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WO2025233480A1 - Système électronique - Google Patents

Système électronique

Info

Publication number
WO2025233480A1
WO2025233480A1 PCT/EP2025/062670 EP2025062670W WO2025233480A1 WO 2025233480 A1 WO2025233480 A1 WO 2025233480A1 EP 2025062670 W EP2025062670 W EP 2025062670W WO 2025233480 A1 WO2025233480 A1 WO 2025233480A1
Authority
WO
WIPO (PCT)
Prior art keywords
dose
drug delivery
delivery device
electronic system
acoustic signals
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/EP2025/062670
Other languages
English (en)
Inventor
Michael Jugl
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi SA
Original Assignee
Sanofi SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanofi SA filed Critical Sanofi SA
Publication of WO2025233480A1 publication Critical patent/WO2025233480A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31565—Administration mechanisms, i.e. constructional features, modes of administering a dose
    • A61M5/31566—Means improving security or handling thereof
    • A61M5/31568—Means keeping track of the total dose administered, e.g. since the cartridge was inserted
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3375—Acoustical, e.g. ultrasonic, measuring means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/35—Communication
    • A61M2205/3546—Range
    • A61M2205/3561—Range local, e.g. within room or hospital
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/50—General characteristics of the apparatus with microprocessors or computers
    • A61M2205/52—General characteristics of the apparatus with microprocessors or computers with memories providing a history of measured variating parameters of apparatus or patient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/58—Means for facilitating use, e.g. by people with impaired vision
    • A61M2205/581—Means for facilitating use, e.g. by people with impaired vision by audible feedback

Definitions

  • drug delivery devices are known from the state of the art, which can measure, store and transmit information about the set or dispensed size of a drug dose.
  • the devices known from the state of the art either do not always provide sufficiently accurate measurements or prove to be too expensive and complex.
  • One aspect of the present disclosure relates to an electronic system for a drug delivery device.
  • the electronic system comprises a monitoring unit.
  • the monitoring unit may be configured to detect distinctive acoustic signals generated by the electronic system and/or generated by the drug delivery device during operation of the electronic system and/or during operation of the drug delivery device by a user.
  • the distinctive acoustic signals are indicative of a change in the set and/or dispensed size of a drug dose.
  • the user may be a patient or a medical assistant treating the patient.
  • the user may be a manufacturer who manufactures and/or configures the electronic system and/or drug delivery device for commercial purposes.
  • the electronic system is configured to assign the detected distinctive acoustic signals to different operational events of the electronic system and/or the drug delivery device which are performed by the user on the electronic system and/or the drug delivery device.
  • the different operational events comprise events during which the size of a set drug dose or the size of a dispensed drug dose is changed.
  • the size of a set and/or dispensed drug dose may be characterized by the number of so-called International Unit (IU), wherein one IU is the biological equivalent of about 45.5 micrograms of pure crystalline insulin (1/22 mg).
  • the size of a set and/or dispensed drug dose may be between 1 and 25 IU.
  • the monitoring unit comprises one or more microphones.
  • the microphones may be configured to convert distinctive acoustic signals into electrical signals.
  • the monitoring unit comprises a processor unit operatively coupled to the microphone or to a plurality of microphones.
  • the processor unit may be configured to assign the detected distinctive acoustic signals to the different operational events.
  • the electronic system comprises an output.
  • the output may be a wireless communications interface for communicating with another device via a wireless network such as Wi-Fi or Bluetooth®, or an interface for a wired communications link, such as a socket for receiving a Universal Series Bus (USB), mini-USB or micro-USB connector.
  • the other device may be a smart device such as a smart phone or smart watch.
  • the output is configured to forward a dose-relevant information to the user or an external device in response to the occurrence of an operational event.
  • the dose-relevant information may be indicative of a dispensed or set size of a drug dose.
  • the output may be connected to the processor unit.
  • the different operational events comprise a dose setting operation comprising a relative movement between two parts of the electronic system and/or the drug delivery device for setting a dose to be dispensed. Additionally or alternatively, the different operational events may comprise a dose correction operation comprising a relative movement between two parts of the electronic system and/or the drug delivery device for correcting a previously set dose. Additionally or alternatively, the different operational events may comprise a dose dispensing operation comprising a relative movement between two parts of the electronic system and/or the drug delivery device for dispensing a set dose. In an embodiment each of the operational events comprises an event signature associated with the corresponding operational event.
  • the electronic system may be configured such that when one of the distinctive acoustic signals corresponds to the event signature, the acoustic signal is associated with that operational event.
  • the electronic system may be configured such that when one of the distinctive acoustic signals corresponds to the event signature, the acoustic signal is associated with exclusively that one operational event.
  • the event signature comprises a characteristic sound volume.
  • One of the distinctive acoustic signals may correspond to the event signature of one of the operational events if the distinctive acoustic signal is characterized by a predefined sound volume.
  • the event signature comprises a characteristic frequency spectrum.
  • One of the distinctive acoustic signals may correspond to the event signature of one of the operational events if the acoustic signal is characterized by a predefined frequency spectrum.
  • the electronic system is configured for enabling a dose-relevant information determination for the drug delivery device based on the detected distinctive acoustic signals and the different operational events to which the distinctive acoustic signals have been assigned.
  • the dose-relevant information determination may include the determination of the size of a set drug dose before a dispensing process is initiated, the size of a drug dose of the currently dispensed dose during a dispensing process, and/or the size of a drug dose of a dispensed dose after a dispensing process has been completed.
  • the electronic system and/or the drug delivery device comprises a generating arrangement for generating the distinctive acoustic signals.
  • the invention may relate to an assembly comprising the electronic system and the drug delivery device.
  • the generating arrangement may comprise a slipping clutch.
  • the slipping clutch may be a two-way slipping clutch.
  • the generating arrangement may comprise components of the drug delivery device that perform a rotational and/or translational movement relative to each other in the course of a setting, correcting or dispensing operation.
  • the generating arrangement comprises a dose setting feedback generator and a dose correction feedback generator.
  • the dose setting feedback generator may be configured to generate an acoustic dose setting signal indicative of a dose setting operation.
  • the dose correction feedback generator may be configured to generate an acoustic dose correction signal indicative of a dose correction operation.
