Patent Description:
Current therapies delivered by means of self-administered injections include drugs for diabetes (both insulin and new GLP-A class drugs), migraine, hormone therapies, anticoagulants etc. Administering an injection is a process which presents a number of risks and challenges for user and healthcare professionals, both mental and physical.

Conventional injection devices typically fall under two categories - manual devices and auto-injectors. In a conventional manual device, a user must provide a force to drive a liquid medicament out of the device, e.g. by depressing a plunger.

Auto-injectors aim to make self-administration of injected therapies easier for users. Auto-injectors are devices which completely or partially replace activities involved in medicament delivery of manual devices. These activities may include removal of a protective syringe cap, insertion of a needle into a patient's skin, injection of the medicament, removal of the needle, shield of the needle and preventing reuse of the device. This overcomes many of the disadvantages of manual devices. Injection forces/button extension, hand-shaking and the likelihood of delivering an incomplete dose are reduced. Triggering may be performed by numerous means, for example a trigger button or the action of the needle reaching its injection depth.

In some injection devices, a driving mechanism is used for driving a piston in a syringe to push liquid medicament out of the syringe during an injection process. Some injection devices adopt a driving mechanism comprising a spring element that is directly supported by a number of plastic components within the housing of the injection device. Due to this direct contact between the plastic components and the spring element of the driving mechanism, creeping of the plastic components may occur because of the stress caused by the spring force stored in the spring element which reduces the shelf life of the injection devices. <CIT> discloses an injection device comprising an actuator and a mechanism for locking the actuator. <CIT> relates to a liquid medicine injection system with prefilled syringe. <CIT> relates to an automatic injection device with pneumatic damping.

According to an aspect of the present invention, there is provided an injection device according to claim <NUM>.

The injection device may further comprise a retractable inner sleeve, wherein a part of the plate member of the locking mechanism is connected to the inner sleeve such that when a pulling force acts on the inner sleeve to move it towards a distal direction, the plate member becomes separated.

The injection device may further comprise a removable cap arranged to be removably engaged with the distal end of the housing, and an engagement mechanism for releasably engaging the removable cap with the inner sleeve.

The engagement mechanism may comprise a protrusion at an external surface of the removable cap and a slot at an inner surface of the inner sleeve, wherein the protrusion is arranged to be releasably engaged with the slot by rotation of the removable cap.

The injection device may further comprise a rib arranged on an inner surface of the housing, wherein the rib is arranged to hold at least a part of the housing member of the driving mechanism when the locking mechanism is released, the rib being further arranged to be actuated so as to release the housing member of the driving mechanism to push the piston towards the distal end.

The locking mechanism may comprise a clamp arranged to clamp the housing member of the driving mechanism in a fixed position in the initial inactive state, wherein the clamp is arranged to be bent by a pushing force to release the housing member such that the driving mechanism can be actuated.

The injection device may further comprise a retractable inner sleeve located adjacent to the clamp, wherein the pushing force is provided by pushing the inner sleeve in the proximal direction of the injection device.

The locking mechanism may comprise a clamp arranged to clamp the housing member of the driving mechanism in a fixed position in the initial inactive state, wherein the clamp is arranged to be released by a pulling force to release the housing member such that the driving mechanism can be actuated.

The injection device may further comprise a retractable inner sleeve located adjacent to the clamp, wherein the clamp is connected to the inner sleeve and the pulling force is provided by pulling the inner sleeve in the distal direction of the injection device.

The locking mechanism may comprise a cotter, a first through-hole at a first side of the housing, a second through-hole at a housing member of the driving mechanism, and a third through-hole at a second side of the housing, the second side being opposite to the first side, wherein the first, second, and third through-holes are aligned such that the cotter can be removably inserted through the housing in a direction perpendicular to a longitudinal axis of the injection device so as to retain the driving mechanism in a fixed position in the initial in active state.

The injection device may contain a liquid medicament.

According to another aspect of the invention, there is provided an injection device according to claim <NUM>.

The injection device may further comprise a retractable inner sleeve.

