Drug delivery device and dose recording system using the drug delivery device

Abstract

The present invention relates to a drug delivery device (1) for setting and dispensing a dose 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 within the housing (10) and 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) along the housing (10) and a dose delivery operation for delivering the set dose by axially displacing the dose setting member (70) along an axis (X). The maximum radial extension perpendicular to the axis (X) of the dose setting member (70) is smaller than the maximum radial extension of a region of the housing (10) located adjacent to the dose setting member (70).

Description

[Technical field]

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

[0002] Pen-type drug delivery devices have applications where regular injections occur by persons without formal medical training, which is increasingly common for patients suffering from diabetes, where self-medication allows such patients to effectively manage their disease. In practice, such drug delivery devices may enable a user to individually select and dispense multiple user-variable doses of a medication, or may be suitable for dispensing a fixed dose, for example by a push-pull mechanism, or for selecting and dispensing a preselected dose.

[0003] There are essentially two types of drug delivery devices: resettable (i.e., reusable) and non-resettable (i.e., disposable). For example, disposable pen delivery devices are supplied as self-contained devices. Such self-contained devices do not have a removable pre-filled cartridge. Rather, the pre-filled cartridge may not be removable and replaceable from these devices without destroying the device itself. Thus, such disposable devices do not need to be equipped with a resettable dose setting mechanism. Reusable drug delivery devices need to have a resettable dose setting mechanism and a refillable drug container, e.g., a removable cartridge holder provided for replacement when the contained drug cartridge is empty. The present invention is equally applicable to disposable and to reusable devices.

[0004] For such drug delivery devices, the ability to record doses dialed and / or delivered from the pen can be valuable to a wide variety of device users as a memory aid or to support detailed recording of dose history. Drug delivery devices using electronic devices for such purposes are therefore becoming increasingly popular both in the pharmaceutical industry and with users or patients. For example, a dose recording system is known from WO 2021 / 116387 A1, comprising 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 that extends radially beyond the housing. A monitoring module may be attached to the housing of the drug injection device.

[0006] US 11141538 B2 discloses a drug delivery device having a dose setting member sandwiched between a housing part and a drug container holder. An activator located at one end of the housing can be pressed to dispense the drug.

[0007] In known drug delivery devices or pen injectors with an essentially round housing, the dose is set by moving the dose setting member (e.g. the dose dial grip) relative to the housing (e.g. by rotating the dose setting member or by pulling the dose setting member axially). Such drug delivery devices have a diameter of the dose setting member that matches or is slightly larger than the housing. This conventional configuration allows good access to the grip surface of the dose setting member and gives the pen a continuous aesthetic look. However, if the pen is intended to be used in conjunction with a separate removable module that comes with a dose setting member, the geometry of the conventional dose setting member becomes problematic, since it requires that the module size must be significantly larger than the diameter of the pen housing. In this situation, if a pen with the form of a conventional dose setting member is attached to a module, delivering a dose is more cumbersome, especially if the dose setting member has to rotate when the dose is delivered. In addition, such devices with attached modules are larger and bulkier to carry / contain in a pouch or carry case. Furthermore, the module is prone to being unintentionally dislodged or damaged, which may affect its correct functioning, and furthermore, due to the relatively large radial extension of the dose setting member to which the module is attached, it is easier for the user to unintentionally apply excessive torque to the dial stop, which may cause unintentional damage and possibly lead to incorrect dosing. Summary of the Invention [Problem to be solved by the invention]

[0008] It is an object of the present disclosure to provide improvements relating to drug delivery devices and dose recording systems that obviate the shortcomings of the prior art devices mentioned above.

[0009] This object is solved, for example, by the subject matter defined in claim 1. Advantageous embodiments and improvements are the subject of the dependent claims. It should be noted, however, that the present disclosure is not limited to the subject matter defined in the appended claims. Rather, the present disclosure may include improvements in addition to or instead of 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 medicament, the device comprising a housing, preferably a housing having an essentially circular cross section, and a dose setting and driving mechanism having a piston rod and a dose setting member. In an embodiment, the housing may contain a cartridge filled with the liquid medicament. Alternatively, a separate cartridge holder may be permanently or removably attachable to the housing. The dose setting and driving mechanism may be at least partially arranged within the housing and may be configured to perform a dose setting (e.g. dialing) action for setting a dose to be delivered by the drug delivery device by moving the dose setting member relative to the housing, and a dose delivery action for delivering the set dose by displacing the piston rod axially along an axis. Preferably, the maximum radial extension of the dose setting member in a direction perpendicular to the axis is smaller than the maximum radial extension of a region of the housing located adjacent to the dose setting member in a direction perpendicular to the axis. For example, in a drug delivery device in which the housing has a substantially cylindrical shape, the maximum outer diameter of the dose setting member is smaller than the outer diameter of the housing in the region of the housing located adjacent to the dose setting member, or even smaller than the maximum outer diameter of the housing. Furthermore, the maximum outer diameter of the dose setting member may be smaller than the inner diameter of the region of the housing located adjacent to the dose setting member. With such a drug delivery device, the above-mentioned disadvantages of conventional pen injectors can be overcome, for example, by providing a dose setting member with an outer diameter that approximately matches the inner diameter of the pen housing, i.e. the inner diameter of the bore. This results in a form that is optimized with respect to maneuverability and size when the module is attached, but that also retains good functionality when the pen is used without the module attached.

[0011] A dose setting operation for setting a dose 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, whereas a dose delivery operation for delivering a set dose may comprise axially displacing the piston rod along an axis, preferably along a central longitudinal axis of the piston rod. Optionally, a dose delivery operation for delivering a set dose may comprise moving the dose setting member relative to the housing, e.g. axially moving the dose setting member.

