Dose setting mechanism for priming a drug delivery device

WO 2010/139634 PCT/EP2010/057473 1

Description

DOSE SETTING MECHANISM FOR PRIMING A DRUG DELIVERY DEVICE

BACKGROUND

Field of the Present Patent Application

The present patent application is generally directed to drug delivery devices. More particularly, the present patent application is generally directed to drug delivery devices, such as pen type drug delivery devices. Such devices provide for self administration of medicinal product from a multi-dose cartridge and permit a user to set the delivery dose. The present application may find application in both resettable (i.e., reusable) and non- resettable (i.e., non-reusable) type drug delivery devices. However, aspects of the invention may be equally applicable in other scenarios as well.

Background

Pen type drug delivery devices have application where regular injection by persons without formal medical training occurs. This is increasingly common among patients having diabetes where self-treatment enables such patients to conduct effective management of their disease.

In certain types of medication delivery devices, such as pen type devices, cartridges of medication are used. These cartridges are housed in a cartridge holder or cartridge housing. Such cartridges include a bung or stopper at one end. At the other end of the cartridge, the cartridge may comprise a pierceable seal. To dispense a dose of medication from such a cartridge, the medication delivery device has a dose setting mechanism that uses a spindle to move in a distal direction towards the cartridge and to press a distal end of the spindle against the bung. This expels a certain set or preselected dose of medication from the cartridge. In order to insure dose accuracy, it 216481/2 2 is important that the distal end of the spindle remains on the bung of the cartridge before, during and after injection of a dose of medicament.

One perceived disadvantage of certain known medication delivery devices is that because of the various tolerance differences that may occur during manufacturing (e.g., tolerance differences that may arise during component molding) of the various parts making up the drug delivery device and the desire to not pre-load the bung axially in the assembled device, there may be a gap between the end of the spindle and the cartridge bung after the medication delivery device has been assembled. In other words, when initially assembled, the cartridge (and hence cartridge bung) may not be in contact with the distal end of the spindle. Therefore, if a user using the drug delivery device for the first time dials a dose, the actual dose received may be equal to the dialed dose less the initial gap between the distal end of the spindle and cartridge bung. The air gap between the cartridge bung and distal end of the spindle may be equivalent to a dose that causes the received dose that is outside preferred dose accuracy limits. For example, this air gap may be equivalent to the loss of between 0 and 10 units (i.e., 0 - 0.14 milliliters) of drug product on the first dose.

There is, therefore, a general need to take these perceived issues into consideration when designing either resettable or non-resettable drug delivery devices, such as pen type drug delivery devices. EP 0 937 472 discloses a medication delivery pen having a repeat-dose feature that is performed by using a pull-push operation. The medication delivery pen includes means for whether the medication delivery pen is armed and a variety of novel drive mechanisms as well as a priming control mechanism that allows the user to easily prime medication delivery pen prior to arming the pen. EP 1 541 185 discloses an automatic syringe with priming mechanism comprises a cartridge-holder and a housing. The cartridge-holder interacts with a nut-member capable of driving the piston rod forward when relatively rotated. The cartridge-holder is rotational coupled to the housing such that rotation of the cartridge-holder relatively 216481/1 2a to the housing causes the nut-member and the piston rod to rotate relatively, thus the relative angular rotation between the cartridge-holder and the housing determines the size of the air shot so performed. 5 WO 1997/010864 discloses a medication delivery pen and a mounting method for this pen having a medication cartridge holder assembly, a pen body assembly and a cap. The reusable pen body assembly includes an improved loading and priming mechanism that allows the user to easily load a new cartridge and prime the pen without having to manually manipulate the pen's lead screw and related driving 10 components.

SUMMARY

It is an object of the present invention to provide an improved dose setting mechanism 15 which is especially suitable for priming a drug delivery device and/or prevents use of the device prior to a priming step.

This object is solved by a device as defined in claims 1 and 10 which requires a rotational movement of a cartridge holder to prime the device and/or to bring the WO 2010/139634 PCT/EP2010/057473 3 device in a condition allowing setting of a dose. Preferably, the condition allowing setting of a dose is the primed condition of the device.

