WO2012118687A1

WO2012118687A1 - Manually operated injector with restricted injection sequence

Info

Publication number: WO2012118687A1
Application number: PCT/US2012/026239
Authority: WO
Inventors: Annaniy Berenshteyn; Mikhail Gotliboym; Wail Rasheed; Aleksandr Zuyev
Original assignee: Merck Sharp & Dohme Corp.
Priority date: 2011-02-28
Filing date: 2012-02-23
Publication date: 2012-09-07

Abstract

An injector prevents a user from performing certain steps of an injection sequence out of order. This injector includes an outer casing with one or more through holes at its distal end, a release adaptor having one or more protrusions at its distal end, a sleeve lock having at least one flexible detent, and a plunger sleeve. Attaching a needle assembly to the injector causes distal movement of the release adaptor by forcing the release adaptors protrusions through the outer casings through holes. Distal movement of the release adaptor in turn causes the sleeve locks detent to release the plunger sleeve. This allows distal movement of the plunger sleeve, thereby permitting a user to prime the injector. Thus, a user is unable to prime the injector or to begin injection before attaching the needle assembly.

Description

MANUALLY OPERATED INJECTOR WITH RESTRICTED INJECTION

SEQUENCE

TECHNICAL FIELD

[0001] The present invention generally relates to devices for injecting a medicament into a patient. More particularly, the present invention relates to manually operated injection devices that restrict users from performing certain steps of an injection sequence out of order.

BACKGROUND

[0002] The desire for readily-available, easy-to-use injection devices has rapidly increased in recent years. One such device is described in U.S. Patent No. 7,402,150, issued to Matsumoto et al. This injection device is a so-called auto-injector, capable of performing an injection sequence automatically upon triggering by a user. As such, there is little risk of the devices being used improperly. There is a disadvantage, however: auto-injectors such as that described by Matsumoto et al. are typically complex and costly devices. Particularly when such devices are disposable, they may be cost prohibitive for certain patients or for certain treatments.

[0003] Typical manual injectors, however, also have a shortcoming: they allow a user to perform the various steps of an injection sequence out of order. For example, a user of these devices may forget to prime the injector before injection or otherwise omit or misplace a key step in the injection sequence. Although these devices are typically less complex and costly than many auto-injection devices, failure to use manual injectors in their intended manner can result in a reduced efficiency or, in some cases, can potentially harm the user.

[0004] Accordingly, there exists a need for a novel, manually operated injector capable of preventing a user from performing key steps of an injection sequence out of the intended order.

SUMMARY

[0005] Certain embodiments of the present invention generally relate to an injector.

The injector includes a medicament cartridge containing at least one medicament, a first piston located within the medicament cartridge, an outer casing configured to receive the medicament cartridge therein, an attachment mechanism at a distal end of the outer casing (wherein the attachment mechanism is configured to receive a needle assembly), a release adaptor provided within the outer casing and outside of the medicament cartridge, a plunger sleeve provided at least partially within the outer casing, a plunger provided at least partially within the plunger sleeve, the outer casing, and the dose setting sleeve, the plunger axially slidable relative to the outer casing and configured to engage with the first piston, and a sleeve lock having at least one flexible detent that prevents distal movement of the plunger sleeve in an initial position of the injector. When a needle assembly is attached to the attachment mechanism of the outer casing, the release adaptor slides in the proximal direction, thereby flexing the at least one flexible detent of the sleeve lock and allowing distal movement of the plunger sleeve beyond the initial position. Accordingly, a user of the injector is prevented from priming the injector or injecting a medicament until a needle assembly is attached.

[0006] Other embodiments of the present invention provide an injector having a medicament cartridge containing at least one solid and one liquid medicament, a first piston located within the medicament cartridge, an outer casing configured to receive the medicament cartridge therein, an attachment mechanism at a distal end of the outer casing (wherein the attachment mechanism is configured to receive a needle assembly), a release adaptor provided within the outer casing and outside of the medicament cartridge, a plunger sleeve provided at least partially within the outer casing, a dose setting sleeve provided on an outer circumferential surface of the plunger sleeve and rotatably fixed to the plunger sleeve, a plunger provided at least partially within the plunger sleeve, the outer casing, and the dose setting sleeve (the plunger axially slidable relative to the outer casing and configured to engage with the first piston), a sleeve lock having at least one flexible detent that prevents distal movement of the plunger sleeve in an initial position, one or more through holes provided at a distal end of the outer casing, one or more protrusions at a distal end of the release adaptor configured to protrude through the one or more through holes of the outer casing in an initial position of the injector, a rear body attached to the proximal end of the outer casing, a key guide provided on an outer circumferential surface of the plunger sleeve, and a plurality of dosing grooves of differing lengths provided on an inner circumferential surface of the rear body, each of the plurality of dosing grooves sized and shaped to accommodate the key guide of the plunger sleeve. Prior to the mixing of the solid and liquid medicaments, the finger of the plunger sleeve is prevented from contracting into the groove of the plunger by a distal circumferential surface toward the distal end of the plunger, and the release adaptor is prevented from moving proximally by contact of the finger with an inwardly-protruding surface at the proximal end of the release adaptor. After the plunger is advanced distally to complete mixing of the solid and liquid medicaments, the finger contracts into the groove of the plunger, thereby allowing proximal movement of the release adaptor. When a needle assembly is attached to the attachment mechanism of the outer casing, a proximal surface of the needle assembly pushes the one or more protrusions through the one or more through holes of the outer casing, which slides the release adaptor in the proximal direction, thereby flexing the at least one flexible detent of the sleeve lock and allowing distal movement of the plunger sleeve beyond the initial position. Accordingly, a user of the injector is then allowed to perform a priming step. Further, a proximal-most surface of the rear body prevents distal movement of the key guide (and therefore the plunger sleeve) when the injector is in a primed state prior to setting a dose. Rotation of the dose setting sleeve rotates the plunger sleeve to align the key guide with one of the plurality of dosing grooves, thereby allowing further distal movement of the key guide. Accordingly, after rotating the dose setting sleeve, a user can begin injection.

