Electronic add-on module and assembly of an electronic add-on module and a drug delivery device

Abstract

The present disclosure is directed to an electronic add-on module (100) configured for attachment to a drug delivery device and to an assembly comprising a drug delivery device and an electronic add-on module (100). The electronic add-on module may comprise a main housing (103) with a coupling portion (108, 109) configured to attach the module (100) on a user interface of a drug delivery device, a module user interface (121) for actuation of the module (100) and an electronic dose recording system configured to determine, store and / or transmit data indicative of at least a condition of the drug delivery device or its use. The electronic dose recording system comprises a control unit configured to be switched from a sleep mode with reduced energy consumption into an operation mode with increased energy consumption by means of a switch comprising a stationary part (123) and a movable part (122) which are movable relative to each other. The module (100) may further comprise a clutch for coupling the coupling portion (108, 109) to the module user interface (121) while permitting limited relative movement between the module user interface (121) and the coupling portion (108, 109). One of the stationary part (123) and the movable part (122) may be constrained to the coupling portion (108, 109) and the other of the stationary part (123) and the movable part (122) may be constrained to the module user interface (121).

Description

[0001] Description

[0002] ELECTRONIC ADD-ON MODULE AND ASSEMBLY OF AN ELECTRONIC ADD-ON MODULE AND A DRUG DELIVERY DEVICE

[0003] The present disclosure is generally directed to an electronic add-on module and to an assembly of an electronic system, e.g. an electronic add-on module, which is configured to be, e.g. releasably, attached to a drug delivery device like.

[0004] Electronic add-on modules may be used attached on to a drug delivery device, e.g. a pen-type injection device. Such drug delivery devices often comprise a housing with a container configured to receive a drug or a cartridge filled with a drug, a dose setting unit comprising a dose dial user interface, e.g. a dial grip, at least rotationally moveable with respect to the housing during dose setting and an injection user interface, e.g. a dose button, at least axially moveable with respect to the housing for causing dose dispensing, and a dose delivery unit comprising a plunger at least axially moveable with respect to the housing during dose dispensing.

[0005] Electronic add-on modules for attachment to drug delivery devices are generally known and often used to measure relevant data with respect to dose setting and / or dose dispensing. To save energy and extend battery lifetime it is generally known to put the electronics of such modules into a sleep mode with significantly reduced power consumption. This may include turning the electronics off. However, to be sure to have the electronics operational e.g. when measuring doses, a wake-up or switch-on mechanism is necessary. WO 2019 / 101962 A1 and WO 2021 / 116387 A1 each disclose modules for drug delivery devices having a low power mode in which sensors are not energized and a high power operation mode in which sensors are energized. The systems may be switched into the high power operation mode by a switch activated by the displacement of an injection button. Further, WO 2022 / 223747 A1 discloses a module in which sensors are used for waking the electronic module from a low-power-con- sumption mode to a further state. A further add-on capture module is known from US 2021 / 220563 A1.

[0006] It is an object of the present disclosure to provide an improved electronic add-on module permitting switching between a mode of relatively low power consumption and a mode of relatively higher power consumption. Further, it is an object of the present disclosure to provide an improved assembly comprising a drug delivery device and such an electronic add-on module. This object is essentially solved by an electronic add-on module according to claim 1.

[0007] According to an aspect of the present disclosure, an electronic add-on module configured for attachment to a drug delivery device may comprise a main housing with a coupling portion configured to attach the module on a user interface, e.g. on a dose dial grip, of a drug delivery device, a module user interface for actuation of the module and an electronic dose recording system configured to determine, store and / or transmit data indicative of at least a condition of the drug delivery device or its use, e.g. to determine the amount of doses selected and / or dispensed from the drug delivery device. The module user interface may be any component part or portion of the module suitable for operating the module. This may include switching between different modes of the module and / or transmitting a movement, a force and / or a torque to the module, especially in order to operate the drug delivery device.

[0008] The electronic dose recording system of the electronic add-on module may further comprise a control unit configured to be switched from a sleep mode with reduced energy consumption into an operation mode with increased energy consumption by means of a switch comprising at least one stationary part and at least one movable part which are movable relative to each other. This relative movement of the switch parts operates the switch. Generally, a sleeping state or mode may be a mode in which some or all functionalities of the module are at minimal or virtually zero power consumption but which does not require a system boot up in the event that the electronic system (or the drug delivery device) is taken out of sleeping mode. In other words, in some embodiments, the sleep mode is a mode in which not all components are fully switched off. In an alternative embodiment, all electronic components may be fully switched off in the sleep mode.

