Patent Description:
Pen type drug delivery devices have application where regular injection by persons without formal medical training occurs. This may be increasingly common among patients having diabetes where self-treatment enables such patients to conduct effective management of their disease. In practice, such a drug delivery device allows a user to individually select and dispense a number of user variable doses of a medicament. The present invention is not directed to so called fixed dose devices which only allow dispensing of a predefined dose without the possibility to increase or decrease the set dose.

There are basically two types of drug delivery devices: resettable devices (i.e., reusable) and non-resettable (i.e., disposable). For example, disposable pen delivery devices are supplied as self-contained devices. Such self-contained devices do not have removable pre-filled cartridges. Rather, the pre-filled cartridges may not be removed and replaced from these devices without destroying the device itself. Consequently, such disposable devices need not have a resettable dose setting mechanism. The present invention is directed to reusable devices which allow resetting of the device and a replacement of a cartridge. Resetting of the device typically involves moving a piston rod or lead screw from an extended (distal) position, i.e. a position after dose dispensing, into a more retracted (proximal) position.

These types of pen delivery devices (so named because they often resemble an enlarged fountain pen) generally comprise three primary elements: a cartridge section that includes a cartridge often contained within a housing or holder; a needle assembly connected to one end of the cartridge section; and a dosing section connected to the other end of the cartridge section. A cartridge (often referred to as an ampoule) typically includes a reservoir that is filled with a medication (e.g., insulin), a movable rubber type bung or stopper located at one end of the cartridge reservoir, and a top having a pierceable rubber seal located at the other, often necked-down, end. A crimped annular metal band is typically used to hold the rubber seal in place.

While the cartridge housing may be typically made of plastic, cartridge reservoirs have historically been made of glass.

The needle assembly is typically a replaceable double-ended needle assembly. Before an injection, a replaceable double-ended needle assembly is attached to one end of the cartridge assembly, a dose is set, and then the set dose is administered. Such removable needle assemblies may be threaded onto, or pushed (i.e., snapped) onto the pierceable seal end of the cartridge assembly.

The dosing section or dose setting mechanism is typically the portion of the pen device that is used to set (select) a dose. During an injection, a spindle or piston rod contained within the dose setting mechanism presses against the bung or stopper of the cartridge. This force causes the medication contained within the cartridge to be injected through an attached needle assembly. After an injection, as generally recommended by most drug delivery device and/or needle assembly manufacturers and suppliers, the needle assembly is removed and discarded.

A further differentiation of drug delivery device types refers to the drive mechanism: There are devices which are manually driven, e.g. by a user applying a force to an injection button, devices which are driven by a spring or the like and devices which combine these two concepts, i.e. spring assisted devices which still require a user to exert an injection force. The spring-type devices involve springs which are preloaded and springs which are loaded by the user during dose selecting. Some stored-energy devices use a combination of spring preload and additional energy provided by the user, for example during dose setting.

<CIT> discloses a drug delivery device with a housing and a cartridge holder which is inserted with its proximal end into the distal end of the housing such that the proximal end of the cartridge holder is axially spaced from a web provided within the housing near its distal end. A guide nut is prevented from axial movement in the distal direction by means of an interaction member. Further, the web prevents axial movement of the guide nut in the proximal direction. A dose dial sleeve is rotated during dose setting and dose dispensing. The dose dial sleeve is in threaded engagement with the housing such that dose setting includes a proximal movement of the dose dial sleeve and dose dispensing includes a distal movement of the dose dial sleeve. In a certain state of the device, further proximal movement of the dose dial sleeve is limited by a stop element which in turn is axially movable relative to the housing.

<CIT> discloses a drug delivery device with a housing and a cartridge holder. An indicator element is provided axially displaceable within the housing.

Unpublished patent application<CIT> refers to a drug delivery device comprising a dose setting member which is axially constrained to an outer housing such that the dose setting member is rotatable with respect to the outer housing. A cartridge holder is attached to the distal end of the outer housing such that the proximal end of the cartridge holder does not overlap the distal end of the dose setting member.

In some cases it may be desirable, to prevent axial detachment of the dose setting member or any further component part from the outer housing even if an axial force is exerted on the dose setting member or the further component part, e.g. by a spring. Thus, it is an object of the present invention to provide an improved drug delivery device and a respective housing.

This object is solved by a housing according to claim <NUM> and a drug delivery device according to claim <NUM>.

According to the invention, a housing for a drug delivery device comprises an outer housing with a distal end and a cartridge holder with a proximal end, which, when the cartridge holder is attached to the outer housing, is inserted into the distal end of the outer housing. The outer housing is provided with a first fixture for axially constraining a further component part, for example a dose setting member, to the outer housing. When the cartridge holder is attached to the outer housing, the proximal end of the cartridge holder preferably axially extends to the first fixture. This includes embodiments, where the proximal end of the cartridge holder axially extends over the first fixture, and embodiments, where the proximal end of the cartridge holder ends, preferably shortly, i.e. less than <NUM>, offset in the distal direction from the first fixture. In other words, the proximal end of the cartridge holder and the further component part are arranged to allow an overlapping of these two component parts. This disables an inward movement or deformation of the further component part, and, thus, prevents detachment of the further component part from the outer housing. The further component part is preferably a dose setting member and/or a display member, like a number sleeve, having markings on its outer surface to display e.g. the set dose.

The proximal end of the cartridge holder may comprise at least one proximally extending protrusion, like a proximally extending finger. When the cartridge holder is attached to the outer housing, the at least one proximally extending protrusion axially extends to the first fixture. In other words, the present invention does not require that the whole cartridge holder extends to the first fixture. Rather, it is sufficient (and in some cases preferred) if only a part of the cartridge holder extends towards the first fixture.

