Abstract:
The present invention relates to a drive mechanism of a drug delivery device for dispensing of dose of a medicament, the mechanism comprising: —an elongated housing ( 30 ) extending in an axial direction ( 1, 2 ), —a piston rod ( 80 ) to operably engage with a piston ( 16 ) of a cartridge ( 14 ) to displace the piston ( 16 ) in a distal axial direction ( 1 ), —a drive sleeve ( 50 ) extending in axial direction ( 1, 2 ) and being rotatable against the action of a spring ( 68 ) during a dose setting procedure, —a dispensing sleeve ( 70 ) rotatably engaged with the piston rod ( 80 ) and being displaceable in axial direction ( 1, 2 ) relative to the drive sleeve ( 50 ) to engage with the drive sleeve ( 50 ) in a torque transmissive way during a dose dispensing procedure.

Description:
[0001]    The present invention relates to a drive mechanism for a drug delivery device and to a respective drug delivery device. In particular, the invention relates to an injection device such like a pen-type injector inter alia comprising a single and/or a last-dose limiting mechanism and further comprising a comparatively large dose indicating display. 
       BACKGROUND AND PRIOR ART 
       [0002]    Drug delivery devices for setting and dispensing a single or multiple doses of a liquid medicament are as such well-known in the art. Generally, such devices have substantially a similar purpose as that of an ordinary syringe. 
         [0003]    Drug delivery devices, in particular pen-type injectors have to meet a number of user-specific requirements. For instance, with patient&#39;s suffering chronic diseases, such like diabetes, the patient may be physically infirm and may also have impaired vision. Suitable drug delivery devices especially intended for home medication therefore need to be robust in construction and should be easy to use. Furthermore, manipulation and general handling of the device and its components should be intelligible and easy understandable. Moreover, a dose setting as well as a dose dispensing procedure must be easy to operate and has to be unambiguous. 
         [0004]    Typically, such devices comprise a housing or a particular cartridge holder, adapted to receive a cartridge at least partially filled with the medicament to be dispensed. The device further comprises a drive mechanism, usually having a displaceable piston rod which is adapted to operably engage with a piston of the cartridge. By means of the drive mechanism and its piston rod, the piston of the cartridge is displaceable in a distal or dispensing direction and may therefore expel a predefined amount of the medicament via a piercing assembly, which is to be releasably coupled with a distal end section of the housing of the drug delivery device. 
         [0005]    The medicament to be dispensed by the drug delivery device is provided and contained in a multi-dose cartridge. Such cartridges typically comprise a vitreous barrel sealed in distal direction by means of a pierceable seal and being further sealed in proximal direction by the piston. With reusable drug delivery devices an empty cartridge is replaceable by a new one. In contrast to that, drug delivery devices of disposable type are to be entirely discarded when the medicament in the cartridge has been completely dispensed or used-up. 
         [0006]    With such multi-dose drug delivery devices at least a last dose limiting mechanism is required to inhibit setting of a dose exceeding the amount of medicament left in the cartridge. This is to avoid a potentially dangerous situation for the user believing that a set dose is entirely injected. There already exist some drug delivery devices with end-of-content mechanisms or last dose mechanisms. 
         [0007]    Drug delivery devices such like pen type injectors also provide a dose indicating mechanism which is operable to display the size of a set dose to a user. Typically, the housing of such drug delivery devices comprises a dose indicating window where a number representing the size of the dose shows up. 
         [0008]    Especially with elderly or visually impaired patients, reading of such dose indicating numbers if sometimes difficult. With devices adapted for injection of e.g. insulin, typical dose sizes may vary between 0 and 120 I.U. (International Units) of insulin. Due to the rather compact design and limited geometrical dimensions of such drug delivery devices the size of such dose indicating numbers is fairly small. For visually impaired persons reading of such tiny numbers may therefore be rather difficult. However, since such drug delivery devices are intended for self-medication treatment, it is of importance, that the user is able to correctly determine the size of dose actually set. 
       OBJECTS OF THE INVENTION 
       [0009]    It is therefore an object of the present invention to avoid disadvantages of known drug delivery devices and to provide a drive mechanism of a drug delivery device allowing for an intuitive operation, both for setting and for dispensing of a dose. It is another object to provide a dose indicating mechanism which is easy and unequivocal to read even for persons suffering impaired vision. 
         [0010]    In another object, the invention serves to provide a drive mechanism of a drug delivery device for setting and dispensing of a dose of a medicament and further featuring a single dose limited mechanism and a last dose limiting mechanism. 
         [0011]    It is a further aim to provide a drug delivery device comprising such a drive mechanism and comprising a cartridge sealed with a piston and being operably engaged with a piston rod of such drive mechanism. 
       SUMMARY OF THE INVENTION 
       [0012]    In a first aspect a drive mechanism of a drug delivery device is provided for dispensing of a dose of a medicament. The drive mechanism comprises an elongated housing extending in an axial direction. Typically, the housing is of substantially tubular or cylindrical shape that allows gripping and operating of the drive mechanism and of the drug delivery device by only one hand of a user. 
         [0013]    The drive mechanism further comprises a piston rod to operably engage with a piston of a cartridge containing the medicament to be dispensed by the drive mechanism. The cartridge comprises a piston, typically at its proximal end, which, by means of a displacement in axial distal direction serves to expel an amount of the medicament from the cartridge. The piston typically seals the cartridge in axial proximal direction. 
         [0014]    The piston rod of the drive mechanism serves to displace the piston of the cartridge in axial distal direction for expelling a predefined amount of the medicament from the cartridge. Hence, the piston rod is operable to apply distally-directed thrust or pressure to the piston of the cartridge for displacing the same in distal direction for a predetermined distance that corresponds to a respective amount or dose of the medicament to be dispensed. 
         [0015]    The drive mechanism comprises a drive sleeve extending in axial direction and being rotatably supported in the housing. The drive sleeve is rotatable with regard to an axis of rotation substantially coinciding with the axial direction of the elongated housing. For setting of a dose, hence during a dose setting procedure, the drive sleeve is rotatable against the action of a spring. By rotating the drive sleeve in a dose setting direction, said spring, being engaged with the drive sleeve, is biased in order to store mechanical energy. 
         [0016]    During a subsequent dose dispensing procedure, when the drive sleeve is released, it may then rotate in an opposite direction under the action of said spring for driving the piston rod in distal direction. Typically, the drive sleeve is operably disengaged or releasable from the piston rod for setting of a dose. During a dose setting procedure, the piston rod remains substantially stationary with respect to the housing while the drive sleeve, operably disconnected and released from the piston rod is rotatable relative to the housing and hence relative to the piston rod. 
         [0017]    The drive mechanism further comprises a dispensing sleeve rotatably engaged with the piston rod and being displaceable in axial direction relative to the drive sleeve to engage with the drive sleeve in a torque transmissive way during a dose dispensing procedure. Here, the dispensing sleeve provides a double function. By way of an axial displacement relative to the drive sleeve, the dispensing sleeve can be selectively rotatably coupled with the drive sleeve, thereby switching the drive mechanism between a dose setting mode, in which dispensing sleeve and drive sleeve are disconnected and a dose dispensing mode, in which dispensing sleeve and drive sleeve are rotatably engaged. 
         [0018]    Moreover, the dispensing sleeve serves as a torque transmission component to transfer a rotative motion of the drive sleeve to the piston rod during a dose dispensing procedure for driving the piston rod in distal direction. 
         [0019]    The mutual engagement of drive sleeve, piston rod and dispensing sleeve allows for a rather compact and robust design of the drive mechanism. Due to the switching function and the torque transmission function of the dispensing sleeve, the overall number of parts the drive mechanism is assembled of can be reduced. This way, mechanical tolerances of the mutually interacting components of the drive mechanism can be reduced. 
         [0020]    In a further embodiment, the drive sleeve is axially displaceable between a dose setting position and a dose dispensing position against the action of at least one drive sleeve spring element. Typically, the drive sleeve is displaceable in distal direction relative to the housing against the action of the at least one drive sleeve spring element. Typically, the dose dispensing position correlates and corresponds to a distal stop position of the drive sleeve whereas a dose setting position corresponds to a proximal stop position of the drive sleeve. 
         [0021]    The drive sleeve is rotatable in a dose setting direction against the action of a helical spring when located in the dose setting position. By displacing the drive sleeve into the dose dispensing position, the drive sleeve may be allowed to rotate in the opposite, hence in a dose dispensing direction under the action of said helical spring. Typically, axially distally-directed displacement of the drive sleeve requires constant exertion of a respective distally-directed thrust or force acting on the drive sleeve to keep the same in the distal dose dispensing position. A decrease of said thrust or distally-directed dispensing force below a predetermined threshold typically leads to a returning of the drive sleeve into the dose setting position under the action of the at least one drive sleeve spring element. Hence, a premature release of e.g. an injection button, by way of which the drive sleeve is displaceable in axial distal direction, may immediately return the drive sleeve into its dose setting position. This way, premature release of an injection button and hence of a drive sleeve axially coupled therewith may instantly interrupt a dose dispensing procedure. 
