Assembly for a drug delivery device

Abstract

An assembly for a drug delivery device (1) is provided, the assembly comprising a piston rod (10) and a force transfer subassembly (16, 17), the force transfer subassembly being arranged and configured, in a driving mode of operation of the assembly, to transfer a driving force (F) to the piston rod in order to drive the piston rod, the force transfer subassembly comprising a first force transfer member (17), and a second force transfer member (16), wherein the first force transfer member and the second force transfer member are operatively coupled to each other via a force-sensitive coupling (27) to transfer the driving force to the piston rod, and wherein, when an excessive force acts on the force-sensitive coupling, the force-sensitive coupling is arranged and configured to be released in order to switch the assembly from the driving mode of operation into a security mode of operation.

Claims

1. An assembly for a drug delivery device, comprising: a piston rod; and a force transfer subassembly, the force transfer subassembly being configured, in a driving mode of operation of the assembly, to transfer a driving force to the piston rod in order to drive the piston rod, the force transfer subassembly comprising: a first force transfer member, and a second force transfer member, wherein the first force transfer member and the second force transfer member are operatively coupled to each other via a force-sensitive coupling, the force-sensitive coupling is configured to transfer the driving force to the piston rod, and wherein the force-sensitive coupling is configured to be released when an excessive force acts on the force-sensitive coupling to switch the assembly from the driving mode of operation into a security mode of operation.

2. The assembly according to claim 1, wherein, in the driving mode of operation, the first force transfer member and the second force transfer member are configured to be moved in a force transfer direction to transfer the driving force to the piston rod, and wherein, when the force-sensitive coupling is established, movement of the first force transfer member relative to the second force transfer member in the force transfer direction is prevented, whereas, when the force-sensitive coupling is released, movement of the first force transfer member relative to the second force transfer member in the force transfer direction is allowed.

3. The assembly according to claim 2, wherein the first and second force transfer members are configured such that when the first force transfer member moves with respect to the second force transfer member in the force transfer direction, the force required for the relative movement is a lost force not being transferred to the piston rod.

4. The assembly according to claim 2, wherein the force transfer direction is an axial direction.

5. The assembly according to claim 1, wherein the driving force is a user generated force.

6. The assembly according to claim 1, wherein the first force transfer member and the second force transfer member are axially guided.

7. The assembly according to claim 1, further comprising a housing, wherein the second force transfer member is retained within the housing and the first force transfer member is accessible from outside of the housing, and wherein the first force transfer member is configured to act as a dose member which can be manipulated by a user.

8. The assembly according to claim 1, wherein the second force transfer member is a drive member configured to act on the piston rod to drive movement of the piston rod.

9. The assembly according to claim 1, wherein the assembly is configured to provide a feedback to the user that the assembly is being switched into the security mode of operation and/or is in the security mode of operation.

10. The assembly according to claim 1, wherein the first force transfer member defines an indicator window which is visible from outside of the assembly and wherein information displayed in the indicator window is different in the driving mode of operation and in the security mode of operation.

11. The assembly according to claim 10, wherein, in the security mode of operation, a surface of the second force transfer member is displayed in the indicator window.

12. The assembly according to claim 1, wherein the first force transfer member and the second force transfer member are engaged with one another to establish the force-sensitive coupling, the engagement being releasable to release the force-sensitive coupling.

13. The assembly according to claim 12, wherein the engagement is configured to provide one or both of the following feedbacks when it is released: audible feedback and tactile feedback.

14. The assembly according to claim 1, wherein the assembly, when in the security mode of operation, is switchable into the driving mode of operation.

