WIRELESS DATA COMMUNICATION CIRCUIT FOR DRUG DELIVERY DEVICES - Patent application

Abstract

Disclosed is a wireless data communication circuit for a drug delivery device (12), the circuit including: a wireless communication processor (108) for processing wireless data communications (130); a battery connector having positive and negative terminals (112, 114), the positive and negative terminals connected to respective terminals (112, 114) of the wireless communication processor (108) for supplying electrical energy from a battery (104) connectable to the battery connector to the wireless communication processor (108); and an arrangement of one or more capacitors (110), each connected in parallel to the positive terminal (112) and negative terminal (114) of the battery connector, provided to back up the supply of electrical energy from a battery (104) connectable to the battery connector to the wireless communication processor (108).

Description

[Technical field]

[0001] The present disclosure relates to wireless data communication circuits for drug delivery devices, particularly drug injection devices. [Background technology]

[0002] There are a variety of illnesses that require regular treatment by delivery of medication, particularly injections. Such injections can be performed by using an injection device applied by a medical professional or by the patient themselves.

[0003] Drug delivery devices, especially for patient self-use, may be equipped with electronics for measuring and storing data related to use. Data related to use may also be transmitted to an external device, such as a smartphone, tablet, or laptop computer, or to the cloud, via a wireless link or a wired connection. For example, US Pat. No. 6,299,333 discloses a drug delivery device, such as an injection pen or a wearable pump, that can be paired with an external device and provide the paired external device with data captured from a flow sensor related to drug delivery to the patient. The device may have Bluetooth® communication and / or near field communication (NFC) circuitry for proximity-based pairing and connection with the external device to transfer the captured data to the external device in real time or with a delay.

[0004] Another drug delivery device is disclosed, for example in US Pat. No. 5,399,633, which includes a microcontroller unit and wirelessly transmits, for example via Bluetooth, a signal representative of the detected dose to a paired remote electronic device.

[0005] An accessory for attachment to a drug delivery device is disclosed, for example, in US Pat. No. 5,399,633. Transmission of data from the accessory to an external device via NFC or Bluetooth is mentioned. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] US Patent Application Publication No. 2019 / 0134305 [Patent Document 2] International Publication No. 2019036576 [Patent Document 3] International Publication No. 2019 / 219824 Summary of the Invention [Means for solving the problem]

[0007] In one aspect, the present disclosure provides a wireless data communication circuit for a drug delivery device, the circuit comprising: a wireless communication processor for processing wireless data communication; a battery connector having positive and negative terminals, the positive and negative terminals being connected to respective terminals of the wireless communication processor for supplying electrical energy from a battery connectable to the battery connector to the wireless communication processor; and an arrangement of one or more capacitors, each capacitor connected in parallel to the positive and negative terminals of the battery connector, provided to back up the supply of electrical energy from a battery connectable to the battery connector to the wireless communication processor. The wireless communication processor is configured to process wireless data communication according to one or more wireless communication technologies, in particular low power wireless communication technologies, such as RF-based technologies such as Bluetooth® Low Energy, ANT (Adaptive Network Technology) from ANT Wireless, ZigBee™, NFC (Near Field Communication), Wi-Fi™, etc. It can be seen that the battery life for operating the wireless communication processor can be extended by connecting one or more capacitor arrangements in parallel to the positive terminal of the battery connector. In particular, this capacitor arrangement can extend battery life in low-power wireless communication technologies that employ a type of burst-mode data transmission periodically after a few seconds or less.

[0008] In some embodiments, each capacitor is permanently connected in parallel to the positive and negative terminals of the battery connector. Thus, one or more capacitors are not "switched" out of the circuit, but are permanently connected. This allows one or more capacitors to have a much lower leakage current than would otherwise be possible.

[0009] In some embodiments, the wireless communications processor includes Bluetooth® communications circuitry having an antenna configured for Bluetooth® communications, the Bluetooth® communications circuitry including a Bluetooth® Low Energy radio circuit for wireless data communications.

[0010] In a more specific embodiment, the one or more capacitor arrangements may consist of four or five capacitors. Some experiments have shown that an arrangement of four or five capacitors, especially with different capacitances, can extend the battery life and fully meet the requirements of drug delivery devices and their usage periods.

