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

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

<CIT> discloses a drug delivery device comprising a drug delivery unit comprising a housing extending along a general axis, a variable volume reservoir and a needle support for receiving a needle assembly the needle support and the variable volume reservoir being capable of diverging relative axial motion from a first relative position to a second relative position and converging relative axial motion from the second relative position to the first relative position, a cap removably mountable onto the drug delivery unit to cover at least a portion of the needle support and a coupling mechanism configured to bring the needle support and the variable volume reservoir from the first relative position to the second relative position in response to the cap being mounted onto the drug delivery unit.

According to a first embodiment there is provided an injection device comprising: a housing arranged to contain a medicament cartridge; a needle holder holding an injection needle; a generally tubular needle sleeve fixed with respect to the needle holder and axially movable with respect to the housing; and a gear assembly comprising a rotary gear fixed to the needle holder, a first gear rack disposed on the needle sleeve and a second gear rack disposed on the housing, wherein the gear assembly is arranged so that movement of the needle sleeve in a proximal axial direction causes movement of the needle holder in the proximal axial direction.

The first and second gear racks may be circumferentially opposite to each other. The housing may comprise a cartridge holder having a generally tubular profile. The second gear rack may be disposed on an inwardly facing surface of the cartridge holder at a distal end thereof. The device may contain a medicament cartridge.

The cartridge may comprise a pierceable septum at a distal end thereof, and wherein the injection needle is arranged to pierce the pierceable septum when the needle holder is urged in the proximal direction.

The device may further comprise a cap that is removably engaged with the housing.

The rotary gear may have a plurality of teeth arranged circumferentially around the gear.

The rotary gear may comprise a circumferential portion with no teeth thereon.

The needle holder may comprise a hollowed recess in the centre thereof to accommodate the distal end portion of a cartridge.

The needle holder may comprise an engaging element configured to lock the distal end portion of the cartridge.

A second embodiment provides a method of operating an injection device, the method comprising: pushing a needle sleeve in a proximal axial direction, thereby causing a linear gear rack disposed thereon to rotate a rotary gear to cause axial displacement of a needle holder in a proximal direction.

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

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

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

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

According to some embodiments of the present disclosure, an exemplary drug delivery device <NUM> is shown in <FIG>. Device <NUM>, as described above, is configured to inject a medicament into a patient's body. Device <NUM> includes a 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.

<FIG> is a schematic cross-sectional view of part of an injection device in an initial state after the cap <NUM> has been removed. A cartridge holder <NUM> holding a cartridge <NUM> is contained within the housing <NUM>. The cartridge holder <NUM> is fixed with respect to the housing <NUM>.

The cartridge <NUM> comprises a pierceable septum 19a at its distal end, and contains liquid medicament which is to be delivered to a patient during injection. The cartridge <NUM> comprises a distal end portion which is shaped to be accommodated into a recess of a needle holder <NUM>. The needle holder <NUM> is located near a distal end of the cartridge <NUM>. The needle holder <NUM> holds the hollow injection needle <NUM> which, in an initial state, is not in contact with the pierceable septum 19a of the cartridge <NUM>, as can be seen in <FIG>.

The needle <NUM> comprises sharp ends at both the proximal and distal ends thereof so that the needle can pierce both the septum 19a of the cartridge <NUM> and the patient's skin.

In embodiments of the invention, a proximal end of the needle <NUM> pierces the septum 19a of the cartridge automatically as the sleeve <NUM> is pushed in a proximal direction. Proximal movement of the sleeve <NUM> to cause the needle <NUM> to pierce the cartridge septum 19a can be done as part of the same step as the injection. In other words, the distal end <NUM> of the device <NUM> may be placed against the injection site and a single continuous action by the user causes both the needle holder to move proximally towards and to pierce the cartridge septum 19a as well as causing the distal end of the needle <NUM> to emerge from the sleeve <NUM> and penetrate the patient's skin.

Alternatively, a two step process may be provided. Firstly, the user pushes the sleeve <NUM> in a proximal direction until the needle <NUM> pierces the septum 19a. This may be accompanied by audible feedback. As a subsequent step, the user may then commence the injection by pushing the distal end of the device <NUM> against the injection site.

The device <NUM> comprises a rotary gear <NUM>. The rotary gear <NUM> is a toothed wheel that is arranged between first and second linear gear racks <NUM>, <NUM>. The first linear gear rack <NUM> is provided on a radially-inward facing surface of the needle sleeve <NUM> towards the distal end of the needle sleeve <NUM>. The second linear rack <NUM> is arranged on a radially-inward facing surface of the cartridge holder <NUM> at a distal end thereof. The first and second linear gear racks <NUM>, <NUM> may be arranged so that are circumferentially opposite one another.