15. A drug delivery device comprising: a housing; an assembly at least partially disposed in the housing, the assembly comprising: a piston rod, and a force transfer subassembly, the force transfer subassembly being configured, in a driving mode of operation of the assembly, to transfer a driving force to the piston rod in order to drive the piston rod, the force transfer subassembly comprising: a first force transfer member, and a second force transfer member, wherein the first force transfer member and the second force transfer member are operatively coupled to each other via a force-sensitive coupling, the force-sensitivity coupling is configured to transfer the driving force to the piston rod, and wherein the force-sensitive coupling is configured to be released, when an excessive force acts on the force-sensitive coupling, wherein releasing the force-sensitive coupling switches the assembly from the driving mode of operation into a security mode of operation; and a reservoir at least partially disposed in the housing, the reservoir comprising a drug to be delivered by the device.

16. The drug delivery device of claim 15, wherein the reservoir comprises a pharmaceutically active compound.

17. A method comprising: applying a force to a proximal end of a drug delivery device, first and second force transfer members of a force-sensitive coupling of the drug delivery device being in a driving mode of operation, the force-sensitive coupling transferring the force to a piston rod of the drug delivery device to drive the delivery of a drug from the drug delivery device, and increasing the applied force above a threshold value, the increased force decoupling the first and second force transfer members and switching the drug delivery device from the driving mode of operation into a security mode of operation, thereby preventing the applied force from being transferred to the piston rod.

Description

(1) Further features, refinements and advantageous embodiments of the present disclosure become apparent from the following description of the exemplary embodiments in conjunction with the appended figures.

(2) FIG. 1 shows an exemplary embodiment of a drug delivery device on the basis of a schematic sectional view.

(3) FIG. 2 shows a section of a piston rod of the drug delivery device.

(4) FIG. 3 shows, on the basis of a schematic sectional view, a section of a drive member of the drug delivery device.

(5) FIG. 4 shows, on the basis of a schematic sectional view, the interaction between the drive member and the piston rod of FIGS. 2 and 3.

(6) FIG. 5 shows the drug delivery device in a driving mode of operation when a dose was set.

(7) FIG. 6 shows the associated sectional view.

(8) FIG. 7 shows, on the basis of a schematic side view, the device in a security mode of operation.

(9) FIG. 8 shows the associated sectional view.

(10) In the figures, identical elements, identically acting elements and elements of the same kinds are designated with the same reference numerals. Furthermore, for a better illustration of the disclosed concepts, certain features of the depicted elements may be depicted in an exaggerated fashion and not true to scale in order to facilitate explanation of the disclosed concepts.

(11) FIG. 1 shows, on the basis of a schematic sectional view, an exemplary embodiment of a drug delivery device 1. The drug delivery device 1 may be an injection device. The drug delivery device 1 may be a pen-type device. The drug delivery device 1 may be a disposable or a reusable device. The drug delivery device 1 may be a fixed dose device. Alternatively, the present concept is also applicable for variable dose devices where the size of the dose to be set can be varied by the user, whereas in fixed dose devices the size of the dose may not be varied by the user but is present by the device design.

(12) It should be noted that the above-mentioned concept with the attenuation member should not be construed to be limited to the particular drug delivery device 1 described herein below although it may be particularly advantageous for this device.

(13) The drug delivery device 1 comprises a cartridge 2. Within the cartridge a drug 3, which may be a liquid drug, is retained. Furthermore, a bung 4 is movably retained in the cartridge 2. The bung 4 seals the cartridge 2 proximally to prevent drug 3 from dripping out of the cartridge 2. If the bung 4 is driven in the distal direction with respect to the cartridge, drug may be dispensed from the cartridge through an outlet 5 of the cartridge, provided that fluid communication between the interior of the cartridge and the exterior is provided, for example by means of a needle unit which pierces membrane 6 which seals the outlet 5.

(14) Distal as used herein refers to the direction or the end of an element facing the dispensing end of the drug delivery device and proximal as used herein refers to the direction or the end of an element facing away from the dispensing end of the drug delivery device.

