Patent Description:
Medicament injection devices can take the form of a syringe, whereby medicament is provided in a tubular barrel having a plunger and an outlet to which a needle is connected. A user connects the needle to the reservoir manually before the injection takes place. The attachment of the needle to the syringe requires some dexterity and is difficult for those having poor coordination, such as patients who have lost a degree of sensation in their hands.

While it is possible to provide injection devices in which the needle is pre-attached to a medicament cartridge, in certain situations it is desirable to provide a device in which the needle is kept separate from the medicament until such time as the user wishes to commence the injection.

<CIT> relates to a liquid administration device, which include a cylindrical body filled with liquid, a needle tube communicable with the cylindrical body, and a gasket slidable within the cylindrical body. An operation member is configured to press the gasket towards the needle and a restricting member is configured to restrict the pressing operation of the operation member. A cover member is moveable in a proximal direction, which moves the needle tube proximally to engage the cylindrical body.

According to a first embodiment, there is provided a medicament injection device comprising: a main body configured to receive a medicament cartridge, a needle sleeve axially movable with respect to the main body, a needle holder holding a needle, and a displacement element coupled to the needle holder and disengageably coupled to the needle sleeve; wherein the displacement element comprises at least one ramped surface and at least one slot; wherein the needle sleeve comprises at least one pin arranged to slide through the slot when the displacement element and the needle sleeve are in rotational alignment; and wherein, upon axial displacement of the needle sleeve by a predefined distance in a proximal direction, the needle holder and needle are displaced axially in a proximal direction.

Further axial movement in the proximal direction of the needle sleeve beyond the predefined distance may cause disengagement of the needle sleeve from the displacement element.

The further axial movement of the needle sleeve may cause a rotational movement of the pin with respect to the ramped surface so that the pin aligns with the slot, thereby causing the disengagement of the needle sleeve from the displacement element.

The needle sleeve may have two pins located circumferentially opposite from each other on an inner circumferential wall of the needle sleeve and the displacement element has two respective slots for receiving the two pins located circumferentially opposite from each other.

The device may contain a medicament cartridge, wherein the axial displacement of the needle holder and needle in a proximal direction causes the proximal end of the needle to pierce a cartridge septum.

The medicament cartridge may comprise a male part and the needle holder may comprise a female part and wherein the male part and female part are configured to form a frictional fit subsequent to displacement of the needle holder by the predefined distance.

The needle holder may further comprise a lip to prevent subsequent axial displacement of the needle holder and needle with respect to the medicament cartridge subsequent to axial displacement of the displacement part by the predefined distance.

The device may contain a medicament cartridge containing a medicament.

According to a second embodiment, there is provided a method of operating a medicament injection device, the method comprising: pushing a needle sleeve comprising at least one pin disengageably coupled to a displacement element comprising at least one ramped surface in a proximal axial direction thereby causing proximal movement of a needle holder and needle, wherein a proximal end of the needle is caused to pierce a penetrable barrier of a medicament cartridge, and wherein further axial displacement of the needle sleeve causes the at least one pin to slide through the at least one slot when the displacement element and the needle sleeve are in rotational alignment to uncouple the needle sleeve from the displacement element such that subsequent further proximal movement of the needle sleeve is capable of causing the needle to emerge from an aperture in the distal end of the needle sleeve.

So that the invention can be fully understood, embodiments thereof will be described with reference to the accompanying drawings, in which:.

Embodiments of the invention provide a mechanism for inserting the needle of an injection device such as an auto-injector or syringe into a medicament cartridge containing the medicament to be injected. Providing such a mechanism allows the medicament cartridge to be sealed until such time as the user wishes to commence the injection. Providing an automated mechanism for inserting the needle into the medicament cartridge also reduces the amount of handling of the needle by the user prior to the injection. Indeed, in embodiments of the invention the user does not need to touch the needle during the steps of inserting the needle into the medicament cartridge and subsequently actuating the injection of the medicament.

