Patent Application
20240207530
A drive subassembly for a drug delivery device is provided. Furthermore, an arrangement comprising such a drive subassembly, a method for assembling a drug delivery device, a container-holder subassembly for a drug delivery device, a kit and a drug delivery device are provided.
Administering an injection is a process which presents a number of risks and challenges for users and healthcare professionals, both mental and physical. A drug delivery device may aim to make self-injection easier for patients. A conventional drug delivery device may provide the force for administering the injection by a spring, and trigger button or another mechanism may be used to activate the injection. Drug delivery devices may be single-use or reusable devices.
An improved drive subassembly for a drug delivery device, an improved arrangement, an improved method for assembling a drug delivery device, an improved container-holder subassembly for a drug delivery device, an improved kit, and an improved drug delivery device are disclosed.
Firstly, the drive subassembly for a drug delivery device is specified.
According to at least one embodiment, the drive subassembly comprises a housing element. The housing element may be hollow and/or elongated. The housing element may be a sleeve, e.g. a cylindrically-shaped sleeve. Particularly, the housing element may be a holder for an energy member such as a drive spring, i.e. an element in which an energy member can be stored. The energy member may be secured to the housing element, e.g. by fixing one end of the drive spring to the housing element.
According to at least one embodiment, the drive subassembly comprises a drive member. The drive member may be arranged rotatably and/or axially movable with respect to the housing element. The drive member may be hollow and/or elongated. The drive member may be a sleeve. For example, the drive member is a rotating collar. The drive member may be configured to be rotated in only one or two opposite rotational directions. The rotational axis of the drive member may define or coincide with a longitudinal axis of the drive subassembly or of the drug delivery device. The drive member may be secured to the energy member, e.g. by fixing a further end of the drive spring to the drive member.
According to at least one embodiment, the drive subassembly comprises an energy member configured to provide energy in order to induce a torque onto the drive member, preferably to drive the drive member. The torque may tend to rotate the drive member in a first rotational direction. In other words, the energy member may be configured to provide energy in order to rotate the drive member relative to the housing element in a first rotational direction. A rotation of the drive member induced by the energy member may be configured to induce a drug delivery process, particularly, when the drive subassembly is assembled into a drug delivery device. The drive member may, e.g., be a plunger rod configured to be directly driven by the energy member or may be a transfer member configured to transfer energy from the drive member to a plunger rod.
The energy member may be a drive spring, e.g. a torsion drive spring, particularly a spiral torsion spring or clock spring or power spring, or another component configured to induce a torque, e.g. a gas cartridge or an electric motor. The drive spring may be formed of metal, e.g. steel. The longitudinal axis may run through the center of the drive spring.
Here and in the following, if not stated otherwise, a movement of a member or element or feature is to be understood as a movement with respect to the housing element.
According to at least one embodiment, the drive subassembly has a first and a second locked state.
According to at least one embodiment, in the first locked state, a first rotation-locking mechanism prevents a movement of the drive member in the first rotational direction induced by the energy member. For example, in the first locked state, the drive member is coupled to the housing element via a first rotation-lock interface, wherein the first rotation-lock interface prevents a movement of the drive member in the first rotational direction induced by the energy member.
According to at least one embodiment, in the second locked state, a second rotation-locking mechanism prevents a rotation of the drive member in the first rotational direction induced by the energy member. Moreover, in the second locked state, an axial-locking mechanism may prevent an axial movement of the drive member. Particularly, the axial-locking mechanism may prevent an axial movement of the drive member in a proximal direction and/or a distal direction.
For example, in the second locked state, the drive member is coupled to the housing element via a second rotation-lock interface preventing a rotation of the drive member in the first rotational direction induced by the energy member and is coupled to the housing element via an axial-lock interface preventing a movement of the drive member in one or both axial directions.
In the first locked state and/or in the second locked state, the energy member may already induce a torque onto the drive member.
According to at least one embodiment, the drive subassembly is configured to be switched from the second locked state into the first locked state by releasing the axial-locking mechanism and moving the drive member in an axial direction, e.g. in proximal direction. The movement in axial direction after releasing the axial-locking mechanism may release the second rotation-locking mechanism and may lock the first rotation-locking mechanism. The drive subassembly may be configured such that the second rotation-locking mechanism can only be released by a movement of the drive member in an axial direction. For example, during movement in axial direction, the first rotation-locking mechanism is locked before the second rotation-locking mechanism is completely released. By way of example, the first rotation-lock interface is established before the second rotation-lock interface is completely resolved.
The first locked state may also be called primed state. The second locked state may also be called pre-primed state. During assembling a drug delivery device, the second locked state may be a state prior to the first locked state. The drive subassembly may also have a released state into which the drive subassembly switches from the first locked state when releasing the first rotation-locking mechanism. In the released state, the drive member rotates in the first rotational direction induced by the energy member, e.g. by at least 360°. The drive member may also move axially, e.g. in proximal direction, in the released state. When the drive subassembly is assembled into a drug delivery device, the released state may be a state in which a drug is administered due to the rotation of the drive member.
In at least one embodiment, the drive subassembly for a drug delivery device comprises a housing element, a drive member arranged rotatably with respect to the housing element and an energy member configured to provide energy in order to induce a torque onto the drive member tending to rotate the drive member in a first rotational direction. The drive subassembly has a first and a second locked state. In the first locked state, a first rotation-locking mechanism prevents a movement of the drive member in the first rotational direction induced by the energy member. In the second locked state, a second rotation-locking mechanism prevents a rotation of the drive member in the first rotational direction induced by the energy member and an axial-locking mechanism prevents an axial movement of the drive member. The drive subassembly is configured to be switched from the second locked state into the first locked state by releasing the axial-locking mechanism and moving the drive member in an axial direction.
With such a drive subassembly an easy an improved assembling of a drug delivery device may be achieved.
The drug delivery device and/or the subassemblies for the drug delivery device specified herein may each be elongated and/or may each comprise a longitudinal axis, i.e. a main extension axis. A direction parallel to the longitudinal axis is herein called an axial direction. By way of example, the drug delivery device and/or the subassemblies may be cylindrically-shaped.
Furthermore, the drug delivery device and/or the subassemblies may comprise a longitudinal end, which may be provided to face or to be pressed against a skin region of a human body. This end is herein called the distal end. A drug or medicament may be supplied via the distal end. The opposing longitudinal end is herein called the proximal end. The proximal end is, during usage, remote from the skin region. The axial direction pointing from the proximal end to the distal end is herein called distal direction. The axial direction pointing from the distal end to the proximal end is herein called proximal direction. A distal end of a member or element of the drug delivery device and/or of the subassemblies is herein understood to be the end of the member/element located most distally. Accordingly, the proximal end of a member or element is herein understood to be the end of the element/member located most proximally.
In other words, “distal” is used herein to specify directions, ends or surfaces which are arranged or are to be arranged to face or point towards a dispensing end of the drug delivery device or components thereof and/or point away from, are to be arranged to face away from or face away from the proximal end. On the other hand, “proximal” is herein used to specify directions, ends or surfaces which are arranged or are to be arranged to face away from or point away from the dispensing end and/or from the distal end of the drug delivery device or components thereof. The distal end may be the end closest to the dispensing end and/or furthest away from the proximal end and the proximal end may be the end furthest away from the dispensing end. A proximal surface may face away from the distal end and/or towards the proximal end. A distal surface may face towards the distal end and/or away from the proximal end. The dispensing end may be a needle end where a needle unit is or is to be mounted to the device, for example.
A direction perpendicular to the longitudinal axis and/or intersecting with the longitudinal axis is herein called radial direction. An inward radial direction is a radial direction pointing towards the longitudinal axis. An outward radial direction is a radial direction pointing away from the longitudinal axis.
The terms “angular direction”, “azimuthal direction” or “rotational direction” are herein used as synonyms. Such a direction is a direction perpendicular to the longitudinal axis and perpendicular to the radial direction.
An element or member or feature being rotationally, axially or radially fixed with respect to another element or member or feature means that a relative movement in rotational direction or axial direction or radial direction between the two elements/members/features is not possible or prevented.
The terms “protrusion” and “boss” are used as synonyms herein. The term “recess” may particularly stand for an indentation or a cut-out or opening or hole.
The drive subassembly specified herein may be configured to be assembled together with a further subassembly into a drug delivery device. The drive subassembly may, in particular, be a rear subassembly to be arranged proximally with respect to a front subassembly.
