Housing element and a drug delivery device having the housing element

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 internal 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 engagement features (4) for axially constraining the housing element to a cartridge holder (9) of the drug delivery device. In order to constrain the cartridge (13) within the housing element (1), it further includes at least one squeezing strip (6) that projects radially inwards into the internal space. The at least one squeezing strip (6) is at an angle of at least 3° with respect to the longitudinal axis (I) of the housing element such that when the cartridge (13) is introduced into the internal space, the at least one squeezing strip (6) folds radially outwards.

Description

[0001] The present invention generally relates to a housing element for a drug delivery device, such as an inner housing part or an outer housing part. The present invention further relates to a drug delivery device comprising such a housing element.

[0002] Pen-type drug delivery devices are suitable for situations where routine injections are carried out by persons without formal medical training. This may be becoming increasingly common among patients suffering from diabetes, for whom self-treatment enables these patients to effectively manage their disease. In practice, such drug delivery devices allow the user to individually select and dispense a plurality of user-variable doses of a medicament.

[0003] Basically, there are two types of drug delivery devices: resetable devices (i.e., reusable) and non-resetable devices (i.e., disposable). For example, disposable pen-type delivery devices are supplied as self-contained devices. Such stand-alone devices do not have a removable pre-filled cartridge. Instead, the pre-filled cartridge cannot be removed and replaced from these devices without destroying the device itself. Thus, such disposable devices do not need to have a resetable dose setting mechanism. The present invention generally applies to both disposable and reusable devices. However, the present invention particularly applies to pre-filled disposable pen-type devices.

[0004] Such drug delivery devices typically include a dose setting and / or driving mechanism to select an individual dose and to deliver that dose by moving a piston in a cartridge containing the medicament. The cartridge, such as a glass ampoule, is held in a cartridge holder or a similar type of receptacle for such a container. Before dose delivery, a needle is fixed to the cartridge holder, thereby piercing the septum of the cartridge. This applies an axial force on the cartridge. However, in order to maintain good dose accuracy, it is important to limit the axial movement of the cartridge relative to the cartridge holder and relative to the dose setting and / or driving mechanism during attachment of the needle and subsequent dose delivery.

[0005] Due to relatively large tolerances in the length and diameter of the cartridge, it is known to provide some deformation of the retaining features in order to ensure restraint of the cartridge at all tolerance extremes. For example, WO 2005 / 018721 A proposes a drug delivery device having an extrusion strip that is molded into the interior of the cartridge holder to hold the cartridge axially fixed between such extrusion strip and the inner surface of the cartridge holder. Two further examples of deformable members engaging the cartridge neck to support the cartridge against axial movement are known from WO 2016 / 065220 A and WO 2016 / 156387 A. In addition, it is known from WO 99 / 038554 A and WO2017 / 001693 A to provide tapered ribs on an insert such that the ribs gradually reduce the internal space for receiving the proximal end of the cartridge.

[0006] The disadvantage of these known solutions is that, depending on the tolerance, either the cartridge is not firmly constrained in the cartridge holder or the force for assembling the cartridge is relatively high, which may cause the glass to break during assembly or in the case of a collision, i.e., if the device is dropped from a relatively high height onto a hard surface.

[0007] Accordingly, the aim is to improve the axial and radial holding and constraining of the cartridge within the drug delivery device.

[0008] For example, the aim is solved by the subject matter defined in the independent claims. Advantageous embodiments and improvements are subject to the dependent claims. However, it should be noted that the present disclosure is not limited to the subject matter defined in the appended claims. Rather, as will become apparent from the following description, the present disclosure may include improvements additional to or alternative to the subject matter defined in the independent claims.

[0009] One aspect of the present disclosure relates to a housing element for a drug delivery device, wherein the housing element has a longitudinal axis and defines an internal 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. Generally, the housing of a drug delivery device may comprise two housing elements, namely an inner body which may constrain and guide the drive mechanism in an exemplary embodiment and an outer body which may form the entire outer surface in an exemplary embodiment, optionally including a cartridge holder. The two housing elements may be formed as a single part, but most likely will be formed as two or more parts for manufacturing reasons. The connection between these parts may be at different locations, depending on the requirements of the device design and manufacturing. In the following, the present disclosure is mainly described with reference to an example where the housing element is the inner body, i.e., the part arranged within the outer body and adapted to hold and / or receive other components of the device. In particular, the inner body may be adapted to guide and / or restrict the movement of components of the drug delivery device. As an alternative, the housing element may be the outer body. The housing element preferably comprises engagement features for axially constraining the housing element to a cartridge holder of the drug delivery device. In other words, although the housing element, such as the inner body, is designed to receive a portion of the cartridge, preferably the proximal portion of the cartridge, the housing element is not the cartridge holder. Instead, the cartridge holder according to the present disclosure is an assembly which receives and holds at least the distal (dispensing end) of the cartridge and allows attachment of a needle by means of at least one attachment feature (such as a threaded interface, a bayonet interface or a Luer lock) provided on the cartridge holder.