According to a first embodiment, a drug delivery device comprises a dose setting mechanism comprising a spindle. A cartridge holder is coupled to the dose setting mechanism. The cartridge holder comprises a cartridge having a movable bung at one end of the cartridge. The cartridge holder is rotated before a dose may be set with the dose setting mechanism. Preferably, the cartridge holder must be rotated less than 360 degrees before a dose may be set with the dose setting mechanism.

In more detail, the cartridge holder must be rotated with respect to the dose setting mechanism before the dose may be set with the dose setting mechanism. Thus, rotation of the cartridge holder may prime the drug delivery device.

According to a preferred development of this embodiment, rotation of the cartridge holder moves the spindle into an abutting engagement with the bung of the cartridge.

It may be advantageous, if rotation of the cartridge holder enables a dose dial sleeve of the dose setting mechanism to rotate which allows a user of the dose setting mechanism to set the dose.

Preferably, after the cartridge holder is rotated, the cartridge holder is rotationally locked to the dose setting mechanism. This rotationally locking of the cartridge holder to the dose setting mechanism may be by way of a one way, non-return detent feature.

To facilitate use of the device, the cartridge holder provides a visual indication that the cartridge holder must be rotated before the dose may be set by the dose setting mechanism.

According to the present invention, the drug delivery device may either be a resettable drug delivery device or a not-resettable (disposable) drug delivery device. WO 2010/139634 PCT/EP2010/057473 4

The terms „drug” or “medicinal product” or “medicament“, as used herein, mean a pharmaceutical formulation containing at least one pharmaceutically active compound, wherein in one embodiment the pharmaceutically active compound has a molecular weight 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 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 an analogue or derivative of exedin-3 or exedin-4.

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. WO 2010/139634 PCT/EP2010/057473 5

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; Β29-Ν-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-^-carboxyheptadecanoyl) human insulin.

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 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] 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), WO 2010/139634 PCT/EP2010/057473 6 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-4 derivative; or an Exendin-4 derivative 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, 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 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] Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, WO 2010/139634 PCT/EP2010/057473 7 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; or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exedin-4 derivative.

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. 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.

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's Pharmaceutical Sciences" 17. ed. Alfonso R. Gennaro (Ed.), WO 2010/139634 PCT/EP2010/057473 8

Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of

Pharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

According to another embodiment of the present invention, a priming mechanism for a drug delivery device comprises a dose setting mechanism. The dose setting mechanism comprises a spindle and a dose dial sleeve. A cartridge holder comprises a cartridge comprising a movable bung and a pierceable seal. A coupling part connects the cartridge holder to the dose dial sleeve. A spindle nut, rotationally coupled to the coupling part, couples the cartridge holder to the spindle. When the cartridge holder is rotated with respect to the dose setting mechanism, the spindle nut is rotated and the coupling part moves the spindle into an abutting engagement with the bung. Thus, priming of the device is effected by a rotation of the cartridge holder.

In the priming mechanism the coupling part, which may comprise a thin metal pressing and/or a rigid coupling component, unlocks the dose dial sleeve so that the dose dial sleeve may be rotated to set a dose.

Preferably, the dose setting mechanism comprises at least one flexible locking element. When the cartridge holder is rotated, the coupling part also rotates to thereby release said flexible locking element and allowing the dose dial sleeve to rotate and allow a user of the medical delivery device to set a dose.

The spindle nut may further comprise a plurality of helical ramps. The plurality of helical ramps drive the spindle nut in a distal direction when the cartridge holder is rotated so that the spindle abuts a first surface of the bung.

