Last dose mechanism and drug delivery device herewith

Abstract

The present disclosure relates to a last dose mechanism for use in a drug delivery device (1) and to a drug delivery device (1) with improved sustainability The last dose mechanism substantially comprises a drive sleeve (12) and a nut (17) in threaded engagement with the drive sleeve (12). The drive sleeve (12) and the nut (17) are both made of polypropylene (PP). The nut (17) is a full ring nut.

Description

[0001] Description

[0002] LAST DOSE MECHANISM AND DRUG DELIVERY DEVICE HEREWITH

[0003] The present disclosure is generally directed to improvements in sustainability of a last dose mechanism for a drug delivery device, e.g. for a pen type injection device, and of a drug delivery device with such a drive mechanism. Pen type drug delivery devices have application where regular injection by persons without formal medical training occurs. This is increasingly common among patients having e,g. diabetes where self-treatment enables such patients to conduct effective management of their disease.

[0004] In certain types of drug delivery devices, such as pen type devices, cartridges filled with a liquid drug 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 comprises a pierceable seal. To dispense a dose of drug from such a cartridge, the drug delivery device has a dose setting and drive mechanism that uses a piston rod or lead screw moving in a distal direction and pressing the bung distally which expels a certain set dose of drug from the cartridge. As drug runs low in the cartridge, a user may attempt to set a dose that exceeds the amount of drug left in the cartridge. In order to ensure dose accuracy, it is important that a drug delivery device is designed to not allow a user to dial a dose that is greater than the amount of drug which can be expelled from the cartridge by means of a so called last dose mechanism. A drug delivery device with such a last dose mechanism is disclosed in EP 1 603 611 B1 and EP 2 437 829 B1.

[0005] More specifically, in EP 1 603 611 B1 , the last dose mechanism comprises a nut component which is a half nut that clips onto a threaded outer region of a drive sleeve which is provided between two radially protruding flanges. During the operation of the device, the last dose nut which is axially displaceable but rotationally constrained within the drug delivery device advances along the threaded region of the rotating drive sleeve in proportion to the size of doses that are selected with the mechanism. When the device has reached the maximum number of permissible doses (equivalent to the contents of the cartridge), a rotational stop feature on the last dose nut engages with a rotational stop feature on the upper flange of the drive sleeve and prevents any further doses to be dialed into the device. A similar device further comprising an annular lock teeth ring on the drive sleeve is disclosed in US 2023 / 014860 A1.

[0006] 3. Dezember 2025 S 100 P 560 WO For such devices which provide for self-administration of a medicinal product from a multi-dose cartridge and permit a user to individually set a variable delivery dose, there is a general distinction between devices which are intended to be reused when the cartridge is empty by replacing the empty cartridge by a new cartridge and devices which are intended to be disposed of when the cartridge is empty. In reusable devices it is required to reset the last dose mechanism before or when replacing the cartridge. An example of such a reusable and resettable drug delivery device is disclosed in EP 2 437 825 B1. In contrast to that, EP 1 603 611 B1 discloses a disposable, i.e. non-reusable and non-resettable, drug delivery device.

[0007] As some users may apply a large turning force (i.e., a large torque load) when attempting to dial a dose that exceeds the amount of drug left in the cartridge, it is important that the last dose mechanism of the drug delivery device be able to withstand a large force. In addition, the drive mechanism of such drug delivery devices is manually operated and it is desirable to keep dispensing forces as low as possible, especially for impaired users. Especially disposable drug delivery devices are produced in very high quantities as mass-produced items and must therefore also be able to be manufactured cost-effectively. For these reasons, such drug delivery devices typically consist of component parts from various different materials, mostly engineering polymers, tailored for the respective needs of these parts. For example, component parts intended to move relative to each other under high forces or torques are often made of PBT (polybutylene terephthalate) which may be modified with PTFE (polytetrafluoroethylene) or POM (polyoxymethylene) which may be modified with PTFE. Stiffer component parts are often made of PC (polycarbonate) whereas component parts with less mechanical requirements are made of PP (polypropylene).

[0008] When considering the life cycle of disposable drug delivery devices compared with reusable drug delivery devices, such single use devices have a higher impact on global warming, nonrenewable energy consumption, mineral resource depletion and water scarcity. Comparing such devices, it can be seen that single use devices have a significantly larger environmental impact especially when the relative volumes of drug delivered in these two formats are taken into account.

[0009] Based on the aforementioned problems, it is an object of the present disclosure to provide an improved last dose mechanism for a drug delivery device, especially for a disposable drug delivery device of the type disclosed in EP 1 603 611 B1 , having sustainability benefits compared to existing disposable drug delivery device while meeting the requirements for safe and reliable operability of the device.

[0010] 3. Dezember 2025 S 100 P 560 WO This object is essentially solved by a last dose mechanism according to claim 1 and a drug delivery device according to claim 7.