  • the acoustic dose setting signal may be different from the acoustic dose correction signal.
  • the electronic system is configured to distinguish the acoustic dose setting signal from the acoustic dose correction signal based on the distinguishable event signatures.
  • the electronic system is configured to assign one or more of the acoustic dose setting signals exclusively to the associated operational event of the dose setting operation, optionally based on the distinguishable event signatures.
  • the electronic system is configured to assign one or more of the acoustic dose correction signals exclusively to the associated operational event of the dose correction operation, optionally based on the distinguishable event signatures.
  • the generating arrangement comprises a dose dispensing feedback generator.
  • the dose dispensing feedback generator may be configured to generate an acoustic dose dispensing signal indicative of a dose dispensing operation.
  • the acoustic dose dispensing signal is different from the acoustic dose setting signal and the acoustic dose correction signal.
  • the electronic system is configured to distinguish the acoustic dose dispensing signal from the acoustic dose setting signal and the acoustic dose correction signal, optionally based on the distinguishable event signatures.
  • the electronic system is configured to assign one or more of the acoustic dose dispensing signals exclusively to the associated operational event of the dose dispensing operation, optionally based on the distinguishable event signatures.
  • the dose setting feedback generator, the dose correction feedback generator and/or the dose dispensing feedback generator may comprise clickers that produce clicking sounds in response to a change in the size of a set or dispensed drug dose.
  • the dose setting feedback generator comprises a dose setting clicker.
  • the dose correction feedback generator comprises a dose correction clicker.
  • the dose dispensing feedback generator comprises a dose dispensing clicker.
  • the drug delivery device contains the dose setting feedback generator and the dose correction feedback generator but does not contain the dose dispensing feedback generator.
  • the drug delivery device contains the dose setting clicker and the dose correction clicker and does not contain the dose dispensing clicker.
  • the dose-relevant information determination comprises counting the number of distinctive acoustic signals assigned to one of, more of, or all of the different operational events to obtain an operational event number of the respective operational event.
  • the dose-relevant information determination comprises forming a difference between operational event numbers of different operational events.
  • the electronic system is configured to count the number of the detected acoustic dose setting signals, the acoustic dose correction signals and/or the acoustic dose dispensing signals during the operation of the electronic system and/or drug delivery device by the user and to perform the dose-relevant information determination based on the counted number of the acoustic dose setting signals, the acoustic dose correction signals and/or the acoustic dose dispensing signals.
  • the detection of one distinctive acoustic signal corresponds to the change in the size of a set or dispensed drug dose by a predefined increment.
  • One predefined increment may be characterized by an III.
  • the detection of one distinctive acoustic signal corresponding to the event signature of the dose setting operation, or the detection of one acoustic dose setting signal corresponds to the increase in the size of a set drug dose by a setting increment.
  • the detection of one distinctive acoustic signal corresponding to the event signature of the dose correction operation, or the detection of one acoustic dose correction signal corresponds to the decrease in the size of a set drug dose by a correction increment.
  • the setting increment has the same size as the correction increment.
  • the setting increment has a different size than the correction increment.
  • the detection of one distinctive acoustic signal corresponding to the event signature of the dose dispensing operation, or the detection of one acoustic dose dispensing signal corresponds to the dispensing of a drug dose by a dispensing increment.
  • the setting increment has the same size as the correction increment and the dispensing increment.
  • the setting increment has the same size as the correction increment, wherein the dispensing increment has a different size than the setting increment and the correction increment.
  • correction or dispensing increment may be characterized by an IU.
  • the distinctive acoustic signals corresponding to an event signature of an operational event can differ from each other.
  • the distinctive acoustic signals corresponding to an event signature of an operational event may have varying sound volumes. Additionally or alternatively, the distinctive acoustic signals corresponding to an event signature of an operational event may have varying frequency spectra.
  • the add-on device comprises the electronic system described above.
  • the add-on device may be configured to be attachable to a proximal end of the drug delivery device.
  • a drug delivery device comprising the electronic system described above. In both cases, the drug delivery device may be configured to retain a drug container with a drug or may comprise a drug container with a drug.
  • the drug delivery device may be a fully functional drug delivery device.
  • the drug may be a medicament.
  • the drug delivery device may not be an auto-injector, meaning that the user must apply force to push the drug out of the container.
  • the drug delivery device may be a dispensing device in which the size of a drug dose to be dispensed can be set manually by the user.
  • the drug delivery device may be a dial extension pen, wherein the drug delivery device lengthens along its longitudinal axis as the dose is increasingly set and shortens along the longitudinal axis as the dose is dispensed.
  • the drug delivery device may be a hand-held pen-type drug delivery device with a manual dose setting function.
  • the drug delivery device may be an autoinjector.
  • the energy for the drug delivery operation may be prestored in an energy storage member. That is to say, the user does not have to provide the energy for the drug delivery operation, e.g. when preparing the drug delivery device for use. Rather, this energy may be preloaded into the drug delivery device by the manufacturer.
  • a drive spring e.g. a spiral spring or flat spiral spring, may be pre-stressed or prebiased to provide the energy for the drug delivery operation.
  • the invention also relates to the method for monitoring the drug delivery device.
  • the method may be a computer-implemented method.
  • the method may comprise the provision of the electronic system described above.
  • the method may comprise detecting distinctive acoustic signals generated during the operation of the drug delivery device by the user of the drug delivery device, e.g. using the electronic system, the add-on device or the drug delivery device as described above.
  • the method may comprise assigning the detected distinctive acoustic signals to different operational events of the drug delivery device which are performed by the user on the drug delivery device.
  • the method may also comprise determining a doserelevant information about the operation of the drug delivery device based on the detected distinctive acoustic signals and the different operational events to which the distinctive acoustic signals have been assigned.
  • a computer program product e.g. a computer program or a computer readable storage medium, comprising machine readable instruction which when carried out by a processor cause the electronic system described above to perform the method for monitoring the drug delivery device.
  • the computer readable storage medium may be hardware memory component.
  • the processor may be different from the processor unit. Contrary to the processor unit, the processor may not be part of the electronic system. Alternatively the processor may be the processor unit.