(15) The term drug, as used herein, preferably means a pharmaceutical formulation containing at least one pharmaceutically active compound,

(16) 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, an enzyme, an antibody or a fragment thereof, a hormone or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound,

(17) 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,

(18) 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,

(19) wherein in a further embodiment the pharmaceutically active compound comprises at least one human insulin or a human insulin analogue or derivative, glucagon-like peptide (GLP-1) or an analogue or derivative thereof, or exendin-3 or exendin-4 or an analogue or derivative of exendin-3 or exendin-4.

(20) 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.

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

(22) 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.

(23) Exendin-4 derivatives are for example selected from the following list of compounds:

(24) H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

(25) H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

(26) des Pro36 Exendin-4(1-39),

(27) des Pro36 [Asp28] Exendin-4(1-39),

(28) des Pro36 [IsoAsp28] Exendin-4(1-39),

(29) des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

(30) des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

(31) des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

(32) des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

(33) des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

(34) des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

(35) des Pro36 [Asp28] Exendin-4(1-39),

(36) des Pro36 [IsoAsp28] Exendin-4(1-39),

(37) des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

(38) des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

(39) des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

(40) des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

(41) des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

(42) des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

(43) wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative;

(44) or an Exendin-4 derivative of the sequence

(45) des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

(46) H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

(47) des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

(48) H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

(49) H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

(50) des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

(51) H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

(52) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

(53) H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

(54) H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

(55) H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

(56) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

(57) des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

(58) H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

(59) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

(60) H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

(61) des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

(62) H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

(63) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

(64) des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

(65) H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

(66) H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

(67) H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

(68) H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1-39)-NH2,

(69) H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

(70) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

(71) des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

(72) H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2,

(73) H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2;

(74) or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exendin-4 derivative.

(75) 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.

(76) 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.

(77) Antibodies are globular plasma proteins (150 kDa) that are also known as immunoglobulins which share a basic structure. As they have sugar chains added to amino acid residues, they are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

(78) The Ig monomer is a Y-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds between cysteine residues. Each heavy chain is about 440 amino acids long; each light chain is about 220 amino acids long. Heavy and light chains each contain intrachain disulfide bonds which stabilize their folding. Each chain is composed of structural domains called Ig domains. These domains contain about 70-110 amino acids and are classified into different categories (for example, variable or V, and constant or C) according to their size and function. They have a characteristic immunoglobulin fold in which two sheets create a sandwich shape, held together by interactions between conserved cysteines and other charged amino acids.

(79) There are five types of mammalian Ig heavy chain denoted by , , , , and . The type of heavy chain present defines the isotype of antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.

(80) Distinct heavy chains differ in size and composition; and contain approximately 450 amino acids and approximately 500 amino acids, while and have approximately 550 amino acids. Each heavy chain has two regions, the constant region (C.sub.H) and the variable region (V.sub.H). In one species, the constant region is essentially identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains , and have a constant region composed of three tandem Ig domains, and a hinge region for added flexibility; heavy chains and have a constant region composed of four immunoglobulin domains. The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain.

(81) In mammals, there are two types of immunoglobulin light chain denoted by and . A light chain has two successive domains: one constant domain (CL) and one variable domain (VL). The approximate length of a light chain is 211 to 217 amino acids. Each antibody contains two light chains that are always identical; only one type of light chain, or , is present per antibody in mammals.

(82) Although the general structure of all antibodies is very similar, the unique property of a given antibody is determined by the variable (V) regions, as detailed above. More specifically, variable loops, three each the light (VL) and three on the heavy (VH) chain, are responsible for binding to the antigen, i.e. for its antigen specificity. These loops are referred to as the Complementarity Determining Regions (CDRs). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chains, and not either alone, that determines the final antigen specificity.

