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WO2024251798A1 - Dispositif d'administration de médicament - Google Patents

Dispositif d'administration de médicament Download PDF

Info

Publication number
WO2024251798A1
WO2024251798A1 PCT/EP2024/065442 EP2024065442W WO2024251798A1 WO 2024251798 A1 WO2024251798 A1 WO 2024251798A1 EP 2024065442 W EP2024065442 W EP 2024065442W WO 2024251798 A1 WO2024251798 A1 WO 2024251798A1
Authority
WO
WIPO (PCT)
Prior art keywords
drug delivery
delivery device
pouch
needle
needles
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/EP2024/065442
Other languages
English (en)
Inventor
Nima AGHAJARI
Uwe Dasbach
Tim GLÄSSER
Moritz KEIM
Matthias Rau
Michael Schabbach
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 WO2024251798A1 publication Critical patent/WO2024251798A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

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
    • A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
    • A61M5/2033—Spring-loaded one-shot injectors with or without automatic needle insertion
    • 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
    • A61M5/24—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic
    • A61M5/2422—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic using emptying means to expel or eject media, e.g. pistons, deformation of the ampoule, or telescoping of the ampoule
    • A61M5/2425—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic using emptying means to expel or eject media, e.g. pistons, deformation of the ampoule, or telescoping of the ampoule by compression of deformable ampoule or carpule wall
    • 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
    • A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
    • A61M5/3205—Apparatus for removing or disposing of used needles or syringes, e.g. containers; Means for protection against accidental injuries from used needles
    • A61M5/321—Means for protection against accidental injuries by used needles
    • A61M5/3243—Means for protection against accidental injuries by used needles being axially-extensible, e.g. protective sleeves coaxially slidable on the syringe barrel
    • A61M5/3271—Means for protection against accidental injuries by used needles being axially-extensible, e.g. protective sleeves coaxially slidable on the syringe barrel with guiding tracks for controlled sliding of needle protective sleeve from needle exposing to needle covering position
    • A61M5/3272—Means for protection against accidental injuries by used needles being axially-extensible, e.g. protective sleeves coaxially slidable on the syringe barrel with guiding tracks for controlled sliding of needle protective sleeve from needle exposing to needle covering position having projections following labyrinth paths
    • 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
    • A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
    • A61M5/3295—Multiple needle devices, e.g. a plurality of needles arranged coaxially or in parallel
    • 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
    • A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
    • A61M2005/2006—Having specific accessories
    • A61M2005/2013—Having specific accessories triggering of discharging means by contact of injector with patient body
    • 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
    • A61M2005/3117—Means preventing contamination of the medicament compartment of a syringe
    • A61M2005/3118—Means preventing contamination of the medicament compartment of a syringe via the distal end of a syringe, i.e. syringe end for mounting a needle cannula
    • A61M2005/312—Means preventing contamination of the medicament compartment of a syringe via the distal end of a syringe, i.e. syringe end for mounting a needle cannula comprising sealing means, e.g. severable caps, to be removed prior to injection by, e.g. tearing or twisting
    • 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
    • A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
    • A61M5/3205—Apparatus for removing or disposing of used needles or syringes, e.g. containers; Means for protection against accidental injuries from used needles
    • A61M5/321—Means for protection against accidental injuries by used needles
    • A61M5/3243—Means for protection against accidental injuries by used needles being axially-extensible, e.g. protective sleeves coaxially slidable on the syringe barrel
    • A61M5/326—Fully automatic sleeve extension, i.e. in which triggering of the sleeve does not require a deliberate action by the user
    • A61M2005/3267—Biased sleeves where the needle is uncovered by insertion of the needle into a patient's body
    • 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
    • A61M5/28—Syringe ampoules or carpules, i.e. ampoules or carpules provided with a needle
    • A61M5/285—Syringe ampoules or carpules, i.e. ampoules or carpules provided with a needle with sealing means to be broken or opened
    • A61M5/288—Syringe ampoules or carpules, i.e. ampoules or carpules provided with a needle with sealing means to be broken or opened by piercing without internal pressure increase