  • the invention also relates to a method for adjusting the electronic system to a drug delivery device.
  • the method may be a computer-implemented method.
  • the method may comprise the provision of the add-on device or drug delivery device described above.
  • the method may comprise executing an operational event with the drug delivery device.
  • the method may comprise analyzing a distinctive acoustic signal during the operational event and forming an event signature corresponding to the operational event.
  • the method may also comprise storing the event signature in the electronic system.
  • a computer program product e.g. a computer program or a computer readable storage medium, comprising machine readable instruction which when carried out by a processor cause an electronic unit, e.g. the electronic described above, to prompt the user to perform the method for adjusting the electronic system to a drug delivery described above.
  • the computer readable storage medium may be hardware memory component.
  • the electronic unit may be comprised by a smart device, such as a smartphone or smartwatch.
  • Figure 1 a schematic sectional view of a part of a dose setting clicker for generating distinctive acoustic signals during the operation of a drug delivery device according to a first embodiment.
  • Figure 2 a schematic sectional view of a part of a dose correction clicker for generating distinctive acoustic signals during the operation of the drug delivery device according to the first embodiment.
  • Figure 3 a schematic sectional view of a part of a dose dispensing clicker for generating distinctive acoustic signals during the operation of the drug delivery device according to the first embodiment.
  • Figure 4 a schematic sectional view of a part of a dose setting clicker for generating distinctive acoustic signals during the operation of a drug delivery device according to a second embodiment.
  • Figure 5 a schematic sectional view of a part of a dose correction clicker for generating distinctive acoustic signals during the operation of the drug delivery device according to the second embodiment.
  • Figure 6 a schematic sectional view of a part of a dose dispensing clicker for generating distinctive acoustic signals during the operation of the drug delivery device according to the second embodiment.
  • Figure 7 an exploded view of an injection device for use with an electronic system according to an embodiment of the invention.
  • Figure 8 an isometric cutaway view of the injection device according to Figure 7 with an add-on device.
  • distal is used herein to specify directions, ends or surfaces which are arranged or are to be arranged to face or point towards a dispensing end of the drug delivery device and/or point away from, are to be arranged to face away from or face away from the proximal end.
  • 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 drug delivery device or components thereof.
  • the distal end may be the end closest to the dispensing end 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 is arranged or a needle or needle unit is or is to be mounted to the device, for example. “Axial” may be used synonymously with “longitudinal”.
  • the present description describes an electronic system.
  • the electronic system can be an addon device suitable for attachment to a drug delivery device.
  • the electronic system can be comprised by an add-on device. It is also possible to arrange the electronic system as an integral part of a drug delivery device, e.g. within the housing of a drug delivery device.
  • the present invention is described below with reference to drug delivery devices such as insulin injection devices. The present invention is however not limited to such application and may equally well be deployed with injection devices that eject other medicaments.
  • the drug delivery device is a pre-filled, disposable injection pen that comprises a housing and contains an insulin container, to which a needle can be affixed.
  • the needle is protected by an inner needle cap and either an outer needle cap or an injection device cap.
  • An insulin dose to be ejected from drug delivery device can be programmed, or 'dialed in' by turning a dosage knob, and a currently programmed dose may then be displayed via a dosage window, for instance in multiples of units.
  • the dosage may be displayed in so-called International Units (IU), wherein one IU is the biological equivalent of about 45.5 micrograms of pure crystalline insulin (1/22 mg).
  • IU International Units
  • Other units may be employed in injection devices for delivering analogue insulin or other medicaments.
  • the drug delivery device is configured to inject or infuse a medicament into a patient.
  • delivery could be sub-cutaneous, intra-muscular, or intravenous. Delivery could be needleless.
  • the drug delivery device could be operated by a patient or care-giver, such as a nurse or physician, and may be one of various types of safety syringe, pen-injector, or autoinjector.
  • the drug delivery device can be operated by a technician who assembles the drug delivery device during the manufacturing process and/or configures it for later use.
  • the drug delivery device can include a cartridge-based system that requires piercing a sealed ampule before use. Volumes of medicament delivered with these various devices may range from about 0.5 ml to about 2 ml.
  • the drug delivery device may be a large volume device ("LVD") or patch pump, configured to adhere to a patient's skin for a period of time (e.g., about 5, 15, 30, 60, or 120 minutes) to deliver a "large" volume of medicament (typically about 2 ml to about 10 ml).
  • the drug delivery device may also be customized in order to operate within required specifications.
  • the drug delivery device may be customized to inject a medicament within a certain time period (e.g., about 3 to about 20 seconds for auto-injectors, and about 10 minutes to about 60 minutes for an LVD).
  • Other specifications can include a low or minimal level of discomfort, or to certain conditions related to human factors, shelf-life, expiry, biocompatibility, environmental considerations, etc. Such variations can arise due to various factors, such as, for example, a drug ranging in viscosity from about 3 cP to about 50 cP. Consequently, the drug delivery device may include a hollow needle ranging from about 25 to about 31 Gauge in size. Common sizes are 27 and 29 Gauge.
  • the drug delivery device can also include one or more automated functions. For example, one or more of needle insertion, medicament injection, and needle retraction can be automated. Energy for one or more automation steps can be provided by one or more energy sources. Energy sources can include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, mechanical energy sources can include springs, levers, elastomers, or other mechanical mechanisms to store or release energy. One or more energy sources can be combined into a single device. Devices can further include gears, valves, or other mechanisms to convert energy into movement of one or more components of a device.
  • the one or more automated functions of such a drug delivery device may each be activated via an activation mechanism.
  • an activation mechanism can include one or more of a button, a lever, a needle sleeve, or other activation component.
  • Activation of an automated function may be a one-step or multi-step process. That is, a user may need to activate one or more activation components in order to cause the automated function. For example, in a one-step process, a user may depress a needle sleeve against their body in order to allow injection of a medicament to be provided.
  • the drug delivery device may require a multi-step activation of an automated function. For example, a user may be required to depress a button and retract a needle shield in order to cause injection.
  • activation of one automated function may activate one or more subsequent automated functions, thereby forming an activation sequence.
  • activation of a first automated function may activate at least two of needle insertion, medicament injection, and needle retraction.
