TEPZZ 6 7¥8_B_T

(19)

(11) EP 2 627 381 B1

(12) EUROPEAN PATENT SPECIFICATION

(45) Date of publication and mention (51) Int Cl.:

of the grant of the patent: A61M 5/315 (2006.01)
28.11.2018 Bulletin 2018/48
(86) International application number:
(21) Application number: 11770734.9 PCT/EP2011/067680

(22) Date of filing: 11.10.2011 (87) International publication number:

WO 2012/049143 (19.04.2012 Gazette 2012/16)

(54) DOSE SETTING MECHANISM

DOSISEINSTELLUNGSMECHANISMUS
MÉCANISME DE RÉGLAGE DE DOSE

(84) Designated Contracting States: (72) Inventors:

AL AT BE BG CH CY CZ DE DK EE ES FI FR GB • BUTLER, Joseph
GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Clifton
PL PT RO RS SE SI SK SM TR Rugby Warwickshire CV23 0DL (GB)
• PLUMPTRE, David
(30) Priority: 31.05.2011 EP 11168193 Droitwich Spa Worcestershire WR9 7RQ (GB)
13.10.2010 US 392756 P
(74) Representative: Keil & Schaafhausen
(43) Date of publication of application: Patent- und Rechtsanwälte PartGmbB
21.08.2013 Bulletin 2013/34 Friedrichstraße 2-6
60323 Frankfurt am Main (DE)
(73) Proprietor: Sanofi-Aventis Deutschland GmbH
65929 Frankfurt am Main (DE) (56) References cited:
WO-A1-2004/028598 WO-A1-2006/089768
WO-A1-2010/139691 US-A1- 2009 275 916
EP 2 627 381 B1

Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent
Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the
Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been
paid. (Art. 99(1) European Patent Convention).

Printed by Jouve, 75001 PARIS (FR)

 EP 2 627 381 B1

Description

[0001] The present disclosure is generally directed to dose setting mechanisms for drug delivery devices that control
minimum and/or maximum possible dose settings. More particularly, the present disclosure is generally directed to drug
5 delivery devices, such as pen type drug delivery devices where therapy demands that a patient receive at least a certain
minimum dose and not exceed a certain maximum dose of a particular medicament. Such devices provide for self-
administration of medicinal product from a multi-dose cartridge and contain dose limiting mechanisms for setting minimum
and/or maximum doses. The present disclosure may find application in both disposable and reusable type drug delivery
devices. However, aspects of the invention may be equally applicable in other scenarios as well, within the scope defined
10 by the appended claims.
[0002] Document US 2009/0275916 A1 discloses a dose setting mechanism for a drug delivery device according to
the preamble of claim 1. Self administered injectable medicaments are often delivered using a variable-dose injection
device. Such a device is known from WO 2004/078239 A1. Prior to the injection the user selects the dose that they
require according to their prescribed dose and/or their current or expected future physical condition. A typical example
15 would be an insulin delivery device for diabetics where a patient’s dose is determined according to their prescribed dose
and their expected food intake and activity level. Typically such devices allow the user to select any dose from 1 unit up
to the maximum units that the device can deliver, typically 60 units or 80 units for a manual device, such as a pen-type
or syringe injection device.
[0003] The drug delivery device of WO 2004/078239 A1 comprises a housing for receiving a dose setting mechanism,
20 a cartridge, a dose dial sleeve with an attached dose dial grip, a clicker, a drive sleeve, a clutch for coupling and decoupling
the dose dial sleeve and the drive sleeve, a rotatable piston rod and a button which is pressed for injecting a set dose.
The full description of the pen-type injection devices is disclosed in WO 2004/078239 A1.
To dial a dose a user rotates the dose dial grip. With the clicker and clutch means engaged, the drive sleeve, the clicker,
the clutch means and the dose dial sleeve rotate with the dose dial grip relative to the housing and relative to the piston
25 rod. Audible and tactile feedback of the dose being dialed is provided by the clicker and the clutch means. Torque is
transmitted through saw teeth between the clicker and the clutch means.
A helical groove on the dose dial sleeve and a helical groove in the drive sleeve have the same lead. This allows the
dose dial sleeve to extend from the housing and the drive sleeve to climb the piston rod at the same rate. At the limit of
travel, a radial stop on the dose dial sleeve engages a stop provided on the housing to prevent further movement.
30 Rotation of the piston rod is prevented due to the opposing directions of overhauled and driven threads on the piston rod.
Should a user inadvertently dial beyond the desired dosage, the pen-type injector allows the dosage to be dialed down
without dispense of medicinal product from the cartridge. The dose dial grip is counter rotated. This causes the system
to act in reverse. The torque transmitted through the clutch means causes the saw teeth to ride over one another to
create the clicks corresponding to dialed dose reduction. Preferably the saw teeth are so disposed that the circumferential
35 extent of each saw tooth corresponds to a unit dose.
[0004] When the desired dose has been dialed, the user may then dispense this dose by depressing the button. This
displaces the clutch means axially with respect to the dose dial sleeve causing dog teeth of the clutch means to disengage.
However the clutch means remains keyed in rotation to the drive sleeve. The dose dial sleeve and associated dose dial
grip are now free to rotate. The axial movement deforms a flexible part of the clicker to ensure the saw teeth cannot be
40 overhauled during dispense. This prevents the drive sleeve from rotating with respect to the housing though it is still free
to move axially with respect thereto. This deformation is subsequently used to urge the clicker and the clutch back along
the drive sleeve to restore the connection between the clutch and the dose dial sleeve when pressure is removed from
the button. The longitudinal axial movement of the drive sleeve causes the threaded piston rod to rotate through a
threaded opening in a housing insert, thereby to advance the piston in the cartridge.
45 [0005] In other words, the drive sleeve moves longitudinally, i.e. only in the axial direction, during an injection. Because
the drive sleeve and the piston rod are engaged via corresponding threads on the outer surface of the piston rod and
an internal face of the drive sleeve, the longitudinal movement of the drive sleeve causes the piston rod to rotate. The
housing insert with the threaded opening which is engaged with the piston rod via corresponding threads is fixed within
the housing, i.e. prevented from rotation. Thus, the rotating piston rod is screwed through the threaded opening in the
50 housing insert, i.e. the piston rod performs a combined rotational and longitudinal movement along a helical path defined
by the corresponding threads of the threaded opening and the piston rod.
[0006] Once the dialed dose has been dispensed, the dose dial sleeve is prevented from further rotation by contact
of a plurality of members extending from the dose dial grip with a corresponding plurality of stops formed in the housing,
thus determining a zero dose position.
55 [0007] Such pen type drug delivery devices have been designed and developed to perform regular injections by
persons without formal medical training. This is increasingly common among patients having diabetes where self-treat-
ment enables such patients to conduct effective management of their disease. Because the patient, and not the health
care worker, may be using such a drug delivery device, one requirement is that the device should be robust in construction.