[0012] The drug delivery device may be suitable for setting and dispensing a variable dose of liquid medication, allowing the user to individually select and dispense multiple user-variable doses of medication. Alternatively, the drug delivery device may be a fixed dose device, e.g., a push-pull type device that is only allowed to dispense a pre-defined fixed dose. As a further alternative, the drug delivery device may be suitable for selecting among one or more pre-set doses, e.g., selecting a dose above or below a threshold, as disclosed in WO 2016 / 128424 A1. Thus, the terms "dose setting", "dose selection" and "dose dialing" are used herein without limiting the drug delivery device to a particular mode of operation.

[0013] The drug delivery device may comprise a dose setting drum. The dose setting drum may simply display the currently set dose without causing dose selection and / or dose delivery, or may cause dose selection and / or dose delivery in addition to displaying the dose (by transmitting a force to the piston rod). The dose setting drum may move, e.g. rotate, together with the dose setting member relative to the housing during at least one of the dose setting and dose delivery operations. In one example, the dose setting drum rotates on a helical path during dose setting and dose delivery, and the dose setting member rotates on a helical path during dose setting and moves axially without rotating during dose delivery. In another example, the dose setting drum and the dose setting member rotate together without moving axially relative to the housing during dose setting and dose delivery.

[0014] Preferably, the drug delivery device, such as a pen injector, is suitable for use with an attachable electronic module configured to capture information regarding the size of the dose to be delivered. The module may be removable from the drug delivery device and / or may be fixed after attachment to the drug delivery device.

[0015] The dose setting member may be provided with a mounting feature for mounting a separate attachable module to the drug delivery device, for example an electronic module for recording a dose set or dispensed with the drug delivery device. The dose setting member may be provided with at least one, e.g. substantially circular, groove extending in the proximal end face of the dose setting member, with a mounting feature provided in or adjacent to the groove. The dose setting member may be provided with two concentric grooves. In one example, the mounting feature may comprise at least one, e.g. two, oppositely located, radial apertures provided in the dose setting member. The apertures may be provided radially outward from the groove in the dose setting member, for example in the outer groove of the two concentric grooves in the proximal end face of the dose setting member.

[0016] In one example, the dose setting member may be provided to be moved (e.g. rotated) by a user to set a dose and to be moved (e.g. pushed) by a user to deliver a dose with the dose delivery device. The dose setting member may comprise two separate components permanently fixed to each other to function as a single component. This may be preferred for manufacturing and / or assembly reasons. In one example, the dose setting member may comprise a tubular sleeve having a ring of radially inwardly extending clutch teeth, a ring of radially inwardly extending ramp teeth, profiling as a gripping surface, and / or a ring of distally extending stop teeth. Additionally or alternatively, the dose setting member may comprise a button. The button may have a proximal end face and a stem extending distally from the end face, the stem comprising at least one axially extending spline. The button may be an actuation button that is pressed by a user to activate or release a drive mechanism of the drug delivery device. These exemplary interfaces of the dose setting member can facilitate dose setting operations for setting the dose to be delivered by the drug delivery device and dose delivery operations for delivering the set dose, and can facilitate switching between dose setting and dose delivery modes of the drug delivery device.

[0017] The electronic module may comprise a rotation sensor for detecting the rotation of a sensed element rotationally fixed to a component of the drug delivery device, the sensed element rotating during dose setting and / or dose delivery relative to the dose setting member to which the electronic module is attached. The sensed element may be fixed to the dose setting drum. The sensing element may be an encoder ring having a pattern (e.g. an optical or magnetic pattern) that can be detected by the rotation sensor. The rotation sensor may comprise at least one optical sensor and / or at least one magnetic sensor.

[0018] The electronic module may use an optical IR emitter / detector set to detect the dose delivered from a drug delivery device, e.g. a variable dose injection pen. To reduce the level of stray IR radiation from, e.g., high ambient light levels, that may interfere with the correct performance of the module sensor when the pen is used outdoors, components of the dose setting member 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 include an IR absorbing masterbatch and / or have an electro-discharge machined textured surface finish.

[0019] A dose recording system according to the present disclosure comprises a drug delivery device as described herein and an electronic module as described herein for removable or fixed attachment to a dose setting member of the drug delivery device. For example, the module may comprise a 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 an attachment feature for attaching the module to the dose setting member. The module may comprise a cap for receiving a proximal end of the dose setting member. The maximum outer diameter of the dose setting member may be equal to or smaller than the inner diameter of the cap, thereby allowing the module to be attached onto the dose setting member. The maximum outer diameter of the module may be equal to, similar to, or slightly larger than the outer diameter of the housing, for example, by about 0 mm to about 5 mm beyond the outer diameter of the housing. This configuration does not interfere with the dose delivery operation even if the dose setting member has to rotate when the dose is delivered. In addition, the risk of the module being unintentionally dislodged or damaged is minimised and unintentional application of excessive torque due to the dose setting member being too large in diameter is prevented.

[0020] When the electronic module of the dose recording system is a reusable module for removable attachment to a drug delivery device, the module may comprise an outer cap having a central axis, a chassis at least partially held in the cap, and a PCB or PCBA comprising a memory and a processor. For example, the PCBA and a power supply may be held in the cap and the chassis. Furthermore, the light source and the optical sensor may be arranged in a circular area around the central axis, with a first light source and a first optical sensor angularly offset from a second light source and a second optical sensor. One or more light pipes 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. Additionally, a light guide may be provided in the chassis to guide light from an internal light source to an outer surface of the module to display information regarding a status or an operating mode of the module.