(83) An antibody fragment contains at least one antigen binding fragment as defined above, and exhibits essentially the same function and specificity as the complete antibody of which the fragment is derived from. Limited proteolytic digestion with papain cleaves the Ig prototype into three fragments. Two identical amino terminal fragments, each containing one entire L chain and about half an H chain, are the antigen binding fragments (Fab). The third fragment, similar in size but containing the carboxyl terminal half of both heavy chains with their interchain disulfide bond, is the crystalizable fragment (Fc). The Fc contains carbohydrates, complement-binding, and FcR-binding sites. Limited pepsin digestion yields a single F(ab)2 fragment containing both Fab pieces and the hinge region, including the HH interchain disulfide bond. F(ab)2 is divalent for antigen binding. The disulfide bond of F(ab)2 may be cleaved in order to obtain Fab. Moreover, the variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv).

(84) 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.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology.

(85) Pharmaceutically acceptable solvates are for example hydrates.

(86) The drug delivery device 1 further comprises a drive mechanism which is arranged and operable to drive movement of the bung in the distal direction with respect to the cartridge to dispense drug 3 from the device. The device 1 described herein is similar to the one described in WO 2008/058665 A1, the disclosure content of which is incorporated by reference herewith into the present application as far as the design of the device and, in particular, of its drive mechanism, is concerned. Elements of the drive mechanism may be housed in a body or housing 7 of the drug delivery device 1. The cartridge may be connected to the body 7, either directly or, as depicted, by means of a cartridge retainer or cartridge holder 8. The cartridge holder 8 may be, releasably or permanently, coupled to the body 7.

(87) The drug delivery device further comprises a cap 9. The cap 9 is releasably attachable to the body 7 or the cartridge holder 8. The cap 9 is suitable to cover the dispensing end of the drug delivery device 1, preferably the cartridge 2 or the cartridge holder 8. For preparing the device for drug delivery, the cap may be removed and a needle unit may be attached to the outlet to provide fluid communication between the interior of the cartridge 2 and the outside.

(88) The drug delivery device 1 further comprises a piston rod 10 which is arranged to transfer a driving force to the bung 4. The piston rod 10 comprises a main body 14. The piston rod 10, in the present case a lead screw, may be threadedly engaged with a nut member 11. The nut member 11 is expediently axially and rotationally secured within the body 7. Thus, if the piston rod 10 is rotated, on account of its threaded engagement with the nut member, it is displaced axially with respect to the body and, consequently, advanced within the cartridge 2 to dispense drug 3 from the cartridge 2.

(89) The piston rod 10, particularly the main body 14, is provided with a piston rod thread 12. By means of the thread 12, the threaded engagement between piston rod 10 and nut member 11 can be established. The piston rod thread 12 is arranged in a distal section of the main body 14.

(90) In a proximal section of the piston rod 10, one or more of elastically displaceable features 13 are arranged. The elastically displaceable features 13 are elastically deformable and may be formed integrally with the main body 14 of the piston rod 10, for example. The elastically displaceable features 13 may alternatively be resiliently mounted to the main body 14. However, with respect to manufacturing costs, an integral formation is expedient. The main body 14 is expediently rigid, whereas the features 13 are flexible, on account of cut-outs in the main body 14. The features 13 extend axially. The features 13 can be embodied as axially extending fingers.

(91) The main body 14 further defines a hollow interior 15 wherein components of the device or of the piston rod 10 can be arranged. The piston rod may be a multi-part component. Alternatively, the piston rod may be a single part.

(92) The drug delivery device 1 comprises a drive member 16. The drive member may be a drive sleeve. The drive member 16 may be designed to transfer a driving force from the user to the piston rod 10. For this purpose, the drive member 16 may be movable in the proximal direction with respect to the body 7 for setting a dose and in the distal direction for delivering the dose. The distal movement may be transferred or converted into movement of the piston rod. During the proximal movement, the piston rod 10 is expediently stationary. The drive member 16 may be rotationally secured to the body such that no relative rotation may be allowed. The piston rod 10, in particular the proximal section with the elastically displaceable features is retained in and preferably in contact with the drive member 16.

(93) The device further comprises a dose member 17. The dose member 17 is operable by a user and movable with respect to the body 7 in the proximal direction to set a dose and in the distal direction for delivering the set dose. In a dispensing mode of operation of the drug delivery device, the dose member is rotationally and axially locked to the drive member, i.e. axial movement of the dose member with respect to the body is permitted, whereas rotational relative movement is prevented.