Definitions

  • drug is often delivered to a user via a needle which pierces the skin of the user (or patient).
  • the drug may be accommodated within a drug container of the drug delivery device, e.g. within a syringe arranged within the drug delivery device.
  • Conventional drug delivery devices comprising syringes and an associated drive mechanism have a shape basically corresponding to the shape of the syringe.
  • conventional drug delivery devices comprising syringes have an elongated cylindrical shape, wherein an axis of the drug delivery device may correspond to an axis of the needle.
  • Such a drug delivery device may often be referred to as pen-type device.
  • the cylindrical form may be hard to handle, in particular if the user has some motoric impairment.
  • a drug delivery device comprising: a housing for receiving a pouch within the housing, the pouch having collapsible walls enclosing a chamber, a dispensing side, and a remote side facing away from the dispensing side, and accommodating a drug within the chamber; a needle arrangement comprising at least one needle being configured to pierce the skin of a user, wherein the needle arrangement is configured to be brought into fluid communication with the dispensing side of the pouch; a pressure member; and an energy storage member coupled to the pressure member, the energy storage member being loaded in an initial state of the drug delivery device and being configured for squeezing the drug out of the chamber of the pouch by the pressure member during a dispensing operation of the drug delivery device.
  • the pressure member is configured for transferring the energy released by the energy storage member to the pouch during the dispensing operation.
  • the pressure member may be arranged on the remote side of the pouch.
  • the pressure member may be used as a bearing, stopper or plunger for squeezing the drug out of the pouch.
  • the pressure member may be arranged such that it is translatory movable relative to the housing, in particular in a dispensing direction towards the pouch.
  • the pressure member may work with air pressure, wherein the air pressure is used to squeeze the drug out of the pouch.
  • the pressure member may be or may comprise a pressure chamber, wherein an over- or underpressure within the pressure chamber may be generated by the energy storage member and wherein the pouch is coupled to the pressure chamber such that the pressure within the pressure chamber may be used for squeezing the pouch.
  • the pressure chamber has an opening, which is sealingly covered by a wall of the pouch.
  • the energy storage member may be a spring.
  • the energy storage member may be preloaded and/or biased in an initial state of the drug delivery device.
  • the energy storage member may be released for initiating the dispensing operation. If the energy storage member is released, the energy storage member may drive the pressure member in the dispensing direction towards the remote side of the pouch.
  • the energy storage member is a conventional spring, which is coupled to the pressure member, and which is loaded and locked in the initial state of the drug delivery device.
  • the spring and the pressure member may be attached to and/or may be arranged within a drive portion.
  • the drive portion may be a part of the housing or may be coupled to the housing.
  • the drive portion comprises a drive portion recess accompanying the spring.
  • the energy storage member may be pre-loaded by biasing the spring within the drive portion.
  • the energy storage member may allow for a given activation dynamic.
  • the drug delivery device may be a fully functional drug delivery device.
  • the drug may be a medicament.
  • the drug delivery device may be an autoinjector.
  • the energy for the drug delivery operation may be prestored in the 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 system by the manufacturer.
  • a drive spring e.g. a spiral spring or flat spiral spring, may be prestressed or pre-biased to provide the energy for the drug delivery operation.
  • Figure 6 illustrates a bottom view of an exemplary embodiment of a needle arrangement.
  • Figure 10 illustrates an exemplary embodiment of a needle sleeve in a first state.
  • Figure 16 illustrates an expanded structural formula, molecular formula, and molecular weight of fitusiran.
  • the drug delivery device 20 may be an autoinjector.
  • the energy for driving the drug delivery operation in an autoinjector may be provided by components integral to the drug delivery device 20 and does not have to be loaded into the drug delivery device 20 by the user during the operation as is the case in many spring driven pen-type variable dose injectors, where, usually, the energy is loaded into a spring by the user during a dose setting procedure.
  • the drug delivery device 20 expediently is a single shot device, i.e. it is provided to dispense only one dose.
  • the drug delivery device 20 may be a disposable drug delivery device 20, that is to say a drug delivery device 20 which is disposed of after its use.
  • the pouch 24 and/or the needle arrangement 52 may be secured within the drug delivery device 20, e.g. within the housing 22. So, the user may have to perform the movement for piercing the skin with the needle arrangement 52 by placing the drug delivery device 20 on the skin.
  • the pouch 24 may be arranged within a cavity of the housing 22.
  • the pouch 24 comprises a dispensing side 28 and a remote side 30 opposite the dispensing side 28.
  • a distance from the dispensing side 28 to the remote side 30 of the pouch 24 may be smaller than a distance from one end of the dispensing side 28 to another end of the dispensing side 28.
  • the distance from the dispensing side 28 to the remote side 30 of the pouch 24 is smaller than a distance from one end of the remote side 30 to another end of the remote side 30.
  • the distance from the dispensing side 28 to the remote side 30 may be referred to as height of the pouch 24.
  • the energy storage member 34 may be a conventional spring, which is coupled to the pressure member 32.
