Patent Description:
Auto injector injection devices usually comprise a drive mechanism that is used to depress a plunger in the injection device in order to expel a medicament from them. Depending on the properties of the medicament to be expelled (such as the filling level of the medicament cartridge, the medicament density and dose, and the correlated gliding force of the primary pack), the force applied to plunger by the drive should be varied to prevent damage to the injection device by the impact force of the injection device plunger on the syringe stopper of the injection device. Furthermore, a high impact force on the stopper can result in a negative user experience when using the injection device. For example, the impact force may cause pain to the user, and/or the injection may occur too quickly.

<CIT> discloses a safety syringe for preventing "needle stick" injury and/or reuse of the syringe includes a body, a plunger mounted within the body, a protuberance on the plunger for connecting the plunger to a needle holder adapted in use to carry a needle at the end of an injection stroke of the plunger whereby subsequent retraction of the plunger withdraws the needle into a shielded position within the body. The syringe includes a braking device disposed between the body and the plunger to retard but not stop the withdrawal of the plunger and needle after the injection stroke.

According to a first aspect, the specification describes an injection device comprising: a medicament container; a stopper translatably disposed within the medicament container; a plunger rod, the plunger rod comprising a plunger head; a drive mechanism for displacing the plunger rod into the medicament container; and a force reduction feature comprising a bore through which the plunger rod can pass, the bore being tapered inwardly into the medicament container, wherein the plunger rod is operable to displace the stopper; and wherein wherein the bore has compressible walls, which are compressible by the plunger head as the plunger head passes through the bore to damp at least a part of a plunger rod motion when the plunger rod is driven by the drive mechanism.

The force reduction feature may be configured to damp the plunger rod motion for at least a part of the displacement of the stopper.

The medicament container, the stopper and the reduction feature may, prior to displacement of the stopper, define a cavity, the cavity having an initial cavity length that is less than a plunger head length.

The plunger head may comprise one or more grooves extending around the plunger head and the force reduction feature comprises one or more pins engageable with the one or more grooves on the plunger head thereby to rotate the plunger head as the plunger is displaced into the medicament container.

The plunger head may comprise a rotatable nut around which the grooves extend.

The force reduction feature may comprise an O-ring mounted on the plunger head, and the O-ring may be arranged to roll along the plunger head when the plunger is displaced into the medicament container.

The O-ring may be arranged to roll off of the plunger head after a predetermined displacement distance of the plunger into the medicament container.

The force reduction feature may comprise a chamfered head on the plunger head and a deformable chock on the stopper for receiving the chamfered head, wherein the deformable chock is arranged to expand upon receiving the chamfered head, thereby to grip walls of the medicament container.

The force reduction feature may comprise one or more indentations on the plunger rod and one or more flexible arms on the injection arranged to catch the one or more indentations on the force reduction head.

The drive mechanism may comprise a spring.

The injection device further may comprise a needle.

Example embodiments will now be described by way of non-limiting example with reference to the accompanying drawings. It is noted that only <FIG> show an injection device according to the invention as defined in the appended claims. The remaining <FIG> show injection devices that do not fall within the scope of the claims.

<FIG> shows a schematic example of an injection device with a force reduction feature. The injection device <NUM> comprises a medicament container <NUM> for retaining a medicament <NUM>. In the embodiment shown, the medicament container <NUM> forms part of a syringe (for one shot devices, for example). In other embodiments, the medicament container <NUM> forms a part of an auto-injector. In such cases, the medicament container <NUM> may be a consumable part of the auto-injector capable of being replaced as required, for example a medicament cartridge. In the embodiment shown, the walls of the medicament container <NUM> are substantially cylindrical. In general, the medicament container <NUM> can have a different cross sectional shape.

The injection device <NUM> further comprise a needle <NUM> via which the medicament <NUM> can be expelled from the medicament container <NUM>. The needle <NUM> is, in some embodiments, an integral part of the medicament container <NUM>. In other embodiments, the needle <NUM> is part of an autoinjector pack into which the medicament container can be inserted. In the following, the needle <NUM> end of the injection device <NUM> will be referred to as the distal end, with the opposite end of the injection <NUM> device referred to as the proximal end.

