Drug delivery device and dose recording system having same

Abstract

The present invention relates to a drug delivery device (1) for setting and dispensing doses of a liquid drug. The device comprises a housing (10) and a dose setting and driving mechanism having a dose setting member (70). The dose setting and driving mechanism is at least partially arranged in the housing (10). The dose setting member (70) is movable relative to the housing (10) and is configured to perform a dose setting operation for selecting a dose to be delivered by the drug delivery device by moving the dose setting member (70) relative to the housing (10), and to perform a dose delivery operation for delivering a set dose by axially displacing the dose setting member (70) along the axis (X). A maximum radial extension of the dose setting member (70) perpendicular to the axis (X) is smaller than a maximum radial extension of a region of the housing (10) adjacent to the dose setting member (70).

Description

[0001] The present invention generally relates to a drug delivery device and a dose recording system comprising a drug delivery device and an electronic module attached to the drug delivery device.

[0002] Pen-type drug delivery devices may be used in situations where regular injections are performed by people without formal medical training. This may be increasingly common in patients with diabetes, where self-treatment enables such patients to effectively manage their disease. In practice, such drug delivery devices may allow the user to select and dispense variable medicament doses for a number of users individually, or may be adapted to dispense fixed doses, such as in a push-pull mechanism, or adapted to select and dispense pre-selected doses.

[0003] There are basically two types of drug delivery devices: resettable devices (i.e., reusable) and non-resettable devices (i.e., disposable). For example, disposable pen-type delivery devices are supplied as stand-alone devices. Such stand-alone devices do not have a removable pre-filled cartridge. Rather, the pre-filled cartridge cannot be removed and replaced from these devices without destroying the device itself. Therefore, such disposable devices do not need to have a resettable dose setting mechanism. Reusable drug delivery devices need to have a resettable dose setting mechanism and a refillable drug container, such as a detachable cartridge holder, which is arranged to replace the contained drug cartridge when it is empty. The present invention is equally applicable to disposable devices as well as reusable devices.

[0004] For such drug delivery devices, the functionality of recording the dose selected and / or delivered from the pen may be valuable to various device users as a memory aid or to support detailed recording of dosage history. Therefore, drug delivery devices using electronics for such purposes are becoming increasingly popular in the pharmaceutical industry and among users or patients. For example, a dose recording system is known from WO 2021 / 116387 A1, which comprises a drug delivery device and an electronic module removably mechanically coupled to the drug delivery device.

[0005] US 2015 / 0018775 A1 discloses a drug injection device having a dose dial member extending radially beyond a housing. A monitoring module may be attached to the housing of the drug injection device.

[0006] US 1 1 ,141 ,538 B2 discloses a medicament delivery device having a dose setting member between a housing portion and a medicament container holder. An actuator at one end of the housing can be pressed to effect medicament dispensing.

[0007] In known drug delivery devices or pen-type injectors with a substantially circular housing, a dose is set by moving a dose setting member (e.g., a dose dial grip) relative to the housing (e.g., rotating the dose setting member or pulling the dose setting member in an axial direction). The dose setting member diameter of such a drug delivery device either matches the diameter of the housing or is slightly larger than the diameter of the housing. This conventional arrangement allows good access to the gripping surface of the dose setting member and gives the pen a continuous aesthetic shape. However, when the pen is intended to be used in conjunction with a separate removable module attached to the dose setting member, the conventional dose setting member geometry becomes problematic because it dictates that the module size must be significantly larger than the diameter of the pen housing. In this case, if a pen with a conventional dose setting member type is equipped with a module, it is more difficult to deliver a dose, especially when the dose setting member must be rotated when delivering a dose. In addition, such a device equipped with a module is larger and more cumbersome to carry / contain in a bag or suitcase. Further, the module is more likely to accidentally fall off or be damaged, which may affect its correct function. Furthermore, due to the relatively large radial extension of the dose setting member to which the module is fitted, it is relatively easy for a user to accidentally apply excessive torque to the dial stop, which may result in accidental damage, potentially leading to dosage errors.

[0008] It is an object of the present disclosure to provide improvements in drug delivery devices and dose recording systems which do not suffer from the above-mentioned disadvantages of conventional devices.

[0009] This object is solved, for example, by the subject matter defined in claim 1. Advantageous embodiments and improvements are the subject matter of the dependent claims. However, it should be noted that the present disclosure is not limited to the subject matter defined in the appended claims. On the contrary, the present disclosure may comprise improvements in addition to or as an alternative to the improvements defined in the independent claims, as will become apparent from the following description.

[0010] One aspect of the present disclosure relates to a drug delivery device for dispensing a dose of a liquid drug, wherein the device comprises a housing, preferably a housing having a substantially circular cross-section, and a dose setting and drive mechanism having a piston rod and a dose setting member. In an example, the housing may contain a cartridge filled with a liquid drug. As an alternative, a separate cartridge holder may be permanently or releasably attached to the housing. The dose setting and drive mechanism may be at least partially arranged in the housing, and may be configured to perform a dose setting (e.g., dialing) operation for setting a dose to be delivered by the drug delivery device by moving the dose setting member relative to the housing, and to perform a dose delivery operation for delivering the set dose by axially displacing the piston rod along an axis. Preferably, the maximum radial extension of the dose setting member in a direction perpendicular to the axis is less than the maximum radial extension of the housing region adjacent to the dose setting member in a direction perpendicular to the axis. For example, in a drug delivery device having a housing having a substantially cylindrical shape, the maximum outer diameter of the dose setting member is less than the outer diameter of the housing in the housing region adjacent to the dose setting member, or even less than the maximum outer diameter of the housing. In addition, the maximum outer diameter of the dose setting member may be smaller than the inner diameter of the housing region adjacent to the dose setting member. With such a drug delivery device, the above-mentioned disadvantages of conventional pen-type injectors may be overcome, for example by providing a dose setting member with an outer diameter that nearly matches the inner diameter (i.e., the bore) of the pen housing. This results in a version that is optimized for usability and size when the module is assembled, but also maintains good functionality when the pen is used without the module assembled.

[0011] The dose setting operation for setting a dose to be delivered by the drug delivery device may comprise rotating and / or translating the dose setting member relative to the housing, e.g. along a helical path, while the dose delivery operation for delivering the set dose may comprise axially displacing the piston rod along an axis, preferably a central longitudinal axis of the piston rod. Alternatively, the dose delivery operation for delivering the set dose may comprise moving the dose setting member relative to the housing, e.g. axially displacing the dose setting member.