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

[0022] According to a further aspect of the present disclosure, the dose setting member may comprise a mechanical coding and the module may comprise a mechanical counter-coding that engages with the mechanical coding when the module is attached to the drug delivery device. This can prevent attaching a mismatched module to the drug delivery device. Additionally, torque may be transmitted from the module to the dose setting member via the mechanical coding and the mechanical counter-coding.

[0023] The electronic module of the dose recording system may comprise an electronic system suitable for use with the drug delivery device to record the dose delivered from the drug delivery device. The electronic system may comprise a power supply, e.g. a battery, such as a coin cell battery, a memory for storing data, and a processor configured to control the operation of the electronic system and coupled to the power supply and the memory. In addition, the electronic system may comprise at least one, preferably two sensors, which may be optical sensor units, e.g. a first light source with a corresponding first optical sensor and a second light source with a corresponding second optical sensor, in communication with the processor. The optical sensor may be suitable for detecting a movement of a segment with a different reflectivity of an encoder of the drug delivery device, in particular of, e.g., a dose sleeve, which movement represents a dose that has been 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 comprise a radiation detector, which comprises an electromagnetic radiation emitter, e.g. an LED, such as an IR-LED, e.g. an NIR-LED, and a radiation detector. The encoder may operate 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 provided to detect the dose delivered by the drug delivery device.

[0025] In one example, the encoder and the optical sensor unit are in a quadrature configuration, i.e. they are out of phase by a quarter wave, meaning that if both light sources emit light simultaneously, only one sensor per distributed unit changes state. For example, this can be achieved by providing two optical sensors offset in the circumferential direction by n x 30° + 15°, where n is an integer. As the encoder and the sensor unit move relative to each other, one of the optical sensors that previously received light will now not receive the emitted light and vice versa. This can be achieved by an encoder that selectively reflects light. For example, a ring of teeth may be provided such that the teeth reflect light while the free space between adjacent teeth does not. Alternatively, light reflecting and light absorbing areas may be provided alternately. As a further alternative, the encoder may selectively block light. In another example, the encoder and the optical sensor unit may be in an anti-phase configuration. In yet a further alternative, the encoder and optical sensor units are not in an anti-phase configuration, so that if both light sources emit light simultaneously, then depending on the relative position of the encoder, either no optical sensor detects light or only one or all of the optical sensors detect light.

[0026] The electronic module of the dose recording system may be configured as a reusable clip-on module for the injection device. Alternatively, the electronic system may be a unit or module permanently attached to the injection device. The terms electronic system and (electronic) module are used below for both alternatives. The ability to record doses may be valuable to a wide variety of device users as a memory aid or to support detailed recording of dose history. It is envisaged that the electronic system, e.g. the electronic module, may be configured to be connectable to a mobile phone or the like to allow dose history to be downloaded periodically from the system.

[0027] The electronic dose recording system may further comprise a communication unit for communicating with another device. Preferably, the electronic module of the dose recording system is configured to switch the electronic module from a first state with lower energy consumption to a second state with higher energy consumption, which may induce the communication unit to establish communication with the other device, such as a synchronization or pairing operation. The electronic control unit may issue an instruction, such as a signal, to another unit of the electronic dose recording system to switch on or become operational. This unit may 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 comprises an RF, WiFi and / or Bluetooth unit as a communication unit. The communication unit may be provided as a communication interface between the dose recording system or the drug delivery device and the outside, such as another electronic device, such as a mobile phone, a personal computer, a laptop, etc. For example, the dose data may be transmitted to the external device by the communication unit. The dose data may be used for a dose log or dose history established in an external device.

[0028] According to yet a further aspect of the present disclosure, the electronic dose recording system further comprises a hibernation state in which the light source is not activated (no power is provided by the power source). The electronic dose recording system may further comprise at least one switch and / or motion sensor suitable for detecting movement of the electronic system. In this example, the processor may be configured to maintain the hibernation state when no switch activation or motion is detected by the at least one motion sensor, and to switch to the first low power consumption state or at least one further state when a switch activation or motion is detected by the at least one motion sensor. In general, a hibernation state or mode may be a mode in which all functionality of the modules is minimal or consumes substantially zero power, but does not require a system boot-up when the electronic system (or drug delivery device) returns from the hibernation mode.

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

[0030] As used herein, the terms "drug" or "medicament" are used interchangeably to refer to a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharma- ceutically acceptable salts or solvates thereof and, optionally, a pharma- ceutically acceptable carrier. An active pharmaceutical ingredient ("API"), in its broadest sense, is a chemical structure that has a biological effect on humans or animals. In pharmacology, drugs or agents are used to treat, cure, prevent, or diagnose disease, or to otherwise enhance physical or mental comfort. Drugs or agents may be used for a limited period of time, or periodically for chronic conditions.

[0031] As described below, a drug or agent may include at least one API, or a combination thereof, in various types of formulations for the treatment of one or more diseases. Examples of APIs may include small molecules with 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 DNA 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 agent may be contained within a primary package or "drug container" adapted for use with the drug delivery device. The drug container may be, for example, a cartridge, a syringe, a reservoir, or other sturdy or flexible vessel configured to provide a suitable chamber for storage (e.g., short-term or long-term storage) of one or more drugs. For example, in some embodiments, the chamber may be designed to store the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chamber may be designed to store the drug for about one month to about two years. Storage may be at room temperature (e.g., about 20° C.) or at refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some cases, the drug container may be or include a dual-chamber cartridge configured to separately store two or more components of a pharmaceutical formulation to be administered (e.g., an API and a diluent, or two different drugs), one in each chamber. In such cases, the two chambers of the dual-chamber cartridge may be configured to allow mixing between two or more components prior to and / or during dispensing into the human or animal body. For example, the two chambers may be configured to be in fluid communication with one another (e.g., by a conduit between the two chambers), allowing the two components to be mixed if desired by a user prior to dispensing. Alternatively or additionally, the two chambers may be configured to allow mixing upon dispensing of the components into the human or animal body.