[0011] In a particular embodiment, a four or five capacitor arrangement may include two capacitors having a capacitance of 220 microfarads and two or three capacitors having a capacitance of 47 microfarads. Such an arrangement has been found to be a suitable solution for extending the battery life of a common button cell, such as a cell type CR1225, having a terminal voltage of about 3 volts and a capacity of about 48 milliamp hours.

[0012] In certain embodiments, the one or more capacitor arrangements may include one or more of the following: ceramic capacitors; film capacitors; polymer capacitors; mica capacitors; electrolytic capacitors; tantalum capacitors. Ceramic capacitors, in particular, have a relatively low ESR (equivalent series resistance) and typically have no ripple current limit, and therefore may be well suited for backing up the power of a wireless communications processor from a battery, such as a button cell.

[0013] In a particular embodiment, the circuitry is disposed on a printed circuit board (PCB) configured to be disposed on a drug delivery device, particularly a drug injection pen, or an accessory to be attached to a drug injection pen. In particular, the PCB may be implemented by two smaller PCBs on which all of the electronics of the drug delivery device are disposed and connected, including the location of the wireless communication processor, the battery connector, and one or more capacitors.

[0014] In a further aspect, the present disclosure provides electronics for a drug delivery device, the electronics including a PCB having a wireless data communication circuit as disclosed herein disposed thereon. The electronics is specifically designed to be located in a body of the drug delivery device, a dose knob of the drug delivery device, or a body of an accessory for attachment to the drug delivery device. For example, the shape of the PCB of the electronics is designed to allow the electronics to be integrated into a component of the drug delivery device or the body of the accessory.

[0015] In some embodiments, the electronic device may include a battery connected to a battery connector, the battery being a button cell, in particular a lithium button cell having a capacity of several milliamp hours, for example about 48 milliamp hours, at a terminal voltage of about 3 volts.

[0016] In a further aspect, the present disclosure provides a drug delivery device including a wireless data communication circuit, the wireless data communication circuit comprising: a wireless communications processor for processing wireless data communications; a battery connector having positive and negative terminals, the positive and negative terminals being connected to respective terminals of the wireless communication processor for supplying the wireless communication processor with electrical energy from a battery connectable to the battery connector; an arrangement of one or more capacitors, each capacitor connected in parallel to a positive terminal and a negative terminal of a battery connector, provided to back up a supply of electrical energy from a battery connectable to the battery connector to a wireless communications processor; The present invention provides a drug delivery device comprising:

[0017] The drug delivery device may further include a body, a dose selection mechanism for selecting a drug dose to be delivered, a dispensing mechanism for delivering the selected drug dose, at least one antenna for wireless communication, and electronics as disclosed herein, wherein the wireless data communication circuitry of the electronics is coupled to the at least one antenna. The drug delivery device may further include a holder, e.g., a cartridge holder, for holding a drug container.

[0018] The antenna and / or electronics are disposed within an actuator, e.g., a dose knob of a drug delivery device. The dose knob is configured for a user to set the dose to be administered by rotating the dose knob. The dose knob is configured for a user to administer the set dose by pressing the dose knob. The dose knob may include a separate push button / injection button or may be a dial grip and injection button in one piece.

[0019] The drug delivery device may be a reusable device with a typical life cycle of several years. The electronics employed may allow the drug delivery device to be used over its typical life cycle without changing the battery. The drug delivery device is equipped by the electronics with the ability to wirelessly exchange data with another device, such as a mobile phone, particularly a smartphone, a computer, particularly a personal computer (PC), a tablet computer, a laptop computer, etc.

[0020] According to a further aspect, the drug delivery device may include a dose setting member rotatable relative to the body during dose delivery. The sensing element is non-rotatably fixed to the dose setting member. The drug delivery device may further include an actuator axially movable during dose delivery but not rotatable relative to the body of the drug delivery device. The actuator is axially and non-rotatably fixed to the dose setting member during dose setting. The actuator may include at least one rotation sensor responsive to relative rotation of the sensing element and the actuator during dose delivery. The actuator may further include electronics having wireless data communication circuitry, the wireless data communication circuitry comprising: a wireless communications processor for processing wireless data communications; a battery connector having positive and negative terminals, the positive and negative terminals being connected to respective terminals of the wireless communication processor for supplying the wireless communication processor with electrical energy from a battery connectable to the battery connector; an arrangement of one or more capacitors, each capacitor connected in parallel to a positive terminal and a negative terminal of a battery connector, provided to back up a supply of electrical energy from a battery connectable to the battery connector to a wireless communications processor; Includes.