[0009] According to a further aspect of the present disclosure, the electronic add-on module further comprises a clutch for coupling the coupling portion to the module user interface while permitting limited relative movement between the module user interface and the coupling portion. The clutch may be configured to transmit a movement, a force and / or a torque from the module user interface and the coupling portion. Especially, the clutch may transmit a movement, a force and / or a torque from the module user interface and the coupling portion after an initial slipping, namely the permitted limited relative movement between the module user interface and the coupling portion. In other words, the clutch may be configured such that a first part of a movement of the module user interface is not transmitted to the coupling portion due to the permitted relative movement between these parts, whereas the following part of the movement is transmitted from the module user interface to the coupling portion. Preferably, the stationary part is constrained to the coupling portion and the movable part is constrained to the module user interface or vice versa. In other words, the limited relative movement between the module user interface and the coupling portion permitted by the clutch actuates the switch, thereby switching the control unit configured from a sleep mode with reduced energy consumption into an operation mode with increased energy consumption.

[0010] The present disclosure is based on the idea that a user of a module which is attached to a drug delivery device may use the module to operate the drug delivery device, e.g. to select a dose and / or to dispense a dose, wherein this operation results in activating the electronics of the module from a sleep mode. This has the benefit that the electronics of the module are activated to be operational when a user operates the drug delivery device via the module without requiring additional steps by the user. In other words, the electronics of the module may be activated automatically when a user starts operating the drug delivery device.

[0011] In an example, the switch may be an electromagnetic switch. In more detail, the stationary part of the switch may comprise at least one magnetic sensor and the movable part of the switch may comprise at least one magnet or vice versa. The relative movement of the movable part relative to the stationary part required for actuating the switch may be reduced by providing several magnets or magnet sections passing by a magnetic sensor during this movement and / or by providing several magnetic sensors along the path of the magnet(s). In an exemplary embodiment, the stationary part of the switch may be a Hall-sensor rotationally constrained to the coupling portion and the movable part of the switch may be a sectional magnetized ring rotationally constrained to the module user interface. The sectional magnetized ring may comprise several magnet portions distributed over the circumference of the ring such that a relatively small angle of rotation can be detected by the magnetic sensor, e.g. the Hall-sensor. For example, if the sectional magnetized ring comprises 18 magnets evenly distributed over the circumference of the ring, a rotation of 20° or more will be detected by the sensor.

[0012] The switch may be configured and adapted to the clutch such that the switch is operated thereby switching the control unit configured from its sleep mode into its operation mode during the limited relative movement between the module user interface and the coupling portion permitted by the clutch. In an example, the clutch may permit relative rotation of the module user interface relative to the coupling portion by about 30° to about 60° until the rotation of the module user interface is transmitted by the clutch to the coupling portion. For this example of the clutch, a sectional magnetized ring comprising 18 magnets evenly distributed over the circumference of the ring would be suitable to detect the rotation in a reliable manner and to wake the module electronics from the sleep mode. The electronic add-on module may comprise a spring-loaded clutch. For example, the clutch may comprise a spring member interposed between the module user interface and the coupling portion or a member, e.g. a housing, rotationally constrained to the coupling portion, such that the module user interface is rotatable relative to the coupling portion against the bias of the spring member for a limited degree. In other words, the bias of the spring member may limit the relative rotation of the module user interface relative to the coupling portion. Thus, the rotation may be transmitted from the module user interface relative to the coupling portion after the spring is strained to a degree overcoming internal friction or resistance in the drug delivery device.

[0013] In an example of the present disclosure, the module user interface may comprise a dose setting drum rotatably mounted on the main housing of the module. One or more ball bearing(s) may be provided between the module user interface and the main housing of the module to allow smooth relative rotation. E.g. for manufacturing reasons, the dose setting drum may be split into two portions.

[0014] According to one aspect of the present disclosure, the dimension, for example the inner diameter, of a first portion can be adapted to fit to different dimensions and / or contours of dose dial user interfaces of different drug delivery devices. In other words, various inner diameters of the first portion can be set in a defined manner. This has the benefit of providing an add-on module which fits onto different drug delivery devices without requiring individual adapter parts.