[0011] A last dose mechanism according to the present disclosure is suitable for use in a drug delivery device, for example in a drug delivery device as disclosed in EP 1 603 611 B1 and / or in a drug delivery device comprising a housing or an insert having a helical thread, a dose dial sleeve having a helical thread engaged with the helical thread of the housing or insert, a drive sleeve releasably connected to the dose dial sleeve by means of a clutch located between the dose dial sleeve and the drive sleeve such that, when the dose dial sleeve and the drive sleeve are coupled, both are allowed to rotate with respect to the housing and, when the dose dial sleeve and the drive sleeve are de-coupled, rotation of the dose dial sleeve with respect to the housing is allowed, whilst rotation of the drive sleeve with respect to the housing is not allowed, whereby axial movement of the drive sleeve is allowed.

[0012] The last dose mechanism according to the present disclosure substantially comprises the drive sleeve and a nut. The drive sleeve may be a single-piece component, e.g. a substantially tubular component part extending along a longitudinal axis from a proximal end to a distal end. The drive sleeve preferably comprises a proximal portion of at least 60% of the axial length of the drive sleeve and a distal portion comprising an outer flange arranged spaced from the distal end of the drive sleeve as well as an external threaded section. The drive sleeve may further comprise an internal helical thread extending over at least 80% of the axial length of the drive sleeve. The pitch of the external threaded section may be significantly smaller than the pitch of the internal helical thread. The term pitch shall preferably mean the distance between consecutive contours on a helical thread, measured parallel to the longitudinal axis. Further, the nut may be engaged with the threaded section of the drive sleeve and configured to be axially guided in the housing of the drug delivery device allowing axial movement of the nut but preventing rotation of the nut with respect to the housing. For a last dose function, the flange of the drive sleeve comprises a rotational stop and the nut comprises a rotational counter-stop which, when abutting each other, prevent rotation of the drive sleeve relative to the nut in one direction. When used in a drug delivery device with a cartridge, the stop and the counter-stop typically abut each other when the maximum number of permissible doses of the drug delivery device is reached, that is when a user has selected a dose equivalent to the remaining contents which can be dispensed from the cartridge.

[0013] According to the present disclosure, at least the drive sleeve and the nut are both made of PP. These component parts are typically made of POM or POM with a PTFE additive in disposable drug delivery devices. Changing the materials of the drive sleeve and the (last dose) nut to PP

[0014] 3. Dezember 2025 S 100 P 560 WO provides a number of potential sustainability benefits. PP has a lower embodied energy than POM, meaning less energy is used during manufacture, reducing carbon generation. Further, PP is already a widely recycled material with established recycling streams, meaning it can potentially be both manufactured using recycled material and can be fed into recycling streams post use. Still further, removing POM components from a drug delivery device brings it closer to being a mono-material product, made mostly of PP. This simplifies the process for recycling, removing the need for disassembly to separate different material types. This reduces the energy (carbon) used for disassembly, and increases the quantity of material that may be efficiently recycled.

[0015] Although PP is known to be suitable for medical device applications and high-volume mass production techniques, simply replacing POM or other engineering polymers by PP is not possible. For example, PP is typically less than half as strong as most engineering polymers, making dial stops weaker and the mechanism more susceptible to failure under misuse loads. Further, PP has approximately half the tensile modulus (stiffness) of POM and so is less resistant to buckling and bending under operating loads, which could impact functions such as dispense force and dose accuracy. Because of its lower stiffness, PP is also less suitable for ratchets and clicker features, for which POM performs well. Still further, PP, especially when running against itself, has a higher coefficient of friction compared to engineering polymer combinations such as POM running on PBT. If not mitigated, this would increase dispense forces. In addition, PP has a lower impact strength than many engineering polymers (especially PC). PP is especially susceptible to brittle failure when cold, e.g. at refrigeration temperature as required for storing some drugs. Finally, the transparency or haze of PP is worse than PC, which makes it less suitable for windows and lens components.

[0016] The key requirement in changing these two parts to PP is to ensure that the last dose functionality is able to meet the required strength as well as maintaining any other functional and manufacturing requirements. According to the present disclosure, the nut is a full ring rather than a half nut as in EP 1 603 611 B1. This increases the robustness of the last dose feature in two ways: The nut is stiffer and stronger, as it cannot so easily be deformed under torsional loads and the likelihood of the nut component being displaced from its threaded engagement with the drive sleeve under load is reduced. The change further requires a revised assembly compared to the device of EP 1 603 611 B1 where the nut with half nut geometry is assembled by clipping it onto the drive sleeve from the side. The full ring nut cannot be assembled in this way and will require the lower (distal) flange of the drive sleeve to be removed such that the nut can be rotationally assembled to the drive sleeve from the distal end of the drive sleeve by engaging the threads on the last dose nut and the drive sleeve. In this respect it may be

[0017] 3. Dezember 2025 S 100 P 560 WO desirable if the distal portion of the drive sleeve has a substantially cylindrical distal end with a diameter being equal to or smaller than the threaded section of the drive sleeve.

[0018] Optionally, the drive sleeve may further comprise an anti-rotation feature at its distal end configured to prevent rotation of the drive sleeve at least during production and / or assembly of the mechanism, e.g. to support the ejection of the part from the injection molding tool. In order to remove the threaded inner core pin for producing the helical thread from the bore of the drive sleeve, anti-rotation features may be useful to prevent rotation of the component while the core is wound out. The anti-rotation feature on the distal end of the drive sleeve component can interface with matching features on the ejection plate of the injection molding tool. The antirotation feature may comprise a non-circular portion, for example several distally facing teeth located at the distal end of the drive sleeve.