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The drug delivery device must also be easy to use both in terms of the drug delivery device manipulation and understanding
of the device’s operation. This is especially true for diabetics who are required to inject themselves repeatedly with insulin
solution and the volume of insulin to be injected may vary from patient to patient and even from injection to injection.
For at least this reason, certain diabetics may require drug delivery devices that allow the patient to inject successive
5 measured dosages of the same or perhaps different preset volumes of insulin solution accurately and with minimum
dexterity challenges. This presents a further design challenge since, in the case of certain diabetics, users may have
impaired vision and/or may be physically infirm with limited dexterity.
[0008] In addition to insulin, other medicaments require a minimum dose to be delivered before they are therapeutically
effective. A variable-dose device that allows the patient to deliver doses below the therapeutically effective minimum
10 dose creates the possibility that the user may deliver the ineffective doses either by an error of dose calculation or by
mistakenly selecting the incorrect dose. Likewise, some medicaments require that a maximum dose is not to be exceeded.
This may be for safety reasons such as increased risk or severity of side-effects or excessive or unwanted actions of
the medicament. Current variable-dose delivery devices typically have a maximum dose that is limited by the maximum
dose that the delivery mechanism can provide, however, this does not necessarily relate to the maximum advised or
15 prescribed dose of the medicament.
[0009] The present invention has at least two applications. First, is the delivery of a single active medicament which
must be a variable dose within a defined dose window, i.e. the dose must be more than a certain minimum dose and
must not exceed a certain maximum dose. The second application relates to the delivery of a combined formulation of
active medicaments where at least one of the medicaments is preferably delivered as a variable dose and at least one
20 other medicament is preferably delivered as a fixed dose, and where this fixed dose can safely be allowed to vary within
a defined dose window, for example by 610% of the nominal fixed dose.
[0010] The minimum and/or maximum dose limited delivery device in accordance with the present invention could be
used for a medicament that requires a minimum dose to be delivered before it becomes therapeutically effective, but
where a degree of dose adjustment may be required. This dose adjustment may be required for a number of reasons,
25 including tailoring a dose to a patient’s body weight or the severity of their medical condition. The minimum and maximum
dose limited device (min/max device) may also be used instead of a fully variable (i.e., 0 to max dose) device in order
to reduce the possibility for dosing errors by the patient. Using the min/max device rather than a variable dose pen
reduces the risk that a patient might accidentally deliver a dose outside the defined dose window, i.e., either too high or
too low.
30 [0011] One example of the utility of the min/max device is where a parent could give the min/max delivery device to
a child for the child to self-administer and the parent would know that the minimum and maximum levels of the min/max
device limited the possible severity of any overdose or under dose. Another example of where such a device might be
applicable is for patients who take long acting insulin. Typically a variable dose pen is required when a patient is "titrating"
their dose to reach their target blood glucose level. However, once the target blood glucose level has been achieved
35 the dose of long acting insulin typically remains more or less constant over relatively long periods of time. During this
period, where their insulin dose is either constant or changes by only a few units on a day-to-day basis, the patient’s
long acting insulin needs could be effectively met by the minimum and maximum dose limited delivery device.
[0012] Table 1 (provided below) shows an example family of delivery devices, "Pen 1" through "Pen 4", which could
be used in place of a single 1-80 unit variable dose device. Each of the Pens 1 - 4 are designed and manufactured
40 around the same basic mechanism, but each pen contains either additional or alternative components which are used
to set a different minimum and maximum dose. Patients would be prescribed a particular Pen according to their stable
long acting insulin dose. For example, according to Table 1 a patient prescribed 30 units per day of long acting insulin
would be prescribed Pen 2, which has a minimum dose of 18 units and a maximum dose of 42 units, respectively. Any
number of mechanical components can be used in such a pen design to ensure these predetermined min/max doses,
45 including axial and/or rotational stops, detents, clutches, compressible fingers, or the like components.
[0013] The insulin dose of diabetic patients may change gradually over time. Therefore there may be a small amount
of dose range overlap between Pens to allow for a smooth transition between Pens as the dose increases. For example,
according to Table 1 a patient prescribed 40 units per day of long acting insulin would be given Pen 2 if they expected
their dose to decrease over time or Pen 3 if they expected their dose to increase over time. The number of pens in the
50 "family" and the selected dose ranges shown in Table 1 are illustrative only. By using the min/max device of the present
invention a mistake when selecting the dose is limited to within the pen’s operating window. Dialing a dose above or
delivering a dose below the pen’s dose range would not be possible and this would alert the patient to their error.
[0014] The min/max device may also be applicable for the delivery of other medicines, particularly where there is a
risk of confusion with similar devices that may lead to dose errors or drug / device mix-ups. One such example would
55 be rapid acting insulin and long acting insulin. Both of these insulins are measured in "units" however the same number
of units of each insulin type will have a very different effect and a patient will be prescribed different doses of each drug
to be taken at different times throughout the day. A mix up of long acting and rapid acting insulin can cause hypoglycemia
and is potentially fatal. Both types of insulin may be delivered by injection pen devices. Patients perform their injections

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on such a routine basis that an "automatic pilot" effect can occur where patients have been known to mix up their insulin
pens, even though the pens are of different design, color, shape and carry different labels.
[0015] The presently proposed min/max device may help to prevent this mix up occurring. For example, assume both
rapid acting and long acting insulins were each provided with a family of min/max devices according to Table 1. A patient
5 is prescribed 50 units per day of long acting insulin (which would require long acting Pen 3) and 15 units of rapid acting
insulin with meals (which would require Pen 1). The most dangerous mix up would occur if the patient mistakenly delivered
50 units of rapid acting insulin rather than long acting insulin. If the patient attempted to do this with the min/max devices
then the patient would pick up the rapid insulin device (Pen 1) and find that they could not dial beyond 22 units. This
should alert them to the fact that this is not the correct insulin pen, and therefore the incorrect insulin type, and prevent
10 the incorrect insulin being delivered. The min/max concepts may be applied equally to both disposable devices and
reusable devices.
[0016] Certain medicines also require the user to perform a "priming" dose to confirm the correct operation of the
delivery device and needle. This is usually accomplished by delivering an "air-shot" of 2 units and then checking that
the medicine can be seen coming out of the needle. The min/max concept shown in Table 1 would not permit this. If
15 priming functionality is required a second permissible "dose window", for example ranging from 1-2 units, may also be
implemented within each pen mechanism. An example of how this could be applied is shown in Table 2. Although both
Tables 1 and 2 show only even numbers of units this is done only for clarity and the device may be configured to deliver
odd and even units or potential © units.
[0017] As mentioned, the presently disclosed devices may also be useful in therapies where the delivery of a combined
20 formulation of active medicaments is needed, where at least one of the medicaments is preferably delivered as a variable
dose and at least one other medicament is preferably delivered as a fixed dose. If a patient requires a combination of
medicines then there is an advantage if those medicines can be provided as a single formulation (i.e. both drugs are
mixed together in predefined proportions and supplied in one primary pack) for delivery by a single injection device in
one injection through a single needle. However, if one of the drugs requires the delivery of a user-selectable variable
25 dose and the second drug requires a dose above a minimum dose to be therapeutically effective and must not exceed
a given maximum dose, then it is beneficial for the drug delivery device to be configured such that it is prevented from
delivering doses that are outside of this range.
[0018] For example, a patient may be prescribed a combination therapy of long acting insulin (typically delivered in
variable dose devices) and GLP-1 (typically delivered as a fixed dose). GLP-1 is a glucagon-like peptide-1, which is
30 derived from the transcription product of the proglucagon gene and is found in the body where it is secreted by the
intestinal L cell as a gut hormone. GLP-1 possesses several physiological properties that make it (and its analogs) a
subject of intensive investigation as a potential treatment of diabetes mellitus. In order to avoid the patient having to
perform two injections the two medicines are pre-mixed into a single formulation. Since both medicaments are pre-mixed
in a fixed ratio it is not possible to vary the long acting insulin dose without also varying the GLP-1 dose. However, it
35 may be acceptable for the GLP-1 dose to vary within a given tolerance, for example 610%, around a fixed nominal
dose. It is therefore possible, using a family of min/max limited devices to provide a family of pre-mix devices which
between them will allow delivery of a variable long acting insulin dose and a GLP-1 dose that always falls within 610%
of a given "fixed" dose.
[0019] Table 3, for example, shows a family of 6 min/max pen-type injection devices that allow the delivery of any long
40 acting insulin dose from 22-76 units along with a GLP-1 dose that is "fixed" to 20mg 610%. Each Pen within the family
would have different minimum and maximum dose thresholds and would be provided with a primary pack or cartridge
of medicament filled with the appropriate mix ratio of the two medicines. The family of pen devices could be provided
as disposable mechanical devices, prefilled with the appropriate mix ratio cartridge of medicament. Alternatively, the
family of devices could be provided as reusable mechanical devices. In the latter case, the devices would be preferably
45 dedicated to a particular mix ratio cartridge, i.e. only the correct mix ratio cartridge can be loaded into each pen family
member.
[0020] A third alternative is to provide the "family" of pen devices via a single electronic device that can be programmed
with the minimum and maximum dose functionality. Preferably, the min/max electronic device would be loaded with a
coded cartridge that would automatically upon being loaded into the device communicate to the device what the required
50 minimum and maximum thresholds should be for that particular cartridge and mix ratio.
[0021] One specific means of achieving a minimum settable dose on a variable dose, drug delivery device, such as
a pen-type device, is to include a mechanism that prevents dosing of the device until a predetermined minimum dose
has been reached. A maximum dose mechanism can also be used with a minimum dose mechanism.
[0022] It is an object of the invention to provide a device that reduces or eliminates the risk that a user of an injection
55 device will set and administer a dose below a preselected minimum effective dose of a particular medicament.
[0023] This object is solved with a dose setting mechanism as defined in claim 1.
[0024] According to one possible exemplary embodiment of the present invention a dose setting mechanism for a
drug delivery device is provided comprising a minimum dose limiting function by means of a clutch ring that is rotationally