The first fixture is preferably suitable for snap engagement with the further component part. For example, the first fixture may comprise a groove or bead located on the inner surface of the outer housing. The groove or bead may extend over the whole circumference of the inner surface of the outer housing or only parts thereof, e.g. forming separate ramps. Preferably, the proximal end of the cartridge holder is located radially inwards of the first fixture, when the cartridge holder is attached to the outer housing. In other words, the further component part may be radially interposed between the cartridge holder and the outer housing.

According to a preferred embodiment of the invention, the housing further comprises a housing insert, which is rotationally and/or axially constrained to the outer housing, preferably at a position axially distal from and/or overlapping with the first fixture. The housing insert may comprise one or more engagement features, like a thread, splines, guiding ribs or grooves and/or a bearing or attachment for a spring. The housing insert may be a separate component part which is permanently or temporarily attached to the outer housing or it may be a one-piece component of the outer housing, like an inner web or flange. Typically, the cartridge holder mainly extends distally from such an insert. However, for interaction with the first fixture and/or a component part attached thereto, it is preferred if the proximal end of the cartridge holder, at least partly, extends through the housing insert. For example, the insert may be attached to the outer housing via radially extending arms having a passage for the proximal end of the cartridge holder between the arms. Alternatively, the insert itself may have at least one passage for the proximal end of the cartridge holder.

As an alternative, the housing may comprise a housing insert, which is rotationally and/or axially constrained to the outer housing and located radially inwards of the first fixture at a position axially overlapping with the first fixture. In a preferred embodiment, a thread for engaging a piston rod is part of the housing, and the insert contains splines for preventing rotation of a drive sleeve. In this embodiment, a number sleeve may have an extended distal rim.

In a preferred embodiment the housing further comprises a second fixture for axially constraining the cartridge holder to the outer housing. The second fixture may be located on the inner surface of the outer housing, e.g. at a position axially distal from the first fixture. In other words, there may be two separate fixtures provided on the inner surface of the outer housing which are axially off-set.

In another preferred embodiment the housing further comprises a separate, third fixture for rotationally constraining the cartridge holder to the outer housing. For example, the third fixture comprises at least one distally extending protrusion of the outer housing having longitudinal splines and a splined portion on the outer surface of the cartridge holder.

In still another preferred embodiment the housing further comprises a separate, fourth fixture for axially and/or rotationally constraining a cap to the outer housing. The cap may be designed to receive the cartridge holder or a part thereof, when the cap is attached to the outer housing. Preferably, the fourth fixture is located on the outer surface of the outer housing, for example at a position axially distal from the first fixture, preferably at the axial position of the first or second fixture. If the fourth fixture is located axially at the same position or in the vicinity of the first or second fixture, forces exerted on the first or second fixture tending to bulge the outer housing may be reacted by the fourth fixture, which may act like a reinforcing material added to the wall thickness of the outer housing. Vice versa, the first or second fixture may act like a reinforcement for the fourth fixture. In addition, the cap on the one hand and the cartridge holder or the further component part on the other hand may mutually react radially directed forces.

A drug delivery device for selecting and dispensing a number of user variable doses of a medicament may comprise a housing, e.g. a housing as defined above, a dose setting element rotatable relative to the outer housing during dose setting and dose dispensing, a drive member coupled to the dose setting member via a clutch, and a piston rod coupled to the outer housing and to the drive member. The dose setting member is preferably axially constrained to the outer housing by a first fixture of the outer housing, for example the first fixture as defined above. The first fixture preferably comprises a groove or bead located on the inner surface of the outer housing and a corresponding bead or groove located on the outer surface of the dose setting member. In other words, a snap engagement is provided for permanently or temporarily attaching the dose setting member to the outer housing. Preferably, this snap engagement is designed such that relative rotation between the dose setting member and the outer housing is allowed, while relative axial movement is prevented.

The dose setting member preferably comprises a portion, e.g. a rim, extending axially distal from the bead or groove of the first fixture. The length of this portion may contribute in preventing unintended detachment of the dose setting member, especially if the dose setting member comprises a recessed groove engaging a bead or protrusion of the first fixture with the distally extending portion of the dose setting member having a larger outer diameter than the recessed groove. For example, the distally extending portion may have a length of <NUM> to <NUM>, e.g. about <NUM>.

To further strengthen attachment of the dose setting member, the at least a portion of the cartridge holder is located radially inwards of the dose setting member and axially overlapping the dose setting member when the cartridge holder is attached to the outer housing. In other words, the dose setting member is radially interposed between the cartridge holder and the outer housing, such that the cartridge holder blocks inward movement of the dose setting member. Thus, as soon as the cartridge holder is fully attached to the outer housing, axial detachment of the dose setting member from the outer housing is prevented.

In a drug delivery device according to the present invention the dose setting member is preferably rotatable relative to the outer housing during dose setting, i.e. increasing or decreasing the dose, and dose dispensing between a minimum dose position and a maximum dose position. The drive member may be rotationally coupled to the dose setting member via a slipping clutch during dose setting and rotationally constrained to the dose setting member during dose dispensing.

The drug delivery device may be a disposable device which is intended to be discarded if the cartridge is empty. As an alternative, the device may be a reusable device requiring resetting, e.g. of a piston rod, when replacing an empty cartridge by a new cartridge. In the latter case, the housing insert may be a reset element which is preferably axially constrained to the dose setting element. In addition, the device may comprise at least one spring acting on the reset element, such that, if the cartridge holder is detached from the outer housing, the reset element is axially moved relative to the outer housing into a position in which the dose setting element is rotationally constrained to the outer housing and the drive member is allowed to rotate relative to the outer housing. In other words, detachment of the cartridge holder from the outer housing may allow an axial movement of the reset element and, preferably, the dose setting element into a resetting position, in which the drive member may be rotated relative to the outer housing and relative to the dose setting member. If the piston rod is coupled to the outer housing and to the drive member, e.g. via a threaded interface with the outer housing and a splined interface with the drive member, resetting of the piston rod requires free rotation of the drive member. Thus, resetting of the drug delivery device may be performed simply by pushing back the piston rod or lead screw after removal of the cartridge holder.