(94) The drive member 16 comprises a drive member thread 18. The drive member thread may be a female thread and/or a helical thread. The drive member thread 18 is disposed along an inner surface of the drive member 1. The drive member thread 18 may be defined by a protrusion 23, which preferably extends along the interior of the drive member 16. The drive member thread 18 is arranged to interact with the elastically displaceable features 13 during operation of the device 1. The protrusion 23 is arranged to interact with the elastically displaceable features 13 during operation of the device 1.

(95) FIG. 1 shows a drug delivery device 1 with a full cartridge 2, i.e. no dose has been delivered yet. As doses of drug are delivered from the cartridge 2 the piston rod 10 is successively moved distally with respect to the body 7 and the drive member 16.

(96) During dose setting, the piston rod 10 is axially and rotationally secured such that when the drive member 16 is moved proximally into a dose set position. During this movement of the drive member 16 the elastically displaceable features 13 of the piston rod 10 are deflected radially inwardly and slide out of engagement with the drive member thread 18 and are thus displaced relative to the main body 14. The deflection is achieved by the section of the protrusion 23 defining the drive member thread 18, while the section abuts the respective elastically displaceable feature 13. The dose setting travel of the drive member 16 just exceeds the length of one pitch of the drive member thread 18. Thus, in the dose set position, the elastically displaceable features of the piston rod 10 re-engage with the drive member thread 18 as they move back towards the undisplaced position on account of the elastic restoring force. The movement towards the undisplaced position may be stopped when the respective elastically displaceable feature hits the drive member 16 and provides an audible and/or tactile feedback that the dose has been set. For dispensing the dose, the drive member is moved in the distal direction with respect to the body 7 towards the position it had before the setting action was performed, i.e. towards the position depicted in FIG. 1. During the dispensing action, the drive member thread 18 is used to rotate the piston rod 10. Particularly, distal facing surfaces of the protrusion 23, engage proximally facing surfaces of the elastically displaceable features 13. Thus, during dose delivery, no elastic displacement of the features 13 is caused, but the piston rod 10 is rotated and thus advanced through the nut member 11. The elastically displaceable features are used to create feedback during dose setting and to drive movement of the piston rod during dose dispensing.

(97) FIG. 4 shows a situation near the end of a dose setting operation where the right elastically displaceable feature 13 is still radially inwardly displaced by a section of the protrusion 23, i.e. a position shortly before the dose setting action has been completed and before the feature 13 engages the space 24, i.e. the next winding of the thread 18. FIG. 2 shows the proximal section of the piston rod 10 and FIG. 3 shows a section of the drive member 16.

(98) During dose delivery, the drive member 16 is moved distally with respect to the body 7 and the elastically displaceable features 13, particularly a proximally facing surface thereof, interact with the drive member thread 18, particularly a distal facing surface of the protrusion defining the thread, such that, as the drive member 16 is rotationally locked to the body 7, the piston rod 10 is caused to rotate and, on account of the threaded engagement with the nut member 11, caused to advance in the distal direction with respect to the body 7. Consequently, the drive member thread 18 is designed as a non self-locking thread which causes the piston rod to rotate when it is subject to an axial load. The threads 18 of the drive member and 12 of the piston rod may have opposite hands. During dose delivery the piston rod 10 is advanced by a distance that corresponds to the relationship between the leads of the piston rod thread 12 and the drive member thread 18 which, of course, may be different. The piston rod thread 12 lead is less than the one of the drive member thread 18. The mechanical advantage may be 3.2:1 or, if some lost motion of the drive member is accounted for which does not drive the piston rod 10, 4:1.