[0021] The actuator may include at least one rotation sensor responsive to relative rotation of the sensing element and the actuator during dose delivery. The electronics may include a controller responsive to said rotation sensor to detect an amount of rotation of the sensing element relative to the actuator during dose delivery.

[0022] The electronics are responsive to the rotation sensor and can determine the amount of drug delivered based on the detected amount of rotation of the sensing element relative to the actuator during dose delivery.

[0023] The at least one rotation sensor may be an optical, magnetic, or acoustic sensor.

[0024] The sensing element may include alternating first and second surface configurations circumferentially spaced around the dose setting member of the drug delivery device.

[0025] The rotation sensor may include a light source that emits light during dose delivery and a light sensor for detecting light reflected off a surface configuration of the sensing element or transmitted by a particular area of ​​the sensing element.

[0026] The wireless communication circuitry is configured to wirelessly transmit data related to the dose delivered by the drug delivery device to another device, such as a mobile phone, in particular a smartphone, or a computer.

[0027] In a further aspect, the present disclosure provides an accessory for attachment to a drug delivery device including electronics having wireless data communication circuitry, the wireless data communication circuitry comprising: a wireless communications processor for processing wireless data communications; a battery connector having positive and negative terminals, the positive and negative terminals being connected to respective terminals of the wireless communication processor for supplying the wireless communication processor with electrical energy from a battery connectable to the battery connector; an arrangement of one or more capacitors, each capacitor connected in parallel to a positive terminal and a negative terminal of a battery connector, provided to back up a supply of electrical energy from a battery connectable to the battery connector to a wireless communications processor; The present invention provides accessories including:

[0028] The accessory may include a housing configured for attachment to a drug delivery device, at least one antenna for wireless communication disposed within the housing, and electronics as disclosed herein, where the electronics is disposed within the housing and the wireless data communication circuitry of the electronics is coupled to the at least one antenna. The accessory is designed as a versatile device and can be attached to a variety of drug delivery devices, providing the drug delivery device with the ability to wirelessly exchange data with another device, such as a mobile phone, particularly a smartphone, a computer, particularly a personal computer (PC), a tablet computer, or a laptop computer.

[0029] The accessory may include at least one rotation sensor configured to detect relative rotation between a sensing element of the drug delivery device and the accessory during dose delivery.

[0030] The accessory electronics may include a controller that responds to the rotation sensor to capture the amount of rotation of the sensing element relative to the actuator during dose delivery.

[0031] The electronics are responsive to the rotation sensor and can determine the amount of drug delivered based on the detected amount of rotation of a sensing element of the drug delivery device relative to the accessory during dose delivery.

[0032] The at least one rotation sensor may be an optical, magnetic, or acoustic sensor.

[0033] The sensing element may include alternating first and second surface configurations circumferentially spaced around the dose setting member of the drug delivery device.

[0034] The rotation sensor may include a light source that emits light during dose delivery and a light sensor for detecting light reflected off a surface configuration of the sensing element or transmitted by a particular area of ​​the sensing element.

[0035] The wireless communication circuitry of the accessory may be configured to wirelessly transmit data relating to the dose delivered by the drug delivery device to another device, such as a mobile phone, particularly a smartphone, or a computer. [Brief description of the drawings]

[0036] [Figure 1] FIG. 1 illustrates an embodiment of a drug delivery device including wireless data communication circuitry. [Diagram 2] FIG. 2 illustrates an embodiment of electronics for the drug delivery device shown in FIG. 1 including a printed circuit board having wireless data communication circuitry. [Diagram 3] 1 is a schematic diagram of an embodiment of a wireless data communication circuit for a drug delivery device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0037] In the following, embodiments of the present disclosure will be described with reference to an injection device, in particular an injection device in the form of a pen, however, the present disclosure is not limited to such use and may be equally well applied in other types of drug delivery devices, in particular having other shapes than pens.

[0038] FIG. 1 shows a drug delivery device 12 in the form of an insulin injection pen. The device 12 includes an elongated body 120 having a pen shape for holding a drug cartridge and a dose selection and delivery mechanism. At the lower end of the body 120, a syringe 122 is provided for expelling a drug dose and injecting this dose into the patient's body. At its other, upper end, the body 120 includes a dial knob 124 for selecting a drug dose and an injection knob 128 for delivering the selected dose. In alternative devices, the dial knob may be an injection knob. A user of the device 12 selects a dose by rotating the dial knob 124 around the longitudinal axis of the body 120. The selected dose is shown on a display 126 integrated in the body 120. After dose selection, the user can press the injection knob 128 in the direction of the longitudinal axis to expel the selected dose through the syringe 122 into the patient's body. The dose selection and delivery mechanism contained within the body may include electronics (not visible in FIG. 1) for detecting, storing and transmitting the dose selected and delivered.