According to at least one embodiment, the drive subassembly comprises a plunger rod being arranged axially movable, i.e. in only one or two opposite axial directions, movable with respect to the housing element. The plunger rod may be hollow or solid. The plunger rod may be cylindrically-shaped, e.g. hollow cylindrically-shaped. In case the plunger rod is hollow, further elements or members, e.g. other than an energy member, may be received in the plunger rod.
According to at least one embodiment, the drive member and the plunger rod are operatively coupled such that a rotation of the drive member in the first rotational direction is converted into a movement of the plunger rod in distal direction. The plunger rod and the drive member may be operatively coupled by a gear, e.g. a threaded interface, transforming a rotational movement of the drive member into an axial movement of the plunger rod. In this case, the drive member is particularly a transfer member. The threaded interface may be formed directly between the plunger rod and the drive member. The threaded interface may transform the rotational movement of the drive member into an axial movement of the plunger rod. The plunger rod may comprise a thread engaged with a thread of the drive member. The thread of the plunger rod may be an external thread, the thread of the drive member may be an internal thread, or vice versa. The drive member may be axially secured to the housing element, e.g. via the energy member. For example, the drive member is secured to the housing element such that, in the released state, a force necessary for moving the drive member in one or both axial directions, particularly in the proximal direction, is greater than a force necessary to axially move the plunger rod.
According to at least one embodiment, the plunger rod is rotationally fixed to the housing element via a splined interface. The splined interface may be formed directly between the plunger rod and the housing element. For example, the plunger rod has a splining element and the housing element has a splining element, e.g. complementarity to and/or mating with the splining element of the plunger rod. The splining elements of the plunger rod and the housing element may engage with each other, e.g. form-lockingly, thereby preventing the rotation of the plunger rod with respect to the housing element. One of the splining elements of the housing element and of the plunger rod may be a groove and the other one of the splining elements of the housing element and the plunger rod may be a protrusion. The protrusion may then engage or project into the groove thereby preventing rotation of the plunger rod. The groove may extend parallel to the longitudinal axis. For example, the groove is formed in the plunger rod and the protrusion is part of the housing element, e.g. integrally formed with the housing element.
Preferably, the splined interface is in close proximity to the threaded interface, e.g. with a distance of at most 1 cm or at most 0.5 cm or at most 0.2 cm. This is beneficial since the torque on the plunger rod is resolved over a short distance reducing the stresses within the plunger rod.
The housing element and/or the plunger rod and/or the drive member may comprise or consist of a plastic. Each of them may be formed in one piece, i.e. be of a unitary construction or integrally formed. Each of them may have a main extension direction parallel the longitudinal axis. The longitudinal axis may run through one or more or every of the mentioned elements/members, e.g. through the center thereof.
The plunger rod may be received in the drive member so that the drive member circumferentially surrounds, e.g. completely circumferentially surrounds, at least a portion of the plunger rod. The drive member may be received in the housing element and/or the energy member so that at least a portion of the drive member is circumferentially surrounded, e.g. completely circumferentially surrounded, by the housing element and/or the energy member.
The energy member may be received in the housing element so that at least a portion of the energy member is circumferentially surrounded, e.g. completely circumferentially surrounded, by the housing element.
According to at least one embodiment, the first rotation-locking mechanism comprises a first rotation-lock element rotationally and/or axially fixed with respect to the drive member and a second rotation-lock element rotationally and/or axially fixed with respect to the housing element. The two rotation-lock elements of the first rotation-locking mechanism may be configured to engage with each other. The first rotation-lock element may be a part of the drive member. The second rotation-lock element may be a part of the housing element.
According to at least one embodiment, at least one of the first and the second rotation-lock elements of the first rotation-locking mechanism, e.g. the second rotation-lock element, is a displaceable rotation-lock element. For example, the displaceable rotation-lock element is displaceable in a second direction other than the first rotational direction. The second direction may be a direction perpendicular to the first rotational direction, e.g. a radial direction, particularly the outward radial direction. The other rotation-lock element of the first rotation locking mechanism may be arranged to be not moveable in the second direction, i.e. fixed in the second direction.
According to at least one embodiment, the displaceable rotation-lock element of the first rotation-locking mechanism is orientated circumferentially. This means, a main extension direction of the displaceable rotation-lock element is along an angular direction. The displaceable rotation-lock element may be elongated. For example, the displaceable rotation-lock element may be a flexible, particularly a resilient arm. One end of the displaceable rotation-lock element may be radially, preferably also rotationally and/or axially, fixed with respect to the housing element and the end of the displaceable rotation-lock element remote from the one end, e.g. as seen along the extension of the displaceable element and/or in the angular direction, may not be radially fixed with respect to the housing element, i.e. it may be a free end, and is therefore displaceable in radial direction. The free end may face in the angular direction.
In other words, the displaceable element may be pivotally connected to or integrated into the housing element, e.g. a main body thereof.
According to at least one embodiment, the first rotation-lock element and the second rotation-lock element of the first rotation-locking mechanism are engaged in the first locked state. For example, in a first position of the displaceable rotation-lock element, the rotation-lock elements of the first rotation-locking mechanism are engaged.
According to at least one embodiment, the engagement of the first and the second rotation-lock elements of the first rotation-locking mechanism prevents an energy member induced movement of the drive member in the first rotational direction. In other words, the engagement may establish a rotation-lock interface.
According to at least one embodiment, a displacement of the displaceable rotation-lock element in the second direction disengages the first rotation-lock element and the second rotation-lock element of the first rotation-locking mechanism and releases the first rotation-locking mechanism such that a movement of the drive member in the first rotational direction induced by the energy member is enabled. For example, in a second position of the displaceable rotation-lock element, the two rotation-lock elements of the first rotation-locking mechanism may be disengaged to release the first rotation-locking mechanism and to enable rotation of the drive member. The second position may be a position downstream along the second direction with respect to the first position.
According to at least one embodiment, the axial-locking mechanism comprises a first axial-lock element axially and/or rotationally fixed with respect to the drive member and a second axial-lock element rotationally and/or axially fixed with respect to the housing element. The first axial-lock element of the axial-locking mechanism may be a part of the drive member. The second axial-lock element of the axial-locking mechanism may be a part of the housing element.
According to at least one embodiment, at least one of the first axial-lock element and the second axial-lock element, e.g. the first axial-lock element, may be a displaceable element displaceable in a third direction, e.g. in radial direction, particularly in inward radial direction. The other axial-lock element may be fixed in the third direction. The displaceable axial-lock element may be oriented in the axial direction. The displaceable axial-lock element may be a pivotable or flexible or resilient arm. The other axial-lock element, e.g. the second axial-lock element, may comprise a recess.
According to at least one embodiment, the two axial-lock elements of the axial-locking mechanism are engaged in the second locked state. For example, in the second locked state, the displaceable axial-lock element may project into the recess of the other axial-lock element.
According to at least one embodiment, the engagement of the axial-lock elements of the axial-locking mechanism prevents switching from the second locked state into the first locked state. Particularly, the engagement prevents an axial movement, e.g. a proximal movement, of the drive member. For example, when trying to move the drive member in an axial direction, the displaceable axial-lock element projecting into the recess contacts an edge of the other axial-lock element delimiting the recess.
According to at least one embodiment, a displacement of the displaceable axial-lock element in the third direction disengages the first axial-lock element and the second axial-lock element and enables a movement of the drive member in an axial direction, e.g. in the proximal direction. For example, in a first position of the displaceable axial-lock element, the two axial-lock elements are engaged and in a second position of the displaceable axial-lock element, which may be arranged downstream of the first position along the third direction, the two axial-lock elements are disengaged.
According to at least one embodiment, the second rotation-locking mechanism comprises a first rotation-lock element rotationally and/or axially and/or radially fixed with respect to the drive member and a second rotation-lock element rotationally and/or axially and/or radially fixed with respect to the housing element. The first rotation-lock element of the second rotation-locking mechanism may be part of the drive member. The second rotation-lock element of the second rotation-locking mechanism may be part of the housing element, e.g. a main body of the housing element.
According to at least one embodiment, the first and the second rotation-lock elements of the second rotation-locking mechanism are engaged in the second locked state. For example, the second-rotation locking mechanism is configured such that the two rotation-lock elements can only be disengaged by an axial movement of the drive member.
