. A prophylactically effective amount of cetuximab may be delivered monthly (or every four weeks) or every two months (or every eight weeks). The non-toxilan may 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).

As an example, a method of reducing AjBR in a patient with hemophilia a or B (with or without inhibitors) may include subcutaneously delivering about 50 mg of etoposide to the patient in need thereof with the device once a month (or four weeks) or once every two months (or eight weeks). About 50 mg of the non-trastulan may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg non-trastulan/mL).

Further, provided herein is a method of reducing AsBR in a patient having hemophilia a or B (with or without an inhibitor), the method comprising subcutaneously delivering a prophylactically effective amount of cetuximab to a patient in need thereof with the device. A prophylactically effective amount of cetuximab may be any of the dosages provided herein, such as from about 1 mg to about 80 mg, from about 1 mg to about 30 mg, or from about 20 mg to about 80 mg. A prophylactically effective amount of cetuximab may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. A prophylactically effective amount of cetuximab may be delivered monthly (or every four weeks) or every two months (or every eight weeks). The non-toxilan may 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).

As an example, a method of reducing AsBR in a patient with hemophilia a or B (with or without inhibitors) may include subcutaneously delivering about 50 mg of etoposide to the patient in need thereof with the device once a month (or four weeks) or once every two months (or eight weeks). About 50 mg of the non-trastulan may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg non-trastulan/mL).

Reference numerals

2 Reservoir body

3 Retainer

4 Plug

5 Drive element

7,7' Activating element

8 Syringe needle

10,10' Self-driven medicament container

21 Drive compartment

22 Medicament compartment

23 Outlet

24-Needle shield

31,31' Opening

32 Guide element

61,61' Shaft

62 Flexible arm

62' Stop bar

63 Contact element

64 Inclined surface

71 Engagement feature

72 Guide groove

90 Guide pin

92 Torsion protector

94 Flexible rod

96 First channel

97 Second channel

98 Bent part

99 Dead end

100 Medicament delivery device

102 Barb

200 Shell

210 Distal wall

211 Opening

212 Projection

221 Blocking arm

300 External button

310 Locking projection

400 Syringe needle sleeve

410 Opening

420 Proximal inner surface

430 Proximal end

500 Needle sleeve spring

600 End cap

700 Guide unit.

Claims

1. A self-driven medicament container (10, 10 ') for storing and expelling a medicament in response to a user interaction, the self-driven medicament container (10, 10') comprising:

A reservoir body (2);

A holder (3);

a plug (4) configured to divide the interior of the reservoir body (2) into a drive compartment (21) and a medicament compartment (22), the medicament compartment (22) containing the medicament and comprising an outlet (23) through which the medicament can be expelled in a dispensing operation, and

A drive element (5);

A plunger having a shaft (61, 61 ') with a locking element (62, 62') configured to engage the holder (3) to prevent distal movement of the plunger relative to the reservoir body (2) and a contact element (63) configured to contact the stopper (4), and

A release mechanism configured to disengage the locking element (62, 62') from the retainer (3) in response to the user interaction, thereby enabling distal movement of the plunger relative to the reservoir body (2),

Wherein the medicament compartment (22) is distal to the drive compartment (21);

wherein the drive element (5) is positioned in the drive compartment (21) before and after disengagement of the locking element (62, 62') from the holder (3);

Wherein the plug (4) is further configured to seal the medicament compartment (22) from the drive compartment (21), and

Wherein the drive element (5) is configured to provide an axial force to the plunger when the locking element (62, 62') is disengaged from the holder (3) in order to move the plunger distally relative to the reservoir body (2), thereby moving the bung (4) relative to the reservoir body (2) and expelling the medicament.

2. The self-driven medicament container (10, 10') of claim 1, wherein the reservoir body (2) has an inner wall surface in contact with the medicament, the inner wall surface defining an inner cross section of the reservoir body (2).

3. The self-driven medicament container (10, 10') of claim 2, wherein the internal cross-section of the reservoir body (2) is constant at least along the length of the reservoir body (2) along which the stopper (4) moves during the dispensing operation.

4. The self-driven medicament container (10, 10') of claim 2 or 3, wherein the interior wall surface of the reservoir body is configured to be continuously connected to an outer surface of the self-driven medicament container.

5. The self-driven medicament container (10, 10') according to any one of claims 2 to 4, wherein the inner cross-section is circular.

