WO2025237664A1

WO2025237664A1 - Medicament delivery device having a plunger rod release mechanism

Info

Publication number: WO2025237664A1
Application number: PCT/EP2025/061616
Authority: WO
Inventors: Meng-Jhen CHIOU; Daniel Scott
Original assignee: SHL Medical AG
Current assignee: SHL Medical AG
Priority date: 2024-05-13
Filing date: 2025-04-29
Publication date: 2025-11-20
Anticipated expiration: 2026-11-13

Abstract

Medicament delivery device comprising: a housing a plunger rod, and a drive spring, a needle cover, and a needle cover spring, an activator, fixed relative to the housing, wherein the outer surface of plunger rod comprises a proximal, an intermediate and a distal recess, wherein the activator comprises at least one proximal and at least one distal arm both flexible radially, and wherein the medicament delivery device is such that: in an initial configuration, the distal arm is constrained in the intermediate recess by the needle cover, in a second configuration, the proximal arm is constrained in the proximal recess by the needle cover, allowing only a limited movement of the plunger rod for priming, in a third configuration, the proximal arm is no longer constrained, and the distal arm is constrained in the distal recess, allowing the rest of the movement of the plunger rod.

Description

Medicament delivery device having a plunger rod release mechanism

TECHNICAL FIELD

The present invention relates to a medicament delivery device equipped with a plunger rod release mechanism.

BACKGROUND

A medicament delivery device, in particular an autoinjector, comprises a housing. The housing is adapted to hold a medicament container, such as a syringe. The syringe may be a pre-filled syringe and have a needle as a medicament delivery member arranged at a proximal end. When the autoinjector and/or the syringe are assembled, a protective needle sheath may be removably coupled to the needle. The protective needle sheath may be made of a flexible shell (for instance composed of rubber) and/or a rigid shell (for instance composed of plastic). A plunger, also called stopper, is arranged for sealing the syringe distally and for expelling a medicament contained in the syringe through the needle. In other exemplary embodiments, the medicament container maybe a cartridge which includes the medicament and engages a removable needle (e.g., by threads, snaps, friction, etc.).

A cap is removably disposed at a proximal end of the housing. The cap may include an element (e.g., a barb, a hook, a narrowed section, etc.) arranged to engage the protective needle sheath, the housing and/or a medicament delivery member cover, also referred to as needle cover, telescoped within the housing. The cap may comprise grip features for facilitating removal of the cap (e.g., by twisting and/or pulling the cap relative to the housing).

A needle cover spring is arranged to bias the needle cover in a proximal direction relative to the housing, before injection. The function of the needle cover before injection is to keep the end user from seeing the needle in case they have needle aversion. The needle cover spring needs to be compressed at the beginning of injection in order to retract the needle cover inside the housing and uncover the needle, thereby activating the device.

A pre-loaded drive spring is arranged within the housing. A plunger rod is used to forward force from the drive spring to the plunger. In an exemplary embodiment, the plunger rod is hollow and the drive spring is arranged within the plunger rod. In another exemplary embodiment, the plunger rod is solid and the drive spring engages a distal end of the plunger rod. When the pre-loaded drive spring is released, the drive spring biases the plunger rod in the proximal direction relative to the housing, releasing the plunger rod.

It is useful to equip such a medicament delivery device with a plunger rod release mechanism arranged for preventing release of the plunger rod prior to retraction of the medicament delivery member cover relative to the housing and for releasing the plunger rod only once the medicament delivery member cover is sufficiently retracted.

In addition, it is useful to equip such a medicament delivery device with a needle cover lockout mechanism to prevent retraction of the needle cover relative to the housing after injection, thereby covering the needle and avoiding injuries after injection.

SUMMARY

The present disclosure relates to a medicament delivery device integrating a plunger rod release mechanism, and optionally a needle cover lockout mechanism as well.

The invention is specified by the independent claim. Preferred embodiments are defined in the dependent claims. In the following description, although numerous features may be designated as optional, it is nevertheless acknowledged that all features comprised in the independent claims are not to be read as optional.