[0012] The drug delivery device may be suitable for setting and dispensing a variable dose of a liquid drug, thereby allowing a user to individually select and dispense a variable dose of a medicament for many users. Alternatively, the drug delivery device may be a fixed dose device, such as a push-pull device that only allows the dispensing of a predefined fixed dose. As another alternative, the drug delivery device may be suitable for selecting between one or more preset doses (e.g., a dose that exceeds or is below a threshold), as disclosed in WO 2016 / 128424 A1. Therefore, the terms "dose setting", "dose selection" and "dose dialing" used herein do not limit the drug delivery device to a specific operating mode.

[0013] The drug delivery device may include a dose setting barrel. The dose setting barrel may only display the currently set dose without causing dose selection and / or dose delivery, or in addition to displaying the dose, it may also cause dose selection and / or dose delivery (by transmitting force to the piston rod). During at least one of the dose setting operation and the dose delivery operation, the dose setting barrel may move, for example rotate, relative to the housing together with the dose setting member. In an example, the dose setting barrel rotates on a spiral path during dose setting and during dose delivery, and the dose setting member rotates on a spiral path during dose setting and during dose delivery, and moves axially without rotating during dose delivery. In another example, the dose setting barrel and the dose setting member rotate together during dose setting and dose delivery without moving axially relative to the housing.

[0014] Preferably, the drug delivery device (e.g., pen-type injector) is suitable for use with an attachable electronic module configured to capture information related to the size of the delivered dose. The module can be detachable from the drug delivery device and / or can be fixed after being attached to the drug delivery device.

[0015] The dose setting member may be provided with attachment features for mounting a separately attachable module to the drug delivery device, such as an electronic module for recording a dose set or dispensed by the drug delivery device. The dose setting member may be provided with at least one, for example substantially circular, groove extending in the proximal face of the dose setting member, wherein the attachment feature is arranged in or near the groove. The dose setting member may be provided with two concentric grooves. In an example, the attachment feature may include at least one (for example two oppositely positioned) radial aperture arranged in the dose setting member. The aperture may be arranged radially outwardly from the groove in the dose setting member, for example in an outer groove of two concentric grooves in the proximal face of the dose setting member.

[0016] In an example, a dose setting member may be arranged to be moved (e.g. rotated) by a user to set a dose, and moved (e.g. pushed) by a user to deliver a dose using a dose delivery device. The dose setting member may include two separate components that are permanently fixed to each other to function as a single component. This may be preferred for manufacturing and / or assembly reasons. In an example, the dose setting member may include a tubular sleeve having a circle of clutch teeth extending radially inward, a circle of bevel teeth extending radially inward, a contour as a gripping surface, and / or a circle of stop teeth extending distally. In addition, or as an alternative, the dose setting member may include a button. The button may have a proximal end face and a rod extending distally from the end face, wherein the rod includes at least one axially extending spline. The button may be an actuation button pushed by a user for driving or releasing a drive mechanism of a drug delivery device. These exemplary interfaces of the dose setting member facilitate a dose setting operation for setting a dose to be delivered by a drug delivery device and a dose delivery operation for delivering a set dose, and may facilitate switching between a dose setting mode and a dose delivery mode of a drug delivery device.

[0017] The electronic module may include a rotation sensor for detecting the rotation of a sensed element fixed to a component of the drug delivery device in a rotational sense, wherein the sensed element rotates relative to the dose setting member to which the electronic module is attached during dose setting and / or dose delivery. The sensed element may be fixed to the dose setting barrel. The sensed element may be an encoder ring with a pattern (e.g., an optical pattern or a magnetic pattern) that can be detected by the rotation sensor. The rotation sensor may include at least one optical sensor and / or at least one magnetic sensor.

[0018] The electronic module may use a set of optical IR emitters / detectors to detect the dose delivered from a drug delivery device (e.g. a variable dose injection pen). In order to reduce the level of stray IR radiation that may interfere with the correct performance of the module sensors (e.g. from high ambient light levels when the pen is used outdoors), the dose setting member components of the pen may have features intended to reduce / suppress the level of reflected IR radiation. In particular, the module components and / or the dose setting member may contain an IR absorbing masterbatch and / or may have a spark eroded texture surface finish.

[0019] The dose recording system according to the present disclosure includes a drug delivery device as described herein and an electronic module for releasably or fixedly attaching to a dose setting member of the drug delivery device as described herein. For example, the module may include a sensor, a processor configured to control the operation of the at least one sensor and process and / or store signals from the at least one sensor, and an attachment feature for attaching the module to the dose setting member. The module may include a cap for receiving the proximal end of the dose setting member. The maximum outer diameter of the dose setting member may be equal to or less than the inner diameter of the cap, thereby allowing the module to be attached to the dose setting member. The maximum outer diameter of the module may be equal to, similar to, or slightly greater than the outer diameter of the housing, for example, exceeding the outer diameter of the housing by about 0 mm to about 5 mm. This configuration will not hinder the dose delivery operation, even if the dose setting member must be rotated when the dose is delivered. In addition, the risk of accidental detachment or damage of the module is minimized, and accidental application of excessive torque due to an excessively large dose setting member diameter is prevented.

[0020] If the electronic module of the dose recording system is a reusable module for releasably attaching to a drug delivery device, the module may include an outer cap having a central axis, a chassis at least partially retained within the cap, and a PCB or PCBA comprising a memory and a processor. For example, the PCBA and the power supply may be retained in the cap and the chassis. Further, the light source and the optical sensor may be arranged in a circular area around the central axis, wherein the first light source and the first optical sensor are angularly offset from the second light source and the second optical sensor. One or more light guides may be provided in the chassis to guide light from the light source to the encoder and / or from the encoder to the optical sensor. In addition, a light guide may be provided in the chassis to guide light from the internal light source to the outer surface of the module so as to display information about the status or operating mode of the module.

[0021] The module may include an attachment feature for releasably mounting or securing the module to a proximal end of a drug delivery device (e.g., to a proximal end of a dose setting member, a button, or a housing). For example, the attachment feature may include at least one flexible clip for securing the module axially and rotationally to the dose setting member. The at least one flexible clip may be received within the cap and may extend substantially distally from a chassis holding the sensor and processor.

[0022] According to further aspects of the present disclosure, the dose setting member may include a mechanical encoding portion, and the module may include a mechanical pairing encoding portion that engages with the mechanical encoding portion when the module is attached to the drug delivery device. This may prevent a non-matching module from being attached to the drug delivery device. Furthermore, torque may be transmitted from the module to the dose setting member via the mechanical encoding portion and the mechanical pairing encoding portion.