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fixed relative to a housing when a dose less than a minimum allowable dose is selected, but not when a dose greater
than the minimum allowable dose is selected. The dose setting mechanism includes a drug delivery device housing and
a dose dial component positioned in the housing and rotatable during a dose setting step. The dose setting mechanism
includes also a drive sleeve positioned within the dose dial component and a spindle positioned within the drive sleeve.
5 A clutch is positioned between the dose dial component and the drive sleeve. As mentioned above, a clutch ring is
rotationally fixed relative to the housing when a dose less than the minimum allowable dose is selected. When the dose
dial component is rotated to select a dose less than a minimum dose, the clutch ring prevents the drive sleeve from
rotating while the spindle disengages from the drive sleeve, thereby preventing the selected dose from being administered.
In known examples of pen-type devices that can incorporate the present invention, e.g. the device described in WO
10 2004/078239, the drive sleeve rotates together with the number sleeve during dose setting, while the drive sleeve is
pushed axially without being able to rotate during dose administration. During dose setting and during dose administration,
the drive sleeve is coupled to the spindle via engaging threads on the outer surface of the spindle and on the inner
surface of the drive sleeve, respectively. In other words, one of the main principles of the present invention is to prevent
(by means of the clutch ring) rotation of the drive sleeve during dose setting as long as the set dose is below a predefined
15 threshold. Preventing rotation of the drive sleeve during this part of dose setting leads to retracting the drive sleeve in
the proximal direction together with the dose dial sleeve which follows a helical path on the thread of the housing. As
the spindle is not allowed to be retracted together with the drive sleeve, the threaded engagement between the spindle
and the drive sleeve disengages such that the drive sleeve and the spindle are allowed to slide relative to each other in
an axial direction. Hence, if a user attempts to administer a set dose below the threshold, the drive sleeve slides (overrides)
20 relative to the spindle in the axial direction without dispensing medicament.
[0025] It is preferred that, when the dose dial component (e.g. a number sleeve) is rotated to select the dose less than
the minimum dose, the clutch ring prevents the clutch from rotating. As the clutch is rotationally coupled to the drive
sleeve, this prevents the drive sleeve from rotating as mentioned above.
[0026] On the other hand, when the dose dial component is rotated further to select a dose greater than the minimum
25 dose, the clutch ring allows the drive sleeve and the clutch to rotate together during subsequent dose setting such that
a dose greater than the minimum dose can be selected and dispensed.
[0027] There are different ways to allow the spindle and the drive sleeve to disengage during dose setting prior to
setting a dose above a predefined threshold. According to a preferred embodiment of the invention, the spindle may
comprise at least one flexible member, which is configured to engage a thread of the drive sleeve. In other words, the
30 flexible member, e.g. a flexible finger, allows engagement and disengagement of the spindle and the drive sleeve. The
at least one flexible member engages an inner thread of the drive sleeve after a dose has been selected that is greater
than the minimum dose.
[0028] Preferably, the inner thread of the drive sleeve comprises a drive sleeve pitch wherein the drive sleeve pitch
is equal to an axial distance that must be dialled by the dose dial component to reach the minimum dose. This allows
35 the thread between the spindle and the drive sleeve to reengage after the minimum dose has been set.
[0029] The clutch ring may be splined to the housing. In more detail, it is preferred if the clutch ring is splined to the
housing only when the dose dial component is rotated to select a dose that is less than the minimum dose. Further, the
clutch ring is no longer splined to the housing when the dose dial component is rotated further to select a dose that is
greater than the minimum dose.
40 [0030] The above mentioned function of the clutch ring may be achieved by providing an interface defined between
a first portion of the clutch ring and a first portion of the dose dial component, which interface may define a clicker. This
clicker may comprise an audible clicker. Further, the clutch and the clutch ring may comprise a unitary clutch mechanism.
[0031] As mentioned above, the clutch ring may be a separate component which may rotate relative to the clutch in
a first state and which may be releasably coupled to the clutch in a second state (condition). As an alternative, the clutch
45 ring may be formed as an integral part of the clutch or the clutch ring may be permanently coupled to the clutch. According
to a further embodiment of the present invention, the clutch ring may be rotationally locked to the drive sleeve, e.g. via
respective splines.
[0032] To allow decoupling of the spindle from the drive sleeve, it is preferred if the drive sleeve is axially locked to
the number sleeve. Thus, the drive sleeve will move axially together with the dose dial sleeve (number sleeve) during
50 dose dialing.
[0033] A protrusion of the clutch ring may be rotationally fixed relative to a keying feature of the housing at least when
a dose is selected that is less than the minimum dose. Preferably, the housing comprises a plurality of keying features
and/or wherein the clutch ring comprises a plurality of protrusions. This facilitates reengagement of the clutch ring and
the housing irrespective of the angular position of the clutch ring relative to the housing.
55 [0034] As mentioned above, the dose setting mechanism may comprise a resettable dose setting mechanism. It is
preferred to couple the dose setting mechanism to a cartridge holder containing a cartridge containing a medicament.
For a resettable mechanism, the dose setting mechanism may be removably coupled to the cartridge holder.
[0035] In an exemplary min/max device, the dose count numbers (which can e.g. be printed on the dose dial component)

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below the minimum dose may be colored a different color such as red to differentiate that the dose dialled is less than
the normal minimum dose. These as well as other advantages of various aspects of our proposed drug delivery device
will become apparent to those of ordinary skill in the art by reading the following detailed description, with appropriate
reference to the accompanying drawings.
5 [0036] Exemplary embodiments are described herein with reference to the drawings, in which:

Figure 1A illustrates an example design of a pen-type drug delivery device;

Figure 1B illustrates a cross-sectional view of a dose setting mechanism of the pen-type drug delivery device of
10 Figure 1A;

Figure 2A illustrates a perspective view of given components of the dose setting mechanism shown in Figure 1B;

Figure 2B illustrates a perspective view of given components of the dose setting mechanism in an initial position
15 before a dose is dialled;

Figure 2C illustrates a perspective view of given components of the dose setting mechanism in a certain position
immediately before a dose less than a minimum dose is dialled;

20 Figure 2D illustrates a perspective view of given components of the dose setting mechanism in a certain position
immediately after a dose greater than a minimum dose is dialled;

Figure 3 illustrates a perspective view of given components of the dose setting mechanism shown in Figure 1B;

25 Figure 4 illustrates a perspective view of given components of an example dose setting mechanism; and

Figure 5 illustrates a perspective view of given components of the example dose setting mechanism shown in Figure 4.