  • the energy storage member 34 e.g. the spring, may be is loaded and locked in the initial state of the drug delivery device 20. In the initial and loaded state, energy is stored in the loaded energy storage member 34, i.e. the spring is biased. If the energy storage member 34 is released, the energy stored in the energy storage member 34 is released and transferred to the pressure member 32 such that the drug is squeezed out of the pouch, e.g. by the pressure member 32.
  • Other potential drive energy sources different from a spring may comprise an electrical power cell or battery for driving the pressure member 32 by a motor or a reservoir suitable to provide gas pressure, where the gas pressure can be used to drive the drug delivery operation.
  • the needle arrangement 52 is configured to pierce the dispensing side 28 of the pouch 24 at a remote side of the needle arrangement 52 and the skin of a user at a dispensing side of the needle arrangement 52 such that the needle arrangement 52 communicates with the chamber 26 and guides the drug under the skin during the dispensing operation.
  • the dispensing side of the needle arrangement faces away from the pouch 24 and the remote side of the needle arrangement 52 faces the pouch 24.
  • the needle arrangement 52 comprises at least one, preferably two or more than two needles 54.
  • the needles 54 may extend in a direction parallel to the dispensing direction 40. In the initial state of the drug delivery device 20, the needles 54 are separated from the fluid-tightly closed pouch 24. A fluid communication between an interior of the pouch 24 and the needles 54 may be only established during operation of the drug delivery device 20.
  • the needles 54 may be formed and arranged such that at least one of the needles 54 provides a first injection depth and that at least one other of the needles 54 provides a second injection depth.
  • the first injection depth may be different from the second injection depth.
  • the first injection depth may be less than the second injection depth.
  • the needle arrangement 52 comprises at least three, e.g. four, needles 54, wherein the needles 54 providing the different injections depths are alternately arranged.
  • at least two of the needles 54 may have different lengths in order to provide the different injection depths.
  • the needle arrangement 52 in particular the needles 54, may be protected by a multi needle shield 50 prior to the use of the drug delivery device 20.
  • the multi needle shield 50 may cover the needles 54 until it is removed by hand.
  • the multi needle shield 50 may comprise a gripping ring 58.
  • the gripping ring 58 may provide a comfortable gripping structure for gripping and removing the multi needle shield 50.
  • the drug delivery device 20 may comprises a flexible pouch sealing member 56.
  • the pouch sealing member 56 may sealingly and/or sterilely separate a section of the housing 22 in which the pouch 24 is arranged from a section of the housing 22 in which the needles 54 are arranged.
  • the pouch sealing member 56 may be flexible.
  • the pouch sealing member 56 may comprise or may be a foil.
  • the flexible pouch sealing member 56 may separate the needles 54 against the pouch 24 in the initial state.
  • the flexible pouch sealing member 56 may be configured for being pierced by the needles 54 for initiating the dispensing operation.
  • the needles 54 may pierce the skin of the user.
  • the needle sleeve 46 may be pushed into the housing 22 when the drug delivery device 20 is arranged on the injection site, e.g. the skin of the user.
  • the drug delivery device 20 is positioned on the skin with a bottom surface of the needle sleeve 46 touching the skin, the needle sleeve 46 is pushed into the housing 22.
  • the needles 54 is exposed and may pierce the skin.
  • the bottom surface of the needle sleeve 46 may provide at least a part of a bearing surface of the drug delivery device 20.
  • the bearing surface is meant for being in contact with the injection site during the dispensing operation, the bearing surface facing away from the drive portion 35.
  • the first release member may also comprise an outer shoulder 39 of the drive portion 35, the outer shoulder 39 extending radially outwardly and being configured for being pushed radially outwardly by the second release member thereby pulling the inner shoulder 37 radially outwardly to release the pressure member 32 for initiating the dispensing operation.
  • the drug delivery device 20 may comprise a needle sleeve spring 48 which is coupled to the needle sleeve 46 and the housing 22.
  • the needle sleeve spring 48 may be operatively couplable to or coupled to the needle sleeve 46 in order to move the needle sleeve 46, e.g. in the dispensing direction relative to the housing 22.
  • the needle sleeve spring 48 may be loaded, if the drug delivery device 20 is arranged on the injection site and if the needle sleeve 46 is pressed into the housing 22.
  • the force of the needle sleeve spring 48 may have to be overcome in order to move the needle sleeve 46 into the housing 22.
  • the needle sleeve 46 may be pushed out of the housing 22 by the needle sleeve spring 48. In a final position, e.g. after the drug delivery operation has been completed and the drug delivery device 20 has been removed from the skin, the needle sleeve 46 may be locked against a further movement with respect to the housing 22, such as by a locking mechanism, as explained below with respect to figures 10 to 15.
  • the needle sleeve 46 may serve as a trigger member of the drug delivery device 20.
  • the needle sleeve 46 as trigger member when displaced from the initial or first position depicted in figure 1 to a second or trigger position depicted in figure 2, may automatically initialize the drug delivery operation, preferably when it is in the second position.
  • Figure 2 illustrates cross-sectional side view of the interior of the drug delivery device 20 of figure 1 in a second state.
  • the needle shield 50 has been removed and the needle sleeve 46 is pushed into the housing 22 in its second position, e.g. by arranging the drug delivery device 20 on the injection site and by pressing the housing 22 towards the injection site.