         [0022]    In a further embodiment, the dispensing sleeve is displaceable in axial distal direction to axially engage with the drive sleeve in an intermediate position. Typically, the drive sleeve and the dispensing sleeve comprise mutually engaging and radially extending portions, such like stop faces by way of which a distally-directed displacement of the dispensing sleeve may correspondingly transfer to a respective distally-directed displacement of the drive sleeve. 
         [0023]    In the intermediate position, dispensing sleeve and drive sleeve may mutually abut or mutually engage in axial direction. A further displacement of the dispensing sleeve into a distal stop position of the dispensing sleeve may then transfer and/or slave the drive sleeve from the dose setting position into the dose dispensing position. Here, the dispensing sleeve serves as a dispensing clutch by way of which the drive sleeve can be pushed from its dose setting position into the dose dispensing position against the action of the drive sleeve spring element. 
         [0024]    Typically, mutual engagement and axial displacement of dispensing sleeve and drive sleeve is characterised by two subsequent steps of displacement. In a first step, the dispensing sleeve is displaceable in axial direction until it reaches the intermediate position, in which it axially and/or rotatably engages with the drive sleeve. During this first step and during such an initial movement of the dispensing sleeve, the drive sleeve remains substantially stationary. Due to the mutual axial and/or rotational engagement of drive sleeve and dispensing sleeve the drive sleeve can be slaved to the dispensing sleeve during the subsequent second displacement step, during in which the dispensing sleeve is further displaceable into a distal stop position. 
         [0025]    During this second step of axial displacement, the dispensing sleeve is operable to push the drive sleeve in distal direction to reach its dose dispensing position. During this distally-directed displacement of the drive sleeve the drive sleeve is operably engaged, typically rotatably locked to the dispensing sleeve. 
         [0026]    In typical embodiments, the drive sleeve is rotatable in the dose setting direction relative to the housing in a step-wise incrementing way against the action of a helical spring. This rotative displacement is typically controlled by a ratchet mechanism, which serves to keep the drive sleeve in a rotated position and to hinder that the drive sleeve immediately returns into an initial configuration, which may resemble a zero dose configuration. It is due to the axial displacement of the drive sleeve from its dose setting position into its dose dispensing position that the drive sleeve is released and disengaged from the ratchet mechanism. 
         [0027]    Hence, when displaced in axial distal direction to the dose dispensing position the drive sleeve is free to rotate under the action of the previously biased helical spring. 
         [0028]    Since the drive sleeve is already rotatably engaged with the dispensing sleeve before it reaches the distal dose dispensing position, the rotation of the drive sleeve relative to the housing equally transfers to a respective rotation of the dispensing sleeve. Since the dispensing sleeve is permanently rotatably engaged with the piston rod, also the piston rod will rotate during a dose setting procedure and may therefore be advance in distal direction for driving the piston of the cartridge accordingly. 
         [0029]    In a further embodiment, the dispensing sleeve is axially displaceable relative to the drive sleeve against the action of at least one dispensing sleeve spring element. Under the action of said dispensing sleeve spring element, the dispensing sleeve can return into an initial axial position, in which dispensing sleeve and drive sleeve are operably disconnected. Typically, the drive sleeve is displaceable from the dose setting position to the dose dispensing position against the action of a drive sleeve spring element, which may extend between the drive sleeve and the housing. 
         [0030]    A further spring element, e.g. a dispensing sleeve spring element may be additionally provided between the drive sleeve and the dispensing sleeve. The spring constants of said drive sleeve spring element and the dispensing sleeve spring element substantially differ so that an almost full compression of the dispensing sleeve spring element may already be attained before the drive sleeve spring element is biased. By appropriately selecting the spring constants of the drive sleeve spring element and the dispensing sleeve spring element a mutual and torque transmitting engagement of drive sleeve and dispensing sleeve can be attained even before the drive sleeve reaches its distal dose dispensing position. 
         [0031]    According to another embodiment the inside wall of the dispensing sleeve and a proximal end section of the piston rod are mutually engaged by means of at least one axially and radially extending protrusion engaging with a correspondingly shaped axially and radially extending recess. Hence, the dispensing sleeve and the piston rod are directly mechanically engaged in a splined way by means of at least one axially extending groove or notch receiving a correspondingly shaped protrusion. Piston rod and dispensing sleeve are rotatably locked and are axially displaceable relative to each other. 
         [0032]    For instance, the dispensing sleeve comprises at least one, preferably at least two diametrically oppositely located radially outwardly extending and axially elongated notches or grooves at an inside wall portion in which correspondingly shaped and radially outwardly extending protrusions or pins of the piston rod are received. In this way, a permanent rotational engagement between dispensing sleeve and piston rod can be attained while the dispensing sleeve is displaceable in axial direction relative to the piston rod. 
         [0033]    Therefore, axial displacement of the dispensing sleeve, either in distal or proximal direction has no substantial influence on the position of the piston rod. It is only due to a threaded engagement of the piston rod with the housing, that a rotative movement of the dispensing sleeve relative to the housing is transferred to the piston rod for driving the same in distal direction during a dose dispensing procedure. 
         [0034]    It is generally also conceivable, that it is the inside wall of the dispensing sleeve which comprises at least one radially inwardly extending protrusion to engage with at least one correspondingly and radially inwardly extending recess or groove of the piston rod. 
         [0035]    In order to homogeneously distribute a torque transmission between the piston rod and the hollow dispensing sleeve is it of particular benefit, that the rotatable engagement of dispensing sleeve and piston rod comprises at least two or more diametrically oppositely located or homogeneously distributed mutually engaging protruding and recessed structures. 
         [0036]    In a further embodiment, the dispensing sleeve extends radially between the piston rod and the drive sleeve. The hollow dispensing sleeve receives the piston rod therein. The dispensing sleeve therefore provides a kind of bearing and guiding function for the piston rod. Additionally, at least a distal end of the dispensing sleeve extends into the drive sleeve in order to selectively engage with the drive sleeve and in order to axially abut with the drive sleeve for driving the same into the distal dose dispensing position in the event of a dose dispensing action. 
         [0037]    Hence, drive sleeve and dispensing sleeve are at least partially interleaved. In this way, dispensing sleeve and drive sleeve may mutually mechanically stabilize. Moreover, the dispensing sleeve and the drive sleeve may comprise axially extending guiding structures by way of which a well defined axial mutual displacement of drive sleeve and dispensing sleeve can be realized. In this way, a mutual and selective torque transmitting coupling of drive sleeve and dispensing sleeve can be attained. 
         [0038]    In another embodiment, the dispensing sleeve is displaceable in distal direction from a proximal dose setting position into a distal dose dispensing position by means of an axially depressable injection button located at a proximal end of the housing of the drive mechanism. The injection button typically closes a proximal end of the drive mechanism&#39;s housing. Typically, the proximal end of the dispensing sleeve extends into the injection button, so that a distally-directed depression of said button directly induces a correspondingly directed distal displacement of the dispensing sleeve. 
         [0039]    A proximal end of the dispensing sleeve may further engage with the drive sleeve in a torque transmissive way when the drive sleeve reaches the above mentioned intermediate position. By means of a further and combined displacement of dispensing sleeve and drive sleeve, a rotational interlock of the drive sleeve may be released so that mechanical energy stored in the helical spring during a dose setting procedure can be released to set the drive sleeve in a dose dispensing directed rotation. 
         [0040]    The rotation of the drive sleeve may be equally transferred to the dispensing sleeve and to the piston rod rotatably engaged therewith. The piston rod is threadedly engaged with the housing. Therefore, a rotation of the piston rod inherently comes along with a distally-directed displacement of the piston rod relative to the housing. 
         [0041]    Typically, the dispensing sleeve is depressable in distal direction against the action of the dispensing sleeve spring element: Moreover, an injection spring may be arranged between the dispensing sleeve and the injection button or may be alternatively arranged between the injection button and the housing. By means of the injection spring, the injection button may return into a proximally-directed initial position as soon as a user no longer depresses said button. 
         [0042]    According to another embodiment a distal end of the dispensing sleeve is releasably rotatably locked with a distal end of the drive sleeve when the dispensing sleeve is in the intermediate position. A clutch to releasably and rotatably engage dispensing sleeve and drive sleeve is located at the distal ends of dispensing sleeve and drive sleeve, respectively. In this way, the dispensing sleeve is axially displaceable between the dose setting position, in which it is released from the drive sleeve, into the intermediate position and further into the dose dispensing position. 
         [0043]    When arriving in the intermediate position the dispensing sleeve rotatably engages or rotatably locks with the drive sleeve. While being rotatably locked a further distally-directed displacement of the dispensing sleeve leads to a corresponding distally-directed displacement of the drive sleeve until the drive sleeve reaches the dose dispensing position. In the dose dispensing position, the drive sleeve is free to rotate relative to the housing under the action of the helical spring that is typically biased during a dose setting procedure. 