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

[0034] Examples of APIs for the treatment and / or prevention of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include insulin, e.g., human insulin, or a human insulin analog or derivative, glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, or an analog or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharma-ceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms "analog" and "derivative" refer to a polypeptide having a molecular structure that is formally derivable from the structure of a naturally occurring peptide, e.g., the structure of human insulin, by deletion and / or replacement of at least one amino acid residue present in the naturally occurring peptide and / or by addition of at least one amino acid residue. The added and / or substituted amino acid residues can be either 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 derivable from the structure of a naturally occurring peptide, such as the structure of human insulin, in which one or more organic substituents (e.g., fatty acids) are attached to one or more of the amino acids. Optionally, one or more amino acids present in the naturally occurring peptide may be deleted and / or substituted by other amino acids, including non-codable amino acids, or amino acids, including non-codable amino acids, may be added to the naturally occurring peptide.

[0035] 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 in which the proline in position B28 can be replaced by Asp, Lys, Leu, Val or Ala and in position B29 Lys can 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 e.g. B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl-LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin. B29-N-palmitoyl-ThrB29LysB30 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-(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, for example, lixisenatide (Lyxumia®), exenatide (exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide produced by the salivary glands of the flatfish), liraglutide (Victoza®), semaglutide, taspoglutide, albiglutide (Syncria®), dulaglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, langrenatide / HM-11260C (Efpeglenatide), HM-1521 1, CM-3, GLP-1 Erigen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexene, 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.

[0038] Examples of oligonucleotides include, for example: mipomersen sodium (Kynamro®), a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia, or RG012 for the treatment of Alport Syndrome.

[0039] Examples of DPP4 inhibitors include linagliptin, vildagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0040] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, choriogonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0041] Examples of polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin, very low molecular weight heparin or derivatives thereof or sulfated forms of the above polysaccharides, such as polysulfated forms, 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 GF 20 (Synvisc®), sodium hyaluronate.

[0042] The term "antibody" as used herein refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of an immunoglobulin molecule include F(ab) and F(ab')2 fragments that retain the ability to bind to an antigen. An antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (e.g., murine) antibody, or a single chain antibody. In some embodiments, an antibody has effector function and can fix complement. In some embodiments, an antibody has reduced or no binding ability to Fc receptors. For example, an antibody can be an isotype or subtype, an antibody fragment, or a mutant that does not support binding to Fc receptors, e.g., an antibody has a mutated or deleted Fc receptor binding region. 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 crossover binding region orientation (CODV).

[0043] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., antibody heavy and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not include the full-length antibody polypeptide but comprises at least a portion of the full-length antibody polypeptide that is still capable of binding to an antigen. An antibody fragment may include truncated portions of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments 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 (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0044] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences in the variable regions 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 in the variable regions of both heavy and light chain polypeptides that are not CDR sequences and that are primarily responsible for maintaining the proper arrangement of the CDR sequences to allow antigen binding. Although the framework region itself typically does not directly participate in antigen binding, as is known in the art, certain residues in the framework region of a particular antibody 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 (e.g., alirocumab), anti-IL-6 mAb (e.g., sarilumab), and anti-IL-4 mAb (e.g., dupilumab).

[0046] Pharmaceutically acceptable salts of any of the APIs described herein are contemplated for use in the drug or medicament in the drug delivery device. Pharmaceutically acceptable salts include, for example, acid addition salts and base salts.

[0047] It will be understood by those skilled in the art that modifications (addition and / or deletions) may be made to the various components of the APIs, formulations, devices, methods, systems, and embodiments described herein without departing from the full scope and spirit of the invention, and that the invention encompasses such modifications and all equivalents thereof.

[0048] Exemplary drug delivery devices may include needle-based injection systems 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 divided into multi-dose container systems and single-dose (with partial or complete evacuation) container systems. The container may be an exchangeable container or an integrated non-exchangeable container.

[0049] As further described in ISO 11608-1:2014(E), a multi-dose container system may include a needle-based injection device with an exchangeable container. In such a system, each container holds multiple doses and may be fixed or variable in size (pre-set by the user). Another multi-dose container system may include a needle-based injection device with an integrated non-exchangeable container. In such a system, each container holds multiple doses and may be fixed or variable in size (pre-set by the user).

[0050] As further described in ISO 11608-1:2014(E), the single-dose container system may include a needle-based injection device with a replaceable container. In one example of such a system, each container holds a single dose, which expels the entire deliverable volume (full expulsion). In a further example, each container holds a single dose, which expels a portion of the deliverable volume (partial expulsion). As also described in ISO 11608-1:2014(E), the single-dose container system may include a needle-based injection device with an integrated non-replaceable container. In one example of such a system, each container holds a single dose, which expels the entire deliverable volume (full expulsion). In a further example, each container holds a single dose, which expels a portion of the deliverable volume (partial expulsion).

