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.

<CIT> discloses an injector for injecting a medicament into a patient. The injector includes a container defining a first chamber, which contains a fluid therein, and a second chamber. The injector also includes an injection conduit configured for directing the fluid fired from the container into the patient. A transfer mechanism is operable by a user to transfer the fluid from the first chamber to the second chamber in a first stage of operation, and a firing mechanism is operable by the user for firing the fluid from the second chamber through the injection conduit in a second stage of operation.

<CIT> discloses an administration device comprising a container and a mixing device for mixing an active substance (in a first chamber) with a dilution liquid (in a second chamber). The container has a membrane seal at one end and is combined with a mixing device for mixing the active substance. The administration device has an injection needle unit with a distal needle portion facing away from the container for piercing the skin, and disposed opposite thereto is a proximal needle portion facing the membrane when the administration device is in the initial position, which is thrust through the membrane into the container in a mixing position.

A first embodiment provides a medicament injection device comprising a main body arranged to receive a medicament cartridge; a needle carrier carrying a needle, wherein the needle carrier is axially movable with respect to the main body; and a rotatable cap at a distal end of the device, wherein the cap is removably coupled to the needle carrier, a releasable arrangement between the main body and the cap comprising a guide element and a slotted link, wherein the slotted link is arranged to cause the guide element to follow a predefined path at least partly in an axial direction during rotational movement of the cap, thereby causing the needle carrier to move axially towards a proximal end of the device as the cap is rotated up to a predefined point, wherein the main body comprises a medicament cartridge holder comprising the guide element depending therefrom for engagement with the cap and wherein the medicament cartridge holder is disposed within the main body, and wherein the needle holder is arranged to become fixed to the medicament cartridge after axial movement thereof in the proximal direction.

The cap may comprise a tubular element, the outer surface of the tubular needle shielding element having the slotted link arranged thereon to receive the guide element.

The tubular element may contain a needle shield.

The slotted link may be configured to cause the cap to move axially in a distal axial direction when the cap is rotated beyond the predefined point.

The slotted link may comprise a portion that is relatively narrow in comparison to the remainder of the slotted link.

The slotted link may comprises an axially straight part.

The needle holder may comprise a lip arranged to cooperate with a head of the medicament cartridge.

The needle holder may be dimensioned to form a frictional fit with the head of the medicament cartridge.

The medicament cartridge holder may contain a medicament cartridge having a penetrable barrier at a distal end thereof, and the axial movement of the needle carrier towards the proximal end may cause the needle to pierce the barrier of the medicament cartridge.

The medicament cartridge may contain a medicament.

A second embodiment provides a method of operating a medicament injection device prior to injection of medicament, the medicament injection device having a rotatable cap, a main body arranged to receive a medicament cartridge, a needle carrier carrying a needle, and a releasable arrangement between the main body and the cap, wherein the releasable arrangement comprises a guide element and a slotted link, the method comprising: rotating the cap, thereby causing the releasable arrangement between the main body and the cap to cooperate to cause the needle to move axially in a proximal direction and to penetrate a separable barrier of the medicament cartridge, wherein the main body comprises a medicament cartridge holder comprising the guide element depending therefrom for engagement with the cap, and wherein the medicament cartridge holder is disposed within the main body.

Further rotation of the cap may cause the cap to move axially in a distal direction.

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

Embodiments 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 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.

Embodiments provide a mechanism whereby a needle holder holding a needle is automatically connected to a medicament cartridge in response to rotation of a device cap.

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> 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 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>& <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 a first embodiment of the invention. The device <NUM> comprises a generally cylindrical main body <NUM> and a generally cylindrical cap <NUM>.

The device <NUM> also comprises a tubular needle sleeve <NUM> that fits inside the main body <NUM> and is arranged to slide axially with respect to the main body <NUM>. The needle sleeve <NUM> is a protective sleeve that prevents unwanted exposure of the needle <NUM>. The needle sleeve <NUM> has a similar shape to the main body and is hollow and generally cylindrical.

The cap <NUM> has an end wall and a curved side wall and a tubular wall 12a extending from the end wall containing a needle shield 12c. The needle shield 12c protects a distal end of the needle <NUM> during storage. The needle shield 12c acts to seal the needle <NUM>. There may be provided a press fit, form fit or adhesive bond between the needle shield 12c and the tubular wall 12a.

The needle shield material can be an elastomer like known needle shields for syringes for auto injectors. The needle shield can also be made out of thermoplastic elastomer (TPE) which may be <NUM> injection moulded into the cap <NUM>.

The needle shield is fixed to the cap regarding movement in an axial direction, so that the needle shield 12c is removed when the cap is removed.

The cap <NUM> fits over the needle sleeve <NUM>. The cap <NUM> is movable axially with respect to the main body <NUM>.

The 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> may be provided to a user separately to the device <NUM>. The user may insert the cartridge <NUM> into the device <NUM>.

The device <NUM> comprises a needle <NUM> which is held towards the proximal end thereof by a needle holder <NUM>. The distal end of the needle <NUM> is covered by the tubular member 12a of the cap <NUM>. The needle holder <NUM> which holds the needle <NUM> is axially movable relative to the main body <NUM> and the cartridge <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 cup-shaped portion 18a is shaped to engage with the head <NUM> of the cartridge <NUM>.