[0023] The electronic module of the dose recording system may include an electronic system for use with a drug delivery device, which is suitable for recording the dose delivered from the drug delivery device. The electronic system may include a power source (e.g., a battery, such as a button cell battery), a memory for storing data, a processor configured to control the operation of the electronic system and connected to the power source and the memory. In addition, the electronic system may include at least one, preferably two sensors, the sensor being an optical sensor unit, such as a first light source having a corresponding first optical sensor and a second light source having a corresponding second optical sensor, which optical sensor units communicate with the processor. The optical sensor may be suitable for detecting the movement of the encoder of the drug delivery device, especially the movement of sections with different reflectivities of the dose sleeve, wherein the movement indicates the dose dialed (i.e., selected) and / or delivered from the drug delivery device. There are several different ways suitable for implementing the optical sensor unit. For example, the optical sensor unit may include a radiation detector, which includes an electromagnetic radiation emitter (e.g., an LED, such as an IR-LED, such as an NIR-LED) and a radiation detector. The encoder may work as described in WO 2019 / 101962 A1.

[0024] Alternatively, the electronic module may comprise one or more mechanically actuated switches, or at least one magnetic sensor arranged to detect a dose delivered by the drug delivery device.

[0025] In one example, the encoder and optical sensor unit are arranged orthogonally, i.e., they are a quarter wavelength out of phase, which means that if two light sources emit light simultaneously, for each assigned unit, only one sensor changes state. For example, this is achieved by setting two optical sensors with a circumferential offset of n*30°+15°, where n is an integer. As the encoder and sensor unit move relative to each other, one of the optical sensors that previously received light now does not receive the emitted light, or one that did not receive light now receives the emitted light. This can be achieved by the encoder selectively reflecting light. For example, a circle of teeth can be set so that the teeth reflect light, while the free space between adjacent teeth does not reflect light. As an alternative, areas that reflect light and areas that absorb light can be arranged alternately. As a further alternative, the encoder can selectively block light. In other examples, the encoder and optical sensor unit can be arranged in anti-phase. In yet another alternative, the encoder and optical sensor unit are not arranged in anti-phase, so that if two light sources emit light simultaneously, no, only one, or all optical sensors detect light, depending on the relative position of the encoder.

[0026] The electronic module of the dose recording system can be configured as a reusable clip-on module for an injection device. As an alternative, the electronic system can be a unit or module permanently attached to the injection device. The terms "electronic system" and "(electronic) module" are used for both alternatives hereinafter. The function of recording doses may be valuable to various device users as a memory aid or to support detailed recording of dose history. It is contemplated that the electronic system (e.g., electronic module) can be configured to be connectable to a mobile phone or the like to enable periodic downloading of dose history from the system.

[0027] The electronic dose recording system may further include a communication unit for communicating with another device. Preferably, the electronic module of the dose recording system is configured so that the electronic module can switch from a first state with lower energy consumption to a second state with higher energy consumption, thereby inducing the communication unit to establish the communication with another device, such as synchronization or pairing operation. The electronic control unit can issue a command, such as a signal, to another unit of the electronic dose recording system so that this unit is turned on or becomes operable. This unit can be a communication unit for communicating with another device, such as a wireless communication interface for communicating with another device via a wireless network such as Wi-Fi or Bluetooth, or even an interface for a wired communication link, such as a socket for receiving a universal serial bus (USB), mini USB or micro USB connector. Preferably, the electronic dose recording system includes an RF, WiFi and / or Bluetooth unit as a communication unit. The communication unit can be set as a communication interface between a dose recording system or a drug delivery device and an external device (e.g., other electronic devices, such as mobile phones, personal computers, laptops, etc.). For example, dose data can be transmitted to an external device by a communication unit. The dose data can be used for a dose record or dose history established in an external device.

[0028] According to yet another aspect of the present disclosure, the electronic dose recording system further has a sleep state, in which the light source is not activated (no power is provided to the light source from the power supply). The electronic dose recording system may further include at least one switch and / or a motion sensor suitable for detecting movement of the electronic system. In this example, the processor may be configured to maintain the sleep state if the at least one motion sensor does not detect switch activation or movement, and to switch to a first low power consumption state or at least one other state if the at least one motion sensor detects switch activation or movement. Typically, the sleep state or mode may be a mode in which all functions of the module are at minimum power consumption or virtually zero power consumption, but the mode does not require the system to be powered on when the electronic system (or drug delivery device) is out of sleep mode.

[0029] The present disclosure further relates to a drug delivery device having an electronic system as described above, which drug delivery device may include a cartridge containing a medicament.

[0030] The terms "drug" or "medicament" are used synonymously herein and describe a pharmaceutical preparation comprising one or more active pharmaceutical ingredients or a pharmaceutically acceptable salt or solvate thereof and optionally a pharmaceutically acceptable carrier. In the broadest sense, an active pharmaceutical ingredient ("API") is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used to treat, cure, prevent, or diagnose disease or to otherwise enhance physical or mental health. A drug or medicament may be used for a limited duration, or periodically for a chronic disorder.

[0031] As described below, a drug or medicament may include at least one API or a combination thereof in different types of formulations for treating one or more diseases. Examples of APIs 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-stranded 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.

[0032] The drug or medicament can be included in a primary package or "drug container" suitable for use with a drug delivery device. The drug container can be, for example, a cartridge, a syringe, a reservoir or other solid or flexible vessel, which is configured to provide a suitable chamber for storing (for example, short-term or long-term storage) one or more drugs. For example, in some cases, the chamber can be designed to store the drug for at least one day (for example, 1 day to at least 30 days). In some cases, the chamber can be designed to store the drug for about 1 month to about 2 years. It can be stored at room temperature (for example, about 20 ° C) or refrigerated temperature (for example, about -4 ° C to about 4 ° C). In some cases, the drug container can be or can include a dual-chamber cartridge, which is configured to store two or more components (for example, API and diluent, or two different drugs) of the pharmaceutical preparation to be applied separately, and one is stored in each chamber. In such a case, the two chambers of the dual-chamber cartridge can be configured to allow mixing between two or more components before and / or during distribution to the human or animal body. For example, the two chambers may be configured so that they are in fluid communication with each other (e.g., via a conduit between the two chambers) and allow the user to mix the two components if desired prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing when dispensing the components into a human or animal body.

[0033] The drugs or medicaments contained in the drug delivery devices as described herein can be used to treat and / or prevent many different types of medical disorders. Examples of disorders include, for example, diabetes or complications associated with diabetes (such as diabetic retinopathy), thromboembolic disorders (such as deep vein or pulmonary thromboembolism). Further examples of disorders are acute coronary syndrome (ACS), angina pectoris, myocardial infarction, tumors, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are examples as described in the following manuals: such as Rote Liste 2014 (for example, but not limited to, main group 12 (antidiabetic drugs) or 86 (oncology drugs)) and Merck Index, 15th edition.

