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.

These types of pen delivery devices (so named because they often resemble an enlarged fountain pen) are generally comprised of 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 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.

Disposable and reusable drug delivery devices have certain perceived disadvantages. One perceived disadvantage is that such devices have a high number of parts and therefore such devices are typically complicated from a manufacturing and from an assembly standpoint. In addition, because such devices use a large number of components parts, such devices tend to be large and bulky, and therefore not easy to carry around or easy to conceal.

A disposable drug delivery device according to the present invention typically comprises a housing, a cartridge holder for retaining a cartridge containing a medicament, a piston rod displaceable relative to the cartridge holder, a driver coupled to the piston rod, a display member for indicating a set dose and being coupled to the housing and to the driver, and a button coupled to the display member and to the driver. The device is delivered to the user in a fully assembled condition ready for use. Such a disposable drug delivery device is known e.g. from <CIT>.

<CIT> and <CIT> each refer to resettable drug delivery devices which are reusable by exchanging an empty cartridge by a new one.

<CIT> and <CIT> each refer to drug delivery devices which may be disposable. Although the number of the component parts of these devices is comparatively low, there is still room for a further reduction of the number of component parts and for making the device less complex to assemble and manufacture.

It is an object of the present invention to provide an improved drug delivery device which has a reduced number of component parts and reduced manufacturing costs while also making the device less complex to assemble and manufacture. It is a further object to simplify the steps required for a user to set and dispense a dose while also making the device less complex and more compact in size.

This object is solved by a disposable, non-resettable drug delivery device according to claim <NUM> for selecting and dispensing a number of user variable doses of a medicament, comprising a housing, a cartridge holder for retaining a cartridge containing the medicament, a piston rod displaceable relative to the cartridge holder, a driver coupled to the piston rod, a display member for indicating a set dose and being coupled to the housing and to the driver, and a button coupled to the display member and to the driver, wherein the driver is in threaded engagement with the piston rod, permanently rotationally locked to the button and axially displaceable relative to the button in a proximal direction against the force of a resilient member which is a one piece component with either the driver or the button (or the button is displaceable relative to the driver in a distal direction). In other words, a spring or the like resilient member for biasing the button in a first direction which is usually provided as a separate component in known devices is integrated in the button or driver to thus reduce the number of component parts and assembling complexity.

Preferably, the driver comprises at least one elastically deformable finger having a free end engaging the button to bias the button in the proximal direction.

According to a second aspect of the present invention, the housing comprises an inner surface with splines and the driver comprises at least one protrusion which in a first axial position of the button relative to the driver is allowed to elastically move in a radial direction and which in a second axial position of the button relative to the driver is forced by the button in a radially outer position thus rotationally locking the driver to the housing. In known devices a clutch member rotationally coupling the driver and the housing or a clicker member for producing a tactile and/or audible feedback during use of the device is usually provided with at least one separate component. In the present embodiment of the invention, these functions of the device are realized without adding component parts.

Preferably, the driver comprises at least one protrusion interacting with splines of the housing wherein the protrusion is elastically movable in a radial direction, and wherein the button comprises a recess or opening suitable for at least partly receiving the protrusion of the driver. If the button is moved relative to the driver, the protrusion cannot engage the recess or opening such that the radially inward movement of the protrusion is prevented, thus locking the protrusion in its radial position.

According to a third aspect of the present invention, a first clicker, which is active during dose setting, is formed by the driver and the housing and a second clicker, which is active during dose dispensing, is formed by the button and the display member. In other words, a clicker for producing a tactile and/or audible feedback during use of the device is provided without adding separate components to the device.

According to a fourth aspect of the present invention, the number of components of the drug delivery device including the cartridge and a cap for shielding the cartridge holder is ten or less. In this respect, the cartridge including its movable rubber type bung, its pierceable rubber seal and e.g. its crimped annular metal band is considered as one component. Known disposable drug delivery devices usually comprise twelve or more parts, often nearly twenty separate component parts. Taking into account that disposable drug delivery devices are mass-produced, such a significant reduction of component parts results in reduced manufacturing costs.