According to at least one embodiment, the engagement of the first and the second rotation-lock elements of the second rotation-locking mechanism prevents an energy member induced movement of the drive member in the first rotational direction. In other words, the engagement of the two rotation-lock elements of the second rotation-locking mechanism may establish a rotation-lock interface.
According to at least one embodiment, the first rotation-lock element of the first rotation-locking mechanism is also the first rotation-lock element of the second rotation-locking mechanism.
According to at least one embodiment, the drive subassembly is configured such that when switched from the second locked state into the first locked state, the first rotation-lock element is moved in an axial direction, e.g. in the proximal direction.
According to at least one embodiment, the drive subassembly is configured such that during movement in axial direction, the first rotation-lock element engages with the second rotation-lock element of the first rotation-locking mechanism before being completely disengaged from the second rotation-lock element of the second rotation-locking mechanism.
According to at least one embodiment, the first rotation-lock element of the first rotation-locking mechanism comprises a locking feature, the first rotation-lock element of the second rotation-locking mechanism comprises a locking feature, the second rotation-lock element of the first rotation-locking mechanism comprises a locking feature and the second rotation-lock element of the second rotation-locking mechanism comprises a locking feature. The locking feature of a displaceable rotation-lock element may be arranged closer to a free end than to an end fixed with respect to the housing element or the drive member.
According to at least one embodiment, the locking features of the second rotation-lock elements are both protrusions and the locking features of the first rotation-lock elements are both recesses or vice versa. The protrusion(s) may be radially, e.g. radially inwardly, oriented.
According to at least one embodiment, when the rotation-lock elements are engaged in the first and the second locked state, the respective protrusion projects into the respective recess.
According to at least one embodiment, the locking feature of the first rotation-lock element of the first rotation-locking mechanism is arranged downstream of, e.g. directly behind, the locking feature of the first rotation-lock element of the second rotation-locking mechanism in an axial direction, particularly in the proximal direction. Said locking features may be aligned or may overlap in rotational and/or radial direction. In other words, the locking features of the second rotation-lock elements of the two rotation-locking mechanisms may be angularly and/or radially aligned and axially offset from one another. At least a section of the locking feature of the second rotation-lock element of the first rotation-locking mechanism may have the same radial extension as and/or the same extension in angular direction as or may even be formed identically with the locking feature of the second rotation-lock element of the second rotation-locking mechanism. Said locking features may also have free ends which are radially aligned. This facilitates an engagement of the same first rotation-lock element with the two different second rotation-lock elements of both rotation-locking mechanisms.
According to at least one embodiment, the drive member comprises a first portion, also called axial-lock portion, and a second portion, also called rotation-lock portion, which are axially offset. The diameter in the first portion may be greater than in the second portion. The first portion may be arranged proximally with respect to the second portion. The first rotation-lock elements of the first and second rotation-locking mechanism may be part of or may be formed by the second portion. The first axial-lock element of the axial-locking mechanism may be part of or may be formed by the first portion. The first and/or the second portion may be disc-shaped.
According to at least one embodiment, a third portion, also called connection portion, of the drive member is arranged between the first portion and the second portion. The third portion may have a smaller diameter than each of the first portion and the second portion. For example, the third portion may be a shaft, e.g. with cylindrical shape. The first and/or the second and/or the third portion may, at least in the first and/or second locked state, be arranged inside the housing element, i.e. be circumferentially surrounded by the housing element. Moreover, at least in the first and/or second locked state, the plunger rod may overlap with one, some or all of the first, second and third portion of the drive member in axial direction.
According to at least one embodiment, the drive subassembly comprises a housing in which the drive member and the energy member are received, e.g. circumferentially, particularly completely circumferentially, surrounded by the housing. Also the plunger rod may be received in the housing. Particularly, the drive member and/or the energy member and/or the plunger rod may be completely received in the housing, e.g. such that the housing completely covers that drive member and/or the energy member and/or the plunger when viewed along a radial direction.
According to at least one embodiment, the housing element is fixed or configured to be fixed to the housing. The housing element may also be integrated in the housing. The housing is preferably axially and rotationally, preferably also radially, fixed with respect to the housing element. The housing element may be part of the housing, e.g. integrally formed with the housing, or maybe a separate element. The housing element may be received, e.g. completely received in the housing.
The housing may comprise or consist of plastic and/or may be formed in one piece. The housing may be hollow and/or elongated and/or hollow cylindrically-shaped. The housing may be a sleeve.
According to at least one embodiment, the housing axially projects beyond the drive member and/or the energy member and/or the plunger rod. For example, the housing projects beyond the drive member and/or the energy member and/or the plunger rod in distal direction and/or in proximal direction.
According to at least one embodiment, the housing is configured to hold or receive a medicament container, e.g. a syringe. The housing may be configured to hold the medicament container such that the medicament container is axially and/or rotationally and/or radially fixed with respect to the housing. For example, the housing is configured such that, when a medicament container with a needle is received in the housing, only the needle projects beyond the housing in distal direction.
According to at least one embodiment, the housing has a length of at least 75% or at least 80% of the length of the drug delivery device. For example, the length of the housing is greater, e.g. at least 1.5 times as great or at least two times as great, as the length of the drive member and/or the energy member and/or the plunger rod. Herein, the length is measured along the longitudinal axis.
According to at least one embodiment, the housing provides an outer surface of the drive subassembly configured to be grabbed by a user. In other words, the housing is the outermost member of the drive subassembly and/or of the drug delivery device in outward radial direction.
Next, the arrangement is specified.
According to at least one embodiment, the arrangement comprises a drive subassembly specified herein. This means, all features disclosed for the drive subassembly are also disclosed for the arrangement and vice versa.
According to at least one embodiment, the arrangement comprises a release subassembly configured to be connected with the drive subassembly in order to assemble a drug delivery device. For example, the drive subassembly and the release subassembly are configured to be telescoped with or into each other. The release subassembly may be a front subassembly configured to be located distally with respect to the drive subassembly.
According to at least one embodiment, the drive subassembly is in the second locked state, particularly before the subassemblies are connected to each other.
According to at least one embodiment, the release subassembly comprises a release element configured to release the axial-locking mechanism of the drive subassembly when telescoping the drive subassembly and the release subassembly. Particularly, the release element may be configured to displace the displaceable axial-lock element in the third direction, e.g. the inward radial direction, in order to disengage the axial-lock elements. The release element may be configured to release the axial-locking mechanism automatically during telescoping the drive subassembly and the release subassembly so that a further release step after telescoping is not necessary.
According to at least one embodiment, the release subassembly comprises a push element configured to push the drive member in an axial direction, particularly in proximal direction, when telescoping the drive subassembly and the release subassembly for switching the drive subassembly from the second locked state into the first locked state. The push element may be configured to push the drive member automatically during telescoping the drive subassembly and the release subassembly so that a further step of moving the drive member after telescoping is not necessary.
The release element and/or the push element may be located in the region of an axial end of the release subassembly, e.g. in the region of the proximal end of the drive subassembly. The release element and/or the push element may be axially and/or rotationally and/or radially fixed to a container-holder of the release subassembly. The release element and/or the push element may be part of the container-holder.
The release element and the push element may be arranged such that when telescoping or connecting the drive subassembly and the release subassembly, the release element first releases the axial-locking mechanism and after that, e.g. immediately after that, the push element pushes the drive member in an axial direction, particularly in the proximal direction.
In other words, the arrangement may be configured such that the release of axial-locking mechanism and/or the movement of the drive member in axial direction for switching from the second locked state into the first locked state happens automatically during telescoping or assembling.
Next, the method for assembling a drug delivery device is specified.
According to at least one embodiment, the method comprises a step in which a drive subassembly specified herein is provided. This means, all features disclosed for the drive subassembly are also disclosed for the method and vice versa. In this step, the drive subassembly is in the second locked state.
According to at least one embodiment, the method comprises a step, in which a release subassembly is provided. The release subassembly may be the release subassembly of the arrangement specified herein. This means, all features disclosed for the release subassembly of the arrangement are also disclosed for the release subassembly of the method and vice versa.
According to at least one embodiment, the method comprises a step of connecting, particularly telescoping, the release subassembly and the drive subassembly, wherein during connecting or telescoping, the release subassembly releases the axial-locking mechanism and pushes the drive member in an axial direction, particularly in the proximal direction, so that the drive subassembly is switched from the second locked state into the first locked state. For example, the drive member is moved by at least 2 mm or at least 5 mm or at least 10 mm and/or at most 30 mm or at most 20 mm in axial direction when switching from the second locked state into the first locked state.