[0019] In the last dose mechanism, the threaded section may comprise a helical groove having a first pitch provided along a first portion of the threaded section and further comprise a second pitch provided along a second portion of the threaded section, wherein the first pitch is different from the second pitch, especially wherein the second pitch is greater than the first pitch. This design of the threaded section enables the drive sleeve to have a fast thread portion at the end of the last dose nut travel. This increases the axial travel of the last dose nut as it approaches the end stop location, which means that the rotational end stop engagement surfaces between the last dose nut and the drive sleeve can be enlarged, further increasing the torsional strength of this interface. The rotational stop and the rotational counter-stop may each comprise a radially extending stop face. The axial length of the stop faces may be within a range of about 0.5 mm to about 2 mm.

[0020] The increased second pitch is located at the end of the threaded section of the drive sleeve just before the radial stop faces engage. As an alternative, the helical groove further comprises a third pitch provided along a third portion of the threaded section at the end of the threaded section of the drive sleeve just before the radial stop faces engage. The third portion has a significantly smaller axial length than the second portion. The first pitch provided along said first portion may be substantially equal to the third pitch. This results in a very precise last dose stop position.

[0021] In order to guide the nut axially and to prevent rotation of the nut, the nut may comprise at least one radially extending protrusion configured to be guided in an axially extending internal groove of the housing of the drug delivery device. To ensure that the last dose functionality is

[0022] 3. Dezember 2025 S 100 P 560 WO able to meet the required strength, several protrusions may be provided distributed about the circumference of the nut.

[0023] A drug delivery device according to the present disclosure may comprise the last dose mechanism as defined above, a housing or an insert having a helical thread, a dose dial sleeve having a helical thread engaged with the helical thread of the housing or insert, wherein the drive sleeve is releasably connected to the dose dial sleeve by means of a clutch located between the dose dial sleeve and the drive sleeve such that, when the dose dial sleeve and the drive sleeve are coupled, both are allowed to rotate with respect to the housing and, when the dose dial sleeve and the drive sleeve are de-coupled, rotation of the dose dial sleeve with respect to the housing is allowed, whilst rotation of the drive sleeve with respect to the housing is not allowed, whereby axial movement of the drive sleeve is allowed, a spring guided in the housing allowing axial movement of the spring but preventing rotation of the spring with respect to the housing, and a cartridge containing a liquid drug. The flange and the threaded section of the drive sleeve and the nut are adapted to the cartridge and comprise the last dose mechanism with its stop faces preventing a user from setting a dose of the drug that is greater than the remaining amount of drug that can be dispensed from the cartridge.

[0024] The housing of the drug delivery device may be any exterior housing (main housing, body, shell) or interior housing (insert, inner body) having a helical thread. The housing may be designed to enable the safe, correct, and comfortable handling of the drug delivery device or any of its mechanism. Usually, it is designed to house, fix, protect, guide, and / or engage with any of the inner components of the drug delivery device or the drive mechanism by limiting the exposure to contaminants, such as liquid, dust, dirt etc. In general, the housing may be unitary or a multipart component of tubular or non-tubular shape. Usually, the exterior housing serves to house or retain a cartridge from which a number of doses of a medicinal product may by dispensed. The term helical thread according to the present disclosure shall preferably mean a full or part thread, e.g., a cylindrical spiral rib / groove, located on the internal and / or external surface of a component of the drug delivery device, having an essentially triangular or square or rounded section designed to allow continuous free rotational and / or axial movement between components.

[0025] The dose dial sleeve may be an essentially tubular component of essentially circular crosssection having a helical thread, especially a helical thread on its outer surface. The helical thread of the dose dial sleeve may have a pitch which is similar to, preferably the same as the pitch of the helical thread of the drive sleeve. The dose dial sleeve may be designed to indicate a selected dose of a dispensable product. This may be achieved by use of markings, symbols,

[0026] 3. Dezember 2025 S 100 P 560 WO numerals, etc., e.g. printed on the external surface of the dose dial sleeve or by laser marks, or the like.

[0027] The clutch and the spring may cooperate to permit and prevent rotation of the drive sleeve relative to the housing in different modes of the drug delivery device. For example, the clutch may be a sleeve permanently rotationally constrained to the drive sleeve, whereas the spring is permanently rotationally constrained to the housing. Axially facing teeth of the spring and corresponding axially facing teeth of the clutch may be designed to slip over each other during dose setting, thereby permitting rotation of the clutch and the drive sleeve relative to the spring and the housing, whereas rotation of the clutch and the drive sleeve relative to the spring and the housing is prevented during dose dispensing when the clutch is pressed against the spring. Thus, the device may be switched between a dose setting mode and a dose dispensing mode by a small axial movement of the clutch relative to the spring. Slipping of the clutch teeth over the spring teeth during dose setting may have the additional function of a clicker generating a tactile and audible feedback to the user.