The injection device may further comprise a retractable inner sleeve located adjacent to the clamp, wherein the clamp is connected to the inner sleeve and the pulling force is provided by pulling the inner sleeve in the distal direction of the injection device. The locking mechanism may comprise a cotter, a first through-hole at a first side of the housing, a second through-hole at a housing member of the driving mechanism, and a third through-hole at a second side of the housing, the second side being opposite to the first side, wherein the first, second, and third through-holes are aligned such that the cotter can be removably inserted through the housing in a direction perpendicular to a longitudinal axis of the injection device so as to retain the driving mechanism in a fixed position in the initial in active state.

According to another aspect of the present invention, there is provided a system comprising: the injection device of any of claims <NUM>, <NUM> or <NUM> to <NUM>; and an apparatus configured to remove the removable cap from the injection device.

According to another aspect of the present invention, there is provided a method according to claim <NUM>.

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

Reference will now be made in detail to the embodiments, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to like elements throughout.

An injection device with an arrangement for activating a driving mechanism is provided. The injection device comprises a housing arranged to contain a syringe with a piston for sealing the syringe and displacing the medicament, the housing having a proximal end and a distal end, wherein the distal end is intended to be applied against an injection site; a driving mechanism arranged between the piston and the proximal end of the housing; and a locking mechanism arranged to retain the driving mechanism in an initial inactive state in which the driving mechanism cannot be actuated; wherein when the locking mechanism is released, the driving mechanism can be actuated to push the piston towards the distal end of the housing to displace the medicament.

By using a locking mechanism to retain the driving mechanism in an initial inactive state, the driving mechanism does not need to be supported directly by other components in the injection device, including some plastic components which are prone to creeping under prolonged stress. Therefore, the phenomenon of plastic creeping causing a change of shape of the plastic components can be prevented. This increases the shelf life of the injection device. In particular, the locking mechanism can prevent any direct contact between the driving mechanism and the piston in the injection device. Therefore, the problem of prolonged pressure on the piston when an injection device is stored for a long period is prevented.

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 housing <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 housing <NUM>. Typically a user must remove cap <NUM> from housing <NUM> before device <NUM> can be operated.

As shown, housing <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 housing <NUM> to permit movement of sleeve <NUM> relative to housing <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 housing <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 housing <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 housing <NUM> relative to sleeve <NUM>.

Another form of insertion is "automated," whereby needle <NUM> moves relative to housing <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 housing <NUM>. However, in other embodiments, button <NUM> could be located on a side of housing <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 housing <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 housing <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 housing <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 housing <NUM>.

Another form of needle retraction can occur if needle <NUM> is moved relative to housing <NUM>. Such movement can occur if the syringe within housing <NUM> is moved in a proximal direction relative to housing <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 housing <NUM> can be locked with a locking mechanism. In addition, button <NUM> or other components of device <NUM> can be locked as required.

Referring now to <FIG>, part of an injection device <NUM> according to an exemplary embodiment of the invention is shown. The injection device <NUM> is in the form of an auto-injector that has similar features to the device <NUM> described above in relation to <FIG>, with like features retaining the same reference numerals. A difference is that the cap <NUM> of the injection device <NUM> described above is omitted and is replaced with an alternative removable cap <NUM>.

A syringe 11a is provided within the housing <NUM> of the injection device <NUM>. The syringe 11a contains liquid medicament which is sealed by a piston, stopper, or bung <NUM> located within the syringe 11a. In an initial state, the piston <NUM> is positioned at a position closest to the proximal end of the housing <NUM>. A driving mechanism <NUM> is provided at the proximal end of the housing <NUM> which is arranged to push the piston <NUM> towards the distal end of the housing <NUM> once it is in an active state and when it is actuated. The syringe 11a further includes a hollow injection needle <NUM> through which medicament is displaced when the piston <NUM> is pushed towards the distal end of the housing <NUM>.

In the present embodiment, the driving mechanism <NUM> comprises a drive spring that is initially in a compressed state, storing spring energy that is to be released when the driving mechanism is actuated.

In an initial state, which will be referred to herein as the "first state", the driving mechanism <NUM> is held in an inactive state by a locking mechanism. In this embodiment, the locking mechanism comprises a plate member <NUM> which is arranged between the drive spring of the driving mechanism <NUM> and the piston <NUM> such that the drive spring of the driving mechanism <NUM> cannot be actuated to push the piston <NUM>, due to the rigidity of the plate member <NUM>. The plate meber <NUM> in this embodiment comprises two parts which can be separated under a pulling force. This will be explained in further detail below.