According to at least one embodiment, when telescoping the release subassembly and the drive subassembly, the release element pushes the displaceable axial-lock element in the third direction, whereby the displaceable axial-lock element disengages from the other axial-lock element.
According to at least one embodiment, when telescoping the release subassembly and the drive subassembly, the push element pushes the drive member in an axial direction thereby switching the drive subassembly from the second locked state into the first locked state.
According to at least one embodiment, the release subassembly comprises a support element. The support element may be a release member, particularly a needle shroud, or part of such a release member, e.g. a wall portion of the release member.
According to at least one embodiment, when telescoping the release subassembly and the drive subassembly, the support element is brought into a support position in which the support element holds the displaceable rotation-lock element of the first rotation-locking mechanism in a first position. In the first position, the displaceable rotation-lock element is arranged to engage or is engaged with the other rotation-lock element of the first rotation-locking mechanism. Particularly, in the support position, the support element is aligned or overlaps with the displaceable rotation-lock element of the first rotation-locking mechanism in axial and/or rotational direction. The support element in the support position may be configured to prevent a disengagement of the rotation-lock elements of the first rotation-locking mechanism by a displacement of the displaceable rotation-lock element. The support element in the support position may be located radially outwardly with respect to the displaceable rotation-lock element of the first rotation-locking mechanism.
For example, the support element is brought into the mentioned support position before the second rotation-locking mechanism is completely released and/or before the first rotation-locking mechanism is locked.
Next, the container-holder subassembly for a drug delivery device is specified.
The container-holder subassembly may be the release subassembly specified herein. Accordingly, all features disclosed for the container-holder subassembly are also disclosed for the release subassembly and vice versa. The container-holder subassembly may be a front subassembly configured to be arranged distally to a rear subassembly, e.g. the drive subassembly specified herein.
According to at least one embodiment, the container-holder subassembly comprises a needle shroud configured to cover a needle of a medicament container. The needle shroud may be configured to circumferentially surround the needle and to, at least in an extended position, project beyond the needle in distal direction.
According to at least one embodiment, the container-holder subassembly comprises a container holder configured to hold a medicament container. The container holder may be configured to hold the medicament container such that the medicament container is axially and/or rotationally and/or radially fixed with respect to the container holder.
The needle shroud and/or the container holder may comprise or consist of a plastic. The needle shroud and/or the container holder may each be formed in one piece. The needle shroud and/or the container holder may be elongated. A main extension direction of the needle shroud and/or the container holder may run parallel to a longitudinal axis of the container-holder subassembly.
According to at least one embodiment, the needle shroud and the container holder are coupled to each other so that the needle shroud is movable with respect to the container holder in axial direction, i.e. in only one or both axial directions. Particularly, the needle shroud may be axially moveable relative to the container holder between an extended position, configured to cover the needle such that the needle does not project beyond the needle shroud in distal direction, and a retracted position, configured such that the needle projects beyond the needle shroud in distal direction.
According to at least one embodiment, the container-holder subassembly is configured to be inserted into a housing for a drug delivery device, particularly into a sleeve-shaped housing, e.g. into the housing of the drive subassembly specified above. For example, the container-holder subassembly is configured such that when inserted into the housing, at least the container holder is completely received in the housing and, e.g., does not project from the housing in distal and/or proximal direction. When inserted into the housing, the container-holder subassembly may be circumferentially surrounded, e.g. completely circumferentially surrounded, by the housing.
In at least one embodiment, the container-holder subassembly for a drug delivery device comprises a needle shroud configured to cover a needle of a medicament container and a container holder configured to hold a medicament container. The needle shroud and the container holder are coupled to each other so that the needle shroud is movable with respect to the container holder in an axial direction. The container-holder subassembly is configured to be inserted into a housing for a drug delivery device. Particularly, the container-holder subassembly may be inserted into the housing as one entity and/or may be preassembled before it is guided into the housing. The housing may be the housing element of the drive subassembly and/or the housing of the drug delivery device. The drive subassembly and the container-holder subassembly may be assembled or connected to each other, e.g. to form the drug delivery device. The connection between the container-holder subassembly and the drive assembly may be permanent or irreleasable.
According to at least one embodiment, an outer surface of the container-holder subassembly is at least partially formed by the container holder and/or the needle shroud. Particularly, the container holder and/or the needle shroud may be freely accessible from a radial direction. This means, when viewed in inward radial direction, at least a portion of the container holder and/or the needle shroud may be exposed, i.e. not covered by other elements. Such a configuration allows to check the position of a medicament container held or received in the container holder. In at least one axial position along the axial extension of the container-holder subassembly, the outer perimeter or boundary of the container-holder subassembly may be defined by at least one portion of the needle shroud, e.g. one arm, and at least one portion of the container holder, e.g. at least one arm or a body thereof. Portions of the container holder and portions of the needle shroud may be alternatingly disposed in the rotational or angular direction when traveling along the outer perimeter or boundary of the container-holder subassembly in the rotational or angular direction in the at least one axial position.
According to at least one embodiment, the container-holder subassembly further comprises a medicament container. The medicament container may comprise a needle. Particularly, the medicament container is received in the container holder. The needle may form the distal end of the medicament container. The needle may distally project from the container holder.
The medicament container may be a syringe, e.g. a prefilled syringe. The container holder may also be referred to as syringe holder. The medicament container may be arranged axially and/or rotationally and/or radially fixed with respect to the container holder, i.e. it is not moved with respect to the container holder during the intended usage of the drug delivery device or of the container-holder subassembly. An end of the medicament container opposite the needle may be sealingly closed by a movable member, e.g. a stopper or piston. The medicament container may comprise a drug or medicament, e.g. a liquid drug or medicament.
According to at least one embodiment, the medicament container is freely accessible from a proximal side of the container-holder subassembly. This means, when viewed from the proximal side of container-holder subassembly along the axial direction, the medicament container is visible or exposed, i.e. not completely covered by other elements of the container-holder subassembly.
According to at least one embodiment, the container holder and the needle shroud are rotationally fixed with respect to each other. Particularly, the container holder and the needle shroud may be coupled to each other by a rotation-lock interface.
According to at least one embodiment, the container holder comprises a first rotation-lock feature and the needle shroud comprises a second rotation-lock feature. The container holder may comprise several, e.g. two or more, first rotation-lock features. Likewise, the needle shroud may comprise several, e.g. two or more, second rotation-lock features. The rotation-lock features may be arranged rotationally symmetrically at the container holder or the needle shroud, respectively. All features disclosed here and in the following for one first rotation-lock feature or one second rotation-lock feature are also disclosed for further first rotation-lock features or second rotation-lock features, respectively.
One of the first and second rotation-lock features may be a protrusion and the other one may be a recess. The protrusion may protrude in a radial direction. For example, the protrusion and/or the recess may be elongated. A main extension direction of the protrusion and/or the recess may extend along the longitudinal axis, respectively. In other words, the protrusion may be a rib and the recess may be a slit or slot. The recess may be longer than the protrusion in order to allow a relative axial movement of the needle shroud and the container holder.
According to at least one embodiment, the two rotation-lock features are engaged with each other and the engagement prevents a rotation of the container holder and the needle shroud with respect to each other. Particularly, the protrusion may project into the recess.
According to at least one embodiment, the container-holder subassembly further comprises a shroud spring coupled to the needle shroud and the container holder. The shroud spring may be configured such that it induces a restoring force acting in distal direction on the needle shroud when the needle shroud is moved in proximal direction with respect to the container holder. Particularly, one end of the shroud spring, e.g. a distal end of the shroud spring, may be coupled or fixed or secured to a distal portion of the needle shroud and a further end, e.g. a proximal end, of the shroud spring may be coupled or fixed or secured to a distal portion of the container holder.
The distal portions of the container holder and/or of the needle shroud may be cylindrically-shaped portions, e.g. hollow cylindrically-shaped portions. The distal portion of the container holder may be located further proximal than the distal portion of the needle shroud.
According to at least one embodiment, the needle shroud comprises two arms, e.g. exactly two arms, extending from a first portion of the needle shroud, e.g. the distal portion, in proximal direction. The two arms of the needle shroud may be arranged with a rotational symmetry, e.g. a 2-fold rotational symmetry, around the longitudinal axis. The two arms of the needle shroud may be spaced from each other in rotational direction.