The invention refers to a medicament delivery device extending generally along a longitudinal axis, and having a proximal end configured to point towards a dose delivery site and a distal end configured to point away from the dose delivery site, the medicament delivery device comprising:

- a housing

- a plunger rod arranged to move axially in a proximal direction relative to the housing to urge a plunger of a medicament container to expel medicament from the medicament container, and a drive spring arranged to bias the plunger rod in the proximal direction,

- a needle cover arranged to move axially relative to the housing, and a needle cover spring arranged to bias the needle cover in the proximal direction,

- an activator, fixed relative to the housing, wherein the outer surface of plunger rod comprises a proximal recess, an intermediate recess and a distal recess, wherein the activator comprises at least one proximal arm and at least one distal arm both flexible radially, and wherein the medicament delivery device is such that:

- in an initial configuration, the distal arm is radially constrained in the intermediate recess by the needle cover to block the proximal movement of the plunger rod, and the proximal arm is in the proximal recess,

- in a second configuration, the distal arm is no longer radially constrained, and the proximal arm is radially constrained in the proximal recess by the needle cover, allowing only a limited amount of the proximal movement of the plunger rod to prime the medicament delivery device, in a third configuration, the proximal arm is no longer radially constrained, and the distal arm is radially constrained in the distal recess by the needle cover, allowing the rest of the proximal movement of the plunger rod to expel the medicament.

Thus, the medicament delivery device is equipped with a plunger rod release mechanism arranged for preventing release of the plunger rod prior to retraction of the medicament delivery member cover relative to the housing and for releasing the plunger rod only once the medicament delivery member cover is sufficiently retracted. The plunger rod release mechanism comprises the proximal arm and the distal arm of the activator, the proximal recess, the intermediate recess and the distal recess on the plunger rod, and the needle cover.

In an embodiment, the activator comprises at least one lockout tab with a circumferential offset relative to the at least one proximal arm and the at least one distal arm, a distal portion of the plunger rod comprises at least one radial protrusion, and in a lockout configuration of the medicament delivery device, the radial protrusion biases the lockout tab radially outwards and a proximally-facing surface of the lockout tab axially abuts a distally-facing surface of a distal portion of the needle cover.

Thus, the medicament delivery device is equipped with a needle cover lockout mechanism. The needle cover lockout mechanism comprises the lockout tab on the activator, and the radial protrusion on the distal portion of the plunger rod.

In an embodiment, the lockout tab is axially located between the at least one proximal arm and distal arm.

In an embodiment, the distal portion of the needle cover comprises at least one flexible arm that is flexible radially and axially aligned with the at least one lockout tab.

Thus, the needle cover lockout mechanism comprises the flexible arm on the distal portion of the needle cover.

In an embodiment, the circumferential offset between the at least one lockout tab and the at least one proximal arm and distal arm is 90°.

In an embodiment, the distal recess extends distally up to a distal end of the plunger rod.

In an embodiment, in a priming configuration of the medicament delivery device, the at least one proximal arm is radially constrained in the proximal recess by the needle cover and axially abuts against a distal end of the proximal recess.

In an embodiment, in the initial configuration, the at least one distal arm axially abuts against a distal end of the intermediate recess.

In an embodiment, the activator comprises two proximal arms and two distal arms.

In an embodiment, the circumferential offset in each pair of arms is i8o°.

In an embodiment, the activator comprises two lockout tabs, the distal portion of the plunger rod comprises two radial protrusions, and for each pair of lockout tabs and radial protrusions, the lockout tabs and radial protrusions are spaced apart circumferentially from each other.

In an embodiment, the circumferential offset of each pair of lockout tabs and radial protrusions is i8o°.

In an embodiment, the distal portion of the needle cover comprises two flexible arms spaced apart from each other.

In an embodiment, the circumferential offset of the flexible arms of the needle cover is i8o°.

In an embodiment, the plunger rod comprises a track comprising a succession of teeth, said track being circumferential spaced apart from the at least one proximal arm and distal arm, and the medicament delivery device comprises at least one hook configured to contact the succession of teeth during the proximal movement of the plunger rod to create a succession of audible signals.

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 members thereof, which during 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 during use of the medicament delivery device is/are located closest to the dose delivery site.

Further, the terms “longitudinal”, “longitudinally”, “axially” and “axial” refer to a direction extending from the proximal end to the distal end and along the device or components thereof, typically 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”, or “circumferentially” refer to a circumference or a circumferential direction relative to an axis, typically a longitudinal axis extending in the direction of the longest extension of the device and/or component. Similarly, “radial” or “radially” refer to a direction extending radially relative to the axis, and “rotation”, “rotational” and “rotationally” refer to rotation relative to the axis.