[0015] The electronic add-on module may be configured for permanent or releasable attachment to a drug delivery device. For example, the coupling portion may comprise clamping elements mounted on the main housing of the module. According to one aspect of the present disclosure, the coupling portion comprises at least one leg and at least one adjustment mechanism. The at least one leg may be mounted in the main housing such that a portion of the leg can be transferred from a radially outer position to a radially inner position. This may allow adapting the module to different drug delivery devices. The adjustment mechanism may comprise at least a first adjustment element movably guided in the main housing and cooperating with the at least one leg such that movement of the first adjustment element relative to the main housing causes that the portion of the leg is transferred from the radially outer position with respect to a first longitudinal axis to the radially inner position. In an example, the electronic add-on module comprises three legs which are each pivot-mounted in the main housing such that a portion of the leg can be pivoted about an axis from a radially inner position to a radially outer position and vice versa, thereby changing or adapting the inner diameter of the module. According to an independent aspect of the present disclosure, the second portion may comprise an electrical power source, e.g. a battery or a rechargeable cell, a printed circuit board assembly (PCBA), e.g. comprising and / or forming a control unit, a sensor arrangement, a communication unit for communicating with another device, e.g. for wireless transfer of data, and / or the switch, e.g. for turning the electronic module on and off and / or for waking the module or its components from a sleeping mode or a low power consumption mode.

[0016] The sensor arrangement may comprise an acoustic sensor and / or a vibrational (acceleration) sensor. For example, an acoustic sensor arrangement comprises at least one microphone. According to an aspect of the present disclosure, the sensor arrangement is configured to detect an acoustic and / or vibration feedback generated by the drug delivery device during dose setting and / or dose dispensing, wherein the feedback is indicative of the selected dose amount and / or dispensed dose amount. In other words, the sensor arrangement may at least indirectly permit detection of relative movements, e.g. a relative rotational movement, between at least two component parts of the drug delivery device which typically move in a predetermined manner during a dose setting operation and / or a dose dispensing operation. An example of such a movement may be a clicker mechanism which generates an acoustic and / or vibration feedback during a dose setting operation and / or a dose dispensing operation.

[0017] An assembly according to the present disclosure comprises a drug delivery device and an electronic add-on module configured for releasable attachment to the drug delivery device. The electronic add-on module may be, e.g. releasably, attached to the drug delivery device by releasably fastening means, for example, interacting mechanical coupling elements or by frictional or elastic engagement. A dose setting unit of a drug delivery device may comprise a dose dial user interface, e.g. a dose dial grip, which is, at least rotationally, e.g. helically, moveable with respect to the housing during dose setting and an injection user interface at least axially moveable with respect to the housing for causing dose dispensing. The injection user interface may be a separate component part, e.g. a dose button, which may be displaced relative to the dose dial user interface for causing dose dispensing. As an alternative, the dose dial user interface and the injection user interface may be portions of one single component part, e.g. a combined dose dial and injection knob.

[0018] The electronic add-on module typically comprises a first portion with a first longitudinal axis and a second portion coupled to the first portion allowing relative axial movement parallel to the first longitudinal axis with respect to the first portion. The first portion defines an auxiliary dose dial user interface and is configured to be releasably attached to the dose dial user interface of the drug delivery device such that the first portion follows the movement of the dose dial user interface and vice versa when attached to the drug delivery device. The second portion defines an auxiliary injection user interface configured to apply pressure onto the injection user interface of the drug delivery device when attached to the drug delivery device.

[0019] According to an independent aspect of the present disclosure, in an assembly comprising a drug delivery device and an electronic add-on module configured for attachment to the drug delivery device, the drug delivery device comprises a dose setting unit with a dose dial user interface at least rotationally moveable with respect to the device housing during dose setting. A reliable wake-up function of the module may be achieved in that the dose dial user interface of the drug delivery device is operable by rotating the module user interface when the module is attached to the drug delivery device by means of the coupling portion, wherein rotation of the module user interface relative to the drug delivery device causes the control unit to switch from its sleep mode into its operation mode prior to transmitting rotation from the module user interface to the dose dial user interface. In more detail, upon rotation of the module user interface relative to the drug delivery device, the clutch prevents transmitting a first part of the rotation to the dose dial user interface and transmits further rotation to the dose dial user interface. Thus, wake up is effected prior to transmitting a movement from the module to the drug delivery device. This allows detecting the selected doses and / or the dispensed doses even if the module was in a sleep mode prior to the use of the drug delivery device.

[0020] Although not required in the context of the present disclosure, the drug delivery device may optionally comprise further components such as a drive sleeve, a number sleeve, a clutch, a cap, a needle, a spring, a lead screw or the like, interacting with the dose button, the dose dial grip, the drive sleeve, the plunger and / or the housing, for example as disclosed in WO 2004 / 078239 A1. However, the present disclosure is not limited to the drug delivery device of WO 2004 / 078239 A1. Other suitable drug delivery devices to be used with such a module may comprise a dial grip for selecting a variable dose and a separate dose button for initiating or performing dose dispensing, e.g. as described in EP 1 570 876 B1 , EP 2 814 547 B1 , EP 2 890 434 B1 , WO 2009 / 132777 A1 , US 6,663,602 B2, US 7,241 ,278 B2 or US 9,937,294 B2. In addition, other suitable drug delivery devices to be used with such a module may comprise a single knob forming a dial grip for selecting a variable dose and a dose button for initiating or performing dose dispensing, e.g. as described in WO 2005 / 018721 A1 or WO 2014 / 033195 A1. Still further, the drug delivery device may be a spring driven device as described in US 2008 / 306446 A1 or US 2009 / 054839 A1.

