WO2024184091A1

WO2024184091A1 - A subassembly of a medicament delivery device

Info

Publication number: WO2024184091A1
Application number: PCT/EP2024/054608
Authority: WO
Inventors: Stephan Müller
Original assignee: SHL Medical AG
Current assignee: SHL Medical AG
Priority date: 2023-03-09
Filing date: 2024-02-23
Publication date: 2024-09-12
Anticipated expiration: 2025-09-09

Abstract

The present disclosure generally relates to medicament delivery devices such as autoinjectors, and particularly concerns a subassembly for a medicament delivery device.

Description

A SUBASSEMBLY OF A MEDICAMENT DELIVERY DEVICE

TECHNICAL FIELD

BACKGROUND

A number of medical conditions require injections. These days, a number of different injection devices exist, including various types of pen injectors, autoinjectors and on-body devices. Although many of these devices have enabled major improvements in the management of a number of medical conditions, various limitations do still exist in the current technology. Not least amongst these are the difficulties faced by patients that require frequent injections and by patients that need to inject particularly viscous drugs. In considering these problems, the applicant has appreciated that various developments could be made to help improve the medicament delivery devices on the market today, for example concerning providing feedback to a user during injection events, which are set out in more detail below.

SUMMARY

An object of the present disclosure is to provide a subassembly for a medicament delivery device which solves, or at least mitigates problems of the prior art.

According to a first aspect of the present disclosure, there is provided a subassembly of a medicament delivery device, the sub-assembly comprising: a housing extending along a longitudinal axis between a distal end and a proximal end, where the distal end points away from a medicament delivery site during use of the medicament delivery device; a rear subassembly arranged with at least a portion radially inside the housing, the rear subassembly is linearly movable along the longitudinal axis with respect to the housing, the rear subassembly comprising a distal-most end plate extending outside the housing, and at least one proximally extending, and radially flexible arm attached to the end plate, the at least one flexible arm comprising a radially outwards extending protrusion, a plunger rod arranged in the housing, the plunger rod comprising a distal portion arranged closer to the longitudinal axis than the flexible arm, the plunger rod being spring loaded by a plunger rod spring, a rigid deformable sheet material arranged to cover at least part of an outer surface of the housing, a distal end of the deformable sheet material being attached to the end plate of the rear subassembly and a proximal end of the deformable sheet material being attached to the housing, wherein, in a first state of the sub-assembly, the distal portion of the plunger rod is arranged to prevent the at least one flexible arm from flexing radially inwards, and the protrusion of the at least one flexible arm abuts against a proximally facing surface fixed in relation to the rear subassembly to prevent the rear subassembly from moving distally with respect to the housing, in the first state of the subassembly the rigid deformable sheet material is in a first shape, in a second state of the subassembly, the distal portion of the plunger rod is proximally arranged with respect to the at least one flexible arm of the rear subassembly, wherein the at least one flexible arm is allowed to flex radially inwards with respect to the proximally facing surface to thereby release the rear subassembly to move distally with respect to the housing, whereby the end plate moves distally away from the housing which alters the shape of the rigid deformable sheet material to a second shape.

It should be noted that the rigid deformable sheet material is sufficiently rigid and/or stiff to sustain a given shape.

Embodiments of the present disclosure advantageously provides for tactile feedback to the user that indicates delivery of a medicament. The tactile feedback is provided by that the rigid deformable sheet material deforms in a way that changes its shape in such a way that a user can feel the altered shape. Thus, as long as the subassembly is in its first state, with the rear subassembly being prevented from moving linearly in the distal direction, the deformable sheet material remains in the first shape, or in its first shape. Once the plunger rod moves, preferably due to the medicament delivery device is activated to perform an injection event, the plunger rod a proximally a distance sufficient for the flexible arm to release the rear subassembly. When the rear subassembly moves, the distance between distal and the proximal ends of the deformable sheet material will be altered which causes the shape of the deformable sheet material to change. This change or alteration in shape, or equally a deformation of the deformable sheet material, can be physically sensed by a user which thereby receives tactile feedback that the medicament delivery device has been activated.

The deformable sheet material may be reversible deformable. That is, the deformable sheet material may be deformed between the different deformation states or shapes caused be the motion of the rear subassembly.

The deformation from of the deformable sheet material is sufficient for a user to sense by touch, and detect by visual inspection, the difference between the deformation states or shapes caused be the motion of the rear subassembly. That is, the deformation is not just an infinitesimal change in shape.

A change in shape may herein be any type of change that preferably cause a noticeable change in a cross-section of the deformable sheet material.

A sheet is herein interpreted as a piece of material which thickness is substantially smaller than the other dimensions of the piece of material.

In the present disclosure, when the term “distal direction” is used, this refers to the direction pointing away from the dose delivery site during use of the medicament delivery device. When the term “distal part/end” is used, this refers to the part/end of the delivery device, or the parts/ends of the components thereof, which under use of the medicament delivery device is/are located furthest away from the dose delivery site. Correspondingly, when the term “proximal direction” is used, this refers to the direction pointing towards the dose delivery site during use of the medicament delivery device. When the term “proximal part/end” is used, this refers to the part/end of the delivery device, or the parts/ends of the members thereof, which under use of the medicament delivery device is/are located closest to the dose delivery site.