[0007] Still other embodiments of the present invention relate to a method of injecting a medicament. One such method includes the steps of providing an injector having an outer casing including an attachment mechanism at a distal end of the outer casing and configured to receive a needle assembly, a medicament cartridge including at least one medicament and provided within the outer casing, a release adaptor axially slidable within the outer casing and including one or more protrusions configured to protrude through one or more through holes provided on a proximal end of the outer casing, a plunger sleeve provided at least partially within the outer casing, and a sleeve lock including at least one flexible detent that prevents distal movement of the plunger sleeve in an initial position; attaching a needle assembly to the attachment mechanism, wherein the attaching the needle assembly causes distal movement of the release adaptor by forcing the one or more protrusions of the release adaptor through the one or more through holes of the outer casing, wherein the distal movement of the release adaptor causes the at least one detent of the sleeve lock to release the plunger sleeve, thereby allowing distal movement of the plunger sleeve; priming the injector after attaching the needle assembly; selecting a dose of a medicament contained within the medicament cartridge after priming the injector; and injecting the dose of the medicament to an injection site.

[0008] The invention may be embodied in numerous devices and through numerous methods and systems. The following detailed description, taken in conjunction with the annexed drawings, discloses examples of the invention. Other embodiments, which incorporate some, all, or more of the features as taught herein, are also possible.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The following drawings, forming part of the disclosure of the present invention, are given by way of illustration only and are not limitative of the present invention. These drawings are as follows:

[0010] FIG. 1 shows a perspective view of an injector in the initial position, in accordance with an embodiment of the present invention;

[0011] FIG. 2 shows an exploded perspective view of the injector of FIG. 1 ;

[0012] FIG. 3A shows a cross-sectional view of an injector in an initial position;

[0013] FIG. 3B shows a cross-sectional view of the injector of FIG. 3 A rotated 90 degrees;

[0014] FIG. 3C shows an enlarged cross-sectional view of the injector of FIG. 3 A;

[0015] FIG. 4 shows a cross-sectional view of an injector at the start of a mixing phase;

[0016] FIG. 5 shows a cross-sectional view of an injector at the completion of the mixing phase;

[0017] FIG. 6A shows a side view of an injector and a needle assembly after completion of a mixing phase but prior to attachment of the needle assembly;

[0018] FIG. 6B shows a perspective view of the injector in FIG. 6A;

[0019] FIG. 6C shows a perspective view of the injector of FIGS. 6A and 6B after the needle assembly has been attached and a needle sheath has been removed;

[0020] FIG. 7 shows a cross-sectional view of the injector of FIGS. 6A - 6C;

[0021] FIG. 8A shows a cross-sectional view of an injector at the completion of a priming phase;

[0022] FIG. 8B shows a rear perspective view of certain components of the injector of

FIG. 8A;

[0023] FIG. 9A shows a rear perspective view of an injector set to a dose;

[0024] FIG. 9B shows an additional rear perspective view of certain components of the injector of FIG. 9A;

[0025] FIG. 10 shows a front perspective view of certain components of the injector ofFIGS. 9A and 9B; [0026] FIG. 11 A shows a cross-sectional view of an injector that has completed an injection; and

[0027] FIG. 1 IB shows a cross-sectional, perspective view of the injector of FIG.

11 A.

DETAILED DESCRIPTION

[0028] As used in this description, the term "distal" refers to the end of a device or component closest to the end to be applied to a patient: that is, the needle end. The term "distally" similarly refers to movement towards the injector's needle end. Likewise,

"proximal" or "proximally" refer to the end or direction opposed to the injector's needle end. In FIG. 1, for example, the distal direction is to the left, while the proximal direction is to the right. The axial direction refers to the longitudinal axis of the device, such that axial movement implies movement in either a distal or proximal direction.

[0029] Certain embodiments of the present invention generally relate to an injector for injecting a medicament into an injection site, such as on a patient. A user of the injector is prevented from attaching a needle assembly prior to completing the mixing of two or more medicaments within the injector. Also, a user cannot prime the injector or inject a

medicament until the needle assembly is attached. Further, a user is prevented from injecting the medicament until a dose is set. Accordingly, certain embodiments of the present invention prohibit a user from performing steps of an injection sequence out of order.

[0030] First, the various components of an exemplary embodiment of the present invention will be described. Next, operation of this embodiment will be detailed. Then, an example method of using an injector in accordance with the present invention will be described. These examples are merely a few of many possible embodiments and are in no way limiting of the present invention. Similarly, the headings provided below merely aide a reader in understanding the disclosure of the present invention and in no way limit the present invention.

[0031] A. Components of an Exemplary Embodiment

[0032] One example of an injector in accordance with an embodiment of the present invention is shown in FIG. 1. As shown in FIG. 2, an injector 1 includes a medicament cartridge 10, an outer casing 20, a release adaptor 30, a plunger sleeve 40, a plunger 50, a rear body 60, a sleeve lock 70, and a dose setting sleeve 80. Each of these components will be described in detail.

[0033] J. Medicament cartridge 10

[0034] Medicament cartridge 10 contains at least one medicament and at least one piston. Medicament cartridge 10 is preferably a dual-chamber cylinder ampoule or two- compartment syringe having a generally cylindrical shape. That is, preferably, cartridge 10 provides two medicaments separately from one another.

[0035] The medicaments may be kept separate from one another by a first piston 11 and a second piston 12 located distal to first piston 11, as shown in FIG. 2. The proximal end of first piston 11 may be configured to engage with a distal end 51 of plunger 50. The pistons may be configured to force medicament out of a distal opening of cartridge 10 by advancing distally. The distal end of cartridge 10. may include a pierceable septum, membrane, or cover that keeps medicament inside the cartridge until a needle is attached.

[0036] Medicament cartridge 10 may also include an overflow channel 14. Channel

14 is configured to allow a liquid medicament 15 contained between first and second pistons 11 and 12 to advance distally past second piston 12 when second piston 12 advances to channel 14. This allows a liquid medicament/solvent 15 to mix with a solid

medicament/solute 17 located distal to second piston 12.