In the present embodiment, the plate member <NUM> is connected to an inner sleeve <NUM> which is arranged on an inner surface of the housing <NUM>. Specifically, a part of the plate member <NUM> is connected to the inner sleeve <NUM> such that when the inner sleeve <NUM> is pulled towards the distal end of the housing <NUM> by a pulling force, the plate member <NUM> separates so as to activate the driving mechanism <NUM>. In this embodiment, the plate member <NUM> of the locking mechanism becomes separated into two parts when released, such that the drive spring of the driving mechanism <NUM> is no long held in the inactive state. When the driving mechanism <NUM> is activated, it can be actuated so as to push the piston <NUM> towards the distal end of the housing <NUM>.

A spring element <NUM> is provided within the housing <NUM> and arranged around the syringe 11a. The spring element <NUM> is initially in a compressed state when the removable cap <NUM> is attached to the housing <NUM>. The spring element <NUM> is supported by a rib (not shown in the drawing) arranged on the inner sleeve <NUM> such that when the inner sleeve <NUM> is pulled towards the distal end, the spring element <NUM> decompresses due to the reduction of compressive force exerted on the spring element <NUM>. After the removable cap <NUM> is disengaged from the housing <NUM>, the inner sleeve <NUM> protrudes from the opening of the housing <NUM> under a spring force provided by the spring element <NUM>, so as to act as a retractable needle shroud. By providing this needle shroud after the removable cap <NUM> is disengaged from the housing <NUM>, the needle shroud prevents both unintentional damage of the needle during handling and access of a user to the needle for avoiding stick injuries. The needle shroud can be retracted into the housing <NUM>, against the bias provided by the spring force, by applying a pushing force on the inner sleeve <NUM> towards the proximal end of the injection device, for example by applying the distal end of the injection device against a patient's skin.

The removable cap <NUM> of the injection device <NUM> of the present embodiment comprises a needle shield <NUM>, an engagement mechanism <NUM>, and a connection mechanism <NUM>. The needle shield <NUM> comprises a recess that is configured to receive a portion of a syringe 11a that is housed in a housing <NUM> of the injection device <NUM>. The friction between the needle shield and an end portion of the syringe 11a is sufficient to hold the needle shield <NUM> in place, covering the hollow injection needle <NUM>.

The removable cap <NUM> in the first state is attached to the housing <NUM> such that the end portion of the syringe 11a is received in the recess of the needle shield <NUM>. Thus, the needle <NUM> is covered by the needle shield <NUM> to keep the needle <NUM> sterile and to prevent the needle <NUM> from causing injury to the patient.

The removable cap <NUM> further comprises a protrusion which in the first state is engaged with a slot provided at the inner sleeve <NUM> of the injection device <NUM>. In this embodiment, the protrusion of the removable cap <NUM> and the slot at the inner sleeve <NUM> forms an engagement mechanism <NUM> that releasably engages the removable cap <NUM> with the housing <NUM>. In this embodiment, the engagement mechanism releasably engages the removable cap <NUM> with the inner sleeve <NUM>. This engagement mechanism can be disengaged by using a rotational force on the removable cap <NUM>. This will be explained in further detail with respect to <FIG>.

The connection mechanism <NUM> of the removable cap <NUM> is arranged to allow the removable cap 24to be connected to an external apparatus, e.g. a tabletop apparatus. In this embodiment, the connection mechanism <NUM> comprises a groove for engaging with another groove, projection, or the like at the external apparatus. The interaction between the connection mechanism <NUM> of the removable cap <NUM> and the external apparatus will be explained in further detail with respect to <FIG>.

<FIG> is a schematic cross-sectional side view of part of the injection device of <FIG> in a second state.

In the second state, i.e. an intermediate state, the removable cap <NUM> is pulled linearly and axially in a direction indicated by 'F' in <FIG>, i.e. away from the proximal end of the housing <NUM>. In this embodiment, this pulling force is applied by the external apparatus (not shown in the drawing) to which the removable cap <NUM> is connected.