A drug delivery device, as described herein, may be configured to inject a medicament into a patient. For example, delivery could be sub-cutaneous, intra-muscular, or intravenous. Such a device could be operated by a patient or care-giver, such as a nurse or physician, and can include various types of safety syringe, pen-injector, or auto-injector. The device can include a cartridge-based system that requires piercing a sealed ampule before use. Volumes of medicament delivered with these various devices can range from about <NUM> to about <NUM>. Yet another device can include a large volume device ("LVD") or patch pump, configured to adhere to a patient's skin for a period of time (e.g., about <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> minutes) to deliver a "large" volume of medicament (typically about <NUM> to about <NUM>).

The delivery devices described herein can also include one or more automated functions. For example, one or more of needle insertion, medicament injection, and needle retraction can be automated. Energy for one or more automation steps can be provided by one or more energy sources. Energy sources can include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, mechanical energy sources can include springs, levers, elastomers, or other mechanical mechanisms to store or release energy. One or more energy sources can be combined into a single device. Devices can further include gears, valves, or other mechanisms to convert energy into movement of one or more components of a device. The one or more automated functions of an auto-injector may each be activated via an activation mechanism. Such an activation mechanism can include one or more of a button, a lever, a needle sleeve, or other activation component. Activation of an automated function may be a one-step or multi-step process. That is, a user may need to activate one or more activation components in order to cause the automated function. For example, in a one-step process, a user may depress a needle sleeve against their body in order to cause injection of a medicament. Other devices may require a multi-step activation of an automated function. For example, a user may be required to depress a button and retract a needle shield in order to cause injection.

According to some embodiments of the present disclosure, an exemplary drug delivery device <NUM> is shown in <FIG>. Device <NUM>, as described above, is configured to inject a medicament into a patient's body. Device <NUM> includes a main body <NUM> which typically contains a reservoir containing the medicament to be injected (e.g., a syringe) and the components required to facilitate one or more steps of the delivery process. Device <NUM> can also include a cap assembly <NUM> that can be detachably mounted to the main body <NUM>. Typically a user must remove cap <NUM> from housing <NUM> before device <NUM> can be operated.

As shown, main body <NUM> is substantially cylindrical and has a substantially constant diameter along the longitudinal axis X. The housing <NUM> has a distal region <NUM> and a proximal region <NUM>. The term "distal" refers to a location that is relatively closer to a site of injection, and the term "proximal" refers to a location that is relatively further away from the injection site.

Device <NUM> can also include a needle sleeve <NUM> coupled to main body <NUM> to permit movement of sleeve <NUM> relative to main body <NUM>. For example, sleeve <NUM> can move in a longitudinal direction parallel to longitudinal axis X. Specifically, movement of sleeve <NUM> in a proximal direction can permit a needle <NUM> to extend from distal region <NUM> of main body <NUM>.

Insertion of needle <NUM> can occur via several mechanisms. For example, needle <NUM> may be fixedly located relative to housing <NUM> and initially be located within an extended needle sleeve <NUM>. Proximal movement of sleeve <NUM> by placing a distal end of sleeve <NUM> against a patient's body and moving main body <NUM> in a distal direction will uncover the distal end of needle <NUM>. Such relative movement allows the distal end of needle <NUM> to extend into the patient's body. Such insertion is termed "manual" insertion as needle <NUM> is manually inserted via the patient's manual movement of main body <NUM> relative to sleeve <NUM>.

Another form of insertion is "automated," whereby needle <NUM> moves relative to main body <NUM>. Such insertion can be triggered by movement of sleeve <NUM> or by another form of activation, such as, for example, a button <NUM>. As shown in <FIG>, button <NUM> is located at a proximal end of main body <NUM>. However, in other embodiments, button <NUM> could be located on a side of main body <NUM>.

Other manual or automated features can include drug injection or needle retraction, or both. Injection is the process by which a bung or piston <NUM> is moved from a proximal location within a syringe (not shown) to a more distal location within the syringe in order to force a medicament from the syringe through needle <NUM>. In some embodiments, a drive spring (not shown) is under compression before device <NUM> is activated. A proximal end of the drive spring can be fixed within proximal region <NUM> of main body <NUM>, and a distal end of the drive spring can be configured to apply a compressive force to a proximal surface of piston <NUM>. Following activation, at least part of the energy stored in the drive spring can be applied to the proximal surface of piston <NUM>. This compressive force can act on piston <NUM> to move it in a distal direction. Such distal movement acts to compress the liquid medicament within the syringe, forcing it out of needle <NUM>.