When a component is said to move proximally, distally, axially in a proximal direction, axially in a distal direction or equivalent terms, the movement is relative to the housing of the injection device, unless mentioned otherwise.

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 element, apparatus, member, component, means, etc. are to be interpreted openly as referring to at least one instance of the element, apparatus, member component, means, etc., unless explicitly stated otherwise. BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present disclosure will now be described by way of example only and with reference to the following accompanying drawings.

Fig. 1A, 1B and 1C show a medicament delivery device according to an example, respectively in an initial configuration, a primed configuration, and an injection start configuration.

Fig. 2A, 2B and 2C show the medicament delivery device respectively in the configurations of Fig. 1A, 1B and 1C, without a housing of the medicament delivery device.

Fig. 3A and 3B show an activator of the medicament delivery device.

Fig. 4 shows a plunger rod of the medicament delivery device.

Fig. 5A and 5B show a part of the medicament delivery device respectively in a configuration happening between an injection end configuration and a needle lockout configuration, and in the needle cover lockout configuration.

Fig. 6A, 6B, 6C, 6D and 6E show a longitudinal sectional view of a part of the medicament delivery device, respectively in the initial configuration, the primed configuration, the injection start configuration, the injection end configuration, and the needle cover lockout configuration.

Fig. 7 show the plunger rod of the medicament delivery device and a drug container, in the prime configuration.

DETAILED DESCRIPTION

The present invention can be employed for various medicament delivery devices. Thus, only the parts relevant for carrying out the disclosure will be described in detail.

In the figures, elements not essential for carrying out the invention have been omitted. In particular, not all figures show a complete outer housing, biasing members, a medicament container, cap, etc. in order not to render the depictions overly complicated and not to blur the scope of the disclosure.

In the following, the term engagement encompasses any kind of interaction between the named features such as abutment, clamping, locking etc.

Fig. 1A, 1B and 1C show a medicament delivery device, in particular an autoinjector, according to the invention. The medicament delivery device extends along a longitudinal axis L and comprises a housing io. Fig. 2A, 2B and 2C show the medicament delivery device without the housing io, for a better understanding.

The housing io is adapted to hold a medicament container 12, such as a syringe, visible for instance on Fig. 2A to 2C or across a window 101 of the housing 10 on Fig. 1A. The syringe may be a pre-filled syringe and have a needle (not represented on the figures) as a medicament delivery member arranged at a proximal end. When the autoinjector and/or the syringe are assembled, a protective needle sheath (not visible on the figures) may be removably coupled to the needle. The protective needle sheath may be made of a flexible shell (for instance composed of rubber) and/or a rigid shell (for instance composed of plastic). A plunger 14, also called stopper, is arranged for sealing the syringe distally and for expelling a medicament contained in the syringe through the needle. In other exemplary embodiments, the medicament container may be a cartridge which includes the medicament and engages a removable needle (e.g., by threads, snaps, friction, etc.).

A cap 16 is removably disposed at a proximal end of the housing 10. The cap 16 may include an element (e.g., a barb, a hook, a narrowed section, etc.) arranged to engage the protective needle sheath, the housing and/or a medicament delivery member cover, also referred to as needle cover 18, telescoped within the housing. The cap 16 may comprise grip features for facilitating removal of the cap (e.g., by twisting and/or pulling the cap relative to the housing). The cap is visible on Fig. 1A and 2 A, showing the medicament delivery device in an initial configuration, that is to say as given to a patient before use.

A needle cover spring 20 (visible on Fig. 2B) is arranged to bias the needle cover 18 in a proximal direction relative to the housing 10, before injection, for safety reasons. Fig. 1B and 2B show the medicament delivery device in a primed configuration, after the cap 16 has been removed and before injection. In the primed configuration, the needle cover is biased in the proximal direction relative to the housing by the needle cover spring.

The needle cover spring 20 needs to be compressed at the beginning of injection in order to retract the needle cover 18 inside the housing 10 and uncover the needle, thereby activating the device. This compression happens when the patient presses the device against its skin. Fig. 1C and 2C show the medicament delivery device in an injection start configuration, just after the device has been activated. In the injection start configuration, the needle cover is retracted in the housing, revealing the needle (not visible on the figures).