In a further development of this embodiment, the clutch between the dose setting element and the drive member is a slipping clutch with first clutch teeth on the drive member and second clutch teeth on a clutch plate, which is rotationally constrained to the dose setting element during dose setting and dose dispensing. For example, the first and/or second clutch teeth may each be distributed as a ring of teeth, preferably facing in the axial direction. The clutch features and the corresponding clutch features may each comprise a series of teeth, preferably saw-teeth, which are allowed to slip over each other if not pressed against each other too firmly. In other words, the clutch features may be overhauled against the bias of a clutch spring by allowing the sleeve and/or the clutch element to translate axially against the force of the clutch spring. This may result in an oscillating axial movement of the sleeve and/or the clutch element due to continued disengagement and following re-engagement into the next detented position. An audible click may be generated by this re-engagement, and tactile feedback may be given by the change in torque input required.

Preferably, the clutch between the drive member and the dose setting element is a slipping clutch which allows relative rotation between the drive member and the dose setting element in both directions during dose setting for increasing or decreasing a set dose. If the device is a spring driven device, the clutch teeth may be designed to provide a different resistance for overcoming the clutch depending on the direction of the relative rotation. For example, the ramp angle may be shallower resulting in a lower resistance in the dose increasing direction and steeper resulting in a higher resistance in the dose decreasing direction.

According to a preferred embodiment, the drug delivery device is a spring driven device. A drive spring, preferably a torsion spring, may be interposed between the housing and the dose setting element. Providing a resilient drive member, such as a torsion spring, generating the force or torque required for dose dispensing reduces the user applied forces for dose dispensing. This is especially helpful for users with impaired dexterity. In addition, the dial extension of the known manually driven devices, which is a result of the required dispensing stroke, may be omitted by providing the resilient member because merely a small triggering stroke may be necessary for releasing the resilient member. The drive spring may be pre-charged, at least partly, and/or may be charged by a user during dose setting.

In another preferred embodiment, the drug delivery device further comprises a gauge element radially interposed between the outer housing and the dose setting element. The gauge element is axially movable relative to the outer housing and in threaded engagement with the dose setting element. The outer housing may comprise at least one aperture and the gauge element may comprise at least one aperture. If the dose setting element is a number sleeve which comprises markings on its outer surface, at least one of the markings is visible through the aperture in the gauge element and the aperture in the outer housing during dose setting and dose dispensing. The term aperture may include a simple opening the outer housing or gauge element or a transparent window or lens. A window in the outer housing may be incorporated using a 'twin-shot' moulding technology. For example, the outer housing is moulded during a 'first shot' in a translucent material, and the outer cover of the outer housing is moulded during a 'second shot' in an opaque material.

The gauge element may be axially guided within the outer housing such that rotation of the dose setting element causes an axial displacement of the gauge element. The position of the gauge element may thus be used to identify the actually set and/or dispensed dose. Different colours of sections of the gauge member may facilitate identifying the set and/or dispensed dose without reading numbers, symbols or the like on a display. As the gauge element is in threaded engagement with the dose setting element, rotation of the dose setting element causes an axial displacement of the gauge element relative to the dose setting element and relative to the outer housing. The gauge element may have the form of a shield or strip extending in the longitudinal direction of the device. As an alternative, the gauge element may be a sleeve. In an embodiment of the invention, the dose setting element is marked with a sequence of numbers or symbols arranged on a helical path. With the dose setting element located radially inwards of the gauge element, this allows that at least one of the numbers or symbols on the dose setting element is visible through the aperture or window. In other words, the gauge element may be used to shield or cover a portion of the dose setting element and to allow view only on a limited portion of the dose setting element. This function may be in addition to the gauge element itself being suitable for identifying or indicating the actually set and/or dispensed dose.

In general, the concept of the gauge element and the dose setting element is applicable for various types of devices with or without a drive spring. In a preferred embodiment, the dose setting element, during dose setting, is adapted to undergo a mere rotational movement within the outer housing and relative to the outer housing. In other words, the dose setting element does not perform a translational movement during dose setting. This prevents that the dose setting element is wound out of the outer housing or that the outer housing has to be prolonged for covering the dose setting element within the outer housing.

The relative movements of the gauge element and the dose setting element may further be used to define the minimum dose position and the maximum dose position. Typically, the minimum settable dose is zero (<NUM> IU of insulin formulation), such that the limiter stops the device at the end of dose dispensing. The maximum settable dose, for example <NUM>, <NUM> or <NUM> IU of insulin formulation, may be limited to reduce the risk of overdosage and to avoid the additional spring torque needed for dispensing very high doses, while still being suitable for a wide range of patients needing different dose sizes. Preferably, the limits for the minimum dose and the maximum dose are provided by hard stop features. For example, the gauge element comprises a minimum dose rotational stop and a maximum dose rotational stop and the dose setting element comprises a minimum dose rotational counter stop and a maximum dose rotational counter stop. Abutment of the respective stop and counter stop blocks further relative movement between the gauge element and the dose setting element. As the dose indicator rotates relative to the gauge element during dose setting and during dose dispensing, these two components are suitable to form a reliable and robust limiter mechanism.