[0037] A broad range of medicaments may be used in the present invention. The at least one medicament contained in the cartridge may be a solid, a liquid, or any other phase. Additionally, any combination of solid, liquid, or other medicaments may be used. In some embodiments, the cartridge contains a solid medicament, which comprises a therapeutic agent, and a liquid medicament, which lacks therapeutic activity, but instead consists of one, two, three or more exicipients. For example, the liquid medicament may consist of a diluent. In some embodiments, the diluent is Sterile Water for Injection, USP. In other embodiments, the diluent is a buffered solution. In some embodiments, the solid medicament is a lyophilized powder comprising at least one peptide, polypeptide or protein as the therapeutic agent and one two, three or more exicipients. The peptide, polypeptide or protein may comprise one or more polymer molecules, such as polyethylene glycol, conjugated to the amino acid molecule. The solid medicament may comprise at least one antigen for use as a vaccine. In some preferred embodiments, the solid medicament comprises an antibody, an antigen binding fragment of an antibody, a receptor:Fc fusion protein, or a cytokine.

[0038] In one preferred embodiment, the solid medicament comprises a pegylated interferon alfa and is approved by a regulatory agency for treating infection with hepatitis C virus. In a more preferred embodiment, the solid medicament is PegIntron® (Peginterferon alfa-2b) Powder for Injection and the liquid medicament is water. Peglntron® (Peginterferon alfa-2b) Powder for Injection, which is available from Schering Corporation, comprises a covalent conjugate of recombinant alfa-2b interferon with monomethoxy polyethylene glycol having an average molecular weight of 12,000 daltons (PEG_12,000) and the following exicipients: dibasic sodium phosphate anhydrous; monobasic sodium phosphate dehydrate, sucrose and polysorbate 80. In a particularly preferred embodiment, the liquid medicament chamber contains 0.7 ml water and the solid medicament chamber contains 67.5 μg, 108 μg, 162 μg, or 202.5 μg of peginterferon alfa-2b, 1.013 mg dibasic sodium phosphate anhydrous, 1.013 mg monobasic sodium phosphate dihydrate, 54 mg sucrose and 0.0675 mg polysorbate 80.

[0039] Medicament cartridge 10 may be constructed of any material suitable for use in an injector. Cartridge 10 may be made of a transparent or translucent material, allowing a user to view the contents of the cartridge. Cartridge 10 may also be opaque. Cartridge 10 may further include hash marks thereon for allowing a user to determine the amount of medicament or the position of the pistons within medicament cartridge 10.

[0040] Medicament cartridge 10 is fixedly provided within outer casing 20.

(Alternatively, medicament cartridge 10 may be removable from outer casing 20 so that injector 1 may be reused with a new medicament cartridge.) Cartridge 10 may either be directly attached to the inner circumferential surface of outer casing 20, or indirectly attached through release adaptor 30. In certain embodiments, cartridge 10 may be rotatably and/or axially fixed to outer casing 20.

[0041] 2. Outer casing 20

[0042] A portion of injector 1 's exterior is formed by outer casing 20. Outer casing 20 preferably defines an inner space for receiving various other components of injector 1, such as medicament cartridge 10 and lock sleeve 70. Outer casing 20 may include a viewing window 23 that allows a user to view the contents of medicament cartridge 10. Casing 20 may also include, at its distal end, one or more through holes 21 that communicate with casing 20's inner space. Viewing window 23 and through holes 21 may be of any suitable size and shape. Additionally, viewing window 23 may include hash marks thereon or thereabout for allowing a user to determine the amount of medicament or the position of the pistons within medicament cartridge 10. Viewing window 23 need not be a physical component, such as a transparent or translucent piece of plastic; alternatively, it may also be a through hole that allows a user to view cartridge 10 contained within casing 20. [0043] Outer casing 20 also provides wings 27 that allow for a user to handle injector

1 more easily. Wings 27 may have a distal-facing surface that is at least partially concave, further increasing the ease of handling and use. Wings 27 may also have a flat distal-facing surface.

[0044] At its distal-most end, outer casing 20 contains a hole that communicates with the inner space of casing 20. During injection, medicament travels through this hole (via a needle) to the injection site.

[0045] The distal-most end of outer casing 20 also includes an attachment mechanism 25 for attaching a needle assembly to the outer casing. Attachment mechanism 25 is preferably configured to receive a needle assembly. Attachment mechanism 25 may be internal or external threads that engage with corresponding threads on a needle assembly. Alternatively, attachment mechanism 25 may be a snap or luer lock connection. Attachment mechanism 25 may also be any other mechanism known in the art and suitable for attaching a needle assembly to an injector. Alternatively, outer casing 20 may include means for attaching a needle assembly to the outer casing, which may have a configuration similar to the attachment mechanism.

[0046] Outer casing 20 has attached, at its proximal end, rear body 60. Rear body 60 may be fixedly attached or snapped to the proximal end of outer casing 20. (Alternatively, rear body 60 may be formed integrally with outer casing 20.)

[0047] 3. Rear body 60

[0048] Another portion of injector 1 's exterior is formed by rear body 60. As shown in FIGS. 8B and 1 IB, rear body 60 includes a plurality of dosing grooves 61a, 61b, 61c, and 6 Id (collectively, 61). Grooves 61 are configured to allow key guide 41 of sleeve 40 to pass through. Each groove is of a different length, corresponding to the dose associated with the particular groove. Larger doses will have longer dosing grooves, while smaller doses will have shorter dosing grooves. This is best shown by comparing groove 61a to groove 61 d in FIG. 1 IB. Preferably, rear body 60 includes one dosing groove for each dose selectable by a user. Although an injector capable of six different doses is shown in the figures, any number of doses of a suitable size and increment are possible. For example, an injector in accordance with the present invention may provide a dose range of 0.2 - 0.5 mL, with dose increments of 0.1 mL. Other ranges and increments, however, are also possible.