A pre-loaded drive spring (not visible on the figures) is arranged within the housing 10. A plunger rod 22 (illustrated on Fig. 4, described later) is used to forward force from the drive spring to the plunger 14. In an exemplary embodiment, the plunger rod is hollow and the drive spring is arranged within the plunger rod. In another exemplary embodiment, the plunger rod is solid and the drive spring engages a distal end of the plunger rod. When the pre-loaded drive spring is released, the drive spring biases the plunger rod 22 in the proximal direction relative to the housing 10, releasing the plunger rod 22.

Besides that, the medicament delivery device comprises an activator 24 fixed relative to the housing 10.

In addition, the medicament delivery device comprises a plunger rod release mechanism arranged for preventing release of the plunger rod prior to retraction of the medicament delivery member cover relative to the housing and for releasing the plunger rod only once the medicament delivery member cover is sufficiently retracted.

The plunger rod release mechanism comprises a pair of proximal arms 241 and a pair of distal arms 242 on the activator 24, visible on Fig. 3A and 3B. The proximal arms 241 are at the same axial position along the longitudinal axis L and have a circumferential offset of 180° relative to each other. Likewise, the distal arms 242 are at the same axial position along the longitudinal axis L and have a circumferential offset of 180° relative to each other. Besides that, one proximal arm 241 and one distal arm 242 extend on an axis parallel to the longitudinal axis L, and the other proximal arm 241 and the other distal arm 242 extend on another axis parallel to the longitudinal axis L.

Moreover, the plunger rod release mechanism comprises a proximal recess 221, an intermediate recess 222 and a distal recess 223 on the plunger rod 22, visible on Fig. 4. The distal recess 221 extends distally up to a distal end of the plunger rod 22, and the intermediate recess extends between the proximal recess 221 and the distal recess 223.

Finally, the plunger rod release mechanism comprises a distal portion 180 of the needle cover 18, said distal portion having an inner diameter narrower than the diameter of the rest of the needle cover 18.

In addition, the medicament delivery device comprises a needle cover lockout mechanism to prevent retraction of the needle cover 18 relative to the housing 10 after injection, thereby covering the needle and avoiding injuries after injection.

The needle cover lockout mechanism comprises a pair of lockout tabs 243 on the activator 24, visible on Fig. 3A and 3B. The lockout tabs 243 are at the same axial position along the longitudinal axis L and have a circumferential offset of 180° relative to each other. The lockout tabs 243 are axially located between the proximal arms 241 and the distal arms 242. Finally, the lockout tabs 243 have a circumferential offset relative to the proximal arms 241 and the distal arms 242.

Moreover, the needle cover lockout mechanism comprises a pair of radial protrusions 224 on a distal portion of the plunger rod 22, visible on Fig. 4. The distal protrusions 224 extend distally up to the distal end of the plunger rod 22. Moreover, the needle cover lockout mechanism comprises a pair of flexible arms 182 on the distal portion 180 of the needle cover 18, visible on Fig. 5A and 5B. The flexible arms 182 are flexible radially, are at the same axial position along the longitudinal axis L and have a circumferential offset of 180° relative to each other. Besides that, one flexible arm 182 and one lockout tab 243 extend on an axis parallel to the longitudinal axis L, and the other flexible arm 182 and the other lockout tab 243 extend on another axis parallel to the longitudinal axis L.

Fig. 6A, 6B, 6C, 6D and 6E show a longitudinal sectional view of a part of the medicament delivery device in different successive configurations: respectively in the initial configuration (with the cap attached), the primed configuration (with the needle cover extending outside of the housing and the plunger rod having moved slightly proximally), the injection start configuration (with the needle cover retracted, pressed against the injection site), the injection end configuration (with the needle cover still retracted, and the plunger rod having completely moved proximally), and the needle cover lockout configuration (with the needle cover extending again outside of the housing).

In the initial configuration, the needle cover 18 is retracted inside the housing 10, and the plunger rod 22 rests axially against a distal end of the housing 10.