  • the drug delivery device may also require a specific sequence of steps to cause the one or more automated functions to occur.
  • the drug delivery device may operate with a sequence of independent steps.
  • the drug delivery device can include one or more functions of a safety syringe, pen-injector, or auto-injector.
  • the drug delivery device includes a dose setting mechanism (as typically found in a pen-injector).
  • the drug delivery device provides a usersettable size of a drug dose to be dispensed.
  • the dose setting mechanism has a correction mechanism so that an already set dose can be changed.
  • the dose setting mechanism comprises a generating arrangement which is configured to generate at least one distinctive acoustic signal in response to a dose setting or dose correction movement of the dose setting mechanism.
  • the generating arrangement comprises a dose setting feedback generator such as a dose setting clicker and dose correction feedback generator such as dose correction clicker.
  • the dose setting clicker is configured to generate an acoustic dose setting signal indicative of the dose setting operation.
  • the dose correction clicker is configured to generate an acoustic dose correction signal indicative of the dose correction operation.
  • the acoustic dose setting signal may be different from the acoustic dose correction signal.
  • the drug delivery device may in principle be designed according to the drug delivery devices disclosed in WO 2006/045526 A1 or WO 2013/116951 A1.
  • the generating arrangement i.e. the arrangement which generates different noises or acoustic signals when a dose is set than when the set dose is corrected, may be designed, for example, according to the second embodiment disclosed in WO 2013/116951 A1.
  • the contacting surfaces or the contacting features of the generating arrangement can be designed to correspond to the partial areas of the clickers as shown in figures 1 and 2.
  • a distinctive acoustic signal can be generated depending on the direction of movement of click features 40 relative to counter features 41 and/or depending on the shape and/or material of click features 40 and counter features 41.
  • the generating arrangement can comprise all components of the drug delivery device that perform a rotational and/or translational relative movement to each other during a does setting, dose correction or dose dispensing process and thereby generate distinctive acoustic signals.
  • the generating arrangement can comprise a two-way slipping clutch that connects a dose sleeve to a dose setting knob that can be rotated relative to the housing of the drug delivery device.
  • the generating arrangement may also comprise a dose dispensing feedback generator such as a dose dispensing clicker.
  • the dose dispensing clicker may be configured to generate an acoustic dose dispensing signal indicative of the dose dispensing operation.
  • the acoustic dose dispensing signal is different from the acoustic dose setting signal and the acoustic dose correction signal.
  • the dose dispensing clicker can be arranged between the inner surface of the housing of the drug delivery device and a drive sleeve, which is moved rotationally and/or translationally relative to the housing during a dispensing process.
  • the drug delivery device may contain the dose setting clicker and the dose correction clicker but does not necessarily have to contain the dose dispensing clicker.
  • the dose setting feedback generator, the dose correction feedback generator and the dose dispensing feedback generator do not necessarily have to be clickers.
  • the dose setting feedback generator, the dose correction feedback generator and/or the dose dispensing feedback generator can be implemented in the form of any conceivable mechanism that generates different acoustic signals.
  • Figure 1 shows a partial area of the dose setting clicker
  • Figure 2 shows a partial area of the dose correction clicker
  • Figure 3 shows a partial area of the dose dispensing clicker according to an embodiment of the drug delivery device.
  • the click features 40 and/or the counter features 41 are designed by shape and/or material in such a way that the drug delivery device generates different and thus distinguishable sounds or acoustic signals during a setting, correction and dispensing operation, which can be assigned to the respective operational events.
  • the acoustic signals that are assigned to a specific operational event or a specific event signature can be characterized by a predefined sound volume. Alternatively or additionally, they can be characterized by a predefined frequency spectrum.
  • the acoustic dose setting signal can be characterized by a sound volume of at least 60 dB, e.g. such as 60, 61, 62, 63, 64, 64, 65, 66, 67, 68, 69 or 70 dB.
  • the acoustic dose setting signal can be characterized by a sound volume of at most 70 dB, e.g. such as 60, 61, 62, 63, 64, 64, 65, 66, 67, 68, 69 or 70 dB.
  • the acoustic dose correction signal can be characterized by a sound volume of at least 40 dB, e.g.
  • the acoustic dose correction signal can be characterized by a sound volume of at most 50 dB, e.g. such as 40, 41, 42, 43, 44, 44, 45, 44, 47, 48, 49 or 50 dB.
  • the acoustic dose dispensing signal can be characterized by a sound volume of at least 20 dB, e.g. such as 20, 21, 22, 23, 22, 22, 25, 22, 27, 28, 29 or 30 dB.
  • the acoustic dose dispensing signal can be characterized by a sound volume of at most 30 dB, e.g. such as 20, 21, 22, 23, 22, 22, 25, 22, 27, 28, 29 or 30 dB.
  • the dose setting clicker (see Figure 1), the dose correction clicker (see Figure 2) and the dose dispensing clicker (see Figure 3) can each have several individual click features 40 that mesh with a corresponding counter feature 41 during the setting, correction or dispensing process, so that different distinctive acoustic signals are generated for each of the three clickers.
  • the distances between the individual click features can be dimensioned in such a way that the traversing of a click feature 40 by the counter feature 41 corresponds to the change in the set or dispensed dose size by one III and simultaneously generates a distinctive acoustic signal.
  • the distances can be dimensioned so that the traversing of the click feature 40 by the counter feature 41 corresponds to the change in the set or dispensed dose size by an increment of less than one I U, such as 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 or 0.9 IU.
  • the distances can be dimensioned such that the traversing of the click feature 40 by the counter feature 41 corresponds to a change in the set or dispensed dose size by an increment of more than one IU, such as 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 IU.
  • Figure 4 shows a partial area of the dose setting clicker
  • Figure 5 shows a partial area of the dose correction clicker
  • Figure 6 shows a partial area of the dose dispensing clicker according to another embodiment of the drug delivery device.
  • the clickers can also be designed in such a way that the distinctive acoustic signals generated in a clicker are different and optionally represent different large changes in the size of the set or dispensed dose.
  • the electronic system may be configured to be adaptable to different drug delivery devices that generate different types of acoustic signals for the individual operational events.