[0034] Examples of APIs for treating and / or preventing type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin (e.g., human insulin, or human insulin analogs or derivatives); glucagon-like peptide (GLP-1), GLP-1 analogs or GLP-1 receptor agonists, or analogs or derivatives thereof; dipeptidyl peptidase-4 (DPP4) inhibitors, or pharmaceutically acceptable salts or solvates thereof; or any mixtures thereof. As used herein, the terms "analogs" and "derivatives" refer to polypeptides having a molecular structure that can be formally derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin) by deleting and / or exchanging at least one amino acid residue present in a naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or exchanged amino acid residues can be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogs are also referred to as "insulin receptor ligands." In particular, the term "derivative" refers to a polypeptide having a molecular structure that is formally derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin), wherein one or more organic substituents (e.g., fatty acids) are bound to one or more amino acids. Alternatively, one or more amino acids present in the naturally occurring peptide may have been deleted and / or replaced by other amino acids (including non-encodable amino acids), or amino acids (including non-encodable amino acids) have been added to the naturally occurring peptide.

[0035] Examples of insulin analogs 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 in which the proline at position B28 is replaced by Asp, Lys, Leu, Val or Ala and in which the Lys at position B29 may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0036] Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (insulin detemir, ); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-γ-glutamyl)-des(B30) human insulin, B29-N-ω-carboxypentadecanoyl-γ-L-glutamyl-des(B30) human insulin (insulindegludec, ); B29-N-(N-lithocholyl-γ-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0037] Examples of GLP-1, GLP-1 analogs and GLP-1 receptor agonists are e.g. lixisenatide Exendin-4 A 39-amino acid peptide produced by the salivary glands of the Gila monster), liraglutide Semaglutide, Taspoglutide, Albiglutide Dulaglutide rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211, CM-3, GLP-1Eligen, ORMD-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, Telportide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN, and Glucagon-Xten.

[0038] Examples of oligonucleotides are, for example: Mipomersen sodium Cholesterol-reducing antisense therapeutics for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrome.

[0039] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0040] Examples of hormones include pituitary hormones or hypothalamic hormones or regulatory activity peptides and their antagonists, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, tocopherol), somatropine (growth hormone), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin and goserelin.

[0041] Examples of polysaccharides include glucosaminoglycanes, hyaluronic acid, heparin, low molecular weight heparin or ultra low molecular weight heparin or derivatives thereof, or sulfated polysaccharides (e.g., polysulfated forms of the above polysaccharides), and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F20 A sodium hyaluronate.

[0042] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen binding portion thereof. Examples of antigen binding portions of immunoglobulin molecules include F (ab) and F (ab') 2 fragments, which retain the ability to bind antigens. The antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized antibody or a humanized antibody, a fully human antibody, a non-human (e.g., mouse) antibody or a single-chain antibody. In some embodiments, the antibody has effector functions and can fix complement. In some embodiments, the ability of the antibody to bind to Fc receptors is reduced or there is no such ability. For example, the antibody can be an isotype or subtype, an antibody fragment or a mutant, which does not support binding to Fc receptors, for example, its Fc receptor binding region has been mutated or deleted. The term "antibody" also includes antigen binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or dual variable region antibody-like binding proteins with cross-binding region orientation (CODV).

[0043] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., antibody heavy chain and / or light chain polypeptide) derived from an antibody polypeptide molecule, which does not include a full-length antibody polypeptide, but still includes at least a portion of a full-length antibody polypeptide that can bind to an antigen. An antibody fragment may include a cleavage portion of a full-length antibody polypeptide, but the term is not limited to such a cleavage fragment. Antibody fragments that can be used 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., double-chain antibodies, three-chain antibodies, four-chain antibodies)), monovalent or multivalent antibody fragments (such as bivalent, trivalent, tetravalent and multivalent antibodies), mini antibodies, chelated recombinant antibodies, three antibodies or double antibodies, intracellular antibodies, nano antibodies, small modular immunopharmaceuticals (SMIP), binding domain immunoglobulin fusion proteins, camelized antibodies and antibodies containing VHH. Other examples of antigen-binding antibody fragments are known in the art.

[0044] The term "complementarity determining region" or "CDR" refers 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 the correct positioning of the CDR sequences to allow antigen binding. Although the framework region itself is typically not directly involved in antigen binding as known in the art, certain residues within the framework region of certain antibodies may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0045] Examples of antibodies are anti-PCSK-9 mAb (eg, Alirocumab), anti-IL-6 mAb (eg, Sarilumab), and anti-IL-4 mAb (eg, Dupilumab).

[0046] 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.

[0047] Those skilled in the art will appreciate that modifications (additions and / or removals) may be made to the various components, formulations, apparatuses, methods, systems and embodiments of the API described herein without departing from the overall scope and spirit of the invention, and that the invention encompasses such modifications and any and all equivalents thereof.

[0048] An example drug delivery device may involve a needle-based injection system as described in Table 1, Section 5.2 of ISO 11608-1:2014(E). As described in ISO 11608-1:2014(E), needle-based injection systems can be broadly divided into multi-dose container systems and single-dose (partially or completely emptied) container systems. The container may be a replaceable container or an integral non-replaceable container.

[0049] 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 sizes 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 integral non-replaceable container. In such a system, each container holds multiple doses, the sizes of which may be fixed or variable (pre-set by the user).

[0050] As further described in ISO 11608-1:2014 (E), a single-dose container system may relate to a needle-based injection device with a replaceable container. In one example of such a system, each container holds a single dose, thereby discharging the entire deliverable volume (completely emptying). In another example, each container holds a single dose, thereby discharging a portion of the deliverable volume (partially emptying). Also as described in ISO 11608-1:2014 (E), a single-dose container system may relate to a needle-based injection device with an integrated non-replaceable container. In one example of such a system, each container holds a single dose, thereby discharging the entire deliverable volume (completely emptying). In another example, each container holds a single dose, thereby discharging a portion of the deliverable volume (partially emptying).

[0051] As used herein, the terms "axial", "radial" or "circumferential" may be used relative to the main longitudinal axis of the device, cartridge / container, housing or cartridge holder (e.g., the axis extending through the proximal and distal ends of the cartridge, cartridge holder or drug delivery device).