A stopper <NUM> is translatably disposed between the walls of the medicament container <NUM>. The stopper <NUM> is translatable in the axial direction of the medicament container <NUM>.

A force reduction feature (also referred to herein as a "reduction feature") <NUM> is provided at the proximal end of the medicament container <NUM>. In embodiment shown, the reduction feature <NUM> is provided in the form of a cap for the medicament container <NUM>. In other embodiments, the force reduction feature <NUM> can be provided as part of an autoinjector. The reduction feature <NUM> is mounted on the open end of the medicament container <NUM>. In the example shown, the reduction feature <NUM> comprises a bore <NUM> through its centre that fluidly connects a cavity <NUM> inside the medicament container <NUM> to the outside of the medicament container <NUM>. In the example shown the bore <NUM> is tapered inwardly into the medicament container <NUM>. The reduction feature <NUM> is mounted on the proximal end of the medicament cartridge <NUM>, for example by being composed of an elastic material that is retained by the inside wall of the medicament container <NUM>. The reduction feature <NUM> may be mounted to the medicament container <NUM> using a transition fit.

The reduction feature <NUM> bore <NUM> walls are formed from a compressible material. For example, rubber or plastic can be used.

The reduction feature <NUM>, stopper <NUM> and medicament container <NUM> walls define a cavity <NUM> at the proximal end of the medicament container <NUM>. The cavity has an initial cavity length <NUM> (S<NUM>) that depends on the position of the stopper <NUM> within the medicament container <NUM>. The cavity <NUM> therefore also has a variable initial cavity volume.

A plunger <NUM> (herein also referred to as a plunger rod or piston rod) is provided which can be depressed into the medicament container <NUM> in order to expel the medicament <NUM> via the needle <NUM>. The plunger <NUM> may be manufactured from plastic or metal, for example. The plunger <NUM> is displaceable in the axial direction of the medicament container <NUM>. When depressed towards the distal end of the medicament container <NUM>, the plunger <NUM> enters the cavity <NUM> of the medicament container though the bore <NUM> in the reduction feature <NUM>. The plunger <NUM> acts to displace the stopper <NUM> towards the needle <NUM>, thereby expelling the medicament <NUM> from the medicament container <NUM> via the needle <NUM>. The plunger <NUM> is displaced into the medicament container <NUM> by means of a drive mechanism <NUM>. In the embodiment shown, the drive mechanism <NUM> comprises a spring located within the plunger rod. In embodiments using an auto-injector, the plunger <NUM> is mounted in and/ or driven by an auto-injector powerpack.

The plunger <NUM> comprises a plunger head <NUM> at the distal end of the plunger. The plunger head <NUM> has an axial length <NUM> (S<NUM>) over which the diameter of the plunger head <NUM> is greater than the diameter of at least a portion of the bore <NUM>. This can allow the plunger rod <NUM> motion to be damped by providing resistance to the plunger rod <NUM> motion as it passes through the bore <NUM>, thereby reducing the net force on the plunger rod <NUM>.

The amount of force reduction provided by the cooperation of the plunger head <NUM> and the bore <NUM> can be varied in several ways. One example is varying the axial length <NUM> of the plunger head <NUM>. This changes the influence of the plunger head <NUM> on the drive mechanism <NUM> working area (stroke). The diameter of the plunger head <NUM> can also be varied to vary the amount of force reduction applied to the plunger <NUM> by the bore <NUM>. The length of the plunger head <NUM> is equal to the length of the primary pack upper dead volume. The plunger head will therefore be released by the bore <NUM> when the force reduction head <NUM> is in contact with the stopper.