  • the add-on device may be attached to the drug delivery device according to the add- on device disclosed in document WO 2016/198516 A1.
  • the add-on device is attachable to a proximal end of the drug delivery device, such as to fit the drug delivery device like a cap.
  • the add-on device is configured such that it can be push-fitted over a dosage knob or dose dialing knob of the drug delivery device.
  • a first portion of the add-on device includes a cavity that receives the dosage knob, and includes a deformable inner surface such as to provide a tight fit over the dosage knob and/or has features that mate closely with external features of the dosage knob.
  • the add-on device can easily be installed on the drug delivery device, and can easily be removed through application of a removal force between the add-on device and the drug delivery device in an axial direction.
  • the add-on device is manipulated by the user in order to effect operation of the drug delivery device.
  • the electronic system is configured to distinguish the acoustic dose setting signal from the acoustic dose correction signal.
  • the electronic system is configured to assign one or more of the acoustic dose setting signals exclusively to the associated operational event of the dose setting operation and to assign one or more of the acoustic dose correction signals exclusively to the associated operational event of the dose correction operation.
  • the electronic system is configured to distinguish the acoustic dose dispensing signal from the acoustic dose setting and dose correction signal.
  • the electronic system is configured to count the number of the acoustic dose setting signals, the acoustic dose correction signals and/or the acoustic dose dispensing signals during the operation of the electronic system and/or drug delivery device by the user and to perform the dose-relevant information determination based on the counted number of the acoustic dose setting signals, the acoustic dose correction signals and/or the acoustic dose dispensing signals.
  • the electronic system comprises a monitoring unit.
  • the monitoring unit comprises at least one microphone.
  • the microphone can be an electret condenser microphone (ECM), a MEMS (microelectromechanical systems) microphone or a dynamic microphone.
  • ECM electret condenser microphone
  • MEMS microelectromechanical systems
  • the monitoring unit can detect click signals generated during the operation of the electronic system and/or the drug delivery device by a user of the electronic system and/or the drug delivery device.
  • the one or more microphones can be arranged outside the drug delivery device, e.g. in the add-on device, or inside the drug delivery device, e.g. in the housing of the drug delivery device.
  • the one or more microphones are positioned in such a way that they are close enough to the dose setting, correction and dispensing clicker to detect the acoustic dose setting, correction and dispensing signals.
  • the monitoring unit may comprise a plurality of microphones, for example, the monitoring unit may comprise a dose setting microphone in the area of the dose setting clicker, a dose correction microphone in the area of the dose correction clicker and a dose dispensing microphone in the area of the dose dispensing clicker.
  • the monitoring unit further comprises a processor unit operatively coupled to the microphone or to a plurality of microphones.
  • the processor unit is configured to assign the detected distinctive acoustic signals to different operational events comprising relative movement between two parts of the electronic system and/or the drug delivery device, such as a dose setting operation, a dose correction operation and a dose dispensing operation.
  • the electronic system comprises an output.
  • the output is configured to forward a dose-relevant information to the user or an external device in response to the occurrence of an operational event.
  • the dose-relevant information may be indicative of a dispensed or set size of a drug dose.
  • the output is connected to the processor unit.
  • the output is a wireless communications interface for communicating with another device via a wireless network or an interface for a wired communications link.
  • the device with which the output communicates can be a smart device such as a smart phone or smart watch. Alternatively or additionally, the output can also include a display that provides the user of the drug delivery device with dose-relevant information regarding the size of a set or dispensed dose.
  • the electronic system can have its own power supply, which supplies the monitoring unit and the output with energy.
  • the power supply can be activated by a switch on the electronic system or drug delivery device.
  • the power supply can be activated by a dose dial.
  • the activation of the power supply may be performed according to the add-on device disclosed in WO 2016/198516 A1.
  • the monitoring unit may comprise a memory unit for storing information captured by the processor unit.
  • the monitoring unit uses the microphone to detect every distinctive acoustic signal that can be assigned to one of the operational events, i.e. the dose setting operation, the dose correction operation or the dose dispensing operation.
  • the processor unit of the monitoring unit does not take into account any acoustic signals that are detected by the microphone and do not correspond to any of the event signatures of the operational events. This means that distinctive acoustic signals that are not caused by the dose setting, dose correction or dose dispensing clicker, such as ambient noise, are not taken into account when determining the dose-relevant information.
  • An event signature may comprise a characteristic sound volume and/or frequency spectrum.
  • a distinctive acoustic signal may correspond to the event signature of one of the operational events if the distinctive acoustic signal is characterized by a predefined sound volume and/or frequency spectrum.
  • the dose setting clicker As soon as the user performs a setting operation, the dose setting clicker generates acoustic dose setting signals.
  • the microphone detects the acoustic signals, converts each of the signals into a parameter that can be processed by the processor unit and forwards the converted signals sequentially to the processor unit.
  • the processable parameter includes, for example, the detected sound volume of the individual signals or the frequency spectrum.
  • the processor unit also has a unit for recording the number of signals received from the microphone, such as a sound counter, so that the processor unit is able to count the number of all acoustic signals detected by the microphone.
  • the processor unit checks and stores which and how many of the detected signals from the microphone correspond to one of the predefined event signatures and assigns the acoustic signals to the corresponding operational event.
  • the processor unit can multiply the number of the detected acoustic dose setting signals by the predefined size and calculate the set dose size and communicate it to the user via the output.
  • the predefined dose size assigned to an acoustic dose setting signal also known as the setting increment, is e.g. 1 III and the user sets a dose size to be dispensed of 5 IU
  • the user generates five acoustic dose setting signals using the dose setting clicker.
  • the output informs the user that a dose size of 5 IU has been set and that this dose size is ready to be dispensed.
  • the dose correction clicker If the user subsequently carries out a dose correction operation, the dose correction clicker generates acoustic dose correction signals.
  • the processor unit checks and stores which and how many of the acoustic signals recorded by the microphone correspond to one of the predefined event signatures and assigns the acoustic dose correction signals to the corresponding operational dose correction event. Since each of the acoustic dose correction signals is representative of a predefined dose size, the processor unit can multiply the number of acoustic signals assigned to the dose correction operation by the predefined dose size and calculate the dose size of the corrected dose, subtract the result from the sum of the previously set dose size already calculated and communicate the updated set dose size to the user via the output.