[0028] According to a further independent aspect of the present disclosure, the drug delivery device can be recycled in a PP waste stream. This means that plastic materials that cannot be recycled in a PP waste stream are eliminated and replaced by other materials, like PP, COC (cyclic olefin copolymer), COP (cyclic olefin polymer) or a PB-1 I PP blend (polybutylene-1 / polypro- pylene blend) that can be recycled within a PP waste stream. This significantly increases the sustainability of the drug delivery device. This does not exclude that the drug delivery device may comprise one or more metal parts, e.g. a spring, which can be easily removed from a PP waste stream during recycling. If the drug delivery device is made from component parts that can be recycled in a PP waste stream, this reduces embodied energy, since greenhouse gas emissions factors for polyolefins are significantly lower than most engineering polymers, typically about half. In addition this simplifies the recycling processes and potentially yields much higher quality recyclate because sorting of the recycled product would become much easier if only one type of polymer is used.

[0029] In more detail, the clutch may comprise a sleeve made of PP. The clutch may surround a portion of the drive sleeve extending proximally from the flange. The clutch may comprise distally facing teeth for engaging the spring. In addition or as an alternative, the clutch may comprise inwardly facing ribs engaging corresponding ribs of the drive sleeve. The latter increases strength and stiffness of the last dose stop because adding ribs down the length of the bore of the clutch allows it to share the torque carried by the drive sleeve. The clutch sleeve

[0030] 3. Dezember 2025 S 100 P 560 WO may further comprise ratchet features, e.g. four ratchet features, interacting with axially extending grooves of the housing generating a feedback during dose dispensing.

[0031] The drug delivery device may further comprise a lead screw or piston rod made of PP which is in threaded engagement with the internal helical thread of the drive sleeve and with a threaded portion of the housing. In more detail, the lead screw may comprise a first helical thread located at a first end and a second helical thread located at a second end, whereby the threads may have opposite dispositions. In addition, the pitch of the first helical thread of the lead screw may be greater than the pitch of the second helical thread of the lead screw.

[0032] According to another aspect, the drug delivery device may further comprise a bearing made of PP. The bearing may be cup-shaped with a radially extending proximal flange wherein the lead screw comprises a tip at its distal end engaging the bearing. The lead screw can then be supported by this bearing and this reduces the risk of buckling if molded in PP. The bearing surface on the end of the lead screw may have a small diameter reducing losses in the dispense force.

[0033] In the drug delivery device, at least one of the housing, the dose dial sleeve, a dial grip constrained to the dose dial sleeve and a button axially fixed to the clutch may be made of PP. Further, if the housing comprises an insert with the helical thread engaging the dose dial sleeve, the insert may be made of COC or COP. The frictional interface between the dose dial sleeve and insert is typically a sensitive interface regarding dispensing forces in the pen and may be lubricated, e.g. with a silicone-based grease. Dissimilar materials of dose dial sleeve and insert may reduce friction because PP, especially when running against itself, has a higher coefficient of friction compared to engineering polymer combinations.

[0034] According to a still further independent aspect of the present disclosure, the cartridge may comprise a body receiving the drug, wherein the body is made of COC or COP. The cartridge may be directly attached to the housing, i.e. without an additional cartridge holder. Thus, the cartridge may comprise retaining features for permanently constraining the body to the housing. The cartridge body may be closed at its proximal end by a stopper made of PB-1 and at its distal end by a pierceable septum made of a PB-1 / PP blend. The stopper may comprise a cavity receiving the bearing which may be co-molded with the stopper. The distal end of the cartridge may comprises a circumferential inner groove configured for clip-on attachment of a needle hub with an injection needle.

[0035] 3. Dezember 2025 S 100 P 560 WO The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.

[0036] As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0037] The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20°C), or refrigerated temperatures (e.g., from about - 4°C to about 4°C). In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dualchamber cartridge may be configured to allow mixing between the two or more components prior to and / or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.

[0038] The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and / or prophylaxis of many different types of medical disorders.

[0039] 3. Dezember 2025 S 100 P 560 WO Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (anti-diabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.

[0040] Examples of APIs for the treatment and / or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipep- tidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and / or exchanging at least one amino acid residue occurring in the naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term ..derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and / or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.

[0041] Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Vai 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.

[0042] Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-pal- mitoyl-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

[0043] 3. Dezember 2025 S 100 P 560 WO human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega- carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(w-carbox- yheptadecanoyl)-des(B30) human insulin and B29-N-(w-carboxyheptadecanoyl) human insulin.

[0044] Examples of GLP-1 , GLP-1 analogues and GLP-1 receptor agonists are, for example, Lix- isenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semag- lutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC-1134- PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211 , CM-3, GLP- 1 Eligen, GRMD-0901 , NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador- GLP-1 , CVX-096, ZYOG-1 , ZYD-1 , GSK-2374697, DA-3091 , MAR-701 , MAR709, ZP-2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651 , ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN and Glucagon-Xten.

[0045] An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cho- lesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom.

[0046] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0047] Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Fol litropi n, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

[0048] Examples of polysaccharides include 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 polysaccharide, 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. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.

[0049] The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigenbinding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has

[0050] 3. Dezember 2025 S 100 P 560 WO reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).

[0051] The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and / or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full- length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0052] The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.

[0053] Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sari- lumab), and anti IL-4 mAb (e.g., Dupilumab).

[0054] Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.