  • the needle sleeve 46 when moved from the first position to the second position and expediently when in the second position, may initiate the drug delivery operation via acting on the first release member of the release mechanism 36. Operating the first release member to initiate the drug delivery operation may only be possible when the needle sleeve 46 is in the second position.
  • the second release member e.g. the chamfer 44
  • the first release member in particular the pin 41 at the outer shoulder 39 of the drive portion 35 such that the flexible walls of the drive portion 35 together with the inner shoulder 37 are pulled radially outwardly thereby releasing the locked pressure member 32 and thereby the biased energy storage member 34.
  • the energy storage member 34 pushes the pressure member 32 in the dispensing direction 40 towards the pouch 24. So, the pressure member 32 may be moved only, if the drug delivery device 20 is positioned on the skin and the needle sleeve 46 exposes the needles 54. In the second state, the pressure member 32 touches the remote side 30 of the pouch 24, but the pouch 24 is not yet squeezed.
  • Figure 3 illustrates cross-sectional side view of the interior of the drug delivery device 20 of figure 1 in a third state.
  • the pouch sealing member 56 may be deformed only as long as the pouch 24 is not yet pierced, because the pressure of the pressure member 32 is transferred to the flexible sealing member 56 by the pressurized but still closed pouch 24.
  • the energy storage member 34 presses the pouch 24 against the pouch sealing member 56 and the needle arrangement 52 such that the pouch sealing member 56 is deformed and that the remote ends of the needles 54 pierce the dispensing side 28 of the pouch 24. So, in the third state, the dispensing side 28 of the pouch 24 and the pouch sealing member 56 are pierced, but the pouch 24 is not yet squeezed further.
  • Figure 4 illustrates cross-sectional side view of the interior of the drug delivery device 20 of figure 1 in a fourth state.
  • the pouch 24 is squeezed by the pressure member 32 in the dispensing direction and the drug is pressed out of the chamber 26 through the needles 54 into the skin of the user (not shown).
  • the needle sleeve 56 is locked such that it may not be moved towards the housing 22 anymore, as explained below with respect to figures 10 to 15.
  • Figure 6 illustrates a bottom view of an exemplary embodiment of a needle arrangement 52, e.g. the above needle arrangement 52.
  • the needles of the needle arrangement 52 are linearly arranged, in particular as a straight line.
  • Figure 7 illustrates a bottom view of an exemplary embodiment of a needle arrangement 52, e.g. the above needle arrangement 52.
  • the needles 54 of the needle arrangement 52 are arranged as an array, in particular as a rectangular, e.g. a quadratic, array. Alternatively, the array may have any polygonal or circular shape.
  • Figure 8 illustrates a cross-sectional side view of an interior of an exemplary embodiment of a drug delivery device 20 in a first state.
  • the first state shown in figure 8 may correspond to the above first state shown in figure 1.
  • the drug delivery device 20 may widely correspond to the above drug delivery device 20. Therefore, only those features of the drug delivery device 20 are explained in the following, in which the drug delivery device 20 shown in figure 8 differs from the above drug delivery device 20.
  • the drug delivery device 20 may comprise a flexible needle sealing member 60.
  • the needle sealing member 60 may sealingly and/or sterilely separates a section of the housing 22 and/or the needle sleeve 46 in which the needle arrangement 52 is arranged from through-recesses within the needle sleeve 46 at the bearing surface of the needle sleeve 46.
  • the needle sealing member 60 may be flexible.
  • the needle sealing member 60 may comprise or may be a foil.
  • the flexible needle sealing member 60 may separate the tips of the needles 54 against the environment in the initial state.
  • the flexible needle sealing member 60 may be configured for being pierced by the needles 54 for initiating the dispensing operation.
  • Figure 9 illustrates a cross-sectional side view of the interior of the drug delivery device 20 of figure 8 in a second state.
  • the flexible needle sealing member 60 may be pierced by the needles 54.
  • the second state shown in figure 9 may correspond to the above second state shown in figure 2.
  • Figure 10 illustrates an exemplary embodiment of the needle sleeve 46 and the housing 22 in a first state.
  • figure 10 illustrates a side view of the needle sleeve 46 and a cutaway side view of the housing 22 in the first state.
  • the drug delivery device 20 is not yet arranged on the skin of the user and the needle sleeve 46 protects the needles 54.
  • the first channel 96 extends firstly with a slide inclination against the vertical direction and then basically verticality towards a bent 98 of the first channel 96 and then back towards a dead end 100 of the first channel 96.
  • the dead end 100 is separated from the rest of the first channel 96 by a barb 102.
  • the guide pin 90 is arranged in a part of the first channel 96 below the dead end 100 and at the beginning of the inclination of the first channel 96.
  • the torsion protection 92 of the needle sleeve 46 is arranged within the second channel 104 and is guided by the second channel 104 during the movement of the needle sleeve 46 relative to the housing 22.
  • the second channel 104 is straight and parallel to the axis 45 and as such parallel to the moving direction of the needle sleeve 46.
  • the torsion protection 92 within the second channel 104 serves as a protection of the needle sleeve 46 against a rotation of the needle sleeve 46.
  • Figure 11 illustrates the needle sleeve 46 and the housing 22 of figure 10 in a second state.
  • the needle sleeve 46 may be partly arranged within the housing 22, e.g. because of the drug delivery device 20 being partly arranged on the skin of the user.
  • the guide pin 90 is moved within the first channel 96 towards the bent 98.