Another example is varying the geometry and/or the material (e.g. to vary the Shore hardness) of the force reduction feature <NUM>. For example, varying the diameter of the bore <NUM> and/or varying the taper of the bore <NUM> can change the amount of force reduction applied. As an example, a narrower diameter of the bore <NUM> can result in a greater force reduction. By providing a means for varying the force reduction (by, for example, varying the bore <NUM> properties), the same drive mechanism <NUM> can be used for different medicament container <NUM> fill levels, drug densities and/or the correlated gliding forces. This can simplify the design of the injection devices.

The plunger head <NUM> has, in this embodiment, an axial length <NUM> equal to or greater than the initial cavity length <NUM> (i.e. S<NUM>≥S<NUM>) so that the plunger rod <NUM> motion is being damped or just released from being damped as it contacts the stopper <NUM>.

In some embodiments (not shown), the plunger head <NUM> is formed from a compressible material, such as rubber or plastic for example. In these alternative embodiments, the force reduction feature <NUM> bore <NUM> may be formed from either a compressible or an incompressible material.

<FIG> show schematic examples of an injection device with a force reduction feature <NUM> in use. With reference to <FIG>, the plunger <NUM> is initially completely outside of the medicament container <NUM>. A user initiates an injection by, for example, pressing a button on an auto-injector pack. This actuates the drive mechanism <NUM> to depress the plunger <NUM> into the medicament container <NUM> via the bore <NUM> in the force reduction feature <NUM>.

With reference to <FIG>, as the drive mechanism <NUM> depresses the plunger <NUM> into the medicament container <NUM> cavity <NUM> the plungerhead <NUM> passes through the bore <NUM> of the cap <NUM>. The plungerhead <NUM> compresses the walls of the bore <NUM> as it moves through the bore <NUM>. This retards the motion of the plunger rod <NUM> by providing resistance to the plunger rod <NUM> motion, thereby reducing the net force on the plunger rod <NUM>.

With reference to <FIG>, as the plunger <NUM> is depressed further into the cavity <NUM> of the medicament container <NUM>, the plunger head will eventually come into contact with the stopper <NUM>. As the axial length <NUM> is equal to or greater than the initial cavity length <NUM> (i.e. S<NUM>≥S<NUM>), the bore <NUM> walls will still be compressed by a portion of the plunger head <NUM> (or, as in the example shown, just have released the force reduction head) at this moment, reducing the net force on the plunger <NUM>. The impact force of the plunger <NUM> on the stopper <NUM> is therefore reduced.

This allows an injection device to use one spring with the highest possible load for multiple different medicament indications.

<FIG> show schematic examples of alternative embodiments an injection device with a force reduction feature comprising a compressible bore.

In the embodiment shown <FIG>, the force reduction feature <NUM> comprises a central bore <NUM> comprising a series of one or more step-changes in the bore <NUM> diameter. In the example shown, there are two step changes in the bore diameter, though fewer or more step changes can be used. The bore diameter is narrowest at the proximal end of the medicament cartridge, with the step changes increasing the bore diameter as the bore <NUM> progresses into the cavity <NUM> of the medicament container <NUM>. The lower, middle and upper stepped portions of the bore <NUM> have lengths a, b and c respectively. In some embodiments, the length of the plunger head <NUM> is equal to or greater than the total length of the bore (a+b+c). Having stepped portions can vary the amount of resistance to the plunger motion as the plunger head <NUM> progresses through the bore <NUM>. This can be beneficial when the plunger <NUM> is driven by a spring.

In the embodiment shown <FIG>, the cap <NUM> comprises a central bore <NUM> that tapers in the axial direction of the medicament cartridge <NUM>. In contrast to the embodiment of <FIG>, the bore diameter increases as the bore <NUM> progresses into the cavity <NUM> of the medicament container <NUM>. In this embodiment, the plunger head <NUM> is also tapered, being wider at the distal end of the plunger head <NUM> than the proximal end. This can lead to a smoother release of the plunger rod by the reduction feature.

In the embodiment shown in <FIG>, the cap <NUM> comprises a shallow central bore <NUM> that is untapered. The plunger head <NUM> comprises a series of steps in diameter. Having stepped portions can vary the amount of resistance to the plunger motion as the plunger head <NUM> progresses through the bore <NUM>. This can be beneficial when the plunger <NUM> is driven by a spring.