[0039] A wireless data communication circuit is integrated into the device 12 or attached to the device 12 as an accessory that can be clipped, for example, to the dial knob 124. The wireless data communication circuit may be part of an electronic device that includes wireless communication means for establishing a communication link 130 with an external device, such as a smartphone 20 or a laptop computer 22, which is paired with the wireless communication means. The term "pairing" may mean that the wireless data communication circuit and the external device 20, 22 share some secret data, such as an encryption key, for establishing and / or protecting the data exchange.

[0040] The wireless data communication circuitry is configured to establish long-range wireless communication with the external device 20, 22 via radio frequency communication, such as a Bluetooth® communication link 130, over a distance of at least a few centimeters, particularly at least one meter, and more particularly several meters. The maximum distance provided for communication may depend on the power requirements of the accessory 10. For example, when the accessory 10 is powered by a one-time use battery that lasts for several months or at least a year or more, the maximum distance is configured by reducing the power requirements of the wireless data communication circuitry to meet the desired battery life. The communication link 130 is secured by a pairing process that is first performed to enable communication.

[0041] 2 shows the electronic device 10 including the wireless data communication circuitry and its integration with the dial knob 124 of the drug delivery device 12. The electronic device 10 includes two printed circuit boards 100, 102 and a button cell battery 104. The battery 104 is "sandwiched" between the positive terminal 112 and the negative terminal 114 of the battery connector formed by the printed circuit boards 100 and 102.

[0042] The printed circuit boards 100, 102 may be non-flexible or flexible circuit boards. The circuit boards 100, 102 are shaped so that they can be placed within a dial knob 128. The circuit boards 100 and 102 may be electrically connected via flexible conductors, including several wires, to exchange data and to supply current from a battery 104 to the circuit boards 100 and 102.

[0043] The battery 104 may be a CR1225 type lithium button cell battery having a terminal voltage of about 3 volts and a capacity of several milliamp hours, in particular about 38 milliamp hours. The battery 104 is selected to last for at least several months, in particular more than a year, under a normal usage scenario of the drug delivery device 12.

[0044] Each circuit board 100, 102 includes electronic devices 106, 108, 110, which may be active and passive electronic devices such as integrated circuits, systems on chips (SoC), capacitors, resistors, etc. The electronic devices 106, 108, 110 may perform measurement of the doses selected and delivered by the drug delivery device 12, and may further implement storage of the measured doses and wireless data communication circuitry for wireless data exchange with the external devices 20 and 22.

[0045] The wireless data communication circuitry may include a wireless communication processor 108 and an arrangement of several capacitors 110 on the circuit board 100. The wireless communication processor 108 may include a Bluetooth® communication circuitry 108, such as a Bluetooth® SoC CYBL 10X6X from Cypress Semiconductor Corporation (San Jose, CA, US), a CC2640R2F wireless microcontroller for Bluetooth® Low Energy applications from Texas Instruments Incorporated (Dallas, TX, US), or an nRF52832 SoC from Nordic Semiconductor (ASA, Trondheim, Norway).

[0046] Each capacitor of the arrangement of multiple capacitors 110 is connected in parallel, typically permanently, to a positive terminal 112 and a negative terminal 114 of the battery connector. The capacitors 110 may be of the same type, e.g., only ceramic, film, polymer, mica, tantalum, or electrolytic capacitors, or may be of different types, e.g., both ceramic and electrolytic capacitors.

[0047] Experiments have shown that battery life can be improved, particularly by the arrangement of "back-up" capacitors permanently connected in parallel to the positive terminal 112 and the negative terminal 114 of the battery connector. For example, for a CR1225 type button cell battery, an arrangement of two or three ceramic capacitors, each having a capacity of 47 microfarads (μF), and two further capacitors, e.g. electrolytic capacitors or larger ceramic capacitors, each having a capacity of 220 μF, has proven advantageous for extending the battery life of the battery.