[0010] In addition, the housing element includes at least one pressing strip that projects radially inwards into the internal space. Preferably, the at least one pressing strip is at an angle of at least 3° relative to the longitudinal axis of the body. Preferably, this causes the at least one pressing strip to fold radially outwards when the cartridge is introduced into the internal space. In other words, the pressing strip defines a plane having a substantially radial orientation relative to the longitudinal axis, wherein this plane is inclined at least 3° relative to the longitudinal axis of the housing element. The at least one pressing strip can be at an angle of at least 5°, preferably about 15°, relative to the longitudinal axis of the body. The at least one pressing strip can be at an angle of up to 45°, preferably less than 25°, relative to the longitudinal axis of the body. If the angle of the pressing strip with respect to the longitudinal axis is too small / shallow, then the pressing strip may bend rather than unfold. This increases the assembly force and there is also a risk that the pressing strip breaks into several small parts, which may be visible inside the cartridge holder or may be harmful to the operation of the pen-injector mechanism.

[0011] Compared with known tapered ribs, the radially inwards edge of the at least one pressing strip can be arranged such that the internal space defined by the at least one pressing strip does not decrease axially. In other words, the radially inwards edge of the at least one pressing strip lies in, for example, at least substantially a cylindrical surface. This includes embodiments having a chamfered inner distal end of the at least one pressing strip. Preferably, the radially inwards edge of the at least one pressing strip lies in a cylindrical or tapered plane having an inclination relative to the longitudinal axis of less than 5°.

[0012] A housing element comprising at least one pressing strip as described above is adapted to axially and radially hold and restrain a cartridge within the housing element and thus within a drug delivery device. In particular, the at least one pressing strip is adapted to limit axial movement of the cartridge relative to the housing element within the device during attachment of the needle and subsequent dose delivery, which is essential for maintaining good dose accuracy. In addition, fixedly restraining the cartridge also reduces the risk of the cartridge breaking during an impact, for example if the device is dropped from a greater height onto a hard surface. Thus, a drug delivery device having such a housing element has improved impact test performance, significantly reducing the case of glass breakage when using these pressing strip features to hold the cartridge. Due to the relatively large tolerances in the length and diameter of the cartridge, the safety restraint at all tolerance extremes requires a predefined deformation of the at least one pressing strip. The above-described housing element having at least one pressing strip only requires a low axial force to assemble the cartridge, thus significantly reducing the risk of glass breakage during the assembly process while maintaining good dose accuracy by preventing movement of the cartridge when installing the needle.

[0013] In one embodiment, the housing element has at least one lateral hole. Preferably, the at least one squeezing strip is located adjacent to and / or coincident with the at least one lateral hole. This allows the at least one squeezing strip to fold into the at least one lateral hole when the cartridge is introduced into the internal space. Thus, excessive forces acting on the cartridge are avoided, and the folding behavior of the at least one squeezing strip is more predictable and predefined. Including a hole also enables the squeezing strip to be molded, otherwise a "undercut" would need to be made in the mold. The hole can be made using a single workpiece of the mold (e.g., a slider) that forms one side of the squeezing strip and mates with another workpiece of the mold (e.g., a core pin) that forms the other side of the squeezing strip. In practice, the mating between these two mold parts also means that there is a passage for air in the mold to escape, which helps the very thin squeezing strip to be properly filled with polymer during the molding process.

[0014] Generally, at least one squeezing strip and the inner surface of the housing element can be used to fix the cartridge within the housing element. However, preferably, the housing element includes a plurality of squeezing strips, such as three squeezing strips spaced approximately 120° apart, such that the cartridge is constrained within the housing element only by the radially inner edges of the squeezing strips.

[0015] Typical cartridge volumes for drug delivery devices include 3 ml and 1.5 ml cartridges. If a small diameter cartridge (1.5 ml) is used that is installed within a device that is also capable of accommodating a larger diameter cartridge (3 ml), the housing element can be adapted without having to adapt the entire dose setting and / or drive mechanism. For example, the housing element can be provided with at least one support structure that extends radially inwards into the internal space, thereby reducing the diameter for receiving the cartridge of the drug delivery device. In one embodiment, the at least one squeezing strip is located on the at least one support structure such that when the cartridge is introduced into the internal space, the at least one squeezing strip folds radially outwards, e.g., folds in the free space next to the support structure. The at least one support structure can include two pairs of radially inwards protruding walls, with one squeezing strip on each of the four walls. Additionally, the two pairs of radially inwards protruding walls can be spaced 180°. For manufacturing reasons, it is preferably to separate the two pairs of squeezing strips by 180°. This is easier when the squeezing strips are radially located within the outer wall of the housing, e.g., if the mold has at most two sliders.

