Patent Description:
Medicament injection devices can take various forms. One form uses a syringe, where medicament is stored in a hollow cylinder, typically formed of glass. The medicament is sealed from the environment with a plunger moveable within the cylinder, and a needle fluidly connected to the syringe's distal end. The needle must remain capped in order to maintain the medicament under sterile conditions.

Another form of injection device uses a cartridge instead of a syringe, the cartridge having a distal seal instead of the syringe's needle. Typically a patient connects a double-ended needle to the cartridge before injection, thereby piercing the cartridge's seal with the proximal tip of the double-ended needle.

While a cartridge can provide handling and storage advantages relative to syringes, they are not without shortcomings. For example, the attachment of a needle to the cartridge requires an additional step. This step can be problematic for patients with limited dexterity, poor coordination, or who have lost a degree of sensation in their hands. Even with such disadvantages, in certain situations it is desirable to provide an injection device in which the needle is kept separate from the medicament until such time as the patient wishes to commence the injection. The injection device described herein aims to overcome one or more problems associated with prior devices.

<CIT> discloses a drug delivery system comprising a drug delivery device which comprises a housing and a cartridge. The drug delivery device has a proximal end and a distal end. The drug delivery system further comprises a needle assembly which is attachable to the drug delivery device. The needle assembly and the drug delivery device are configured such that the cartridge is moved in the proximal direction with respect to the housing when the needle assembly is attached to the drug delivery device.

<CIT> discloses an injection device including a sterile injection needle, the injection device including a container for an injectable product including an outlet for the product at a front end sealed by a membrane, the injection needle, which has a front needle portion facing away from the container for injecting into tissue and a rear needle portion which, in an initial state of the injection device lies opposite and faces the membrane and which is injected through the membrane into the container for an injection, a needle support which holds the injection needle in a central needle portion, and a casing which supports the needle support and the container and movably guides them relative to each other for piercing the membrane, wherein, in the initial state of the injection device, the needle support forms a sterile chamber for the rear needle portion, the chamber sealed by a sealing element on a rear side of the chamber facing the outlet of the container, and wherein the front end of the container for piercing the membrane penetrates through the sealing element into the sterile chamber.

A first embodiment provides a medicament injection device comprising a main body configured to receive a medicament cartridge sealed with a penetrable barrier, a needle holder holding a needle, a needle sleeve arranged around at least a portion of the needle holder and needle, and arranged to be axially movable with respect to the main body; and a retainer coupled to the needle holder and to the needle sleeve and axially movable with respect to the main body along the main axis of the device; wherein the retainer is coupled to the needle holder so that, upon displacement of the needle sleeve and the retainer by a predefined distance towards a proximal end of the main body, the needle holder and needle are displaced axially towards the proximal end of the main body and decouple from the retainer; and wherein the needle sleeve is configured to disengage from the needle holder upon axial displacement of the needle sleeve in the proximal direction beyond the predefined distance.

The needle holder is configured to dock with a medicament cartridge received by the main body.

In a first position, the needle sleeve may be coupled to the retainer so that axial movement of the needle sleeve in a proximal direction causes the axial displacement of the retainer, the needle carrier and the needle in a proximal direction.

The needle holder may comprise a female part arranged to dock with a medicament cartridge having a male part to form a frictional fit with respect to each other subsequent to displacement of the needle holder by the predefined distance.

The needle holder further may comprise a lip configured to prevent subsequent axial displacement of the needle holder and needle with respect to the medicament cartridge subsequent to the needle holder docking with the medicament cartridge.

The main body may comprise a slotted ramp and the retainer may comprise one or more radial members, wherein axial movement of the one or more radial members over the slotted ramp causes outward radial movement of the radial members, thereby causing the retainer to disengage from the needle holder.

The needle holder may comprise a flexible lever configured to flex and disengage from the retainer in response to the retainer moving axially by the predefined distance in the proximal direction.

The retainer may comprise one or more radial members each configured to separate into two parts subsequent to axial displacement by the predefined distance.

The device may contain a medicament cartridge and wherein the needle penetrates the barrier of the medicament cartridge upon displacement of the needle holder displacement member by a predefined distance in the proximal direction.

The device may contain a medicament cartridge containing a medicament.

The device may be an auto-injector device.

A second embodiment provides a method according to independent claim <NUM>.

Exemplary embodiments of the present invention are described with reference to the accompanying drawings, in which:.

Embodiments of the current disclosure provide a mechanism for inserting a needle of an injection device into a cartridge containing a medicament for injection by a patient or care giver. The mechanism allows the medicament cartridge to remain sealed until such time as the user wishes to commence the injection. Automating a 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 some embodiments described below, the user does not touch the needle when the needle is inserted into the medicament cartridge.