Due to the engagement mechanism arranged between the removable cap <NUM> and the inner sleeve <NUM>, as the removable cap <NUM> is pulled in direction 'F', the inner sleeve <NUM> is pulled axially together towards the same direction. However, because the engagement mechanism cannot be released unless a rotational force is applied on the removable cap <NUM>, the removable cap <NUM> remains attached with the inner sleeve <NUM> in the second state. The spring element <NUM> is decompressed due to the reduction of compressive force on the spring element <NUM> to the inner sleeve <NUM>, as shown in <FIG>.

At the same time, since the inner sleeve <NUM> is pulled linearly and axially towards the direction 'F' (i.e. away from the proximal end of the housing <NUM>), the plate member <NUM> is snapped by this pulling force which causes it to separate into two different parts 29a and 29b. The first plate part 29a remains in place between the piston <NUM> and the driving mechanism <NUM>, while the second plate part 29b is attached to the inner sleeve <NUM> and moves along with the inner sleeve <NUM> as it is being pulled away from the proximal end of the housing <NUM>.

Since the plate member <NUM> is separated, the driving mechanism <NUM> is no longer held in an inactive state. In this embodiment, the drive spring of the driving mechanism <NUM> is no longer held in place by the plate member <NUM>. Therefore, the driving mechanism <NUM> can now be actuated by e.g. pressing a button, so as to push the piston <NUM> towards the distal end of the housing <NUM>.

<FIG> is a schematic cross-sectional side view of part of the injection device of <FIG> in a third state.

In the third state, i.e. a final state, the removable cap <NUM> is rotated in a direction as shown by the curved arrow in <FIG>. The engagement mechanism is released by this rotational movement of the removable cap <NUM>. Specifically, the protrusion of the removable cap <NUM> becomes disengaged from the slot at the inner sleeve <NUM> of the injection device <NUM> with this rotational movement. The removable cap <NUM> can therefore be disengaged from the rest of the injection device <NUM> as shown in <FIG>.

In the third state, the inner sleeve <NUM> act as a retractable needle shroud to shield the needle before and after injection, since it is biased to protrude from the opening of the housing <NUM> by the spring force provided by the spring element <NUM>. As explained above, by providing this needle shroud after the removable cap <NUM> is disengaged from the housing <NUM>, the needle shroud prevents both unintentional damage of the needle during handling and access of a user to the needle for avoiding stick injuries.

A sequence of the operation of the injector device <NUM> of the present embodiment is described as follows:
The removable cap <NUM> is disengaged from the housing <NUM>, either manually by a user or using an external apparatus (such as one illustrated in <FIG>). Removal of the removable cap <NUM> from the housing <NUM> may be achieved by a user exerting a force on the removable cap <NUM> (in the direction of arrow 'F' in <FIG> and <FIG>) to urge the cap <NUM> axially away from the housing <NUM> and then rotating the cap <NUM> so as to release the engagment mechanism <NUM>, i.e. disengaging the protrusion of the removable cap <NUM> from the slot at the inner sleeve <NUM>.

Before the release of the engagement mechanism <NUM> (by rotating the removable cap <NUM>), the linear axial movement of the removable cap <NUM> causes a linear axial movement of the inner sleeve <NUM>. As the inner sleeve <NUM> moves away from the distal end of the housing <NUM>, the plate member <NUM> of the locking mechanism becomes separated into two parts due to the attachment of a part of the plate member <NUM> to the inner sleeve <NUM>. Therefore, the driving mechanism <NUM> is no longer in the inactive state and can now be actuated so as to push the piston <NUM>. Moreover, due to the linear axial movement of the inner sleeve <NUM> away from the proximal end of the housing <NUM>, the initially-tensioned spring element <NUM> decompresses and biases the inner sleeve <NUM> to protrude from the opening of the housing <NUM> due to the reduction of compressive force on the spring element <NUM>. The protruding inner sleeve <NUM> from the housing <NUM> acts as a retractable needle shroud to prevent needle stick injuries or unintentional damage to the needle <NUM>.

To inject medicament, the user grabs the injection device <NUM> with their whole hand and pushes the distal end of the injection device <NUM> against the injection site. As the user exerts pressure on the inner sleeve <NUM> by applying it against the injection site, the inner sleeve <NUM> retracts into the housing <NUM> against the bias provided by the spring element <NUM> so as to fully expose the needle <NUM> for injection. After the needle <NUM> has been inserted into the injection site, the user then acts on the actuator (not shown in the drawings) which activates the driving mechanism <NUM>. The drive spring of the driving mechanism <NUM> releases and decompresses so as to exert a force on the piston <NUM> towards the distal end of the housing <NUM> to inject medicament contained in the syringe 11a.