<FIG> shows a further embodiment of an injection device with a plunger head <NUM> comprising an O-ring. In this embodiment, the injection device <NUM> comprises a medicament cartridge <NUM>, medicament <NUM>, needle <NUM> and stopper <NUM> as described in relation to <FIG>. The injection device <NUM> is provided with a plunger <NUM> comprising a drive mechanism <NUM>, also as described in relation to <FIG>. The stopper <NUM> and the opening <NUM> of the medicament container define a length S<NUM> <NUM>. In the embodiment shown, no bored force reduction feature is provided. In other embodiments a bored force reduction feature, as disclosed in any of the capped embodiments described herein, can be provided. In some embodiments, a stopper <NUM> with a tapered bore can be used.

The plunger <NUM> comprises a plunger head <NUM>. The plunger head <NUM> comprises a force reduction feature in the form of a groove <NUM> into which an O-ring <NUM> is fitted. The groove <NUM> is located towards the distal end of the plunger head. The plunger head <NUM> has a length 125in the axial direction from the groove <NUM> to the proximal end of the plunger head of S<NUM>. In some embodiments S<NUM>≥S<NUM>.

The O-ring <NUM> can be manufactured from an elastic material, such as rubber. The material and/or the O-ring <NUM> thickness can be varied to vary the reduction force applied during operation of the plunger <NUM>.

<FIG> show schematic examples of an injection device with a force reduction head comprising an O-ring in use.

With reference to <FIG>, the plunger <NUM> is initially completely outside of the medicament container <NUM>. A user initiates an injection by, for example, pressing a button on an auto-injector pack. This actuates the drive mechanism <NUM> to depress the plunger <NUM> into the medicament container <NUM>.

With reference to <FIG>, as the plunger <NUM> is depressed into the medicament cartridge, the O-ring <NUM> catches on the lip of the medicament container <NUM>. As the plunger <NUM> is depressed further into the medicament cartridge <NUM>, the O-ring <NUM> rolls along the plunger head length <NUM>, which provides resistance to the plunger <NUM> motion.

With reference to <FIG>, continued depression of the plunger <NUM> by the drive mechanism <NUM> results in the plunger head <NUM> coming into contact with the stopper <NUM>. The stopper <NUM> will then be displaced towards the distal end of the injection device <NUM>, thereby expelling medicament <NUM> via the needle <NUM>. In embodiments where S<NUM>≥S<NUM>, the O-ring <NUM> is still retarding the motion of the plunger as the plunger head <NUM> makes contact with the stopper <NUM>, thereby reducing the initial force on the stopper <NUM>.

As the plunger <NUM> continues to be depressed, the O-ring <NUM> reaches the end of the plunger head length <NUM>. The rest of the plunger <NUM> has a narrower diameter than the plunger head <NUM>, and the O-ring <NUM> can therefore contract away from the lip of the medicament container <NUM>. In this position, the O-ring <NUM> ceases to retard the motion of the plunger <NUM>.

<FIG> shows a further embodiment of an injection device with a chock and chamfered force plunger head. <FIG> shows an example of the injection device with a chock and chamfered plunger head in use.

In these embodiments, the plunger head <NUM> is chamfered such that it reduces in diameter towards the needle end of the injection device <NUM>. The stopper <NUM> comprises a deformable chock <NUM> into which the plunger head <NUM> can be received. The deformable chock <NUM> comprises a central recess <NUM> to receive the force reduction head <NUM>. The central recess <NUM> has chamfered walls. The plunger head <NUM> has a larger volume than the central recess <NUM> of the deformable chock <NUM>. This causes the deformable chock <NUM> to deform when the plunger head <NUM> is received by the central recess <NUM>. The deformable chock can be manufactured from a material comprising a rubber or plastic material, for example TPE or PP.

As the drive mechanism <NUM> drives the plunger into contact with the stopper <NUM>, the plunger head <NUM> is driven into the central recess <NUM> of the deformable chock <NUM>. The difference in the volumes between the plunger head <NUM> and the central recess <NUM> causes the deformable chock <NUM> to deform outwardly.