  • Figure 12 illustrates the needle sleeve 46 and the housing 22 of figure 10 in a third state.
  • the needle sleeve 46 In the third state of the needle sleeve 46, the needle sleeve 46 is pressed into the housing 22 completely, e.g. because of the user arranging the drug delivery device 20 on his/her skin. So, in the third state of the needle sleeve 46, the needles 54 is exposed by the needle sleeve 46. In this situation, the guide pin 90 has arrived in the bent 98 of the first channel 96 and may be moved perpendicular to the moving direction of the needle sleeve 46 within the bent 98. In the third state of the needle sleeve 46, the biased flexible bars 94 force the guide pin 90 through the bent 98.
  • Figure 13 illustrates the needle sleeve 46 and the housing 22 of figure 10 in a fourth state.
  • the flexible bars 94 are released and the guide pin 90 has moved perpendicular to the moving direction of the needle sleeve 46 within the bent 98.
  • Figure 14 illustrates the needle sleeve 46 and the housing 22 of figure 10 in a fifth state.
  • the drug delivery device 20 may be partly removed from the skin of the user.
  • the guide pin 90 is forced over the barb 102 of the first channel 100 such that the flexible bars 94 are biased again.
  • the needle sleeve 46 may be pushed out of the housing 22, for example by the needle sleeve spring 48 such that the guide pin 90 is forced over the barb.
  • Figure 15 illustrates the needle sleeve 46 and the housing 22 of figure 10 in a sixth state.
  • the drug delivery device 20 may be completely removed from the skin of the user.
  • the needle sleeve 46 may completely cover the needles 54.
  • the guide pin 90 snaps into the dead end 100 of the first channel 96 such that the needle sleeve 46 is fixedly engaged to the housing 22.
  • 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 pharmaceutical 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 reservoir” adapted for use with a drug delivery device.
  • the drug reservoir 101a may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel (bag) configured to provide a suitable chamber for storage (e.g., short- or 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.
  • the drug reservoir may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber.
  • the two chambers of the dualchamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body.
  • 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, GRMD-0901 , NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1 , CVX-096, ZYOG-1, ZYD-1 , GLP
  • an 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.
  • mipomersen sodium Korean, a benzyl alcohol, a benzyl ether, a benzyl ether, a benzyl ether, a benzyl-containing asen 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.
  • Gonadotropine Follitropin, Lutropin, Choriongonadotropin, Menotropin
  • Somatropine Somatropin
  • Desmopressin Terlipressin
  • Gonadorelin Triptorelin
  • Leuprorelin Buserelin
  • Nafarelin Nafarelin
  • Goserelin 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, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.
  • SMIP small modular immunopharmaceuticals
  • 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
  • APIs for the prophylaxis of hemophilia A or B, with or without inhibitors include an siRNA targeting antithrombin.
  • An example of an siRNA targeting antithrombin is fitusiran.
  • prophylaxis and prophylactic treatment are used interchangeably herein
  • 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).
  • 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 injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).
  • Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).
  • a single-dose container system may involve a needle-based injection 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 injection device with an integrated non-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).
  • Fitusiran is a synthetic, chemically modified double-stranded small interfering RNA (siRNA) oligonucleotide covalently linked to a tri-antennary N-acetyl-galactosamine (GalNAc) ligand targeting AT3 mRNA in the liver, thereby suppressing the synthesis of antithrombin.
  • siRNA small interfering RNA
  • GalNAc tri-antennary N-acetyl-galactosamine
  • the nucleosides in each strand of fitusiran are connected through either 3’-5’ phosphodiester or phosphorothioate linkages, thus forming the sugar-phosphate backbone of the oligonucleotide.
  • the sense strand and the antisense strand contain 21 and 23 nucleotides, respectively.
  • the 3’ end of the sense strand is conjugated to the GalNAc containing moiety (referred to herein as L96) through a phosphodiester linkage.
  • the sense strand contains two consecutive phosphorothioate linkages at its 5’ end.
  • the antisense strand contains four phosphorothioate linkages, two at the 3’ end and two at the 5’ end.
  • the 21 nucleotides of the sense strand hybridize with the complementary 21 nucleotides of the antisense strand, thus forming 21 nucleotide base pairs and a two-base overhang at the 3’-end of the antisense strand. See also U.S. Pat. 9,127,274, U.S. Pat. 11 ,091,759, US2020/0163987A1, and WO 2019/014187, the entire contents each of which are expressly incorporated herein by reference.
  • sense strand 5’Gf-ps-Gm-ps-Uf-Um-Af-Am-Cf-Am-Cf-Cf-Af-Um-Uf-Um-Af-Cm-Uf-Um-Cf-Am-
  • Af-L96 3’ (SEQ ID N0:1), and antisense strand: 5’
  • Fitusiran is shown in Figure 16 in sodium salt form.
  • the device delivers fitusiran in an aqueous solution, wherein fitusiran is at a concentration of about 40 to about 200 mg/mL (e.g., about 50 to about 150 mg/mL, about 80 to about 110 mg/mL, or about 90 to about 110 mg/mL).
  • fitusiran is at a concentration of about 40 to about 200 mg/mL (e.g., about 50 to about 150 mg/mL, about 80 to about 110 mg/mL, or about 90 to about 110 mg/mL).
  • values intermediate to recited ranges and values are also intended to be part of this disclosure.
  • ranges of values using a combination of any of recited values as upper and/or lower limits are intended to be included.
  • the pharmaceutical formulation comprises fitusiran in an aqueous solution at a concentration of about 40, about 50, about 75, about 100, about 125, about 150, or about 200 mg/mL.