  • the predefined dose size assigned to an acoustic dose correction signal also known as the correction increment
  • the user corrects the previously set dose size to be dispensed by 2 I U
  • the user generates two acoustic dose correction signals using the dose correction clicker.
  • the output informs the user that a dose size of 3 IU has been set and is ready to be dispensed.
  • the electronic system can record any number of changes to the size of the set dose in this way and thus continuously update the dose-relevant information provided by the output to the user.
  • the dose dispensing clicker If the user subsequently performs a dose dispensing operation, the dose dispensing clicker generates acoustic dose dispensing signals. Again, the processor unit checks and stores which and how many of the detected signals by the microphone correspond to one of the predefined event signatures and assigns the acoustic dose dispensing signals to the corresponding dose dispensing operation. Since each of the acoustic dose dispensing signals is representative of a predefined size of a dispensed dose, the processor unit can multiply the number of acoustic dose dispensing signals by the predefined dose size and calculate the size of the dispensed dose and communicate the dispensed dose size to the user via the output.
  • the predefined dose size assigned to the dose dispensing signal is 1 IU and the user dispenses a set dose size of 3 IU
  • the user generates three acoustic dose dispensing signals using the dose dispensing clicker.
  • the output provides the user with the information that a dose size of 3 IU has been dispensed.
  • the output is also suitable for displaying the dispensed dose size step by step at the same time as the dispensing process takes place, i.e. in this example, first the value 1 IU, then the value 2 IU and finally the value 3 IU is communicated to the user.
  • the processor unit can calculate the difference between the dose size of the dispensed dose and the set dose. If these two sizes are not identical, a warning can be sent to the user using the output, informing the user that the set dose has not been fully dispensed.
  • the predefined dose sizes or increments assigned to the acoustic dose setting, correction and dispensing signals can be different from each other.
  • the clickers can be designed in such a way that a clicker generates different acoustic signals that are assigned to an event signature representing one of the operational events, i.e. the dose setting operation, the dose correction operation or the dose dispensing operation.
  • the acoustic signals generated by a clicker as shown in Figures 1-3 can have a different sound volume due to a changing distance from the microphone to the clicker during dose setting or dose dispensing.
  • the electronic system can be used in different drug delivery devices.
  • the event signatures can be set manually. This is done by carrying out one of the operational events after activating the electronic system.
  • the monitoring unit analyzes the resulting acoustic signals of the operational event, uses them to create an event signature and stores the event signature in the electronic system as belonging to the operational event performed. This process can be repeated for a correction process and/or a dispensing process. In order to increase the assignment accuracy, these training processes can also be carried out several times.
  • the instructions for adapting the electronic system to a drug delivery device can be provided to the user, for example, via software stored on a hardware component.
  • the hardware component can be provided by the electronic system or an external device such as a smart device or a computer readable storage medium.
  • the adapting of the electronic system to a drug delivery device can be performed by the user or a machine.
  • Figure 7 shows an example of a drug delivery device as described above, for which the electronic system may be used, wherein Figure 8 shows the drug delivery device of Figure 7 together with the above-described add-on device attached to the proximal end of the drug delivery device.
  • the drug delivery device of Figure 7 is an injection device 1 comprising the housing 10 and containing the insulin container 14, to which the needle 15 can be affixed.
  • the needle 15 is protected by the inner needle cap 16 and either the outer needle cap 17 or the injection device cap 18.
  • the insulin dose to be ejected from injection device 1 can be set by turning the dosage knob 12 and the currently set dose is then displayed via the dosage window 13, for instance in multiples of units.
  • the injection device 1 may be configured to administer e.g. human insulin or another medicament.
  • the dosage is displayed in International Units (IU). Other units may be employed for delivering analogue insulin or other medicaments.
  • IU International Units
  • Other units may be employed for delivering analogue insulin or other medicaments.
  • the dosage window 13 may be in the form of an aperture in the housing 10, which permits the user to view a limited portion of the number sleeve 50 that is configured to move when the dosage knob 12 is turned, to provide the visual indication of the currently set dose.
  • the shown number sleeve 50 or a not shown drive sleeve may directly or indirectly mechanically interact with a not shown piston rod which drives the piston into insulin container 14 to dispense a dose of medication through needle 15.
  • a not shown piston rod which drives the piston into insulin container 14 to dispense a dose of medication through needle 15.
  • injection button 11 When needle 15 is stuck into a skin portion of a patient, and then injection button 11 is pushed, the insulin dose displayed in display window 13 will be ejected from injection device 1. It may be necessary for the needle 15 of injection device 1 to remain for a certain time in the skin portion after the injection button 11 is pushed, so that a high percentage of the dialed dose is actually injected into the patient's body.
  • the dosage knob 12 may return to its initial position in an axial movement, that is to say without rotation, while the number sleeve 50 and the dosage knob may be rotated and move axially to return to its initial position, e.g. to display a dose of zero units.
  • the electronic system may alternatively be used with a drug delivery device which has a unitary dosage knob and injection button (only one dose knob) used both for dose setting (e.g. by being rotated by a user) and dose dispensing (e.g. by being pushed by a user).
  • a unitary dosage knob and injection button only one dose knob used both for dose setting (e.g. by being rotated by a user) and dose dispensing (e.g. by being pushed by a user).
  • dose setting e.g. by being rotated by a user
  • dose dispensing e.g. by being pushed by a user
  • Injection device 1 may be used for several injection processes until either the insulin container 14 is empty or the expiration date of the medicament in the injection device 1 (e.g. 28 days after the first use) is reached.
  • the distal end of the add-on device 2 comprising the electronic system is attached to the proximal end of the injection device 1.
  • the add-on device 2 is push-fitted over the dosage knob 12 of the injection device 1.
  • the add-on device 2 includes a cavity that receives the dosage knob 12 and the injection button 11 , and includes a deformable inner surface such as to provide the tight fit over the dosage knob and/or has features (e.g. snap features) that mate closely with external features of the dosage knob.
  • the add-on device 2 can easily be installed on the injection device 1 , and can easily be removed through application of a removal force between the add-on device 2 and the injection device 1 in an axial direction. When installed, the add-on device 2 is manipulated by the user in order to effect operation of the injection device 1.