         [0044]    The dispensing sleeve has a twofold functionality. Since it is permanently rotatably engaged with the piston rod it serves as a kind of a drive member to set the piston rod in rotation during and for a dose dispensing procedure. Further and due to the axial displacement relative to the piston rod and relative to the housing the dispensing sleeve also provides axial thrust transfer across the drive mechanism in order to selectively release and engage a rotational coupling between the drive sleeve and the piston rod. 
         [0045]    According to another embodiment the drive sleeve is axially displaceable relative to the housing in distal direction from the dose setting position into the dose dispensing position against the action of a drive sleeve spring element. In the dose setting position the drive sleeve is rotatably locked to the housing, typically by way of a clutch or ratchet mechanism. By displacing the drive sleeve in distal axial direction relative to the housing said clutch or ratchet mechanism is released so that the drive sleeve is free to rotate under the action of the helical spring when reaching the dose dispensing position, which typically corresponds to a distal stop position. 
         [0046]    This distally-directed displacement, which may be induced by the axial sliding displacement of the dispensing sleeve is conducted against the action of the drive sleeve spring element, which is typically located between a distal end of the drive sleeve and a radially inwardly extending protrusion or rim of the housing. The drive sleeve spring element serves to return the drive sleeve into its dose setting position as soon as an axially and distally-directed dispensing force is no longer present. 
         [0047]    According to a further embodiment the dispensing sleeve is axially displaceable relative to the housing. Moreover, the dispensing sleeve is also permanently rotatably engaged with the piston rod. The permanent rotational engagement between the dispensing sleeve and the piston rod allows that the dispensing sleeve is axially displaceable, hence axially slidable relative to the piston rod as well as relative to the housing. When initially depressed in distal direction, e.g. by means of a proximally located injection button, the dispensing sleeve is distally displaceable relative to the housing and relative to the drive sleeve against the action of the dispensing sleeve spring element, which is typically located between the dispensing sleeve and the drive sleeve. 
         [0048]    By means of the dispensing sleeve spring element a torque transferring clutch between the dispensing sleeve and the drive sleeve can either be closed or activated, typically, when the dispensing sleeve spring element is compressed. Upon release and upon axial extension of the dispensing sleeve spring element the dispensing sleeve is displaceable relative to the drive sleeve in proximal direction so as to release a torque transmissive or rotative coupling thereof. 
         [0049]    When the dispensing sleeve is in the intermediate position the dispensing sleeve spring element is typically compressed so that the clutch or coupling between the dispensing sleeve and the drive sleeve is closed or active. A further distally-directed displacement of the dispensing sleeve relative to the housing then serves to push and to slave the drive sleeve also in distal direction so as to liberate and to release a clutch or ratchet mechanism acting between the drive sleeve and the housing. 
         [0050]    As soon as the drive sleeve is released to rotate relative to the housing this rotation is equally transferred to the dispensing sleeve and hence to the piston rod, which due to its threaded engagement with a threaded support of the housing is driven in distal direction for dispensing of a dose. 
         [0051]    In still another embodiment a proximal end of the piston rod is rotatably locked with the dispensing sleeve while a distal end of the piston rod comprises an outer thread by way of which it is threadedly engaged with a threaded support of the housing. A rotational lock between piston rod and dispensing sleeve is also attainable by means of at least one longitudinally or axially extending slit intersecting the outer thread of the piston rod, wherein a radially inwardly extending protrusion of the dispensing sleeve engages with this slit. 
         [0052]    In this way, the dispensing sleeve and the piston rod are rotatably locked in order to unequivocally transfer a torque or a rotative movement of the dispensing sleeve towards the piston rod. Such a rotational locking or rotational coupling may be permanent. Due to its threaded engagement with the housing&#39;s threaded support the piston rod advances in a screw-like motion in distal direction when the dispensing sleeve is subject to rotation. Since the piston rod and the dispensing sleeve are axially slidably engaged, the piston rod may can advance in distal direction while the dispensing sleeve rests in the distal stop position or in the dose dispensing position. 
         [0053]    In a further embodiment the drive mechanism also comprises a dose dial button rotatably supported at the proximal end of the housing and being selectively rotatably engageable with a dose setting sleeve extending in axial direction. The dose dial button may comprise a geometric shape of a sleeve effectively surrounding a distal end of the cup-shaped dispensing button. The dose dial button is axially fixed to the housing and may be rotated either clockwise or counter clockwise for setting of a dose. Setting of a dose refers to both, incrementing of a dose as well as decrementing of a dose in the event, that a selected dose should be too large and has to be corrected in size. 
         [0054]    The dose dial button is rotatably engaged with the dose setting sleeve when the drive mechanism is in a dose setting mode. In a dose dispensing mode of the drive mechanism, the dose dial button may be disengaged from the dose setting sleeve. In this way, a counter-directed dose dispensing rotation of e.g. the drive sleeve has no influence on the dose dial button. 
         [0055]    Typically and according to another embodiment, a distal end of the dose setting sleeve is rotatably engaged with the drive sleeve, when the drive sleeve is in dose setting position. The dose setting sleeve therefore serves to transfer the angular momentum of the dose dial button to the drive sleeve during a dose setting procedure. Since the dose dial button is operably disconnected from the dose setting sleeve when the drive mechanism is in injection mode, the dose setting sleeve does not necessarily have to be disconnected from the drive sleeve. Generally, the dose setting sleeve could be permanently connected and engaged with the drive sleeve. 
         [0056]    The dose setting sleeve is only selectively engaged with the drive sleeve when the drive mechanism is in dose setting mode. In dose dispensing mode the dose setting sleeve is typically disengaged and released from the drive sleeve, when the drive sleeve is released and is allowed to rotate in a dose dispensing direction. The selective coupling of dose setting sleeve and drive sleeve is beneficial in terms of providing a last dose limiting mechanism as will be explained below. 
         [0057]    A torque transmissive and rotational engagement of the dose setting sleeve and the drive sleeve is obtainable by a direct and mutual engagement of the dose setting sleeve&#39;s distal end section with a proximal end section of the drive sleeve. In order to allow for a rather compact design of the drive mechanism the dose setting sleeve and the drive sleeve co-align in axial direction. A mutual torque transmissive engagement of dose setting sleeve and drive sleeve may then be provided by mutually corresponding crown wheel portions at the distal end face of the dose setting sleeve and the proximal end face of the drive sleeve. 
         [0058]    The dose setting sleeve is axially fixed relative to the housing. This means, the dose setting sleeve remains stationary relative to the housing in both, the dose setting mode and the dose dispensing mode. It is typically the drive sleeve which is selectively displaceable in distal direction to transfer the drive mechanism into the dose dispensing mode, thereby disengaging the mutually corresponding crown wheel portions of the dose setting sleeve and the drive sleeve. 
         [0059]    By disengaging the drive sleeve and the dose setting sleeve in the dose dispensing mode of the drive mechanism, the dose setting sleeve will not rotate in a dose dispensing direction during a dose dispensing procedure. This allows to implement a last dose limiting mechanism on the basis of the dose setting sleeve which is only operable and which will exclusively rotate during a dose setting operation of the drive mechanism. 
         [0060]    In a further embodiment the drive mechanism also comprises a dose indicating mechanism for displaying a size of the dose actually set by the drive mechanism. The dose indicating mechanism comprises a base rotatably supporting a first spool and a second spool at a predefined distance with respect to each other and in a substantially parallel orientation. 
         [0061]    First and second spools extend in axial direction. Hence, first and second spools rotate about respective axis of rotations which extend parallel to the longitudinal direction or the axial direction of the housing. First and second spools are arranged at a radial distance from the piston rod and/or from the drive sleeve. The spools are typically arranged radially outside the drive sleeve. They are positioned beneath the housing and may be arranged in substantially identical or at least partially overlapping axial positions with respect to each other. 
         [0062]    The dose indicating mechanism further comprises a dose indicating tape or belt which is coiled onto at least the second spool in an initial, hence zero dose configuration. Said dose indicating tape is further fixed with another end to an outer circumference of the first spool. The dose indicating tape therefore extends between the first and second spools and can be selectively and alternately coiled onto first and second spools in an alternating way. 
         [0063]    During a dose setting procedure the first spool is typically rotatably coupled with the drive sleeve, thereby coiling up the dose indicating tape to the first spool to a certain extent. Depending on the number of revolutions of the first spool during a dose setting procedure, the dose indicating tape will be transferred from the second spool towards the first spool. 
         [0064]    The dose indicating mechanism is typically arranged inside the housing of the drive mechanism in such a way, that the dose indicating tape extending between first and second spools shows up below a dose indicating window of the housing. Since the dose indicating tape is selectively coiled up onto first and second spools, the tape can be rather long and may provide almost unlimited space for printing numbers thereon. The numbers presented on the dose indicating tape may therefore be comparatively large allowing for a good visibility and for a sufficient and unequivocal reading, even by patients or users suffering impaired vision. 