[0037] Referring to Figure 1A, there is shown a drug delivery device 100 in accordance with an exemplary pen-type
30 design arrangement. The drug delivery device 100 comprises a housing having a first cartridge retaining part 102, and
a dose setting mechanism 104. The drug delivery device may be a resettable drug delivery device (i.e., a reusable
device) or alternatively a non-resettable drug delivery device (i.e., a non-reusable device). A first end of the cartridge
retaining part 102 and a second end of the dose setting mechanism 104 are secured together by connecting features.
For non-resettable devices, these connecting features would be permanent and non-reversible. For resettable devices,
35 these connecting features would be releasable.
[0038] In this illustrated arrangement, the cartridge retaining part 102 is secured within the second end of the dose
setting mechanism 104. A removable cap (not shown) is releasably retained over a second end or distal end of a cartridge
retaining part or cartridge housing. The dose setting mechanism 104 comprises a dose dial grip 112 and a window or
lens 114. A dose scale arrangement is viewable through the window or lens 114. To set a dose of medication contained
40 within the drug delivery device 100, a user rotates the dose dial grip 112 such that a dialled dose will become viewable
in the window or lens 114 by way of the dose scale arrangement.
[0039] Figure 1A illustrates the medical delivery device 100 with the cover cap removed from a distal end 118 of the
medical delivery device 100. This removal exposes the cartridge housing 106. Preferably, a cartridge (not shown) from
which a number of doses of a medicinal product may be dispensed, is provided in the cartridge housing 106. Preferably,
45 the cartridge contains a type of medicament that can be administered relatively often, such as once or more times a
day. One such medicament is either long acting or short acting insulin or an insulin analog; however, any medicament
or combination of medicaments is possible. The cartridge comprises a bung or stopper that is retained near a second
end or a proximal end of the cartridge. The medical delivery device also comprises a drive sleeve and a spindle (not
illustrated in Figure 1A, but is illustrated as items 124 and 126, respectively, in Figure 1B).
50 [0040] The cartridge housing 106 has a distal end and a proximal end. Preferably, the distal end of the cartridge
housing 106 comprises a hub 108 for attaching a removable needle assembly. However, other needle assembly con-
nection mechanisms could also be used. If the drug delivery device 100 comprises a resettable device, the cartridge
proximal end is removably connected to the dose setting mechanism 104. In one preferred embodiment, cartridge
housing proximal end is removably connected to the dose setting mechanism 104 via a bayonet connection. However,
55 as those of ordinary skill in the art will recognize, other types of removable connection methods such as threads, partial
threads, ramps and detents, snap locks, snap fits, and luer locks may also be used.
[0041] As previously mentioned, the dose setting mechanism 104 of the drug delivery device illustrated in Figure 1A
may be utilized as a reusable drug delivery device. (i.e., a drug delivery device that can be reset) Where the drug delivery

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 EP 2 627 381 B1

device 100 comprises a reusable drug delivery device, the cartridge is removable from the cartridge housing 106. The
cartridge may be removed from the device 100 without destroying the device 100 by merely having the user disconnect
the dose setting mechanism 104 from the cartridge housing 106.
[0042] In use, once the cap is removed, a user can attach a suitable needle assembly to the hub 108 provided at the
5 distal end of the cartridge housing 106. Such needle assembly may be, for example, screwed onto a distal end of the
housing 106 or alternatively may be snapped onto this distal end. After use, the replaceable cap may be used to recover
the cartridge housing 106. Preferably, the outer dimensions of the replaceable cap are similar or identical to the outer
dimensions of the dose setting mechanism 104 so as to provide an impression of a unitary whole when the replaceable
cap is in position covering the cartridge housing 106 when the device is not in use.
10 [0043] A first exemplary dose setting mechanism in accordance with our disclosure is described with reference to
Figure 1B through Figure 3. Figure 1B illustrates a cross-sectional view of drug delivery device 100, and in particular
shows a detailed cross-sectional view of a first dose setting mechanism 104. Dose setting mechanism 104 includes a
drug delivery device housing 120 and a dose dial component 122 positioned in housing 120. The dose dial component
122 is rotatable during a dosing step. In an example, the dose dial component 122 comprises a number sleeve. The
15 dose setting mechanism 104 also includes a drive sleeve 124 positioned in the dose dial component 122 and a spindle
(i.e., lead screw) 126 positioned within the drive sleeve 124. The dose setting mechanism 104 also includes a clutch
128 positioned between the dose dial component 122 and the drive sleeve 124. Further, the dose setting mechanism
104 includes a clutch ring 130. According to a first embodiment depicted in Figures 1B to 3, the clutch ring 130 is a
separate component which is generally free to be rotated relative to the dose dial sleeve 122 and relative to the clutch
20 128 but which may be coupled to these components as will be explained below in detail. Further, the clutch ring 130 is
generally free to be displaced axially relative to the dose dial sleeve 122 and relative to the clutch 128, at least for a
limited distance.
[0044] In general, the dose setting mechanism 104 operates to ensure that a user dials a dose greater than a prede-
termined minimum dose before a user can administer a medicament dose. In order to ensure this, the clutch ring 130
25 is rotationally fixed to the housing 120 when a dose less than the minimum dose is selected. As such, when the dose
dial component 122 is rotated to select a dose less than a minimum dose, the clutch ring 130 prevents the drive sleeve
124 from rotating and the spindle disengages from the drive sleeve, thereby preventing the selected dose from being
administered.
[0045] The clutch ring 130 is in engagement with the number sleeve 122, clutch 128, and a biasing element, such as
30 metal spring 132. The clutch ring 130 may include one or more protrusions that key the clutch ring to the drug delivery
device housing 120 when a dose less than the minimum dose is selected. That is, the clutch ring 130 remains keyed to
the device housing 120 until a user has dialled at least a minimum dose. In one example, the clutch ring 130 is splined
to the housing 120. For example, Figure 2B illustrates a perspective view of given components of the dose setting
mechanism 104 in an original or initial position before a dose is dialled. This original position is a position where the
35 dose dial mechanism 104 has yet to dial a dose. As can be seen from Figures 2B and 2C, the clutch ring 130 comprises
a protrusion 131 along an outer surface 133 of the clutch ring 130. Although only one protrusion is illustrated, those of
skill in the art will recognize that a plurality of such protrusions may also be provided.
[0046] In addition, an inner surface 121 of the housing 120 comprises a plurality of grooves or keying features, such
as keying feature 123. As illustrated in this initial position, the clutch ring protrusion 131 resides in one of the keying
40 features 123 and resides at a most distal end of the keying feature 123.
[0047] In an alternative arrangement, the clutch ring 130 may be keyed to the housing 120 in other ways. For instance,
the clutch ring 130 may be splined to a fixed member (e.g., an insert) that is attached to the housing 120.
[0048] The clutch 128 is rotationally locked to the drive sleeve 124, and the clutch 128 is capable of limited axial travel
relative to the drive sleeve 124. Further, the drive sleeve 124 is axially locked to the number sleeve 122 but is not directly
45 rotationally locked. Under certain dose dialling conditions, the clutch ring 130 may rotationally lock the clutch 128 -- and
therefore also the drive sleeve 124 -- to the number sleeve 122. The metal spring 132 is keyed to the housing 120 at all
times, and therefore cannot rotate.
[0049] The spindle 126 comprises at least one flexible arm, such as flexible arms 134a-b (see figure 1B). These flexible
arms 134 a, b on the spindle 126 may be designed such that the drive sleeve 124 can travel in a proximal direction 136
50 without drive sleeve 124 rotating during a given length of travel. When the drive sleeve 124 travels in a proximal direction
when a user initially sets a dose, this travel causes the arms 134 a, b to deflect inwards disengaging them from the drive
sleeve drive internal thread 138. For example, in one arrangement, the geometry of the threaded portion of the flexible
arms 134 a, b and the internal drive sleeve drive internal thread 138 includes an angled surface on one face of the
threads. In such an arrangement, if the drive sleeve is moved out in a proximal direction during dose dialling (i.e., without
55 rotation), the angled thread faces causes the spindle arms 134 a, b to deflect inwardly. Therefore the spindle 126 remains
stationary as the drive sleeve 124 moves axially as the dose is dialled up from a zero dose to a minimum dose value.
[0050] The drive sleeve drive internal thread 138 pitch (i.e., the distance from one thread groove to an adjacent thread
groove) may be equal to the axial distance dialled to reach the minimum dose. Therefore, once the minimum dose is