<FIG> are schematic cross-sectional side views of an injection device according to another exemplary embodiment in a first state, a second state, and a third state, respectively.

Referring to <FIG>, an injection device <NUM> according to a different embodiment of the invention is shown. The injection device <NUM> is in the form of an auto-injector that has similar features to that shown in <FIG>, with like features retaining the same reference numerals. A difference between the injection device <NUM> of <FIG> and the injection device of <FIG> is the locking mechanism comprises a clamp <NUM> for retaining the driving mechanism <NUM> in an initial inactive state in a first state of the injection device <NUM>. A rib <NUM> is provided on an inner surface of the housing <NUM> for holding the driving mechanism after the locking mechanism is related and before actuation of the driving mechanism, as will be explained in more detail below.

In the present embodiment, the driving mechanism comprises a drive spring that is initially in a compressed state, storing spring energy that is to be released when the driving mechanism is actuated. The driving mechanism further comprises a housing member which is arranged to house the drive spring and is arranged to move towards the distal end of the housing <NUM> when the driving mechanism is actuated.

In the first state, the driving mechanism <NUM> is held in an inactive state by the locking mechanism, which comprises the clamp <NUM>. In this embodiment, the clamp <NUM> is arranged to clamp onto the housing member which houses the drive spring such that the driving mechanism <NUM> cannot be actuated to push the piston <NUM>.

In the present embodiment, the clamp <NUM> of the locking mechanism is arranged within the housing <NUM> such that when the inner sleeve <NUM> is pushed towards the proximal end of the housing <NUM> by a pushing force (e.g. when the opening of the housing <NUM> is applied against a patient's skin, or by use of a tabletop apparatus), the inner sleeve <NUM> pushes against the clamp <NUM> and bends the clamp <NUM>, as shown in the second state in <FIG>, so as to release the locking mechanism which in turn activates the driving mechanism <NUM>. As shown in <FIG>, when the locking mechanism is released, a part of the housing member of the driving mechanism <NUM> is held against the rib <NUM>. The rib <NUM> can then be actuated, for example by means of a push button, so as to release the housing member of the driving mechanism <NUM> to push the piston <NUM> towards the distal end of the housing <NUM>, as illustrated in the third states in <FIG>.

As a result, a two-step operation is required in order to actuate the driving mechanism in this embodiment. In the first step, the user is required to bend the clamp <NUM> by way of for example applying the opening of the housing <NUM> against a patient's skin so as to activate the driving mechanism. In the second step, the user is required to actuate the rib <NUM> by means of for example a push button so as to release the housing member of the driving mechanim to push the piston <NUM>.

In the first state, the driving mechanism <NUM> is held in an inactive state by the locking mechanism, which comprises the clamp <NUM>. In this embodiment, the clamp <NUM> is arranged to clamp onto the housing member housing the drive spring such that the driving mechanism <NUM> cannot be actuated to push the piston <NUM>.

In the present embodiment, the clamp <NUM> of the locking mechanism is arranged within the housing <NUM> and fixedly connected to the inner sleeve <NUM>. When the inner sleeve <NUM> moves towards the distal end of the housing <NUM> due to the reduction of compressive force as the removable cap (not shown in this drawing) is being disengaged from the housing <NUM>, the clamp <NUM> becomes bent due to its connection to the inner sleeve <NUM>, as shown in <FIG>, so as to release the locking mechanism which in turn activates the driving mechanism <NUM>. As shown in <FIG>, when the locking mechanism is released, a part of the housing member of the driving mechanism <NUM> is held against the rib <NUM>. The rib <NUM> can be actuated, for example by means of a push button, so as to release the housing member of the driving mechanism <NUM> to push the piston <NUM> towards the proximal end of the housing <NUM>, as illustrated in the third states in <FIG>.

In this embodiment, similarly a two-step operation is required in order to actuate the driving mechanism. In the first step, the user is required to bend the clamp <NUM> by way of for example disengaging the removable cap from the housing to move the inner sleeve towards the distal end of the injection device, so as to activate the driving mechanism. In the second step, the user is required to actuate the rib <NUM> by means of for example a push button so as to release the housing member of the driving mechanim to push the piston <NUM>.