These as well as other advantages of various aspects of the present invention will become apparent to those of ordinary skill in the art by reading the following detailed description, with appropriate reference to the accompanying drawings. WO 2010/139634 PCT/EP2010/057473 9

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments are described herein with reference to the drawings, in which:

Figure 1 illustrates an arrangement of a drug delivery device in accordance with the one aspect of the present invention;

Figure 2 illustrates the drug delivery device of Figure 1 with a cap removed and with a dose having been selected;

Figure 3 illustrates a close up view of a drug delivery device before a priming step, such as the drug delivery device illustrated in Figure 1;

Figure 4 illustrates a close up view of the drug delivery device illustrated in Figure 3 after completion of a priming step;

Figure 5 illustrates a close up view of a connection between a dose setting mechanism and cartridge housing of a drug delivery device in a non-priming state, such as drug delivery device illustrated in Figures 3 and 4;

Figure 6 illustrates a close up view of the connection between the dose setting mechanism and the cartridge illustrated in Figure 5, in a priming state;

Figure 7 illustrates a close up view of a proximal end of the cartridge housing illustrated in Figures 5 and 6, including a coupling part;

Figure 8 illustrates how the coupling part illustrated in Figure 7 may be used to engage a dose dial sleeve of a dose setting mechanism, such as the dose setting mechanism illustrated in Figures 5 and 6;

Figure 9 illustrates the coupling part illustrated in Figure 8 in a non-primed state; WO 2010/139634 PCT/EP2010/057473 10

Figure 10 illustrates the coupling part illustrated in Figure 9 in a primed state;

Figure 11 illustrates a close up view of the stop faces provided along the distal end of the dose dial sleeve illustrated in Figure 10;

Figure 12 illustrates a spindle nut that may be used to couple the coupling part to a dose setting member and to a cartridge housing; and

Figure 13 illustrates the spindle nut coupled to the coupling part and dose dial sleeve of a dose setting mechanism.

DETAILED DESCRIPTION

Referring to Figure 1, there is shown a drug delivery device 1 in accordance with an exemplary arrangement. The drug delivery device 1 comprises a housing having a first cartridge retaining part 2, and a dose setting mechanism 4. 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 2 and a second end of the dose setting mechanism 4 are secured together by connecting features. For non-resettable devices, these connecting features would be permanent and non-reversible. For resettable devices, these connecting features would be releasable.

In this illustrated arrangement, the cartridge housing 2 is secured within the second end of the dose setting mechanism 4. A removable cap 3 is releasably retained over a second end or distal end of a cartridge retaining part or cartridge housing. The dose setting mechanism 4 comprises a dose dial grip 12 and a window or lens 14. A dose scale arrangement 16 is viewable through the window or lens 14. To set a dose of medication contained within the drug delivery device 1, a user rotates the dose dial grip 12 such that a dialed dose will become viewable in the window or lens 14 by way of the dose scale arrangement 16. WO 2010/139634 PCT/EP2010/057473 11

Figure 2 illustrates the medical delivery device 1 of Figure 1 with the cover 3 removed from a distal end 19 of the medical delivery device 1. This removal exposes the cartridge housing 6. As illustrated, a cartridge 25 from which a number of doses of a medicinal product may be dispensed, is provided in the cartridge housing 6.

Preferably, the cartridge 25 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. The cartridge 25 comprises a bung or stopper (not illustrated in Figure 2) that is retained near a second end or a proximal end 33 of the cartridge 25. The medical delivery device also comprises a driver having a spindle (not illustrated in Figure 2). As discussed above, before the device is primed, there may or may not be a gap between the end of the spindle and the cartridge bung.

The cartridge housing 6 has a distal end 23 and a proximal end 27. Preferably, the cartridge distal end 23 of the cartridge housing 6 comprises a groove 8 for attaching a removable needle assembly. However, other needle assembly connection mechanisms could also be used. If the drug delivery device 1 comprises a resettable device, the cartridge proximal end 27 is removably connected to the dose setting mechanism 4. In one preferred embodiment, cartridge housing proximal end 27 is removably connected to the dose setting mechanism 4 via a bayonet connection. However, 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.