The device may further comprise a dispensing button or trigger. The button is preferably a user operable element located proximally of the drive sleeve and the clutch element. When used in a drug delivery device, the button may extend from the proximal end of the device and, preferably, does not change its axial position during dose setting. The button is preferably coupled to a user operable dose selector and may be releasably coupled to a number sleeve component and/or a stationary housing component. In an alternative embodiment, the button may be part of a dose setting arrangement or may be the dose setting member. The button may be a multi-functional element having in addition to the above features e.g. a clicker feature.

The drug delivery device may further comprise a last dose protection mechanism for preventing the setting of a dose, which exceeds the amount of liquid left in a cartridge. This has the advantage that the user knows how much will be delivered before starting the dose delivery. It also ensures that dose delivery stops in a controlled manner without the bung entering the neck portion of the cartridge where the diameter is smaller which may result in an underdose. For example, the last dose protection mechanism comprises a nut member interposed between the drive member and the dose setting element (number sleeve) or any other component which rotates during dose setting and dose dispensing. In a preferred embodiment, the dose setting element rotates during dose setting and during dose dispensing, whereas the drive member only rotates during dose dispensing together with the dose setting element. Thus, in this embodiment, the nut member will only move axially during dose setting and will remain stationary with respect to these components during dose dispensing. Preferably, the nut member is threaded to the drive member and splined to the dose setting member. As an alternative, the nut member may be threaded to the dose setting member and may be splined to the drive member. The nut member may be a full nut or a part thereof, e.g. a half nut.

The injection device may comprise at least one clicker mechanism for generating a tactile and/or audible feedback. A feedback may be generated during dose setting (increasing and/or decreasing a dose), dose dispensing and/or at the end of dose dispensing.

The drug delivery device may comprise a cartridge containing a medicament. The term "medicament", as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound,.

Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists as listed in Rote Liste, ed. <NUM>, Chapter <NUM>, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.

Antibodies are globular plasma proteins (-<NUM> kDa) that are also known as immunoglobulins which share a basic structure. As they have sugar chains added to amino acid residues, they are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

Non-limiting, exemplary embodiments of the invention will now be described with reference to the accompanying drawings, in which:.

<FIG> shows a drug delivery device in the form of an injection pen. The device has a distal end (left end in <FIG>) and a proximal end (right end in <FIG>). The component parts of the drug delivery device are shown in <FIG>. The drug delivery device comprises a body or housing <NUM>, a cartridge holder <NUM>, a lead screw (piston rod) <NUM>, a drive sleeve <NUM>, a nut <NUM>, a dose indicator (number sleeve) <NUM>, a button <NUM>, a dial grip or dose selector <NUM>, a torsion spring <NUM>, a cartridge <NUM>, a gauge element <NUM>, a clutch plate <NUM>, a clutch spring <NUM> and a bearing <NUM>. A needle arrangement (not shown) with a needle hub and a needle cover may be provided as additional components, which can be exchanged as explained above. All components are located concentrically about a common principal axis I of the mechanism which is shown in <FIG>.

The housing <NUM> or body is a generally tubular element having a proximal end with an enlarged diameter. The housing <NUM> provides location for the liquid medication cartridge <NUM> and cartridge holder <NUM>, windows 11a, 11b for viewing the dose number on the number sleeve <NUM> and the gauge element <NUM>, and a feature on its external surface, e.g. a circumferential groove, to axially retain the dose selector <NUM>. An insert <NUM> comprises an inner thread engaging the piston rod <NUM>. The housing <NUM> further has at least one internal, axially orientated slot or the like for axially guiding the gauge element <NUM>. In the embodiment shown in the Figures, the distal end is provided with an axially extending strip <NUM> partly overlapping cartridge holder <NUM>. The Figures depict the housing <NUM> as a single housing component. However, the housing <NUM> could comprise two or more housing components which may be permanently attached to each other during assembly of the device. The housing <NUM> comprises a fixture for engaging number sleeve <NUM>, which fixture has the form of an inner bead <NUM>. The bead <NUM> is located at a distal region of housing <NUM> on its inner surface.

The cartridge holder <NUM> is located at the distal side of housing <NUM> and permanently attached thereto. The cartridge holder may be a transparent or translucent component which is tubular to receive cartridge <NUM>. The distal end of cartridge holder <NUM> may be provided with means for attaching a needle arrangement. A removable cap (not shown) may be provided to fit over the cartridge holder <NUM> and may be retained via clip features on the housing <NUM>. The cartridge holder <NUM> has an extension <NUM> in the form of a proximally extending finger (<FIG>).

The piston rod <NUM> is rotationally constrained to the drive sleeve <NUM> via a splined interface. When rotated, the piston rod <NUM> is forced to move axially relative to the drive sleeve <NUM>, through its threaded interface with the insert <NUM> of housing <NUM>. The lead screw <NUM> is an elongate member with an outer thread engaging the corresponding thread of the insert <NUM> of housing <NUM>. The interface comprises at least one longitudinal groove or track and a corresponding protrusion or spline of the driver <NUM>. At its distal end, the lead screw <NUM> is provided with an interface for clip attachment of the bearing <NUM>.

The drive sleeve <NUM> is a hollow member surrounding the lead screw <NUM> and arranged within number sleeve <NUM>. It extends from an interface with the clutch plate <NUM> to the contact with the clutch spring <NUM>. The drive sleeve <NUM> is axially movable relative to the housing <NUM>, the piston rod <NUM> and the number sleeve <NUM> in the distal direction against the bias of clutch spring <NUM> and in the opposite proximal direction under the bias of clutch spring <NUM>.