7
 EP 2 627 381 B1

dialled, the flexible arms 134 a, b may reengage with the drive sleeve drive internal thread 138. A larger dose can be
dialled if required, and since the drive sleeve 124 is now free to rotate the flexible arms 134 a, b remain engaged to the
drive sleeve internal thread 138. After a dose greater than or equal to the minimum dose is set, a user may deliver the
dose. During dose delivery, the flexible arms have to be engaged with the drive sleeve drive internal thread 138. Thus,
5 the drive sleeve 124 moves axially thereby causing rotation of the spindle 126 and hence transmitting the dispense force
to a cartridge bung.
[0051] In accordance with various examples, the minimum dose that must be dialled may be varied from device to
device. As described above, the length of the key feature along the inner surface 121 of the housing 120 that prevents
rotation of the clutch ring 130 may equate to the pitch of the drive sleeve drive thread 138. Therefore, changing these
10 values will change the minimum dose that must be dialled.
[0052] The operation of dose setting mechanism 104 is described in greater detail below with reference to the noted
Figures. In Figures 2-3, sections of the clutch ring 130 are removed from the figures in order to show internal detail.
First, the operation is described with reference to when a user dials a dose that is greater than a zero dose but less than
the minimum dose of the device. The number sleeve 122 is rigidly fixed to the dial grip 112, and therefore rotating the
15 dial grip 112 also rotates the number sleeve 122. As mentioned above, the clutch ring 130 is keyed to the housing 120
when a dose less than the minimum dose is selected and therefore below this minimum dose value, the clutch ring 130
cannot rotate.
[0053] The number sleeve 122 may include teeth 140 on the distal end of the number sleeve 122 (see figure 2A).
Further, the clutch ring 130 may include (i) teeth 144 on the proximal end 146 of the clutch ring, (ii) teeth 148 on the
20 distal end 150 of the clutch ring, and (iii) inner teeth 152 on an inner portion 154 of the clutch ring. When a user is dialing
a dose less than the minimum dose, the distal teeth 140 of the number sleeve 122 overhaul the clutch ring upper teeth
144. This in turn causes the clutch ring 130 to oscillate axially against the metal spring 132 as the number sleeve 122
rotates. At this point, the number sleeve 122 and the clutch ring 130 interface (i.e., teeth 140 and 144) may create an
audible and tactile "clicker" feedback to the user, which may provide the user with confirmation that a dose is being
25 selected.
[0054] The outer thread 156 of the number sleeve 122 causes the number sleeve 122 to rotate and travel axially in a
proximal direction as the dose is set. As this is happening, the protrusion 131 on the clutch ring 130 and the key feature
123 on the housing 120 prevent rotation of the clutch ring 130. The inner teeth 152 the clutch ring may be of a larger
size than the upper teeth 144 of the clutch ring so as to help ensure that the clutch 128 and hence drive sleeve 124 do
30 not rotate whilst the clutch ring 130 oscillates and over-rides the number sleeve teeth 140 creating the tactile "clicking"
feedback. In other words, the size of the teeth 152 and the corresponding teeth on the clutch is large enough to stay
engaged even if the clutch ring 130 oscillates by a distance defined by the (smaller) size of the teeth 140 overhauling
teeth 144. As the dose is being set and the drive sleeve 124, the clutch 128, and the clutch ring 130 travel axially in a
proximal direction 136 with the number sleeve 122, flexible arms 134 a, b of the spindle 126 deflect inwards as the drive
35 sleeve 124 travels, disengaging from their drive thread 138. This allows the drive sleeve 124 to travel axially in the
proximal direction without rotating whilst ensuring the spindle 126 remains stationary, thereby ensuring dose accuracy.
[0055] If the user attempted to deliver a dose when less than the minimum dose has been dialled, the drive sleeve
124 will travel axially in a distal direction 160 as a user depresses a dose button 113 of the device. However, the spindle
drive arms 134 a, b and thus drive thread 138 will not be engaged with the drive sleeve 124. Therefore, the spindle 126
40 will not rotate, and consequently a dose will not be delivered. The mechanism will return to its original position as
illustrated in Figure 2B at which point the protrusion 131 returns to the most distal position of a keying feature 123 and
at which point the spindle drive arms 134 a, b will reengage with the drive sleeve thread 138.
[0056] After the minimum user dose has been dialled, the spindle flexible arms 134 a, b will engage with the drive
sleeve inner thread 138. In addition, at this time, the protrusion of the clutch ring 130 will exit the key features that were
45 rotationally locking it to the housing 120. For example, Figure 2D illustrates a perspective view of given components of
the dose setting mechanism 104 immediately after a dose greater than a minimum dose has been dialled. As illustrated,
the protrusion 131 has exited the keying feature 123. Therefore, as a larger dose is dialled the dual clutch ring 130 is
now free to rotate with the number sleeve 122, thereby also rotating the clutch 128 and hence drive sleeve 124 and the
clutch 128. During this dialling operation, the clutch ring 130 rotates and causes oscillation of the metal spring 132 as
50 the clutch ring lower teeth 148 overhaul the metal spring 132 teeth 162. Therefore, at this stage of operation, the metal
spring 132 and clutch ring 130 interface may create an audible "clicker" feedback.
[0057] After the user dials a dose greater than the minimum dose, the user may administer a dose. Figure 3 depicts
the clutch 128, clutch ring 130, number sleeve 122, and drive sleeve 124 during a dose administration step. Depressing
dose button 113 acts on the clutch 128. Then, clutch 128, utilizing its limited axial travel relative to the drive sleeve 124,
55 forces the clutch ring 130 to disengage from the number sleeve 122, as shown in Figure 3. The metal spring 132 is
compressed by the clutch ring 130, and this acts to prevent rotation of the clutch 128 and hence also acts to prevent
rotation of the drive sleeve 124. As the dose is delivered, the number sleeve 122 rotates back and travels axially whilst
the drive sleeve 124 and the clutch 128 travel axially without rotation, thereby forcing the spindle 126 to rotate and thus

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advance delivering dose delivery.