(99) The piston rod 10 further comprises an adjusting member 19. The adjusting member is retained within the interior 15 of the main body 14. The adjusting member 19 is threadedly engaged with the main body 14 of the piston rod 10, particularly with a thread in the region of the distal end of the main body. By means of the adjusting member 19 a length of the piston rod 10 can be varied. A distal end of the adjusting member may be provided with a bearing member 20 which is designed to abut the bung 4 to advance the bung when the piston rod 10 is moved distally. The threaded engagement between the adjusting member 19 and the main body 14 can be designed such that it is a self-locking, i.e. no relative rotation occurs when the adjusting member 19 or the main body 14 is subject to an axial load. Accordingly, it is avoided that the adjusting member 19 rotates with respect to the main body 14 when the piston rod advances axially. By means of the adjusting member the length of the piston rod can be varied. Consequently, a gap between the piston rod and the bung which gap could be present if the piston rod had a fixed length during the assembling of the device may be reduced or even eliminated by varying the length of the piston rod 10 by means of the adjusting member 19. Thus, already the first dose of drug delivered form a new cartridge by the drug delivery device 1 can be used by the user and no priming or prime shot is necessary to remove tolerances in the drug delivery device.

(100) The adjusting member 19 may be rotationally locked with respect to a locking member 21. Locking member 21 may be retained within the main body 14 of the piston rod 10. The locking member 21 may be used during assembly of the device to rotate the adjusting member and thus to vary the length of the piston rod 10. The locking member may be accessible from the proximal end of the piston rod 10 during assembly, e.g. before the dose member is secured to the drive member. Once the desired length of the piston rod has been reached, the locking member 21 may be moved axially with respect to the main body 14 and the adjusting member 19 and, during this movement, be rotationally secured with respect to the main body 14 and also axially secured against movement in the proximal and/or distal direction, for example by a snap-fit engagement, with respect to the adjusting member 19. The rotational locking between the locking member 21 and the main body 14 may be achieved by splines provided on the locking member and slots on an interior surface of the main body in a section of the main body, the splines engaging the slots when the locking member 21 is moved distally with respect to the main body 14. The proximal end section 22 of the interior 15 of the main body 14 may be open, as depicted, or closed.

(101) If the adjusting member 19 is dispensed with, the piston rod 10 may be a single partif applicable with a separate bearing 20.

(102) The device depicted in FIG. 1 is fully operable to set and dispense doses of the drug 3. In addition to the functions of the drug delivery device already described above, the drug delivery device comprises a security or protection mechanism. This mechanism ensures that excessive forces do not reach interior components of the device such as piston rod 10, bung 4 or drug 3. Consequently, damage or inaccurate operation of the device may be prevented by the security mechanism. Embodiments of the security mechanism were already described in the general part of the description to which it is also referenced in the present context.

(103) In the following text, an exemplary embodiment of a security mechanism is described in conjunction with FIGS. 5 to 8. Therein, FIG. 5 shows the drug delivery device in a driving mode of operation when a dose was set. FIG. 6 shows the associated sectional view. FIG. 7 shows, on the basis of a schematic side view, the device in a security mode of operation. FIG. 8 shows the associated sectional view.

(104) For the security mechanism a force transfer subassembly is provided which comprises a first force transfer member and a second force transfer member. These members transfer a driving force through the device in a driving mode of operation and, due to a force-sensitive coupling established between them, prevent an excessive force from being transferred in the device to the bung or the drug when the device is switched in a security mode of operation from the driving mode.

(105) The described exemplary embodiment of the force transfer subassembly comprising the first and the second force transfer members is described below using the dose member 17 as the first force transfer member and the drive member 16 as the second force transfer member. However, it will be readily apparent to one of skill in the art that other members which are transferring a force through a device could be used for a force transfer subassembly, especially in other drug delivery devices for which the disclosed concepts may also apply. However, for the currently described device using dose member 17 and drive member 16 as first and second force transfer members, respectively, is particularly advantageous. Accordingly, references above and below to the dose member 17 and the drive member 16 may be regarded as references to the first force transfer member and the second force transfer member, respectively.