[0051] The terms "axial", "radial" or "circumferential" as used herein may be used with respect to the main longitudinal axis of a device, cartridge / container, housing or cartridge holder, e.g., an axis extending through the proximal and distal ends of a 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. [Brief description of the drawings]

[0053] [Figure 1] 1 illustrates an embodiment of a drug delivery device in a perspective view. [Diagram 2] 2 shows the components of the device of FIG. 1. [Figure 3a] 2 shows the device of FIG. 1 together with an electronic module in cross-sectional view. [Figure 3b] 2 shows the device of FIG. 1 in cross-section with an attached electronic module; [Figure 4] 2 shows a view of the proximal end of the dose setting member button of the device of FIG. 1. [Diagram 5] 2 shows a view of the proximal end of the device of FIG. 1. [Figure 6] 2 shows a cross-sectional view of the proximal end of the device of FIG. 1. [Figure 7] FIG. 2 shows the dose setting drum of the device of FIG. 1 with an enlarged detailed view. [Figure 8] 2 shows a housing for the device of FIG. 1; [Figure 9] 2 shows a dose setting member sleeve of the device of FIG. 1. [Figure 10] 10 shows the proximal end of the dose setting member sleeve of FIG. [Figure 11] The proximal end of the dose setting drum of Figure 7 is shown together with the dose setting member of Figure 9. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0054] In the figures, identical elements, identically functioning elements, or elements of the same type may be labeled with the same reference numbers.

[0055] In the following, some embodiments are described with reference to an insulin infusion device, however, the present disclosure is not limited to such application and can be equally deployed with infusion devices configured to expel other medicaments, or with drug delivery devices in general, preferably pen devices and / or infusion devices.

[0056] Embodiments are provided that relate to injection devices, and in particular to variable dose injection devices, that record and / or track data regarding the dose delivered by the device. 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 configurations of sensing elements, and power management techniques (e.g., to allow for small batteries and / or efficient power usage).

[0057] The drug delivery device 1 shown in the figures is based on the same general operating principles as the disposable injection pen disclosed in EP 2890434 B1, to which reference is made with respect to its main functions and modes of operation. However, the embodiment shown in the figures has been improved in several aspects and adapted for use with an attachable electronic module 2, as described in more detail below. Non-limiting examples of such modules are disclosed in WO 2021 / 116387 A1 and PCT / EP2021 / 060631, to which reference is made with respect to the main functions and modes of operation of the electronic module.

[0058] Although described with reference to a disposable injection pen similar to that disclosed in EP 2 890 434 B1, the disclosure is applicable to other disposable or reusable drug delivery devices, including, but not limited to, the injection devices disclosed in one of WO 2004 / 078239 A1, WO 2014 / 033195 A1, WO 2009 / 132777 A1, WO 005 / 018721, U.S. Pat. No. 5,693,027, U.S. Pat. No. 6,663,602 or U.S. Pat. No. 7,241,278.

[0059] In this specification, "distal" is used to designate a direction, end, or surface that is or will be arranged to face or point towards the dispensing end of the drug delivery device or a component thereof, and / or that faces away from, faces away from, or faces away from the proximal end. On the other hand, "proximal" is used to designate a direction, end, or surface that is or will be arranged to face away from the dispensing end and / or the distal end of the drug delivery device or a component thereof. The distal end may be the end closest to the dispensing end and / or the end furthest from the proximal end, and the proximal end may be the end furthest from the dispensing end. The proximal surface may face away from the distal end and / or face towards the proximal end. The distal surface may face towards the distal end and / or face away from the proximal end. The dispensing end may be, for example, the needle end at which the needle unit is or will be attached to the device.

[0060] Figures 1 and 2 show a medication or drug delivery device 1 comprising an outer housing 10, an inner housing insert 20, a piston rod 30, a drive sleeve 40, a nut 50, a dose setting drum 60, a dose setting member 70, a cartridge 80 and a cap 90. As additional components a needle arrangement (not shown) may be provided comprising a needle hub and e.g. a needle cover.

[0061] The outer housing 10 is a generally tubular element having a distal portion forming a cartridge holder 11 for receiving the cartridge 80 and provided with threads 12 or the like for mounting a needle hub, and a proximal portion which receives the components of the dose setting and drive mechanism. In a preferred embodiment, the outer housing 10 is transparent, optionally provided with an opaque layer in the proximal portion. The housing 10 comprises a transparent window 13. A cross-sectional view of the housing 10 is shown in Figure 8, where a series of counter stop teeth 14 formed on the inner surface of the housing 10 are visible. The housing 10 has a central axis X and an outer diameter D H is shown in Figure 6.

[0062] The inner housing insert 20 is an inner body having a generally tubular configuration with different diameter regions. The inner housing insert 20 is received in the proximal portion of the housing 10 and is permanently secured therein to prevent any relative movement of the inner housing insert 20 with respect to the housing 10. The inner housing insert 20 is provided with external threads 21 on its outer surface. Additionally, the inner housing insert 20 is splined on its inner surface and provided with internal threads at its distal end.

[0063] The piston rod 30 is an elongated element with two external threads with different leads, preferably with overlapping opposite threads. One of these threads engages with the internal threads of the inner housing insert 20. A disc-shaped bearing 31 may be attached to 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 an integral component through a predetermined break point.

[0064] The drive sleeve 40 is a generally tubular element with different diameter regions. 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 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 clicker arm formed by a U-shaped opening at the bottom of the drive sleeve 40. The clicker arm engages an internal spline in the inner housing insert 20 and is capable of bending radially inward during relative rotation between the drive sleeve 40 and the inner housing insert 20. This radial bending is permitted as long as the clicker arm is aligned with a pocket in the dose setting member 70, but is prevented when the clicker arm is not aligned with a pocket in the dose setting member 70, thereby preventing relative rotation between the drive sleeve 40 and the inner housing insert 20. At its proximal end, the drive sleeve 40 may be provided with a spring arm that 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 that permanently engages a spline on the dose setting member 70, such that any rotation of the dose setting member 70 is transmitted to the drive sleeve 40.