Further, the term “longitudinal”, “longitudinally”, “axially” or “axial” refer to a direction extending from the proximal end to the distal end, typically along the device or components thereof in the direction of the longest extension of the device and/or component.

Similarly, the terms “transverse”, “transversal” and “transversally” refer to a direction generally perpendicular to the longitudinal direction.

Further, the terms “circumference”, “circumferential”, “circumferentially” refer to a circumference or a circumferential direction 301 relative to an axis 102, typically a central axis extending in the direction of the longest extension of the device and/or component. Similarly, “radial” or “radially” refer to a direction 302 extending radially relative to the axis, and “rotation”, “rotational” and “rotationally” refer to rotation relative to the axis.

According to one embodiment, the rigid deformable sheet material may comprise a metal material. Preferably, the deformable sheet material is made from a metal. Advantageously, metals can be made into a sheet without braking. Furthermore, a metal is hard enough so that the change in shape is maintained so that the user can sense, by touch, the change in shape.

According to one embodiment, the rigid deformable sheet material may comprise a predefined structure that is configured to controllably deform. The sheet material may for example comprise grooves, trenches, or structurally weakening patterns along which the rigid deformable sheet material naturally deform.

According to one embodiment, the second shape of the rigid deformable sheet material is substantially cylindrical. Thus, the rigid deformable sheet material may take the shape of a flat or straight cylinder as the second shape. The outer surface of the rigid deformable sheet material is then curved and preferably relatively smooth which advantageously provides one shape that is easily sensed and identified by a user.

According to one embodiment, the first shape of the rigid deformable sheet material may comprise ridges and valleys. Although the general shape of the rigid deformable sheet material is cylindrical, the curved outer surface provided in the second shape may here instead constitute sensible ridges and valleys. In other words, in the second shape, the distance of the outer surface relative to the axis undulates in both the circumferential and longitudinal directions.

According to one embodiment, the outer surface of the rigid deformable sheet material in the second shape may be relatively even compared to the outer surface in the first shape of the rigid deformable sheet material.

According to one embodiment, the rigid deformable sheet material may be longitudinally stretched in the second shape compared to in the first shape. Thus, irregularities in the first shape of the rigid deformable sheet material are straighten in the second of the shape rigid deformable sheet material, thereby providing a detectable difference in shape by the sense of touch.

According to one embodiment, the protrusion of the at least one flexible arm comprises an inclined distally facing surface arranged to slide against the fixed proximally facing surface to cause the flexible arm to flex radially inwards when the distal portion of the plunger rod has moved proximally away from the at least one flexible arm. The inclined surface advantageously simplifies for the flexible arm to move inwards.

According to one embodiment, the subassembly may comprise a rear link assembly arranged in and fixedly attached to the housing at the distal end of the housing, the rear link assembly comprising the fixed proximal surface that prevents the rear subassembly from moving distally in the first state of the subassembly. The fixed proximal surface advantageously prevents too early deformation of the rigid deformable sheet material. According to one embodiment, the radially extending protrusion of the at least one flexible arm may be a first radially extending protrusion, the at least one flexible arm comprising a second radially extending protrusion arranged distally with respect to the first radially extending protrusion.

According to one embodiment, the rear link assembly may comprise a second proximally facing surface distally arranged with respect to the fixed proximally facing surface that prevents the rear subassembly from moving distally in the first state of the subassembly, wherein the second radially extending protrusion abuts against the second proximally facing surface to limit the distal motion of the rear subassembly in the second state of the subassembly. Thereby, the rear subassembly is prevented from being pushed out from and removed from the subassembly.

According to one embodiment, the first shape of the rigid deformable sheet material is indicative of a state prior injection and the second shape of the rigid deformable sheet material indicates an end of injection. Thereby, clear and distinct indications are provided to a user.

According to one embodiment, the rear subassembly may comprise two parallel flexible arms. Thereby a more stable rear subassembly with more reliable release to more in the distal direction is provided.

There is further provided a medicament delivery device comprising the subassembly of any of the herein disclosed embodiments.

Generally, all terms used in the claims are to be interpreted according to their ordinary meaning in the technical field, unless explicitly defined otherwise herein. All references to "a/an/the member, apparatus, component, means, etc.” are to be interpreted openly as referring to at least one instance of the member, apparatus, component, means, etc., unless explicitly stated otherwise. BRIEF DESCRIPTION OF THE DRAWINGS

The specific embodiments of the inventive concept will now be described, by way of example, with reference to the accompanying drawings, in which:

Fig. 1 is a perspective view of an autoinjector according to embodiments of the present disclosure;

Fig. 2 is an exploded view of a subassembly according to embodiments of the present disclosure;

Fig. 3 is a perspective view of a re subassembly according to embodiments of the present disclosure;

Fig. 4 is a perspective view of a rear link assembly according to embodiments of the present disclosure;

Fig. 5A is a perspective view of a rigid deformable sheet material according to embodiments of the present disclosure;

Fig. 5B is a perspective view of a rigid deformable sheet material according to embodiments of the present disclosure;

Fig. 6A is a perspective view of a plunger rod according to embodiments of the present disclosure;

Fig. 6B is a perspective view of a plunger rod according to embodiments of the present disclosure;

Fig. 7A is a perspective view of a rotator according to embodiments of the present disclosure;

Fig. 7B is a perspective view of a rotator according to embodiments of the present disclosure;

Fig. 8A is a cross section of a subassembly before use according to embodiments of the present disclosure; Fig. 8B is a perspective view of a subassembly before use according to embodiments of the present disclosure;

Fig. 9A is a cross section of a subassembly in a triggered state according to embodiments of the present disclosure;

Fig. 9B is a perspective view of a subassembly in a triggered state according to embodiments of the present disclosure;

Fig. 10A is a cross section of a subassembly after use according to embodiments of the present disclosure; and

Fig. 10B is a perspective view of a subassembly after use according to embodiments of the present disclosure.