[0049] Further, rear body 60 includes a plurality of click grooves 63a, 63b, 63c, and

63d (collectively, 63) on its internal surface towards its distal end, as shown in FIGS. 8 A, 10, and 1 IB. Click grooves 63 are configured to engage with detent 45 on plunger sleeve 40 to provide haptic and/or audible feedback during dose setting. That is, a user feels a slight vibration and/or hears a click as dose setting sleeve 80 is rotated to each dose. Click grooves 63 may be of equal length, as shown in FIG. 1 IB. Alternatively, these grooves may vary in length or depth as needed.

[0050] Rear body 60 may also include a plurality of dose indicating marks 62 on its proximal surface, as best shown in FIGS. 8B and 9A. These marks aide a user in identifying and selecting a dose. Rear body 60 may also include wings 67 that fit inside wings 27 of outer casing 20, as shown in FIGS. 2 and 4.

[0051] 4. Release adaptor 30

[0052] Between outer casing 20 and medicament cartridge 10, release adaptor 30 is provided. Release adaptor 30 may be a sleeve- or tube-like component that is axially slidable relative to outer casing 20 and medicament cartridge 10. That is, release adaptor 30 is capable of both distal and proximal movement relative to outer casing 20. Release adaptor 30 is suitably configured to allow for viewing of cartridge 10 through viewing window 23 of outer casing 20.

[0053] At its distal end, release adaptor 30 includes one or more protrusions 31 configured to pass through the one or more holes 21 in outer casing 20. In the initial position, protrusions 31 protrude through holes 21. A cover or other suitable component may enclose or otherwise shield protrusions 31 to prevent inadvertent pressing of protrusions 31 prior to attaching a needle assembly. At its proximal end, adaptor 30 includes tabs 33 configured to push apart one or more detents 73 on sleeve lock 70 (to be described later). In general, release adaptor 30 extends beyond medicament cartridge 10 in both the proximal and distal directions, as shown in FIG. 3 A.

[0054] Release adaptor 30 may further include an inwardly-protruding surface 35, as best seen in FIG. 3C. Surface 35 preferably protrudes radially inward so as to contact a portion of plunger sleeve 40. This contact prevents proximal movement of release adaptor 30 until the completion of a mixing step.

[0055] 5. Plunger sleeve 40

[0056] Partially within both outer casing 20 and rear body 60, plunger sleeve 40 is provided. Plunger sleeve 40 may be a hollow sleeve- or tube-like component. Plunger sleeve 40 is configured to receive plunger 50 therein. Accordingly, plunger sleeve 40 may have an inner cross-sectional profile that matches that cross-section of plunger 50. Preferably, plunger sleeve 40 has a circular outer circumferential surface, such that it is able to rotate within outer casing 20. [0057] Plunger sleeve 40 is also configured to engage with rear body 60, sleeve lock

70, and dose setting sleeve 80, as will be described. As best seen in FIG. 1 IB, plunger sleeve 40 includes a flexible detent 45. Detent 45 prevents backup of the sleeve after injection is complete. Detent 45 also provides haptic and/or audible feedback (such as clicking) to a user during dose setting by engaging with click grooves 63 as shown in FIG. 10.

[0058] Plunger sleeve 40 further includes a key guide 41 , which may be a solid, raised projection on an outer circumferential surface of sleeve 40. As best seen in FIGS. 8A and 8B, key guide 41 prevents distal movement of plunger sleeve 40 after priming but prior to dose setting. Key guide 41 is also sized and shaped so as to be accommodated by dosing grooves 61 of rear body 60.

[0059] Plunger sleeve 40 also includes a plurality of dose end tabs 47a, 47b, 47c, 47d, and 47e (collectively, 47) around its outer circumference toward its distal end, as shown in FIGS. 10 and 11 A. Tabs 47 are of various widths based on the dose selected by a user. Tabs 47, in conjunction with an end-of-dose-indicating tab 71 on sleeve lock 70, provide haptic and/or audible feedback to a user at the end of injection. In addition, tabs 47 prevent plunger sleeve 40 from backing out in the proximal direction after injection has completed.

[0060] Plunger sleeve 40 further includes a finger 49 that extends axially from its distal end. Finger 49 is preferably flexible. Finger 49 is configured to "snap" or otherwise contract into a longitudinal groove 55 on the outer circumferential surface of plunger 50. As described in detail later, the contact of finger 49 with plunger 50 prevents a user from attaching a needle assembly to injector 1 before the medicaments have fully mixed.

Accordingly, this contact prevents a user from performing subsequent steps (such as attaching a needle assembly) prior to completing a mixing step.

[0061] 6. Plunger 50

[0062] Partially disposed within plunger sleeve 40, is plunger 50. Plunger 50, best seen in FIG. 2, is preferably of a cylindrical shape and may include a latch 52 for engaging with plunger sleeve 40. Plunger 50 need not have a circular cross-section, however. Rather, plunger 50 may be of a non-circular shape in order to prevent rotation of the plunger within plunger sleeve 40. Latch 52 prevents backup of plunger 50. Plunger 50 may also have a distal end surface 51 configured to engage with first piston 11. Further, plunger 50 may include a proximal end having a larger diameter than the rest of plunger 50. This proximal end may further include a concave proximal-most surface shaped to receive a user's thumb. During mixing, priming, and injection, a user presses the proximal surface of plunger 50 to advance the plunger distally. [0063] As indicated previously, plunger SO includes longitudinal groove 55 on its outer circumferential surface, as best seen in FIG. 3C. Groove 55 may be of any size, length, width, and shape suitable to the particular application. Preferably, groove 55 is configured to allow finger 49 to slide axially therein.

[0064] As best seen in FIG. 3C, plunger 50 also includes a distal circumferential surface 57 between the distal-most end of groove 55 and distal end surface 51. Prior to the completion of a mixing step (to be described later), surface 57 prevents finger 49 from snapping or otherwise contracting into groove 55. Accordingly, the length of surface 57 may be varied to ensure that complete mixing of the medicaments in cartridge 10 takes place prior to finger 49 engaging in groove 55 and releasing release adaptor 30. Alternatively, the length of surface 57 may be determined based on a desire to limit other steps of an injection sequence.