[0021] If the drug delivery device has a similar working principle as in the example of WO 2004 / 078239 A1 , during dose setting components of the drug delivery device may perform the following movements. A housing may be stationary and may be used as a reference system for the further movements of other components. A plunger may be stationary and may be guided in a housing thread. A drive sleeve may be provided rotationally coupled to the dose dial grip during dose setting and rotationally constrained to the housing during dose dispensing. In other words, the drive sleeve may be guided in the housing to perform a purely axial movement during dose dispensing. The drive sleeve may perform a helical movement, i.e. a combined axial and rotational movement, and may be in threaded engagement with the plunger. A dial grip may perform a helical movement. A dose button may be free to rotate but axially constrained to the drive sleeve. For example, the dose button may be axially retained to the drive sleeve by a clutch. An optional clutch may perform a helical movement and may couple a number sleeve to the drive sleeve. An optional clutch spring may perform an axial movement and may be guided in housing splines and may click over clutch teeth. An optional number sleeve may be permanently fixed on the dial grip and may perform a helical movement and may be guided in a housing thread. An optional last dose nut may perform a helical movement on a drive sleeve track of the drive sleeve and may be rotationally constrained to the housing. Hence, the last dose nut may perform axial movement relative to the housing and a helical movement with respect to the drive sleeve.

[0022] During dose dispensing components of the drug delivery device may perform the following movements. The housing may remain stationary as a reference system for the further movements of other components. The plunger may perform a helical movement and may be guided in the housing thread. The drive sleeve may perform a pure axial movement and may be in threaded engagement with the plunger. The dose dial grip may perform a helical movement and may be permanently fixed on the number sleeve. The dose button may perform an axial movement if coupled to the drive sleeve and / or the clutch. The optional clutch may perform pure axial movement and may de-couple the number sleeve from the drive sleeve. The optional clutch spring may perform pure axial movement and may be rotationally constrained to the clutch due to a pressure applied to the dose button. The optional number sleeve may perform a helical movement and may be guided in the housing thread. The optional last dose nut may maintain its axial position on the drive sleeve track and may be rotationally constrained to the housing.

[0023] According to an independent aspect of the present disclosure, the assembly comprises a drug delivery device having a clicker mechanism generating an acoustic and / or vibrational feedback signal during specific use conditions, e.g. at least during dose setting. Such a feedback signal may be detected by the electronic module and the module may determine an amount of dose selected and / or dispensed. For example, the clicker mechanism may generate one clicking sound for every III dispensed, like e.g. in WO 2004 / 078239 A1 , WO 2014 / 033195 A1 , WO 2005 / 018721 A1 or EP 1 570 876 B1.

[0024] The electronic add-on module may be an electronic dose recording system for determining, storing and / or transmitting data indicative of at least a condition of the drug delivery device or its use. For example, the system may detect if the drug delivery device is switched between a dose setting mode and a dose dispensing mode and vice versa. In addition or as an alternative, the system may detect if a dose is set and / or if a dose is dispensed. Still further, the system may detect the amount of dose selected and / or the amount of dose dispensed. The electronic add-on module may further comprise a communication unit for communicating with another device, e.g. a wireless communications interface for communicating with another device via a wireless network such as Wi-Fi or Bluetooth, or even an interface for a wired communications link, such as a socket for receiving a Universal Series Bus (USB), mini-USB or micro-USB connector. Preferably, the electronic add-on module comprises an RF, Wi-Fi and / or Bluetooth unit as the communication unit. The communication unit may be provided as a communication interface between the electronic add-on module and the exterior, such as other electronic devices, e.g. mobile phones, personal computers, laptops and so on. For example, dose data may be transmitted by the communication unit to the external device. The dose data may be used for a dose log or dose history established in the external device.

[0025] The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.

[0026] As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated. The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20°C), or refrigerated temperatures (e.g., from about - 4°C to about 4°C). In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dualchamber cartridge may be configured to allow mixing between the two or more components prior to and / or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.

[0027] The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and / or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (anti-diabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.

[0028] Examples of APIs for the treatment and / or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipep- tidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and / or exchanging at least one amino acid residue occurring in the naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term ..derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and / or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.

[0029] Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Vai or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0030] Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-pal- mitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega- carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(w-carbox- yheptadecanoyl)-des(B30) human insulin and B29-N-(w-carboxyheptadecanoyl) human insulin.