In the drug delivery device of the present invention the housing may comprise an outer body and an inner body with the outer body being a one-piece component with the cartridge holder. Combining the cartridge holder and the outer body part of the housing into one single component reduces the number of component parts and thus assembling complexity. Further, the risk of a misuse, where a user attempts to exchange an empty cartridge in a disposable drug delivery device, is reduced.

In the drug delivery device of the present invention a first rotationally acting clutch may be formed by the button and the display member which is in its coupled state during dose setting and in its decoupled state during dose dispensing, and a second rotationally acting clutch may be formed by the driver and the housing which is in its decoupled state during dose setting and in its coupled state during dose dispensing. In known devices clutches usually require additional components either being interposed between the components to be coupled or decoupled or being used for actuation of the clutch. In contrast to that, with the present invention two clutches are provided without additional component parts.

Preferably, the button comprises a set of clutch teeth and the display member comprises a further set of corresponding clutch teeth, wherein axial movement of the button relative to the display member engages or disengages the sets of clutch teeth. The second clutch may be formed by the above mentioned at least one protrusion of the driver interacting with splines of the housing.

The housing may comprise a transparent or translucent outer body, wherein at least a part of the outer body is coated by an opaque layer. This is especially preferred if the outer body is a one-piece component with usually the transparent or translucent cartridge holder. A further benefit of the outer body being transparent or translucent is that additional window inserts may be omitted. The opaque, i.e. not-transparent and not-translucent, layer may cover the part of the outer body containing the mechanical dosing components. Especially, the display member, which is typically provided with numbers or the like for displaying the set dose, may be at least partly shielded by the opaque layer such that only the number corresponding to the actually set dose is visible. The opaque layer may be an inner or outer coloured layer, a label or tag attached to the outer body, a lining attached or otherwise fixed to the outer body or a frosted or scarified surface.

Preferably, the piston rod is a double threaded piston rod having a first outer thread engaging an internal thread of the housing and a second outer thread engaging an internal thread of the driver, wherein the first and second outer threads may overlap each other at least partially. This allows to provide a mechanical advantage, i.e. a transmission (gear) ratio, in the device. Typically, the dial extension of the button, i.e. the distance the button winds out of the housing during dose setting, will be larger than the distance the piston rod is displaced relative to the cartridge holder and thus the cartridge. This allows dispensing even small amounts of a medicament with a maximum of dispensing control by the user.

A further reduction of the number of component parts may be achieved if the piston rod comprises a bearing attached to the piston rod by at least one predefined breakage point. The bearing is axially constrained but rotatable with respect to the piston rod after detachment of the bearing by destroying the at least one predefined breakage point during or after assembly. Thus, only one single component has to be handled during assembly which in use fulfils the function of two separate components.

According to a preferred embodiment, the driver is a tubular element having a distal portion engaging a nut interposed between the housing and the driver, and a proximal portion which at least partly surrounds a tubular portion of the button. Preferably, one of the housing and the driver comprises at least one spline and the other of the housing and the driver comprises a threaded portion with the nut interposed between the housing and the driver, wherein the nut comprises at least one protrusion engaging the at least one spline and a thread engaging the threaded portion, and wherein the threaded portion of the housing or the driver comprises a rotational end stop. If the nut abuts the rotational end stop, further movement of the nut in the thread is prevented which thus prevents further rotation of the driver relative to the housing which is required during dose setting. Thus, the nut may be used to limit the settable dose. This is e.g. required to prevent setting a dose exceeding the amount of medicament in the cartridge.

Preferably, one of the driver and the display member comprises a circular groove or a circular track defined by two walls and the other of the driver and the display member comprises a circular bulge engaging the groove or track. This allows to constrain the driver and the display member in the axial direction but to allow relative rotation.