[0048] 3 shows a schematic diagram of a wireless data communication circuit including a Bluetooth® SoC 108 as a wireless communication processor and an arrangement of five “backup” capacitors 110 connected in parallel to the positive and negative terminals 112, 114 of a connector for a battery 104. The capacitors 110 may include two electrolytic capacitors 110′ and 110″, which may have the same capacitance, for example, in particular 220 μF, and three ceramic capacitors 110′″, 110″″, 110′″″, which may have the same capacitance, for example, in particular 47 μF. All the capacitors 110 are connected in parallel, in particular permanently, to the positive and negative terminals 112 and 114 as well as to the power pins of the SoC 108, so that a sudden rise in current demand from the battery 104 by the SoC 108, caused for example by a data exchange operation via a Bluetooth® antenna 111 connected to the antenna connector 109, is at least partially backed up with the electrical energy stored in the capacitors 110.

[0049] The terms "drug" or "medicament" are used interchangeably herein to describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or their pharma- ceutically acceptable salts or solvates, 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 medicines are used to treat, cure, prevent, or diagnose diseases or otherwise improve physical or mental well-being. Drugs or medicines can be used for a limited duration or periodically for chronic disorders.

[0050] As described below, drugs or agents may include at least one API or combinations thereof in various types of formulations for the treatment of one or more diseases. Examples of APIs may include small molecules with molecular weights of 500 Da or less, polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes), carbohydrates and polysaccharides, as well as nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0051] The drug or agent can be contained in a primary package or "drug container" adapted for use in a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir, or other rigid or flexible vessel configured to provide a chamber suitable for storage (e.g., short-term or long-term storage) of one or more drugs. For example, in some cases, the chamber can 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 can be designed to store the drug for about one month to about two years. Storage can 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 can 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 can be configured to allow mixing between two or more components prior to and / or during administration to the human or animal body. For example, the two chambers can be configured to be in fluid communication with each other (e.g., via a conduit between the two chambers) and to allow mixing of the two components by a user, if desired, prior to administration. Alternatively or additionally, the two chambers can be configured to allow mixing upon administration of the components to the human or animal body.

[0052] The drugs or agents contained in the drug delivery devices described herein can be used for the treatment and / or prevention of many different types of medical disorders. Examples of disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, thromboembolic disorders, such as deep vein thromboembolism or pulmonary thromboembolism. Further examples of disorders are acute coronary syndromes (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those found in handbooks such as Rote Liste 2014 (e.g., but not limited to, main groups 12 (antidiabetic agents) or 86 (oncology agents)) and the Merck Index, 15th edition.

[0053] Examples of APIs for the treatment and / or prevention of type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes 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, 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 replaced amino acid residue can be either a codable amino acid residue or another naturally occurring residue or a purely synthetic amino acid residue. Insulin analogs are also referred to as "insulin receptor ligands". In particular, the term "derivative" refers to a polypeptide having a molecular structure formally derivable from the structure of a naturally occurring peptide, e.g., the molecular 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 are deleted and / or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable ones, are added to the naturally occurring peptide.

[0054] 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 may be replaced by Asp, Lys, Leu, Val or Ala and in which the Lys in position B29 may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0055] 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. ; 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-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0056] Examples of GLP-1, GLP-1 analogs and GLP-1 receptor agonists include, 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, CM-3, GLP-1 Erigen, ORMD-0901, 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, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, exenatide-XTEN and glucagon-Xten.

[0057] An example of an oligonucleotide is, for example, mipomersen sodium (Kynamro®), a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia.

[0058] Examples of DPP4 inhibitors are vidagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

[0059] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0060] Examples of polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or very low molecular weight heparin or derivatives thereof, or sulfated polysaccharides, such as the above-mentioned polysaccharides in polysulfated form, and / or their pharma- ceutically acceptable salts. An example of a pharma-ceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F20 (Synvisc®), sodium hyaluronate.

[0061] 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 is capable of fixing 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., with a mutation or deletion of the 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 (CODV) with crossover binding region orientation.

[0062] 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 can 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.

[0063] 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 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.

[0064] Exemplary antibodies are anti-PCSK-9 mAb (eg, alirocumab), anti-IL-6 mAb (eg, sarilumab), and anti-IL-4 mAb (eg, dupilumab).

[0065] 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.

[0066] It will be understood by those skilled in the art that modifications (addition and / or removal) of various components of the APIs, formulas, apparatus, methods, systems, and embodiments described herein may be made without departing from the overall scope and spirit of the invention, and that the invention encompasses such modifications and all equivalents thereof.