[0058] When the clutch ring 130 returns to the axial position corresponding to the minimum dose during dose dispense,
the protrusion 131 of the clutch ring 130 reengages with the keying feature 123 in the housing 120 as illustrated in Figure
2C. This reengagement will serve to prevent rotation of the clutch ring 130 during the setting of the next dose. In an
5 exemplary arrangement, since during dose dispense, the clutch ring 130 does not rotate but rather only moves axially
in a distal direction, the clutch ring 130 may not return in the same angular orientation each time. Therefore, in an example
dose setting mechanism, there may be a plurality of grooves on either clutch ring 130 or housing 122 that can engage
protrusions on the other part in any of the possible rotational positions.
[0059] As illustrated in Figures 2B-D, the internal surface 121 of this housing 120 comprises a plurality of such grooves
10 or keying features.
[0060] In this described arrangement, clutch ring 130 and clutch 128 move together both axially and in rotation.
However, the teeth features 144 and 148 of the clutch ring could be incorporated into a combined clutch / clutch ring.
For instance, the clutch ring may integrated into the clutch, such that the clutch is keyed to the housing prior to a minimum
dose being selected (i.e., the clutch (and hence drive sleeve) can only rotate after a minimum dose is dialled).
15 [0061] In an example dose setting mechanism in accordance with the present invention, the dose count numbers
below the minimum dose may be coloured a different colour such as red to differentiate that the dose dialled is less than
the normal minimum dose. Alternatively, the dose count numbers may not be visible until the minimum dose has been
dialled.
[0062] An alternative exemplary arrangement is described with reference to Figures 4 to 5. The dose setting mechanism
20 of this example is similar in certain respects to the dose setting mechanism 104 shown in Figure 1B, and thus is not
described in as great level of detail. This alternative arrangement includes a modified dual clutch ring and drive sleeve.
Figures 4 to 5 illustrates the number sleeve, clutch, clutch ring, and drive sleeve of the modified example arrangement.
[0063] In this alternative arrangement, a clutch ring 200 is provided that is in engagement with a number sleeve
component 202 and a metal spring 204. The clutch ring 200 is keyed to drive sleeve 206 such that the clutch ring 200
25 cannot rotate, but can travel axially, relative to the drive sleeve 206. The clutch ring 200 may be keyed to the drive sleeve
206 in a variety of ways. For example, drive sleeve 206 may include at least one protrusion 208, and clutch ring 200
may include at least one corresponding protrusion 210. In Figure 4, a section is removed from clutch ring 200 to show
the internal detail of exemplary protrusions. As just one example, protrusions 208 and 210 may interact to prevent clutch
ring 200 from rotating relative to the drive sleeve 206.
30 [0064] In one arrangement, the clutch ring is provided with a plurality of protrusions that engage a spline provided on
an inner surface of the housing. As just one example, the clutch ring 200 may be provided with features such as protrusions
(not shown) that key the ring 200 to the device housing until a minimum dose has been selected. Further, the drive
sleeve 206 is axially locked to the dose dial component 202, but it is not directly rotationally locked to the dose dial
component 202. The metal spring 204 is keyed to the device housing at all times, and hence cannot rotate.
35 [0065] As a user dials a dose, the clutch ring 200 is keyed to the housing and thus cannot rotate. The number sleeve
202 rotates, which causes the clutch ring 200 to oscillate axially against the metal spring 204 as the number sleeve 202
teeth over-ride the upper teeth of the dual clutch ring 200. The drive sleeve 206 travels axially in a proximal direction
without rotating. As discussed above with reference to the first arrangement, the flexible arms of the spindle (not shown)
operate as per the first arrangement. In this stage of operation, the "clicker" feedback may be created by the number
40 sleeve 202 to clutch ring 200 interface. As in the first arrangement, a user is prevented from administering a dose that
is less than the minimum dose due to the drive sleeve being disengaged from the spindle.
[0066] After the minimum user dose has been dialled, the spindle flexible arms reengage with the drive sleeve drive
thread. The protrusion of the clutch ring 200 also exits the keying feature that were rotationally locking it to the housing
as previously discussed. Therefore, as a larger dose is dialled, the clutch ring 200 is now free to rotate along with the
45 number sleeve 202. Since the drive sleeve 206 is keyed to the clutch ring 200, the drive sleeve 206 can now rotate along
with the number sleeve 202. In this stage of operation, the "clicker" feedback may be created by the metal spring 204
to dual clutch ring 200 interface.
[0067] After a dose greater than the minimum dose is set, a user may deliver the dose. To deliver a dose, a user may
depress a dose button. Depressing the dose button acts on the clutch 212 disengaging the clutch ring 200 from the
50 number sleeve 202. The metal spring 204 is compressed by the clutch ring 200 and acts to prevent rotation of the clutch
ring 200 and therefore rotation of the drive sleeve 206. As the dose is delivered, the dose dial component 202 rotates
and travels axially whilst the drive sleeve 206 travels axially without rotation, therefore forcing the spindle to rotate and
thus advance delivering the dose.
[0068] As per the first arrangement, the dual clutch ring 200 and clutch 212 move together both axially and in rotation.
55 In an example, the upper and lower teeth features of the dual clutch ring could be incorporated into a combined clutch
/ clutch ring.
[0069] In a preferred embodiment a master drug compound, such as insulin, contained within a multiple dose, user
selectable device could be used with a single use, user replaceable, module that contains a single dose of a secondary

9
 EP 2 627 381 B1

medicament and the single dispense interface. When connected to the primary device, the secondary compound is
activated/delivered on dispense of the primary compound. Although the present application specifically mentions insulin,
insulin analogs or insulin derivatives, and GLP-1 or GLP-1 analogs as two possible drug combinations, other drugs or
drug combinations, such as an analgesics, hormones, beta agonists or corticosteroids, or a combination of any of the
5 above-mentioned drugs could be used with our invention.
[0070] For the purposes of our invention the term "insulin" shall mean Insulin, insulin analogs, insulin derivatives or
mixtures thereof, including human insulin or a human insulin analogs or derivatives. Examples of insulin analogs are,
without limitation, 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,
10 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 or Des(B30) human insulin. Examples of insulin derivatives are, without limitation, 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-
15 glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyhepta-
decanoyl)-des(B30) human insulin and B29-N-(ω-carboxyhepta¬decanoyl) human insulin.
[0071] As used herein the term "GLP-1" shall mean GLP-1, GLP-1 analogs, or mixtures thereof, including without
limitation, exenatide (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-
20 NH2), Exendin-3, Liraglutide, or AVE0010 (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-Ser-Lys-Lys-Lys-Lys-Lys-Lys-
NH2).
[0072] Examples of beta agonists are, without limitation, salbutamol, levosalbutamol, terbutaline, pirbuterol, procaterol,
metaproterenol, fenoterol, bitolterol mesylate, salmeterol, formoterol, bambuterol, clenbuterol, indacaterol.
25 [0073] Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides
and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine
(Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.
[0074] The term "medicament", as used herein, means a pharmaceutical formulation containing at least one pharma-
ceutically active compound, wherein in one embodiment the pharmaceutically active compound has a molecular weight
30 up to 1500 Da and/or is a peptide, a proteine, a polysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, an
antibody, a hormone or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound,
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
35 infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis,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, 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 exedin-3 or exedin-4 or
40 an analogue or derivative of exedin-3 or exedin-4.
[0075] 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. Insulin derivates are for example
45 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 in-
sulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmi-
toyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(ω-carbox-
yheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyhepta¬decanoyl) human insulin.
50 [0076] 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. Exendin-4 derivatives are for example selected from the following list of compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2, H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2, des
55 Pro36 [Asp28] Exendin-4(1-39), des Pro36 [IsoAsp28] Exendin-4(1-39), des Pro36 [Met(O)14, Asp28] Exendin-
4(1-39), des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39), des
Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39), des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), des Pro36
[Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or des Pro36 [Asp28] Exendin-4(1-39), des Pro36 [IsoAsp28]

10
 EP 2 627 381 B1

Exendin-4(1-39), des Pro36 [Met(O)14, Asp28] Exendin-4(1-39), des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),
des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39), des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39), des Pro36
[Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),
wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4derivative; or an Exendin-4 derivative
5 of the sequence H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2, des Asp28 Pro36, Pro37, Pro38Exendin-
4(1-39)-NH2, H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2, H-Asn-(Glu)5des Pro36, Pro37, Pro38
[Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36,
Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-
4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, H-des Asp28 Pro36,
10 Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-
4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37,
Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]
Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-
NH2, H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2, des Met(O)14 Asp28 Pro36, Pro37, Pro38
15 Exendin-4(1-39)-NH2, H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, H-Asn-(Glu)5-
des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Met(O)14, Asp28]
Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,
H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Lys6-des Pro36
[Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]
20 Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, H-Asn-(Glu)5-
des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Met(O)14,
Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]
Exendin-4(S1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-
4(1-39)-(Lys)6-NH2;
25
or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exedin-4 derivative.
[0077] 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, Chor-
iongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leu-
30 prorelin, Buserelin, Nafarelin, Goserelin.
[0078] 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 pharmaceu-
tically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium.
35 [0079] Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are
e.g. HCI 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
40 described in "Remington’s Pharmaceutical Sciences" 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing Company,
Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology. Pharmaceutically acceptable solvates
are for example hydrates.