[0052] Non-limiting exemplary embodiments of the present disclosure will now be described with reference to the accompanying drawings, in which:

[0053] Figure 1 shows a perspective view of an embodiment of a drug delivery device;

[0054] Figure 2 Shows Figure 1 Components of the device;

[0055] Figure 3a Shows Figure 1 A cross-sectional view of the device together with the electronic module;

[0056] Figure 3b Shows Figure 1 A cross-sectional view of the device together with an attached electronic module;

[0057] Figure 4 Shows Figure 1 a view of the proximal end of a dose setting member button of the device;

[0058] Figure 5 Shows Figure 1 a view of the proximal end of the device;

[0059] Figure 6 Shows Figure 1 a cross-sectional view of a proximal end of a device;

[0060] Figure 7 Shown in magnified detail Figure 1 a dose setting cylinder of a device;

[0061] Figure 8 Shows Figure 1 a housing of a device;

[0062] Fig. 9 Shows Figure 1 a dose setting member sleeve of a device;

[0063] Fig.10 Shows Fig. 9 a proximal end of a dose setting member sleeve; and

[0064] Fig.11 Shows that there is Fig. 9 Dose setting member of the sleeve Figure 7 The proximal end of the dose setting barrel.

[0065] In the figures, identical elements, elements with the same function or elements of the same kind may be provided with the same reference symbols.

[0066] In the following, some embodiments will be described with reference to an insulin injection device. However, the present disclosure is not limited to this application and may also be used for injection devices configured to eject other medicaments or general drug delivery devices, preferably pen-type devices and / or injection devices.

[0067] Embodiments are provided regarding injection devices, particularly regarding variable dose injection devices, which record and / or track data regarding doses delivered therefrom. Such data may include the size of the selected dose and / or the size of the actual delivered dose, the time and date of administration, the duration of administration, etc. Features described herein include arrangements of sensing elements and power management techniques (e.g., to facilitate small batteries and / or to achieve efficient power usage).

[0068] The drug delivery device 1 shown in the figure is based on the same general operating principle as the disposable injection pen disclosed in EP 2 890 434 B1, to which document reference is made with respect to the main functions and operating modes. However, the embodiment depicted in the drawings is improved in some aspects as described in more detail below and is suitable for use with a detachable electronic module 2. Non-limiting examples of such modules are disclosed in WO2021 / 116387 A1 and PCT / EP 2021 / 060631, to which reference is made with respect to the main functions and operating modes of the electronic module.

[0069] Although described with reference to a disposable injection pen similar to the one disclosed in EP 2 890 434 B1, the present disclosure is applicable to other disposable or reusable drug delivery devices, including but not limited to the injection devices disclosed in one of the following documents: WO 2004 / 078239A1, WO 2014 / 033195 A1, WO 2009 / 132777A1, WO 2005 / 018721, US 5,693,027, US 6,663,602 or US 7,241,278.

[0070] "Distal" is used herein to specify a distribution end that is arranged or to be arranged to face or point to a drug delivery device or its parts and / or a direction, end or surface that faces away from, is arranged to face away from, or faces away from the proximal end. On the other hand, "proximal" is used to specify a distribution end that is arranged or to be arranged to face away from or face away from a drug delivery device or its parts and / or a direction, end or surface of the distal end. The distal end can be the end closest to the distribution end and / or farthest from the proximal end, and the proximal end can be the end farthest from the distribution end. The proximal surface can face away from the distal end and / or face the proximal end. The distal surface can face the distal end and / or face away from the proximal end. For example, the distribution end can be a needle end, at which the needle unit is mounted to or to be mounted to the device.

[0071] Figure 1 and Figure 2 A medication delivery device or drug delivery device 1 is depicted, comprising an outer housing 10, an inner housing insert 20, a piston rod 30, a drive sleeve 40, a nut 50, a dose setting barrel 60, a dose setting member 70, a cartridge 80 and a cap 90. A needle arrangement (not shown) comprising a needle hub and, for example, a needle cover may be provided as an additional component.

[0072] The outer housing 10 is a generally tubular element having a distal portion forming a cartridge holder 11 for receiving a cartridge 80 and provided with threads 12 for attaching a needle hub, etc., and a proximal portion enclosing the components of the dose setting and drive mechanism. In a preferred embodiment, the outer housing 10 is transparent, wherein the proximal portion is optionally provided with an opaque layer. The housing 10 comprises a transparent window 13. Figure 8 A cross-sectional view of the housing 10 is depicted, wherein a series of mating stop teeth 14 formed on the inner surface of the housing 10 can be seen. The central axis X and the outer diameter D of the housing 10 H Instructions Figure 6 middle.

[0073] The inner housing insert 20 is an inner body of a generally tubular configuration having different diameter areas. The inner housing insert 20 is received in the proximal portion of the housing 10 and is permanently fixed therein to prevent any relative movement of the inner housing insert 20 relative to the housing 10. An external thread 21 is provided on the outer surface of the inner housing insert 20. Further, a spline is provided on the inner surface of the inner housing insert 20, and an internal thread is provided at its distal end.

[0074] The piston rod 30 is an elongated element with two external threads of different leads, preferably in opposite directions of rotation, overlapping each other. One of these threads engages with the internal thread of the inner housing insert 20. A disc-shaped bearing 31 may be attached at the distal end of the piston rod 30 to allow relative rotation between the bearing 31 and the piston rod 30. Alternatively, the bearing may be attached to the piston rod 30 as a one-piece component via a predetermined break point.

[0075] The drive sleeve 40 is a generally tubular element having regions of different diameters. The distal region of the drive sleeve 40 has an external thread 41. The inner surface of the drive sleeve 40 has an internal thread that engages with one of the external threads of the piston rod 30. The drive sleeve 40 surrounds the piston rod 30 and is at least partially located within the inner housing insert 20. The drive sleeve 40 further has a flexible snap arm formed by a U-shaped opening on the skirt of the drive sleeve 40. The snap arm engages an internal spline in the inner housing insert 20 and is allowed to flex radially inwardly during relative rotation between the drive sleeve 40 and the inner housing insert 20. Such radial deflection is allowed as long as the snap arm is aligned with a recess in the dose setting member 70, but if the snap arm is not aligned with a recess in the dose setting member 70, such radial deflection is blocked, thereby preventing relative rotation between the drive sleeve 40 and the inner housing insert 20. At its proximal end, the drive sleeve 40 may comprise a spring arm which abuts the dose setting member 70 and biases the drive sleeve 40 distally relative to the dose setting member 70. The inner surface of the drive sleeve 40 is provided with at least one axially extending groove which permanently engages a spline on the dose setting member 70 such that any rotation of the dose setting member 70 is transferred to the drive sleeve 40.

[0076] A nut 50 is provided between the inner housing insert 20 and the drive sleeve 40. The outer ribs of the nut 50 engage the inner splines of the inner housing insert 20. The inner threads of the nut 50 engage the outer threads 41 of the drive sleeve 40. As an alternative, splines and ribs may be provided on the interface between the nut 50 and the drive sleeve 40, and threads may be provided on the interface between the nut 50 and the inner housing insert 20. As a further alternative, the nut 50 may be designed as a half nut, for example. Further, at least one (e.g., four) rotational hard stops are provided on the nut 50 for interacting with corresponding stops on the drive sleeve 40 at the proximal end of the threads 41.