[0055] Those of skill in the art will understand that modifications (additions and / or removals) of various components of the APIs, formulations, apparatuses, methods, systems and

[0056] 3. Dezember 2025 S 100 P 560 WO embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

[0057] An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1 :2014(E). As described in ISO 11608-1 :2014(E), needle-based injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container.

[0058] As further described in ISO 11608-1 :2014(E), a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).

[0059] As further described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with a replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation). As also described in ISO 11608- 1 :2014(E), a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).

[0060] The terms “axial”, “radial”, or “circumferential” as used herein may be used with respect to a longitudinal axis of the drug delivery device which is identical with the longitudinal axis of the drive sleeve. "Distal" is used herein to specify directions, ends or surfaces which are arranged or are to be arranged to face or point towards dispensing end of the drug delivery device and / or point away from, are to be arranged to face away from or face away from the proximal end. The dispensing end may be the needle end where a needle unit is or is to be mounted to the device, for example. On the other hand, “proximal” is used to specify directions, ends or surfaces which are arranged or are to be arranged to face away from or point away from the dispensing end of the drug delivery device or components thereof.

[0061] In the following, non-limiting, examples of the assembly of the drug delivery device are described in more detail by making reference to the drawings, in which:

[0062] 3. Dezember 2025 S 100 P 560 WO Figure 1 shows a sectional view of a prior art drug delivery device;

[0063] Figure 2 shows a last dose mechanism according to the present disclosure;

[0064] Figure 3 a detail of a drive sleeve according to the present disclosure;

[0065] Figure 4 a detail of a further example of a drive sleeve according to the present disclosure;

[0066] Figure 5 a partially cut away view of a detail of a drug delivery device according to the present disclosure;

[0067] Figure 6 a sectional view of a cartridge according to the present disclosure;

[0068] Figure 7 a perspective view of the cartridge of Figure 6;

[0069] Figure 8 a sectional view of a further example of a cartridge according to the present disclosure;

[0070] Figure 9 a cartridge with a needle hub according to the present disclosure; and

[0071] Figure 10 a sectional view of the cartridge and needle hub according to the present disclosure.

[0072] Figure 1 shows a cross-sectional view of a drug delivery device 1 according to the prior art with the same working principle as the device disclosed in EP 1 603 611 B1. The drug delivery device 1 extends from a distal end D to a proximal end P along a longitudinal axis I of the drug delivery device 1. The drug delivery device 1 comprises a drive mechanism 2 and a cartridge sub-assembly 3 with a cartridge holder 4, which is configured to accommodate a glass ampoule cartridge 5 containing the drug to be dispensed. A stopper 6 is retained in a proximal end of the cartridge 5. A removable cap 7 is releasably retained over a distal end of the cartridge subassembly 3 and can be replaced with an injection needle unit (not shown).

[0073] The mechanism 2 comprises a housing 8, a button 9, a clutch sleeve 10, a dial grip 11 , a drive sleeve 12, a lead screw 13, a spring 14, a dose dial sleeve 15 an insert 16 and a nut 17 which is a half nut. The cartridge sub-assembly 3 is secured to the housing 8.

[0074] 3. Dezember 2025 S 100 P 560 WO The button 9 is axially fixed to the clutch sleeve 10. A ratchet is provided by the clutch sleeve 10 which engages axially extending grooves in the dose dial sleeve 15. The clutch sleeve 10 is rotationally constrained to the drive sleeve 12 but can be displaced axially with respect to the drive sleeve 12 for a limited distance.

[0075] The dial grip 11 is rotationally and axially locked to the dose dial sleeve 15 which comprises numbers or markings arranged on a helical path which are visible through the insert 16. The dose dial sleeve 15 and the clutch sleeve 10 comprise corresponding sets of teeth for rotation- ally coupling and de-coupling the dose dial sleeve 15 and the clutch 10.

[0076] The drive sleeve 12 comprises a proximal portion surrounded by the clutch sleeve 10 and a distal portion with two flanges spaced from each other with a threaded section between the flanges. The nut 17 engages this threaded section and is splined to the housing 8 such that the nut 17 is prevented from rotation relative to the housing 8 but can be displaced axially with respect to the housing 8. The proximal flange of the drive sleeve 12 and the nut 17 each comprise stop features configured to prevent rotation of the drive sleeve 12 relative to the housing 8 in one direction when the stop features abut each other.

[0077] The lead screw 13 is threadedly engaged with the housing 8 in a threaded circular opening of the housing 8. The lead screw 13 is further threadedly engaged with the drive sleeve 12. A tip of the lead screw 13 or a bearing plate attached thereto abuts the stopper 6.

[0078] The spring 14 is interposed between the proximal flange of the drive sleeve 12 and the clutch sleeve 10. The spring 14 comprises radial protrusions engaging the axially extending grooves in the housing 8. Proximally facing teeth of the spring 14 engage with distally facing teeth of the clutch sleeve 10.

[0079] The insert 16 is secured against rotational or longitudinal movement relative to the housing 8 and comprises an internal helical thread engaging an external helical thread of the dose dial sleeve 15.

