Housing element and drug delivery device comprising same - Patents.com

Abstract

The present invention relates to a housing element (1) for a drug delivery device. The housing element (1) includes a longitudinal axis (I) and defines an interior space for receiving components (11, 12) of a drive mechanism of the drug delivery device and at least a portion of a cartridge (13) of the drug delivery device. The housing element includes an engagement feature (4) for axially restraining the housing element to a cartridge holder (9) of the drug delivery device. To restrain the cartridge (13) of the housing element (1), the housing element further includes at least one crush web (6) protruding radially inward into the interior space. The at least one crush web (6) is inclined at least 3° with respect to the longitudinal axis (I) of the housing element such that the at least one crush web (6) is folded radially outward when the cartridge (13) is introduced into the interior space.

Description

[Technical field]

[0001] The present invention is generally directed to a housing element, such as an inner or outer housing component, for a drug delivery device. Further, the present invention relates to a drug delivery device comprising such a housing element. [Background technology]

[0002] Pen-type drug delivery devices have applications where regular injections are administered by individuals without formal medical training. This may become increasingly common among diabetic patients, where self-treatment allows the patient to effectively manage their disease. In practice, such drug delivery devices allow the user to individually select and dispense multiple user-variable doses of a medication.

[0003] There are essentially two types of drug delivery devices: resettable devices (i.e., reusable) and non-resettable devices (i.e., disposable). For example, disposable pen delivery devices are supplied as self-contained devices. Such self-contained devices do not have a removable pre-filled cartridge. Rather, the pre-filled cartridge cannot be removed or replaced from these devices without destroying the device itself. As a result, such disposable devices do not need to have a resettable dose setting mechanism. The present invention is generally applicable to disposable and reusable devices. However, the present invention is particularly applicable to pre-filled disposable pen devices.

[0004] Such drug delivery devices typically include a dose setting and / or drive mechanism for selecting an individual dose and delivering this dose by displacing a piston in a cartridge containing the medicament. The cartridge, e.g. a glass ampoule, is held in a cartridge holder, or a similar type of receptacle for such a container. Prior to dose delivery, a needle is secured to the cartridge holder, thereby piercing a septum of the cartridge. This exerts an axial force on the cartridge. However, in order to maintain good dose accuracy, it is important to constrain the cartridge from axial movement relative to the cartridge holder, and the dose setting and / or drive mechanism, during needle attachment and subsequent dose delivery.

[0005] Due to the relatively large tolerances in length and diameter of the cartridge, it is known to provide some deformation in the retaining feature to ensure the restraint of the cartridge at the extremes of all tolerances. For example, US Pat. No. 5,399,436 proposes a drug delivery device with crush ribs molded on the inside of the cartridge holder and holding the cartridge axially fixed between such crush ribs and the inner surface of the cartridge holder. Two other examples of deformable members that engage with the neck portion of the cartridge to support it against axial movement are known from US Pat. No. 5,399,436 and US Pat. No. 5,399,436. Furthermore, it is known from US Pat. No. 5,399,436 and US Pat. No. 5,399,436 to provide a tapered rib in the insert to provide a gradually smaller internal space for the rib to receive the proximal end of the cartridge.

[0006] These known solutions have the disadvantage that, depending on the tolerances, the cartridge is not securely restrained in the cartridge holder or the forces for assembling the cartridge are relatively large, with the result that the glass can break during assembly or in the event of an impact, i.e. if the device is dropped from a considerable height onto a hard surface. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2005 / 018721A [Patent Document 2] International Publication No. 2016 / 065220A [Patent Document 3] International Publication No. 2016 / 156387A [Patent Document 4] International Publication No. 99 / 038554A [Patent Document 5] International Publication No. 2017 / 001693A Summary of the Invention [Problem to be solved by the invention]

[0008] It is therefore an objective to improve the axial and radial retention and restraint of a drug cartridge within a drug delivery device. [Means for solving the problem]

[0009] This object is solved, for example, by the subject matter defined in the independent claims. Advantageous embodiments and improvements are subject to the dependent claims. It should be noted, however, that the present disclosure is not limited to the subject matter defined in the appended claims. Rather, the present disclosure may include improvements in addition to or as an alternative to those defined in the independent claims, as will become apparent from the following description.