In the initial configuration, the distal arms 242 of the activator 24 are radially constrained in the intermediate recess 222 of the plunger rod 22 by the distal portion 180 of the needle cover 18. The distal portion 180 of the needle cover 18 prevents the distal arms 242 of flexing radially out. Hooks at the end of the distal arms 242 are axially biased against a distal end of the intermediate recess 122, preventing the plunger rod 22 from moving forward.

In the initial configuration, the proximal arms 241 of the activator 24 are in the proximal recess 221 of the plunger rod 22, but are not radially constrained by the needle cover 18 as they are not facing the distal portion 180 of the needle cover 18 (it is reminded that the distal portion 180 of the needle cover 18 has a narrow inner diameter compared to the rest of the needle cover 18). It should be noted that in the initial configuration, the proximal arms 241 are positioned proximally compared to a distal end of the proximal recess 221.

In the primed configuration, the cap 16 has been removed and consequently the needle cover 18 extends outside of the housing 10.

In the primed configuration, since the needle cover has moved proximally, the distal arms 242 are not radially constrained anymore by the distal portion 180 of the needle cover 18. Thus, between the initial configuration and the primed configuration, the distal arms 242 have flexed radially outwards, enabling the plunger rod 22 to move forward under the action of the drive spring. The distal arms 242 have then flexed radially inwards in the distal recess 223 of the plunger rod 22, still unconstrained.

In the primed configuration, the proximal arms 241 of the activator 24 are radially constrained in the proximal recess 221 of the plunger rod 22 by the distal portion 180 of the needle cover 18. The proximal arms 241 are axially biased against a distal end of the proximal recess 221 of the plunger rod 22, preventing the plunger rod 22 from moving forward.

In the injection start configuration, the needle cover 18 is retracted again inside the housing 10, axially pressed against the injection site by the patient.

In the injection start configuration, and all along the injection, the distal portion 180 of the needle cover 18 faces the distal arms 242 of the activator 24, which radially constrains the distal arms 242 of the activator 24 in the distal recess 223 of the plunger rod 22.

In the injection start configuration, and all along the injection, the proximal arms 241 are not radially constrained anymore by the distal portion 180 of the needle cover 18. Thus, the proximal arm 241 are free to flex radially outwards, and move from the proximal recess 221 to the intermediate recess 222, and then from the intermediate recess 222 to the distal recess 223 during the proximal movement of the plunger rod 22.

In the injection end configuration, the proximal movement of the plunger rod 22 is over. The protrusions 224 on the distal portion of the plunger rod 22 bias the lockout tabs radially outwards.

Between the injection end configuration and the needle lockout configuration, as the patient removes the medicament delivery device from the injection site, the needle cover 18 extends outside of the housing 10. The flexible arms 182 on the distal portion 180 of the needle cover flex radially outwards to pass the lockout tabs 243 of the activator 24, then flex radially inwards when the lockout tabs 243 have been passed (as visible on Fig 5A).

In the needle cover lockout configuration, a proximally-facing surface of each lockout tabs 242 axially abuts a distally-facing surface of the corresponding flexible arm 182 of the needle cover 18 (as visible on Fig. 5B), axially locking the needle cover 18.

Besides that, in an optional embodiment illustrated on Fig. 7, the plunger rod 22 comprises a track 225 comprising a succession of teeth all extending along the plunger rod 22. The track 225 is circumferential spaced apart from the proximal arms 241 and distal arms 242 of the activator 24. Besides that, the medicament delivery device comprises a medicament container carrier 25 comprising a hook 250 configured to contact the succession of teeth during the proximal movement of the plunger rod 22, creating a succession of audible signals as a feedback of the progression of the injection for the patient.

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, hi dradenitis 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, Behqet'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 (CDW123) 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.

Various modifications to the embodiments described are possible and will occur to those skilled in the art without departing from the invention which is defined by the following claims.