         [0065]    In another embodiment, the second spool is rotatable relative to the base against the action of a spring while the first spool is permanently rotatably engaged with the drive sleeve. Hence, unwinding of the dose indicating tape from the second spool may only occur against the action of a respective spool spring. By means of the spool spring, the dose indicating tape can be sufficiently strained between first and second spools in order to stay free of any slacks. 
         [0066]    Additionally, the spring spool serves to return the dose indicating tape onto the second spool in the event of a dose dispensing procedure. The numbers of the dose indicating tape that will show up in a dose indicating window of the housing will then decrement accordingly. 
         [0067]    The rotative engagement of the first spool and the drive sleeve is invariant to a distally-directed displacement of the drive sleeve relative to the housing and/or relative to the at least first spool of the dose indicating mechanism. The first spool and the drive sleeve are rotatably engaged by means of gear wheels featuring an axial extension which allows for an axial displacement of the drive sleeve relative to the first spool when switching the drive mechanism between dose setting mode and dose dispensing mode. By means of the mutually engaging gearwheels of the first spool and the drive sleeve also a predefined transmission ratio regarding the revolutions of drive sleeve and first spool can be implemented. 
         [0068]    In a further embodiment, the dose setting sleeve comprises an outer threaded section to threadedly engage with an inside facing thread of a last dose limiting member rotatably locked to the housing. The dose limiting member is splined with an inside facing side wall portion of the housing. Correspondingly, the last dose limiting member, which may be of semi-circular or arc shape is arranged radially between the dose setting sleeve and the housing. The last dose limiting member is splined to the housing, e.g. by means of at least one axially and radially extending protrusion engaging with a correspondingly shaped axially and radially extending recess. 
         [0069]    It may be the last dose limiting member that comprises a radially outwardly extending protrusion to engage with a correspondingly shaped radially outwardly extending recess provided at an inside facing sidewall portion of the housing. However, also an opposite arrangement is conceivable, wherein an outer portion of the last dose limiting member comprises a recess to mate with a radially inwardly extending protrusion provided at an inside wall of the housing. 
         [0070]    Since the dose setting sleeve is exclusively operable during dose setting, the dose limiting member experiences a distally-directed displacement along the housing when the dose setting sleeve is subject to rotation. This way, the axial position of the last dose limiting member relative to the dose setting sleeve may be indicative of the total amount of doses set and dispensed by the drive mechanism. 
         [0071]    In a further embodiment also the drive sleeve comprises an outer threaded section to threadedly engage with an inside facing thread of a single dose limiting member which is rotatably locked to the housing. Similar as already described with respect to the last dose limiting member also the single dose limiting member may be rotatably locked to the housing by way of at least one axially and radially extending protrusion engaging with a correspondingly shaped axially and radially extending recess. 
         [0072]    The protrusion may be provided at an outer circumference of the ring-shaped or semi-ring-shaped dose limiting member while the radially extending recess may be provided at an inside facing sidewall portion of the housing. 
         [0073]    Since the drive sleeve is operable to rotate in a dose setting direction during dose setting and into an opposite dose dispensing direction during dose dispensing, the single dose limiting member will accordingly be displaced in distal and proximal direction during dose setting and dose dispensing, respectively. 
         [0074]    In another embodiment, the last and/or the single dose limiting member abut with a radially outwardly extending radial stop of the dose setting sleeve and/or the drive sleeve, respectively. Typically, the last dose limiting member as well as the single dose limiting member comprise a trailing and a leading edge which may abut with correspondingly shaped radially outwardly extending stops of the last dose limiting member and/or the single dose limiting member when an end of content configuration or when a maximum dose setting configuration of the drive mechanism will be reached. 
         [0075]    As soon as for instance the last dose limiting member gets in abutment with a last dose stop of the dose setting sleeve, a further dose incrementing rotation of the dose setting sleeve is blocked. Hence, a dose exceeding the amount of medicament left in the cartridge cannot be set. A dose setting procedure will then be stopped or interrupted accordingly. 
         [0076]    The same may apply with the single dose limiting member during a dose setting procedure. When the single dose limiting member abuts with the radially outwardly extending radial stop of the drive sleeve, the drive sleeve cannot be further rotated in a dose setting direction. Consequently, a dose setting procedure will be limited and stop. In this way, setting of a dose exceeding a predefined dose size of e.g. 120 I.U. can be effectively prevented. 
         [0077]    Since the drive sleeve is subject to a counter-directed dose dispensing rotation during a subsequent dose dispensing procedure, also the single dose limiting member will return into an initial axial position relative to the drive sleeve. Here, it is of particular benefit, when the single dose limiting member audibly engages with a zero dose stop when reaching an initial configuration that coincides with the termination or end of a dose dispensing procedure. By providing the single dose limiting member with a clicking element, reaching of a zero dose configuration may come along with an audible click sound indicating to a user, that the end of a dose dispensing procedure has been reached. 
         [0078]    According to another aspect, the invention also relates to a drug delivery device for dispensing of a dose of a medicament. The drug delivery device comprises a drive mechanism as described above and a cartridge at least partially filled with the medicament to be dispensed by the drug delivery device. The cartridge is arranged in the housing of the drive mechanism or in a cartridge holder of the drug delivery device which is fixed to the housing either releasably or non-releasably, e.g. in case of a disposable drug delivery device. Consequently, the drug delivery device comprises a cartridge holder to receive and to accommodate a cartridge filled with the medicament. 
         [0079]    Apart from that, the drug delivery device and the drive mechanism may comprise further functional components, such like an injection button, by way of which a user may trigger and control the drug delivery device and its drive mechanism for dispensing of a dose of the medicament. 
         [0080]    In the present context, the distal direction points in the direction of the dispensing and of the device, where, a needle assembly is provided having a double-tipped injection needle that is to be inserted into biological tissue or into the skin of a patient for delivery of the medicament. 
         [0081]    The proximal end or proximal direction denotes the end of the device or a component thereof, which is furthest away from the dispensing end. Typically, an actuating member is located at the proximal end of the drug delivery device, which is directly operable by a user to be rotated for setting of a dose and which is operable to be depressed in distal direction for dispensing of a dose. 
         [0082]    The term “drug” or “medicament”, as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound, 
         [0083]    wherein in one embodiment the pharmaceutically active compound has a molecular weight up to 1500 Da and/or is a peptide, a protein, a polysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or a fragment thereof, a hormone or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound, 
         [0084]    wherein in a further embodiment the pharmaceutically active compound is useful for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism, acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis, 
         [0085]    wherein in a further embodiment the pharmaceutically active compound comprises at least one peptide for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, 
         [0086]    wherein in a further embodiment the pharmaceutically active compound comprises at least one human insulin or a human insulin analogue or derivative, glucagon-like peptide (GLP-1) or an analogue or derivative thereof, or exendin-3 or exendin-4 or an analogue or derivative of exendin-3 or exendin-4. 
         [0087]    Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) human insulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin. 
         [0088]    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-carboxyheptadecanoyl) human insulin. 
         [0089]    Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2. 
         [0090]    Exendin-4 derivatives are for example selected from the following list of compounds: 
         [0091]    H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2, 
         [0092]    H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2, 
         [0093]    des Pro36 Exendin-4(1-39), 
         [0094]    des Pro36 [Asp28] Exendin-4(1-39), 
         [0095]    des Pro36 [IsoAsp28] Exendin-4(1-39), 
         [0096]    des Pro36 [Met(O)14, Asp28] Exendin-4(1-39), 
         [0097]    des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), 
         [0098]    des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39), 
         [0099]    des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
         [0100]    des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), 
         [0101]    des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or 
         [0102]    des Pro36 [Asp28] Exendin-4(1-39), 
         [0103]    des Pro36 [IsoAsp28] Exendin-4(1-39), 
         [0104]    des Pro36 [Met(O)14, Asp28] Exendin-4(1-39), 
         [0105]    des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), 
         [0106]    des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39), 
         [0107]    des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
         [0108]    des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), 
         [0109]    des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
         [0110]    wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative; 
         [0111]    or an Exendin-4 derivative of the sequence 
         [0112]    des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010), 
         [0113]    H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0114]    des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2, 
         [0115]    H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2, 
         [0116]    H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2, 
         [0117]    des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0118]    H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0119]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0120]    H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0121]    H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2, 
         [0122]    H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
         [0123]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
         [0124]    des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0125]    H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0126]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0127]    H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0128]    des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2, 
         [0129]    H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
         [0130]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
         [0131]    des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0132]    H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0133]    H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0134]    H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0135]    H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1-39)-NH2, 
         [0136]    H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
         [0137]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
         [0138]    des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0139]    H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2, 
         [0140]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2; 
         [0141]    or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exendin-4 derivative. 
         [0142]    Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists as listed in Rote Liste, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin. 