The cartridge holder <NUM> is generally tubular and is coaxial with respect to the main body <NUM>. The main wall of the cartridge holder <NUM> extends around the body <NUM> of the cartridge <NUM> and extends towards the distal end of the device <NUM> so that it surrounds the head <NUM> of the cartridge <NUM>, the needle holder <NUM> and a proximal end portion of the tubular member 12a of the cap <NUM>. The cartridge holder <NUM> has a diameter greater than that of the cartridge <NUM> and needle holder <NUM>. The cartridge holder <NUM> has ribs <NUM> extending inwardly from the main wall to support the cartridge <NUM> along the length of the cartridge <NUM>. Alternatively, the cartridge holder <NUM> has a diameter approximately equal to that of the cartridge <NUM> so that a frictional fit is provided between the cartridge <NUM> and the cartridge holder <NUM> so that the ribs are not necessary. The cartridge holder <NUM> has a diameter approximately equal to that of the tubular member 12a so that a frictional fit is achieved when the cap <NUM> is attached to the rest of the device <NUM>, as shown in <FIG>.

The cartridge holder <NUM> has a guide element 20a such as a pin extending from the inner surface of the main wall of the cartridge holder <NUM>. The guide element 20a engages with a slotted link 12b which is a groove provided in the outer surface of the tubular member 12a of the cap <NUM>.

The slotted link 12b defines a path followed by the guide element 20a as the cap <NUM> is rotated by the user and as the cap is pulled away from the main body.

<FIG> is a projection of the path defined by the slotted link 12b onto a two-dimensional surface. The slotted link 12b is generally hooked shaped in this projection. The curved portion shown in <FIG> defines the path taken by the guide element 20a as the user rotates the cap <NUM>. The curved path defined by the slotted link varies axially as well as running circumferentially around the tubular member 12a. Therefore movement of the fixed guide element 20a along the path defined by the slotted link results in axial movement of the cap <NUM> as the cap <NUM> is rotated relative to the main body <NUM>.

The straight portion of the slotted link 12b defines the path taken by the guide element 20a as the user pulls the cap <NUM> from the main body <NUM> subsequent to rotation of the cap <NUM> and the attachment of the needle holder <NUM> to the medicament cartridge <NUM>. The slotted link 12b prevents detachment of the cap <NUM> before the cap has been rotated sufficiently to ensure attachment of the needle holder <NUM> to the medicament cartridge <NUM>.

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>. 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.

<FIG> shows the device <NUM> as the user rotates the cap <NUM>. The guide element 20a moves along a curved portion of the path defined by the slotted link 12b. In <FIG>, the guide element 20a is located in the part of the slotted link 12b furthest away from the proximal end of the tubular member 12a. Since the position of the guide element 20a is fixed axially with respect to the main body <NUM> and medicament cartridge <NUM> and cap <NUM> are axially movable with respect to the main body <NUM> and medicament cartridge <NUM>, the rotation of the cap <NUM> from the position shown in <FIG> leads to an axial movement of the cap <NUM> towards the medicament cartridge <NUM>. The tubular member 12a abuts the needle holder <NUM> thereby causing axial movement of the needle holder towards the medicament cartridge <NUM>.

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>.

After moving axially towards the medicament cartridge, the cup-shaped part 18a of the needle holder <NUM> fits over the head <NUM> of 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>.

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

As the cap <NUM> is rotated beyond the position shown in <FIG>, the guide element 20a is guided along the curved portion of the slotted link 12b between the guide element 20a position shown in <FIG> and the axially straight portion of the path. Because of the direction of the curve of the slotted link, rotation of the cap at this stage causes the cap <NUM> to move axially away from the needle holder <NUM> and the medicament cartridge <NUM>.

<FIG> show the device <NUM> as the cap <NUM> is removed. The guide element 20a reaches the axially straight portion of the slotted link 12b. The cap <NUM> can no longer be rotated because of the axial direction of the slotted link 12b. The user pulls the cap <NUM> away from the main body <NUM> in the distal direction.

Once the cap <NUM> has been removed, the user may commence the injection. The distal end of the device <NUM> is held against the patient's injection site and the device actuated.

In some embodiments, as shown in <FIG>, the slotted link may 12b may have a narrowed portion <NUM> that is narrower than the rest of the slotted link 12b. This helps to prevent accidental rotation of the cap <NUM> so that the needle <NUM> is not inserted into the cartridge <NUM> prematurely.

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., shortor 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-(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-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>) comprising:
a main body (<NUM>) arranged to receive a medicament cartridge (<NUM>);
a needle carrier (<NUM>) carrying a needle (<NUM>), wherein the needle carrier (<NUM>) is axially movable with respect to the main body (<NUM>); and
a rotatable cap (<NUM>) at a distal end of the device (<NUM>), wherein the cap (<NUM>) is removably coupled to the needle carrier (<NUM>),
a releasable arrangement between the main body (<NUM>) and the cap (<NUM>) comprising a guide element (20a) and a slotted link (12b), wherein the slotted link (12b) is arranged to cause the guide element (20a) to follow a predefined path at least partly in an axial direction during rotational movement of the cap (<NUM>), thereby causing the needle carrier (<NUM>) to move axially towards a proximal end of the device (<NUM>) as the cap (<NUM>) is rotated up to a predefined point;
wherein the main body (<NUM>) comprises a medicament cartridge holder (<NUM>) comprising the guide element (20a) depending therefrom for engagement with the cap (<NUM>), and wherein the medicament cartridge holder (<NUM>) is disposed within the main body (<NUM>), and wherein the needle carrier (<NUM>) is arranged to become fixed to the medicament cartridge (<NUM>) after axial movement thereof in the proximal direction.