The deformable chock <NUM> is arranged such that the deformation caused by the plunger head <NUM> entering the recess <NUM> causes the side walls of the deformable chock <NUM> to contact the inside surface of the medicament cartridge walls. The force of the deformable chock <NUM> against the medicament cartridge walls acts to decelerate the plunger <NUM> and reduces the total force on the plunger <NUM> over the complete injection stroke. The deformable chock <NUM> is designed in such a way that a surface pressure between the medicament cartridge wall and the deformable chock exists when the plunger rod is driven into the chock, which can act to prevent glass breakage.

The chamfered plunger head <NUM> and the deformable chock <NUM> therefore cooperate to provide a force reduction feature.

<FIG> illustrates an example of an injection device having a rotatable nut on the plunger rod. <FIG> shows a perspective view of the plunger rod of <FIG>. In this embodiment, the plunger head <NUM> comprises a rotatable pitch nut. The pitch nut comprises one or more groves <NUM> that wind around the axial direction of the force reduction head <NUM> body. The plunger has a length in the axial direction <NUM> of S<NUM> (not shown to scale in <FIG> and <FIG>). The grooves <NUM> extend along this length. The remaining body of the plunger has a radius less than that of the grooves <NUM> of the plunger head <NUM>.

The injection device cap <NUM> comprises a central bore <NUM> with one or more pins <NUM> (in the example shown, there are two pins) extending inwardly into the bore from the bore edge. The pins <NUM> are engageable with the one or more grooves <NUM> winding around the plunger head <NUM>, and act as "counter bearings". The cap <NUM>, stopper <NUM> and medicament container <NUM> walls define a cavity <NUM> with a cavity length <NUM> of S<NUM> (not shown to scale).

In use, the drive mechanism <NUM> (which in the example shown is a spring) drives the plunger <NUM> into the medicament container <NUM> via the bore <NUM> in the cap <NUM>. As it does so, the grooves <NUM> in the plunger head <NUM> engage with the pins <NUM> extending into the bore <NUM> of the cap <NUM>. This provides resistance to the motion of the plunger <NUM>. As the plunger <NUM> is depressed further by the drive mechanism <NUM>, the plunger head <NUM> rotates relative to the plunger <NUM> main body and the medicament container <NUM>, effectively "screwing" into the bore. This provides resistance to the plunger motion. As the plunger <NUM> is depressed even further, the pins <NUM> will eventually reach the end of the grooves <NUM> and exit them. A damping force will then no longer be applied to the plunger <NUM> by the pins <NUM>.

Where S<NUM>≥S<NUM> the plunger head <NUM> will be rotating as it makes contact with the stopper <NUM>, thereby reducing the initial impact force of the plunger <NUM> on the stopper <NUM>. The cooperation of the plunger head grooves <NUM> and pins <NUM> thereby provides a force reduction feature.

<FIG> shows an alternative embodiment of a plunger head for use in embodiments of injection devices as described in <FIG>. In this embodiment, the plunger head <NUM> is fixed relative to the main body of the plunger, and the plunger rod <NUM> as a whole rotates as the plunger rod <NUM> is driven into the medicament container <NUM> by the drive mechanism <NUM>. In embodiments where the drive mechanism <NUM> is a spring, a rotary plate <NUM> is provided inside the plunger head <NUM> on which the spring rests. The rotary plate <NUM> allows the plunger rod <NUM> to rotate around the spring without twisting the spring.

When the plunger <NUM> is driven into the medicament cartridge, the pins <NUM> and the grooves <NUM> cause the plunger <NUM> to rotate, reducing the forces on the plunger rod <NUM> and its speed. The plunger rod <NUM> has a lead-in pitch to the grooves <NUM> to ensure connectivity between the grooves <NUM> and the pins <NUM>. The gradient of the grooves <NUM> corresponds to the required force and speed reduction.