DETAILED DESCRIPTION

The inventive concept will now be described more fully hereinafter with reference to the accompanying drawings, in which exemplifying embodiments are shown. The inventive concept may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided by way of example so that this disclosure will be thorough and complete, and will fully convey the scope of the inventive concept to those skilled in the art. Like numbers refer to like members throughout the description.

Fig 1 shows an example of a medicament delivery device 1 such as an autoinjector according to embodiments of the present disclosure. The medicament delivery device 1 is configured to expel medicament from a medicament container via a medicament delivery member such as a needle, to a user at a dose delivery site. The medicament delivery device 1 extends from a proximal end la to a distal end lb relative to the axis 102.

The medicament delivery device 1 comprises a housing 3 with a window 4. The housing 3 has a proximal end 3a and a distal end 3b. A needle shield 6 configured to cover a needle extends out from the proximal end 3a of the housing 3.

A deformable sheet material 5 is arranged to cover at least part of an outer surface of the housing 3.

The medicament delivery device 1 comprises a subassembly 2 which will now be described in more detail with reference to subsequent drawings.

An exploded view of the medicament delivery device 1 and the subassembly 2 according to one embodiment is shown in fig. 2.

The medicament delivery device 1 comprises the housing 2, the deformable sheet material 5, the needle shield 6, a spring 7 arranged to apply a spring force on the needle shield 6 in the proximal direction, a rotator 8, a plunger rod 9, a plunger rod spring 11, a rear link assembly 13, and a rear subassembly 15.

The rotator 8 arranged in the housing 3 and is rotatable about the longitudinal axis 102 with respect to the housing 3. The rotator 8 is generally arranged to provide lock-out and activation functionalities for the device 1.

The plunger rod 9 is arranged radially inside the housing 3 and is spring biased by the plunger rod spring 11 arranged inside the hollow plunger rod 9. The plunger rod 9 is adapted to be pushed by the plunger rod spring 11 onto a medicament container to force expulsion of a medicament out from the medicament container via a needle.

The subassembly 2 comprises housing 3, the rear subassembly 15, the plunger rod 13, the rear subassembly 15, the rigid deformable sheet material 5, optionally the rear link assembly 13, and optionally the needle shield 6. The components of the subassembly 2 will now be described in more detail.

Fig. 3 is a perspective view of the rear subassembly 15. The rear subassembly 15 is arranged at the distal end lb of the medicament delivery device 1 and is arranged with at least part of it inside the housing 3. The rear subassembly 15 comprises a distal-most end plate 17 and at least one proximally extending, and radially flexible arm 19 attached to the end plate 17. In this embodiment, the rear subassembly 15 comprises two parallel flexible arms 19 extending from a proximally facing surface 21 of the distal end plate 17.

The flexible arms 19 comprises radially outwards extending protrusion 23 each comprises a distally facing inclined surface 24 inclined with respect to the longitudinal axis 102. The protrusions 23 are each a first protrusion of the flexible arms 19 and are arranged at the proximal end 19a being a free end of the flexible arms 19. The distal ends 19b of the straight flexible arms are fixed ends that are attached at the proximally facing surface 21 of the end plate 17.

Distally located with respect to the first protrusions 23 a set of second radially extending protrusions 25 are located. The second protrusions 25 extend in parallel with the first protrusions 23 on the respective flexible arm 19. Furthermore, the second protrusions 25 comprise distally facing surfaces 22 that are generally orthogonal to the longitudinal axis 102.

Fig. 4 is a schematic view of a rear link assembly 13. The rear link assembly 13 comprises a through-hole 27 in which the flexible arms 19 of the rear subassembly 15 are arranged and the proximally facing surface 21 of the distal end plate 17 is supported on the distally facing surface 29 of the rear link assembly 13. Moreover, the rear link assembly 13 comprises flexible arms 26 with protrusions that engage with the plunger rod before activation of the device 1.

The rear link assembly 13 comprises internal proximally facing surfaces that engage with the protrusions 23 and 25 of the rear subassembly 15 as will be described in more detail with reference to subsequent drawings.

Fig. 5A is a perspective view of a rigid deformable sheet 5 or film formed as a tube. The deformable sheet 5 may comprise or be made of a metal such as aluminium. The deformable sheet 5 is generally tubular and is preconditioned such that is deforms controllable to the here shown crinkled or somewhat longitudinally compressed shape. Herein termed the first shape where the rigid deformable sheet 5 comprises ridges 31 and valleys 33. To controllable deform and form the ridges 31 and valleys 33 the rigid deformable sheet material 5 comprises a predefined structure that is configured to controllably deform accordingly.