According to at least one embodiment, the container holder comprises two arms, e.g. exactly two arms, extending from a first portion of the container holder, e.g. the distal portion or a support portion, in proximal direction. The two arms of the container holder may be arranged with a rotational symmetry, e.g. a 2-fold rotational symmetry, around the longitudinal axis. The two arms of the container holder may be spaced from each other in rotational direction.
The first rotation-lock feature of the container holder may be arranged in the first portion of the container holder, particularly in a support portion of the container holder. The first portion of the container holder may be cylindrically-shaped, e.g. hollow cylindrically-shaped. The support portion may be arranged axially between the distal portion and the arms of the container holder.
The second rotation-lock feature of the needle shroud may be arranged in an arm of the needle shroud. The arms of the needle shroud may be aligned or may overlap with the first portion of the container holder in axial and/or rotational direction.
According to at least one embodiment, the arms of the needle shroud are arranged between the arms of the container holder in angular direction. Particularly, at least a portion of the outer surface of the container-holder subassembly may alternatingly be formed by the arms of the needle shroud and the arms of the container holder when viewed along the angular direction. The arms of the needle shroud and the container holder may overlap in axial direction.
According to at least one embodiment, the container holder, particularly the arms of the container holder, project beyond the needle shroud, particularly beyond the arms of the needle shroud, in proximal direction. The arms of the container holder may comprise or may form the release element and/or the push element specified above. The release element and/or the push element may be formed in the region of the proximal end of the arms of the container holder. The arms of the container holder and/or the arms of the needle shroud may form the proximal end of the container holder or the needle shroud, respectively.
According to at least one embodiment, the container holder comprises at least one window through which a medicament container held in the container holder can be observed. The window may be formed in an arm of the container holder or in the first portion of the container holder, e.g. in the support portion. For example, the container holder comprises several windows. The window(s) may have an elongated shape, e.g. an oval shape. A main extension direction of the window(s) may run along the longitudinal axis. In angular direction, the windows may be formed between the first rotation-lock features.
According to at least one embodiment, the container holder comprises a snap feature. The snap feature may be arranged next to the window. The snap feature may be configured for axially and/or rotationally and/or radially fixing the container holder to the housing. For example, the snap feature is arranged at the proximal end and/or at the distal end of the window. The snap feature may be a protrusion protruding in radial outward direction.
The container holder may comprise several such snap features, e.g. for each window two snap features arranged at the distal and proximal end thereof.
The snap feature(s) may be configured to engage with corresponding snap feature(s) of the housing. The snap feature(s) of the housing may be protrusions or recesses.
According to at least one embodiment, the container-holder subassembly comprises a cap arranged at the distal end of the container-holder subassembly. The cap may be configured to cover a distal portion of the needle shroud.
According to at least one embodiment, the cap is releasably coupled to the needle shroud. For example, the cap is coupled to the distal portion of the needle shroud and may completely cover the distal portion of the needle shroud when coupled to the needle shroud.
Next, the kit is specified. The kit may comprise the drive subassembly specified herein and the container-holder subassembly specified herein. The drive subassembly and the container-holder subassembly may be configured to be telescoped with each other or coupled to each in order to assemble a drug delivery device. The drive subassembly and the container-holder subassembly may be assembled to a drug delivery device with the method specified herein.
Next, the drug delivery device specified.
The drug delivery device may be an auto-injector. The drug delivery device may comprise a drive subassembly as specified herein and/or a container-holder subassembly as specified herein. The drive subassembly and the container-holder subassembly may be coupled to each other and fixed, e.g. axially and/or rotationally fixed, to each other. The drive assembly and the container-holder subassembly may be permanently or irreleasably connected to one another. The drug delivery device may comprise a medicament container, e.g. a syringe. The medicament container may be received in the container holder. The drug delivery device may be configured to empty the medicament container when the first rotation-locking mechanism is released. In other words, the medicament container may comprise medicament in an amount sufficient for just one drug delivery operation. The drug delivery operation may be performed when the drug delivery device has been switched from the first locked state into a released state. The drug delivery device may be a single use device and/or a disposable device.
Hereinafter, the subassemblies for a drug delivery device, the method for assembling a drug delivery device and the drug delivery device described herein will be explained in more detail with reference to drawings on the basis of exemplary embodiments. Same reference signs indicate same elements in the individual figures. However, the size ratios involved are not necessarily to scale, individual elements may rather be illustrated with exaggerated size for a better understanding.
The drug delivery device 1000 according to the first exemplary embodiment is an auto-injector. The auto-injector 1000 comprises a housing 100. A cap 110 is removably attached or coupled to the housing 100 at a distal end of the housing 100. The housing 100 may be formed in one piece and may extend from the cap 110 to the proximal end of the auto-injector 1000. The housing 100 is a cylindrically-shaped sleeve.
As can be further seen in
The drive spring holder 4 is fixed to the housing 100 so that the drive spring holder 4 can neither be rotated nor axially nor radially moved with respect to the housing 100. For example, the drive spring holder 4 is fixed with help of clips (not shown) to the housing 100. Alternatively, the drive spring holder 4 may be part of the housing 100, e.g. integrally formed with the housing 100. The drive spring holder 4 is received in the housing 100. The housing 100 circumferentially completely surrounds the drive spring holder 4.
The torsion drive spring 3 is connected to the drive spring holder 4 at a connection point. At a further connection point, the torsion drive spring 3 is connected to the rotating collar 2. The rotating collar 2 is arranged axially and rotationally movable with respect to the drive spring holder 4. The torsion drive spring 3 circumferentially surrounds a portion of the rotating collar 2. When the torsion drive spring 3 is biased, it induces a torque onto the rotating collar 2. This torque results in a rotation of the rotating collar 2 with respect to the drive spring holder 4, if the rotating collar 2 is not prevented from rotating by a locking mechanism (see explanations further down below). The rotational axis of the rotating collar 2 may define or coincide with the longitudinal axis A.
The auto-injector 1000 further comprises a release member 5 or protection member 5, respectively, in the form of a needle shroud 5 and a medicament container holder 6 in the form of a syringe holder 6. The syringe holder 6 may be axially and preferably also rotationally fixed with respect to the housing 100. The syringe holder 6 is configured to hold a syringe. The syringe holder 6 comprises windows 60 which overlap/are aligned with the windows 120 in the housing 100. In this way, the syringe or medicament container can be observed through the windows 60, 120.
The needle shroud 5 is arranged axially movable with respect to and telescopically coupled to the housing 100 or the drive spring holder 4, respectively. Particularly, the needle shroud 5 can be moved from an extended position, which is the position shown in
The needle shroud 5 and the syringe holder 6 are moveably coupled to each other via a shroud spring 7. One end of the shroud spring 7 is connected to the syringe holder 6 and the other end of the shroud spring 7 is connected to the needle shroud 5. The coupling is such that a movement of the needle shroud 5 in the proximal direction P with respect to the syringe holder 6 results in a compression of the shroud spring 7 inducing a force onto the needle shroud 5 pointing in distal direction D.
The housing 100, the housing element 4, the plunger rod 1, the rotating collar 2, the needle shroud 5, the syringe holder 6 and the cap 110 may all comprise or consist of plastic. All these members may each be formed in one piece. The drive spring 3 and the shroud spring 7 may comprise or consist of a metal, e.g. steel.
It can be seen in
In
When the cap 110 is removed from the housing 100, the grabber 111 pulls of the needle shield 83 from the needle 80. Afterwards, the needle 80 is circumferentially only surrounded by the retractable needle shroud 5.
In the position of
In the position of
In the first locked state, a proximal end of the rotating collar 2 is axially spaced from a proximal end-stop of the housing 100. This allows an axial movement of the rotating collar 2 in proximal direction P. Moreover, in the first locked state, a distal end of the plunger rod 1 is axially spaced from the stopper 82 of the syringe 8. Thus, the plunger rod 1 can axially move in the distal direction D for a predetermined distance before hitting the stopper 82.
As indicated in
In
In the third locked state of the auto-injector 1000 shown in
The distal end of the syringe holder 6 is formed by a distal portion 6a in the form of a cylindrically-shaped portion 6a. This portion 6a is configured to hold the shroud spring 7. The cylindrically-shaped portion 6a is inserted into the shroud spring 7 so that an edge of the syringe holder 6 abuts against the proximal end of the shroud spring 7. The shroud spring 7 circumferentially surrounds the cylindrically-shaped portion 6a of the syringe holder 6. The shroud spring 7 may be fixed to the cylindrically-shaped portion 6a, e.g. by a glue or a mechanical radial interference with the proximal coil of the shroud spring 7.