<FIG> shows a schematic of a further embodiment of an injection device with a plunger head comprising a plurality of flexible arms. <FIG> shows a top view of the plunger and flexible arms. In this embodiment, the plunger head comprises one or more indentations <NUM>. The injection device comprises one or more flexible arms <NUM> which engage with the indentations <NUM> on the plunger head <NUM>. In the embodiment shown, <NUM> flexible arms <NUM> are provided, though a fewer or greater number of arms can be used. The flexible arms <NUM> may be provided as a part of the medicament cartridge <NUM>, for example as part of a cap or integrated with the medicament cartridge <NUM>. Alternatively, the flexible arms <NUM> can be provided as part of a separate syringe drive plate <NUM>, as shown in <FIG>. The flexible arms <NUM> can, for example, be manufactured from stamped metal.

In some embodiments, the plunger rod <NUM> further comprises one or more serrations <NUM> arranged to catch the flexible arms <NUM> as the plunger is depressed into the medicament cartridge <NUM>, thereby providing additional resistance/damping to the plunger rod <NUM> motion. The serrations <NUM> can, in some embodiments, extend along the full length of the plunger rod <NUM>, thereby providing damping to the plunger rod <NUM> motion throughout the whole of an injection event. The serrations <NUM> catching on the flexible arms <NUM> can also provide audible feedback to the user.

When the plunger <NUM> is driven into medicament cartridge <NUM>, the flexible arms caught in the indentation flex, applying a force to the plunger head <NUM> that opposes its motion. The plunger rod <NUM> motion is thereby damped. As the plunger rod <NUM> is depressed further into the medicament cartridge, the flexible arms are increasingly flexed, until eventually they release the plunger rod. The cooperation of the indentations and the flexible arms provides a force reduction feature.

<FIG> and <FIG> show an embodiment of an injection device with a force reduction feature comprising a flexible lip.

In this embodiment, the cap <NUM> comprises a bore <NUM> have a flexible lip <NUM>. The flexible lip <NUM> is arranged to grip the plunger rod <NUM> as it passes into the medicament container <NUM>. The flexible lip <NUM> provides additional resistanvce to the plunger rod <NUM> motion, acting as a force reduction feature.

The flexible lip <NUM> forms a substantially airtight seal with the plunger rod <NUM>.

In some embodiments, the flexible lip <NUM> is arranged to grip a plunger head (not shown in <FIG>) on the plunger rod <NUM>. The plunger head has a greater diameter than the rest of the plunger body. Once the plunger head has passed the flexible lip, the plunger rod <NUM> is no longer in contact with the flexible lip, and the plunger rod <NUM> motion is no longer retarded by the flexible lip <NUM>.

In other embodiments, the plunger rod <NUM> comprises one or more slits <NUM> in the plunger rod body at a predefined distance along the plunger rod <NUM>, such that the flexible lip <NUM> releases the plunger rod <NUM> as the slits <NUM> pass across the flexible lip <NUM>, as illustrated in more detail in <FIG>. Therefore a force reduction is applied to the plunger rod <NUM> for the length of the plunger rod <NUM> between its distal end and the position of the slits <NUM>.

Two or more of the force reduction features described above may be combined into a single force reduction feature. For example, a compressible bore may also be supplied with an O-ring on the corresponding plunger head, with both the bore being compressed and the O-ring being displaced as the force reduction head passes into the medicament cartridge.

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

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 medicament container (<NUM>);
a stopper (<NUM>) translatably disposed within the medicament container;
a plunger rod (<NUM>), the plunger rod comprising a plunger head (<NUM>);
a drive mechanism (<NUM>) for displacing the plunger rod into the medicament container; and
a force reduction feature (<NUM>) mounted on the proximal end of the medicament container (<NUM>) and comprising a bore through which the plunger rod can pass, the bore being tapered inwardly into the medicament container,
wherein the plunger rod is operable to displace the stopper; and
wherein the bore has compressible walls, which are compressible by the plunger head as the plunger head passes through the bore to damp at least a part of a plunger rod motion when the plunger rod is driven by the drive mechanism.