[0031] Examples of GLP-1 , GLP-1 analogues and GLP-1 receptor agonists are, for example, Lix- isenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semag- lutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC-1134- PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211 , CM-3, GLP- 1 Eligen, GRMD-0901 , NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador- GLP-1 , CVX-096, ZYOG-1 , ZYD-1 , GSK-2374697, DA-3091 , MAR-701 , MAR709, ZP-2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651 , ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN and Glucagon-Xten. An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cho- lesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom.

[0032] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0033] Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Fol litropi n, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

[0034] Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and / or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.

[0035] The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigenbinding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).

[0036] The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and / or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full- length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0037] The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.

[0038] Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sari- lumab), and anti IL-4 mAb (e.g., Dupilumab).

[0039] 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.

[0040] Those of skill in the art will understand that modifications (additions and / or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof. An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1 :2014(E). As described in ISO 11608-1 :2014(E), needle-based injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container.

[0041] As further described in ISO 11608-1 :2014(E), a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).

[0042] As further described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with a replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation). As also described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).

[0043] The terms “axial”, “radial”, or “circumferential” as used herein may be used with respect to a first longitudinal axis of the electronic add-on module, the first portion, the second portion, the drug delivery device, the cartridge, the housing, the cartridge holder or the assembly of the drug delivery device and the electronic add-on module, e.g. the axis which extends through the proximal and distal ends of the cartridge.

[0044] "Distal" is used herein to specify directions, ends or surfaces which are arranged or are to be arranged to face or point towards dispensing end of the electronic add-on module or the drug delivery device or components thereof and / or point away from, are to be arranged to face away from or face away from the proximal end. On the other hand, “proximal” is used to specify directions, ends or surfaces which are arranged or are to be arranged to face away from or point away from the dispensing end and / or from the distal end of the electronic add-on module or the drug delivery device or components thereof. The distal end may be the end closest to the dispensing and / or furthest away from the proximal end and the proximal end may be the end furthest away from the dispensing end. A proximal surface may face away from the distal end and / or towards the proximal end. A distal surface may face towards the distal end and / or away from the proximal end. The dispensing end may be the needle end where a needle unit is or is to be mounted to the device, for example. Similarly, a distal element compared to a proximal element is located closer to the dispensing end than to the proximal end. Furthermore, when the electronic add-on module is considered alone, the term "distal" may be used with regard to the more distal end of the electronic add-on module, which is located closer to the dispensing end of the drug delivery device when attached to the drug delivery device, and the term "proximal" may be used with regard to the proximal end of the electronic add-on module, which is located further away from the dispensing end of the drug delivery device when attached to the drug delivery device. In the following, non-limiting, examples of the electronic add-on module, the drug delivery device and the assembly of the drug delivery device and the electronic add-on module are described in more detail by making reference to the drawings, in which:

[0045] Figure 1 is a perspective view of a module according to a first embodiment of the present disclosure;

[0046] Figures 2a, b is partially cut away views of the module of Figure 1 ;

[0047] Figure 3 is a perspective view of some parts of the module of Figure 1 ;

[0048] Figures 4 shows a detail of the module of Figure 1 ;

[0049] Figures 5a, b show a further detail of the module of Figure 1 ;

[0050] Figures 6a, b show different positions of an adjustment ring of the module of Figure 1 ;

[0051] Figure 7 is a sectional view of the module of Figure 1 in a home position;

[0052] Figure 8 is a sectional view of the module of Figure 1 with a lifted adjustment ring;

[0053] Figure 9 is a sectional view of the module of Figure 1 with a depressed second portion;

[0054] Figures 10a-c show different positions of the legs of the module of Figure 1 ; and

[0055] Figure 11 shows an exploded view of the module of Figure 1.

[0056] Figures 1 to 3 show an exemplary embodiment of an electronic add-on module 100 suitable for releasable attachment to a user interface of a drug delivery device (not shown). The module 100 substantially comprises a first portion 101 and a second portion 102 which are coaxially arranged on a first longitudinal axis X.

[0057] The first portion 101 comprises a main housing 103 with a circumferential groove 104, a first adjustment ring 105, a second adjustment ring 106, a spring 107 and three legs 108 each having a rubber portion 109. The second portion 102 comprises a button housing 110, a printed circuit board assembly (PCBA) 111 , a battery 112 and a bumper 113. The main housing 103 is a sleeve-like component with an inwardly protruding, ring-shaped web 114. The outer surface of the main housing 103 comprises the groove 104. The main housing 103 has three bearing holes 115 on its inner side, each defining a second axis Y parallel to the main longitudinal axis X. These bearing holes 115 receive bearing pins of the respective legs 108 such that the legs 108 are free to swivel about the respective axes Y.