[0065] The nut 50 is provided between the inner housing insert 20 and the drive sleeve 40. An outer rib of the nut 50 engages with an inner spline of the inner housing insert 20. An inner thread of the nut 50 engages with an outer thread 41 of the drive sleeve 40. Alternatively, splines and ribs can be provided at the interface between the nut 50 and the drive sleeve 40, and threads can be provided at the interface between the nut 50 and the inner housing insert 20. As a further alternative, the nut 50 may be designed, for example, as a half nut. Furthermore, at least one, for example four, rotational hard stops are provided on the nut 50 for interaction with a corresponding stop on the drive sleeve 40 at the proximal end of the threads 41.

[0066] The dose setting drum 60 is a generally tubular element with an internal thread engaging with the external thread 21 of the inner housing insert 20. The dose setting drum 60 is thus sandwiched 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 drum 60, forming an indicia member. The numbers are arranged on a spiral line, so that only one number or only a few numbers are visible through the window 13 of the housing 10. The dose setting drum 60 is provided with a ring of clutch teeth 61 near its proximal end for engaging with corresponding clutch teeth 73 of the dose setting member 70, as will be explained in more detail below (FIG. 7). Furthermore, an optional clicker arm 62 may be provided, e.g. near the distal end of the dose setting drum 60, for engaging with a ratchet profile 74 of the dose setting member 70.

[0067] The dose setting member 70 comprises two separate components, a tubular sleeve 71 (FIG. 9) and a button 72, which are permanently fixed together to function as a single component. The tubular sleeve 71 of the dose setting member 70 comprises an inner ring of clutch teeth 73 near its proximal end, an inner ring of ramp teeth forming a ratchet profile 74, and a stop tooth 75 at its distal end for engaging a counter stop tooth 14 of the housing 10. The button 72 comprises a proximal end face and a stem extending distally from said end face. As shown in FIG. 4, two radial apertures 76 and two axial apertures 77 are both formed in an outer groove 78 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 comprises a pocket into which the clicker arm of the drive sleeve 40 can be curved and comprises at least one axially extending spline that permanently engages a corresponding groove formed in the drive sleeve 40.

[0068] 3a and 6, the tubular sleeve 71 of the dose setting member 70 may be provided with a profiled proximal region to facilitate gripping and rotating the dose setting member 70. The maximum outer diameter D of the dose setting member 70, in particular of the tubular sleeve 71, G is the outer diameter D of the housing 10 H (see FIG. 6 ). More specifically, the maximum outer diameter D G is approximately equal to or slightly smaller than the inner diameter of the area of ​​the housing 10 located adjacent the dose setting member 70.

[0069] The cartridge 80 contains a pre-filled, constricted cartridge reservoir, which may typically be made of glass. A rubber bung or stopper is located at the proximal end of the cartridge reservoir, and a pierceable rubber seal is located at the other distal end. A crimped annular metal band is used to hold the rubber seal in place. The cartridge 80 is mounted in the cartridge holder 11 with the bearing 31 of the piston rod 30 abutting the bung.

[0070] 1 shows the device 1 without the 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 removably snapped onto the housing 10 and may be removed for use of the device 1.

[0071] The electronic module 2 may be removably 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 comprise a cup-shaped outer cap 3 holding a PCBA 4 with a processor and a battery 5. The module 2 further comprises a sensor arrangement operable to connect to the processor and to generate measurement data indicative of the dose setting and / or dose delivery operations. To this end, the sensor arrangement comprises at least one LED and one or more photodetectors, which together form an optical sensor. In addition to or as an alternative to the LED and the photodetector, alternative sensor types can 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 comprise or be connected to a communication unit, for example comprising a wireless Bluetooth® communication interface operable to connect to the processor and to establish communication with another (external) device, for example a smartphone. The communication unit is operable to transmit data, for example measurement data, to the other devices mentioned above. Still further, an electronic user feedback generator may be coupled to the processor and operable to generate a feedback signal to the user. In an exemplary configuration, the electronic user feedback generator comprises an LED for generating an optical feedback signal. In addition to or as an alternative to an LED, the electronic user feedback generator may comprise a sounder and / or a vibration motor.

[0072] The module 2 further comprises a chassis, which engages the cap 3 with a snap fit, thus constraining the cap and the chassis axially and rotationally. The chassis may be transparent or translucent and made of polycarbonate or the like. The chassis houses the PCB unit 4. The chassis further comprises two light pipes 6, which are axially extending protrusions of the chassis, with polished side walls and diffusive end faces forming the sensor end and the encoder end. In other words, light can enter or exit the light pipes at the opposite sensor end and the encoder end, but is guided (reflected) by the side walls. In one example, the light pipes 6 may be rotationally offset 45° from each other. The light pipes 6 are configured to fit or extend through one of the apertures 77 in the button 72 when the module 2 is attached to the drug delivery device 1. To this end, the chassis further comprises mounting features in the form of two flexible clips 7 , for example rotationally offset by 180°, for engaging radial apertures 76 in the button 72 .

[0073] The dose setting and driving 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.