Fig. 5B is another perspective view of a rigid deformable sheet 5. The housing 3 of the subassembly 2 fits inside the tubular deformable sheet 5 in the through-hole 35 that run longitudinally along the rigid deformable sheet 5 formed as a tube.

Fig. 6A is a perspective view of a plunger rod 9 comprising a proximal end 9a and a distal end 9b. The plunger rod is cylindrical and has an open end 10 for fitting of a plunger rod spring 11. The proximal end 9a is configured to cause expulsion of medicament from a medicament container under the spring force from the plunger rod spring. A cavity or hole 37 is arranged to receive the flexible arms 26 of the rear link assembly that holds the plunger rod 9 in place before an injection event.

Fig. 6B is another perspective view of the plunger rod 9 seen from the open end 10. The proximal end 9a includes a plate 39 on which the plunger rod spring 11 abuts.

Fig. 7A is a perspective view of the rotator 8. The rotator 8 comprises an inclined surface 43 formed in a slot 45 on the outer face of the rotator 8. The inclined surface 45 faces proximally and is adapted to receive a protrusion of the needle shield as the needle shield is moving distally. This causes the rotator 8 to rotate about the longitudinal axis.

Fig. 7B is another perspective view of the rotator 8 where the inner side of the rotator 8 can be seen. A slot 47 of the rotator is aligned with the flexible arms 26 of the rear link assembly only after the rotator 8 has been rotated. This allows the flexible arms 26 to flex radially outwards into the slots to thereby release the plunger rod 9. Fig. 7A is a cross-section of the subassembly 2 and fig. 7B is a perspective view of the medicament delivery device in before use. The rear subassembly is arranged with at least a portion radially inside the housing. That is, the flexible arms 19 extend inside the housing 3 but the end plat 17 is outside the housing 3.

The tubular rigid deformable sheet 5 is arranged to cover at least part of an outer surface of the housing 3. That is, the housing 3 is partly arranged inside the tubular sheet 5. A distal end 5b of the deformable sheet material 5 is attached to the end plate 17 of the rear subassembly and a proximal end 5a of the deformable sheet material 5 is attached to the housing 3. The attachment between the deformable sheet material 5 and the housing 3 and the end plate 17 may be made by various means such as welding, gluing, or fixing in trenches or grooves of the housing 3 and the end plate 17.

The plunger rod 9 is arranged closer to the longitudinal axis 102 than the flexible arms 19. The plunger rod 9 is further spring loaded by the plunger rod spring 11.

In this first state of the sub-assembly, the distal portion 9b of the plunger rod 9 is arranged to prevent the at least one flexible arm 19 from flexing radially inwards. Thus, a part of the rigid plunger rod 9 lies inside the flexible arms 19 so that the flexible arms 19 cannot flex inwards. Furthermore, the protrusions 23 of the at least one flexible arm 19 abuts against a proximally facing surface 41 fixed in relation to the rear subassembly 15. This prevents the rear subassembly 15 from moving distally with respect to the housing 3. In this embodiment, it is the inclined surfaces 24 that abut against the proximally facing surface 41. In the first state of the subassembly the rigid deformable sheet material 5 has a first shape, here being a crinkled shape with ridges 33 and valleys 35. The rigid deformable sheet material 5 may be longitudinally compressed to form the first shape. The first shape of the rigid deformable sheet material 5 is indicative of a state prior injection. The fixed proximal surface 41 that prevents the rear subassembly 13 from moving distally in the first state of the subassembly may be part of rear link assembly 13 arranged in and fixedly attached to the housing 3 at the distal end of the housing.

Furthermore, the protrusion of the flexible arm 26 of the rear-link assembly 13 is arranged in the hole 37 of the plunger rod. The orientation of the rotator 8 does not allow the flexible arm 26 to flex outwards so that the plunger rod 9 can be released.

Fig 9A is a cross-section of the subassembly once the plunger rod 9 is released. In this triggered state, the needle shield 6 a needle shield 6 has moved inside the housing 3 in an axial direction from an extended position, see fig. 8A, to a retracted position, see also fig. 9B, in which a needle may be exposed at the proximal end. During this motion, a radially inwards extending protrusions of the needle shield slide against the inclined surface 43 of the rotator 8 to cause a rotation of the rotator with respect to the plunger rod 9. In this way the inner slot 47 of the rotator are rotated into alignment with the flexible locking arms 26 of the rear link assembly 13 that flex into the slot whereby the plunger rod 9 is released and is pushed proximally by the plunger rod spring 11.

When the plunger rod 9 is released, the distal end 9b moves past the flexible arms 19 of the rear subassembly 19. The at least one flexible arm 19 is thus allowed to flex radially inwards with respect to the proximally facing surface 41 to thereby release the rear subassembly to move distally with respect to the housing 3. The inclined distally facing surface 24 of the protrusions of the flexible arms 19 slide against the fixed proximally facing surface 41 to facilitate for the flexible arms 19 to flex radially inwards.

The motion of the rear subassembly 15 causes a stretching of the rigid deformation sheet material 5.