A splined tooth interface with the housing <NUM> prevents rotation of the drive sleeve <NUM> during dose setting. This interface comprises a ring of radially extending outer teeth at the distal end of drive sleeve <NUM> and corresponding radially extending inner teeth of the housing component <NUM>. When the button <NUM> is pressed, these drive sleeve <NUM> to housing <NUM> spline teeth are disengaged allowing the drive sleeve <NUM> to rotate relative to housing <NUM>. A further splined tooth interface with the number sleeve <NUM> is not engaged during dialling, but engages when the button <NUM> is pressed, preventing relative rotation between the drive sleeve <NUM> and number sleeve <NUM> during dispense. In a preferred embodiment this interface comprises inwardly directed splines on a flange on the inner surface of the number sleeve <NUM> and a ring of radially extending outer splines of drive sleeve <NUM>. These corresponding splines are located on the number sleeve <NUM> and the drive sleeve <NUM>, respectively, such that axial movement of the drive sleeve <NUM> relative to the (axially fixed) number sleeve <NUM> engages or disengages the splines to rotationally couple or decouple the drive sleeve <NUM> and the number sleeve <NUM>.

A further interface of the drive sleeve <NUM> comprises a ring of ratchet teeth located at the proximal end face of drive sleeve <NUM> and a ring of corresponding ratchet teeth on the clutch plate <NUM>.

The driver <NUM> has a threaded section providing a helical track for the nut <NUM>. In addition, a last dose abutment or stop is provided which may be the end of the thread track or preferably a rotational hard stop for interaction with a corresponding last dose stop of nut <NUM>, thus limiting movement of the nut <NUM> on the driver thread. At least one longitudinal spline of the driver <NUM> engages a corresponding track of the lead screw <NUM>.

The last dose nut <NUM> is located between the number sleeve <NUM> and the drive sleeve <NUM>. It is rotationally constrained to the number sleeve <NUM>, via a splined interface. It moves along a helical path relative to the drive sleeve <NUM>, via a threaded interface, when relative rotation occurs between the number sleeve <NUM> and drive sleeve <NUM> which is during dialling only. As an alternative, the nut <NUM> may be splined to the driver <NUM> and threaded to the number sleeve <NUM>. A last dose stop is provided on nut <NUM> engaging a stop of drive sleeve <NUM> when a dose is set corresponding to the remaining dispensable amount of medicament in the cartridge <NUM>.

The dose indicator or number sleeve <NUM> is a tubular element as shown in <FIG> in more detail. The number sleeve <NUM> is rotated during dose setting (via dose selector <NUM>) and dose correction and during dose dispensing by torsion spring <NUM>. Together with gauge element <NUM> the number sleeve <NUM> defines a zero position ('at rest') and a maximum dose position. Thus, the number sleeve <NUM> may be seen as a dose setting member.

For manufacturing reasons the number sleeve <NUM> of the embodiment shown in the Figures comprises a number sleeve lower 60a which is rigidly fixed to a number sleeve upper 60b during assembly to form the number sleeve <NUM>. Number sleeve lower 60a and number sleeve upper 60b are separate components only to simplify number sleeve <NUM> mould tooling and assembly. As an alternative, the number sleeve <NUM> may be a unitary component. The number sleeve <NUM> is constrained to the housing <NUM> by snap engagement to allow rotation but not translation. The number sleeve <NUM> comprises an annular recess or groove <NUM> near its distal end which engages a corresponding bead on an inner surface of the housing <NUM>. The number sleeve lower 60a is marked with a sequence of numbers, which are visible through the gauge element <NUM> and the openings 11a, 11b in the housing <NUM>, to denote the dialled dose of medicament.

Further, the number sleeve lower 60a has a portion with an outer thread engaging the gauge element <NUM>. End stops are provided at the opposite ends of thread to limit relative movement with respect to the gauge element <NUM>.

Clutch features which have the form of a ring of splines are provided inwardly directed on number sleeve upper 60b for engagement with splines of the button <NUM> during dose setting and dose correction. A clicker arm is provided on the outer surface of number sleeve <NUM> which interacts with the drive sleeve <NUM> and the gauge member <NUM> for generating a feedback signal. In addition, the number sleeve lower 60a is rotationally constrained to the nut <NUM> and to the clutch plate <NUM> via a splined interface comprising at least one longitudinal spline. Further, number sleeve lower 60a comprises an interface for attachment of the torsion spring <NUM>.

The button <NUM> which forms the proximal end of the device is permanently splined to the dose selector <NUM>. A central stem extends distally from the proximal actuation face of the button <NUM>. The stem is provided with a flange carrying the splines for engagement with splines of the number sleeve upper 60b. Thus, it is also splined via splines to the number sleeve upper 60b when the button <NUM> is not pressed, but this spline interface is disconnected when the button <NUM> is pressed. The button <NUM> has a discontinuous annular skirt with splines. When the button <NUM> is pressed, splines on the button <NUM> engage with splines on the housing <NUM>, preventing rotation of the button <NUM> (and hence the dose selector <NUM>) during dispense. These splines disengage when the button <NUM> is released, allowing a dose to be dialled. Further, a ring of ratchet teeth is provided on the inner side of button flange for interaction with clutch plate <NUM>.

The dose selector <NUM> is axially constrained to the housing <NUM>. It is rotationally constrained, via the splined interface, to the button <NUM>. This splined interface which includes grooves interacting with spline features formed by the annular skirt of button <NUM> remains engaged irrespective of the dose button <NUM> axial positions. The dose selector <NUM> or dose dial grip is a sleeve-like component with a serrated outer skirt.