[0010] One aspect of the present disclosure relates to a housing element for a drug delivery device, the housing element having a longitudinal axis and defining an interior space for receiving components of a drive mechanism of the drug delivery device and for receiving at least a portion of a cartridge of the drug delivery device. In general, the housing of the drug delivery device can include two housing elements, namely an inner body, which in an exemplary embodiment can restrain and guide the drive mechanism, and an outer body, which in an exemplary embodiment can form the entire outer surface and possibly includes a cartridge holder. The two housing elements are formed as a single member, but for manufacturing reasons, they will most likely be formed as two or more members. The joint between these members can be in various positions, as determined by the needs of the device design and manufacturing considerations. Hereinafter, the present disclosure will be described mainly with respect to examples in which the housing element is a component disposed within the inner body, i.e. the outer body, suitable for holding and / or receiving other components of the device. In particular, the inner body can be suitable for guiding and / or restricting the movement of the components of the drug delivery device. Alternatively, the housing element can be the outer body. The housing element preferably includes an engagement feature for axially restraining the housing element to a cartridge holder of a drug delivery device. In other words, the housing element, e.g., the inner body, is designed to receive a portion of the cartridge, preferably the proximal end portion of the cartridge, but the housing element is not a cartridge holder. Rather, a cartridge holder according to the present disclosure is a component that receives and holds at least the distal end (dosing end) of the cartridge and allows attachment of a needle by at least one attachment feature provided on the cartridge holder, e.g., a threaded interface, a bayonet interface, or a luer lock.

[0011] Furthermore, the housing element includes at least one crush web that protrudes radially inwardly into the interior space. Preferably, the at least one crush web is inclined at least 3° relative to the longitudinal axis of the body. Preferably, this results in the at least one crush web folding radially outward when the cartridge is introduced into the interior space. In other words, the crush web defines a plane that is generally radially oriented relative to the longitudinal axis, which plane is inclined at least 3° relative to the longitudinal axis of the housing element. The at least one crush web can be inclined at least 5°, preferably about 15°, relative to the longitudinal axis of the body. The at least one crush web can be inclined at most 45°, preferably less than 25°, relative to the longitudinal axis of the body. If the angle of the crush web relative to the longitudinal axis is too small / shallow, the web can buckle instead of folding in the middle. This increases the assembly forces and also risks the web breaking into several small parts which may be visible in the cartridge holder or which may be detrimental to the operation of the pen injector mechanism.

[0012] In contrast to known tapered ribs, the radially inwardly facing edge of the at least one crush web is configured such that the interior space defined by the at least one crush web gradually becomes smaller in the axial direction. In other words, the radially inwardly facing edge of the at least one crush web lies, for example, at least substantially in a cylindrical plane. This includes embodiments having a chamfered inner distal end of the at least one crush web. Preferably, the radially inwardly facing edge of the at least one crush web lies in a cylindrical or conical plane with an inclination of less than 5° relative to the longitudinal axis.

[0013] A housing element comprising at least one crush web as defined above is suitable for axially and radially retaining and restraining a drug cartridge within the housing element and thus within the drug delivery device. In particular, the at least one crush web is suitable for restraining axial movement of the cartridge relative to the housing element within the device during needle attachment and subsequent dose delivery, which is essential for maintaining good dose accuracy. Moreover, secure restraint of the cartridge also reduces the risk of cartridge cracking during impact, such as when the device is dropped from a significant height onto a hard surface. Thus, a drug delivery device having such a housing element has an improved impact test performance, where cases of glass breakage are significantly reduced when using these crush web features to hold the cartridge. Due to the relatively large tolerances on the length and diameter of the cartridge, secure restraint at the extremes of any tolerance requires a predetermined deformation of at least one crush web. A housing element having at least one crush web as defined above requires only a small axial force to assemble the cartridge, thereby significantly reducing the risk of glass breakage during assembly, while maintaining good dose accuracy by preventing cartridge movement when attaching the needle.

[0014] In one embodiment, the housing element comprises at least one lateral aperture. Preferably, the at least one crush web is located adjacent to and / or coincident with the at least one lateral aperture. This allows the at least one crush web to be folded into the at least one lateral aperture when the cartridge is introduced into the interior space. Thus, excessive forces acting on the cartridge are avoided and the folding behavior of the at least one crush web is more predictable and predefined. The provision of an aperture also allows the crush web to be shaped, which would otherwise form an "undercut" in the tool. The aperture is created using a separate tool piece (e.g., a "slide") that forms one side of the crush web and blocks another tool piece (e.g., a core pin) that forms the other side of the web. In practice, this "blocking" between the two tool members also means that there is a path for the air in the forming tool to escape, which helps to accurately fill the very thin crush web with polymer during the forming process.