(106) FIG. 5 shows the drug delivery device 1 in a dose set position, i.e. a position in which the dose member 17 has been moved in the proximal direction with respect to the housing from an initial position to a dose set position in order to set a dose. The dose member 17 comprises an indicator window 25 which is provided in a side surface of the dose member, i.e. a surface extending away, particularly in the distal direction, from an end surface or actuation surface 26, which is designed to be contacted by a user's finger, e.g. the thumb, when moving the dose member 17 into the distal direction with respect to the housing for delivering a set dose. The dose member may, consequently, be a dose button.

(107) The dose member 17 is designed as a hollow component which, in its interior, has received at least a part of the drive member 16. As can be gathered from FIG. 6, the drive member 16 in the dose set position, is spaced apart from the indicator window 25 and not visible within the indicator window.

(108) Furthermore, the drive member 16 and the dose member 17 are coupled to each other via the force-sensitive coupling 27. The coupling 27 is designed such that during regular operation of the device, i.e. in the dispensing mode where setting and dispensing movements can be performed, the dose member and the drive member are coupled. Particularly, they are coupled in the axial direction, i.e. that direction in which forces are transferred by means of the force transfer subassembly. Within body 7, dose member 17 and drive member 16 may be axially guided, i.e. they are prevented from rotation with respect to the body. A guide slot and a cooperating protrusion may be provided for this purpose. In the dispensing mode of operation of the drug delivery device 1, the dose member 17 and the drive member 16 act as a single part. The coupling 27 is preferably so stable that regularly applied forces for dose setting and/or dose delivery, i.e. setting forces and dispensing forces, are reliably transferred via the force transfer subassembly comprising drive member 16 and dose member 17.

(109) If the device is in the dose set position as depicted in FIG. 1, there are a plurality of potential unpredictable events which can occur and which may significantly increase the force acting on the device, e.g. the force which would be required to inject or eject medicament from the cartridge 2, potentially to an extent which negatively affects the dose accuracy of the device or even damages the device. One of these events is a blocked needle. The force which would be required to dispense liquid from the blocked needle may be so high that interior components would be seriously damaged if the force was tried to be transferred within the device. Another possible event is that the device is dropped on the floor in the dose set position of the dose member. When this happens, the actuation surface 26 may hit the floor with a significant force acting on the dose member 16, the force also being so high that it potentially damages interior components of the device or affects the dose accuracy.

(110) In order to prevent negative effects of this kind, the coupling 27 is designed to be a force-sensitive coupling. The force-sensitive coupling is designed such that it transfers regularly occurring forces during setting and dispensing reliably but is released once an excessive force, such as an impact force when the device hits the ground or a force being exerted by a user when the needle is blocked, acts on the coupling. For this purpose, an exemplary embodiment of the coupling 27 comprises a protrusion 28 provided at the dose member 17. The protrusion extends radially inwardly into the interior of the dose member 17. The protrusion 28 may be formed circumferentially, preferably ring-like. The coupling 27 further comprises an indentation 29. The indentation 29 is provided at the drive member 16. The indentation extends particularly in the radial direction. The indentation 29 may be provided on an outer surface of the drive sleeve 16. As long as the protrusion 28 engages the indentation 29, the force transfer subassembly transfers forces within the device and particularly it transfers forces directed into the distal axial direction to the piston rod. Usually driving forces are higher than setting forces so that it is particularly expedient to design the force-sensitive coupling to at least transfer regular driving forces within the device.