As previously mentioned, the dose setting mechanism 4 of the drug delivery device illustrated in Figure 2 may be utilized as a reusable drug delivery device. (i.e., a drug delivery device that can be reset) Where the drug delivery device 1 comprises a reusable drug delivery device, the cartridge 25 is removable from the cartridge housing 6. The cartridge 25 may be removed from the device 1 without destroying the device 1 by merely having the user disconnect the dose setting mechanism 4 from the cartridge housing 6. WO 2010/139634 PCT/EP2010/057473 12

In use, once the cap 3 is removed, a user can attach a suitable needle assembly to the groove 8 provided at the distal end 23 of the cartridge housing 6. Such needle assembly may be, for example, screwed onto a distal end 23 of the housing 6 or alternatively may be snapped onto this distal end 23. After use, the replaceable cap 3 may be used to re-cover the cartridge housing 6. Preferably, the outer dimensions of the replaceable cap 3 are similar or identical to the outer dimensions of the dose setting mechanism 4 so as to provide an impression of a unitary whole when the replaceable cap 3 is in position covering the cartridge housing 6 when the device is not in use.

In accordance with an exemplary arrangement, it may be beneficial to force a user to prime the drug delivery device of Figures 1 and 2 before the user dials and injects the first dose. In order to achieve this forced priming, as will be discussed in greater detail below, the drug delivery device 1 preferably forces a user to prime the device before they are permitted to select the first dose.

The process of forcing a user to prime the cartridge before they can select and dispense the first dose reduces a potential risk of injecting the prime dose. The idea of forced priming is particularly advantageous for disposable devices where there is oftentimes a gap between a distal end of the spindle and the cartridge bung before the device is used. This gap is a consequence of the tolerances associated with the assembled parts as well as the desire not to pre-load the bung axially in the assembled device.

If the device is designed so that this gap between a distal end of the spindle and the bung is removed (i.e., the device primed) before the user is able to dial a dose, then this is advantageous. In one preferred arrangement, the drug delivery device achieves this by the user rotating the cartridge holder relative to the housing in order to both prime the device and also to unlock the number sleeve so the user can subsequently rotate the dose dial sleeve to set the first dose. Preferably, once the device has been primed, the cartridge holder is locked rotationally and therefore cannot be rotated with respect to the dose setting mechanism. WO 2010/139634 PCT/EP2010/057473 13

Figure 3 illustrates a close up view of a drug delivery device 50 before a priming step, such as the drug delivery device 1 illustrated in Figure 1. Figure 4 illustrates a close up view of the drug delivery device 50 illustrated in Figure 3 after completion of a priming step. As illustrated, the drug delivery device 50 comprises a dose setting mechanism 52 coupled to a cartridge housing 54. Where the drug delivery device 50 comprises a re-settable drug delivery device, this coupling mechanism comprises a releasable coupling mechanism (i.e., a thread, a bayonet lock, a luer lock, a snap fit or snap lock, etc.) Where the drug delivery device 50 comprises a non-resettable drug delivery device (i.e., a disposable drug delivery device), this coupling this coupling mechanism comprises a non-reversible coupling mechanism.

In this preferred arrangement of drug deliver device 50, the dose setting mechanism 52 comprises various markings and indications along an outer surface 53. As can be seen in this arrangement, this marking comprises a marking indicating a locked position (i.e., un-primed state) 58 and a marking indicating an unlocked position (i.e., primed state) 62. In addition, various intermediate markings 59 are provided between the locked and unlocked position markings 58, 62, respectively.

In addition, the cartridge housing 54 comprises markings along its outer surface 63 and these markings include a positional indicator (i.e., an arrow) 56 that is used to indicate the relative position of the cartridge housing 54 with respect to the outer surface 53 of the dose setting mechanism 52. In this preferred arrangement, to prime the drug delivery device 50, the cartridge housing 54 is rotated in direction of arrow 60. Preferably, the cartridge housing 54 is rotated in the direction of arrow 60 with respect to the dose setting mechanism 52 so that the arrow 56 moves from the locked marking 58 and then aligns with the unlocked designation 62, as shown in Figure 4. In this final position, the drug delivery device 50 now resides in a primed state. That is, the spindle contained in the dose setting mechanism 52 now resides adjacent or abuts the bung provided in the cartridge of the cartridge housing 54. In addition, in a preferred arrangement, the drug delivery device 50 is also now unlocked so that the dose setting mechanism 52 may now be used to set a dose (as illustrated in Figure 2). Most WO 2010/139634 PCT/EP2010/057473 14 preferably, in this final position, the cartridge holder 54 is also rotationally locked and can therefore no longer be rotated with respect to the dose setting mechanism 52.