[0015] Generally, the cartridge can be secured within the housing element using at least one crush web and the inner surface of the housing element, however, it is preferred that the housing element includes several crush webs, for example three crush webs, spaced at approximately 120° intervals, such that the cartridge is restrained within the housing element only by the radially inner edges of the crush webs.

[0016] Typical cartridge volumes for drug delivery devices include 3ml and 1.5ml cartridges. When using a small diameter cartridge (1.5ml) mounted in a device that can also accommodate a larger diameter cartridge (3ml), the housing element is adapted without the need to adapt the entire dose setting and / or drive mechanism. For example, the housing element can include at least one support structure that extends radially inward into the interior space, thereby reducing the diameter for receiving the cartridge of the drug delivery device. In one embodiment, the at least one crush web is located on the at least one support structure such that when the cartridge is introduced into the interior space, the at least one crush web is folded radially outward, for example in a free space adjacent to the support structure. The at least one support structure can include two pairs of radially inwardly projecting walls, with one crush web located on each of the four walls. Furthermore, the pairs of radially inwardly projecting walls are arranged at 180° intervals. For manufacturing reasons, it may be preferable to mold two pairs of crush webs located at 180° intervals. This is easier if the crush web is radially inside the outer wall of the housing, for example if the forming tool has at most two slides.

[0017] In one embodiment, the at least one crush web has a thickness of at least 0.1 mm and up to about 0.3 mm, preferably about 0.15 mm or about 0.2 mm. If the crush web is too thick and protrudes radially, it will not buckle, but will have to plastically yield and generate a much higher assembly force. This will generate much higher stresses in the glass wall of the cartridge, with the risk of cracking during assembly, or even after assembly during storage or use. This assembly force can vary considerably depending on the length and diameter tolerance of the cartridge, but by promoting the folding behavior of the at least one crush web rather than buckling or fracturing, this variation will be within acceptable parameters that do not result in glass breakage.

[0018] In order to improve the predetermined folding behavior of the at least one crush web so that it folds radially outward when the cartridge is inserted, the housing element can have a locally reduced wall thickness where the at least one crush web joins with the housing element. The crush web is thus prone to deform when the cartridge is inserted and to fold in the middle due to the inclined geometry. Since the crush web is, for example, only 0.15 mm thick, this requires only a small assembly force, which does not change significantly when the cartridge is inserted further axially.

[0019] In one embodiment, the housing element includes a distal portion having a larger diameter for receiving at least a portion of a cartridge of the drug delivery device and a proximal portion having a smaller diameter compared to the distal portion for receiving a component of a drive mechanism of the drug delivery device, for example, the distal and proximal portions being connected to each other by a radially extending flange wall.

[0020] In one embodiment, the housing element is an inner body for a drug delivery device configured to interact with components of a dose setting and / or drive mechanism of the drug delivery device. For example, the housing element, e.g., the proximal portion, can include an internal thread for engaging with a threaded piston rod of the drug delivery device. Additionally or alternatively, the housing element, e.g., the proximal portion, can include an external thread for engaging with a dose dial sleeve (number sleeve) of the drug delivery device. Additionally or alternatively, the housing element, e.g., the proximal portion, can include an axially extending internal spline for engaging with a drive sleeve of the drug delivery device. Furthermore, the housing element, e.g., the distal portion, includes an engagement feature, which can be a circumferentially extending bead or groove provided on the outer surface of the housing element.

[0021] The present invention further relates to a drug delivery device comprising a housing element, preferably an inner body as defined above. In one embodiment, the drug delivery device comprises a housing element, a cartridge containing a medicament, a drive mechanism for driving a piston in the cartridge, and an additional housing element such as an outer body axially constrained to the housing element by an engagement feature. Optionally, the outer body surrounds the housing element and the cartridge, i.e. the outer body may extend from the distal end to the proximal end of the device such that the outer body is also a cartridge holder with an interface for mounting, for example, a needle.

[0022] The present invention is particularly applicable to disposable pen-type devices where cost prohibits the use of a metal spring element to axially bias the cartridge towards the needle end of the cartridge holder.

[0023] In one embodiment, the cartridge has a nominal outer diameter that radially interferes with the at least one crush web when introduced into the interior space of the housing element.