The torsion spring <NUM> is attached at its distal end to the housing <NUM> and at the other end to the number sleeve <NUM>. The torsion spring <NUM> is located inside the number sleeve <NUM> and surrounds a distal portion of the drive sleeve <NUM>. The torsion spring <NUM> is pre-wound upon assembly, such that it applies a torque to the number sleeve <NUM> when the mechanism is at zero units dialled. The action of rotating the dose selector <NUM>, to set a dose, rotates the number sleeve <NUM> relative to the housing <NUM>, and charges the torsion spring <NUM> further.

The cartridge <NUM> is received in cartridge holder <NUM>. The cartridge <NUM> may be a glass ampoule having a moveable rubber bung at its proximal end. The distal end of cartridge <NUM> is provided with a pierceable rubber seal which is held in place by a crimped annular metal band. In the embodiment depicted in the Figures, the cartridge <NUM> is a standard <NUM>,<NUM> cartridge. The device is designed to be disposable in that the cartridge <NUM> cannot be replaced by the user or health care professional. However, a reusable variant of the device could be provided by making the cartridge holder <NUM> removable and allowing backwinding of the lead screw <NUM> and the resetting of nut <NUM>.

The gauge element <NUM> is constrained to prevent rotation but allow translation relative to the housing <NUM> via a splined interface. The gauge element <NUM> has a helical feature on its inner surface which engages with the helical thread cut in the number sleeve <NUM> such that rotation of the number sleeve <NUM> causes axial translation of the gauge element <NUM>. This helical feature on the gauge element <NUM> also creates stop abutments against the end of the helical cut in the number sleeve <NUM> to limit the minimum and maximum dose that can be set.

The gauge element <NUM> has a generally plate or band like component having a central aperture or window and two flanges extending on either side of the aperture. The flanges are preferably not transparent and thus shield or cover the number sleeve <NUM>, whereas the aperture or window allows viewing a portion of the number sleeve lower 60a. Further, gauge element <NUM> has a cam and a recess interacting with the clicker arm of the number sleeve <NUM> at the end of dose dispensing.

The clutch plate <NUM> is a ring-like component. The clutch plate <NUM> is splined to the number sleeve <NUM> via splines. It is also coupled to the drive sleeve <NUM> via a ratchet interface. The ratchet provides a detented position between the number sleeve <NUM> and drive sleeve <NUM> corresponding to each dose unit, and engages different ramped tooth angles during clockwise and anti-clockwise relative rotation. A clicker arm is provided on the clutch plate <NUM> for interaction with ratchet features of the button <NUM>.

The clutch spring <NUM> is a compression spring. The axial position of the drive sleeve <NUM>, clutch plate <NUM> and button <NUM> is defined by the action of the clutch spring <NUM>, which applies a force on the drive sleeve <NUM> in the proximal direction. This spring force is reacted via the drive sleeve <NUM>, clutch plate <NUM>, and button <NUM>, and when 'at rest' it is further reacted through the dose selector <NUM> to the housing <NUM>. The spring force ensures that the ratchet interface between drive sleeve <NUM> and clutch plate <NUM> is always engaged. In the 'at rest' position, it also ensures that the button splines are engaged with the number sleeve splines, and the drive sleeve teeth are engaged with teeth of the housing <NUM>.

The bearing <NUM> is axially constrained to the piston rod <NUM> and acts on the bung within the liquid medicament cartridge. It is axially clipped to the lead screw <NUM>, but free to rotate.

With the device in the 'at rest' condition as shown in <FIG>, the number sleeve <NUM> is positioned against its zero dose abutment with the gauge element <NUM> and the button <NUM> is not depressed. Dose marking '<NUM>' on the number sleeve <NUM> is visible through the window 11b of the housing <NUM> and gauge element <NUM>, respectively.

The torsion spring <NUM>, which has a number of pre-wound turns applied to it during assembly of the device, applies a torque to the number sleeve <NUM> and is prevented from rotating by the zero dose abutment.

The user selects a variable dose of liquid medicament by rotating the dose selector <NUM> clockwise, which generates an identical rotation in the number sleeve <NUM>. Rotation of the number sleeve <NUM> causes charging of the torsion spring <NUM>, increasing the energy stored within it. As the number sleeve <NUM> rotates, the gauge element <NUM> translates axially due to its threaded engagement thereby showing the value of the dialled dose. The gauge element <NUM> has flanges either side of the window area which cover the numbers printed on the number sleeve <NUM> adjacent to the dialled dose to ensure only the set dose number is made visible to the user.

A specific feature of this invention is the inclusion of a visual feedback feature in addition to the discrete dose number display typical on devices of this type. The distal end of the gauge element <NUM> creates a sliding scale through the small window 11a in the housing <NUM>. As an alternative, the sliding scale could be formed using a separate component engaged with the number sleeve <NUM> on a different helical track.

As a dose is set by the user, the gauge element <NUM> translates axially, the distance moved proportional to the magnitude of the dose set. This feature gives clear feedback to the user regarding the approximate size of the dose set. The dispense speed of an auto-injector mechanism may be higher than for a manual injector device, so it may not be possible to read the numerical dose display during dispense. The gauge feature provides feedback to the user during dispense regarding dispense progress without the need to read the dose number itself. For example, the gauge display may be formed by an opaque element on the gauge element <NUM> revealing a contrasting coloured component underneath. Alternatively, the revealable element may be printed with coarse dose numbers or other indices to provide more precise resolution. In addition, the gauge display simulates a syringe action during dose set and dispense.

The drive sleeve <NUM> is prevented from rotating as the dose is set and the number sleeve <NUM> rotated, due to the engagement of its splined teeth with teeth of the housing <NUM>. Relative rotation must therefore occur between the clutch plate <NUM> and drive sleeve <NUM> via the ratchet interface.