[0065] 7. Sleeve lock 70

[0066] Sleeve lock 70 is provided inside outer casing 20 between release adaptor 30 and outer casing 20 toward the casing's proximal end, as shown in FIG. 3A. Sleeve lock 70 engages with outer casing 20 such that it is both rotatably and axial fixed to casing 20. In certain embodiments, sleeve lock 70 is formed integrally with outer casing 20. In other embodiments, sleeve lock 70 is a separate component Sleeve lock 70 may include a flexible, end-of-dose-indicating tab 71, as best seen in FIG. 11 A. Sleeve lock 70 further includes one or more flexible detents 73, as best seen in FIGS. 3 A and 7, that prevent distal movement of plunger sleeve 40 until a user attaches a needle assembly. Flexible detent 73 may be a fingerlike member.

[0067] 8. Dose setting sleeve 80

[0068] Dose setting sleeve 80 is rotatably locked to plunger sleeve 40 via one or more grooves 43 on plunger sleeve 40, as best seen in FIG. 8B. These grooves engage with tabs or similar protrusions on dose setting sleeve 80 to rotatably couple the two components to one another. Thus, rotation of dose setting sleeve 80 results in rotation of plunger sleeve 40.

[0069] Dose setting sleeve 80 may include a marker 83 or similar visual aid to assist the user in selecting a dose, as best seen in FIG. 9A. Further, dose setting sleeve 80 may have grooves or raised projections on its outer circumferential surface that aide a user in rotating dose setting sleeve 80.

[0070] 9. Needle assembly 90

[0071] Injector 1 is configured to receive, via attachment mechanism 25, a needle assembly 90, as shown in FIGS. 6A - 6C. Needle assembly 90 may include a needle sheath 91 for protecting individuals handling injector 1 or assembly 90 from a needle 93. Needle 93 may be of any suitable gauge and length. Preferably, needle 93 is a double-ended needle so that, upon attaching needle assembly 90 to outer casing 20, the proximal end of needle 93 pierces the septum/membrane of medicament cartridge 10, as shown in FIG. 7. Needle 93 preferably includes an internal lumen that delivers medicament from cartridge 10 to an injection site.

[0072] The proximal end of needle assembly 90 includes a mechanism or means

(such as threads or a luer lock) configured to engage with attachment mechanism 25 of the outer casing.

[0073] 10. Additional features/embodiments

[0074] The injector need not include springs, pressurized chambers, or other means for automatic movement of one or more components. Although a manual injector has been described, however, the principles of the present invention may also be applied to auto- injectors.

[0075] Preferably, the injector is used by the patient, but it may also be used by medical professionals, such as doctors and nurses, or the patient's family members. Although an injector is described throughout, the principles of the present invention may also be applied to a patient trainer for training users on the injection procedure for an actual injector. Similarly, although a variable dose injector is described, the principles of the present invention may also be applied to a fixed dose injector. An injector in accordance with other embodiments of the present invention may be disposable or reusable.

[0076] Preferably, the injector is a dual-chamber cylinder ampoule (or "two compartment") injection device that mixes a solid medicament or solute with a liquid medicament or solvent prior to injection. In this context, "dual-chambered" does not necessarily mean that separate medicament containers are provided in the injector. Rather, this term preferably describes a medicament container— such as medicament cartridge 10 in FIG. 2— in which the solid and liquid medicaments are separated by one or more pistons.

[0077] The injector may also include electronic components that display a selected dose to a user, provide audible feedback, or otherwise assist in the injection sequence. These electronic components may include a database that stores use data or other user information. Alternatively, the components may include an interface— such as a universal serial bus (USB)— that allows the data to be sent to a computer or other electronic device. The components may also include transmitters capable of wirelessly transferring data from the injector to a separate electronic device. These electronic components will have appropriate programming to carry out their respective functions.

[0078] The above components described in sections 1 - 9 and shown in the figures may be made of any material suitable for injectors and similar devices. Preferably, the various components are made of lightweight materials such as plastics.

[0079] The above list of components is not exhaustive. And certain features or components clearly illustrated by the drawings are not described in detail here.

[0080] B. Operation of the Exemplary Embodiment

[0081] Operation of injector 1 includes five basic steps: mixing, needle attachment, priming, dose setting, and injection. First, an initial position of injector 1 is described. Then each of the steps in the injection sequence is discussed in detail.

[0082] 1. Initial Position

[0083] FIGS. 3A - 3C depict injector 1 in an initial position. In this position, plunger

50 is extended in the proximal direction. Further, both pistons 11 and 12 are proximal of overflow channel 14. Also in this position, solid medicament 17 remains unmixed with the liquid medicament.

[0084] In the initial position shown in FIGS. 3A and 3B, plunger sleeve 40 is prevented from advancing distally by flexible detents 73 of sleeve lock 70. As shown in FIG. 3 A, the proximal ends of detents 73 catch on a ledge on the distal end of plunger sleeve 40.

[0085] Further, dose setting sleeve 80 is prevented from moving distally by an engagement with plunger sleeve 40. As shown in FIG. 1 IB, dose setting sleeve 80 has, toward its proximal end, protrusions 83 that engage with grooves 43 in plunger sleeve 40.

[0086] Additionally, in this position latch 52 of plunger 50 engages with the plunger sleeve so as to prevent further proximal movement of plunger 50. Specifically, the inclined surface of latch 52 allows for distal, but not proximal, movement of plunger 50 in this position. This prevents plunger 50 from backing out of the injector 1.

[0087] Also in the initial position, as shown in FIG. 3C, finger 49 is prevented from contracting inward by distal circumferential surface 57 of plunger 50. That is, surface 57 blocks finger 49 from moving inward. Finger 49 in turn prevents release adaptor 30 from moving proximally due to the contact of inwardly-protruding surface 35 with finger 49. That is, finger 49 blocks proximal movement of release adaptor 30. As such, a user is unable to attach a needle assembly in the initial position because protrusions 31 cannot move proximally to allow the assembly to attach to outer casing 20.