[0024] According to a preferred embodiment, the dimensions of at least one crush web are adapted to the nominal outer diameter of the cartridge, so that when the cartridge is introduced into the internal space of the body, each crush web exerts a force of about 2.5N-5N, preferably 3N-4.5N, after the first engagement between the respective crush web and the cartridge, for example after a relative movement between the respective crush web and the cartridge of 0.2mm-1.5mm. This is achieved if the crush web is inclined at least 3°, preferably 15°, relative to the axis of the housing, such that when the cartridge is assembled, the web folds / rolls into the aperture while maintaining axial and radial restraint on the cartridge in all tolerance conditions. Typical tolerance conditions for the cartridge and related device components are within the region of ±0.6mm of the assembly height of the proximal end face of the cartridge.

[0025] The invention is applicable to devices that are manually actuated, for example by the user applying force to an injection button, devices actuated by a spring or the like, and devices that combine these two concepts, i.e., spring-assisted devices that still require the user to exert the injection force. Spring-type devices involve a preloaded spring and a spring that is loaded by the user during dose selection. Some stored energy devices use a combination of a spring preload and additional energy provided by the user, for example during dose setting.

[0026] The drug delivery device may include a cartridge that contains the medication.

[0027] The terms "drug" or "medicament" are used interchangeably herein to describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or their pharma- ceutically acceptable salts or solvates, and optionally a pharma- ceutically acceptable carrier. An active pharmaceutical ingredient ("API"), in its broadest sense, is a chemical structure that has a biological effect on humans or animals. In pharmacology, drugs or medicines are used to treat, cure, prevent, or diagnose diseases or otherwise improve physical or mental well-being. Drugs or medicines can be used for a limited duration or periodically for chronic disorders.

[0028] As described below, a drug or agent may include at least one API or a combination thereof in various types of formulations for the treatment of one or more diseases. Examples of APIs may include small molecules with molecular weights of 500 Da or less; polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids, such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems, such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0029] The drug or agent can be contained in a primary package or "drug container" adapted for use in a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir, or other rigid or flexible vessel configured to provide a chamber suitable for storage (e.g., short-term or long-term storage) of one or more drugs. For example, in some cases, the chamber can be designed to store the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chamber can be designed to store the drug for about one month to about two years. Storage can be at room temperature (e.g., about 20° C.) or at refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some cases, the drug container can be or include a dual-chamber cartridge configured to separately store two or more components of a pharmaceutical formulation to be administered (e.g., an API and a diluent, or two different drugs), one in each chamber. In such cases, the two chambers of the dual-chamber cartridge can be configured to allow mixing between two or more components prior to and / or during administration to the human or animal body. For example, the two chambers can be configured to be in fluid communication with each other (e.g., via a conduit between the two chambers) and to allow mixing of the two components by a user, if desired, prior to administration. Alternatively or additionally, the two chambers can be configured to allow mixing upon administration of the components to the human or animal body.

[0030] The drugs or agents contained in the drug delivery devices described herein can be used for the treatment and / or prevention of many different types of medical disorders. Examples of disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, thromboembolic disorders, such as deep vein thromboembolism or pulmonary thromboembolism. Further examples of disorders are acute coronary syndromes (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those found in handbooks such as Rote Liste 2014 (e.g., but not limited to, main groups 12 (antidiabetic agents) or 86 (oncology agents)) and the Merck Index, 15th edition.

[0031] Examples of APIs for the treatment and / or prevention of type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin, e.g., human insulin, or a human insulin analog or derivative, glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, analog or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharma-ceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms "analog" and "derivative" refer to a polypeptide having a molecular structure that is formally derivable from the structure of a naturally occurring peptide, e.g., the structure of human insulin, by deletion and / or replacement of at least one amino acid residue present in the naturally occurring peptide and / or by addition of at least one amino acid residue. The added and / or replaced amino acid residue can be either a codable amino acid residue or another naturally occurring residue or a purely synthetic amino acid residue. Insulin analogs are also referred to as "insulin receptor ligands". In particular, the term "derivative" refers to a polypeptide having a molecular structure formally derivable from the structure of a naturally occurring peptide, e.g., the molecular structure of human insulin in which one or more organic substituents (e.g., fatty acids) are attached to one or more of the amino acids. Optionally, one or more amino acids present in the naturally occurring peptide are deleted and / or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable ones, are added to the naturally occurring peptide.