[0074] During a dose setting operation, the clutch teeth 61 of the dose setting drum 60 engage with the clutch teeth 73 of the dose setting member 70. Thus, the dose setting drum 60, the dose setting member 70 and the drive sleeve 40 (splined to the dose setting member 70) are rotationally coupled. A user can set a dose by rotating the tubular sleeve 71 of the dose setting member 70 such that the dose setting drum 60, the dose setting member 70 and the drive sleeve 40 exit the housing 10 while rotating along a helical path defined by the threads 21 of the inner housing insert 20 which guide the threads of the dose setting drum 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 drum 60, whereby the piston rod 30 is held stationary in the inner housing insert 20 by its threaded interface. The selected dose is visible through the window 13 of the housing 10. During this rotation of the dose setting drum 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 illustrated exemplary embodiment, one rotation of the dose setting member corresponds to 24 dose increments. For example, if the injection device 1 is configured to administer human insulin, the dose increments may be expressed in so-called international units (IU), where 1 IU is bioequivalent to approximately 45.5 micrograms (1 / 22 mg) of highly pure crystalline insulin.

[0075] At the maximum settable dose, for example 80 units, the stop feature engages and prevents further setting (e.g. dialing). Furthermore, during dose setting, the drive sleeve 40 rotates relative to the inner housing insert 20, causing the nut 50, which is rotationally fixed to the inner housing insert 20 via axially extending ribs and splines, to move on the threads 41 of the drive sleeve 40. The last dose nut 50 provides the function of counting the number of units dispensed. The nut 50 locks the device 1 at end of life, so that no more medication can be dialed or dispensed by the user. Rotation of the drive sleeve 40 during setting advances the nut 50 along the threads 41. The nut 50 is free to slide axially within the inner housing insert 20 at all times, thereby allowing the nut 50 to advance. In the end of life condition, the stop feature of the last dose nut 50 contacts a corresponding feature on the drive sleeve 40. The splined contact with the inner housing insert 20 reacts to any torque transmitted by these stop features 47 .

[0076] Once the desired dose has been dialed in, the device 1 is ready for dose dispensing. Dispensing essentially requires pushing the dose setting member 70, which will result in disengagement of the clutch teeth 61, 73. As mentioned above, when setting a dose, the dose setting member 70 is "biased out" by the flexible arms of the drive sleeve 40 and the clutch teeth 61, 73, which rotationally lock and engage the drive sleeve 40, the dose setting member 70 and the dose setting drum 60 together. Once the dose setting member 70 is pushed in, the clutch teeth 61, 73 are disengaged, allowing relative rotation between the dose setting drum 60 and the dose setting member 70. In all conditions, the drive sleeve 40 and the dose setting member 70 remain rotationally locked. Thus, when the clutch is disengaged (when the dose setting member 70 is pushed in), the dose setting member 70 and the drive sleeve 40 are rotationally locked together, with the dose setting member 70, the drive sleeve 40 and the dose setting drum 60 still axially coupled. At the same time, the relative axial movement of the dose setting member 70 with respect to the drive sleeve 40 results in the pocket on the stem shifting relative to the flexible clicker arms. Thus, the flexible clicker arms are prevented from bending inwards. This activation of the lockout feature prevents the flexible clicker arms from overcoming the splines of the inner housing insert 20 when the dose setting member 70 is pushed in. In this condition, the drive sleeve 40 and the dose setting member 70 are rotationally constrained with respect to the inner housing insert 20, thus preventing any rotation with respect to the housing 10.

[0077] Once the desired dose is set, the dose setting member 70 can be depressed and the piston rod 30 is driven forward to dispense the drug from the cartridge. The mating threaded interaction 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, a dispense clicker is actuated involving a ratchet profile 74 of the dose setting member 70 and a clicker arm 62 of the dose setting drum 60. The dispense clicker provides audible feedback to the user that 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. Thus, the rotational position of the nut 50 does not change during dose delivery and the nut 50 remains in its position on the drive sleeve 40 that was set during dose setting or dialing.

[0078] The dose setting member 70, more specifically the tubular sleeve 71, has at its distal end a set of axially oriented stop teeth 75. These teeth 75 are formed on the proximal rim of the tubular sleeve 71 and are configured to engage a set of counter 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 "justify" the rotational position of the dose setting member 70 relative to the housing 10 and the dose setting drum 60 at the end of each dose. It is important to ensure that the clutch teeth 61, 73 between the dose setting member 70 and the dose setting drum 60 are aligned so that when the dose setting member 70 is released, they re-engage correctly (allowing the subsequent dose to be dialed in). Furthermore, it is important for the correct functioning of the module 2 that the rotational position of the dose setting member 70 is aligned relative to the dose setting drum 60 at the end of each dose. This is because the module 2 is intended to accurately detect all relative rotational movements of the clutch teeth 61 on the dose setting drum 60 with respect to the dose setting member 70 in order to determine the size of the delivered dose. Without 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 would only be measured by the dial clicker (the flexible clicker arm of the drive sleeve 40 and the axial spline of the inner housing insert 20). However, since the dial clicker is intentionally designed to yield to a relatively small torque, it does not provide particularly accurate rotational data. Furthermore, if the dose setting member 70 is pressed in when the pen 1 is in the 0U dial state, the engagement of these teeth 14, 75 prevents the user from rotating the dose setting member 70 with respect to the housing 10. Rotating the dose setting member 70 in this state would allow the user to operate the pen mechanism to advance or retract the piston rod 30, possibly leading to an incorrect dose.

[0079] The drug delivery device 1 is suitable for use with or without the module 2. When the module 2 fits onto the dose setting member 70, the flexible clip 7 engages and snaps into the radial aperture 76 of the button 72, while the light pipe 6 extends into the axial aperture 78. When used in conjunction with the module 2, the ring of clutch teeth 61 of the dose setting drum 60 has the additional function of an encoder.