Following injection, needle <NUM> can be retracted within sleeve <NUM> or main body <NUM>. Retraction can occur when sleeve <NUM> moves distally as a user removes device <NUM> from a patient's body. This can occur as needle <NUM> remains fixedly located relative to main body <NUM>. Once a distal end of sleeve <NUM> has moved past a distal end of needle <NUM>, and needle <NUM> is covered, sleeve <NUM> can be locked. Such locking can include locking any proximal movement of sleeve <NUM> relative to main body <NUM>.

Another form of needle retraction can occur if needle <NUM> is moved relative to main body <NUM>. Such movement can occur if the syringe within main body <NUM> is moved in a proximal direction relative to main body <NUM>. This proximal movement can be achieved by using a retraction spring (not shown), located in distal region <NUM>. A compressed retraction spring, when activated, can supply sufficient force to the syringe to move it in a proximal direction. Following sufficient retraction, any relative movement between needle <NUM> and main body <NUM> can be locked with a locking mechanism. In addition, button <NUM> or other components of device <NUM> can be locked as required.

<FIG> shows a side-on cross-section of an auto-injector device <NUM> according to an embodiment of the invention.

The auto-injector device <NUM> comprises a cartridge <NUM> which is held in place by a cartridge holder <NUM>. The cartridge holder <NUM> and cartridge <NUM> are connected and fixed relative to the main body <NUM> of the device <NUM>. The cartridge <NUM> has a cartridge body <NUM> a neck <NUM> and a head <NUM>. The head <NUM> is wider than the neck <NUM>, thereby forming a flanged end. The neck <NUM> and head <NUM> contain a passage allowing medicament to pass therethrough as well as to receive the needle <NUM> once inserted. The head <NUM> is provided with a penetrable barrier such as a septum <NUM> to close off the passage and to seal the contents of the medicament cartridge <NUM>. The cartridge body <NUM>, neck <NUM> and head <NUM> may be generally cylindrical in shape. However, alternative shapes may be employed.

The needle holder <NUM> which holds the needle <NUM> is axially movable relative to the main body <NUM> and the cartridge <NUM>. The needle holder has a generally cup-shaped portion 18a and a passage through which the needle <NUM> passes. The cup-shaped portion 18a is shaped to engage with the head <NUM> of the cartridge <NUM>. The cup-shaped portion 18a comprises a lip 18b which serves to clip onto the head <NUM> to prevent detachment of the needle holder <NUM> from the cartridge <NUM> subsequent to attachment of the needle holder <NUM> to the cartridge <NUM>.

The device <NUM> comprises a tubular needle sleeve <NUM>. The needle sleeve <NUM> is a protective sleeve that prevents unwanted exposure of the needle <NUM>. The needle sleeve has a generally similar shape to the main body and is hollow and generally cylindrical. The needle sleeve <NUM> fits inside the main body <NUM>. The needle sleeve <NUM> is arranged so that it can slide axially relative to the main body <NUM>. The needle sleeve <NUM> has an aperture <NUM> at the distal end thereof to allow the needle to contact the patient's skin.

The device shown in <FIG> shows the components of the device in their initial position prior to insertion of the needle into the medicament cartridge in preparation for the injection of medicament into the user.

As shown in <FIG>, the needle holder displacement element <NUM> is generally circular in cross-section. The needle holder displacement element <NUM> comprises two ramped semicircular surfaces <NUM> separated by grooves <NUM> arranged circumferentially opposite to each other. The central part of the needle holder displacement element <NUM> comprises a tubular portion <NUM> arranged to receive the needle <NUM> and needle holder <NUM> therein.