[0077] The dose setting barrel 60 is a generally tubular element having an internal thread that engages with the external thread 21 of the inner housing insert 20. The dose setting barrel 60 is thus interposed between the inner housing insert 20 and the housing 10. A series of numbers is provided (e.g. printed) on the outer surface of the dose setting barrel 60, which numbers form a display member. These numbers are arranged on a spiral line so that only one number or a few numbers can be seen in the through-going window 13 of the housing 10. As will be explained in more detail below, the dose setting barrel 60 has a plurality of numbers near its proximal end ( Figure 7 ) is provided with a circle of clutch teeth 61 for engaging corresponding clutch teeth 73 of the dose setting member 70. Further, an optional click arm 62 may be provided, for example, near the distal end of the dose setting barrel 60, for engaging a ratchet profile 74 of the dose setting member 70.

[0078] The dose setting member 70 comprises two separate parts permanently fixed to each other to function as a single part, namely a tubular sleeve 71 ( Fig. 9 ) and a button 72. The tubular sleeve 71 of the dose setting member 70 comprises a circle of inner clutch teeth 73 near its proximal end, a circle of inner bevel teeth forming a ratchet profile 74, and a stop tooth 75 at its distal end for engaging the mating stop tooth 14 of the housing 10. The button 72 comprises a proximal end face and a rod extending distally from the end face. Figure 4 As shown in FIG. 1 , two radial apertures 76 and two axial apertures 77 are formed simultaneously in an outer groove 78 which is arranged concentrically with respect to an inner groove 79 formed in the end face of the button 72 of the dose setting member 70. The stem of the button 72 is provided with a recess into which the clicker arm of the drive sleeve 40 can be flexed, and comprises at least one axially extending spline which permanently engages a corresponding groove formed in the drive sleeve 40.

[0079] like Figure 3a and Figure 6 As shown in , the tubular sleeve 71 of the dose setting member 70 may be provided with a profiled proximal region facilitating gripping and rotation of the dose setting member 70. The maximum outer diameter D of the dose setting member 70, in particular the tubular sleeve 71 G Smaller than the outer diameter D of the housing 10 H (See Figure 6 In more detail, the maximum outer diameter D of the dose setting member 70 is G Almost equal to or slightly smaller than the inner diameter of the region of the housing 10 adjacent to the dose setting member 70 .

[0080] The cartridge 80 comprises a pre-filled, necked-down cartridge reservoir which may be typically made of glass. A rubber-type stopper or bung is located at the proximal end of the cartridge reservoir and a pierceable rubber seal is located at the other distal end. The rubber seal is held in place using a crimped annular metal band. The cartridge 80 is disposed within the cartridge holder 11 with the bearing 31 of the piston rod 30 abutting against the stopper.

[0081] Figure 1 The device 1 is shown without a cap 90. The cap 90 may be attached to the distal end of the device 1, thus covering the cartridge holder 11. The cap 90 may be releasably snapped onto the housing 10, and may be removed to use the device 1.

[0082] The electronic module 2 may be releasably attached or fixed to the proximal end of the drug delivery device 1, for example to the dose setting member 70, thereby forming a dose recording system. The module 2 may include a cup-shaped outer cap 3, which holds a PCBA 4 with a processor and a battery 5. The module 2 further includes a sensor arrangement, which is connected to the processor and is operable to generate measurement data indicative of a dose setting operation and / or a dose delivery operation. For this purpose, the sensor arrangement includes at least one LED and one or more light detectors that together form an optical sensor. In addition to the LEDs and light detectors, or as an alternative thereto, alternative sensor types may be implemented. Such alternative sensor types may include, but are not limited to, optical sensors, acoustic sensors, capacitive sensors, electrical switches. The PCBA 4 may further include or may be connected to a communication unit, which includes, for example, a wireless A communication interface is connected to the processor and is operable to establish communication with another (external) device (e.g., a smartphone). The communication unit is operable to transmit data, such as measurement data, to the other device. Further, an electronic user feedback generator can be connected to the processor and is operable to generate a feedback signal to the user. In an exemplary arrangement, the electronic user feedback generator includes an LED for generating an optical feedback signal. In addition to the LED, or as an alternative, the electronic user feedback generator can include a sounder and / or a vibration motor.

[0083] The module 2 further includes a chassis that is snap-fitted with the cap 3, thereby constraining the cap and chassis axially and in a rotational sense. The chassis is transparent or translucent and can be made of polycarbonate or the like. The chassis receives the PCB unit 4. Further, the chassis includes two light guides 6, which are axially extending protrusions of the chassis, with polished side walls and diffuse end faces forming sensor-side ends and encoder-side ends. In other words, light can enter or leave the light guide at the opposite sensor-side end and encoder-side end, but is guided (reflected) by the side walls. In the example, the light guides 6 can be offset 45° in a rotational sense relative to each other. The light guide 6 is arranged to fit into one of the apertures 77 in the button 72 or extend through the aperture when the module 2 is attached to the drug delivery device 1. For this purpose, the chassis further includes an attachment feature in the form of two flexible clips 7, which are rotationally offset, for example, by 180°, for engaging the radial apertures 76 in the button 72.

[0084] The dose setting and drive mechanism of the drug delivery device is configured to perform a dose setting operation for selecting a dose to be delivered by the drug delivery device, and a dose delivery operation for delivering the set dose.

[0085] During a dose setting operation, the clutch teeth 61 of the dose setting barrel 60 engage the clutch teeth 73 of the dose setting member 70. Thus, the dose setting barrel 60, the dose setting member 70 and the drive sleeve 40 (which is splined to the dose setting member 70) are coupled in a rotational sense. The user can set a dose by rotating the tubular sleeve 71 of the dose setting member 70 so that the dose setting barrel 60, the dose setting member 70 and the drive sleeve 40 are turned out of the housing 10 along a helical path defined by the thread 21 of the inner housing insert 20 guiding the thread of the dose setting barrel 60. The pitch of the threaded interface between the piston rod 30 and the drive sleeve 40 corresponds to the pitch of the threaded interface between the inner housing insert 20 and the dose setting barrel 60, so that the piston rod 30 is kept stationary by its threaded interface with the inner housing insert 20. The amount of the selected dose can be seen through the window 13 in the housing 10. During such rotation of the dose setting barrel 60, the dose setting member 70 and the drive sleeve 40 relative to the housing, the flexible clicker arms of the drive sleeve 40 snap onto the internal axial splines of the inner housing insert 20, thereby defining discrete rotational positions. In the exemplary embodiment depicted, one full rotation of the dose setting member corresponds to 24 dose increments. For example, in the case where the injection device 1 is configured to administer human insulin, the dose increments may be displayed in so-called international units (IU), where one IU is the biological equivalent of approximately 45.5 micrograms of pure crystalline insulin (1 / 22 mg).