  • fitusiran is provided in an aqueous solution at a concentration of about 100
  • the term “approximately” or “about” refers to a value that is within an acceptable error range for a particular value determined by a person of ordinary skill, a portion of which will depend on how the measurement or determination is made. For example, “approximately” or “about” may mean a range of up to 10% (ie, ⁇ 10%). Therefore, “approximately” or “about” can be understood as greater than or less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1 %, 0.05%, 0.01%, or 0.001%. When a specific value is provided in this disclosure, unless otherwise stated, the meaning of “approximately” or “about” should be assumed to be within an acceptable error range for that specific value.
  • fitusiran dosage weight described herein refers to the weight of fitusiran free acid (active moiety)
  • administration of fitusiran to patients herein refers to administration of fitusiran sodium (drug substance) provided in a pharmaceutically suitable aqueous solution (e.g., a phosphate-buffered saline at a physiological pH).
  • a pharmaceutically suitable aqueous solution e.g., a phosphate-buffered saline at a physiological pH.
  • fitusiran means about 100 mg of fitusiran free acid (equivalent to about 106 mg fitusiran sodium, the drug substance) per ml_.
  • a fitusiran weight recited in the present disclosure is the weight of fitusiran free acid (the active moiety).
  • a pharmaceutical formulation in the device comprises fitusiran in a phosphate-buffered saline.
  • the phosphate concentration in the solution may be about 1 to about 10 mM (e.g., about 2, about 3, about 4, about 5, about 6, about 7, about 8, or about 9 mM), with a pH of about 6.0-8.0.
  • the pharmaceutical formulations herein may include a stabilizing agent such as EDTA.
  • the pharmaceutical formulations may be preservative-free.
  • the fitusiran pharmaceutical formulation in the device is preservative-free and comprises, consists of, or consists essentially of about 100 mg of fitusiran per mL of an approximately 5 mM phosphate buffered saline (PBS) solution.
  • PBS phosphate buffered saline
  • the fitusiran pharmaceutical formulation in the device is preservative-free and comprises, consists of, or consists essentially of fitusiran in an approximately 5 mM phosphate buffered saline (PBS) solution.
  • PBS phosphate buffered saline
  • the PBS solution is composed of sodium chloride, dibasic sodium phosphate (heptahydrate), and monobasic sodium phosphate (monohydrate).
  • Sodium hydroxide solution and diluted phosphoric acid may be used to adjust the pH of the pharmaceutical formulation to about 7.0 or about 7.1.
  • the fitusiran pharmaceutical formulation in the device for subcutaneous delivery contains fitusiran in a 5 mM phosphate buffered saline having 0.64 mM Na ⁇ PC , 4.36 mM N32HPO4, and 84 mM NaCI at pH 7.0.
  • the pharmaceutical formulation of fitusiran solution for subcutaneous delivery is shown in Table 1 below:
  • the device may be used to deliver a single dose of fitusiran wherein the single dose comprises about 20 to about 80 mg of fitusiran (e.g., about 20 mg, about 25 mg, about 30 mg, about 40 mg, about 50 mg, or about 80 mg). In some embodiments, the device may be used to deliver single dose of fitusiran, wherein the single dose comprises about 1 to about 30 mg of fitusiran (e.g., about 1.25 mg, about 2.5 mg, about 5 mg, about 10 mg, about 20 mg, or about 30 mg).
  • the single dose comprises about 1 to about 30 mg of fitusiran (e.g., about 1.25 mg, about 2.5 mg, about 5 mg, about 10 mg, about 20 mg, or about 30 mg).
  • the device may be used to deliver a single dose of about 80 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 50 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 20 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 30 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 10 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 5 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 2.5 mg of fitusiran. In one embodiment, the device may be used to deliver a single dose of about 1.25 mg of fitusiran.
  • the single dose of fitusiran may be delivered in about 0.5 mL to about 1 mb delivery volumes (e.g., about 0.5 mb, about 0.6 mb, about 0.7 mb, about 0.8 mb, about 0.9 mb, or about 1 mb). Other delivery volumes described herein may also be used.
  • the device may be used to deliver a single dose of about 80 mg of fitusiran in about 0.8 mb (about 100 mg fitusiran/mL).
  • the device may be used to deliver a single dose of about 50 mg of fitusiran in about 0.5 mL (about 100 mg fitusiran/mL).
  • the device may be used to deliver a single dose of about 20 mg of fitusiran in about 0.5 mL (about 40 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 30 mg of fitusiran in about 0.5 mL (about 60 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 10 mg of fitusiran in about 0.5 mL (about 20 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 5 mg of fitusiran in about 0.5 mL (about 10 mg fitusiran/mL).
  • the device may be used to deliver a single dose of about 2.5 mg of fitusiran in about 0.5 mL (about 5 mg fitusiran/mL). In one embodiment, the device may be used to deliver a single dose of about 1.25 mg of fitusiran in about 0.5 mL (about 2.5 mg fitusiran/mL).
  • the device delivers fitusiran at a prophylactically effective amount to prophylactically treat hemophilia (e.g., hemophilia A or B, in a patient with or without inhibitors) in a patient in need thereof (e.g., a hemophilia A or B patient, with or without inhibitors).
  • “Prophylactically effective amount” refers to the amount of fitusiran that helps the patient with hemophilia A or B, with or without inhibitors to achieve a desired clinical endpoint such as reducing the Annualized Bleeding Rate (ABR), Annualized Joint Bleeding Rate (AjBR), Annualized Spontaneous Bleeding Rate (AsBR), or the frequency of bleeding episodes.
  • ABR Annualized Bleeding Rate
  • AjBR Annualized Joint Bleeding Rate
  • AsBR Annualized Spontaneous Bleeding Rate