[0032] Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin in which the proline in position B28 may be replaced by Asp, Lys, Leu, Val or Ala and in which the Lys in position B29 may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0033] Examples of insulin derivatives are e.g. 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.

[0034] Examples of GLP-1, GLP-1 analogs and GLP-1 receptor agonists are, for example, lixisenatide (Lyxumia®), exenatide (exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide produced by the salivary glands of the flathead monster), liraglutide (Victoza®), semaglutide, taspoglutide, albiglutide (Syncria®), dulaglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, langrenatide / HM-11260C (efpegrenatide). , HM-15211, CM-3, GLP-1 Erigen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexene, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, ZP -DI-70, TT-401 (Pegapamodtide), BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN and Glucagon-Xten.

[0035] Examples of oligonucleotides are, for example: the cholesterol-lowering antisense therapeutic mipomersen sodium (Kynamro®) for the treatment of familial hypercholesterolemia, or RG012 for the treatment of Alport Syndrome.

[0036] Examples of DPP4 inhibitors are linagliptin, vidagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

[0037] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0038] Examples of polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or very low molecular weight heparin or derivatives thereof, or sulfated polysaccharides, such as the above-mentioned polysaccharides in polysulfated form, and / or their pharma- ceutically acceptable salts. An example of a pharma-ceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F20 (Synvisc®), sodium hyaluronate.

[0039] The term "antibody" as used herein refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of an immunoglobulin molecule include F(ab) and F(ab')2 fragments that retain the ability to bind to an antigen. An antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (e.g., murine) antibody, or a single chain antibody. In some embodiments, an antibody has effector function and is capable of fixing complement. In some embodiments, an antibody has reduced or no binding ability to Fc receptors. For example, an antibody can be an isotype or subtype, an antibody fragment, or a mutant that does not support binding to Fc receptors, e.g., with a mutation or deletion of the Fc receptor binding region. The term antibody also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or dual variable region antibody-like binding proteins (CODV) with crossover binding region orientation.

[0040] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., antibody heavy and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not include the full-length antibody polypeptide but comprises at least a portion of the full-length antibody polypeptide that is still capable of binding to an antigen. An antibody fragment can include truncated portions of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments, such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments, such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0041] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences in the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences in the variable regions of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the proper arrangement of the CDR sequences to allow antigen binding. Although the framework region itself typically does not directly participate in antigen binding, as is known in the art, certain residues in the framework region of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0042] Exemplary antibodies are anti-PCSK-9 mAb (eg, alirocumab), anti-IL-6 mAb (eg, sarilumab), and anti-IL-4 mAb (eg, dupilumab).

[0043] Pharmaceutically acceptable salts of any of the APIs described herein are contemplated for use in the drug or medicament in the drug delivery device. Pharmaceutically acceptable salts include, for example, acid addition salts and base salts.

[0044] Those skilled in the art will appreciate that modifications (addition and / or removal) of the various components of the APIs, formulations, devices, methods, systems, and embodiments described herein may be made without departing from the full scope and spirit of the invention, which encompasses such modifications and all equivalents thereof.

[0045] Exemplary drug delivery devices can include needle-based injection systems as described in Table 1 of Section 5.2 of ISO11608-1:2014(E). As described in ISO11608-1:2014(E), needle-based injection systems can be broadly distinguished into multi-dose container systems and single-dose (with partial or complete ejection) container systems. The container may be an exchangeable container or an integrated non-exchangeable container.

[0046] As further described in ISO11608-1:2014(E), a multi-dose container system can include a needle-based injection device with an exchangeable container. In such a system, each container holds multiple doses and the size may be fixed or variable (pre-set by the user). Another multi-dose container system can include a needle-based injection device with an integrated non-exchangeable container. In such a system, each container holds multiple doses and the size may be fixed or variable (pre-set by the user).

[0047] As further described in ISO11608-1:2014(E), the single-dose container system can include a needle-based injection device with a replaceable container. In one example of such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full expulsion). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial expulsion). As further described in ISO11608-1:2014(E), the single-dose container system can include a needle-based injection device with an integrated non-replaceable container. In one example of such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full expulsion). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial expulsion).