As can further be seen in
One difference between the auto-injector 1000 according to the second exemplary embodiment and the auto-injector according to the first exemplary embodiment is that, in the second exemplary embodiment, the housing 100 now comprises two parts instead of one part. A first part forming the distal part of the housing 100 and a second part forming the proximal part of the housing 100. The two parts of the housing 100 are connected to each other, e.g. with help of clips (not shown). For example, the two parts of the housing 100 are fixed to each other such that they are neither axially nor rotationally nor radially movable with respect to each other.
An exploded view of the rear subassembly RSA of the auto-injector 1000 according to the second exemplary embodiment is shown in
The conversion of the rotational movement of the rotating collar 2, induced by the torsion drive spring 3, into an axial movement of the plunger rod 1 (drive mechanism) is explained in more detail in the following in connection with
As can be seen in
The rotating collar 2 is received in the drive spring holder 4. A proximal end of the rotating collar 2 projects out of the drive spring holder 4 in proximal direction P. The rotating collar 2 comprises a shaft 20, and two portions 21, 22 with larger diameters than the shaft 20. The two portions 21, 22 are axially spaced from one another and are connected via the shaft 20. In this exemplary embodiment, the two portions 21, 22 are disc-shaped but other shapes might also be possible. The first portion 21 has a greater diameter than the second portion 22. The first portion 21 is located in the first section 4a of the drive spring holder 4 and the second portion 22 is located in the second section 4b of the drive spring holder 4. The diameters of the portions 21, 22 are substantially the same as the inner diameters of the assigned sections 4a, 4b but sufficiently smaller to allow a rotation of the rotating collar 2 with respect to the drive spring holder 4. Moreover, the diameter of the first portion 21 is greater than the inner diameter of the second section 4b which limits the axial movement of the rotating collar 2 in distal direction D.
As can be further seen in
The torsion drive spring 3 is received in the first section 4a and is fixed to the first section 4a at a connection point. The rotating collar 2 is received in the torsion drive spring 3 so that the torsion drive spring 3 circumferentially surrounds the shaft 20 of the rotating collar 2 at a proximal side of the first section 21. The shaft 20 of the rotating collar 2 is connected to the torsion drive spring 3 at a further connection point. The first portion 21 is offset with respect to the torsion drive spring 3 in distal direction D. In the first locked state, shown in
The plunger rod 1 is received in the rotating collar 2. In the first locked state, a portion of the plunger rod 1 projects from the rotating collar 2 in distal direction D. The stopper 82 of the syringe 8 is offset from the distal end of the plunger rod 1 in distal direction D.
During the axial movement of the plunger rod 1 induced by the rotation of the rotating collar 2, the plunger rod 1 itself does not rotate. This is realized by a coupling between the plunger rod 1 and the drive spring holder 4 via a splined interface. This is further illustrated in
In the exemplary embodiments, the splined interface is in close proximity to the threaded interface, e.g. with a distance of at most 1 cm or at most 0.5 cm. This is beneficial since the torque on the plunger rod 1 is resolved over a short distance reducing the stresses within the plunger rod 1. The plunger rod 1 is often a small member likely to deform.
As can be further seen in
In the released state, the plunger rod 1 pushes the stopper 82 in distal direction D until the stopper 82 hits against a bottom region of the cartridge 81. A further distal movement of the stopper 82 and the plunger rod 1 is then prevented. After movement of the plunger rod 1 and the rotating collar 2 is finished, a portion of the plunger rod 1 is still received in the rotating collar 2.
An example of the dimensions of the plunger rod 1 is as follows: The plunger rod 1 has a diameter of 8.0 mm and the pitch of the outer thread is 3.17 mm. The coefficient of friction is 0.3. The mean contact radius, i.e. the position of the threaded face from the central axis of the plunger rod 1, is 3.75 mm.
An example of the torsion drive spring is 3 as follows: The material is polished and blued SAE 1095 steel. The height of the torsion drive spring is 12.0 mm, the thickness of the material is 0.168 mm, the length is 840.749 mm, the outer diameter is 20.0 mm, the arbor diameter is 10.0 mm. The bending stress limit is 2000 N·mm−2, the Youngs Modulus is 20000 N·mm−2, the number of revolutions before being biased is 3.
In general, the following conditions for the torsion drive spring turned out to be advantageous: The arbor diameter is between 12 to 25 times the thicknesses of the material. The length is between 5000 to 15000 times the thickness. The area of the torsion drive spring 3 is half the area of the drive spring holder 4 (e.g. in the first section 4a)+−10%. The bending stress for tempered polished and blued SAE 1095 steel should not exceed 2000 MPa.
An example of the used syringe 8 might be as follows: The drug inside the cartridge 81 has a volume of 2 ml. The viscosity of the material is 50 cP at room temperature. The inner needle diameter is 0.29 mm. The inner cartridge diameter is 8.65 mm. The friction of the stopper 82 is 10 N. The stopper gap, i.e. the initial clearance between the proximal end of the stopper 82 and the distal end of the plunger rod 1, is 2 mm.
The previously mentioned first locking mechanism or first rotation-locking mechanism, respectively, and how it is released is described in further detail in the following in connection with the
The resilient arm 41 comprises a protrusion 410 projecting radially inwardly, i.e. in a radial direction pointing towards the longitudinal axis A. The protrusion 410 tapers radially inwardly. The protrusion 410 comprises a beveled surface 410a, which essentially runs parallel to the longitudinal axis A and which is tilted with respect to the radial direction R and with respect to the angular direction C. For example, the angle α between the beveled surface 410a and the radial direction R is at least 10° and at most 80°, preferably between 30° and 55°.
In the first locked state, shown in
The first radial position may be the relaxed position of the resilient arm 41 which it would occupy if no further forces pointing radially inwardly and radially outwardly were acting on the resilient arm 41. Alternatively, the resilient arm 41 may be biased in the first radial position, such that the first radial position is a stressed position of the resilient arm 41.
As long as the resilient arm 41 is in the first radial position in which the protrusion 410 projects into the recess 220, a rotation of the rotating collar 2 in the first rotational direction induced by the torsion drive spring 3 is prevented. However, the torque acting on the rotating collar 2 presses a surface of the second portion 22 delimiting the recess 220 against the beveled surface 410a of the protrusion 410 of the resilient arm 41. This results in a force trying to move the resilient arm 41 radially outwardly from the first radial position into a second radial position. In other words, the torque induced by the torsion drive spring 3 biases the resilient arm 41 radially outwardly. If a movement in radial outward direction would be allowed, the first locking mechanism would be released automatically and the auto-injector 1000 would transfer into the released state.
In the first locked state, an arm 5b of the needle shroud 5 is located at the height of, i.e. axially overlapping or aligned with, the resilient arm 41 and prevents the resilient arm 41 from moving radially outwardly out of and away from the first radial position. Indeed, the resilient arm 41 abuts against the needle shroud 5 in outward radial direction such that an outward radial movement is blocked. The resilient arm 41 comprises a further protrusion 411 which projects radially outwardly and which abuts against the needle shroud 5. An outward radial movement of the needle shroud 5 is prevented, e.g. by the housing 100 circumferentially surrounding the needle shroud 5.
As an numerical example: Assuming a torque induced by the torsion drive spring 3 onto the rotating collar 2 of 102 Nmm, a radius at which the rotating collar 2 abuts against the protrusion 410 of 7.5 mm and an angle α of 39° would result in a force on the resilient arm 41 in radial direction of about 10.57 N. Assuming a friction coefficient of 0.3, the friction force would be about 3.17 N. Assuming further that the force for compressing the shroud spring 7 is about 6 N, the activation force would be about 9 N.