[0088] 2. Mixing (Step 1) [0089] A user triggers the first step, mixing, by advancing plunger 50 distally, as shown in FIG. 4. Distal movement of plunger 50 allows the plunger's distal-most end to engage with first piston 1 1, thereby advancing first piston 11 distally within medicament cartridge 10. Movement of piston 11 also advances the liquid medicament, which advances second piston 12 and solid medicament 17. When plunger 50 has advanced piston 12 past the proximal end of overflow channel 14, liquid medicament/solvent contained between pistons 11 and 12 flows through channel 14 around second piston 12, thereby mixing with solid medicament/solute 17, dissolving the solid into the liquid. During this movement, latch 52 of plunger 50 is pressed inward to allow distal movement of plunger 50, as shown in FIG. 5.

[0090] Mixing is completed once all of the liquid medicament mixes with the solid medicament, as shown in FIG. 5. Preferably, plunger 50 advances at this point so as to be recessed or counter-sunk within a proximal recess or opening in dose setting sleeve 80. Also, in this position, latch 52 of plunger 50 engages with a distal edge of plunger sleeve 40, thereby preventing backing out of plunger 50.

[0091] Additionally, after mixing is complete, finger 49 snaps or otherwise contracts radially inwardly into groove 55. This releases the engagement of finger 49 with surface 35, thereby allowing the release adaptor to advance proximally. Surface 35 may be inclined, as shown in the figures, so that, as release adaptor 30 advances proximally, surface 35 can push finger 49 radially inward if finger 49 fails to contract on its own. Similarly, finger 49 may also have an inclined surface (as shown in FIG. 5) that facilitates this action.

[0092] 3. Needle Attachment (Step 2)

[0093] After mixing is complete, the user moves on to the second step: needle attachment. As shown in FIGS. 6A and 6B, a user attaches a needle assembly 90 to the distal end of outer casing 20 via attachment mechanism 25. Attachment of needle assembly 90 causes the proximal end of needle 93 to pierce the septum membrane of medicament cartridge 10, as shown in FIG. 7. Piercing of medicament cartridge 10 relieves a portion of the pressure inside cartridge 10. (This pressure release may cause second piston 12 to advance distally.) After attaching the needle, a user removes a needle sheath 91, revealing a needle 93, as shown in FIG. 6C.

[0094] As shown in FIG. 7, attachment of needle assembly 90 to outer casing 20 pushes release adaptor 30 proximally, the release adaptor now being able to travel proximally due to the contraction of finger 49 into groove 55. Adaptor 30 advances proximally because the proximal end of assembly 90 forces protrusions 31 on adaptor 30 inside holes 21 in casing 20. Proximal movement of release adaptor 30 causes tabs 33 to push apart detents 73 of sleeve lock 70, thereby allowing distal movement of plunger sleeve 40.

[0095] 4. Priming (Step 3)

[0096] Full flexing of detents 73 after needle attachment allows a user to prime the injector in the third step. As shown in FIGS. 8A and 8B, release of plunger sleeve 40 allows dose setting sleeve 80— which is blocked from moving distally relative to sleeve 40— to advance distally with plunger sleeve 40. As shown in FIGS. 8A and 8B, dose setting sleeve 80 advances distally until a key guide 41 of plunger sleeve 40 contacts a proximal-most face of rear body 60. (In FIG. 8B, plunger 50 and dose setting sleeve 80 are removed for clarity.)

[0097] J. Dose Setting (Step 4)

[0098] After priming is complete, a user is permitted to begin the fourth step: dose setting. As shown in FIG. 9A, a user selects a desired dose by rotating dose setting sleeve 80. Rotating setting sleeve 80 also rotates plunger sleeve 40 (due to their coupling via grooves 43). A user may change doses by rotating the dose setting sleeve 80 any number of times prior to beginning injection.

[0099] As shown in FIG. 9B, rotation of dose setting sleeve 80 aligns key guide 41 of plunger sleeve 40 with a particular dosing groove 61a. (Dose setting sleeve 80 is removed from FIG. 9B for clarity.) This rotation during dose setting also indicates to the user that a new dose is being selected. This indication may take the form of a slight vibration and/or clicking sound due to engagement of detent 45 of sleeve 40 with grooves 61, as best seen in FIG. 10. (For clarity, only dose setting sleeve 80, rear body 60, plunger 50, and plunger sleeve 40 are shown in FIG. 10.)

[00100] 6. Injection (Step 5)

[00101] After dose selection, a user is able to proceed to the final step: injection. Now that key guide 41 is aligned with dosing groove 61a, a user may further advance plunger 50 (along with plunger sleeve 40 and dose setting sleeve 80, which are attached to plunger 50) in the distal direction. This distal movement further advances pistons 11 and 12, as shown in FIG. 11 A, thereby injecting the mixed medicament to the injection site.

[00102] Also at this time, the end-of-dose-indicating tab 71 on sleeve lock 70 slides across an inclined surface of and snaps behind dose end tab 47a. This provides haptic and/or audible feedback to a user, thereby indicating that the injection has completed. The engagement of tab 71 with tab 47a also prevents backing out of plunger sleeve 40 upon completion of injection. [00103] As shown in FIG. 11 B, upon completion of injection, plunger sleeve 40 (along with plunger 50 and dose setting sleeve 80) is prevented from further distal movement by dosing groove 61a. That is, guide key 41 has reached the end of dosing groove 61a and can no longer advance distally. Therefore, once injection is complete, plunger sleeve 40, plunger SO, and dose setting sleeve 80 are prevented from both distal and proximal movement.

[00104] A user of the previously described injector is prohibited from performing the injection sequence out of turn. That is, due to the contact of finger 49 with surface 57 in the initial position, a user is unable to attach a needle assembly until mixing is complete.

Additionally, due to the engagement of sleeve lock 70 with plunger sleeve 40, a user is unable to select a dose or to inject the medicament until needle assembly 90 is attached. Further, due to the engagement of guide key 41 with a proximal surface of rear body 60, a user cannot inject the medicament until a dose is selected. This provides a significant improvement over typical manual injectors, which allow users to perform steps out of order.