[0048] Non-limiting exemplary embodiments of the present invention will now be described with reference to the accompanying drawings. [Brief description of the drawings]

[0049] [Figure 1] FIG. 1 shows a perspective view of a housing for a drug delivery device according to a first embodiment of the present invention. [Diagram 2] 2 shows a cutaway view of the inside of the housing of FIG. 1. [Diagram 3] FIG. 2 shows a perspective view of a detail of a housing for a drug delivery device according to a second embodiment of the present invention. [Figure 4] 4 shows a cross-sectional view of the housing of FIG. 3. [Diagram 5] FIG. 4 shows a side view of the housing of FIG. 3. [Figure 6] FIG. 13 shows a perspective view of a housing for a drug delivery device according to a third embodiment of the present invention. [Figure 7] FIG. 7 shows a perspective view of the housing of FIG. 6. [Figure 8] FIG. 13 shows a cross-sectional view of a housing for a drug delivery device according to a fourth embodiment of the present invention. [Figure 9]4 shows a graph of the force exerted by the crush web in response to axial movement of the cartridge. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0050] In the drawings, identical elements, identically acting elements or elements of the same type are given the same reference signs.

[0051] As used herein, the terms "axial", "radial" or "circumferential" are used with respect to the main longitudinal axis I of the device, cartridge, housing or cartridge holder, e.g., the axis extending through the proximal and distal ends of the cartridge, cartridge holder or drug delivery device.

[0052] As used herein, "distal" is used to identify a direction, end, or surface that faces or is configured to point toward the dosing end of the drug delivery device or a component thereof, and / or that faces in a direction opposite to the proximal end or that faces in a direction opposite to the proximal end. On the other hand, "proximal" is used to identify a direction, end, or surface that faces or is configured to point in a direction opposite to the dosing end and / or the distal end of the drug delivery device or a component thereof. The distal end may be the end closest to the dosing end and / or the end furthest from the proximal end, and the proximal end may be the end furthest from the dosing end. The proximal face may face in a direction away from the distal end and / or towards the proximal end. The distal face may face in a direction toward the distal end and / or away from the proximal end. The dosing end may be, for example, the needle end at which the needle unit is or will be attached to the device.

[0053] A first embodiment of the invention is depicted in Figures 1 and 2. These figures show diagrammatically a housing element 1 for use in a drug delivery device. The housing element 1 comprises a proximal body part 2 having a smaller diameter and a distal body part 3 having a larger diameter compared to the proximal body part 2. The proximal body part 2 and the distal body part 3 are connected by a flange-like wall extending substantially perpendicular to the longitudinal axis I. The distal body part 3 comprises a circumferentially extending groove 4 forming an engagement feature for axially restraining the housing 1 to another component of the drug delivery device, for example for axially restraining the housing element 1 to a cartridge holder (not shown in Figures 1 and 2).

[0054] The housing element 1 may be the internal housing or inner body of the drug delivery device, e.g., an internal component that houses components of the drive mechanism and / or the dose setting mechanism of the drug delivery device. Alternatively, the housing element 1 may be the external housing or outer body of the drug delivery device, i.e., an outer shell that encases all components of the drug delivery device.

[0055] As shown in Figures 1 and 2, the distal body portion 3 includes an aperture 5. In the exemplary embodiment, the aperture 5 is generally rectangular and inclined relative to the longitudinal axis I of the housing 1. However, the shape and orientation of the aperture 5 is not limited to the depicted example. Furthermore, there may be multiple apertures 5, as shown in Figures 1 and 2.

[0056] FIG. 2 shows a partial cutaway view of the inside of the distal body portion 3. The crush web 6 is provided adjacent the aperture 5 inside the distal body portion 3. In other words, the crush web 6 extends in a generally radially inward direction. As seen in FIG. 2, the crush web 6 extends in a plane inclined at about 15° with respect to the longitudinal axis I of the housing. The radially inward facing edge of the crush web 6 extends in a cylindrical plane parallel to the cylindrical distal body portion 3. In other words, the radially inward facing edge does not taper with respect to the distal body portion 3. Furthermore, in the exemplary embodiment, the crush web 6 has a generally constant thickness of about 0.15 mm. FIG. 2 shows the crush web as being rather thick for illustrative purposes.

[0057] The interior space of the distal body portion 3 of the housing element 1 is intended to receive the proximal end of a cartridge (not shown) during assembly of the drug delivery device. The crush web 6 is positioned such that the nominal outer diameter of the cartridge radially interferes with the crush web 6. Thus, when the cartridge is assembled, the crush web 6 folds / rolls into the aperture 5 while maintaining axial and radial restraint on the cartridge in all tolerance conditions.