[0086] At the maximum settable dose (e.g. 80), the unit stop feature may engage to prevent further setting (e.g. dialing). Further, during dose setting, the drive sleeve 40 rotates relative to the inner housing insert 20 so that the nut 50, which is rotationally fixed to the inner housing insert 20 via axially extending ribs and splines, moves on the threads 41 of the drive sleeve 40. The last dose nut 50 provides the function of counting the number of dispensed units. The nut 50 locks the device 1 at the end of the use period so that no more medicament can be dialed or dispensed by the user. The rotation of the drive sleeve 40 during setting causes the nut 50 to advance along the threads 41. The nut 50 is always free to slide axially within the inner housing insert 20, which allows the nut 50 to advance. In the end of use condition, the stop feature of the last dose nut 50 contacts the corresponding feature on the drive sleeve 40. The spline contact with the inner housing insert 20 reacts against any torque transmitted by these stop features 47.

[0087] With the desired dose dialed, the device 1 is ready for dose dispensing. This essentially requires pushing the dose setting member 70, which will disengage the clutch teeth 61, 73. As described above, when setting a dose, the dose setting member 70 is "biased out" by the flexible arm of the drive sleeve 40 and engages the clutch teeth 61, 73 that lock the drive sleeve 40, the dose setting member 70 and the dose setting barrel 60 together in a rotational sense. When the dose setting member 70 is pressed, the clutch teeth 61, 73 are disengaged and a relative rotation between the dose setting barrel 60 and the dose setting member 70 is possible. Under all conditions, the drive sleeve 40 and the dose setting member 70 remain locked in a rotational sense. Therefore, with the clutch disengaged (the dose setting member 70 is pushed in), the dose setting member 70 and the drive sleeve 40 are locked together in a rotational sense, while the dose setting member 70, the drive sleeve 40 and the dose setting barrel 60 are still axially coupled. At the same time, the relative axial movement of the dose setting member 70 relative to the drive sleeve 40 causes the recess on the rod to shift relative to the flexible clicker arm. Thus, the flexible clicker arms are prevented from flexing inwardly. If the dose setting member 70 is pressed, such activation of the locking feature prevents the flexible clicker arms from overcoming the splines of the inner housing insert 20. In this condition, the drive sleeve 40 and the dose setting member 70 are rotationally constrained to the inner housing insert 20, thus preventing any rotation relative to the housing 10.

[0088] With the desired dose set, the dose setting member 70 can be depressed and the piston rod 30 driven forward to dispense the drug from the cartridge. The interaction of the mating threads between the piston rod 30, the drive sleeve 40 and the inner housing insert 20 provides a mechanical advantage, for example 2:1. During dose dispensing, the dispensing chime is active, which involves the ratchet profile 74 of the dose setting member 70 and the chime arm 62 of the dose setting barrel 60. The dispensing chime mainly provides the user with audible feedback that the drug is being dispensed. Relative rotation is only allowed in one direction. During dose delivery, the drive sleeve 40 does not rotate relative to the inner housing insert 20. Therefore, the rotational position of the nut 50 does not change during dose delivery, and the nut 50 maintains its position set on the drive sleeve 40 during dose setting or dialing.

[0089] The dose setting member 70, more specifically the tubular sleeve 71, has a set of axially directed stop teeth 75 at its distal end. These teeth 75 are formed on the proximal edge of the tubular sleeve 71 and are configured to engage a set of mating stop teeth 14 formed on the inner surface of the housing 10 at the end of the delivery of the dose. These teeth 14, 75 control and "tune" the rotational position of the dose setting member 70 relative to the housing 10 and the dose setting barrel 60 at the end of each dose. This is important to ensure that the clutch teeth 61, 73 between the dose setting member 70 and the dose setting barrel 60 are aligned so that they are correctly re-engaged when the dose setting member 70 is released (thereby allowing the subsequent dose to be dialed). In addition, for the accurate function of the module 2, it is important that the rotational position of the dose setting member 70 is consistent relative to the dose setting barrel 60 at the end of each dose. This is because the module 2 is intended to accurately detect the total relative rotational movement of the clutch teeth 61 on the dose setting barrel 60 relative to the dose setting member 70 to determine the size of the delivered dose. In the absence of the above-mentioned teeth 14, 75 between the dose setting member 70 and the housing 10, the relative rotational position of these two parts at the end of the dose will be determined only by the dial click (the flexible click arm of the drive sleeve 40 and the axial splines of the inner housing insert 20). However, because the dial click is deliberately designed to be overcome with a relatively low torque, it does not provide particularly accurate rotational data. Further, if the dose setting member 70 is pushed in when the pen 1 is in the 0U dial condition, the engagement of these teeth 14, 75 prevents the user from rotating the dose setting member 70 relative to the housing 10. Rotating the dose setting member 70 under such conditions would allow the user to manipulate the pen mechanism in a way that could advance or retract the piston rod 30, potentially leading to dose errors.

[0090] The drug delivery device 1 is suitable for use with or without the module 2. If the module 2 is assembled on the dose setting member 70, the flexible clip 7 engages and snaps into the radial aperture 76 of the button 72, while the light guide 6 extends into the axial aperture 78. When used in combination with the module 2, this circle of clutch teeth 61 of the dose setting barrel 60 has the additional function of an encoder.

[0091] These radially outwardly protruding clutch teeth 61 located on the outer diameter of the dose setting barrel 60 at its proximal end can be detected by the optical sensor. In other words, an array of proximally facing encoder features formed in a circular (e.g. annular) pattern is provided by this circle of clutch teeth 61. Figure 7 As shown in the exemplary embodiment, there are only twelve equally spaced clutch teeth 61, however the clutch teeth in combination with a set of twenty-four mating teeth 73 on the dose setting member 70 provide twenty-four discrete engagement positions (thus achieving 24 selectable dose increments per revolution of the dose setting member when setting and delivering a dose). This arrangement has many advantages. If the clutch teeth 61 protrude radially from the outer diameter of the dose setting barrel 60, they interact with the teeth 73 formed on the inner diameter of the dose setting member 70, thereby transmitting torque over the maximum possible diameter. This means that they are stronger and more resistant to torque applied by the user. A smaller number of wide teeth (i.e. 12 "double width" teeth instead of 24 single width teeth) also provides a stronger means of transmitting torque from the dose setting barrel 60 to the dose setting member 70. A smaller number of wide teeth 61 also provides a much better target for the optical detector of the module 2, as the individual reflective / non-reflective areas are wider and therefore provide a better optical signal response and are more adaptable to angular tolerance variability (relative over-travel or under-travel) when the dose setting drum 60 is rotated relative to the dose setting member 70.