Fig. 10A is a cross-section of the subassembly after use and fig 10B is a perspective view of the device 1 after use. The motion of the rear subassembly is linearly along the longitudinal axis with respect to the housing finally results in a second state of the subassembly 2. The needle shield 6 has returned to an extended state.

The second protrusions 25 of the flexible arms 19 abut against a second proximally facing surface 49 distally arranged with respect to the fixed proximally facing surface 41. This engagement to limit the distal motion of the rear subassembly 15 in the second state. That is the rear subassembly 15 cannot move further distally once the second proximally facing surface 49 abuts against the distally facing surface 22 of the protrusions 25.

The rear assembly 15 has moved further distally by the force apply by the plunger rod spring 11 whereby the end plate moves distally away from the housing which alters the shape of the rigid deformable sheet material to a second shape. This causes further stretch of the rigid deformation sheet material 5 since the ends 5b and 5a have moved further apart. Thus, the rigid deformable sheet material 5 is longitudinally stretched in the second shape compared to in the first shape.

The rigid deformation sheet material 5 has transformed to a second shape that is different from the first shape and indicates an end of injection.

The second shape of the rigid deformable sheet material is substantially cylindrical. The outer surface of the rigid deformable sheet material 5 in the second shape is relatively even compared to the outer surface in the first shape of the rigid deformable sheet material.

A medicament delivery device (such as an autoinjector) may generally include various other components. For example, a sensor unit which may recognize injection events, such as the autoinjector inserted into an attachment portion of e.g., a pad, injection started, and injection ends, a memory unit which is configured to store the recorded data during the injection, a connectivity unit configured to transmit the stored data to a smart device or the network directly, a processing unit configured to control the entire system and processes the data before transmitting it, and/or user interface units that are configured to provide feedback to the patient, such as status LEDs, haptic, and/or audio feedback.

When the medicament delivery device is placed into the attachment portion, the sensors inside of the support pad are configured to recognize the event and give feedback to the patient via haptic/visual or audio elements.

When the injection finishes, the sensors are configured to recognize the event and give feedback to the patient again. Further, the collected data is stored in the memory unit and maybe transmitted to the smart device/network via the connectivity unit after the injection event finishes.

The sensor can be one of or the combination of the following: a mechanical switch, a Hall-effect sensor, an accelerometer.

The mechanical switch, hall-effect sensor, or accelerometer can be used for detection of the insertion of the auto-injector into an injection port.

The accelerometer can be used for detecting injection events.

Possible wireless communication methods include Bluetooth and Cellular Networks.

Bluetooth connectivity requires a smart device to transmit the stored data to the network and it requires a pairing action between the support pad and the smart device before being able to use the supporting pad. But it’s a cheaper alternative and it requires less space on PCB.

The cellular network does not require any pairing process, it can be used as a plug-n-play device, no prior setup is needed, but it’s more expensive and it requires more space on PCB.

Depending on the requirements of the product any of those two technologies can be used.

Such processing units may comprise a logic circuit or control unit including a microprocessor, microcontroller, programmable digital signal processor or another programmable device. The processing circuitry may also, or instead, each include an application specific integrated circuit, a programmable gate array or programmable array logic, a programmable logic device, or a digital signal processor. Where the processing circuitry includes a programmable device such as the microprocessor, microcontroller or programmable digital signal processor mentioned above, the processor may further include computer executable code that controls operation of the programmable device.

The delivery devices described herein can be used for the treatment and/or prophylaxis of one or more of many different types of disorders.

Exemplary disorders include, but are not limited to: rheumatoid arthritis, inflammatory bowel diseases (e.g. Crohn’s disease and ulcerative colitis), hypercholesterolaemia and/or dyslipidemia, cardiovascular disease, diabetes (e.g. type 1 or 2 diabetes), psoriasis, psoriatic arthritis, spondyloarthritis, hidradenitis suppurativa, Sjogren's syndrome, migraine, cluster headache, multiple sclerosis, neuromyelitis optica spectrum disorder, anaemia, thalassemia, paroxysmal nocturnal hemoglobinuria, hemolytic anaemia, hereditary angioedema, systemic lupus erythematosus, lupus nephritis, myasthenia gravis, Behcet's disease, hemophagocytic lymphohistiocytosis, atopic dermatitis, retinal diseases (e.g., age-related macular degeneration, diabetic macular edema), uveitis, infectious diseases, bone diseases (e.g., osteoporosis, osteopenia), asthma, chronic obstructive pulmonary disease, thyroid eye disease, nasal polyps, transplant, acute hypoglycaemia, obesity, anaphylaxis, allergies, sickle cell disease, Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, systemic infusion reactions, immunoglobulin E (IgE)-mediated hypersensitivity reactions, cytokine release syndrome, immune deficiencies (e.g., primary immunodeficiency, chronic inflammatory demyelinating polyneuropathy), enzyme deficiencies (e.g., Pompe disease, Fabry disease, Gaucher disease), growth factor deficiencies, hormone deficiencies, coagulation disorders (e.g., hemophilia, von Willebrand disease, Factor V Leiden), and cancer. Exemplary types of drugs that could be included in the delivery devices described herein include, but are not limited to, small molecules, hormones, cytokines, blood products, enzymes, vaccines, anticoagulants, immunosuppressants, antibodies, antibody-drug conjugates, neutralizing antibodies, reversal agents, radioligand therapies, radioisotopes and/or nuclear medicines, diagnostic agents, bispecific antibodies, proteins, fusion proteins, peptibodies, polypeptides, pegylated proteins, protein fragments, nucleotides, protein analogues, protein variants, protein precursors, protein derivatives, chimeric antigen receptor T cell therapies, cell or gene therapies, oncolytic viruses, or immunotherapies.