         [0143]    A polysaccharide is for example 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, 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. 
         [0144]    Antibodies are globular plasma proteins (˜150 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. 
         [0145]    The Ig monomer is a “Y”-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds between cysteine residues. Each heavy chain is about 440 amino acids long; each light chain is about 220 amino acids long. Heavy and light chains each contain intrachain disulfide bonds which stabilize their folding. Each chain is composed of structural domains called Ig domains. These domains contain about 70-110 amino acids and are classified into different categories (for example, variable or V, and constant or C) according to their size and function. They have a characteristic immunoglobulin fold in which two β sheets create a “sandwich” shape, held together by interactions between conserved cysteines and other charged amino acids. 
         [0146]    There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ, and μ. The type of heavy chain present defines the isotype of antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively. 
         [0147]    Distinct heavy chains differ in size and composition; α and γ contain approximately 450 amino acids and δ approximately 500 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has two regions, the constant region (C H ) and the variable region (V H ). In one species, the constant region is essentially identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains γ, α and δ have a constant region composed of three tandem Ig domains, and a hinge region for added flexibility; heavy chains μ and E have a constant region composed of four immunoglobulin domains. The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain. 
         [0148]    In mammals, there are two types of immunoglobulin light chain denoted by λ and κ. A light chain has two successive domains: one constant domain (CL) and one variable domain (VL). The approximate length of a light chain is 211 to 217 amino acids. Each antibody contains two light chains that are always identical; only one type of light chain, κ or λ, is present per antibody in mammals. 
         [0149]    Although the general structure of all antibodies is very similar, the unique property of a given antibody is determined by the variable (V) regions, as detailed above. More specifically, variable loops, three each the light (VL) and three on the heavy (VH) chain, are responsible for binding to the antigen, i.e. for its antigen specificity. These loops are referred to as the Complementarity Determining Regions (CDRs). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chains, and not either alone, that determines the final antigen specificity. 
         [0150]    An “antibody fragment” contains at least one antigen binding fragment as defined above, and exhibits essentially the same function and specificity as the complete antibody of which the fragment is derived from. Limited proteolytic digestion with papain cleaves the Ig prototype into three fragments. Two identical amino terminal fragments, each containing one entire L chain and about half an H chain, are the antigen binding fragments (Fab). The third fragment, similar in size but containing the carboxyl terminal half of both heavy chains with their interchain disulfide bond, is the crystalizable fragment (Fc). The Fc contains carbohydrates, complement-binding, and FcR-binding sites. Limited pepsin digestion yields a single F(ab′)2 fragment containing both Fab pieces and the hinge region, including the H-H interchain disulfide bond. F(ab′)2 is divalent for antigen binding. The disulfide bond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, the variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv). 
         [0151]    Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g. salts having a cation selected from alkali or alkaline, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharmaceutically acceptable salts are described in “Remington&#39;s Pharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology. 
         [0152]    Pharmaceutically acceptable solvates are for example hydrates. 
         [0153]    It will be further apparent to those skilled in the pertinent art that various modifications and variations can be made to the present invention without departing from the spirit and scope of the invention. Further, it is to be noted, that any reference signs used in the appended claims are not to be construed as limiting the scope of the present invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0154]    In the following, various embodiments of the invention will be described by making reference to the drawings, in which: 
           [0155]      FIG. 1  schematically illustrates the assembled drug delivery device in a longitudinal cross section, 
           [0156]      FIG. 2  shows a cross section along A-A according to  FIG. 1 , 
           [0157]      FIG. 3  shows a cross-section along B-B according to  FIG. 1 , 
           [0158]      FIG. 4  shows a cross-section along C-C according to  FIG. 1 , 
           [0159]      FIG. 5  is indicative of a cross-section along D-D according to  FIG. 1 , 
           [0160]      FIG. 6  shows a cross-section along E-E according to  FIG. 1 , 
           [0161]      FIG. 7  shows a cross-section along F-F according to  FIG. 1 , 
           [0162]      FIG. 8  shows a cross-section along G-G according to  FIG. 1  and 
           [0163]      FIG. 9  shows a cross-section along H-H according to  FIG. 1 , 
           [0164]      FIG. 10  shows an exploded view of the drug delivery device in perspective illustration, 
           [0165]      FIG. 11  shows a perspective view of the drive mechanism without the surrounding housing, 
           [0166]      FIG. 12  shows the drive mechanism according to  FIG. 11  assembled in the housing, 
           [0167]      FIG. 13  is illustrative of a cross-section along I-I according to  FIG. 1 , 
           [0168]      FIG. 14  shows the drive sleeve assembled in the housing in a perspective illustration, 
           [0169]      FIG. 15  shows a perspective illustration of the dose indicating mechanism, 
           [0170]      FIG. 16  shows the dose indicating mechanism assembled in the housing and interacting with the drive sleeve, 
           [0171]      FIG. 17  is illustrative of an enlarged view of the single dose limiting member engaged with a radial stop of the drive sleeve, 
           [0172]      FIG. 18  shows a perspective illustration of the single dose limiting member in a different stop configuration on a threaded portion of the drive sleeve, 
           [0173]      FIG. 19  shows an enlarged view of the configuration according to  FIG. 17 , 
           [0174]      FIG. 20  is a side view of the last dose limiting member engaging with a radial stop of the dose setting sleeve, 
           [0175]      FIG. 21  shows a side view of the last dose limiting member engaging with a last dose stop of the dose setting sleeve and 
           [0176]      FIG. 22  is a perspective illustration of the last dose limiting member threadedly engaged with a threaded portion of the dose setting sleeve, 
           [0177]      FIG. 23  shows an enlarged longitudinal cut through the proximal end of the drive mechanism, 
           [0178]      FIG. 24  is a perspective view of the mutual engagement of the dose setting clutch with the dose dial button, 
           [0179]      FIG. 25  shows a distally located clicking member of the drive sleeve engaging with the housing and 
           [0180]      FIG. 26  shows an enlarged longitudinal cut through the drive mechanism. 
       
    
    
     DETAILED DESCRIPTION 
       [0181]    In  FIGS. 1 ,  10  and  26  the drive mechanism  3  of a drug delivery device  10  is illustrated in an assembled and in an exploded view, respectively. The drug delivery device  10  is of pen-injector type and comprises a substantially cylindrical and axially elongated shape. Throughout the Figures the axial distal direction is denoted with reference number  1  and the opposite proximal direction is denoted with reference number  2 . The drug delivery device  10  comprises a proximal housing component  30  to receive the drive mechanism  3 . 
         [0182]    In distal direction  1 , the housing  30  is connected with a cartridge holder  12  which is adapted to accommodate and to receive a cartridge  14  containing the medicament to be dispensed by the drug delivery device  10 . The cartridge  14  typically comprises a vitreous barrel  18  of cylindrical shape which is sealed in distal direction  1  by a pierceable sealing member, such like a septum. 
         [0183]    In proximal direction  2 , the cartridge  14  is sealed by a piston  16  slidably arranged in the vitreous barrel  18  of the cartridge  14 . Displacement of the piston  16  in distal direction  1  leads to a respective built-up of a fluid pressure inside the cartridge  14 . When the distal outlet of a cartridge  14  is connected with e.g. a needle assembly  20 , as shown in  FIG. 1 , a predefined amount of the liquid medicament contained in the cartridge  14  can be expelled and dispensed via an injection needle  22  of the needle assembly  20 . 
         [0184]    In  FIG. 1  however, a needle cap  24  to protect the double-tipped injection needle  22  is indicated. The needle assembly  20  is typically arranged on a distal end portion of the cartridge holder  12 . Typically, a distally located socket of the cartridge holder  12  and the needle assembly  20  comprise mutually corresponding threads to screw the needle assembly  20  onto the cartridge holder  12  in a releasable and removable way. 
         [0185]    The cartridge holder  12  and hence the cartridge  14  is to be protected and covered by a protective cap  26  which is shown in  FIGS. 2 and 3 . Prior to setting and/or dispensing of a dose, the protective cap  26  as well as the inner needle cap  24  are to be removed. After dispensing or injecting of the medicament into biological tissue, the needle assembly  20  is typically to be discarded and the distal end of the drug delivery device  10  is to be covered by the protective cap  26 . 
         [0186]    The drive mechanism  3  as illustrated in an exploded view in  FIG. 10  and as shown in cross section in its fully assembled configuration in  FIGS. 1 and 26  comprises numerous functional components by way of which a dose of variable size can be set and subsequently dispensed. 
         [0187]    The dose dispensing procedure comes along with a distally directed advancing displacement of the piston rod  80  relative to the housing  30 . The drive mechanism  3  therefore comprises at least a housing  30 , a piston rod  80  a drive sleeve  50  and a dispensing sleeve  70  which can be selectively and operably coupled for setting and dispensing of a dose respectively. 