[00105] C. Exemplary Method

[00106] Certain embodiments of the present invention also provide a method of injecting a medicament. One example of a method in accordance with the present invention includes the steps of providing an injector having the components discussed previously, attaching a needle assembly to the attachment mechanism of the injector, priming the injector after attaching the needle assembly, selecting a dose after priming the injector, and injecting the dose to an injection site. After injection, the user may wait a prescribed period of time (such as five seconds) before removing the injector from the injection site. The prescribed time period may be shortened, lengthened, or omitted altogether based on the particular application.

[00107] In this example method, attaching the needle assembly causes distal movement of the release adaptor by forcing the one or more protrusions of the release adaptor through the one or more through holes of the outer casing. The distal movement of the release adaptor in turn causes the at least one detent of the sleeve lock to release the plunger sleeve, which allows distal movement of the plunger sleeve, thereby permitting a user to proceed to the priming step. Thus, in this method, a user is unable to prime the injector before inserting the needle assembly.

[00108] In another embodiment, the step of selecting a dose includes rotating the dose setting sleeve, and the plunger sleeve rotatably fixed thereto, to align the key guide with one of the plurality of dosing grooves, as shown in FIG. 9B. This permits further distal movement of the key guide, and therefore the plunger sleeve, allowing a user to inject the selected dose. Preferably, this step is performed after priming the injector but prior to injecting a dose.

[00109] Yet another embodiment of a method in accordance with the present invention involves a step of mixing a first medicament and a second medicament within the

medicament cartridge. This step preferably occurs prior to attaching the needle assembly. The mixing can incur in the manner described above; that is, mixing may occur by depressing a plunger so as to advance a piston beyond an overflow channel in the medicament cartridge, as shown in FIG. 4. Also in this embodiment, prior to the mixing of the solid and liquid medicaments, the finger of the plunger sleeve is prevented from radially contracting into the groove of the plunger by a distal circumferential surface of the plunger. Thus, the release adaptor is prevented from moving proximally by contact of the finger with an inwardly- protruding surface at the proximal end of the release adaptor. After the plunger is advanced distally to complete mixing, the finger contracts into the groove of the plunger, thereby allowing proximal movement of the release adaptor.

[00110] Injectors and methods in accordance with the present invention may be used to treat a broad range of diseases, disorders, and other medical conditions. For example, the injector may be used to treat hepatitis C.

[00111] The previous descriptions of various examples of an injector are not limiting. Rather, any number of modifications, combinations, and alternatives of these examples may be employed to facilitate the effectiveness of providing a manual injector that prevents a user from performing an injection sequence out of order.

[00112] Numerous other embodiments may be implemented without departing from the spirit and scope of these exemplary embodiments. Moreover, while certain features of the invention may be shown on only certain embodiments, these features may be exchanged, added, and removed from and between the various embodiments. Likewise, methods described may also be performed in various sequences, with some or all of the disclosed steps being performed in a different order than described while still remaining within the spirit and scope of the present invention.

Claims

WE CLAIM; 1. An injector, comprising:

a medicament cartridge containing at least one medicament; a first piston located within the medicament cartridge;

an outer casing configured to receive the medicament cartridge therein;

an attachment mechanism at a distal end of the outer casing, wherein the attachment mechanism is configured to receive a needle assembly;

a release adaptor provided within the outer casing;

a plunger sleeve provided at least partially within the outer casing;

a plunger provided at least partially within the plunger sleeve and the outer casing, the plunger axially slidable relative to the outer casing and configured to engage with the first piston; and

a sleeve lock having at least one flexible detent that prevents distal movement of the plunger sleeve in an initial position of the injector;

wherein, when a needle assembly is attached to the attachment mechanism of the outer casing, the release adaptor slides in the proximal direction, thereby flexing the at least one flexible detent of the sleeve lock and allowing distal movement of the plunger sleeve beyond the initial position.

2. The injector of claim 1 , wherein:

the at least one medicament comprises a solid medicament and a liquid medicament,

the medicament cartridge includes a second piston located distal to the first piston,

the solid medicament is located distal to the second piston and the liquid medicament is located between the first and second pistons, and

the medicament cartridge further includes an overlap channel that allows mixing of the solid and liquid medicaments.

3. The injector of claim 2, wherein: the plunger sleeve includes a finger extending from a distal end of the plunger sleeve,

the plunger includes a longitudinal groove on an outer circumferential surface of the plunger, the groove being configured to receive the finger of the plunger sleeve, prior to the mixing of the solid and liquid medicaments, the finger of the plunger sleeve is prevented from contracting into the groove of the plunger by a distal circumferential surface toward the distal end of the plunger, and the release adaptor is prevented from moving proximally by contact of the finger with an inwardly- protruding surface at the proximal end of the release adaptor, and

after the plunger is advanced distally to complete mixing, the finger contracts into the groove of the plunger, thereby allowing proximal movement of the release adaptor.

4. The injector of claim 3, wherein the medicament cartridge is a dual-chamber

cylindrical ampoule.

5. The injector of claim 3, wherein the solid medicament comprises a pegylated

interferon alfa-2b and the liquid medicament consists of water.

6. The injector of claim 1 , further comprising a dose setting sleeve provided on an outer circumferential surface of the plunger sleeve and rotatably fixed to the plunger sleeve.

7. The injector of claim 6, further comprising:

a rear body attached to the proximal end of the outer casing;

a key guide provided on an outer circumferential surface of the plunger sleeve; and

a plurality of dosing grooves of differing lengths provided on an inner circumferential surface of the rear body, each of the plurality of dosing grooves sized and shaped to accommodate the key guide of the plunger sleeve,

wherein a proximal-most surface of the rear body prevents distal movement of the key guide, and wherein rotation of the dose setting sleeve rotates the plunger sleeve to align the key guide with one of the plurality of dosing grooves, thereby allowing further distal movement of the key guide.

8. The injector of claim 7, wherein the rear body includes a proximal surface having a plurality of dose-indicating markings thereon.

9. The injector of claim 1 , wherein both the medicament container and the sleeve lock are rotatably and axially fixed to the outer casing.