The interior surface of the wall of the needle sleeve <NUM> is provided with needle sleeve pins <NUM>. In this embodiment, two pins <NUM> are provided, circumferentially opposite to each other. In use, the needle sleeve pins <NUM> push against the needle holder displacement member <NUM> when the needle sleeve <NUM> is pushed in the direction shown by the bold arrows in <FIG>, i.e. towards the proximal end of the device <NUM>. The engagement between the needle sleeve pins <NUM> and the semicircular surfaces <NUM> of the needle holder displacement member <NUM> causes the needle holder displacement member <NUM> to move axially towards the medicament cartridge <NUM> as the needle sleeve <NUM> is moved. The needle holder displacement member <NUM> receives a distal portion of the needle holder <NUM> in the tubular portion <NUM> thereof. The axial movement of the needle holder displacement member <NUM> therefore causes the needle holder <NUM> and needle <NUM> to move axially towards the medicament cartridge <NUM>.

<FIG> shows a side-on cross-section of the auto-injector device <NUM> as the user pushes the needle sleeve <NUM> in the proximal direction as shown by the bold arrows. The needle sleeve <NUM> is coaxial with respect to main body and slides along inside the main body <NUM> of the device <NUM>. After moving axially by a predefined distance, the cup-shaped part 18a of the needle holder <NUM> fits over the head <NUM> of the medicament cartridge <NUM>. The diameter of the cup shaped part 18a and the diameter of the head <NUM> of the medicament cartridge <NUM> are arranged to ensure a close frictional fit between the needle holder <NUM> and the medicament cartridge <NUM>. Moreover, the lip 18b extending around the cup-shaped part 18a of the needle holder further serves to fix the needle holder <NUM> to the medicament cartridge <NUM>. The lip 18b has a tapered leading edge to allow the cup shaped part to fit over the head <NUM>. However, once the needle holder <NUM> is fitted to the medicament cartridge <NUM>, axial movement of the needle holder away (in a distal direction), and separation from, the medicament cartridge <NUM> is prevented by the lip and the frictional fit.

As shown in <FIG>, the needle <NUM> pierces the septum <NUM> of the medicament cartridge <NUM>, thereby establishing a passage for the medicament to flow from the medicament cartridge <NUM> to the distal end of the needle <NUM>. Both ends of the needle <NUM> are sharp. The proximal end is sufficiently sharp to enable the needle <NUM> to penetrate the septum <NUM> of the medicament cartridge <NUM>. The distal end of the needle <NUM> is sufficiently sharp to allow the needle to penetrate the patient's skin.

The attachment of the needle holder <NUM> with the medicament cartridge <NUM> may provide audible feedback, such as a clicking sound, informing the user that the needle has been inserted into the medicament cartridge <NUM>.

Once the needle <NUM> has been inserted in to the medicament cartridge <NUM> and the needle holder <NUM> attached thereto, the device is ready to commence injection of the medicament. The distal end of the device <NUM> may then be placed against the injection site located on the patient's skin.

<FIG> shows a side-on cross-section of the auto-injector device <NUM> as the needle sleeve <NUM> moves, relative to the main body <NUM>, in the proximal direction of the bold arrows beyond the predefined distance.

This relative movement can be caused by a user gripping the main body <NUM> and pushing the needle sleeve <NUM> towards the proximal end of the device <NUM>. Alternatively, the distal end of the needle sleeve <NUM> may be held against the patient's skin at the injection site. As the user pushes the device <NUM> against the injection site, the outer wall of the main body <NUM> slides over needle sleeve <NUM>, causing the needle sleeve <NUM> to retract relative to the main body <NUM>.

Since the needle <NUM> and needle holder <NUM> are no longer coupled to the needle sleeve <NUM> and are instead fixed with respect to the medicament cartridge <NUM> and the main body <NUM>, this further axial movement of the needle sleeve <NUM> causes the needle <NUM> to emerge from the aperture <NUM> in the distal end of the needle sleeve <NUM>. If the device <NUM> has been placed against the injection site the needle <NUM> pierces the patient's skin.

Once the needle holder <NUM> is fixed to the head of the medicament cartridge <NUM>, the needle holder displacement member <NUM> cannot be displaced axially. Therefore, any subsequent proximal axial force applied to the needle sleeve <NUM>, leads to a rotation of the needle sleeve pins <NUM> against the ramped surfaces <NUM> of the needle holder displacement member <NUM>. The needle sleeve pins <NUM> become aligned with the grooves <NUM> located in the needle holder displacement member <NUM>. The axial force applied to the needle sleeve <NUM> causes the needle sleeve pins <NUM> to pass through the grooves <NUM> located in the needle holder displacement member <NUM>. The needle sleeve <NUM> thus disengages with the needle holder <NUM>.