<FIG> are schematic cross-sectional side views of a part of an injection device according to another exemplary embodiment in a first state and a second state respectively.

Referring to <FIG>, a part of an injection device <NUM> according to a different embodiment of the invention is shown. The injection device <NUM> is in the form of an auto-injector that has similar features to that shown in <FIG>, with like features retaining the same reference numerals. A difference between the injection device <NUM> of <FIG> and the injection device of <FIG> is a cotter <NUM>, first through-hole 40a, second through-hole 40b, and third through-hole 40c together form the locking mechanism for retaining the driving mechanism <NUM> in an inactive state in a first state of the injection device <NUM>. A rib <NUM> is provided on an inner surface of the housing <NUM> for holding the driving mechanism after the locking mechanism is related and before actuation of the driving mechanism, as will be explained in more detail below.

In the first state, the driving mechanism <NUM> is held in an inactive state by the locking mechanism, which comprises the cotter <NUM> and the first, second, and third through-holes 40a, 40b, 40c. As shown in <FIG>, in the first state the cotter <NUM> is removably inserted through the first, second, and third through-holes 40a, 40b, 40c, which are respectively positioned at a first side of the housing <NUM>, the housing member of the driving mechanism <NUM>, and a second side of the housing <NUM> which is opposite to the first side. The first, second, and third through-holes 40a, 40b, 40c are configured to be aligned with each other such that the cotter <NUM> can be removably inserted through the housing <NUM> in a direction perpendicular to the longitudinal axis of the injection device <NUM>. In the first state, as the cotter <NUM> is engaged with the first, second, and third through-holes 40a, 40b, 40c, the driving mechanism <NUM> is held in place at the proximal end of the injection device <NUM>. Specifically, the housing member of the driving mechanism <NUM> is held in place in the inactive state by the presence of the cotter <NUM> through the second through-hole 40b at the housing member. Therefore, in the first state, the driving mechanism <NUM> cannot be actuated to push the piston (not shown in the drawing).

The locking mechanism can be released by removing the cotter <NUM> from the first, second, and third through-holes 40a, 40b, 40c. When the locking mechanism is released, the housing member of the driving mechanism <NUM> is no longer held at the proximal end of the housing <NUM> and therefore the driving mechanism <NUM> becomes activated. As shown in <FIG>, when the locking mechanism is released, a part of the housing member of the driving mechanism <NUM> is held against the rib <NUM>. The rib <NUM> can be actuated, for example by means of a push button, so as to release the housing member of the driving mechanism <NUM> to push the piston (not shown in this drawing) towards the distal end of the housing <NUM> to displace medicament.

<FIG> is a system comprising an injection device and a tabletop apparatus, according to another exemplary embodiment.

As shown in <FIG>, the system <NUM> comprises an injection device <NUM> and a tabletop apparatus <NUM>. The injection device <NUM> is as described with respect to <FIG>. The tabletop apparatus <NUM> comprises a button <NUM> which is positioned at an upper surface of the apparatus <NUM>. The tabletop apparatus <NUM> in this embodiment is configured to remove the removable cap <NUM> from the injection device <NUM>.

The tabletop apparatus <NUM> is an example of an external apparatus at which the removable cap <NUM> of the injector device <NUM> as illustrated in <FIG> can be engaged. Specifically, the connection mechanism <NUM> of the removable cap <NUM> as illustrated in <FIG> can be connected to the tabletop apparatus <NUM> in the manner shown in <FIG>, i.e. vertically connected with the upper surface of the tabletop apparatus <NUM>. An interface (not shown) is provided at the upper surface of the tabletop apparatus <NUM>, the interface comprises a movable projection which engages with (e.g. grips) the connection mechanism <NUM> of the removable cap <NUM>.

The button <NUM> of the tabletop apparatus <NUM> is configured such that when it is pressed, the movable projection acts on the connection mechanism <NUM> of the removable cap <NUM> such that the removable cap <NUM> is moved axially away from the housing <NUM> and rotated to release the engagement mechanism. The removable cap <NUM> is therefore removed simply by a press of the button <NUM> of the tabletop <NUM>. At the same time, the axial movement of the removable cap <NUM> causes an axial movement of the inner sleeve <NUM> of the injection device <NUM>, which in turn causes the plate member <NUM> to become separated into different parts. The driving mechanism <NUM> is therefore no longer in an inactive state and can be actuated to push the piston to displace medicament.