Figure 5 illustrates a close up view of a connection between a dose setting mechanism and cartridge housing of a drug delivery device 70, such as drug delivery device 50 illustrated in Figures 3 and 4. In Figure 5, the drug delivery device 70 is in a pre primed state. Therefore, with the drug delivery device illustrated in Figure 5, a user could not set a dose until the device is primed. As illustrated, the dose setting mechanism 74 is rotationally coupled to the cartridge housing 72. In this arrangement, the cartridge housing 72 comprises a rib 76 that engages with an internally formed cavity on an inner surface of the dose setting mechanism 74. This configuration allows for relative rotational movement only between the dose setting mechanism 74 and the cartridge housing 76 and no axial movement. This rotational relative movement occurs when the cartridge holder 72 is rotated from the locked position (i.e., Figure 5) to the unlocked position (i.e., Figure 6).

Figure 7 illustrates a close up view of a proximal end 68 of the cartridge housing 72 illustrated in Figures 5 and 6. Figure 7 also illustrates a coupling part 80 that may be used to couple the cartridge housing 72 to a dose setting mechanism, such as the dose setting mechanism 74 illustrated in Figure 5 and 6. In this preferred arrangement, this cartridge housing 72 comprises an L shaped cavity 73 provided along a first outer surface 75 of the cartridge housing 72. As described with respect to Figure 5 and 6 and as will be described in greater detail below, this cavity 73 is used to engage a portion of a coupling part so as to allow relative rotation between the cartridge holder 72 and the dose setting mechanism.

In this preferred arrangement, coupling part 80 comprises a thin metal pressing.

However, those of ordinary skill will recognize that alternative coupling part arrangements may also be used. In this preferred arrangement, the coupling part 80 comprises a first set of axial projecting members 82a, 82b that project in an axial direction towards the distal end 69 of the cartridge housing 72. These projecting members 82a, 82b rotationally affix or engage a first portion 75 of the cavity 73. In WO 2010/139634 PCT/EP2010/057473 15 addition, the coupling part 80 rotationally couples to a spindle nut and therefore a spindle of a dose setting mechanism and also acts upon a dose dial sleeve of the dose setting mechanism.

The coupling part 80 further comprises a second set of axial projecting members 86a, 86b. This second set of projecting members 86a, 86b extend in a proximal direction away from the proximal end 68 of the cartridge housing 72. This second set of projecting members 86a, 86b engage a portion of the dose setting mechanism, specifically an inner housing of the dose setting mechanism. As described below, the coupling part 80 further comprises two inwardly extending arms 84a, 84b that engage a spindle nut of the dose setting mechanism.

Figure 8 illustrates how the coupling part 80 illustrated in Figure 7 may be used to engage an inner housing 92 of a dose setting mechanism, such as the dose setting mechanism illustrated in Figures 5 and 6. As illustrated, the inner housing 92 comprises a first and a second flexible locking elements 98a, 98b located near a distal end 93 of the inner housing 92. Also near this distal end 93 is a circular shaped housing portion 94. This housing portion 94 defines a cavity portion 101 having an inner surface and along this inner surface there are two internally radially directed recesses 96a and 96b.