  • the dosage knob 12 of figure 8 is rotated on a helical path with respect to the housing 10 when turned during dose setting or dose correction.
  • the dosage knob 12 is moved in a distal direction along the longitudinal axis of the injection device 1. It further might rotate during dose delivery.
  • the injection device 1 is configured so that turning the dosage knob 12 to dial a dose causes mechanical click sounds to provide acoustical feedback to the user.
  • the injection device 1 is configured such that turning the dosage knob 12 causes click sounds during the dose setting movement and during the dose correction movement, wherein the click sounds of the dose setting movement differ from the click sounds of the dose correction movement.
  • the mechanical click sounds provide the acoustic dose setting signals and the acoustic dose correction signals.
  • the injection device 1 comprises the generating arrangement, wherein the generating arrangement comprises the dose setting feedback generator, i.e. the dose setting clicker, and the dose correction feedback generator, i.e. the dose correction clicker, as described above with regard to figures 1-6.
  • the generating arrangement comprises the dose setting feedback generator, i.e. the dose setting clicker, and the dose correction feedback generator, i.e. the dose correction clicker, as described above with regard to figures 1-6.
  • the dose setting clicker and the dose correction clicker can be designed as a direct or indirect interface between the number sleeve 50 and the housing 10.
  • the interface may comprise a two-way slip clutch.
  • the dose setting clicker and the dose correction clicker may be arranged between the inner surface of the housing 10 and a drive sleeve (not visible in Figures 7 and 8), which is moved rotationally and/or translationally relative to the housing 10 during the dispensing process.
  • the injection device 1 may further comprise a dose dispensing clicker, configured to generate an acoustic dose dispensing signal indicative of the dose dispensing operation.
  • the dose dispensing clicker can, for example, be positioned between the outer surface of the number sleeve 50 and the inner surface of the housing 10.
  • the add-on device 2 comprises the electronic system.
  • the electronic system comprises the monitoring unit.
  • the monitoring unit comprises the power source 20, or battery, in the form of a coin cell.
  • the power source 20 provides power to the electronic components of the electronic system.
  • the power source 20 is located distally in the axial direction of the add-on device 2 to a printed circuit board (PCB) 23.
  • the monitoring unit comprises the microphone 21.
  • the microphone 21 can be positioned at the distal end of the add-on device 2.
  • the monitoring unit comprises the processor unit 22.
  • the processor unit 22 is operatively coupled to the microphone 21 or to a plurality of microphones.
  • the processor unit 22 is configured to assign the detected distinctive acoustic signals to the different operational events.
  • the electronic system comprises the output 30, configured to forward dose-relevant information indicative of a dispensed or set size of a drug dose to the user.
  • the dose-relevant information can be provided to the user either directly by a notification that is recognizable to the user, e.g. a message on a screen of the injection device 1 or add-on device 2, or indirectly by means of an external device, such as a smartphone or smartwatch.
  • the output 30 and the processor unit 22 are arranged on the printed circuit board (PCB) 23 in the proximal area of the add-on device 2.
  • the electronic system can alternatively be an integral part of the drug delivery device, i.e. the injection device 1 , so that no add-on device is required in order to use the electronic system.
  • the monitoring unit comprising the power source 20, the microphone 21 and the processor unit 22 as well as the output 30 are exclusively comprised by the injection device 1.
  • the power source 20, the microphone 21 , and the processor unit 22 can be arranged, for example, on the inner surface of the housing 10 in the region of the proximal opening of the housing 10, while the output 30 can be arranged on the outer surface of the housing 10.
  • an add-on device comprising an electronic module as described above may be an add-on device to be attached to the housing of a drug delivery device 1 and not to the proximal end of the drug delivery device, e.g. snapped sideways onto the housing 10 at a position distally displaced from the window 13 or longitudinally slipped over the housing from the proximal end until it reaches a final distal position relative to the housing of the drug delivery device.
  • 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.
  • 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.
  • 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., shorter long-term storage) of one or more drugs.
  • the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days).
  • 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).
  • the drug container may be or may include a dualchamber 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.
  • the two chambers of the dual-chamber 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.
  • 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.
  • the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.
  • 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.
  • 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 (antidiabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.
  • ACS acute coronary syndrome
  • APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (antidiabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.
  • 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 dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof.
  • an insulin e.g., human insulin, or a human insulin analogue or derivative
  • GLP-1 glucagon-like peptide
  • DPP4 dipeptidyl peptidase-4
  • 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".
  • 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.
  • 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.
  • insulin analogues examples include 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.
  • 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- 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-g
  • GLP-1 , GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, 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, ORMD-0901 , NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1 , CVX-096, ZYOG-1 , ZYD-1 ,
  • oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom.
  • DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.
  • hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.
  • 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.
  • 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.
  • antibody refers to an immunoglobulin molecule or an antigenbinding portion thereof.
  • 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.
  • the antibody has effector function and can fix complement.
  • the antibody has reduced or no ability to bind an Fc receptor.
  • 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).
  • TBTI tetravalent bispecific tandem immunoglobulins
  • CODV cross-over binding region orientation
  • fragment refers 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, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and immunoglobulin single variable domains.
  • SMIP small modular immunopharmaceuticals
  • immunoglobulin single variable domain (ISV), interchangeably used with “single variable domain”, defines immunoglobulin molecules wherein the antigen binding site is present on, and formed by, a single immunoglobulin domain.
  • immunoglobulin single variable domains are capable of specifically binding to an epitope of the antigen without pairing with an additional immunoglobulin variable domain.
  • the binding site of an immunoglobulin single variable domain is formed by a single heavy chain variable domain (VH domain or VHH domain) or a single light chain variable domain (VL domain).
  • VH domain or VHH domain single heavy chain variable domain
  • VL domain single light chain variable domain
  • An immunoglobulin single variable domain can be a heavy chain ISV, such as a VH (derived from a conventional four-chain antibody), or VHH (derived from a heavy-chain antibody), including a camelized VH or humanized VHH.