The use of the tabletop apparatus <NUM> can therefore reduce the required force to remove the removable cap <NUM> from the injection device <NUM> as well as the required force to separate the plate member <NUM> so as to activate the driving mechanism <NUM>.

A sequence of operation of the system <NUM> as illustrated in <FIG> is described as follows:
The injection device <NUM> is first engaged with the interface on the upper surface of the tabletop apparatus <NUM> such that the connection mechanism <NUM> of the removable cap <NUM> is engaged with the movable projection at the interface. The movable projection grips at the connection mechanism <NUM>, and when the user presses the button <NUM> of the tabletop apparatus <NUM>, the movable projection acts on the connection mechanism <NUM> so as to pull the removable cap <NUM> axially away from the housing <NUM>.

This linear and axial movement of the removable cap <NUM> causes a linear and axial movement of the inner sleeve <NUM> of the injection device <NUM>. As the inner sleeve <NUM> moves away from the proximal end of the housing <NUM>, the plate member <NUM> becomes separated (due to the attachment of mechanism part of the plate member <NUM> to the inner sleeve <NUM>) so as to release the driving mechanism <NUM>. In other words, the driving mechanism <NUM> is no longer in the inactive state and can now be actuated so as to push the piston <NUM>.

Immediately afterwards, the movable projection also acts on the connection mechanism <NUM> to rotate the removable cap <NUM>. This releases the engagement mechanism, i.e. disengages the protrusion <NUM> of the removable cap <NUM> from the slot at the inner sleeve <NUM>. As the removable cap <NUM> is being disengaged from the rest of the injection device <NUM>, the inner sleeve <NUM> protrudes from the opening of the housing <NUM> due to the reduction of compressive force exerted on the inner sleeve <NUM>. After the removable cap <NUM> is disengaged from the housing <NUM>, the inner sleeve <NUM> protrudes from the opening of the housing <NUM> so as to act as a retractable needle shroud. By providing this needle shroud after the removable cap <NUM> is disengaged from the housing <NUM>, the needle shroud prevents both unintentional damage of the needle during handling and access of a user to the needle for avoiding stick injuries.

To inject medicament, the user grabs the injection device <NUM> with their whole hand, removes it from the tabletop apparatus <NUM>, and pushes the distal end of the injection device <NUM> against the injection site which causes the inner sleeve <NUM> to retract into the housing <NUM> and exposing the needle <NUM>. After the needle <NUM> has been inserted into the injection site, the user then acts on the actuator (not shown in the drawings) which activates the driving mechanism <NUM>. The drive spring of the driving mechanism <NUM> releases and decompresses so as to exert a force on the piston <NUM> towards the distal end of the housing <NUM> to inject medicament contained in the syringe 11a.

<FIG> are schematic cross-sectional views illustrating interaction between part of the removable cap of <FIG> and part of the tabletop apparatus of <FIG>.

As shown in <FIG>, a connection mechanism <NUM> is provided at the removable cap <NUM>, the connection mechanism <NUM> being arranged to be engaged with the tabletop apparatus <NUM>. In this embodiment, the connection mechanism <NUM> comprises a groove for engaging with a projection <NUM> at the tabletop apparatus <NUM>. Specifically, the connection mechanism <NUM> of the removable cap <NUM> can be vertically engaged with the upper surface of the tabletop apparatus <NUM> through the engagement between the groove and the protrusion. In this embodiment, the projections <NUM> are positioned at an interface of the tabletop apparatus <NUM> and is arranged to be movable so as to receive the connection mechanism <NUM>. The interface at the tabletop apparatus <NUM> also comprises a recess to receive at least a part of the removable cap <NUM>.

Spring elements are provided around the movable projections <NUM> such that when the removable cap <NUM> is pushed against the interface of the tabletop apparatus <NUM> vertically, the movable projections <NUM> move apart, as shown in <FIG>, to allow accommodation of a part of the removable cap <NUM> and the engagement between the connection mechanism <NUM> and the movable projections <NUM>. Furthermore, the movable projections <NUM> may also be configured such that they can move apart when an actuation member (not shown in ths drawing) is actuated. For example, an additional push button may be provided at the tabletop apparatus <NUM> such that when the button is pushed, the movable projections <NUM> move apart to allow the removable cap <NUM> to be disengaged with the tabletop apparatus <NUM>.