Exemplary drugs that could be included in the delivery devices described herein include, but are not limited to, immuno-oncology or bio-oncology medications such as immune checkpoints, cytokines, chemokines, clusters of differentiation, interleukins, integrins, growth factors, coagulation factors, enzymes, enzyme inhibitors, retinoids, steroids, signaling proteins, pro- apoptotic proteins, anti-apoptotic proteins, T-cell receptors, B-cell receptors, or costimulatory proteins.

Exemplary drugs that could be included in the delivery devices described herein include, but are not limited to, those exhibiting a proposed mechanism of action, such as human epidermal growth factor receptor 2 (HER-2) receptor modulators, interleukin (IL) modulators, interferon (IFN) modulators, complement modulators, glucagon-like peptide-i (GLP-i) modulators, glucose-dependent insulinotropic polypeptide (GIP) modulators, cluster of differentiation 38 (CD38) modulators, cluster of differentiation 22 (CD22) modulators, Ci esterase modulators, bradykinin modulators, C-C chemokine receptor type 4 (CCR4) modulators, vascular endothelial growth factor (VEGF) modulators, B-cell activating factor (BAFF), P-selectin modulators, neonatal Fc receptor (FcRn) modulators, calcitonin gene-related peptide (CGRP) modulators, epidermal growth factor receptor (EGFR) modulators, cluster of differentiation 79B (CD79B) modulators, tumor- associated calcium signal transducer 2 (Trop-2) modulators, cluster of differentiation 52 (CD52) modulators, B-cell maturation antigen (BCMA) modulators, enzyme modulators, platelet-derived growth factor receptor A (PDGFRA) modulators, cluster of differentiation 319 (CD319 or SLAMF7) modulators, programmed cell death protein 1 and programmed death-ligand 1 (PD-1/PD-L1) inhibitors/modulators, B-lymphocyte antigen cluster of differentiation 19 (CD19) inhibitors, B-lymphocyte antigen cluster of differentiation 20 (CD20) modulators, cluster of differentiation 3 (CD3) modulators, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) modulators, T cell immunoreceptor with Ig and ITIM domains (TIGIT) modulators, V-domain Ig suppressor of T cell activation (VISTA) modulators, indoleamine 2,3-dioxygenase (IDO or INDO) modulators, poliovirus receptor-related immunoglobulin domain-containing protein (PVRIG) modulators, lymphocyte-activation gene 3 (LAG3; also known as cluster of differentiation 223 or CD223) antagonists, cluster of differentiation 276 (CD276 or B7-H3) antigen modulators, cluster of differentiation 47 (CD47) antagonists, cluster of differentiation 30 (CD30) modulators, cluster of differentiation 73 (CD73) modulators, cluster of differentiation 66 (CD66) modulators, cluster of differentiation W137 (CDW137) agonists, cluster of differentiation 158 (CD158) modulators, cluster of differentiation 27 (CD27) modulators, cluster of differentiation 58 (CD58) modulators, cluster of differentiation 80 (CD80) modulators, cluster of differentiation 33 (CD33) modulators, cluster of differentiation 159 (CD159 or NKG2) modulators, glucocorticoid-induced TNFR-related (GITR) protein modulators, Killer Ig- like receptor (KIR) modulators, growth arrest-specific protein 6 (GAS6)/AXL pathway modulators, A proliferation-inducing ligand (APRIL) receptor modulators, human leukocyte antigen (HLA) modulators, epidermal growth factor receptor (EGFR) modulators, B-lymphocyte cell adhesion molecule modulators, cluster of differentiation W123 (CDwi23) modulators, Erbb2 tyrosine kinase receptor modulators, endoglin modulators, mucin modulators, mesothelin modulators, hepatitis A virus cellular receptor 2 (HAVCR2) antagonists, cancer-testis antigen (CTA) modulators, tumor necrosis factor receptor superfamily, member 4 (TNFRSF4 or 0X40) modulators, adenosine receptor modulators, inducible T cell co-stimulator (ICOS) modulators, cluster of differentiation 40 (CD40) modulators, tumorinfiltrating lymphocytes (TIL) therapies, or T-cell receptor (TCR) therapies.

Exemplary drugs that could be included in the delivery devices described herein include, but are not limited to: etanercept, abatacept, adalimumab, evolocumab, exenatide, secukinumab, erenumab, galcanezumab, fremanezumab-vfrm, alirocumab, methotrexate (amethopterin), tocilizumab, interferon beta-ia, interferon beta-ib, peginterferon beta-ia, sumatriptan, darbepoetin alfa, belimumab, sarilumab, semaglutide, dupilumab, reslizumab, omalizumab, glucagon, epinephrine, naloxone, insulin, amylin, vedolizumab, eculizumab, ravulizumab, crizanlizumab-tmca, certolizumab pegol, satralizumab, denosumab, romosozumab, benralizumab, emicizumab, tildrakizumab, ocrelizumab, ofatumumab, natalizumab, mepolizumab, risankizumab-rzaa, ixekizumab, and immune globulins.