[0092] like Figure 6As shown in , the dose button 72 of the pen-type injector 1 constitutes the proximal side of the pen-type injector 1 and has two concentric grooves 78, 79 formed in its proximal surface, i.e. the grooves can be formed as depressions or cutouts in the proximal face and can extend in the distal direction. These grooves 78, 79 accommodate features of the module 2, thereby allowing the module to rotate relative to the dose button 72 to find the correct rotational alignment during attachment. The grooves 78, 79 serve as the following means, by which a set of features (i.e. dedicated features) are discretely provided on the dose button 72 of the pen, which prevent the attachment of incorrect types of modules 2, these grooves allow the module 2 to be securely attached via the clip features 7, and allow access to the clutch teeth 61 of the pen mechanism, which allow the dose value to be detected / encoded by the module 2. As mentioned above, the features used by the module 2 to detect the size of the delivered dose are the clutch teeth 61, which are formed as an array of features arranged at equal intervals around the outer circumference at the proximal end of the dose setting barrel 60. While these encoder features need not be clutch teeth 61 , but may simply be "flags" of an optical encoder system that rotates with the dose setting barrel 60, the arrangement of apertures 77 is useful to allow access to such encoder features if the module 2 is fitted to the pen 1 .

[0093] Because the module 2 uses a set of optical IR emitters / detectors to encode the dose delivered from the pen 1, if the pen 1 is used outdoors, it is preferred to reduce the level of "stray" IR radiation that may interfere with the correct performance of the module sensors, for example from high ambient light levels. The components of the dose setting member 70 may have features intended to reduce / suppress the level of reflected IR radiation. In particular, the tubular sleeve 71 and / or the button 72 may contain an IR absorbing masterbatch and / or may have a spark eroded texture surface finish.

[0094] Reference numerals

[0095] 1 Drug delivery device (pen)

[0096] 60 Dose setting cylinder

[0097] 2 Electronic module 61 Clutch gear

[0098] 3 Cap 62 Ringing Arm 4 PCBA (processor, sensor)

[0099] 5 Battery 70 Dose setting member

[0100] 6 Light guide 71 Tubular sleeve 7 Flexible clip 72 Button

[0101] 73 Clutch teeth 10 Housing 74 Ratchet profile (bevel teeth)

[0102] 11 Cartridge holder 75 Stop tooth

[0103] 12 Thread 76 Radial Orifice

[0104] 13 Dosage window 77 Axial orifice 14 Mating stop tooth 78 External groove

[0105] 79 inner groove

[0106] 20 Inner housing insert

[0107] 21 Thread 80 Cartridge

[0108] 30 Piston rod 90 Cap 31 Bearing

[0109] X axis

[0110] 40 Drive sleeve

[0111] 41 Thread D G The diameter of the dose setting member 70 50 Nut D H The diameter of the housing 10

Claims

1. A drug delivery device for setting and dispensing a dose of a liquid drug, the device comprising a housing (10), preferably a housing having a substantially circular cross-section, which at least partially encloses a dose setting and drive mechanism having a piston rod (30) and a dose setting member (70), wherein: The dose setting and drive mechanism is configured to perform a dose setting operation for setting a dose to be delivered by the drug delivery device by moving the dose setting member (70) relative to the housing (10), and to perform a dose delivery operation for delivering the set dose by axially displacing the piston rod (30) along an axis (X), characterized in that a maximum radial extension of the dose setting member (70) perpendicular to the axis (X) is smaller than a maximum radial extension of a region of the housing (10) adjacent to the dose setting member (70) perpendicular to the axis (X).

2. The drug delivery device according to claim 1, characterized in that The outer diameter of the dose setting member (70) is smaller than or equal to the inner diameter of a region of the housing (10) adjacent to the dose setting member (70).

3. A drug delivery device according to any one of the preceding claims, characterized in that The dose setting member (70) is provided with attachment features (76) for mounting a separately attachable module (2).

4. The drug delivery device according to claim 3, characterized in that The dose setting member (70) is provided with a substantially circular recess (78) extending in a proximal face of the dose setting member (70), wherein the attachment features (76) are provided in or adjacent to the recess (78).

5. The drug delivery device according to claim 3 or 4, characterized in that: The attachment features are radial apertures (76) provided on the dose setting member (70).

6. A drug delivery device according to any one of the preceding claims, characterized in that The dose setting member (70) comprises two separate parts (71, 72) permanently fixed to each other to function as a single component.

7. The drug delivery device according to claim 6, characterized in that The dose setting member (70) comprises a tubular sleeve (71) comprising a circle of clutch teeth (73) extending radially inwardly, a circle of bevel teeth (74) extending radially inwardly, a contour as a gripping surface and / or a circle of stop teeth (75) extending distally, and / or the dose setting member (70) comprises a button (72) having a proximal end face and a stem extending distally from the end face, wherein the stem comprises at least one axially extending spline.

8. A drug delivery device according to any one of the preceding claims, characterized in that The dose setting member (70) is made of a plastic material having an IR absorbing masterbatch and / or has a light absorbing surface finish.

9. A dose recording system comprising a drug delivery device (1) according to any one of the preceding claims and an electronic module (2) for attachment to a dose setting member (70) of the drug delivery device, wherein: The module (2) comprises: -sensor, a processor configured to control the operation of the at least one sensor and to process and / or store signals from the at least one sensor, and - Attachment features for attaching the module to the dose setting member (70).

10. The dose recording system according to claim 9, wherein: The maximum outer diameter of the dose setting member (70) is equal to or smaller than the inner diameter of the module (2).

11. The dose recording system according to any one of claims 9 or 10, wherein: The maximum outer diameter of the module (2) is equal to or slightly larger than the outer diameter of the housing (10).

12. The dose recording system according to any one of claims 9 to 11, wherein: The module (2) comprises an attachment feature (6) for attaching the module (2) to the proximal end of the drug delivery device.

13. The dose recording system according to claim 12, wherein: The attachment features include at least one flexible clip (6) for securing the module (2) to the dose setting member (70).

14. The dose recording system according to claim 13, wherein: The at least one flexible clip (6) is received within the module (3) and extends substantially distally from a chassis holding the sensor and the processor.

15. The dose recording system according to any one of claims 9 to 14, wherein: The dose setting member (70) comprises a mechanical encoding portion (79), and the module (2) comprises a mechanical counterpart encoding portion which engages with the mechanical encoding portion (79) when the module (2) is attached to the drug delivery device (1).

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