If the housing comprises an outer body and an inner body, the inner body may be rotationally and axially constrained within the outer body such that a cylindrical gap exists between the inner body and the outer body. Preferably, the inner body comprises an outer thread engaging an inner thread of the display member and comprises at least one inner spline engaging a protrusion of the driver.

In a standard embodiment, the splines of the inner body are axially aligned with the pen device. In an alternative embodiment, it is possible to reduce dispense force, increase the velocity ratio and to increase the thread pitch of the display member (i.e. increase of friction coefficient asymptote), by providing the inner body with at least one inner spline which is helically twisted. In other words, the splines are not axially aligned, which results in the driver and the button traveling helically during dose dispensing. This may require adding an over-cap for the button as an additional component preventing relative rotation with respect to a user's hand, typically the thumb, during dose dispensing.

The basic function of the drug delivery device according to the present invention may include that a dose is selected by rotating a button component, which travels helically during dose setting. A dose may be delivered by pressing on the same button component, which now moves axially during dispensing. Preferably, any dose size can be selected, in predefined increments, between zero and a predefined maximum dose, e.g. <NUM> units. It is a further advantage if the mechanism permits cancelling of a dose without medicament being dispensed, e.g. by rotation of the button component in the opposite direction to when selecting a dose.

It is preferred if during dose setting the button is rotated which entrains the driver and the display member such that the button, the driver and the display member are moved on a helical path with respect to the housing and the piston rod. Further, during dose dispensing the button is axially displaced which entrains the driver and the display member such that the button, the driver and the display member are axially moved with respect to the housing and the piston rod, with the display member and the piston rod rotating with respect to the housing, the button and the driver.

To prevent malfunction or misuse of the device, the dose setting mechanism may be provided with stops preventing dialling of a dose below zero units or dialling of a dose above a maximum dose. Preferably, rotational hard stops are provided, e.g. between the display member and the inner body as a zero unit stop and/or as a maximum units stop.

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,.

Insulin derivates are for example B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyhepta-decanoyl) human insulin.

or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exendin-<NUM> derivative.

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.

Heavy and light chains each contain intra-chain disulfide bonds which stabilize their folding.

Exemplary embodiments of the invention will now be described with reference to the accompanying drawings, in which:.

<FIG> shows a drug delivery device <NUM> in the form of an injection pen. The device has a distal end (upper end in <FIG>) and a proximal end (lower end in <FIG>). The component parts of the drug delivery device <NUM> are shown in <FIG> in more detail. The drug delivery device <NUM> comprises an outer housing part <NUM>, an inner body <NUM>, a piston rod <NUM>, a driver <NUM>, a nut <NUM>, a display member <NUM>, a button <NUM>, a cartridge <NUM> and a cap <NUM>, i.e. in total nine separate component parts. As shown in <FIG>, a needle arrangement comprising a needle hub <NUM> and a needle cover <NUM> may be provided as additional components, which can be exchanged as explained above.

The outer housing part <NUM> is a generally tubular element having a distal part, which forms a cartridge holder <NUM> for receiving cartridge <NUM>, and a proximal part, which forms an outer body <NUM>. In a preferred embodiment, the outer housing part <NUM> is transparent, with the outer body <NUM> being provided with an opaque layer <NUM>. In <FIG>, the opaque layer <NUM> covers most of the outer body <NUM> with the exception of a transparent window <NUM>. Apertures <NUM> may be provided in the cartridge holder <NUM>. Further, at its distal end the cartridge holder <NUM> has a thread <NUM> or the like for attaching the needle hub <NUM>.

The inner body <NUM> is a generally tubular element having different diameter regions. As can be seen in <FIG>, the inner body <NUM> is received in the outer body <NUM> and permanently fixed therein to prevent any relative movement of the inner body <NUM> with respect to the outer body <NUM>. An external thread <NUM> is provided on the outer surface of the inner body <NUM>. Further, splines <NUM> are provided on the inner surface of the inner body <NUM> which are shown in <FIG> and <FIG>. As can be taken from <FIG>, the inner body <NUM> has near its distal end an inner thread <NUM>.