10. The injector of claim 1 , further comprising:

one or more through holes provided at a distal end of the outer casing;

one or more protrusions at a distal end of the release adaptor configured to protrude through the one or more through holes of the outer casing in the initial position of the injector,

wherein, when the needle assembly is attached to the attachment mechanism, a proximal end of the needle assembly forces the one or more protrusions through the one or more through holes, thereby pushing the release adaptor in the proximal direction to release the plunger sleeve from the sleeve lock.

11. The injector of claim 1 , wherein the release adaptor is provided outside of the

medicament cartridge.

12. The injector of claim 1, wherein the at least one medicament comprises an antibody.

13. An injector, comprising:

a medicament cartridge containing at least one solid and one liquid

medicament;

a first piston located within the medicament cartridge;

an outer casing configured to receive the medicament cartridge therein;

an attachment mechanism at a distal end of the outer casing, wherein the attachment mechanism is configured to receive a needle assembly; a release adaptor provided within the outer casing and outside of the medicament cartridge;

a plunger sleeve provided at least partially within the outer casing, the plunger sleeve including a finger extending from a distal end of the plunger sleeve;

a dose setting sleeve provided on an outer circumferential surface of the plunger sleeve and rotatably fixed to the plunger sleeve;

a plunger provided at least partially within the plunger sleeve, the outer casing, and the dose setting sleeve, the plunger axially slidable relative to the outer casing and configured to engage with the first piston, the plunger including a longitudinal groove on an outer circumferential surface of the plunger, the groove being configured to receive the finger of the plunger sleeve;

a sleeve lock having at least one flexible detent that prevents distal movement of the plunger sleeve in an initial position;

one or more through holes provided at a distal end of the outer casing;

one or more protrusions at a distal end of the release adaptor configured to protrude through the one or more through holes of the outer casing in an initial position of the injector;

a rear body attached to the proximal end of the outer casing;

wherein, prior to mixing of the solid and liquid medicaments, the finger of the plunger sleeve is prevented from contracting into the groove of the plunger by a distal circumferential surface toward the distal end of the plunger, and the release adaptor is prevented from moving proximally by contact of the finger with an inwardly- protruding surface at the proximal end of the release adaptor,

wherein, after the plunger is advanced distally to complete mixing of the solid and liquid medicaments, the finger contracts into the groove of the plunger, thereby allowing proximal movement of the release adaptor,

wherein, when a needle assembly is attached to the attachment mechanism of the outer casing, a proximal surface of the needle assembly pushes the one or more protrusions through the one or more through holes of the outer casing, which slides the release adaptor in the proximal direction, thereby flexing the at least one flexible detent of the sleeve lock and allowing distal movement of the plunger sleeve beyond the initial position,

wherein a proximal-most surface of the rear body prevents distal movement of the key guide, and

wherein rotation of the dose setting sleeve rotates the plunger sleeve to align the key guide with one of the plurality of dosing grooves, thereby allowing further distal movement of the key guide.

14. The injector of claim 13, wherein the solid medicament comprises a pegylated

interferon alfa-2b and the liquid medicament is water.

15. A method of injecting a medicament, the method comprising the steps of:

providing an injector having an outer casing including an attachment mechanism at a distal end of the outer casing and configured to receive a needle assembly, a medicament cartridge including at least one medicament and provided within the outer casing, a release adaptor axially slidable within the outer casing and including one or more protrusions configured to protrude through one or more through holes provided on a proximal end of the outer casing, a plunger sleeve provided at least partially within the outer casing, and a sleeve lock including at least one flexible detent that prevents distal movement of the plunger sleeve in an initial position;

attaching a needle assembly to the attachment mechanism,

wherein the attaching the needle assembly causes distal movement of the release adaptor by forcing the one or more protrusions of the release adaptor through the one or more through holes of the outer casing, wherein the distal movement of the release adaptor causes the at least one detent of the sleeve lock to release the plunger sleeve, thereby allowing distal movement of the plunger sleeve; priming the injector after attaching the needle assembly;

selecting a dose of a medicament contained within the medicament cartridge after priming the injector; and

injecting the dose of the medicament to an injection site.

16. The method of claim 15, wherein the injector further includes a dose setting sleeve on an outer circumferential surface of the plunger sleeve, a rear body attached to the proximal end of the outer casing, a key guide provided on an outer circumferential surface of the plunger sleeve, and a plurality of dosing grooves of differing lengths provided on an inner circumferential surface of the rear body, each of the plurality of dosing grooves sized and shaped to accommodate the key guide of the plunger sleeve, wherein a proximal-most surface of the rear body prevents distal movement of the key guide, and therefore the plunger sleeve, when the injector is in a primed state prior to setting of a dose, and

wherein the step of selecting a dose comprises rotating the dose setting sleeve, and the plunger sleeve rotatably fixed thereto, to align the key guide with one of the plurality of dosing grooves, thereby allowing further distal movement of the key guide, and therefore the plunger sleeve.

17. The method of claim 16, wherein the step of rotating the dose setting sleeve occurs after the step of priming the injector and prior to the step of injecting the dose.

18. The method of claim 15, wherein:

the at least one medicament comprises a solid medicament and a liquid medicament, and

19. The method of claim 18, wherein:

the plunger sleeve includes a finger extending from a distal end of the plunger sleeve,

the plunger includes a longitudinal groove on an outer circumferential surface of the plunger, the groove being configured to receive the finger of the plunger sleeve, prior to the mixing of the solid and liquid medicaments, the finger of the plunger sleeve is prevented from contracting into the groove of the plunger by a distal circumferential surface toward the distal end of the plunger, and the release adaptor is prevented from moving proximally by contact of the finger with an inwardly- protruding surface at the proximal end of the release adaptor, and after the plunger is advanced distally to complete mixing of the solid and liquid medicaments, the finger contracts into the groove of the plunger, thereby allowing proximal movement of the release adaptor.

20. The method of claim 15, wherein:

the at least one medicament comprises a first medicament and a second medicament, and

the method further comprises the step of mixing the first medicament with the second medicament prior to attaching the needle assembly.