Exemplary drugs that could be included in the delivery devices described herein may also include, but are not limited to, oncology treatments such as ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, cemiplimab, rituximab, trastuzumab, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan-nxki, pertuzumab, transtuzumab-pertuzumab, alemtuzumab, belantamab mafodotin-blmf, bevacizumab, blinatumomab, brentuximab vedotin, cetuximab, daratumumab, elotuzumab, gemtuzumab ozogamicin, 90-Yttrium-ibritumomab tiuxetan, isatuximab, mogamulizumab, moxetumomab pasudotox, obinutuzumab, ofatumumab, olaratumab, panitumumab, polatuzumab vedotin, ramucirumab, sacituzumab govitecan, tafasitamab, or margetuximab.

Exemplary drugs that could be included in the delivery devices described herein include “generic” or biosimilar equivalents of any of the foregoing, and the foregoing molecular names should not be construed as limiting to the “innovator” or “branded” version of each, as in the non-limiting example of innovator medicament adalimumab and biosimilars such as adalimumab- afzb, adalimumab-atto, adalimumab-adbm, and adalimumab-adaz. Exemplary drugs that could be included in the delivery devices described herein also include, but are not limited to, those used for adjuvant or neoadjuvant chemotherapy, such as an alkylating agent, plant alkaloid, antitumor antibiotic, antimetabolite, or topoisomerase inhibitor, enzyme, retinoid, or corticosteroid. Exemplary chemotherapy drugs include, by way of example but not limitation, 5-fluorouracil, cisplatin, carboplatin, oxaliplatin, doxorubicin, daunorubicin, idarubicin, epirubicin, paclitaxel, docetaxel, cyclophosphamide, ifosfamide, azacitidine, decitabine, bendamustine, bleomycin, bortezomib, busulfan, cabazitaxel, carmustine, cladribine, cytarabine, dacarbazine, etoposide, fludarabine, gemcitabine, irinotecan, leucovorin, melphalan, methotrexate, pemetrexed, mitomycin, mitoxantrone, temsirolimus, topotecan, valrubicin, vincristine, vinblastine, or vinorelbine.

Exemplary drugs that could be included in the delivery devices described herein also include, but are not limited to, analgesics (e.g., acetaminophen), antipyretics, corticosteroids (e.g. hydrocortisone, dexamethasone, or methylprednisolone), antihistamines (e.g., diphenhydramine or famotidine), antiemetics (e.g., ondansetron), antibiotics, antiseptics, anticoagulants, fibrinolytics (e.g., recombinant tissue plasminogen activator [r-TPA]), antithrombolytics, or diluents such as sterile water for injection (SWFI), 0.9% Normal Saline, 0.45% normal saline, 5% dextrose in water, 5% dextrose in 0.45% normal saline, Lactated Ringer’s solution, Heparin Lock Flush solution, 100 U/mL Heparin Lock Flush Solution, or 5000 U/mL Heparin Lock Flush Solution.

Pharmaceutical formulations including, but not limited to, any drug described herein are also contemplated for use in the delivery devices described herein, for example pharmaceutical formulations comprising a drug as listed herein (or a pharmaceutically acceptable salt of the drug) and a pharmaceutically acceptable carrier. Such formulations may include one or more other active ingredients (e.g., as a combination of one or more active drugs), or may be the only active ingredient present, and may also include separately administered or co-formulated dispersion enhancers (e.g. an animal-derived, human-derived, or recombinant hyaluronidase enzyme), concentration modifiers or enhancers, stabilizers, buffers, or other excipients.

Exemplary drugs that could be included in the delivery devices described herein include, but are not limited to, a multi-medication treatment regimen such as AC, Dose-Dense AC, TCH, GT, EC, TAC, TC, TCHP, CMF, FOLFOX, mF0LF0X6, mFOLFOXy, FOLFCIS, CapeOx, FLOT, DCF, FOLFIRI, FOLFIRINOX, FOLFOXIRI, IROX, CHOP, R-CHOP, RCHOP-21, Mini- CHOP, Maxi-CHOP, VR-CAP, Dose-Dense CHOP, EPOCH, Dose-Adjusted EPOCH, R-EPOCH, CODOX-M, IVAC, HyperCVAD, R-HyperCVAD, SC- EPOCH-RR, DHAP, ESHAP, GDP, ICE, MINE, CEPP, CDOP, GemOx, CEOP, CEPP, CHOEP, CHP, GCVP, DHAX, CALGB 8811, HIDAC, MOpAD, 7 + 3, 5 +2, 7 + 4, MEC, CVP, RBAC500, DHA-Cis, DHA-Ca, DHA-Ox, RCVP, RCEPP, RCEOP, CMV, DDMVAC, GemFLP, ITP, VIDE, VDC, VAI, VDC-IE, MAP, PCV, FCR, FR, PCR, HDMP, OFAR, EMA/CO, EMA/EP, EP/EMA, TP/TE, BEP, TIP, VIP, TPEx, ABVD, BEACOPP, AVD, Mini-BEAM, IGEV, C- MOPP, GCD, GEMOX, CAV, DT-PACE, VTD-PACE, DCEP, ATG, VAC, VelP, OFF, GTX, CAV, AD, MAID, AIM, VAC-IE, ADOC, or PE.