The piston rod <NUM> is an elongate element having two external threads <NUM>, <NUM> with opposite hand which overlap each other. One of these threads <NUM> engages the inner thread <NUM> of the inner body <NUM>. A disk-like bearing <NUM> is provided at the distal end of the piston rod <NUM>. As shown in <FIG>, the bearing <NUM> may be attached to the piston rod <NUM> as a one-piece component via a predetermined breaking point. This allows that the bearing <NUM> is separated from the piston rod <NUM> such that the bearing <NUM> remains seated on the distal end of the piston rod <NUM> to allow relative rotation between the bearing <NUM> and the piston rod <NUM>.

The driver <NUM> is a generally tubular element having different diameter regions. A distal region of the driver <NUM> has an external thread <NUM>. An inner surface of the driver <NUM> has an inner thread <NUM> (<FIG>) engaging one of the external threads <NUM> of the piston rod <NUM>. The driver <NUM> surrounds the piston rod <NUM> and is at least partly located within inner body <NUM>. The driver has at least one proximal opening <NUM> which will be explained in more detail below. Further, a resilient finger <NUM> (<FIG>) is provided on the driver <NUM> by a U-shaped cut in the skirt of the driver <NUM>. The finger <NUM> is allowed to flex in the axial direction and engages button <NUM>. In addition, a flexibly hinged protrusion <NUM> (<FIG> and <FIG>) is provided on the driver <NUM> by a similar cut out in the skirt of the driver <NUM>. The protrusion <NUM> is allowed to flex radially inwardly and is provided with lateral flaps <NUM>. Protrusion <NUM> engages splines <NUM> of the inner body <NUM>.

The nut <NUM> is provided between the inner body <NUM> and the driver <NUM>. External ribs <NUM> of the nut <NUM> engage splines <NUM> of the nut <NUM>. An internal thread <NUM> of the nut engages the external thread <NUM> of the driver <NUM>. As an alternative, splines and ribs could be provided on the interface between the nut <NUM> and the driver <NUM> and threads could be provided on the interface between the nut <NUM> and the inner body <NUM>. As a further alternative, the nut <NUM> may be designed as e.g. a half nut. Further, in the embodiment of <FIG>, four rotational hard stops <NUM> are provided on nut <NUM> for interaction with corresponding stops <NUM> on the driver <NUM> at the proximal end of thread <NUM>.

The display member <NUM> is a generally tubular element with an internal thread <NUM> engaging the external thread <NUM> of the inner body <NUM>. Thus, the display member <NUM> is interposed between the inner body <NUM> and the outer body <NUM>. A series of numbers is provided, e.g. printed, on the outer surface of the display member <NUM>. The numbers are arranged on a helical line such that only one number or only a few numbers are visible in through window <NUM> of the outer body <NUM>. As will be explained in more detail below, the display member <NUM> is attached to the driver <NUM> preventing relative axial movement but allowing relative rotation.

<FIG> show in more detail a zero unit rotational hard stop formed by a stop wall <NUM> in thread <NUM> of the display member <NUM> and a corresponding stop face <NUM> on the inner body <NUM>. <FIG> show in more detail a maximum dose (e.g. a <NUM> units) rotational hard stop formed by a finger <NUM> at the distal end of the display member <NUM> and a protrusion <NUM> in thread <NUM> of the inner body <NUM>. Thus, a user is prevented from dialing below zero units and above e.g. <NUM> units.

The button <NUM> has a proximal end with an, e.g. serrated, flange or outer skirt <NUM> allowing a user to easily grip and dial button <NUM>. A sleeve-like part <NUM> of the button <NUM> with a reduced diameter extends in the distal direction and is inserted into the driver <NUM> such that a limited relative axial movement is allowed but relative rotation is prevented. This is achieved by a rib <NUM> on the sleeve-like part <NUM> which is guided in a proximal opening <NUM> of the driver <NUM>. A recess <NUM> which generally has the outline of the protrusion <NUM> and its lateral flaps <NUM> is provided in the sleeve-like part <NUM> of button <NUM>.