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50 Exemplary embodiments of the present drug delivery device have been described. Those skilled in the art will understand,
however, that changes and modifications may be made to these embodiments without departing from the true scope of
the presently proposed dose setting mechanism for a drug delivery device, which is defined by the claims.

55 Claims

1. A dose setting mechanism for a drug delivery device, the mechanism comprising:

14
 EP 2 627 381 B1

a drug delivery device housing (102);

a dose dial component (122; 202) positioned at least partly in the housing (120) and
rotatable during a dose setting step;
a drive sleeve (124; 206) positioned within the dose dial component (122; 202);
5 a spindle (126) positioned within the drive sleeve (124; 206);
a clutch (128; 212) positioned between the dose dial component (122; 202) and the drive sleeve (124; 206); and
a clutch ring (130; 200) rotationally fixed relative to the housing (120) when a dose less than the minimum
allowable dose is selected, characterised in that, when the dose dial component (122; 202) is rotated to select
a dose less than a minimum dose, the clutch ring (130; 200) prevents the drive sleeve (124; 206) from rotating,
10 causing the spindle (126) to be disengaged from the drive sleeve (124; 206), thereby preventing the selected
dose from being administered.

2. The mechanism of claim 1 wherein, when the dose dial component (122; 202) is rotated to select the dose less than
the minimum dose, the clutch ring (130; 200) prevents the clutch (128; 212) from rotating.
15
3. The mechanism of claim 1 wherein, when the dose dial component (122; 202) is rotated to select a dose greater
than the minimum dose, the clutch ring (130; 200) allows the drive sleeve (124; 206) and the clutch (128; 212) to
rotate together during subsequent dose setting such that a dose greater than the minimum dose can be selected
and dispensed.
20
4. The mechanism of claim 1 wherein the spindle (126) comprises at least one flexible member (134a, b), the at least
one flexible member configured to engage a thread (138) of the drive sleeve (124; 206).

5. The mechanism of claim 4 wherein the at least one flexible member (134a, b) engages the inner thread (138) of the
25 drive sleeve (124; 206) after a dose has been selected that is greater than the minimum dose.

6. The mechanism of claim 5 wherein the drive sleeve (124; 206) drive inner thread (138) comprises a drive sleeve
(124; 206) pitch wherein the drive sleeve pitch is equal to an axial distance that must be dialled by the dose dial
component (122; 202) to reach the minimum dose.
30
7. The mechanism of claim 1 wherein the clutch ring (130; 200) is splined to the housing (120).

8. The mechanism of claim 7 wherein the clutch ring (130; 200) is splined to the housing (120) only when the dose
dial component (122; 202) is rotated to select a dose that is less than the minimum dose.
35
9. The mechanism of claim 7 wherein the clutch ring (130; 200) is no longer splined to the housing (120) when the
dose dial component (122; 202) is rotated to select a dose that is greater than the minimum dose.

10. The mechanism of claim 1 wherein an interface (140, 144) defined between a first portion of the clutch ring (130;
40 200) and a first portion of the dose dial component (122; 202) defines a clicker.

11. The mechanism of claim 1 wherein the clutch (128; 212) and the clutch ring (130; 200) comprise a unitary clutch
mechanism.

45 12. The mechanism of claim 1 wherein the clutch ring (200) is rotationally locked to the drive sleeve (206).

13. The mechanism of claim 1 wherein the drive sleeve (124; 206) is axially locked to the number sleeve (122; 202).

14. The mechanism of claim 1 wherein a protrusion of the clutch ring (130; 200) is rotationally fixed relative to a keying
50 feature (123) of the housing (120) at least when a dose is selected that is less than the minimum dose.

15. The mechanism of claim 14 wherein the housing (120) comprises a plurality of keying features (123) and/or wherein
the clutch ring (130; 200) comprises a plurality of protrusions (131).

55
Patentansprüche

1. Dosiseinstellungsmechanismus für eine Medikamenten-Verabreichungsvorrichtung, wobei der Mechanismus das

15
 EP 2 627 381 B1

Folgende umfasst:

ein Gehäuse (102) der Medikamenten-Verabreichungsvorrichtung;

eine Dosiswahlkomponente (122; 202), die zumindest teilweise im Gehäuse (120) angeordnet ist und während
5 eines Dosiseinstellungsschritts drehbar ist;
eine Antriebshülse (124; 206), die innerhalb der Dosiswahlkomponente (122; 202) angeordnet ist;
eine Spindel (126), die innerhalb der Antriebshülse (124; 206) angeordnet ist;
eine Kupplung (128; 212), die zwischen der Dosiswahlkomponente (122; 202) und der Antriebshülse (124; 206)
angeordnet ist; und
10 einen Kupplungsring (130; 200), der bezüglich des Gehäuses (120) drehfest befestigt ist, wenn eine Dosis, die
geringer als die zulässige Mindestdosis ist, gewählt wird,
dadurch gekennzeichnet, dass der Kupplungsring (130; 200) eine Drehung der Antriebshülse (124; 206)
verhindert, wenn die Dosiswahlkomponente (122; 202) zum Wählen einer Dosis gedreht wird, die geringer als
eine Mindestdosis ist, wodurch die Spindel (126) aus ihrem Eingriff mit der Antriebshülse (124; 206) gelöst wird,
15 so dass eine Verabreichung der gewählten Dosis verhindert wird.

2. Mechanismus nach Anspruch 1, wobei der Kupplungsring (130; 200) eine Drehung der Kupplung (128; 212) ver-
hindert, wenn die Dosiswahlkomponente (122; 202) zum Wählen der Dosis gedreht wird, die geringer als die Min-
destdosis ist.
20
3. Mechanismus nach Anspruch 1, wobei der Kupplungsring (130; 200) eine gemeinsame Drehung der Antriebshülse
(124; 206) und der Kupplung (128; 212) während einer anschließenden Dosiseinstellung erlaubt, wenn die Dosis-
wahlkomponente (122; 202) zum Wählen einer Dosis gedreht wird, die größer als die Mindestdosis ist, so dass eine
Dosis, die größer als die Mindestdosis ist, gewählt und abgegeben werden kann.
25
4. Mechanismus nach Anspruch 1, wobei die Spindel (126) zumindest ein flexibles Element (134a, b) umfasst, wobei
das zumindest eine flexible Element dazu ausgelegt ist, ein Gewinde (138) der Antriebshülse (124; 206) in Eingriff
zu nehmen.

30 5. Mechanismus nach Anspruch 4, wobei das zumindest eine flexible Element (134a, b) das Innengewinde (138) der
Antriebshülse (124; 206) in Eingriff nimmt, nachdem eine Dosis gewählt wurde, die größer als die Mindestdosis ist.

6. Mechanismus nach Anspruch 5, wobei das Antriebsinnengewinde (138) der Antriebshülse (124; 206) eine Steigung
der Antriebshülse (124; 206) umfasst, wobei die Antriebshülsensteigung einem axialen Abstand gleicht, der von
35 der Dosiswahlkomponente (122; 202) gewählt werden muss, um die Mindestdosis zu erreichen.