Claims

1. A drug delivery device (12), comprising: A main body (120); a dose selection mechanism (124, 126, 128) for selecting the dose of drug to be delivered; a delivery mechanism for delivering a selected drug dose; At least one antenna (109, 111) for wireless communication; an actuator and a dose dial sleeve; wherein the electronics are disposed within the actuator, the actuator including at least one rotation sensor responsive to relative rotation between a sensing element fixed to the dose dial sleeve and the actuator during dose delivery; An electronic device (10) disposed within a body (120); Here, the electronic device (10) includes a printed circuit board (100) having wireless data communication circuitry (108, 110) disposed thereon; The wireless data communication circuitry (108, 110) of the electronic device (10) is coupled to at least one antenna (109, 111); The wireless data communication circuit (108, 110) of the electronic device (10) comprises: a wireless communication processor (108) for processing wireless data communications (130); a battery connector having positive and negative terminals (112, 114) connected to respective terminals (112, 114) of a wireless communication processor (108) for supplying electrical energy to the wireless communication processor (108) from a battery (104) connectable to the battery connector; an arrangement of at least two capacitors (110, 110'-110'''''), each capacitor (110, 110'-110''''') connected in parallel to a positive terminal (112) and a negative terminal (114) of a battery connector, and provided to back up a supply of electrical energy from a battery (104) connectable to the battery connector to a wireless communication processor (108); The drug delivery device comprising:

2. The drug delivery device of claim 1 , wherein each capacitor (110, 110'-110''''') is permanently connected in parallel to a positive terminal (112) and a negative terminal (114) of the battery connector.

3. 3. The drug delivery device of claim 1 or 2, wherein the wireless communication processor includes a Bluetooth® communication circuit (108) having an antenna (109, 111) configured for Bluetooth® communication, the Bluetooth® communication circuit including a Bluetooth® Low Energy radio circuit for wireless data communication.

4. The drug delivery device of claim 1, 2 or 3, wherein the arrangement of one or more capacitors (110) consists of four capacitors or five capacitors (110'-110''''').

5. 5. The drug delivery device of claim 4, wherein the four or five capacitor arrangement includes two capacitors (110', 110'') having a capacitance of 220 microfarads, and two or three capacitors (110'''-110''''') having a capacitance of 47 microfarads.

6. The drug delivery device of any one of claims 1 to 5, wherein the arrangement of one or more capacitors (110) comprises one or more of a ceramic capacitor, a film capacitor, a polymer capacitor, a mica capacitor, an electrolytic capacitor, a tantalum capacitor.

7. A drug delivery device according to any one of claims 1 to 6, arranged on a printed circuit board (100) configured to be arranged or attached to a drug delivery device (12), in particular a drug injection pen or an accessory to be attached to the drug delivery device.

8. The drug delivery device of claim 1, wherein the electronics includes a battery (104) connected to battery connectors (112, 114).

9. The drug delivery device of claim 1 , wherein the wireless communication circuitry is configured to transmit data related to a dose of the drug delivered by the drug delivery device.

10. 10. The drug delivery device of claim 1 comprising a cartridge of pharmaceutical agent.

11. 1. An accessory for attachment to a drug delivery device, comprising: a housing configured for attachment to a drug delivery device; At least one antenna (109, 111) for wireless communication disposed within the housing; at least one rotation sensor responsive to rotation of a sensing element of the drug delivery device relative to a housing of the accessory during dose delivery; An electronic device (10) disposed within the housing; Here, the electronic device (10) includes a printed circuit board (100) having wireless data communication circuitry (108, 110) disposed thereon; The wireless data communication circuitry (108, 110) of the electronic device (10) is coupled to at least one antenna (109, 111); The wireless data communication circuit (108, 110) of the electronic device (10) comprises: a wireless communication processor (108) for processing wireless data communications (130); a battery connector having positive and negative terminals (112, 114) connected to respective terminals (112, 114) of a wireless communication processor (108) for supplying electrical energy to the wireless communication processor (108) from a battery (104) connectable to the battery connector; an arrangement of at least two capacitors (110, 110'-110'''''), each capacitor (110, 110'-110''''') connected in parallel to a positive terminal (112) and a negative terminal (114) of a battery connector, and provided to back up a supply of electrical energy from a battery (104) connectable to the battery connector to a wireless communication processor (108); The accessory.

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