         [0188]    The dose dispensing procedure comes along with a distally-directed advancing displacement of a piston rod  80  relative to the housing  30 . As illustrated for instance in  FIGS. 1 and 26 , the piston rod  80  comprises an outer threaded portion  84  at a distal end which is threadedly engaged with a radially centrally located and threaded support  31  of the housing. Advancing of the piston rod  80  in distal direction may therefore be achieved by a rotational movement of the piston rod  80  relative to the housing  30 . 
         [0189]    In the following, setting of a dose is described. 
         [0190]    For setting of a dose, a user takes the drug delivery device  10  and starts to rotate the proximally located dose dial button  100  relative to the housing  30 . The dose dial button  100  is of sleeve-like shape and is axially fixed to a proximal end of the housing  30  by way of axially extending and radially outwardly biased latch elements  102 . As for instance indicated in  FIG. 23 , the latch elements  102  engage with a radially inwardly extending flange portion  38  provided at the distal end face of the housing  30 . 
         [0191]    As further shown in  FIG. 23  the dose dial button  100  also axially abuts against the proximal end face of the housing  30 , hence against the flange portion  38  so that the dose dial button  100  is axially fixed with respect to the housing  30 . The mutual engagement of the dose dial button  100  and the housing  30  allows for a free rotation of the dose dial button  100  relative to the housing  30 . 
         [0192]    As shown in cross-section of  FIG. 2  and  FIG. 23 , the dose dial button  100  comprises a toothed section  104  protruding radially inwardly from an inside facing sidewall portion  106  of the dose dial button  100 . 
         [0193]    As shown in  FIG. 2 , there is provided a dose setting clutch  110  inside the dose dial button  100 . The sleeve-like dose setting clutch  110  comprises two radially outwardly extending teeth  112  that engage with the toothed section  104  of the dose dial button  100 . Hence, a dose setting rotation of the dose dial button  100  leads to a corresponding rotation of the dose setting clutch  110 . Moreover, the dose setting clutch  110  receives and is engaged with a dose setting sleeve  40  extending therethrough in axial direction. 
         [0194]    In particular, the dose setting sleeve  40  is splined with the dose setting clutch. As shown in  FIG. 2 , the dose setting sleeve  40  comprises one radially outwardly extending protrusion  41  extending into an axially extending recess  116  provided at the inside of the dose setting clutch  110 . Therefore, a rotation of the dose dial button  100  not only rotates the dose setting clutch  110  but also the dose setting sleeve  40 . 
         [0195]    As illustrated in the longitudinal cross-sections of  FIG. 1  and  FIG. 26 , the dose setting sleeve  40  extends axially inwardly into the housing  30  of the drive mechanism  3  and engages with a drive sleeve  50  by means of mutually corresponding crown wheel portions  45 ,  55 . As indicated in  FIG. 1 , a crown wheel portion  45  provided at a distal end face of the dose setting sleeve  40  engages with a correspondingly crown wheel portion  55  provided at a proximal end face of the drive sleeve  50 . In this way, and at least in dose setting mode, dose setting sleeve  40  and drive sleeve  50  are rotatably engaged. Hence, a dose setting rotation of the dose setting sleeve  40  equally transfers to a corresponding rotation of the drive sleeve  50 . 
         [0196]    The drive sleeve  50  is biased with respect to the housing  30  by means of a helical spring  68 . As indicated in  FIG. 5 ,  14  and in  FIG. 26  the drive sleeve  50  comprises a radially outwardly extending mount  66  to receive one end of the helical spring  68 , which axially and circumferentially extends around a cylindrical portion of the drive sleeve  50 . An opposite end of the helical spring  68  is fastened to the housing  30 . In this way, rotation of the drive sleeve  50  in a dose setting direction  4  as illustrated in  FIG. 4  will typically occur against the action of the helical spring  68 . 
         [0197]    The drive sleeve  50  further comprises a radially outwardly extending ratchet member  52  which is engaged with a toothed inner surface  122  of a toothed ring  120  when in dose setting mode. The toothed ring  120  is fastened and fixed in the housing  30 . The ratchet member  52  is arc-shaped and is therefore resiliently deformable in radial direction. It may further comprise a radially outwardly extending tooth or nose that mates with the correspondingly shaped toothed inner surface  122  of the toothed ring  120 . As indicated in cross-section according to  FIG. 4 , the ratchet member  52  meshes with the toothed inner surface  122  when rotated clockwise, e.g. in dose setting direction  4 . Passing of the ratchet member  52  along the consecutive teeth of the toothed inner surface  122  generates an audible feedback to the user, thereby indicating, that the dose is step-wise incremented. 
         [0198]    The geometry of the toothed surface  122  of the toothed ring  120  and the free end of the ratchet member  52  is designed such, that the spring force arising from the helical spring  68  and acting in opposite, hence dose dispensing direction  5  is not large enough to rotate the drive sleeve  50  in the dose dispensing direction  5 . In this way, mechanical energy can be stored by and in the helical spring  68  which is to be released only on demand during a subsequent dose dispensing procedure. For dispensing of a dose the mutual engagement of the ratchet member  52  and the toothed inner surface  122  is released. 
         [0199]    Moreover, the toothed inner surface  122  and the ratchet member  52  of the drive sleeve  50  engage in such a way, that a dose decrementing rotation of the drive sleeve  50  is indeed possible, e.g., when a user exerts a respective counter-directed angular momentum to the dose dial button  100 , which exceeds the resilient resistance provided by the mutual engagement of ratchet member  52  and toothed inner surface  122 . 
         [0200]    The drive sleeve  50  further comprises a gear wheel  51  or a respective geared section axially adjacent to the toothed ring  120 . As shown in  FIGS. 12 and 16 , the gear wheel  51  meshes with a corresponding gear wheel  145  of a first spool  140  of a dose indicating mechanism  130  which is separately illustrated in  FIG. 15 . The dose indicating mechanism  130  comprises a base  130  featuring a support section  134  and two laterally extending branches  131  and  133 . On each of said branches  131 ,  133  a bearing  136 ,  138  for a first spool  140  and for a second spool  142  is provided, respectively. As shown in  FIG. 15 , the first spool is rotatably supported by the bearing  136  on the branch  131  while the second spool is arranged on the second branch  133  by the bearing  138 . 
         [0201]    The two spools  140 ,  142  are further interconnected by means of a dose indicating tape  146 . In an initial configuration, the dose indicating tape featuring a sequence of dose indicating numbers  148  is almost completely coiled up on the second spool  142 . A free end of said tape  146  is connected and attached to the outer circumference of the first spool  140 . Due to the geared interaction of drive sleeve  50  and first spool  140 , rotation of the drive sleeve  50  during a dose setting procedure comes along with a corresponding rotation of the first spool  140 , thereby coiling up at least a portion of the dose indicating tape  146  onto the first spool  140 . 
         [0202]    As it is further indicated in  FIGS. 10 and 15 , an unwinding rotation of the second spool  142  will only occur against the action of a spool spring  144 , which comprises a helical spring element  144  located inside the spool  142 . By means of such a spool spring  144 , the dose indicating tape  146  can be strained in order to reduce a potential slack between the two spools  140 ,  142  to a minimum. Moreover, by means of the helical or torsion spool spring  144 , the entire dose indicating mechanism  130  can be pre-stressed during pre-assembly of the device. 
         [0203]    The dose indicating mechanism  130  can be assembled in its entirety into the housing  30  as indicated in  FIG. 16 . Depending on the degree of rotation of the drive sleeve  50  during a dose setting procedure, the dose indicating tape  146  will be wound up to the first spool  140 . Above the support section  134  of the base  132  a respective number  148  representing the size of the said dose will show up. In its fully assembled configuration, the dose indicating mechanism  130  will be covered by a closure  32  of the housing  30  as indicated in  FIG. 10 . 
         [0204]    Said closure  32  comprises a dose indicating window  34 , through which a comparatively large number  148  provided on the dose indicating tape  146  is clearly visible. By means of the winding mechanism provided by the dose indicating mechanism  130  the numbers  148  can be printed and displayed comparatively large in order to allow a good and sufficient legibility of the size of the said dose. When appropriately mounted to the housing  30  the closure  32  typically flushes with the outer side wall of the adjacent housing. Hence, the closure  32  forms part of the housing  30  and is effectively integrated therein. 
         [0205]    During a dose dispensing operation, which will be explained in greater detail below, the drive sleeve  50  is allowed to rotate in the opposite, hence in the dose dispensing direction  5 . Also in the dose dispensing mode, the drive sleeve  50  stays geared with the gear wheel  145  of the first spool  140 . Under the action of the spool spring  144 , the tape  146  will then return and will coil up on the second spool  142 . Correspondingly the numbers showing up in the dose indicating window will successively count down. 
         [0206]    In the cross-section of  FIGS. 3 and 6 , the geared engagement of the drive sleeve  50  with the first spool  140  is not explicitly illustrated. However, from the  FIG. 16  the permanent geared interaction of the drive sleeve  50  with the first spool  140  is clearly visible. 