6. The self-driven medicament container (10, 10') according to any of the preceding claims, wherein the drive element (5) is a spring.

7. The self-driven medicament container (10, 10 ') according to any of the preceding claims, wherein the release mechanism comprises an activation element (7, 7') configured to disengage the locking element (62, 62 ') from the holder (3) when an activation movement is performed, wherein the activation movement comprises an axial and/or rotational movement of the activation element (7, 7') relative to the reservoir body (2).

8. The self-driven medicament container (10, 10 ') according to any one of the preceding claims, wherein the shaft (61, 61 ') extends into the reservoir body (2) through an opening (31, 31 ') in the holder (3) such that the locking element (62, 62 ') is proximal to the holder (3) before said disengagement, and wherein the opening (31, 31 ') is configured such that the locking element (62, 62 ') can pass through the holder (3) when the locking element (62, 62 ') has been disengaged from the holder (3).

9. The self-driven medicament container (10, 10 ') of claim 7 or 8, wherein an abutment can be established between an engagement feature formed on one of the locking element (62, 62') and the activation element (7, 7 ') and an inclined surface provided on the other of the locking element (62, 62') and the activation element (7, 7 '), wherein the locking element (62, 62') is disengaged from the retainer (3) when the abutment has been established and the engagement feature moves relative to, e.g. slides along, the inclined surface.

10. The self-driven medicament container (10, 10 ') of one of claims 7 to 9, wherein the locking element (62, 62') is formed by two or more flexible arms (62) configured to deflect radially in response to movement of the activation element (7) relative to the reservoir body (2).

11. The self-driven medicament container (10, 10') of claim 10, wherein the flexible arms (62) are evenly distributed in the circumferential direction.

12. The self-driven medicament container (10, 10 ') of one of claims 7 to 9, wherein the locking element (62, 62 ') is formed by a stopper rod (62 ') configured to abut a proximal surface of the holder (3) prior to the user interaction, and wherein the locking element (62 ') is configured to rotate relative to the holder (3) in response to the user interaction so as to be aligned with an opening (31 ') of the holder (3) such that the locking element (62 ') is capable of passing through the opening (31 ') in a distal direction.

13. The self-driven medicament container (10, 10') according to any of the preceding claims, wherein the holder (3) is mounted to the proximal end of the reservoir body (2) or to an inner wall of the reservoir body (2).

14. The self-driven medicament container (10, 10') of any one of the preceding claims, wherein the drive element (5) is fully accommodated in a drive compartment (21) of the reservoir body (2).

15. The self-driven medicament container (10, 10') according to any one of the preceding claims, wherein the distally facing end surface of the contact element (63) is a closing surface configured to contact the stopper (4) over its entire cross-section.

16. The self-driven medicament container (10, 10 ') according to any of the preceding claims, wherein the longitudinal axis of the shaft (61, 61 ') is parallel to the longitudinal axis of the reservoir body (2) before the locking element (62, 62 ') is disengaged from the holder (3).

17. A medicament delivery device (100, 100') comprising:

Self-driven medicament container (10, 10') according to any of the preceding claims,

-A needle (8) connected to the outlet (23);

An elongate housing (200) against which the self-driven medicament container (10, 10') abuts, wherein the elongate housing (200) has a distal wall (210) with an opening (211) through which the needle (8) protrudes distally beyond the housing (200), and

An external button (300) connected to a proximal portion of the housing (200) and configured to interact with a release mechanism of the self-driven medicament container (10, 10 ') such that the locking element (62, 62') is disengaged from the retainer (3) when the external button (300) is moved distally relative to the housing (200).

18. The medicament delivery device (100, 100') according to claim 17, further comprising:

A needle cannula (400) movably connected to the housing (200) and protruding distally beyond the tip of the needle (8) in a first position;

Wherein the housing (200) comprises a button lock (221) configured to engage with the external button (300) to block distal movement of the external button (300) relative to the housing (200) when the needle cannula (400) is in its first position, and configured to disengage from the external button (300) when the needle cannula (400) is moved proximally relative to the housing (200) to a second position.

19. The medicament delivery device (100, 100') of claim 18, wherein the push button lock (221) comprises at least two blocking arms (221) configured to deflect radially outwards due to interaction with the needle cannula (400) when the needle cannula (400) is moved proximally relative to the housing (200) from its first position to its second position.