[0080] In a dose setting mode, without load applied by a user to button 9, the spring 14 biases the clutch sleeve 10 into its coupled position where the teeth engage corresponding teeth of the dose dial sleeve 15. To dial a dose, a user rotates the dial grip 11 and the dose dial sleeve 15. The drive member 12 and the clutch 10 rotate together with the dial grip 11 due to the clutch engagement. The dose dial sleeve 15 and the drive member 12 are moved in the proximal

[0081] 3. Dezember 2025 S 100 P 560 WO direction relative to the piston rod 13 which remains stationary. During dose setting, the nut 17 travels proximally on the threaded section of the drive sleeve 12 towards the proximal flange in proportion to the size of doses that are selected with the mechanism.

[0082] When a desired dose has been dialed, the user may dispense the dose by depressing the button 9. This displaces the clutch 10 axially with respect to the dose dial sleeve 15, thereby disengaging the clutch 10 from the dose dial sleeve 15. This switches the device into the dose dispensing mode. By depressing the button 9, the drive sleeve 12 is moved axially in the distal direction. This causes the lead screw 13 to rotate through the threaded circular opening in the housing 8, thereby advancing the stopper 6 in the cartridge in the distal direction. During dose dispensing, the drive sleeve 12 and the nut 17 are prevented from rotation with respect to the housing 8 such that the nut 17 maintains its relative position on the threaded section of the drive sleeve 12. The nut 17 is axially displaced together with the drive sleeve 12. After dose dispensing, the clutch 10 and the dose dial sleeve 15 are reengaged under force provided by the spring 14.

[0083] The drive sleeve 12 and the nut 17 form a last dose mechanism. Initially, when the drug delivery device 1 comprises a full cartridge 5, the nut 17 is located on the threaded section of the drive sleeve 12 near the distal flange. As described above, the nut 17 travels proximally on the threaded section of the drive sleeve 12 towards the proximal flange during dose setting in proportion to the size of doses that are selected with the mechanism, and the nut 17 maintains its relative position on the threaded section of the drive sleeve 12 during dose dispensing. When the device has reached the maximum number of permissible doses equivalent to the contents of the cartridge which can be dispensed (typically, a small amount of drug remains in the cartridge and cannot be dispensed due to the distal neck portion of the cartridge into which the stopper cannot enter), the rotational stop feature on the nut 17 engages with the rotational stop feature on the proximal flange of the drive sleeve 12 and prevents any further doses to be dialed into the device. However, if the last dose stop position is reached, the dose set can still be dispensed.

[0084] Figures 2 to 10 depict details of a drug delivery device with a last dose mechanism having considerable sustainability benefits compared to existing disposable drug delivery device of Figure 1. The general working principle remains identical such that in the Figures, identical elements and components as well as elements and components acting substantially identical or provided for the same purposes but belong to different examples, are provided with the same reference signs.

[0085] 3. Dezember 2025 S 100 P 560 WO Figures 2 and 3 depict a drive sleeve 12 made of PP. While the proximal portion 18 of the drive sleeve 12 is, with the exception of the material, substantially the same as in Figure 1 , the distal portion 19 differs in that only one flange 20 is provided located proximally of a threaded section 21 which engages nut 17. The nut 17 is a full ring so that it has to be mounted from the distal end of the drive sleeve 12. The nut has several radial protrusions 22 configured to engage groves in the housing. At the distal end, the drive sleeve comprises anti-rotation features 23, here exemplified by axially facing teeth. Figure 3 shows the anti-rotation feature 23 engaged with an ejection plate of the injection molding tool which prevents drive sleeve 12 from rotating when a core is wound out at the end of the molding process. The nut 17 and the flange 20 each have at east one stop face 24 abutting each other in the last dose stop position, thereby preventing that a user sets a dose exceeding the available amount left in the cartridge. An internal thread (not shown) extends substantially over the whole length of the drive sleeve 12 and is configured for engagement with the lead screw 13.

[0086] An alternative is depicted in Figure 4 which shows the proximal end of threaded section 21 with several stop faces 24 with increased contact areas of the faces that increase strength of the last dose stop mechanism between the nut and the drive sleeve. In more detail, the axial length a of the stop faces 24 is increased in the example of Figure 4. In Figure 4, the threaded section 21 comprises a helical groove having a first pitch provided along a first (distal) portion of the threaded section 21 , a second pitch provided along a second portion near the proximal end of the threaded section and a third pitch provided along a third proximal portion of the threaded section 21. The first pitch is significantly smaller than the second pitch and may be about the same as the third pitch. Thus, the drive sleeve 12 has a fast thread section with the second pitch at the end of the last dose nut travel. This increases the axial travel of the nut 17 as it approaches the end stop location defined by the flange 20, which means that the rotational end stop engagement surfaces between the nut and drive sleeve can be enlarged, further increasing the torsional strength of this interface.

[0087] Figure 5 shows a portion of drive sleeve 12 with spring 14 abutting flange 20 and engaging teeth of clutch sleeve 10. Further, a portion of insert 16 is shown threadedly engaging a portion of dose dial sleeve 15. The dose dial sleeve 15 may be made of PP whereas the insert 16 may be made of COC or COP. This threaded interface may be lubricated e.g. with a silicone-based grease in order to reduce friction and, thus dispensing force.