The protrusion 411 of the resilient arm 41 comprises a slide feature 411a in the form of a beveled surface 411a. The beveled surface 411a and the longitudinal axis may include, e.g., an angle between 10° and 80° inclusive. An edge of the needle shroud 5 delimiting the recess 50b in proximal direction P may contact this beveled surface 411a when the needle shroud 5 moves in distal direction D. Due to the beveled surface 411a, the resilient arm 41 is pushed radially inwardly when the edge hits the protrusion 411. In this way, the movement of the needle shroud 5 back into the retracted position is possible without the needle shroud 5 jamming up with the resilient arm 41. The slide feature may additionally or alternatively be formed in the needle shroud 5 (see
In the case the resilient arm 41 indeed abuts against the edge of needle shroud 5 when the needle shroud 5 is moved in distal direction D, the movement of the resilient arm 41 in inward radial direction is possible, since the rotating collar 2, particularly the second portion 22 of the rotating collar 2, has moved in proximal direction P. Thus, the second portion 22 is now offset in proximal direction P with respect to the resilient arm 41. For this reason, it is particularly beneficial if the rotating collar 2 moves in the proximal direction immediately when the plunger rod 1 starts to move in distal direction, i.e. before the plunger rod 1 hits the stopper 82. If the user lifts the auto-injector 1000 early from the skin, e.g. before the drug is started to be administered, the needle shroud 5 can then still move back in distal direction and the third locking mechanism explained below can be activated.
A third locking mechanism or post-released locking mechanism, respectively, is described in further detail in the following in connection with the
As can be seen in
Simultaneously to extending in proximal direction P, the resilient arm 51 also extends radially inwardly, i.e. a main extension direction of the resilient arm 51 has a component along the proximal direction P and a component along the inward radial direction. Thus, a proximal end of the resilient arm 51 is located further radially inwardly than a distal end of the resilient arm 51. The proximal end of the resilient arm 51 is free and displaceable in the radial direction. The distal end of the resilient arm 51 is connected to the rest of the needle shroud 5. A kink is formed between the distal end of the resilient arm 51 and the rest of the needle shroud 5.
In
In the released state of the auto-injector 1000, the rotating collar 2 moves in proximal direction P from a nonlocking position into a locking position, as it is indicated in
When the resilient arm 51 hits against the surface 22a of the second portion 22, a lock interface is formed between the resilient arm 51 and the surface 22a. For this purpose, a recess 221 or notch 221 is formed in the surface 22a which engages with the proximal end of the resilient arm 51 when the resilient arm 51 hits against the surface 22a. The recess 221 is delimited by a beveled surface 221a which is tilted with respect to the longitudinal axis A and the radial direction. For example, an angle between the beveled surface 221a and the longitudinal axis and/or the radial direction is between 10° and 80° inclusive. When the proximal end of the resilient arm 51 engages into the recess 221, the resilient arm 51 hits against the beveled surface 221a and slides along the beveled surface 221a thereby being forced to move radially inwardly. The recess 221 with the beveled surface 221a thus prevents the resilient arm 51 from sliding along the surface 22a in outward radial direction.
The surface 22a of the second portion 22 may circumferentially extend around the longitudinal axis and/or the rotational axis of the rotating collar 2 by at least 270° and may have a constant geometrical form along its extension along the angular direction. In this way, the functionality of the third locking mechanism is almost independent on how far the rotating collar 2 has rotated in the released state.
As can be further seen in
The main difference to the first exemplary embodiment is that, in the third locked state of the auto-injector 1000, when moving the needle shroud 5 towards the retracted position, the resilient arm 51 does not hit against a stop feature axially fixed to the rotating collar 2 but against a stop feature 40a axially fixed to the drive spring holder 4. The stop feature 40a is formed by an edge of the drive spring holder 4. The edge 40a delimits a recess/cut-out in the drive spring holder 4 in proximal direction P.
A flap 46, which is axially fixed to the drive spring holder 4, e.g. integrally formed with the drive spring holder 4, partially fills this recess. A distal end of the flap 46 is connected to the drive spring holder 4 and a proximal end of the flap 46 is free and displaceable in radial direction. The proximal end of the flap 46 is spaced from the edge 40a by a small gap.
In the first locked state, when the needle shroud 5 is still in the extended position, the rotating collar 2, particularly the second portion 22 of the rotating collar 2, abuts against the flap 46 of the drive spring holder 4 in outward radial direction and holds the flap 46 in a first radial position, in which the flap 46 substantially terminates flush with the edge 40a in outward radial direction. The second portion 22 prevents the flap 46 from being displaced in the inward radial direction. On the other hand, the flap 46 abuts against the resilient arm 51 of the needle shroud 5. In the first radial position of the flap 46, the flap 46 holds the resilient arm 51 in its first radial position.
When now moving the needle shroud 5 in proximal direction P, the resilient arm 51 can pass the edge 40a without jamming up with the edge 40a, since the flap 46 terminates flush with the edge 40a and since the flap 46 is held in its first radial position by the second portion 22. Moving the needle shroud 5 further into its retracted position releases the first locking mechanism, the auto-injector 1000 switches from the first locked state into the released state and the rotating collar 2 together with the second portion 22 moves in proximal direction P into a locking position. The needle shroud 5 being in its retracted position is shown in
When moving the needle shroud 5 back from its retracted position into the extended position, the resilient arm 51 passes the edge 40a and stops at the height of the flap 46. This position is shown in
The flap 46 being in the second radial position does no longer terminate flush with the edge 40a of the drive spring holder 4. Thus, when moving the needle shroud 5 from the extended position towards the retracted position, the resilient arm 51 will hit against the edge 40a which prevents a further movement of the needle shroud 5 in proximal direction P.
An exemplary embodiment of a drop protection mechanism is described in further detail in the following in connection with the
For this purpose, the protrusion 410 of the resilient arm 410 is a stepped protrusion having two sections 410b, 410c (see also
The first part of the drop protection mechanism described in connection with
In
In the position shown in
The protrusion 110b is located at a proximal end of the resilient arm 110a of the cap 110. Normally, when the drug delivery device is not dropped, the edge of the needle shroud 5 delimiting the recess 52 in distal direction D is located further distal as to what is shown in
What can be seen in
In
The syringe holder 6 further comprises snap features 62, namely ribs, protruding in outward radial direction. A respective snap feature 62 is located at the distal end and at the proximal end of the window 60. The snap features 62 are configured to engage with the housing 100 to fix the syringe holder 6 to the housing 100 such that an axial and a rotational movement of the syringe holder 6 with respect to the housing 100 is prevented. The housing 100 and the syringe holder 6 can be permanently and irreleasably connected in this way.
In
As can be seen in
As can be seen in
The second locking mechanism comprises also a protrusion 45 (see also
In the second locked state, the protrusion 45 projects into the recess 220 (see
The second rotation-locking mechanism does not need the needle shroud 5 for retaining the second locked state as the protrusion 45 is not displaceable in radial direction. Thus, as long as the rotating collar 2 is not moved in proximal direction P, a rotation of the rotating collar 2 is not possible.
As can be seen in
At the same time or later during telescoping the rear subassembly into the front subassembly, the push element 63 hits against the first section 21 of the rotating collar 2 and pushes the rotating collar 2 in proximal direction P (see also
The feedback mechanism comprises a plunger rod 1 received in a rotating collar 2. The rotating collar 2 may be designed as described in connection with the previous figures. Particularly, the rotating collar 2 is a sleeve. The plunger rod 1 is hollow, e.g. hollow cylindrically-shaped. A feedback energy member 14 in the form of a spring 14, e.g. compression spring, is received in the plunger rod 1, i.e. in a cavity thereof. Furthermore, a feedback element 12 in the form of a piston 12 is received in the plunger rod 1. The spring 14 is connected to the piston 12 and to the plunger rod 1 and is compressed. The spring 14 induces a force onto the piston 12 pointing in proximal direction P, i.e. the piston 12 is biased in proximal direction P relative to the plunger rod 1.
The plunger rod 1 comprises displaceable arms 13 oriented in axial direction. The displaceable arms 13 may be resilient arms 13 and are located at the proximal end of the plunger rod 1. The displaceable arms 13 each comprise a stop feature 130 in the form of a protrusion 130 at their respective proximal end. The displaceable arms 13 together with their protrusions 130 are each displaceable in radial direction. The displaceable arms 13 are each in a first radial position. They may be biased in the outward radial direction. However, the displaceable arms 13 are held in the first radial position by a sidewall of the rotating collar 2 circumferentially surrounding the plunger rod 1 at least at the height of the displaceable arms 13.
The protrusions 130 of the displaceable arms 13 project into the cavity of the plunger rod 1. The proximal end of the piston 12 abuts against the protrusions 130. This prevents a movement of the piston 12 in proximal direction P driven by the spring 14 beyond the protrusions 130.