[0058] Each leg 108 is substantially arch-shaped with the bearing pin on one end and a free opposite end as shown in Figure 4. The radially inwards facing side of each leg 108 may have an overmolded rubber portion 109, e.g. with a hardness of 50 shore-A. The radially outwards facing side of each leg 108 is wedge-shaped, i.e. inclined such that the side facing towards the bearing pin is thinner than the side of the free end. A distally facing bead of the leg 108 may have a uniform thickness, i.e. only a portion of the leg may be wedge-shaped.

[0059] The first adjustment ring 105 comprises three radially inwardly protruding bosses 116 extending distally. In the depicted example, the first adjustment ring 105 is substantially disc-shaped. However, in an alternative example, the first adjustment ring 105 may have a sleeve-like configuration with the bosses 116 formed as internal ribs. Figures 5a and 5b depict the main housing 103 (partially transparent) with only one leg 108 and the first adjustment ring 105. A boss 116 extends in the radial space between leg 108 and main housing 103 thereby abutting the wedge-shaped outer side of leg 108. Rotating the first adjustment ring 105 with respect to the main housing 103 and the leg 108 from the position depicted in Figure 5a to the position depicted in Figure 5b thus forces the free end of the leg 108 with the overmolded rubber portion 109 to pivot radially inwards as the boss 116 slides along the wedge-shaped outer side of the leg 108. An opposite rotation would allow the leg 108 to pivot back into the position of Figure 5a. As depicted in Figures 10a, 10b and 10c this radial movement of the free ends of the legs 108 widens or narrows the inner diameter of the module 100. In other words, by pivoting the free ends of the legs 108 inwardly or outwardly, the module 100 can be adapted to different dimensions of user interfaces of different drug delivery devices. Typically, the inner diameter may be adjusted in a range between about 14.5mm to about 19mm.

[0060] Further, the first adjustment ring 105 comprises proximally facing guides 117 for mating engagement with distally facing pins 118 in the second (upper) adjustment ring 106. Guides 117 and pins 118 are always in engagement, thereby rotationally constraining the first and second adjustment rings 105, 106 while permitting small relative axial movement as shown in Figure 6a. In other words, the second adjustment ring 106 may be lifted from the position shown in Figure 6b to the position shown in Figure 6a. Spring 107 has a plate-like form and is clamped between the web 114 of the main housing 103 and the second portion 102. Lateral protrusions of spring 107 are fixed in the second adjustment ring 106. Thus, spring 107 is elastically deflected when second adjustment ring 106 is lifted (see Figure 8) from a home position (see Figure 7). In other words, spring 107 biases second adjustment ring 106 back into the home position where guides 117 fully engage with pins 118.

[0061] The second adjustment ring 106 may have a small proximal bead radially protruding over main housing 103 in order to allow a user to grip and lift the second adjustment ring 106 with a suitable tool. A peg 119 is provided on the distal face of the bead of second adjustment ring 106 and the main housing 103 comprises three proximally facing recesses 120 adapted to each receive peg 119. In other words, peg 119 and recesses 120 define three dedicated relative rotational positions between the second adjustment ring 106 and the main housing 103. These three dedicated positions correspond to three predefined inner diameters of the module, e.g. 17.8mm, 16.2mm and 14.6mm, defined by legs 108.

[0062] The second portion 102 is partially retained in the cavity of the first portion 101 , specifically by the cavity of the second adjustment ring 106. The button housing 110 of the second portion 102 has an enlarged upper portion which encases the PCBA 111 and the battery 112 and a smaller lower portion which extends towards the web 114 of the main housing 103. The bumper 113 extends through the web 114 an comprises snap arms for attaching into the button housing 110, thereby restricting the relative axial movement of the second portion 102 relative to the first portion 101.

[0063] Spring arms provided on spring 107 abut the button housing 110 such that the second portion 102 is biased into the home position depicted in Figure 7 relative to the first portion 101. The second portion 102 may be pressed by a user into the first portion 101 against the force of the spring arms as shown in Figure 9. Thus, the button housing 110 forms an auxiliary injection user interface. By pressing the second portion 102 into the first portion 101 , the bumper 113 is moved distally with respect to the main housing 103. Thus, bumper 113 may exert pressure on a user interface, e.g. a dose button, of a drug delivery device when the module 100 is attached to a drug delivery device.