[0088] Figure 6 to 8 depict details of a cartridge 5 which replaces the glass ampoule and the cartridge holder 4 of Figure 1. The cartridge 5 comprises retaining features 25 at its proximal end configured to permanently secure the cartridge to the housing 8.

[0089] 3. Dezember 2025 S 100 P 560 WO Cartridge 5 is a single COC or COP molding component part with a co-molded septum 26 using e.g. a PB-1 / PP blend which is also permitting recycling in a PP waste stream.

[0090] Comparing Figures 6 and 7 with Figure 1 , the format of the cartridge 5 is changed to shorten the device (bigger bore, shorter length) thereby reducing the overall size of the pen. This also reduces the extension of the lead screw 13, which increases the robustness of the thread interface with the drive sleeve 12 by increasing the axial engagement of the lead screw 13 with the drive sleeve 12 when these two parts are relatively positioned so that they are least well engaged with each other. This has benefits especially in the condition arising when the amount of fluid remaining in the cartridge equates to the maximum selectable dose and the device is dialed to the maximum selectable dose position.

[0091] Further, the stopper 6 is designed to incorporate a cup-shaped bearing 27 receiving the distal tip of the lead screw 13 (see Figure 8). The compliant parts could be co-molded from PB-1 I PP. The core could become PP, allowing the stopper 6 to be fully recyclable with the PP pen. The PP core of the stopper 6 could have a hollow structure, saving polymer content. The bearing 27 is a part of the stopper 6. This adds stiffness to achieve high dose accuracy. The tip of the lead screw 13 is supported by the bearing 27 which reduces the risk of buckling if molded in PP. The bearing surface on the tip of the lead screw 13 has a small diameter, reducing losses in the dispense force.

[0092] Figures 9 and 10 show an improved needle unit for use with the drug delivery device 1 , especially as depicted in Figures 2 to 8. The needle unit comprises a clip-on needle hub 28 with a needle 29 that engages a circumferential inner groove at the septum 26 engagement region. This is also easy and safer to remove with a simple clip on and off using the existing outer needle cover of Figure 1. This avoids the need to rotate the cover. The needle 29 may be covered by a removable inner cover 30 which in turn is covered together with the needle hub 28 in an outer cover 31. A reduced plastic use in the needle and cover(s) has sustainability benefits.

[0093] The improved drug delivery device 1 as shown in Figures 2 to 10 reduces the embodied energy, since greenhouse gas emissions factors for polyolefins are significantly lower than most engineering polymers (typically about half). In addition, the use of PP, COC, COP and PB-1 simplifies recycling processes and potentially yield much higher quality recyclate because sorting of the recycled product is much easier if substantially only one type of polymer is used.

[0094] 3. Dezember 2025 S 100 P 560 WO Reference Numerals

[0095] 1 drug delivery device 20 flange

[0096] 2 drive mechanism 21 threaded section

[0097] 3 cartridge sub-assembly 22 protrusion

[0098] 4 cartridge holder 23 anti-rotation feature

[0099] 5 cartridge 24 stop face

[0100] 6 stopper 25 retaining features

[0101] 7 cap 26 septum

[0102] 8 housing 27 bearing

[0103] 9 button 28 needle hub

[0104] 10 clutch sleeve 29 needle

[0105] 11 dial grip 30 inner cover

[0106] 12 drive sleeve 31 outer cover

[0107] 13 lead screw

[0108] 14 spring a axial length of stop face 24

[0109] 15 dose dial sleeve

[0110] 16 insert D distal end

[0111] 17 nut P proximal end

[0112] 18 proximal portion I longitudinal axis

[0113] 19 distal portion

[0114] 3. Dezember 2025 S 100 P 560 WO

Claims

Claims1. A last dose mechanism for use in a drug delivery device (1) comprising a housing (8) or an insert (16) having a helical thread, a dose dial sleeve (15) having a helical thread engaged with the helical thread of the housing or insert, a drive sleeve (12) releasably connected to the dose dial sleeve (15) by means of a clutch (10) located between the dose dial sleeve (15) and the drive sleeve (12) such that, when the dose dial sleeve (15) and the drive sleeve (12) are coupled, both are allowed to rotate with respect to the housing (8) and, when the dose dial sleeve (15) and the drive sleeve (12) are de-coupled, rotation of the dose dial sleeve (15) with respect to the housing (8) is allowed, whilst rotation of the drive sleeve (12) with respect to the housing (8) is not allowed, whereby axial movement of the drive sleeve (12) is allowed, the last dose mechanism comprising the drive sleeve (12) and a nut (17), wherein the drive sleeve (12) comprises a proximal portion of at least 60% of the axial length of the drive sleeve (12) and a distal portion comprising an outer flange (20) spaced from the distal end of the drive sleeve (12) and an external threaded section (21), and wherein the drive sleeve (20) comprises an internal helical thread extending over at least 80% of the axial length of the drive sleeve (12), wherein the nut (17) is engaged with the threaded section (21) of the drive sleeve (12) and configured to be axially guided in the housing (8) of the drug delivery device allowing axial movement of the nut (17) but preventing rotation of the nut (17) with respect to the housing (8), and wherein the flange of the drive sleeve (12) comprises a rotational stop (24) and the nut (17) comprises a rotational counter-stop which, when abutting each other, prevent rotation of the drive sleeve (12) relative to the nut (17) in one direction, characterized in that the drive sleeve (12) and the nut (17) are both made of polypropylene (PP), that the nut (17) is a full ring nut and that the distal portion of the drive sleeve (12) comprises an anti-rotation feature (23) configured to prevent rotation of the drive sleeve (12) during production.