7. Mechanismus nach Anspruch 1, wobei der Kupplungsring (130; 200) am Gehäuse (120) verkeilt ist.

8. Mechanismus nach Anspruch 7, wobei der Kupplungsring (130; 200) nur dann am Gehäuse (120) verkeilt ist, wenn
40 die Dosiswahlkomponente (122; 202) zum Wählen einer Dosis gedreht wird, die geringer als die Mindestdosis ist.

9. Mechanismus nach Anspruch 7, wobei der Kupplungsring (130; 200) nicht mehr am Gehäuse (120) verkeilt ist,
wenn die Dosiswahlkomponente (122; 202) zum Wählen einer Dosis gedreht wird, die größer als die Mindestdosis ist.

45 10. Mechanismus nach Anspruch 1, wobei eine Schnittstelle (140, 144), die zwischen einem ersten Abschnitt des
Kupplungsrings (130; 200) und einem ersten Abschnitt der Dosiswahlkomponente (122; 202) definiert ist, einen
Klicker definiert.

11. Mechanismus nach Anspruch 1, wobei die Kupplung (128; 212) und der Kupplungsring (130; 200) einen einheitlichen
50 Kupplungsmechanismus umfassen.

12. Mechanismus nach Anspruch 1, wobei der Kupplungsring (200) drehfest an der Antriebshülse (206) arretiert ist.

13. Mechanismus nach Anspruch 1, wobei die Antriebshülse (124; 206) axial an der Nummernhülse (122; 202) arretiert
55 ist.

14. Mechanismus nach Anspruch 1, wobei ein Vorsprung des Kupplungsrings (130; 200) bezüglich eines Keilmerkmals
(123) des Gehäuses (120) zumindest dann drehfest befestigt ist, wenn eine Dosis gewählt wird, die geringer als

16
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die Mindestdosis ist.

15. Mechanismus nach Anspruch 14, wobei das Gehäuse (120) eine Vielzahl von Keilmerkmalen (123) umfasst und/oder
wobei der Kupplungsring (130; 200) eine Vielzahl von Vorsprüngen (131) umfasst.
5

Revendications

1. Mécanisme de réglage de dose pour un dispositif d’administration de médicaments, le mécanisme comprenant :

10
un boîtier de dispositif d’administration de médicaments (102) ;
un composant de sélection de dose (122 ; 202) positionné au moins en partie dans le boîtier (120) et pouvant
tourner lors d’une étape de réglage de dose ;
un manchon d’entraînement (124 ; 206) positionné à l’intérieur du composant de sélection de dose (122 ; 202) ;
15 une broche (126) positionnée à l’intérieur du manchon d’entraînement (124 ; 206) ;
un embrayage (128 ; 212) positionné entre le composant de sélection de dose (122 ; 202) et le manchon
d’entraînement (124 ; 206) ; et
une bague d’embrayage (130 ; 200) fixée en rotation par rapport au boîtier (120) lorsqu’une dose inférieure à
la dose minimale admissible est sélectionnée,
20 caractérisé en ce que
lorsque le composant de sélection de dose (122 ; 202) est tourné pour sélectionner une dose inférieure à une
dose minimale, la bague d’embrayage (130 ; 200) empêche la rotation du manchon d’entraînement (124 ; 206),
entraînant le désengagement de la broche (126) du manchon d’entraînement (124 ; 206), ce qui empêche
l’administration de la dose sélectionnée.
25
2. Mécanisme selon la revendication 1, dans lequel, lorsque le composant de sélection de dose (122 ; 202) est tourné
pour sélectionner la dose inférieure à la dose minimale, la bague d’embrayage (130 ; 200) empêche la rotation de
l’embrayage (128 ; 212).

30 3. Mécanisme selon la revendication 1, dans lequel, lorsque le composant de sélection de dose (122 ; 202) est tourné
pour sélectionner une dose supérieure à la dose minimale, la bague d’embrayage (130 ; 200) permet au manchon
d’entraînement (124 ; 206) et à l’embrayage (128 ; 212) de tourner ensemble au cours du réglage de dose subsé-
quent, de telle sorte qu’une dose supérieure à la dose minimale puisse être sélectionnée et distribuée.

35 4. Mécanisme selon la revendication 1, dans lequel la broche (126) comprend au moins un organe flexible (134a, b),
l’au moins un organe flexible étant configuré pour venir en prise avec un filetage (138) du manchon d’entraînement
(124 ; 206).

5. Mécanisme selon la revendication 4, dans lequel l’au moins un organe flexible (134a, b) vient en prise avec le
40 filetage interne (138) du manchon d’entraînement (124 ; 206) après la sélection d’une dose qui est supérieure à la
dose minimale.

6. Mécanisme selon la revendication 5, dans lequel le filetage interne d’entraînement (138) du manchon d’entraînement
(124 ; 206) comprend un pas de manchon d’entraînement (124 ; 206), le pas de manchon d’entraînement étant
45 égal à une distance axiale qui doit être sélectionnée par le composant de sélection de dose (122 ; 202) pour atteindre
la dose minimale.

7. Mécanisme selon la revendication 1, dans lequel la bague d’embrayage (130 ; 200) est cannelée sur le boîtier (120).

50 8. Mécanisme selon la revendication 7, dans lequel la bague d’embrayage (130 ; 200) est cannelée sur le boîtier (120)
seulement lorsque le composant de sélection de dose (122 ; 202) est tourné pour sélectionner une dose qui est
inférieure à la dose minimale.

9. Mécanisme selon la revendication 7, dans lequel la bague d’embrayage (130 ; 200) n’est plus cannelée sur le boîtier
55 (120) lorsque le composant de sélection de dose (122 ; 202) est tourné pour sélectionner une dose qui est supérieure
à la dose minimale.

10. Mécanisme selon la revendication 1, dans lequel une interface (140, 144) définie entre une première portion de la

17
 EP 2 627 381 B1

bague d’embrayage (130 ; 200) et une première portion du composant de sélection de dose (122 ; 202) définit un
cliqueur.

11. Mécanisme selon la revendication 1, dans lequel l’embrayage (128 ; 212) et la bague d’embrayage (130 ; 200)
5 comprennent un mécanisme d’embrayage unitaire.

12. Mécanisme selon la revendication 1, dans lequel la bague d’embrayage (200) est verrouillée en rotation au manchon
d’entraînement (206).

10 13. Mécanisme selon la revendication 1, dans lequel le manchon d’entraînement (124 ; 206) est verrouillé axialement
au manchon chiffré (122 ; 202).

14. Mécanisme selon la revendication 1, dans lequel une saillie de la bague d’embrayage (130 ; 200) est fixée en
rotation par rapport à un clavetage (123) du boîtier (120) au moins lorsqu’une dose inférieure à la dose minimale
15 est sélectionnée.

15. Mécanisme selon la revendication 14, dans lequel le boîtier (120) comprend une pluralité de clavetages (123) et/ou
dans lequel la bague d’embrayage (130 ; 200) comprend une pluralité de saillies (131).

20

25

30

35

40

45

50

55

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19
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20
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21
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22
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23
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REFERENCES CITED IN THE DESCRIPTION

This list of references cited by the applicant is for the reader’s convenience only. It does not form part of the European
patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be
excluded and the EPO disclaims all liability in this regard.

Patent documents cited in the description

• US 20090275916 A1 [0002] • WO 2004078239 A [0024]

• WO 2004078239 A1 [0002] [0003]

Non-patent literature cited in the description

• Remington’s Pharmaceutical Sciences. Mark Pub-

lishing Company, 1985 [0079]

24