As visible in
In a region of the distal end of the rotating collar 2, namely in the region between the first section 21 and the second section 22, the side wall of the rotating collar 2 is interrupted by a recess 23. When the plunger rod 1 reaches a feedback position, the displaceable arms 13 or the protrusions 130, respectively, axially and rotationally overlap with this recess 23. Thus, the displaceable arms 13 are no longer held in the first radial position. As they are biased radially outwardly, the displaceable arms 13 leave the first radial position and move in outward radial direction into a second radial position. In the second radial position, the piston 12 is no longer prevented from moving in proximal direction P relative to the plunger rod 1 driven by the spring 14 beyond the protrusions 130. This is illustrated in
In
The auto-injector 1000 comprises a housing 100 with a window 120. The window 120 may be used for inspecting the fill level of a medicament container or a syringe or a progress of a stopper inside the housing 100 or the drug clarity or the degradation of the drug.
The auto-injector 1000 further comprises a protection member 5 in the form of a needle shroud 5 which is telescopically coupled to the housing 100 and is axially movable with respect to the housing 100.
Furthermore, the auto-injector 1000 comprises a shroud spring 7 which couples the needle shroud 5 to the housing 100. The coupling via the shroud spring 7 is such that a proximal movement of the needle shroud 5 with respect to the housing 100 compresses the shroud spring 7. This compression biases the needle shroud 5 in distal direction D relative to the housing 100.
The housing 100, the housing element 4, the plunger rod 1, the rotating collar 2, the needle shroud 5 and the activation element 9 may all comprise or consist of plastic. All these members may each be formed in one piece. The drive spring 3 and the shroud spring 7 may comprise or consist of a metal, e.g. steel.
It can be seen in
In
For using the auto-injector 1000, the distal end of the auto-injector 1000 formed by the needle shroud 5 may be pressed against a body, e.g. a human body. As a consequence of that, the needle shroud 5 moves from its extended position in the proximal direction P with respect to the housing 100. This results in the needle 80 being exposed and projecting in distal direction D so that it can now pierce into the tissue of the body.
In the position shown in
In the locked state, a proximal end of the rotating collar 2 may be axially spaced from a proximal end-stop of the housing 100. This allows an axial movement of the rotating collar 2 in proximal direction P. Moreover, in the locked state, a distal end of the plunger rod 1 is axially spaced from the stopper 82 of the syringe 8. Thus, the plunger rod 1 can axially move in the distal direction D for a predetermined distance before hitting the stopper 82.
The needle shroud 5 may be moved in the proximal direction P into a retracted position. This releases the locking mechanism so that the rotating collar 2 is no longer prevented from rotating. The auto-injector switches from the locked state into a released state. The torque induced by the torsion drive spring 3 onto the rotating collar 2 forces the rotating collar 2 to rotate in a first rotational direction (clockwise or counterclockwise). For example, the rotating collar 2 rotates several times around its rotational axis. A drive mechanism, e.g. the drive mechanism described before, converts the rotation of the rotating collar 2 into an axial movement of the plunger rod 1 in the distal direction D. After having moved the predetermined distance in the distal direction D, the plunger rod 1 hits the stopper 82 of the syringe 8 and can now push the stopper 82 in distal direction D which results in the drug in the cartridge 81 being pressed out through the needle 80 into the tissue.
The rotating collar 2 may not only rotate but also moves in proximal direction P until the proximal end of the rotating collar 2 hits the proximal end-stop of the housing 100. The end-stop comprises is a protrusion 101 which tapers in distal direction D. The protrusion 101 may be a cone. The proximal end of the rotating collar 2 comprises an indentation 200. For example, the surface of the proximal end of the rotating collar 2 is concavely shaped. The protrusion 101 can penetrate into the indentation 200 when the proximal end of the rotating collar 2 hits the end-stop of the housing 100. The protrusion 101 and the indentation 200 may each be designed rotationally symmetric or circular symmetric with respect to the rotational axis of the rotating collar 2. In this way, a low friction interface is formed between the housing 100 and the rotating collar 2 so that a low friction rotation of the rotating collar 2 is enabled also when the proximal end of the rotating collar 2 abuts against the housing 100. Particularly, the radius at which the friction between the rotating collar 2 and the end-stop acts is approaching zero or is zero, therefore the resulting torque from the friction also tends to zero significantly reducing losses allowing a reduced spring force and/or enhance injection performance.
The auto-injector 1000 further comprises a rear subassembly RSA, with the plunger rod 1, the rotating collar 2, the torsion drive spring 3, the drive spring holder 4 and the activation collar 9.
When assembling the front subassembly FSA and the rear subassembly RSA, a syringe 8 is first telescoped into the housing 100 of the front subassembly FSA and then the rear subassembly RSA is telescoped into the housing 100. Finally the rear cap 102 is attached to the proximal end of the housing 100 and may be fixed to the housing 100 via a clip.
The drive mechanism of the auto-injector according to the third exemplary embodiment may be designed as the previously described drive mechanism.
The upper part of
Considering first
In the lower part of
On the other hand, the second section of the recess 92 is delimited by an edge of the activation collar 9 only in proximal direction P. In distal direction D, the second section of the recess 92 is open and not delimited by an edge of the activation collar 9. Thus, if the protrusion of the resilient arm 53 would engage into the second section of the recess 92, the protrusion would hit against an edge of the activation collar 9 when moving the needle shroud 5 in proximal direction P which would force the activation collar 9 to also move in proximal direction P. A movement of the needle shroud 5 in distal direction D, however, would result in a disengagement of the resilient arm 53 and the recess 92.
Furthermore, it can be seen in
The first rotation-lock interface is established by a slit 91a in the activation collar 9 and a rib 47 of the drive spring holder 4 engaging into the slit 91. The rib 47 and the slit 91 are each elongated with a main extension direction along the longitudinal axis. As can be seen in
As can be seen in
However, the rotation of the activation collar 9 by the predetermined angle in the first rotational direction has as a consequence that the resilient arm 53 of the needle shroud 5 now engages into the second section of the recess 92 of the activation collar 9 which results in a decoupling of the activation collar 9 and the needle shroud 5 in distal direction D. In other words, the coupling of the needle shroud 5 and the activation collar 9 in distal direction D is released.
Furthermore, the movement of the activation collar 9 further in proximal direction P had as a consequence that a second coupling feature 90 of the activation collar 9, namely a clip 90, has engaged into a coupling feature 48 of the drive spring holder 4, namely a recess 48. The engagement between the clip 90 and the recess 48 is such that a movement of the activation collar 9 in distal direction D is prevented. When moving the needle shroud 5 from the retracted position back towards or into the extended position, the activation collar 9 does not and cannot follow. A movement of the needle shroud 5 in distal direction D relative to the activation collar 9 is enabled since the resilient arm 53 engages into the second section of the recess 92 as described above.
The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.
As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.
The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20° C.), or refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.
The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (anti-diabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.
Examples of APIs for the treatment and/or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue. The added and/or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as “insulin receptor ligands”. In particular, the term “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide. Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.
Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N—(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N—(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.
Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide/HM-11260C (Efpeglenatide), HM-15211, CM-3, GLP-1 Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN and Glucagon-Xten.
An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RGO12 for the treatment of Alport syndrom.
Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.
Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.
Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.
The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab′)2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).
The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full-length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful with embodiments described in the present disclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.
The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.
Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).
Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.
Those of skill in the art will understand that modifications (additions and/or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof. An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1:2014(E). As described in ISO 11608-1:2014(E), needle-based injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container.
As further described in ISO 11608-1:2014(E), a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).
As further described in ISO 11608-1:2014(E), a single-dose container system may involve a needle-based injection device with a replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation). As also described in ISO 11608-1:2014(E), a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).
The embodiments described herein are not limited by the description in conjunction with the exemplary embodiments. Rather, any of the embodiments described herein may comprise any new feature as well as any combination of features, particularly including any combination of features in the patent claims, even if said feature or said combination per se is not explicitly stated in the patent claims or exemplary embodiments.
| Number | Date | Country | Kind |
|---|---|---|---|
| 20315475.2 | Dec 2020 | EP | regional |
The present application is the national stage entry of International Patent Application No. PCT/EP2021/083842, filed on Dec. 1, 2021, and claims priority to Application No. EP 20315475.2, filed on Dec. 2, 2020, the disclosures of which are incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2021/083842 | 12/1/2021 | WO |