[0064] The PCBA 111 may comprise or form a control unit, a sensor arrangement and / or a communication unit. Preferably, the PCBA 111 comprises an acoustic sensor for detecting clicking sounds generated by a drug delivery device when attached to the module 100. Further, the control unit preferably determines the amount of medicament dispensed from the drug delivery device on the basis of the clicking sounds detected by the sensor. This data may be transmitted to an external device by means of the communication unit. To adjust the clamping diameter of the module 100, the legs 108 are turned around the respective axes Y by a small angle. This moves the rubberized part 109 of the legs 108 nearer to or farer from the center line X of the module 100. The movement is forced by the first (lower) adjustment ring 105 which is movable + / 30°, i.e. in total about 60°. The first adjustment ring 105 is actuated by the second (upper) adjustment ring 106. This second adjustment ring 106 must be turned by hand. To set the correct clamping mechanism diameter for dedicated insulin pens the recesses 120 form three idents in the main housing 103 where the second adjustment ring 106 is locked. The second adjustment ring 106 must be lifted by hand, e.g. using a tool, afterwards turned and is then forced back into the idents when released. The force to set the second adjustment ring 106 back is provided by the spring-plate 107. The same spring plate 107 generates a resistance when pressing the button housing 110 down. This button housing 110 is pressed to trigger the injection. The button housing 110 also serves as housing for the electronics. The bumper 113 assures the correct distance between button housing 110 and the second adjustment ring 106 to hold the spring plate 107 at a certain preload. The bumper 113 also ensures that the parts stay in the main housing 103.

[0065] To extend the battery 112 lifetime the status of the electronics may be set into a sleep mode. The module 100 may be able to measure the dose volume preset for injection. One possible measurement technology could be realized with a microphone in the electronics button housing 110 and counting the generated clicks when up dialing the dose volume. To make the microphone operational a wake-up functionality has to be installed to set the electronics into recording mode before the first click is generated by the insulin pen mechanics.

[0066] The wake-up mechanism consists of a spring-loaded clutch 121 surrounding the main housing 103, a sectional magnetized ring 122 and a small magnetic sensor 123, e.g. a Hall-sensor, inside the electronics button housing 110. The clutch 121 comprises two parts attached to the main housing 103 by a spring 124 and guided by ball bearings 125. When attached to a drug delivery device, the clutch 121 forms an auxiliary dose dial user interface replicating a dose dial user interface, e.g. a dose dial grip, of the drug delivery device. The clutch 121 may be structured, e.g. by ribs and / or grooves as depicted, to facilitate gripping and rotating the main housing 103. The clutch 121 is spring-loaded by spring 124 which is received in groove 104 of the main housing 103. By means of spring 124 the clutch 121 is always forced into an idle or home position depicted in Figure 2a when no momentum is applied by the user. When the user starts the dialing up process the clutch 121 and the magnetized ring 122 are rotated for about 30°- 60° relative to the main housing 103 (and the further component parts received therein) without transforming the momentum to the main housing 103 of the module. This is depicted in Figure 2b.

[0067] The sectional magnetized ring 122 comprises 18 magnets evenly distributed about the circum- ference of the ring such that the magnets are spaced by 20°. Rotation of the ring 122 by 20° or more thus results in a magnet fully passing by the magnetic sensor 123. The relative movement of the magnetized ring 122 will be detected by the magnetic sensor 123 and this wakes up the electronics of the module 100 and starts the recording process of the electronics. This arrangement of the elements allows that the magnetic sensor 123 in the button housing 110 to stay anywhere within 360° around the middle axis X of the module.

[0068] After the first rotation of 30°- 60° of the clutch 121 the momentum applied by a user is transferred by the main housing 103 to the dial grip of the drug delivery device (not shown), i.e. clutch 121 entrains all parts, and the up dialing and click generation starts.

[0069] Reference Numerals

[0070] 100 electronic add-on module

[0071] 101 first portion

[0072] 102 second portion

[0073] 103 main housing

[0074] 104 groove

[0075] 105 first (lower) adjustment ring

[0076] 106 second (upper) adjustment ring

[0077] 107 spring plate

[0078] 108 leg

[0079] 109 rubber portion

[0080] 110 button housing

[0081] 111 PC BA

[0082] 112 battery

[0083] 113 bumper

[0084] 114 web

[0085] 115 bearing hole

[0086] 116 boss

[0087] 117 guide

[0088] 118 pin

[0089] 119 peg

[0090] 120 recess

[0091] 121 clutch

[0092] 122 magnetized ring

[0093] 123 sensor

[0094] 124 spring

[0095] 125 ball bearing

[0096] X first Longitudinal axis (of the first portion)

[0097] Y second longitudinal axis

Claims

Claims1. An electronic add-on module (100) configured for attachment to a drug delivery device, the electronic add-on module comprising:• a main housing (103) with a coupling portion (108, 109) configured to attach the module (100) on a user interface of a drug delivery device,• a module user interface (121) for actuation of the module (100)• an electronic dose recording system configured to determine, store and / or transmit data indicative of at least a condition of the drug delivery device or its use, wherein the electronic dose recording system comprises a control unit configured to be switched from a sleep mode with reduced energy consumption into an operation mode with increased energy consumption by means of a switch comprising a stationary part (123) and a movable part (122) which are movable relative to each other, characterized in that, the module (100) further comprises a clutch for coupling the coupling portion (108, 109) to the module user interface (121) while permitting limited relative movement between the module user interface (121) and the coupling portion (108, 109), wherein one of the stationary part (123) and the movable part (122) is constrained to the coupling portion (108, 109) and the other of the stationary part (123) and the movable part (122) is constrained to the module user interface (121).