Further axial movement of the needle sleeve <NUM> with respect to the main body <NUM> leads to exposure of the needle <NUM> from the distal end of the needle sleeve, as shown in <FIG>. The configuration shown in <FIG> illustrates when the device <NUM> is held against an injection site <NUM>. The further axial movement of the needle sleeve <NUM> causes insertion of the needle <NUM> into the patient's skin.

While the embodiments of the invention described above refer to auto-injector devices, it should be borne in mind that other embodiments may be used in conjunction with other medicament delivery devices, for example syringes.

The term "drug delivery device" shall encompass any type of device or system configured to dispense a drug or medicament into a human or animal body. Without limitation, a drug delivery device may be an injection device (e.g., syringe, pen injector, auto injector, large-volume device, pump, perfusion system, or other device configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), skin patch (e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal or pulmonary), an implantable device (e.g., drug- or API-coated stent, capsule), or a feeding system for the gastro-intestinal tract. The presently described drugs may be particularly useful with injection devices that include a needle, e.g., a hypodermic needle for example having a Gauge number of <NUM> or higher.

The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body.

The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste <NUM>, for example, without limitation, main groups <NUM> (antidiabetic drugs) or <NUM> (oncology drugs), and Merck Index, <NUM>th edition.

Examples of APIs for the treatment and/or prophylaxis of type <NUM> or type <NUM> diabetes mellitus or complications associated with type <NUM> or type <NUM> diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-<NUM>), GLP-<NUM> analogues or GLP-<NUM> receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-<NUM> (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms "analogue" and "derivative" refer to any substance which is sufficiently structurally similar to the original substance so as to have substantially similar functionality or activity (e.g., therapeutic effectiveness). In particular, the term "analogue" refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue. The added and/or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term "derivative" refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.

Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(w-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(w-carboxyheptadecanoyl) human insulin.

Examples of GLP-<NUM>, GLP-<NUM> analogues and GLP-<NUM> receptor agonists are, for example, Lixisenatide (Lyxumia®, Exenatide (Exendin-<NUM>, Byetta®, Bydureon®, a <NUM> amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-<NUM>, CJC-<NUM>-PC, PB-<NUM>, TTP-<NUM>, Langlenatide / HM-<NUM>1260C, CM-<NUM>, GLP-<NUM> Eligen, ORMD-<NUM>, NN-<NUM>, NN-<NUM>, NN-<NUM>, Nodexen, Viador-GLP-<NUM>, CVX-<NUM>, ZYOG-<NUM>, ZYD-<NUM>, GSK-<NUM>, DA-<NUM>, MAR-<NUM>, MAR709, ZP-<NUM>, ZP-<NUM>, TT-<NUM>, BHM-<NUM>. MOD-<NUM>, CAM-<NUM>, DA-<NUM>, ARI-<NUM>, ARI-<NUM>, Exenatide-XTEN and Glucagon-Xten.

An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia.

Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')<NUM> fragments, which retain the ability to bind antigens. In some embodiments, the antibody has effector function and can fix a complement. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).

Claim 1:
A medicament injection device (<NUM>) comprising:
a main body (<NUM>) configured to receive a medicament cartridge (<NUM>),
a needle sleeve (<NUM>) axially movable with respect to the main body (<NUM>),
a needle holder (<NUM>) holding a needle (<NUM>), and
a displacement element (<NUM>) coupled to the needle holder (<NUM>) and disengageably coupled to the needle sleeve (<NUM>);
wherein the displacement element (<NUM>) comprises at least one ramped surface (<NUM>) and at least one slot;
wherein the needle sleeve (<NUM>) comprises at least one pin (<NUM>) arranged to slide through the slot when the displacement element (<NUM>) and the needle sleeve (<NUM>) are in rotational alignment; and
wherein, upon axial displacement of the needle sleeve (<NUM>) by a predefined distance in a proximal direction, the needle holder (<NUM>) and needle (<NUM>) are displaced axially in a proximal direction.