         [0207]    In the following, dispensing of a dose is described. 
         [0208]    The drive mechanism  3  further comprises a dispensing sleeve  70  and an injection button  90 . The dispensing sleeve  70  extends almost through the entire drive mechanism  3  in axial direction while the cup-shaped injection button  90  is located at a proximal end of the drive mechanism  3 , hence at a proximal end of the entire drug delivery device  10 . The injection button  90  is axially secured to the housing  30  by means of an axially and radially inwardly extending latch element  92  adapted to engage with a correspondingly shaped latch element  114  provided at a proximal end of the dose setting clutch  110 . 
         [0209]    The latch element  92  of the injection button  90  extends axially inwardly and protrudes from a radially inwardly extending latch  94 , which may form a distal end section of the sidewall portion  93  of the injection button  90 . The injection button  90  is operable to be depressed in distal direction as indicated in  FIG. 23 . In a central portion of its proximal end face the injection button  90  may comprise an integrated spring, e.g. an injection spring  91  which engages with a proximal end face of the dispensing sleeve  70 . 
         [0210]    Distally-directed depression of the injection button  90  therefore induces a corresponding distally-directed displacement of the dispensing sleeve  70 . At the same time, the dose setting clutch  110  is displaced in distal direction so that its radially outwardly extending teeth  112  disengage from the toothed section  104  of the dose dial button  100 . In this way, the dose dial button  100  can be decoupled from the dose setting clutch  110  and accordingly from the dose setting sleeve  40 . Any further rotation of the dose dial button  100  during a dose dispensing procedure is therefore substantially effectless and will not lead to a further rotation of the dose setting sleeve  40 . 
         [0211]    Distally-directed displacement of the dispensing sleeve  70  acts against the action of at least one spring element  57 ,  58 . Moreover, as illustrated in the longitudinal cross-sections of  FIGS. 1 and 26  the distal end section of the dispensing sleeve  70  axially abuts and axially engages with the drive sleeve  50 . This way, an axially and distally directed displacement of the dispensing sleeve  70  can be transferred to a respective distally-directed displacement of the drive sleeve  50 . 
         [0212]    While the drive sleeve  50  is in a proximal dose setting position during a dose setting mode of the drive mechanism  3  it can now be pushed or slaved into a distal dose dispensing position. The drive sleeve  50  is supported in axial direction relative to the housing  30  by means of a distally located drive sleeve spring element  57 , which may axially abut against the threaded support  31  of the housing  30 . Additionally, there may be provided a further dispensing sleeve spring element  58  between the dispensing sleeve  70  and the drive sleeve  50 . 
         [0213]    As shown in cross-sections of  FIGS. 1 and 26 , the drive sleeve  50  comprises a radially inwardly extending inner sleeve portion  56  at its distal end, which is adapted to form an annular receptacle to receive a correspondingly shaped distally extending extension  73  of the dispensing sleeve  70 . In this way, dispensing sleeve  70  and drive sleeve  50  can be secured and fixed with respect to each other in radial direction. 
         [0214]    Moreover, the additional spring element  57 , to be denoted as drive sleeve spring element  57 , may be positioned in the interface formed by the dispensing sleeve  70  and the drive sleeve  50  in order to separate the dispensing sleeve from the drive sleeve as soon as the injection button  90  is no longer depressed. 
         [0215]    The dispensing sleeve  70  further comprises a ring-shaped receptacle at a distal end to receive the free end of the proximally extending inner sleeve portion  56  of the drive sleeve  50 . The receptacle  75  may be suitable to receive another spring element  58  to be denoted as dispensing sleeve spring element  58 . 
         [0216]    As further illustrated in  FIG. 5  and  FIG. 26 , the drive sleeve  50  comprises a radially inwardly extending flange portion  64  protruding from the proximal end of the inner sleeve portion  56 . On said flange portion  64  there are provided at least two axially and proximally extending pins  65  adapted to engage with a punched structure  74  provided at the distal end face of the dispensing sleeve  70 . In this way, a torque transmitting engagement of dispensing sleeve  70  and drive sleeve  50  can be provided. A dose dispensing rotation of the drive sleeve  50  may then equally transfer to the dispensing sleeve  70 . 
         [0217]    The dispensing sleeve  70  is further rotatably locked with the piston rod  80 . For this purpose, the dispensing sleeve  70  comprises an axially and radially extending recess  72  to receive at least one correspondingly shaped and radially outwardly extending protrusion  82  of the piston rod  80  as shown in cross-section in  FIG. 8 . With such a splined engagement, any rotative movement of the dispensing sleeve  70  can be equally transferred to a corresponding rotation of the piston rod. 
         [0218]    Since at least a distal end of the piston rod  80  is provided with an outer thread  84  which is threadedly engaged with the threaded support  31  of the housing  30 , any rotation of the dispensing sleeve  70  and a corresponding rotation of the piston rod  80  will lead to a distally-directed advancing of the piston rod  80  and its distally located pressure foot  86  relative to the housing  30  for driving the piston  16  of the cartridge  14  further into the barrel  18  of the cartridge  14 , thereby expelling a predefined amount of the medicament contained in the cartridge  14 . Due to the splined and direct engagement of the dispensing sleeve  70  and the piston rod  80 , any axially-directed displacement of the dispensing sleeve  70  relative to the piston rod  80  has no influence on the axial position of the piston rod  80 . 
         [0219]    Axially and distally-directed displacement of the dispensing sleeve  70  may be conducted in two consecutive steps. In a first step, the dispensing sleeve  70  is displaced in distal direction until a mutual and axial engagement with the drive sleeve  50  is attained. In such an intermediate position of the dispensing sleeve  70  the dispensing sleeve  70  rotatably engages with the drive sleeve  50  since the pins  65  of the drive sleeve engage and enter the punched structure  74  of the dispensing sleeve  70 . 
         [0220]    In this intermediate configuration the drive sleeve  50  is still engaged with the toothed ring  120  and the drive sleeve  50  is still hindered to rotate relative to the housing  30 . It is only due to a further distally-directed displacement of the dispensing sleeve  70 , that the drive sleeve  50  is displaced in distal direction  1  against the action of the spring element  57 . When reaching a distal stop configuration, in which for instance a distally located radially outwardly extending flange  53  of the drive sleeve  50  abuts with a radially inwardly extending ledge  35  of the housing  30  or in which the radially outwardly extending ratchet member  52  axially engages with the axial stop  36  of the housing  30 , as indicated in  FIG. 14 , the combined distally directed motion of the dispensing sleeve  70  and the drive sleeve  50  can be stopped. 
         [0221]    The two consecutively and sequentially depressable spring elements  57 ,  58  typically comprise different spring constants so that a rotative coupling of dispensing sleeve  70  and drive sleeve  50  can be established before the drive sleeve  50  and its ratchet member  52  is axially displaced from the toothed ring  120  such that the drive sleeve  50  may freely rotate under the action of the helical spring  68 . 
         [0222]    As further illustrated in  FIG. 26 , axial displacement of the drive sleeve  50  in distal direction  1  also decouples and releases the drive sleeve  50  from the dose setting sleeve  40 . The dose setting sleeve  40  is axially fixed with respect to the housing  30 . By the separation of the drive sleeve  50  from the dose setting sleeve  40  during a dose dispensing procedure, the dose setting sleeve  40  never rotates in the dose dispensing direction  5  but always incrementally rotates in the opposite dose setting direction  4 . 
         [0223]    The drive sleeve  50  further comprises an arc-shaped clicking member  67  extending in distal direction  1  from the distal flange portion  53  of the drive sleeve  50 . As indicated in  FIG. 25 , and when rotating during dose dispensing the clicking member  67  consecutively engages with feedback element  37 , which may be provided in form of axially extending protrusions or recesses on a ledge  35  of the housing  30 . As indicated in the cross-section according to  FIG. 9  numerous feedback elements  37  are arranged around the ledge  35  of the housing  30 . When the drive sleeve  50  revolves under the action of the spring  68 , the clicking member  67  generates a frequently repeating clicking sound which is audible by the patient or user of the device  10 , thereby indicating to the user, that a dispensing action is actually in progress. 
         [0224]    The dose dispensing procedure requires that the injection button  90  is permanently depressed in distal direction against the action of the injection spring  91  as well as against the action of the spring elements  57 ,  58 . A premature release of the injection button  90  will sequentially lead to a proximally-directed displacement of the drive sleeve  50  into its dose setting position, in which the ratchet member  52  re-engages with the toothed ring  120 , thereby rotatably interlocking the drive sleeve  50  to the housing  30 . 
         [0225]    At the same time also a rotative engagement of the dose setting sleeve  40  and the drive sleeve  50  is re-established. Finally also the dose setting clutch  110  will return into its initial configuration as shown in  FIG. 23 . This may either occur under the action of an additional spring element  170  as shown in  FIGS. 11 and 12 . Alternatively, a proximally-directed displacement of the dose setting clutch  110  may be governed by the mutual engagement of the latch members  92  and  114  of the injection button  90  and the dose setting clutch  110 , respectively. 