2. The electronic add-on module (100) according to claim 1 , wherein the switch is an electromagnetic switch.

3. The electronic add-on module (100) according to claim 1 or 2, wherein the stationary part of the switch comprises at least one magnetic sensor (123) and wherein the movable part of the switch comprises at least one magnet (122) or vice versa.

4. The electronic add-on module (100) according to any one of the preceding claims, wherein the stationary part of the switch is a Hall-sensor (123) rotationally constrained to the coupling portion (108, 109) and wherein the movable part of the switch is a sectional magnetized ring (122) rotationally constrained to the module user interface (121).

5. The electronic add-on module (100) according to any one of the preceding claims, wherein the switch is configured and adapted to the clutch such that the switch is operated thereby switching the control unit configured from its sleep mode into its operation mode duringthe limited relative movement between the module user interface (121) and the coupling portion (108, 109) permitted by the clutch.

6. The electronic add-on module (100) according to any one of the preceding claims, wherein the clutch is spring-loaded.

7. The electronic add-on module (100) according to claim 6, wherein the clutch comprises a spring member (124) interposed between the module user interface (121) and the coupling portion (108, 109) or a member (103) rotationally constrained to the coupling portion (108, 109), such that the module user interface (121) is rotatable relative to the coupling portion (108, 109) against the bias of the spring member (124), wherein the bias of the spring member (124) limits the rotation of the module user interface (121) relative to the coupling portion (108, 109).

8. The electronic add-on module (100) according to any one of the preceding claims, wherein the module user interface (121) comprises a dose setting drum rotatably mounted on the main housing (103) of the module (100).

9. The electronic add-on module (100) according to claim 8, wherein at least one ball bearing (125) is provided between the module user interface (121) and the main housing (103) of the module (100).

10. The electronic add-on module (100) according to any one of the preceding claims, wherein the coupling portion (108, 109) comprises clamping elements mounted on the main housing (103) of the module (100).

11. The electronic add-on module (100) according to any one of the preceding claims, wherein the coupling portion (108, 109) comprises at least one leg (108) and at least one adjustment mechanism, wherein the at least one leg (108) is mounted in the main housing (103) such that a portion (109) of the leg (108) can be transferred from a radially outer position to a radially inner position, and wherein the adjustment mechanism comprises at least a first adjustment element (105) movably guided in the main housing (103) and cooperating with the at least one leg (108) such that movement of the first adjustment element (105) relative to the main housing (103) causes that the portion (109) of the leg (108) is transferred from the radially outer position with respect to the first axis (X) to the radially inner position.

12. The electronic add-on module (100) according to claim 11 , wherein the at least one leg (108) is pivot-mounted in the main housing (103) such that a portion (109) of the leg (108) can be pivoted about an axis (Y) from a radially inner position to a radially outer position and vice versa.

13. The electronic add-on module (100) according to any one of the preceding claims, wherein the electronic dose recording system comprises an electrical power source (112), a printed circuit board assembly (111), a sensor arrangement, for example an acoustic sensor arrangement, configured to detect a relative rotational movement between at least two component parts of the drug delivery device and / or a communication unit for communicating with another device.

14. An assembly comprising a drug delivery device and an electronic add-on module (100) according to any one of the preceding claims configured for attachment to the drug delivery device, wherein the drug delivery device comprises a dose setting unit comprising a dose dial user interface at least rotationally moveable with respect to the device housing during dose setting, characterized in that the dose dial user interface of the drug delivery device is operable by rotating the module user interface (121) when the module (100) is attached to the drug delivery device by means of the coupling portion (108, 109), wherein rotation of the module user interface (121) relative to the drug delivery device causes the control unit to switch from its sleep mode into its operation mode prior to transmitting rotation from the module user interface (121) to the dose dial user interface.

15. The assembly according to claim 14, wherein upon rotation of the module user interface(121) relative to the drug delivery device, the clutch (121) prevents transmitting a first part of the rotation to the dose dial user interface and transmits further rotation to the dose dial user interface.

Images