A clutch is provided between the display member <NUM> and the button <NUM> by corresponding teeth <NUM> and <NUM> (<FIG>). If teeth <NUM> of the button <NUM> engage teeth <NUM> of the display member <NUM>, these components are rotationally locked. The resilient finger <NUM> of the driver <NUM> biases the button <NUM> in the proximal direction of the device <NUM>, i.e. in a direction engaging the clutch teeth. The clutch can be released allowing relative rotation by shifting the button <NUM> axially with respect to the display member <NUM> against the bias of finger <NUM>.

Further, a dispense clicker is provided by flexible arms <NUM> on the display member <NUM> and a toothed profile <NUM> on the inner side of flange <NUM> of button <NUM>. This clicker is shown in <FIG>.

The cartridge <NUM> includes a pre-filled, necked-down cartridge reservoir <NUM>, which may be typically made of glass. A rubber type bung <NUM> or stopper is located at the proximal end of the cartridge reservoir <NUM>, and a pierceable rubber seal (not shown) is located at the other, distal, end. A crimped annular metal band <NUM> is used to hold the rubber seal in place. The cartridge <NUM> is provided within the cartridge holder <NUM> with bearing <NUM> of piston rod <NUM> abutting bund <NUM>.

<FIG> shows the cap <NUM> attached to the distal end of the device <NUM>, thus covering the cartridge holder <NUM>. The cap <NUM> may be releasable snapped onto the outer housing <NUM> and can be taken off for use of the device <NUM>.

In the following, the function of the disposable drug delivery device <NUM> and its components will be explained in more detail.

To use the device, a user has to select a dose. In the start (at rest) condition as shown in <FIG> and <FIG> the display member <NUM> indicates the number of doses dialed to the user. The number of dialed units can be viewed through the dose window <NUM> in the outer body <NUM>. Due to the threaded engagement between the display member <NUM> and the inner body <NUM> rotation of the button <NUM> in a clockwise fashion causes the display member <NUM> to wind out of the device and incrementally count the number of units to be delivered. <FIG> shows an intermediate stage of dialing (<NUM> of <NUM> units).

During dose setting button <NUM>, driver <NUM> and display member <NUM> are rotationally locked together via clutch teeth <NUM>, <NUM>. Further, button <NUM>, driver <NUM> and display member <NUM> are axially coupled. Thus, these three components wind out of the outer housing <NUM> during dose setting.

Clockwise rotation of the button <NUM> causes the driver <NUM> to rotate and in doing so it advances along the piston rod <NUM> which remains fixed throughout dialing.

The protrusion <NUM> and splines <NUM> form a clicker arrangement that provides tactile and audible feedback to the user when dialing doses. This clicker arrangement has the further functions of defining discrete positions for the display member <NUM> when dialing and of providing a method of locking the rotation of the driver <NUM> and hence button <NUM> when dosing. During dialing (dose setting) the button <NUM> is in an axial position relative to the driver <NUM> such that the pocket or recess <NUM> is located radially inwards of the protrusion. Thus, the protrusion <NUM> is allowed to flex radially inwards to overcome splines <NUM> thereby providing a tactile and audible feedback to the user. <FIG> shows the flexible protrusion arm <NUM> located between splines <NUM> which are e.g. <NUM>° apart.

At the maximum settable dose of <NUM> units, the stop features <NUM>, <NUM> shown in <FIG> engage to prevent further dialing. This position of the device is shown in <FIG> and <FIG>.