2. The mechanism according to claim 1 , wherein the threaded section (21) comprises a helical groove having a first pitch provided along a first portion of the threaded section (21), and further comprises a second pitch provided along a second portion of the threaded section (21), wherein the first pitch is different from the second pitch.

3. Dezember 2025 S 100 P 560 WO3. The mechanism according to claim 2, wherein, the helical groove further comprises a third pitch provided along a third portion of the threaded section (21), wherein said first pitch provided along said first portion is substantially equal to said third pitch.

4. The mechanism according to any one of the preceding claims, wherein the nut (17) comprises at least one radially extending protrusion (22) configured to be guided in an axially extending internal groove of the housing (8) of the drug delivery device (1).

5. The mechanism according to any one of the preceding claims, wherein the rotational stop (24) and the rotational counter-stop each comprise a radially extending stop face, wherein the axial length (a) of the stop faces is within a range of about 0.5 mm to about 2 mm.

6. The mechanism according to any one of the preceding claims, wherein the anti-rotation feature (23) comprises several distally facing teeth located at the distal end of the drive sleeve (12).

7. A drug delivery device (1) comprising the last dose mechanism according to any one of the preceding claims, a housing (8) or an insert (16) having a helical thread, a dose dial sleeve (15) having a helical thread engaged with the helical thread of the housing or insert, wherein the drive sleeve (12) is releasably connected to the dose dial sleeve (15) by means of a clutch (10) located between the dose dial sleeve (15) and the drive sleeve (12) such that, when the dose dial sleeve (15) and the drive sleeve (12) are coupled, both are allowed to rotate with respect to the housing (8) and, when the dose dial sleeve (15) and the drive sleeve (12) are de-coupled, rotation of the dose dial sleeve (15) with respect to the housing (8) is allowed, whilst rotation of the drive sleeve (12) with respect to the housing (8) is not allowed, whereby axial movement of the drive sleeve (12) is allowed, a spring (14) guided in the housing (8) allowing axial movement of the spring but preventing rotation of the spring (14) with respect to the housing (8), and a cartridge (5) containing a liquid drug, wherein the flange (20) and the threaded section (21) of the drive sleeve (12) and the nut (17) are adapted to the cartridge (5) and comprise a last dose mechanism with stop faces (24) preventing a user from setting a dose of the drug that is greater than the remaining amount of drug that can be dispensed from the cartridge (5).

3. Dezember 2025 S 100 P 560 WO8. A drug delivery device (1), for example according to claim 7, which can be recycled in a PP waste stream and / or which comprises only plastic parts from the group of PP, COC, COP or a PB-1 I PP blend.

9. The drug delivery device (1) according to claim 7 or 8, wherein the clutch (10) comprises a sleeve made of polypropylene surrounding a portion of the drive sleeve (12) extending proximally from the flange (20), and wherein the sleeve comprises distally facing teeth for engaging the spring (14) and / or wherein the sleeve comprises inwardly facing ribs engaging corresponding ribs of the drive sleeve (12).

10. The drug delivery device (1) according to any one of claims 7 to 9, further comprising a lead screw (13) made of polypropylene which is in threaded engagement with the internal helical thread of the drive sleeve (12) and with the housing (8).11 . The drug delivery device (1) according to any one of claims 7 to 10, further comprising a bearing (27) made of polypropylene, wherein the bearing (27) is cup-shaped with a radially extending proximal flange, and wherein the lead screw (13) comprises a tip at its distal end engaging the bearing (27).

12. The drug delivery device (1) according to any one of claims 7 to 11 , wherein at least one of the housing (8), the dose dial sleeve (15), a dial grip (11) constrained to the dose dial sleeve (15) and a button (9) axially fixed to the clutch (10) is made of polypropylene and / or wherein the insert is made of cyclic olefin copolymer.

13. The drug delivery device (1) according to any one of claims 7 to 12, wherein the cartridge (5) comprises a body receiving the drug, wherein the body is made of cyclic olefin copolymer or cyclic olefin polymer and comprises retaining features (25) for permanently constraining the body to the housing (8), and wherein the body is closed at its proximal end by a stopper (6) made of and at its distal end by a pierceable septum (26) made of a polybutylene- 1 / polypropylene blend.

14. The drug delivery device (1) according to claims 11 and 13, wherein the stopper (6) comprises a cavity receiving the bearing (27), and wherein the bearing (27) is co-molded with stopper.

3. Dezember 2025 S 100 P 560 WO15. The drug delivery device (1) according to any one of claims 7 to 14, wherein the distal end of the cartridge (5) comprises a circumferential inner groove configured for clip-on attachment of a needle hub (28) with an injection needle (29).

3. Dezember 2025 S 100 P 560 WO

Images