(111) From the position depicted in FIG. 6, a distally acting force F may be exerted by a user. If the device operates normally and the force F is less than the maximum acceptable driving force, this force is transferred to the piston rod 10 and the bung 4 within the cartridge 2 and results in a dose of drug 3 being dispensed from the device 1. If, however, one of the above events occurs, the force-sensitive coupling 27 is released when the user applies an excessive force, thereby permitting relative movement between the dose member 17 and the drive member 16. In order to release the coupling, the drive member and/or the dose member may be slightly deformed, particularly in a radial direction and/or elastically. Thereby the engagement between the drive member and the dose member may be released, particularly by the protrusion 28 disengaging the indentation 29. The release may generate an audible noise and/or a vibration which the user may experience. This informs the user that the device does not operate in a normal way and is being switched into the security mode of operation. After the engagement has been released, the dose member 17 is axially displaced in the distal direction with respect to the drive member 16 without the drive member 16 being displaced in the distal direction with respect to the body 7. Consequently, the force F is not transferred to the drive member, i.e. the second force transfer member, and consequently not to the piston rod 10. Rather, this force is only used for the relative movement between dose member 17 and drive member 16.

(112) The maximum admissible dispensing force which may be transferred via the force-sensitive coupling can be adjusted by means of the interfaces between the protrusion 28 and the indentation 29, for example by the radial extension of the protrusion and/or the indentation. Relative movement between the dose member and the drive member in the dose setting direction may be prevented in the driving mode. That is to say, the force-sensitive coupling may be designed as non-releasable when the force transfer subassembly is moved for setting a dose in the dose setting direction. This prevents that the device can be easily disassembled by the user. The proximal face of the protrusion may be steeper than the distal face for this purpose (not explicitly illustrated). It is, of course, readily apparent to a person of skill that the protrusion may also be arranged on the drive member 16 and the indentation on the dose member 17. Further, other force-sensitive couplings may readily apparent to a person of skill depending on in what kind of device the force-sensitive coupling is applied for.

(113) FIGS. 7 and 8 show the drug delivery device with the dose member 17 having resumed its end position with respect to drive member 16 after having performed the relative movement. In this position, an outer surface of the drive member 16 is displayed in the window. The drive member 16 is preferably coloured, e.g. red, such that a user may easily identify that the device is in the security mode of operation and that the dose he tried to deliver was not properly delivered, for example, due to a blocked needle. Accordingly, various feedbacks are provided to the user that the device does not function properly in case an excessive force is applied to the dose member 17.

(114) Thus, by means of the proposed security mechanism it is ensured that the device components are not getting damaged and also that the user is informed that the device does not function properly.

(115) The coupling 27 may be designed to be re-establishable, for example by proximal movement of the dose member 17 with respect to the drive member 16. After a subsequent dose setting movement has been performed, this again results in a dose set position which is depicted in FIG. 6. If the cause for the switching into the security mode, for example the blocked needle, is removed, the device may be used normally. Alternatively, in case the coupling is not re-establishable the device may be locked out and not be used again, as it has functioned improperly only once.

(116) Although the security mechanism has been described in detail herein only with respect to the drug delivery device described in conjunction with FIGS. 1 through 4, it should be readily apparent to a person of skill that the disclosed concept could also apply to other devices, e.g. devices using a toothed rod instead of a lead screw as the piston rod or employing different drive mechanisms. Particularly, it need not be an axial force which is transferred and used to release the force-sensitive coupling. It could also be a rotational force and/or a force comprising rotational and axial components. Some examples suitable for other mechanisms are disclosed in the general part of the description to which it is referred in this regard.

(117) The scope of protection of the invention is not limited to the examples given hereinabove. The invention is embodied in each novel characteristic and each combination of characteristics, which particularly includes every combination of any features which are stated in the claims, even if this feature or this combination of features is not explicitly stated in the claims or in the examples.

REFERENCE NUMERALS

(118) 1 drug delivery device 2 cartridge 3 drug 4 bung 5 outlet 6 membrane 7 body 8 cartridge holder 9 cap 10 piston rod 11 nut member 12 piston rod thread 13 elastically displaceable feature 14 main body 15 interior 16 drive member 17 dose member 18 drive member thread 19 adjusting member 20 bearing member 21 locking member 22 proximal end section 23 protrusion 24 space 25 indicator window 26 surface 27 coupling 28 protrusion 29 indentation F force