The last dose nut <NUM> provides the function of counting the number of dispensed units. The nut <NUM> locks the device <NUM> at the end of life and as such no more drug can be dialed or dispensed by the user. The last dose nut <NUM> and the driver <NUM> are connected via a threaded interface <NUM>, <NUM> as explained above. Further, the last dose nut <NUM> is assembled into splines <NUM> as shown in <FIG> such that the nut <NUM> and the inner body <NUM> are rotationally locked together (at all times). Rotation of the driver <NUM> during dialing causes the nut <NUM> to advance along the driver <NUM> thread <NUM>. The nut <NUM> is free to slide axially within the inner body <NUM> at all times which allows advancement of the nut. The change in pitch shown in <FIG> towards the final doses axially accelerates the advancement of the nut <NUM> towards the end of life lockout condition. At the end of life condition, the stop features <NUM> of the last dose nut <NUM> contact the corresponding features <NUM> on the driver <NUM>. The splined contact with inner body <NUM> reacts any torque transmitted by these stop features <NUM>.

With the desired dose dialed, the device <NUM> is ready for dose dispensing. This basically requires pushing button <NUM> which will result in a disengagement of the clutch teeth <NUM>, <NUM>. As mentioned above, when dialing a dose the button <NUM> is 'biased out' and the clutch features <NUM>, <NUM> which rotationally lock the driver <NUM>, button <NUM> and display member <NUM> together are engaged as shown in <FIG>. Upon pressing the button <NUM> the clutch features <NUM>, <NUM> disengage as shown in <FIG> and relative rotation between the display member <NUM> and the button <NUM> is possible. In all conditions the driver <NUM> and the button <NUM> are rotationally locked together by engagement rib <NUM> and opening <NUM>. Thus, with the clutch <NUM>, <NUM> disengaged (button <NUM> pushed in) button <NUM> and driver <NUM> are rotationally locked together with the button <NUM>, the driver <NUM> and the display member <NUM> still being axially coupled.

At the same time the relative axial movement of the button <NUM> with respect to the driver <NUM> results in the pocket or recess <NUM> being shifted relative to the protrusion <NUM>. Thus, the protrusion <NUM> is prevented from flexing inwards because flaps <NUM> rest on a non-recessed area of button <NUM>. A comparison of <FIG> shows this activation of the lockout feature preventing the flexible protrusion arm <NUM> from overcoming splines <NUM> if the button <NUM> is pressed. In this condition, the driver <NUM> and the button <NUM> are rotationally constrained to the inner body <NUM> thus preventing any rotation relative to the outer housing <NUM> if the splines <NUM> are axially aligned with the device as shown in <FIG>. The above mentioned alternative embodiment with twisted splines <NUM> is shown in <FIG>.

With the desired dose dialed the button <NUM> can be depressed and the piston rod <NUM> driven forward to dispense drug from the cartridge. The interaction of mating threads between the piston rod <NUM>, driver <NUM> and inner body <NUM> delivers a mechanical advantage of <NUM>:<NUM>. The sequence of dispensing is depicted in <FIG> with <FIG> showing the device <NUM> with <NUM> units dialed prior to pushing button <NUM>, <FIG> shows the device <NUM> with <NUM> units dialed and button <NUM> pushed and <FIG> shows the device <NUM> with <NUM> units dispensed.

Claim 1:
A disposable, non-resettable drug delivery device for selecting and dispensing a number of user variable doses of a medicament, comprising a housing (<NUM>, <NUM>), a cartridge holder (<NUM>) for retaining a cartridge (<NUM>) containing the medicament, a piston rod (<NUM>) displaceable relative to the cartridge holder (<NUM>), a driver (<NUM>) coupled to the piston rod (<NUM>), a display member (<NUM>) for indicating a set dose and being coupled to the housing (<NUM>, <NUM>) and to the driver (<NUM>), and a button (<NUM>) coupled to the display member (<NUM>) and to the driver (<NUM>), characterized in that the driver (<NUM>) is in threaded engagement with the piston rod (<NUM>), permanently rotationally locked to the button (<NUM>) and axially displaceable relative to the button (<NUM>) in a proximal direction against the force of a resilient member (<NUM>) which is a one piece component with either the driver (<NUM>) or the button (<NUM>).