  • the term “treat” “treating,” or “treatment” includes prophylactic treatment of the disease and refers to achievement of a desired clinical
  • a hemophilia A or B patient with inhibitors refers to a patient who has developed alloantibodies to the factor he/she has previously received (e.g., factor VIII for hemophilia A patients or factor IX for hemophilia B patients).
  • a hemophilia A or B patient with inhibitors may become refractory to replacement coagulation factor therapies.
  • a patient without inhibitors refers to a patient who does not have such alloantibodies.
  • the present treatment methods may be beneficial for hemophilia A patients with inhibitors, as well as for hemophilia B patients with inhibitors.
  • the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 50 mg of fitusiran once every two months (or every eight weeks). In other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 50 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 80 mg of fitusiran every two months (or every eight weeks).
  • the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 80 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 20 mg of fitusiran every two months (or every eight weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 20 mg of fitusiran every month (or every four weeks).
  • the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of about 10 mg of fitusiran every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 30 mg every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 5 mg every month (or every four weeks).
  • the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 2.5 mg every month (or every four weeks). In yet other embodiments, the device may be used to prophylactically treat a patient with hemophilia A or B, with or without inhibitors, with a subcutaneous dose of fitusiran at about 1.25 mg every month (or every four weeks).
  • a method of prophylactic treatment of a patient with hemophilia A or hemophilia B, with or without inhibitors comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof.
  • the prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg.
  • the prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg.
  • the prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks).
  • Fitusiran may be delivered in about 0.5 mL to about 1 mb delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).
  • a method of prophylactic treatment of a patient with hemophilia A or hemophilia B, with or without inhibitors may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks).
  • the about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran/mL).
  • the prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg.
  • the prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg.
  • the prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks).
  • Fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).
  • a method of reducing the frequency of bleeding episodes in a patient with hemophilia A or B, with or without inhibitors may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks).
  • the about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran/mL).
  • a method of reducing the ABR in a patient with hemophilia A or B, with or without inhibitors comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof.
  • the prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg.
  • the prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg.
  • the prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks).
  • Fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).
  • a method of reducing the ABR in a patient with hemophilia A or B, with or without inhibitors may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks).
  • the about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran/mL).
  • a method of reducing the AjBR in a patient with hemophilia A or B, with or without inhibitors comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof.
  • the prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg.
  • the prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg.
  • the prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks).
  • the fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).
  • a method of reducing the AjBR in a patient with hemophilia A or B, with or without inhibitors may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks).
  • the about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran/mL).
  • a method of reducing the AsBR in a patient with hemophilia A or B, with or without inhibitors comprising subcutaneously delivering with the device a prophylactically effective amount of fitusiran to the patient in need thereof.
  • the prophylactically effective amount of fitusiran may be any dose provided herein, such as about 1 to about 80 mg, about 1 to about 30 mg, or about 20 to about 80 mg.
  • the prophylactically effective amount of fitusiran may be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg.
  • the prophylactically effective amount of fitusiran may be delivered every month (or every four weeks) or once every two months (or every eight weeks).
  • Fitusiran may be delivered in about 0.5 mL to about 1 mL delivery volumes (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).
  • a method of reducing the AsBR in a patient with hemophilia A or B, with or without inhibitors may comprise subcutaneously delivering with the device about 50 mg of fitusiran to the patient in need thereof every month (or every four weeks) or once every two months (or every eight weeks).
  • the about 50 mg of fitusiran may be delivered in about 0.5 mL PBS (at a concentration of about 100 mg fitusiran/mL).
  • the above drug delivery device 20 may comprise a pressure member, which works with air pressure, wherein the air pressure is used to squeeze the drug out of the pouch 24.
  • the pressure member may be or may comprise a pressure chamber, wherein an over- or underpressure within the pressure chamber may be generated by the energy storage member 34 and wherein the pouch 24 is coupled to the pressure chamber such that the pressure within the pressure chamber may be used for squeezing the pouch 24.
  • the pressure chamber has an opening, which is sealingly covered by a wall of the pouch 24.