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 main body <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 main body <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> (see <FIG>) 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 of main body <NUM>.

Insertion of needle <NUM> can occur via several mechanisms. For example, needle <NUM> may be fixedly located relative to main body <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. 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 a first 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 23a 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 <NUM> comprises a retainer <NUM> which is annular or tubular in shape. As shown in <FIG>, the retainer <NUM> has a generally circular cross-section. The retainer <NUM> has first and second radial members <NUM> which extend from the curved wall of the retainer <NUM> inwardly to engage with the needle holder <NUM>. Each of the radial members <NUM> is provided with a hole <NUM> which, as explained below, is arranged to receive the needle sleeve <NUM> as the retainer <NUM> is moved axially towards the cartridge <NUM>. The curved wall of the retainer <NUM> is provided with one or more expansion elements <NUM>. The expansion elements <NUM> are configured to enlarge the cross-sectional circumference of the retainer <NUM> as the retainer <NUM> moves over the ramped portion of the main body <NUM>.

As shown in <FIG>, each of the radial members <NUM> extend through apertures located in the wall of the needle sleeve <NUM> and through elongate slits <NUM> in the wall of the main body <NUM>. The ends of the radial members <NUM> extending through the slits <NUM> are flanged so that the flanges sit on the outer surface of the main body <NUM>.

The main body <NUM> comprises a slotted ramp 11a around each of the slits <NUM>. The ramp 11a is arranged so that the outer diameter of the wall of the main body <NUM> (from one slit <NUM> to the second slit <NUM> shown in <FIG>) is greater at the end of the slits <NUM> proximate the head <NUM> of the medicament cartridge <NUM> than it is at end of the slits <NUM> located away from the head <NUM> of the medicament cartridge <NUM> and towards the distal end of the device <NUM>. As explained in more detail below, the ramp configuration causes the retainer <NUM> to expand as it moves axially towards the medicament cartridge <NUM>, eventually leading to the radial members <NUM> decoupling from the needle holder <NUM> once the retainer <NUM> moves axially beyond a predefined distance towards the medicament cartridge <NUM>.

<FIG> show the components of the device <NUM> in their initial position prior to insertion of the needle into the medicament cartridge in preparation for the injection of medicament into the patient.

<FIG> shows a side-on cross-section of the auto-injector device <NUM> as the user pushes the needle sleeve <NUM> in the direction of the bold arrows up to the predefined distance d at which point the retainer <NUM> decouples from the needle holder <NUM>.

The needle sleeve <NUM> is coaxial with respect to main body <NUM> and slides along inside the main body <NUM> of the device <NUM>. The axial movement of the sleeve <NUM> causes the retainer <NUM> to move axially towards the medicament cartridge <NUM> since the radial members <NUM> abut the needle sleeve and are fixed relative to the needle sleeve <NUM>. Each of the radial members <NUM> abuts at one end thereof to the needle holder <NUM>. The axial movement of the radial members <NUM> thereby causes the needle holder <NUM> and the needle <NUM> to move axially towards the medicament cartridge <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 lip 18b extending around the cup-shaped part 18a of the needle holder 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, and separation from, the medicament cartridge <NUM> is prevented by the lip.

Alternatively, the diameter of the cup shaped part 18a and the diameter of the head <NUM> of the medicament cartridge <NUM> may be arranged to ensure a close frictional fit between the needle holder <NUM> and the medicament cartridge <NUM>. In embodiments having a close frictional fit, no lip may be provided.

As shown in <FIG>, the needle <NUM> pierces the septum 23a 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 23a 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.

During axial movement towards the medicament cartridge <NUM>, the radial members <NUM> are guided along the respective slits <NUM> located in the wall of the main body <NUM>. Since the part of the wall of the main body <NUM> containing the slits is ramped, the flanged ends of the radial members <NUM> extending through the slits <NUM> causes a radial displacement of each of the radial members <NUM>. As such, the retainer <NUM> decouples from the needle holder <NUM> at the point shown in <FIG>. The holes <NUM> in the radial members <NUM> align radially with the needle sleeve <NUM>. The needle sleeve <NUM> is provided with longitudinal slits (not shown) to allow the needle sleeve <NUM> to slide through the radial members <NUM> as the needle sleeve <NUM> is displaced axially subsequent to attachment of the needle holder <NUM> to the medicament cartridge <NUM>, as shown in <FIG>.

The decoupling of the retainer <NUM> from the needle holder <NUM> and the docking 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 direction of the bold arrows beyond the predefined distance at which point the needle sleeve <NUM> decouples from the needle holder <NUM>.

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 the needle sleeve <NUM> thereby causing the needle sleeve <NUM> to retract relative to the main body <NUM>.