The rotary gear <NUM> is pivoted on a shaft on the needle holder <NUM> or on an additional part which acts as a slide and is fixated to the needle holder <NUM>. The needle holder <NUM> may comprise a hollowed recess in the centre so as to accommodate the distal end portion of the cartridge <NUM>. The needle holder <NUM> may also comprise an engaging element which is configured to lock the distal end portion of the cartridge <NUM> in place once it has fitted into the hollowed recess of the needle holder <NUM>. The needle holder <NUM> is mounted to the sleeve <NUM> so it can be driven axially by the rotary gear <NUM>.

By pushing the sleeve <NUM> in a proximal direction, the gear racks <NUM>, <NUM> drive the rotary gear <NUM> so that the needle <NUM> moves towards the cartridge <NUM> and pierces the septum 19a thereof. This is shown in <FIG>.

For further movement of the sleeve, in some embodiments the rotary gear <NUM> or gear rack may disengage. The disengagement may be brought about by providing a rotary gear <NUM> having a circumferential portion with no teeth thereon so that the rotary gear <NUM> disengages from the first linear rack <NUM> disposed on the sleeve <NUM>. Alternatively, a latch may be provided to disengage the rotary gear <NUM> from the first linear rack <NUM>. The injection can then be activated in a manner described above. After the injection, the sleeve <NUM> returns to the initial position shown in <FIG>.

In some embodiments, the needle <NUM> moves forwards with the sleeve <NUM> in a distal direction to the position shown in <FIG>.

Alternatively, the engagement between the first gear rack <NUM> and the rotary gear <NUM> is released so the gear rack <NUM>, <NUM> do not drive the needle holder <NUM> any more.

The injection device <NUM> comprises a removable cap <NUM>. A needle shield may be provided within the removable cap <NUM>. The distal end of the hollow injection needle <NUM> may be covered by the needle shield arranged within the removable cap <NUM> when the removable cap <NUM> is engaged with the housing <NUM>.

The rotary gear <NUM> is a pinion gear rotatably mounted between the cartridge holder and the needle sleeve <NUM> such that the teeth of the rotary gear <NUM> are engaged with both the teeth of the first linear gear rack <NUM> and the second linear gear rack <NUM>. The gear assembly is configured such that linear movement of the needle sleeve <NUM> in a proximal direction (i.e. into the housing <NUM>) rotates the rotary gear <NUM>, thereby causing a linear movement of the needle holder <NUM> also in a proximal direction.

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

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

The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as<NPL>), and<NPL>on.

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

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

Examples of GLP-<NUM>, GLP-<NUM> analogues and GLP-<NUM> receptor agonists are, for example, Lixisenatide ( Lyxumia®, Exenatide (Exendin-<NUM>, Byetta®, Bydureon®, a <NUM> amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-<NUM>, CJC-<NUM>-PC, PB-<NUM>, TTP-<NUM>, Langlenatide / HM-11260C, CM-<NUM>, GLP-<NUM> Eligen, ORMD-<NUM>, NN-<NUM>, NN-<NUM>, NN-<NUM>, Nodexen, Viador-GLP-<NUM>, CVX-<NUM>, ZYOG-<NUM>, ZYD-<NUM>, GSK-<NUM>, DA-<NUM>, MAR-<NUM>, MAR709, ZP-<NUM>, ZP-<NUM>, TT-<NUM>, BHM-<NUM>. MOD-<NUM>, CAM-<NUM>, DA-<NUM>, ARI-<NUM>, ARI-<NUM>, Exenatide-XTEN and Glucagon-Xten.

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

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

Claim 1:
An injection device (<NUM>) comprising:
a housing (<NUM>) arranged to contain a medicament cartridge (<NUM>);
a needle holder (<NUM>) holding an injection needle (<NUM>);
a generally tubular needle sleeve (<NUM>) fixed with respect to the needle holder and axially movable with respect to the housing; and
a gear assembly comprising a rotary gear (<NUM>) fixed to the needle holder, a first gear rack (<NUM>) disposed on the needle sleeve and a second gear rack (<NUM>) disposed on the housing,
wherein the gear assembly is arranged so that:
movement of the needle sleeve in a proximal axial direction causes movement of the needle holder in the proximal axial direction; and
a single continuous action by a user causes both the needle holder to move proximally towards and to pierce a cartridge septum (19a) of the medicament cartridge as well as causing a distal end of the injection needle to emerge from the needle sleeve for penetrating a patient's skin.