The user torque required to rotate the dose selector <NUM> is a sum of the torque required to wind up the torsion spring <NUM>, and the torque required to overhaul the ratchet interface. The clutch spring <NUM> is designed to provide an axial force to the ratchet interface and to bias the clutch plate <NUM> onto the drive sleeve <NUM>. This axial load acts to maintain the ratchet teeth engagement of the clutch plate <NUM> and drive sleeve <NUM>. The torque required to overhaul the ratchet in the dose set direction is a function of the axial load applied by the clutch spring <NUM>, the clockwise ramp angle of the ratchet teeth, the friction coefficient between the mating surfaces and the mean radius of the ratchet interface.

As the user rotates the dose selector <NUM> sufficiently to increment the mechanism by one increment, the number sleeve <NUM> rotates relative to the drive sleeve <NUM> by one ratchet tooth. At this point the ratchet teeth re-engage into the next detented position. An audible click is generated by the ratchet re-engagement, and tactile feedback is given by the change in torque input required.

Relative rotation of the number sleeve <NUM> and the drive sleeve <NUM> is allowed. This relative rotation also causes the last dose nut <NUM> to travel along its threaded path, towards its last dose abutment on the drive sleeve <NUM>.

With no user torque applied to the dose selector <NUM>, the number sleeve <NUM> is now prevented from rotating back under the torque applied by the torsion spring <NUM>, solely by the ratchet interface between the clutch plate <NUM> and the drive sleeve <NUM>. The torque necessary to overhaul the ratchet in the anti-clockwise direction is a function of the axial load applied by the clutch spring <NUM>, the anti-clockwise ramp angle of the ratchet, the friction coefficient between the mating surfaces and the mean radius of the ratchet features. The torque necessary to overhaul the ratchet must be greater than the torque applied to the number sleeve <NUM> (and hence clutch plate <NUM>) by the torsion spring <NUM>. The ratchet ramp angle is therefore increased in the anti-clockwise direction to ensure this is the case whilst ensuring the dial-up torque is as low as possible.

The user may now choose to increase the selected dose by continuing to rotate the dose selector <NUM> in the clockwise direction. The process of overhauling the ratchet interface between the number sleeve <NUM> and drive sleeve <NUM> is repeated for each dose increment. Additional energy is stored within the torsion spring <NUM> for each dose increment and audible and tactile feedback is provided for each increment dialled by the re-engagement of the ratchet teeth. The torque required to rotate the dose selector <NUM> increases as the torque required to wind up the torsion spring <NUM> increases. The torque required to overhaul the ratchet in the anti-clockwise direction must therefore be greater than the torque applied to the number sleeve <NUM> by the torsion spring <NUM> when the maximum dose has been reached.

If the user continues to increase the selected dose until the maximum dose limit is reached, the number sleeve <NUM> engages with its maximum dose abutment on the maximum dose abutment of gauge element <NUM>. This prevents further rotation of the number sleeve <NUM>, clutch plate <NUM> and dose selector <NUM>.

Depending on how many increments have already been delivered by the mechanism, during selection of a dose, the last dose nut <NUM> may contact its last dose abutment with stop face of the drive sleeve <NUM>. The abutment prevents further relative rotation between the number sleeve <NUM> and the drive sleeve <NUM>, and therefore limits the dose that can be selected. The position of the last dose nut <NUM> is determined by the total number of relative rotations between the number sleeve <NUM> and drive sleeve <NUM>, which have occurred each time the user sets a dose.

With the mechanism in a state in which a dose has been selected, the user is able to deselect any number of increments from this dose. Deselecting a dose is achieved by the user rotating the dose selector <NUM> anti-clockwise. The torque applied to the dose selector <NUM> by the user is sufficient, when combined with the torque applied by the torsion spring <NUM>, to overhaul the ratchet interface between the clutch plate <NUM> and drive sleeve <NUM> in the anti-clockwise direction. When the ratchet is overhauled, anti-clockwise rotation occurs in the number sleeve <NUM> (via the clutch plate <NUM>), which returns the number sleeve <NUM> towards the zero dose position, and unwinds the torsion spring <NUM>. The relative rotation between the number sleeve <NUM> and drive sleeve <NUM> causes the last dose nut <NUM> to return along its helical path, away from the last dose abutment.

With the mechanism in a state in which a dose has been selected, the user is able to activate the mechanism to commence delivery of a dose. Delivery of a dose is initiated by the user depressing the button <NUM> axially in the distal direction.

When the button <NUM> is depressed, splines between the button <NUM> and number sleeve <NUM> are disengaged, rotationally disconnecting the button <NUM> and dose selector <NUM> from the delivery mechanism, i.e. from number sleeve <NUM>, gauge element <NUM> and torsion spring <NUM>. Splines on the button <NUM> engage with splines on the housing <NUM>, preventing rotation of the button <NUM> (and hence the dose selector <NUM>) during dispense. As the button <NUM> is stationary during dispense, it can be used in the dispense clicker mechanism. A stop feature in the housing <NUM> limits axial travel of the button <NUM> and reacts any axial abuse loads applied by the user, reducing the risk of damaging internal components.

The clutch plate <NUM> and drive sleeve <NUM> travel axially with the button <NUM>. This engages the splined tooth interface between the drive sleeve <NUM> and number sleeve <NUM>, preventing relative rotation between the drive sleeve <NUM> and number sleeve <NUM> during dispense. The splined tooth interface between the drive sleeve <NUM> and the housing <NUM> disengages, so the drive sleeve <NUM> can now rotate and is driven by the torsion spring <NUM> via the number sleeve <NUM>, and clutch plate <NUM>.

Rotation of the drive sleeve <NUM> causes the piston rod <NUM> to rotate due to their splined engagement, and the piston rod <NUM> then advances due to its threaded engagement to the housing <NUM>. The number sleeve <NUM> rotation also causes the gauge element <NUM> to traverse axially back to its zero position whereby the zero dose abutment stops the mechanism.