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  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

L'invention concerne un dispositif d'administration de médicament (20). Le dispositif d'administration de médicament (20) comprend : un boîtier (22) pour recevoir une poche (24) à l'intérieur du boîtier (22), la poche (24) ayant des parois pliables entourant une chambre (26), un côté de distribution (28), et un côté distant (30) opposé au côté de distribution (28), et recevant un médicament à l'intérieur de la chambre (26) ; un agencement d'aiguille (52) comprenant au moins une aiguille (54) conçue pour percer la peau d'un utilisateur, l'agencement d'aiguille (52) étant conçu pour être mis en communication fluidique avec le côté de distribution (28) de la poche (24) ; un élément de pression (32) ; et un élément de stockage d'énergie (34) couplé à l'élément de pression (32), l'élément de stockage d'énergie (34) étant chargé dans un état initial du dispositif d'administration de médicament (20) et étant configuré pour presser le médicament hors de la chambre (26) de la poche (24) par l'élément de pression (32) pendant une opération de distribution du dispositif d'administration de médicament (20).
PCT/EP2024/065442 2023-06-05 2024-06-05 Dispositif d'administration de médicament Pending WO2024251798A1 (fr)

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EP23315233.9 2023-06-05
EP23315233 2023-06-05

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WO2024251798A1 true WO2024251798A1 (fr) 2024-12-12

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WO (1) WO2024251798A1 (fr)

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WO2008107381A1 (fr) * 2007-03-02 2008-09-12 Novo Nordisk A/S Dispositif d'administration de médicament avec une pompe à bolus préréglé
WO2012110040A1 (fr) * 2011-02-15 2012-08-23 Injector Aps Injecteur jetable pour injecter un liquide dans un patient
WO2014109012A1 (fr) * 2013-01-09 2014-07-17 テルモ株式会社 Instrument pour administration de liquide
US20150141934A1 (en) * 2013-11-18 2015-05-21 Excelsior Medical Corporation Medicant injection device
US9127274B2 (en) 2012-04-26 2015-09-08 Alnylam Pharmaceuticals, Inc. Serpinc1 iRNA compositions and methods of use thereof
WO2019014187A1 (fr) 2017-07-10 2019-01-17 Genzyme Corporation Procédés et compositions pour le traitement d'un événement de saignement chez un sujet atteint d'hémophilie
US11091759B2 (en) 2015-12-07 2021-08-17 Genzyme Corporation Methods and compositions for treating a Serpinc1-associated disorder
US20220273923A1 (en) * 2021-03-01 2022-09-01 Deka Products Limited Partnership Medical Agent Dispensing Systems, Methods, and Apparatuses
KR20230064764A (ko) * 2021-11-04 2023-05-11 (주)제이엠바이오텍 멀티 니들의 주입 깊이 조절이 가능한 약물 주입 장치
US20230166050A1 (en) * 2017-01-26 2023-06-01 Allergan Industrie, Sas Needle array device

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008107381A1 (fr) * 2007-03-02 2008-09-12 Novo Nordisk A/S Dispositif d'administration de médicament avec une pompe à bolus préréglé
WO2012110040A1 (fr) * 2011-02-15 2012-08-23 Injector Aps Injecteur jetable pour injecter un liquide dans un patient
US9127274B2 (en) 2012-04-26 2015-09-08 Alnylam Pharmaceuticals, Inc. Serpinc1 iRNA compositions and methods of use thereof
WO2014109012A1 (fr) * 2013-01-09 2014-07-17 テルモ株式会社 Instrument pour administration de liquide
US20150141934A1 (en) * 2013-11-18 2015-05-21 Excelsior Medical Corporation Medicant injection device
US11091759B2 (en) 2015-12-07 2021-08-17 Genzyme Corporation Methods and compositions for treating a Serpinc1-associated disorder
US20230166050A1 (en) * 2017-01-26 2023-06-01 Allergan Industrie, Sas Needle array device
WO2019014187A1 (fr) 2017-07-10 2019-01-17 Genzyme Corporation Procédés et compositions pour le traitement d'un événement de saignement chez un sujet atteint d'hémophilie
US20200163987A1 (en) 2017-07-10 2020-05-28 Genzyme Corporation Methods and compositions for treating a bleeding event in a subject having hemophilia
US20220273923A1 (en) * 2021-03-01 2022-09-01 Deka Products Limited Partnership Medical Agent Dispensing Systems, Methods, and Apparatuses
KR20230064764A (ko) * 2021-11-04 2023-05-11 (주)제이엠바이오텍 멀티 니들의 주입 깊이 조절이 가능한 약물 주입 장치

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"Rote Liste", 2014
PASI ET AL., N ENGL J MED., vol. 377, no. 9, 2017, pages 819 - 28

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