  • the immunoglobulin single variable domain may be a (single) domain antibody, a "dAb” or dAb or a Nanobody® ISV (such as a VHH, including a humanized VHH or camelized VH) or a suitable fragment thereof.
  • Nanobody® is a registered trademark of Ablynx N.V.]; other single variable domains, or any suitable fragment of any one thereof.
  • VHH domains also known as VHHs, VHH antibody fragments, and VHH antibodies, have originally been described as the antigen binding immunoglobulin variable domain of “heavy chain antibodies” (i.e. , of “antibodies devoid of light chains”; Hamers-Casterman et al. 1993 (Nature 363: 446-448).
  • VHH domain has been chosen in order to distinguish these variable domains from the heavy chain variable domains that are present in conventional 4- chain antibodies (which are referred to herein as “VH domains”) and from the light chain variable domains that are present in conventional 4-chain antibodies (which are referred to herein as “VL domains”).
  • VHH domains For a further description of VHH’s, reference is made to the review article by Muyldermans 2001 (Reviews in Molecular Biotechnology 74: 277-302).
  • CDR complementarity-determining region
  • 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.
  • 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.
  • antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).
  • PCSK-9 mAb e.g., Alirocumab
  • anti IL-6 mAb e.g., Sarilumab
  • anti IL-4 mAb e.g., Dupilumab
  • 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.
  • 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), needlebased 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.
  • a multi-dose container system may involve a needle-based drug delivery 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 drug delivery 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).
  • a single-dose container system may involve a needle-based drug delivery device with a replaceable container.
  • each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation).
  • each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).
  • a single-dose container system may involve a needle-based drug delivery 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).
  • each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).
  • PCB printed circuit board

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  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

L'invention concerne un système électronique pour un dispositif d'administration de médicament (1) comprenant une unité de surveillance (20, 21, 22) configurée pour détecter des signaux acoustiques distinctifs générés lors du fonctionnement du dispositif d'administration de médicament par un utilisateur, le système électronique étant configuré pour attribuer les signaux acoustiques distinctifs détectés à différents événements opérationnels du dispositif d'administration de médicament qui sont effectués par l'utilisateur, et les différents événements opérationnels comprenant des événements au cours desquels la taille d'une dose définie ou d'une dose distribuée est modifiée.
PCT/EP2025/062670 2024-05-10 2025-05-08 Système électronique Pending WO2025233480A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP24315230 2024-05-10
EP24315230.3 2024-05-10

Publications (1)

Publication Number Publication Date
WO2025233480A1 true WO2025233480A1 (fr) 2025-11-13

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Country Link
WO (1) WO2025233480A1 (fr)

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004068820A2 (fr) 2003-01-23 2004-08-12 Unspam, Llc. Procede et appareil destines a un systeme de liste de numeros interdits a ne pas divulguer
WO2005018629A1 (fr) 2003-08-12 2005-03-03 Yarbrough William M Traitement de l'acne simple et procede d'utilisation
WO2006003388A2 (fr) 2004-06-30 2006-01-12 Domantis Limited Compositions et procedes pour le traitement de troubles inflammatoires
WO2006030220A1 (fr) 2004-09-17 2006-03-23 Domantis Limited Compositions monovalentes pour la liaison au cd40l et procedes d'utilisation
WO2006045526A1 (fr) 2004-10-21 2006-05-04 Novo Nordisk A/S Mecanisme a disque se deplacant vers le bas pour des seringues automatiques
US20090069742A1 (en) * 2006-03-20 2009-03-12 Andre Larsen Electronic Module for Mechanical Medication Delivery Devices
WO2013116951A1 (fr) 2012-02-09 2013-08-15 Tecpharma Licensing Ag Équipement d'injection destiné à administrer ou transporter un produit fluide
US20150290396A1 (en) * 2012-10-23 2015-10-15 Insuline Medical Ltd. Drug dispensing-tracking device, system and method
WO2016198516A1 (fr) 2015-06-09 2016-12-15 Sanofi-Aventis Deutschland Gmbh Dispositif de collecte de données pour fixation sur un dispositif d'injection
WO2024046932A1 (fr) * 2022-08-30 2024-03-07 Sanofi Dispositif complémentaire pour dispositif d'injection

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004068820A2 (fr) 2003-01-23 2004-08-12 Unspam, Llc. Procede et appareil destines a un systeme de liste de numeros interdits a ne pas divulguer
WO2005018629A1 (fr) 2003-08-12 2005-03-03 Yarbrough William M Traitement de l'acne simple et procede d'utilisation
WO2006003388A2 (fr) 2004-06-30 2006-01-12 Domantis Limited Compositions et procedes pour le traitement de troubles inflammatoires
WO2006030220A1 (fr) 2004-09-17 2006-03-23 Domantis Limited Compositions monovalentes pour la liaison au cd40l et procedes d'utilisation
WO2006045526A1 (fr) 2004-10-21 2006-05-04 Novo Nordisk A/S Mecanisme a disque se deplacant vers le bas pour des seringues automatiques
US20090069742A1 (en) * 2006-03-20 2009-03-12 Andre Larsen Electronic Module for Mechanical Medication Delivery Devices
WO2013116951A1 (fr) 2012-02-09 2013-08-15 Tecpharma Licensing Ag Équipement d'injection destiné à administrer ou transporter un produit fluide
US20150290396A1 (en) * 2012-10-23 2015-10-15 Insuline Medical Ltd. Drug dispensing-tracking device, system and method
WO2016198516A1 (fr) 2015-06-09 2016-12-15 Sanofi-Aventis Deutschland Gmbh Dispositif de collecte de données pour fixation sur un dispositif d'injection
WO2024046932A1 (fr) * 2022-08-30 2024-03-07 Sanofi Dispositif complémentaire pour dispositif d'injection

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* Cited by examiner, † Cited by third party
Title
HAMERS-CASTERMAN ET AL., NATURE, vol. 363, 1993, pages 446 - 448
HOLT ET AL., TRENDS BIOTECHNOL., vol. 21, 2003, pages 484
MUYLDERMANS, REVIEWS IN MOLECULAR BIOTECHNOLOGY, vol. 74, 2001, pages 277 - 302
WARD ET AL., NATURE, vol. 341, 1989, pages 544

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