[0058] One or more crush webs are molded into the housing element 1 of the device, with one side of the crush rib 6 adjacent / matching the aperture 5 through the side wall of the housing element 1 and inclined at least 3°, preferably 15°, relative to the longitudinal axis I of the housing element 1 such that when the cartridge is assembled, the web 6 is folded / rolled into the aperture 5 to maintain axial and radial restraint on the cartridge under all tolerance conditions. An example of such an embodiment including three crush webs 6 spaced 120° apart is shown in the exemplary embodiment of Figures 3-5. For example, as seen in Figure 4, the distal body portion 3 can have a locally reduced wall thickness where each crush web 6 joins with the outer wall of the distal body portion 3. Additionally, Figure 4 shows a threaded interface 7 provided on the interior of the proximal body portion 2. This threaded interface may be suitable for engagement with a threaded piston rod or the like.

[0059] In Fig. 4 the cartridge is shown by two concentric circles D1 (external diameter of the cartridge) and D2 (internal diameter of the cartridge). As can be seen, the crush ribs 6 are designed to interfere with the glass of the cartridge and to deform during assembly of the mechanism.

[0060] The first and second embodiments shown in Figures 1 to 5 show a housing element 1 suitable for receiving a 3 ml cartridge, but at least one crush web 6 according to the present disclosure is provided in the housing for other cartridge sizes. An example of a housing element 1 suitable for a 1.5 ml cartridge variant is depicted in the third embodiment in Figures 6 and 7. The diameter of the distal body portion 3 is identical to that in the second embodiment of Figures 3 to 5, but the outer diameter of the cartridge is substantially smaller in the third embodiment. The reduced diameter of the cartridge is indicated in Figure 7 by the outer diameter D1 and the inner diameter D2 of the cartridge.

[0061] In this third embodiment, the distal body portion 3 comprises two pairs of radially extending support walls 8 spaced 180° apart. A crush web 6 is provided on the radially inwardly facing edge of each of the four support walls 8. When the cartridge is inserted into the housing element 1, the crush web 6 interferes with the outer diameter of the cartridge, folding the crush web 6 into the space between the inner edges of the support walls 8 and the distal body portion 3.

[0062] 8 shows a fourth embodiment of the invention, where the housing element 1 is an inner body held within an outer body or shell 9. The inner housing element 1 is axially constrained to the outer body 9 by inwardly extending beads of the outer body 9 that engage grooves 4 in a distal body portion 3 of the inner housing element 1. The outer body 9 extends from the distal end to the proximal end of the drug delivery device and not only houses the dose setting and drive mechanisms but also functions as a cartridge holder. Alternatively, a separate cartridge holder is provided attached to the housing element 1 and / or the outer body 9.

[0063] The inner housing element 1 has a threaded interface on the outside of the proximal body part 2 for engaging with a dose dial or number sleeve 10. Furthermore, a splined interface provided on the inside of the proximal body part 2 engages and guides a driver 11 of the drug delivery device. Furthermore, a threaded piston rod 12 is guided in the threaded interface 7. In the state shown in FIG. 8, a cartridge 13 having a bung or piston 14 is inserted into the device such that the proximal end of the cartridge 13 is received in the distal body part 3 of the inner housing element 1. By inserting the cartridge 13 into the distal body part 3, the crush webs 6 are deformed, whereby the cartridge 13 is constrained axially and radially within the inner housing element 1.

[0064] FIG. 9 is a graph comparing the force exerted by the tapered prior art ribs (dotted line) with the force exerted by the crush webs of the present disclosure (solid line) as the cartridge 13 is inserted into the housing element 1. The tapered prior art ribs apply a gradually increasing force to the cartridge, whereas the crush webs of the present disclosure apply a substantially constant force to the cartridge. More specifically, after initial engagement of the crush webs 6, the force rises to about 3N for about 0.2mm of relative movement between the cartridge 13 and the crush webs 6, and only rises to less than 4N for the next 1.2mm of movement. This is ideal because it can accommodate a ±0.6mm tolerance in the assembly height of the end faces of the cartridge 13 relative to the housing element 1 while still exerting 3-4N per crush web 6. The crush webs 6 deform as the cartridge 13 is inserted, and tend to fold in the middle due to their angled geometry. Since the crush web 6 is only 0.15 mm thick, this requires only a small assembly force, which does not change significantly as the cartridge is inserted further axially.