Tactile feedback during dose dispense is provided via the compliant cantilever clicker arm integrated into the clutch plate <NUM>. This arm interfaces radially with ratchet features on the inner surface of the button <NUM>, whereby the ratchet tooth spacing corresponds to the number sleeve <NUM> rotation required for a single increment dispense. During dispense, as the number sleeve <NUM> rotates and the button <NUM> is rotationally coupled to the housing <NUM>, the ratchet features engage with the clicker arm to produce an audible click with each dose increment delivered.

Delivery of a dose continues via the mechanical interactions described above while the user continues to depress the button <NUM>. If the user releases the button <NUM>, the clutch spring <NUM> returns the drive sleeve <NUM> to its 'at rest' position (together with the clutch plate <NUM> and button <NUM>), engaging the splines between the drive sleeve <NUM> and housing <NUM>, preventing further rotation and stopping dose delivery.

During delivery of a dose, the drive sleeve <NUM> and number sleeve <NUM> rotate together, so that no relative motion in the last dose nut <NUM> occurs. The last dose nut <NUM> therefore travels axially relative to the drive sleeve <NUM> during dialling only.

Once the delivery of a dose is stopped, by the number sleeve <NUM> returning to the zero dose abutment, the user may release the button <NUM>, which will re-engage the spline teeth between the drive sleeve <NUM> and housing <NUM>. The mechanism is now returned to the 'at rest' condition.

At the end of dose dispensing, additional audible feedback is provided in the form of a 'click', distinct from the 'clicks' provided during dispense, to inform the user that the device has returned to its zero position via the interaction of the clicker arm on the number sleeve <NUM> with the ramp on the drive sleeve <NUM> and the cam and the recess on the gauge element <NUM>. This embodiment allows feedback to only be created at the end of dose delivery and not created if the device is dialled back to, or away from, the zero position.

The attachment of cartridge holder <NUM> to outer housing <NUM> is now described in more detail with reference to <FIG>, <FIG> and <FIG>. <FIG> is illustrated with a simplified representation of the full device. The button <NUM>, dose selector <NUM>, clutch plate <NUM>, last dose nut <NUM>, gauge <NUM>, drive spring <NUM>, piston rod <NUM>, bearing <NUM>, cartridge <NUM> and clutch spring <NUM> are not shown.

In the embodiment shown in <FIG>, the outer housing <NUM> consists of two parts: a twin-shot moulding where the first shot is a translucent material, and the second shot is an opaque material; and the housing insert <NUM> which is a separate part that becomes rigidly fixed to the outer housing <NUM> during assembly. As an alternative, the housing insert may be combined with the moulding of outer housing <NUM>, or the translucent and opaque sections of the outer housing <NUM> may be separate components. After assembly of the housing insert <NUM>, the number sleeve <NUM> is inserted into the outer housing <NUM> from the proximal end. Its distal end contacts the bead <NUM>, which is a clip feature in the outer housing <NUM> which forces the distal end of the number sleeve <NUM> to deflect radially inwards, allowing the bead <NUM> in the outer housing <NUM> to engage with the recess <NUM> near the distal end of the number sleeve.

This clip feature <NUM>, <NUM> is sufficient to retain the number sleeve <NUM> during subsequent assembly operations, but the flexibility of the number sleeve <NUM> may allow it to disengage, e.g. during impact. The proximally extending protrusion <NUM> on the cartridge holder <NUM> is used to improve the retention strength (<FIG>). This protrusion overlaps axially with the end of the number sleeve <NUM>. If the number sleeve <NUM> deflects radially inwards, it contacts the protrusion <NUM> on the cartridge holder <NUM>, which in turn contacts the housing insert <NUM> in the outer housing <NUM>. This limits the allowable deflection, helping to prevent disengagement from the clip in the outer housing <NUM>, and this significantly increases the retention strength of the number sleeve <NUM> within the outer housing <NUM>.

In an alternative embodiment shown in <FIG>, the retention strength is increased by extending the number sleeve <NUM> in the distal direction, rather than extending the cartridge holder <NUM>. In the embodiment of <FIG>, the number sleeve <NUM> comprises a rim <NUM> located distally from recess <NUM>. This provides increased surface area of the number sleeve <NUM> that may be used for printing.

It is apparent that the feature of increasing retention strength as described above is not limited to devices with a design and function as shown in <FIG> nor to increase retention strength for a number sleeve. Rather, the cartridge holder <NUM> may be used to lock any component part, e.g. to the outer housing <NUM>, by engaging a clip attachment from the inside (or even from the outside). In other words, the number sleeve retention features may be included in any pen injector, reducing the likelihood of damage during use and impact.

Claim 1:
Housing for a drug delivery device, the housing comprising an outer housing (<NUM>) with a distal end and a cartridge holder (<NUM>) with a proximal end, which, when the cartridge holder (<NUM>) is attached to the outer housing (<NUM>), is inserted into the distal end of the outer housing (<NUM>), characterized in that, the outer housing (<NUM>) is provided with a first fixture (<NUM>) for axially constraining a further component part (<NUM>) of the drug delivery device to the outer housing (<NUM>) by snap engagement which is designed such that relative rotation between the further component part (<NUM>) and the outer housing (<NUM>) is allowed, while relative axial movement is prevented, wherein, when the cartridge holder (<NUM>) is attached to the outer housing (<NUM>), the proximal end of the cartridge holder (<NUM>) overlaps with the further component part (<NUM>) such that the further component part (<NUM>) is radially interposed between the cartridge holder (<NUM>) and the outer housing (<NUM>).