Claims

1. Medicament delivery device (1) extending generally along a longitudinal axis (L), and having a proximal end configured to point towards a dose delivery site and a distal end configured to point away from the dose delivery site, the medicament delivery device (1) comprising:

- a housing (io)

- a plunger rod (22) arranged to move axially in a proximal direction relative to the housing (10) to urge a plunger (14) of a medicament container (12) to expel medicament from the medicament container (12), and a drive spring arranged to bias the plunger rod (22) in the proximal direction,

- a needle cover (18) arranged to move axially relative to the housing (10), and a needle cover spring (20) arranged to bias the needle cover (18) in the proximal direction,

- an activator (24), fixed relative to the housing (10), wherein the outer surface of plunger rod (22) comprises a proximal recess (221), an intermediate recess (222) and a distal recess (223), wherein the activator (24) comprises at least one proximal arm (241) and at least one distal arm (242) both flexible radially, and wherein the medicament delivery device (1) is such that:

- in an initial configuration, the distal arm (242) is radially constrained in the intermediate recess (222) by the needle cover (18) to block the proximal movement of the plunger rod (22), and the proximal arm (241) is in the proximal recess (241),

- in a second configuration, the distal arm (242) is no longer radially constrained, and the proximal arm (241) is radially constrained in the proximal recess (221) by the needle cover (18), allowing only a limited amount of the proximal movement of the plunger rod (22) to prime the medicament delivery device (1), in a third configuration, the proximal arm (241) is no longer radially constrained, and the distal arm (242) is radially constrained in the distal recess (223) by the needle cover (18), allowing the rest of the proximal movement of the plunger rod (22) to expel the medicament.

2. Medicament delivery device (1) according to the previous claims, wherein the activator (24) comprises at least one lockout tab (243) with a circumferential offset relative to the at least one proximal arm (241) and the at least one distal arm (243), wherein a distal portion of the plunger rod (22) comprises at least one radial protrusion (224), and wherein in a lockout configuration of the medicament delivery device (1), the radial protrusion (224) biases the lockout tab (243) radially outwards and a proximally-facing surface of the lockout tab (243) axially abuts a distally-facing surface of a distal portion (180) of the needle cover (18).

3. Medicament delivery device (1) according to the previous claim, wherein the lockout tab (243) is axially located between the at least one proximal arm (241) and distal arm (242).

4. Medicament delivery device (1) according to claim 2 or claim 3, wherein the distal portion (180) of the needle cover (18) comprises at least one flexible arm (182) that is flexible radially and axially aligned with the at least one lockout tab (243).

5. Medicament delivery device (1) according to any of claims 2 to 4, wherein the circumferential offset between the at least one lockout tab (243) and the at least one proximal arm (241) and distal arm (242) is 90°.

6. Medicament delivery device (1) according to any of the previous claims, wherein the distal recess (223) extends distally up to a distal end of the plunger rod (22).

7. Medicament delivery device (1) according to any of the previous claims, wherein in a priming configuration of the medicament delivery device (i), the at least one proximal arm (241) is radially constrained in the proximal recess (221) by the needle cover (18) and axially abuts against a distal end of the proximal recess (221).

8. Medicament delivery device (1) according to any of the previous claims, wherein in the initial configuration, the at least one distal arm

(242) axially abuts against a distal end of the intermediate recess (222).

9. Medicament delivery device (1) according to any of the previous claims, wherein the activator (24) comprises two proximal arms (241) and two distal arms (242).

10. Medicament delivery device (1) according to the previous claim, wherein the circumferential offset in each pair of arms (241, 242) is 180°.

11. Medicament delivery device (1) according to any of the previous claims and claim 2, wherein the activator (24) comprises two lockout tabs

(243), wherein the distal portion of the plunger rod (22) comprises two radial protrusions (224), and wherein for each pair of lockout tabs (243) and radial protrusions (224), the lockout tabs (243) and radial protrusions (224) are spaced apart circumferentially from each other.

12. Medicament delivery device (1) according to the previous claim, wherein the circumferential offset of each pair of lockout tabs (243) and radial protrusions (224) is 180°.

13. Medicament delivery device (1) according to any of the previous claims and claim 4, wherein the distal portion (180) of the needle cover (18) comprises two flexible arms (182) spaced apart from each other. 14- Medicament delivery device (1) according to the previous claim, wherein the circumferential offset of the flexible arms (182) of the needle cover (18) is 180°.

15. Medicament delivery device (1) according to any of the previous claims, wherein the plunger rod (22) comprises a track (225) comprising a succession of teeth, said track (225) being circumferential spaced apart from the at least one proximal arm (241) and distal arm (242), and wherein the medicament delivery device (1) comprises at least one hook (250) configured to contact the succession of teeth during the proximal movement of the plunger rod (22) to create a succession of audible signals.