[0065] The small axial force to assemble the cartridge prevents glass breakage during assembly. Additionally, this maintains good dose accuracy by preventing cartridge movement when attaching the needle (not shown) and exhibits improved impact test performance with significantly reduced instances of glass breakage when using these crush webs 6 to hold the cartridge 13. [Explanation of symbols]

[0066] 1 (inner) housing element 2. Proximal Body Part 3. Distal Body Part 4 Engagement groove 5 Aperture 6. Crash Web 7 Threaded Interface 8. Wall 9 Outer body (shell) 10 Number Sleeve 11 Drivers 12 Piston rod 13 Cartridge 14 Piston D1 Cartridge outer diameter D2 Cartridge Inner Diameter I Longitudinal axis

Claims

1. A housing element for a drug delivery device, comprising a longitudinal axis (I) and defining an interior space for receiving components (11, 12) of a drive mechanism of the drug delivery device and at least a part of a cartridge (13) of the drug delivery device, comprising engagement features (4) for axially restraining the housing element to a cartridge holder (9) of the drug delivery device, and further comprising at least one crush web (6) protruding radially inwardly into the interior space, wherein the at least one crush web (6) is inclined by at least 3° with respect to the longitudinal axis (I) of the housing element such that when the cartridge (13) is introduced into the interior space, the at least one crush web (6) is folded radially outwardly.

2. 2. A housing element according to claim 1, wherein at least one crush web (6) is inclined by at least 5° to the longitudinal axis (I) of the housing element.

3. 3. A housing element according to claim 1 or 2, comprising at least one lateral aperture (5), wherein the at least one crush web (6) is positioned adjacent and / or coincident with the at least one lateral aperture (5) such that when the cartridge (13) is introduced into the interior space, the at least one crush web (6) is folded into the at least one lateral aperture (5).

4. A housing element according to any one of claims 1 to 3, comprising three crush webs (6) arranged at intervals of 120°.

5. 3. A housing element as described in claim 1 or 2, comprising at least one support structure (8) extending radially inward into the interior space, thereby reducing the diameter for receiving a cartridge (13) of a drug delivery device, wherein the at least one crush web (6) is positioned on the at least one support structure (8) such that when the cartridge (13) is introduced into the interior space, the at least one crush web (6) is folded radially outward.

6. 6. A housing element according to claim 5, wherein the at least one support structure (8) comprises two pairs of radially inwardly projecting walls (8), one crush web (6) being located on each of the four walls (8).

7. 7. A housing element according to claim 6, wherein pairs of radially inwardly projecting walls (8) are arranged at 180° intervals.

8. A housing element according to any one of the preceding claims, wherein the at least one crush web (6) has a thickness of at least 0.1 mm.

9. A housing element according to any one of the preceding claims, wherein at least one crush web (6) has a locally reduced wall thickness where it joins with the housing element.

10. A housing element according to any one of claims 1 to 9, comprising an internal thread (7) for engagement with a threaded piston rod (12) of a drug delivery device, and / or comprising an external thread for engagement with a dose dial sleeve (10) of the drug delivery device, and / or comprising axially extending internal splines for engagement with a drive sleeve (11) of the drug delivery device.

11. A housing element according to any one of claims 1 to 10, comprising a distal body part (3) having a larger diameter for receiving at least a part of a cartridge (13) of a drug delivery device and a proximal body part (2) having a smaller diameter compared to the distal body part (3) for receiving a component (10, 11) of a drive mechanism of the drug delivery device, wherein the distal body part (3) and the proximal body part (2) are connected to each other by a radially extending flange wall.

12. A housing element according to any one of the preceding claims, wherein the engagement feature (4) is a circumferentially extending bead or groove (4) provided on the outer surface of the housing element.

13. A drug delivery device comprising a housing element (1) according to any one of claims 1 to 12, comprising a cartridge (13) containing a medicament, a drive mechanism for driving a piston (14) in the cartridge (13), and an outer body (9) axially constrained to the housing element (1) by an engagement feature (4).

14. 14. The drug delivery device according to claim 13, wherein the outer body (9) surrounds the housing element (1) and the cartridge (13).

15. A drug delivery device as described in claim 13 or 14, wherein the cartridge (13) has a nominal outer diameter (D1) that radially interferes with at least one crush web (6) when the cartridge (13) is introduced into the interior space of the housing element.

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