After the radial members <NUM> have each separated from the needle holder <NUM>, axial movement of the needle sleeve <NUM> towards the proximal end of the device <NUM> is no longer coupled to corresponding movement of the needle holder <NUM>. In other words, once the needle sleeve <NUM> is pushed beyond the predefined distance, the needle sleeve <NUM> disengages from the needle holder <NUM> which remains fixed to the medicament cartridge <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.

While the axial movement of the needle holder <NUM> may be caused by the user pushing the needle sleeve <NUM> thereby pushing the retainer <NUM>, as shown in <FIG>, it is also possible for the user to push the retainer <NUM> directly, thereby causing the needle sleeve <NUM> and needle holder <NUM> to move axially towards the proximal end of the device <NUM>. The ends of the radial members <NUM> extending through the slits <NUM> may have an enlarged surface to allow the user to push the radial members <NUM> directly.

In the embodiment shown in <FIG>, the retainer <NUM> is provided with two radial members <NUM>. However, in alternative embodiments, more members may be provided.

An alternative embodiment of the invention, which is a variation of the embodiments described above with reference to <FIG>, is shown in <FIG>.

A device <NUM> may be provided having an overall structure similar to the device <NUM> described above. Aspects of the device <NUM> that are substantially the same as aspects described above with respect to the device <NUM> will not be repeated.

The device <NUM> has a needle holder <NUM> which is similar to the needle holder <NUM> except that the needle holder <NUM> has one or more bending elements or levers <NUM> that are arranged to engage with a retainer <NUM>. The main body <NUM> and the needle sleeve <NUM> are both provided with apertures through which the retainer <NUM> extends.

As either the retainer <NUM> or needle sleeve <NUM> is pushed axially in a similar manner to that described above the needle holder <NUM> is pushed axially in a proximal direction towards the medicament cartridge <NUM>. As above, the needle holder <NUM> becomes fixed to the medicament cartridge <NUM> by virtue of a close frictional fit and/or the clip around the head of the medicament cartridge <NUM>. The needle <NUM> is thereby inserted into the cartridge <NUM>.

As either the retainer <NUM> or needle sleeve <NUM> is pushed further, the levers <NUM> bend and decouple from the retainer <NUM>, as shown between <FIG>.

The force needed to bend the levers <NUM> must be larger than the force needed to attach the needle holder <NUM> to the cartridge <NUM> so that the decoupling of the levers <NUM> from the retainer <NUM> occurs subsequent to the attachment of the needle holder <NUM> to the cartridge <NUM>.

In the embodiment shown in <FIG>, no ramp is required since the decoupling is achieved by bending the levers <NUM> rather than causing an outward radial movement of radial members of the retainer, as shown in <FIG>.

Further alternative embodiments provide for decoupling of the needle holder from a retainer by breaking the levers once the retainer has been pushed beyond a predetermined point. This can be done using predetermined breaking points on the lever or by pushing the lever against a sharp edge (which may be fixed to the cartridge holder) once the needle holder is attached to the medicament cartridge.

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 <NPL>, for example, without limitation, main groups <NUM> (antidiabetic drugs) or <NUM> (oncology drugs), and <NPL>on.

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-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-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-11260C, 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>, <NUM>) comprising:
a main body (<NUM>, <NUM>) configured to receive a medicament cartridge (<NUM>) sealed with a penetrable barrier (23a),
a needle holder (<NUM>, <NUM>) holding a needle (<NUM>),
a needle sleeve (<NUM>, <NUM>) arranged around at least a portion of the needle holder (<NUM>, <NUM>) and needle (<NUM>), and arranged to be axially movable with respect to the main body (<NUM>, <NUM>); and
a retainer (<NUM>, <NUM>) coupled to the needle holder (<NUM>, <NUM>) and to the needle sleeve (<NUM>, <NUM>) and axially movable with respect to the main body (<NUM>, <NUM>) along the main axis of the device (<NUM>, <NUM>);
characterised in that
the retainer (<NUM>, <NUM>) is coupled to the needle holder (<NUM>, <NUM>) so that, upon displacement of the needle sleeve (<NUM>, <NUM>) and the retainer (<NUM>, <NUM>) by a predefined distance towards a proximal end of the main body (<NUM>, <NUM>), the needle holder (<NUM>, <NUM>) and needle (<NUM>) are displaced axially towards the proximal end of the main body (<NUM>, <NUM>) and decouple from the retainer (<NUM>, <NUM>) and dock with the medicament cartridge received by the main body; and
wherein the needle sleeve (<NUM>, <NUM>) is configured to disengage from the needle holder (<NUM>, <NUM>) upon axial displacement of the needle sleeve (<NUM>, <NUM>) in the proximal direction to the predefined distance and is configured to be displaced in the proximal direction beyond the predefined distance.