Although it is described above that a pulling force on the removable cap is applied by an external apparatus, in alternative embodiments the pulling force may be applied manually by a user.

Although it is descibred above that the tabletop device is used in connection with the injection device as illustrated in <FIG>, in alternative embodiments, the tabletop apparatus may be used in connection with the injection devices as illustrated in the other drawings (<FIG>). For example, the tabletop device may be configured such that when the injection device as illustrated in <FIG> is mounted onto the tabletop device, it is capable of pushing the inner sleeve of the injection device towards the proximal end so as to bend the clamp in the injection device. In this example, the tabletop apparatus may comprise a hollow cylinder-shaped member so as to push the inner sleeve towards the proximal end of the injection device.

In alternative embodiments, the protrusion at the removable cap may be replaced by a slot and the slot at the inner sleeve by the replaced by a protrusion. The principle of the engagement mechanism in these embodiments remains the same, i.e. unlocking by rotating the removable cap.

In alternative embodiments, instead of configuring the inner sleeve and the locking mechanism such that when the inner sleeve is pulled away from the housing, the plate member is separated into different parts, the inner sleeve may be arranged such that when it is pushed into the housing, it causes the plate member mechanism to be separated so as to activate the driving mechanism.

In alternative embodiments, the injection device may not comprise a retractable inner sleeve. In these alternative embodiments, automatic needle insertion technology may be used at the injection device. In these alternative embodiments, the locking mechanism may be coupled with the removable cap or an additional user element, such as a slider or a button.

In alternative embodiments, a lever may be provided at the tabletop apparatus instead of the push button. The lever may be configured such that when it is actuated, the movable projection acts on the connection mechanism of the removable cap such that the removable cap is moved axially away from the housing of the injection device and rotated to release the engagement mechanism.

In alternative embodiments, an electronic tabletop apparatus may be provided which comprises a recess, an interface, and an electronic engaging unit configured to engage with the connection mechanism of the removable cap and to remove the cap by moving and rotating the removable cap axially away from the housing of the injection device.

Although claims have been formulated in this application to particular combinations of features, it should be understood that the scope of the disclosure also includes any novel features or any novel combinations of features disclosed herein either explicitly or implicitly or any generalization thereof, whether or not it relates to the same invention as presently claimed in any claim and whether or not it mitigates any or all of the same technical problems as does the present invention. The applicant hereby gives notice that new claims may be formulated to such features and/or combinations of features during the prosecution of the present application or of any further application derived therefrom.

Those skilled in the art will understand that modifications (additions and/or removals) of various components of the substances, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope of the claims, which encompass such modifications.

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 gastrointestinal 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> (anti-diabetic drugs) or <NUM> (oncology drugs), and Merck Index, 15th 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-(ω-carboxyhepta¬decanoyl) 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:
An injection device (<NUM>) comprising:
a housing (<NUM>) arranged to contain a syringe (11a) with a piston (<NUM>) for sealing the syringe (11a) and displacing the medicament, the housing (<NUM>) having a proximal end and a distal end, wherein the distal end is intended to be applied against an injection site;
a driving mechanism (<NUM>) arranged between the piston (<NUM>) and the proximal end of the housing (<NUM>); and
a locking mechanism comprising a plate member (<NUM>) arranged between the driving mechanism (<NUM>) and the piston (<NUM>) to retain the driving mechanism (<NUM>) in an initial inactive state in which the driving mechanism (<NUM>) cannot be actuated, wherein when the locking mechanism is released, the plate member (<NUM>) becomes separated into at least two parts so as to allow actuation of the driving mechanism (<NUM>) to push the piston (<NUM>) towards the distal end of the housing (<NUM>) to displace the medicament, wherein the driving mechanism (<NUM>) comprises a housing member which houses a drive spring, the drive spring being in a compressed state when the driving mechanism is in the inactive state, and wherein the drive spring is configured to decompress when the locking mechanism is released so as to push the piston (<NUM>) towards the distal end of the housing (<NUM>).