[0080] These radially outwardly projecting clutch teeth 61 located on the outer diameter at the proximal end of the dose setting drum 60 can be detected by an optical sensor. In other words, an array of proximally facing encoder features formed in a circular, e.g. ring-shaped pattern is provided by the ring of clutch teeth 61. As shown in FIG. 7, in the exemplary embodiment, there are only 12 equally spaced clutch teeth 61, but these combine with 24 mating teeth 73 on the dose setting member 70 to provide 24 distinct engagement positions (thus allowing 24 selectable dose increments per revolution of the dose setting member when setting and delivering a dose). This configuration has several advantages. As the clutch teeth 61 project radially from the outer diameter of the dose setting drum 60, they interact with the teeth 73 formed on the inner diameter of the dose setting member 70 to transmit torque at the largest possible diameter. This means that they are stronger and have a greater resistance to torque applied by the user. The smaller number of wide teeth (i.e. 12 "double wide" teeth rather than 24 single wide teeth) also provides a stronger means of transmitting torque from the dose setting drum 60 to the dose setting member 70. The smaller number of wide teeth 61 also provides a much better target for the photodetector of module 2 as the individual reflective / non-reflective areas are wider and better accommodate variations in angular tolerance (for too much or too little movement) when the dose setting drum 60 rotates relative to the dose setting member 70.

[0081] As shown in FIG. 6, the dose button 72 of the pen injector 1 constitutes the proximal side of the pen injector 1 and has two concentric grooves 78, 79 formed in its proximal face, i.e., the grooves may be formed as recesses or notches in the proximal face and may extend distally. These grooves 78, 79 accommodate the features of the module 2 and allow the module to rotate relative to the dose button 72 to find the correct rotational alignment during installation. The grooves 78, 79 serve as a means to provide separate sets of features on the dose button 72 of the pen, namely, a specialization feature that prevents installation of the wrong type of module 2, a feature that allows the module 2 to be securely attached via the clip feature 7, and a feature that provides access to the clutch teeth 61 of the pen mechanism that allows the module 2 to detect / encode the dose value. As previously mentioned, the feature used by the module 2 to detect the size of the delivered dose is the clutch teeth 61 formed as an array of equally spaced features around the circumference at the proximal end of the dose setting drum 60. These encoder features may not necessarily be clutch teeth 61, but could simply be "flags" for an optical encoder system that rotates with the dose setting drum 60, and the configuration of aperture 77 is useful for allowing access to such encoder features when module 2 is fitted into pen 1.

[0082] Since the module 2 uses an optical IR emitter / detector set to encode the dose delivered from the pen 1, it is preferable to reduce the level of "stray" IR radiation, e.g. from high ambient light levels when the pen 1 is used outdoors, which may interfere with the correct performance of the module sensor. 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 comprise an IR absorbing masterbatch and / or have an electro-discharge machined textured surface finish. [Explanation of symbols]

[0083] 1 Drug delivery devices (pens) 2 Electronic Module 3 Cap 4 PCBA (processor, sensor) 5 Battery 6 Light Pipe 7 Flexible Clip 10. Housing 11 Cartridge holder 12 Screws 13 Dose window 14 Counter Stop Teeth 20 Inner Housing Insert 21 Screw 30 Piston rod 31 Bearing 40 Drive sleeve 41 Screw 50 Nut 60 dosed drums 61 clutch teeth 62 Clicker Arm 70 Dose setting member 71 Tubular sleeve 72 Buttons 73 clutch teeth 74 Ratchet profile (ramp teeth) 75 stop teeth 76 Radial Aperture 77 Axial Aperture 78 Outer groove 79 Inner groove 80 Cartridges 90 Cap X-axis D G Diameter of dose setting member 70 D H Housing 10 diameter

Claims

1. 1. A drug delivery device for setting and dispensing a dose of a liquid drug, the device comprising a housing (10), preferably having an essentially circular cross-section, at least partially enclosing a dose setting and driving mechanism having a piston rod (30) and a dose setting member (70), the dose setting and driving mechanism being 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 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 perpendicular to the axis (X) of the dose setting member (70) is smaller than a maximum radial extension perpendicular to the axis (X) of a region of the housing (10) located adjacent to the dose setting member (70).

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

3. A drug delivery device according to claim 1 or 2, characterized in that the dose setting member (70) is provided with attachment features (76) for mounting a separate attachable module (2).

4. The drug delivery device of claim 3, characterized in that the dose setting member (70) is provided with a substantially circular groove (78) extending in a proximal end face of the dose setting member (70), and the mounting feature (76) is provided within or adjacent to the groove (78).

5. A drug delivery device according to claim 3 or 4, characterized in that the attachment feature is a radial aperture (76) provided in the dose setting member (70).

6. A drug delivery device according to any one of claims 1 to 5, characterized in that the dose setting member (70) comprises two separate components (71, 72) permanently fixed to each other and functioning as a single component.

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

8. A drug delivery device according to any one of claims 1 to 7, characterized in that the dose setting member (70) is made from 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 claims 1 to 8 and an electronic module (2) attached to the dose setting member (70) of the drug delivery device, said module (2) comprising: a sensor; a processor configured to control the operation of at least one said sensor and to process and / or store signals from at least one said sensor; - mounting features for attaching said module to said dose setting member (70).

10. 10. The dose recording system of 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. Dose recording system according to claim 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 mounting the module (2) to a proximal end of the drug delivery device.

13. The dose recording system according to claim 12, wherein the mounting feature comprises at least one flexible clip (6) for axially and rotationally fixing the module (2) to the dose setting member (70).

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

15. A dose recording system according to any one of claims 9 to 14, wherein the dose setting member (70) is provided with a mechanical coding (79) and the module (2) is provided with a mechanical counter-coding, which engages with the mechanical coding (79) when the module (2) is attached to the drug delivery device (1).

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