During assembly, the coupling part 80 will be positioned to slide into the cavity 101 of the housing portion 94 such that the second set of protruding members 86a, 86b of the coupling part 80 slide through recesses 96a, 96b of the housing portion 94, respectively. The second members 86a, 86b will then be positioned to reside over an external surface of the inner housing flexible elements 98a, 98b, respectively. In this position, the drug delivery device will not be primed but rather the dose dial sleeve 103 will be locked out and prevented from rotating. As such, a user of such a drug delivery device will be prevented from selecting a dose, that is, the user will be prevented from rotating the dose dial sleeve 103 before the user has under taken a drug delivery device priming step. WO 2010/139634 PCT/EP2010/057473 16

Figure 9 illustrates the coupling part 80 engaged with the distal end 93 of the inner housing 92. As illustrated, the coupling part 80 is in an initial position or in a non- primed state, before device priming occurs. In this initial position, the set of protruding elements 86a, 86b reside over the surface of the flexible elements 98a, and 98b, respectively. Therefore, when a cartridge holder is connected to the housing and is rotated (as illustrated in Figures 4 and 5), the coupling part 80 also rotates. As the coupling part 80 is rotated in the direction of arrow D1, the first set of protruding elements 86a, 86b rotate over the flexible locking elements 98a, 98b and end up releasing these flexible locking elements, and therefore stop faces 106a, 106b from the dose dial sleeve. Figure 10 illustrates the coupling part 80 and inner housing 92 after rotating the coupling part to release the flexible locking elements and thereby completing of the priming step. As illustrated, the coupling part 80 has been rotated to a final or stop position 102 and the coupling part 80 has now been is rotated less than 360 degrees so as to push the inner housing flexible elements 98a, 98b radially inward. This releases the inner housing stop faces 106a, 106b, from the dose dial sleeve 103. Figure 11 illustrates a close up view of the stop faces 106a, 106b provided along the distal end of the inner housing 92. The dose dial sleeve 103 is also illustrated with a scale arrangement 104 provided along an outer surface of this dose dial sleeve 103.

The dose dial sleeve 103 has mating stop faces 97a, 97b that engage with stop faces 106a, 106b on the inner housing. A spindle nut 114 is coupled to the coupling part 80 so that when the coupling part 80 rotates the spindle nut 114 rotates to drive a spindle 124 distally. As illustrated, this spindle nut 114 is circular in shape and comprises a first and a second helical ramp 116a, 116b. The spindle nut 114 further comprises a circular cavity having a male groove member 118. Once assembled, the spindle nut 114 is rotationally coupled to the coupling part 80 so that when a cartridge holder is coupled to a dose setting member and the cartridge holder is rotated, the spindle nut 114 rotates along with the cartridge holder. The first and second helical ramps 116a, 116b serve to drive the spindle nut 114 in a distal direction (i.e., towards the injection site) when the cartridge holder is rotated. Where the spindle nut 114 is used in a non-resettable drug delivery device, these helical ramps lock the cartridge holder rotationally at the end of the WO 2010/139634 PCT/EP2010/057473 17 priming step. However, where the spindle nut is used in a resettable drug delivery device, the helical ramps are detented so as to allow the cartridge housing 72 to be rotated back and removed to enable a new cartridge to be fitted. 5 The height of the helical ramps 116a, 116b help to offset any slack in the drive mechanism that drives the spindle of the dose setting mechanism forwards to dispense a dose. In this manner, rotating the cartridge holder is generally equivalent to pressing on a dose button of the dose setting mechanism so as to take up slack in the drive mechanism. 10

Figure 13 illustrates the spindle nut 114 coupled to the coupling part 80 and inner housing 92 of a dose setting mechanism. In this illustration, the coupling part 80 is rotated by the cartridge holder (not illustrated). This in turn rotates the spindle nut 114. As illustrated, this spindle has at least two overlapping grooves. Preferably, one of 15 these grooves 130 is engaged with a portion of the drug deliver device and could be either helical or axially extending along its length.

Because in one arrangement the spindle 124 is threaded to a portion of the drug delivery device, as the spindle nut 114 rotates, it advances the spindle 124 axially in 20 the distal direction D2 128 so as to prime the drug delivery device. The rotation of the cartridge housing, as mentioned, also unlocks the dose dial sleeve 103 to allow a user to now sett a first dose of medication for the drug delivery device.

Exemplary embodiments of the present invention have been described. Those skilled 25 in the art will understand, however, that changes and modifications may be made to these embodiments without departing from the true scope and spirit of the present invention, which is defined by the claims.