         [0226]    In order to provide an end of content mechanism the dose setting sleeve  40  comprises a threaded portion  44  at its outer circumference. Said threaded portion  44  is engaged with a last dose limiting member  160  comprising a corresponding thread on its inside facing portion. The last dose limiting member  160  is arc-shaped as illustrated in  FIG. 8  and it is radially sandwiched between the outer circumference of the threaded portion  44  of the dose setting sleeve  40  and an inside facing sidewall portion of the housing  30 . 
         [0227]    The last dose limiting member  160  is threadedly engaged with the dose setting sleeve  40  but is allowed to axially slide along the housing  30 . The last dose limiting member  160  is further rotatably locked to the housing  30 . For this purpose, the housing comprises axially and radially outwardly extending recesses  39  on its inside facing side wall portion to receive correspondingly shaped radially outwardly extending protrusions  162  of the last dose limiting member  160 . 
         [0228]    During a dose setting procedure the dose setting sleeve  40  rotates relative to the housing which leads to a respective axial displacement of the last dose limiting member  160 . Accordingly, with consecutive dose setting procedures the last dose limiting member  160  travels step-by-step along the recesses  39  of the housing  30 . Since the dose setting sleeve  40  is exclusively rotated during dose incrementing or dose decrementing, the axial position of the last dose limiting member  160  relative to the dose setting sleeve  40  is directly indicative of the total amount of doses set and dispensed by the drive mechanism  3  during consecutive dose setting and dose dispensing procedures. 
         [0229]    The threaded portion  44  of the dose setting sleeve  40  further comprises a distally located radial stop  42  which is adapted to engage with a stop face  166  of the last dose limiting member  160 . In a final assembly configuration, the axially and radially extending stop face  166  is brought in abutment with the radial stop  42 , thereby representing a zero dose stop configuration. This way, a dose decrementing rotation of the dose setting sleeve  40  can be effectively prevented. 
         [0230]    The opposite circumferential end of the last dose limiting member  160  provides a comparable stop face  164  which his adapted to engage with a radial stop  43  provided at the opposite end of the threaded portion  44  of the dose setting sleeve  40 . This stop configuration serves as an end of content stop and prevents a further rotation of the dose setting sleeve when the accumulated amount of medicament already set would otherwise exceed the amount of medicament left in the cartridge  14 . 
         [0231]    The last dose limiting configuration as for instance illustrated in  FIG. 21  may correspond to a maximum size of a cartridge  14  of e.g. 450 I.U. 
         [0232]    In other embodiments, also an inside facing portion of the housing  30  could provide a corresponding stop to engage with the last dose limiting member  160 . 
         [0233]    In a rather similar way also the drive sleeve  50  comprises a threaded portion  54  extending between a distal flange portion  53  and a proximal flange portion  59  as illustrated in  FIGS. 14 and 18 . The threaded portion  54  is threadedly engaged with a single dose limiting member  150 , which is also of arc-shape and which comprises radially outwardly extending protrusions  152  to engage with correspondingly shaped radially outwardly and axially extending recesses or grooves  33  of the housing  30 , as illustrated in  FIG. 7 . 
         [0234]    This way, a rotation of the drive sleeve  50  in the dose setting direction  4  comes along with an axial displacement of the single dose limiting member  150  along the threaded portion  54  of the drive sleeve  50 . In a zero dose configuration as illustrated in detail in  FIGS. 17 and 19  a stop face  154  and a circumferential end of the single dose limiting member  150  is in abutment with a radially extending stop  61  provided on the distal flange  53 . 
         [0235]    Since the single dose limiting member  150  is threadedly engaged with the drive sleeve  50  and since the single dose limiting member  150  is rotatably locked to the housing  30 , the engagement of the stop face  154  with the radial stop  61  inhibits a rotation of the drive sleeve  50  in the dose dispensing direction  5 . In the opposite circumferential direction, the arc-shaped single dose limiting member  150  comprises another stop face  158  which is adapted to engage with another radial stop  60  provided in or on the outer threaded portion  54  of the drive sleeve  60 . 
         [0236]    The radial stop  60  is provided near a proximal flange portion  59  of the drive sleeve  50  as shown in  FIG. 18 . The mutual engagement of the stop face  158  with the radial stop  60  serves to limit a maximum dose to be set during a dose setting procedure. Since the single dose limiting member  150  is rotatably locked to the housing  30 , the drive sleeve  50  is hindered to rotate any further when the radial stop  60  engages with the stop face  158 . The configuration as illustrated in  FIG. 18  may therefore correspond to a maximum single dose size of e.g. 120 I.U. 
         [0237]    Since the drive sleeve  50  rotates in dose setting direction  4  during dose setting and in a dose dispensing direction  5  during dose correction or dose decrementing as well as during dose dispensing, the single dose limiting member  150  will always return into the zero dose configuration at the end of a dose dispensing procedure. In order to generate an audible signal, that the end of a dose injection has reached, the single dose limiting member  150  is further equipped with a circumferentially extending or tangentially extending clicking member  156 , which is resiliently deformable in axial direction. 
         [0238]    The clicking member  156  provides a kind of a releasable latch which engages with a protrusion  63  axially extending from the radial stop  61  of the drive sleeve. The protrusion  63  and the clicking member  156  are shaped and configured such, that an audible click sound is generated when the zero dose configuration as shown in  FIGS. 17 and 19  is reached. 
         [0239]    The zero dose stop, hence the radial stop  42  of the drive sleeve  40  may be implemented only optionally since the single dose limiting member  150  provides a zero-dose stop functionality. 
         [0240]    Generally, with all threaded engagements of the last dose limiting member  160  and the single dose limiting member  150  with the dose setting sleeve  40  or with the drive sleeve  50  the last thread of threaded sleeves  40 ,  50  in close or direct vicinity of a respective stop  42 ,  43  or  60 ,  61  could feature an increased lead in order to allow for an increase of the size of the radial extension of the respective stops. In this way the stop  42 ,  43 ,  60 ,  61  would be provided with an increased mechanical stability thus allowing to improve the performance of the respective stop. 
         [0241]    Alternative to the radially extending stops  42 ,  43 ,  60 ,  61  it is generally conceivable to implement axially acting stops with respective radially and circumferentially extending stop faces. But since axial stops  42 ,  43 ,  60 ,  61  featuring radially and axially extending stop faces, exhibit a well-defined and more precise stopping behaviour when engaging with respective stop faces of the single- and/or last dose limiting members  150 ,  160  use of radially extending stops  42 ,  43 ,  60 ,  61  may be of advantage. 
       LIST OF REFERENCE NUMERALS 
       [0000]    
       
           1  distal direction 
           2  proximal direction 
           3  drive mechanism 
           4  dose setting direction 
           5  dose dispensing direction 
           10  drug delivery device 
           12  cartridge holder 
           14  cartridge 
           16  piston 
           18  barrel 
           20  needle assembly 
           24  needle cap 
           26  protective cap 
           30  housing 
           31  threaded support 
           32  closure 
           33  recess 
           34  dose indicating window 
           35  ledge 
           36  axial stop 
           37  feedback element 
           38  flange portion 
           39  recess 
           40  dose setting sleeve 
           41  protrusion 
           42  radial stop 
           43  radial stop 
           44  threaded portion 
           45  crown wheel portion 
           50  drive sleeve 
           51  gear wheel 
           52  ratchet member 
           53  flange portion 
           54  threaded portion 
           55  crown wheel portion 
           56  inner sleeve portion 
           57  drive sleeve spring element 
           58  dispensing sleeve spring element 
           59  flange portion 
           60  radial stop 
           61  radial stop 
           63  protrusion 
           64  flange portion 
           65  pin 
           67  clicking member 
           68  spring 
           70  dispensing sleeve 
           71  proximal face 
           72  recess 
           73  extension 
           75  punched structure 
           80  receptacle 
           82  piston rod 
           84  protrusion 
           84  thread 
           86  pressure foot 
           90  injection button 
           91  injection spring 
           92  latch element 
           93  sidewall 
           94  ledge 
           100  dose dial button 
           102  latch element 
           104  toothed section 
           106  inside wall portion 
           110  dose setting clutch 
           112  tooth 
           114  latch element 
           116  recess 
           120  toothed ring 
           122  toothed inner surface 
           130  dose indicating mechanism 
           131  branch 
           132  base 
           133  branch 
           134  support section 
           136  bearing 
           138  bearing 
           140  spool 
           142  spool 
           144  spool spring 
           145  gear wheel 
           146  dose indicating tape 
           148  number 
           150  single dose limiting member 
           152  protrusion 
           154  stop face 
           156  clicking member 
           158  stop face 
           160  last dose limiting member 
           162  protrusion 
           164  stop face 
           166  stop face 
           170  spring element