The inventive concept has mainly been described above with reference to a few examples. However, as is readily appreciated by a person skilled in the art, other embodiments than the ones disclosed above are equally possible within the scope of the inventive concept, as defined by the appended claims.

Claims

1. A sub-assembly (2) of a medicament delivery device (1), the subassembly comprising: a housing (3) extending along a longitudinal axis (102) between a distal end (3a) and a proximal end (3b), where the distal end points away from a medicament delivery site during use of the medicament delivery device; a rear subassembly (15) arranged with at least a portion radially inside the housing, the rear subassembly is linearly movable along the longitudinal axis with respect to the housing, the rear subassembly comprising a distal- most end plate (17) extending outside the housing, and at least one proximally extending, and radially flexible arm (19) attached to the end plate, the at least one flexible arm comprising a radially outwards extending protrusion (23), a plunger rod (9) arranged in the housing, the plunger rod comprising a distal portion arranged closer to the longitudinal axis than the flexible arm, the plunger rod being spring loaded by a plunger rod spring, a rigid deformable sheet material (5) arranged to cover at least part of an outer surface of the housing, a distal end (5b) of the deformable sheet material being attached to the end plate of the rear subassembly and a proximal end (5a) of the deformable sheet material being attached to the housing, wherein, in a first state of the sub-assembly, the distal portion of the plunger rod is arranged to prevent the at least one flexible arm from flexing radially inwards, and the protrusion of the at least one flexible arm abuts against a proximally facing surface (41) fixed in relation to the rear subassembly to prevent the rear subassembly from moving distally with respect to the housing, in the first state of the subassembly the rigid deformable sheet material has a first shape, in a second state of the sub-assembly, the distal portion of the plunger rod is proximally arranged with respect to the at least one flexible arm of the rear subassembly, wherein the at least one flexible arm is allowed to flex radially inwards with respect to the proximally facing surface to thereby release the rear subassembly to move distally with respect to the housing, whereby the end plate moves distally away from the housing which alters the shape of the rigid deformable sheet material to a second shape.

2. The subassembly of the previous claim, wherein the rigid deformable sheet material comprises a predefined structure that is configured to controllably deform.

3. The subassembly of any one of the preceding claims, wherein the second shape of the rigid deformable sheet material is substantially cylindrical.

4. The subassembly of any one of the preceding claims, wherein the rigid deformable sheet material comprises ridges and valleys in the first shape.

5. The subassembly of any one of the preceding claims, wherein the outer surface of the rigid deformable sheet material in the second shape is relatively even compared to the outer surface in the first shape of the rigid deformable sheet material.

6. The subassembly of any one of the preceding claims, wherein the rigid deformable sheet material is longitudinally stretched in the second shape compared to in the first shape.

7. The subassembly of any one of the preceding claims, wherein the protrusion of the at least one flexible arm comprises an inclined distally facing surface (24) arranged to slide against the fixed proximally facing surface to cause the flexible arm to flex radially inwards when the distal portion of the plunger rod has moved proximally away from the at least one flexible arm.

8. The subassembly of any one of the preceding claims, comprising a rear link assembly (13) arranged in and fixedly attached to the housing at the distal end of the housing, the rear link assembly comprising the fixed proximal surface that prevents the rear subassembly from moving distally in the first state of the subassembly.

9. The subassembly of any one of the preceding claims, wherein the radially extending protrusion of the at least one flexible arm is a first radially extending protrusion (19), the at least one flexible arm comprising a second radially extending protrusion (25) arranged distally with respect to the first radially extending protrusion.

10. The subassembly of claims 8 and 9, wherein the rear link assembly comprises a second proximally facing surface (49) distally arranged with respect to the fixed proximally facing surface that prevents the rear subassembly from moving distally in the first state of the subassembly, wherein the second radially extending protrusion abuts against the second proximally facing surface to limit the distal motion of the rear subassembly in the second state of the subassembly.

11. The subassembly of any one of the preceding claims, wherein the first shape of the rigid deformable sheet material is indicative of a state prior injection and the second shape of the rigid deformable sheet material indicates an end of injection.

12. The subassembly of any one of the preceding claims, the rear subassembly comprising two parallel flexible arms.

13. The subassembly of claim 1, comprising: a needle shield (6) configured to surround a needle at a proximal end of the medicament delivery device, the needle shield being movable inside the housing in an axial direction of the housing between a retracted position in which the needle is exposed at the proximal end of the needle shield, and an extended position in which the needle is covered by the needle shield, a rotator (8) arranged inside the needle shield, wherein the needle shield comprises radially inwards extending protrusions and the rotator comprises surfaces (43) that are inclined with respect to the longitudinal axis, when the needle shield moves between the extended position and the retracted position, the radially inwards extending protrusions of the needle shield slide against the inclined surface of the rotator to cause a rotation of the rotator with respect to the plunger rod, so that slots of the rotator are rotated into alignment with flexible locking arms (26) of the rear link assembly that flex into the through-holes to release the plunger rod.

14. A medicament delivery device comprising the sub-assembly according to any one of the preceding claims.