[0016] In one embodiment, the at least one extrusion strip has a thickness of at least 0.1 mm to about 0.3 mm, preferably about 0.15 mm or about 0.2 mm. If the extrusion strip is too thick and radially protruding, it will not bend but must plastically yield, resulting in a greater assembly force. This in turn creates higher stresses in the glass wall of the cartridge, and the glass wall may crack during assembly or even during storage or use after assembly. The assembly force can vary significantly with the tolerances of the cartridge length and diameter, but by promoting the folding behavior of the at least one extrusion strip rather than buckling or extrusion, the variation is controlled within acceptable parameters that do not cause glass breakage.

[0017] To improve the predetermined folding performance of the at least one extrusion strip so as to fold radially outward when the cartridge is inserted, the housing element may have a locally reduced wall thickness at the location where the at least one extrusion strip is connected to the housing element. Thus, when the cartridge is inserted, the extrusion strip deforms and tends to fold due to the angled geometry. Since the extrusion strip is, for example, only 0.15 mm thick, this requires a lower assembly force, and the assembly force does not change significantly as the cartridge is further axially inserted.

[0018] In one embodiment, the housing element includes a distal portion and a proximal portion. The distal portion has a larger diameter for receiving at least a portion of the cartridge of the drug delivery device, and the proximal portion has a smaller diameter compared to the distal portion for receiving components of the drive mechanism of the drug delivery device. For example, the distal portion and the proximal portion are interconnected by a radially extending flange wall.

[0019] In one embodiment, the housing element is an internal body for a drug delivery device and is configured to interact with components of the dose setting and / or drive mechanism of the drug delivery device. For example, the housing element, such as the proximal portion, may include an internal thread for engaging a threaded piston rod of the drug delivery device. Additionally or alternatively, the housing element, such as the proximal portion, may include an external thread for engaging a dose selection sleeve (digital sleeve) of the drug delivery device. Additionally or alternatively, the housing element, such as the proximal portion, may include an internal axially extending spline for engaging a drive sleeve of the drug delivery device. Further, the housing element, such as the distal portion, includes engagement features, which may be a circumferentially extending bead or groove provided on the outer surface of the housing element.

[0020] The present invention also relates to a drug delivery device comprising a housing element as described above, preferably an inner body. In one embodiment, a 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 which is similar to an outer body axially constrained on the housing element by engagement features. Optionally, the outer body surrounds the housing element and the cartridge, i.e., the outer body can extend from the distal end to the proximal end of the device such that the outer body is also a cartridge holder, e.g., having an interface for attaching a needle.

[0021] The present invention is particularly applicable to disposable pen-type devices where the cost precludes the use of a metal spring element to axially bias the cartridge to the needle end of the cartridge holder.

[0022] In one embodiment, the cartridge has a nominal outer diameter which radially interferes with the at least one squeezing strip when the cartridge is introduced into the inner space of the housing element.

[0023] According to a preferred example, the at least one squeezing strip is dimensioned to fit the nominal outer diameter of the barrel, i.e., when the barrel is introduced into the inner space of the body, after an initial engagement between the respective squeezing strip and the barrel, e.g., after a relative travel between the respective squeezing strip and the barrel of 0.2 mm and up to 1.5 mm, each squeezing strip exerts a force of about 2.5 N to 5 N, preferably between 3 N and 4.5 N. This can be achieved if the squeezing strip is at an angle of at least 3°, preferably 15°, relative to the axis of the housing so that when the cartridge is assembled, the squeezing strip folds / curls into the hole to maintain axial and radial restraint of the cartridge under all tolerance conditions. Typical tolerance conditions for the cartridge and associated device components are within + / - 0.6 mm of the assembled height of the proximal end face of the cartridge.

[0024] The present invention is applicable to devices manually driven, for example, by a user applying a force to an injection button, to devices driven by a spring, etc., and to devices combining both concepts (i.e., spring-assisted devices where the user still needs to apply an injection force). Spring-type devices relate to pre-loaded springs and springs loaded by the user during the dose selection process. For example, during the dose setting process, some energy storage devices use a combination of spring pre-loading and additional energy provided by the user.

[0025] The drug delivery device may comprise a cartridge containing a medicament.

[0026] The terms "drug" or "medicament" are used synonymously herein and describe a pharmaceutical formulation that contains one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof and optionally a pharmaceutically acceptable carrier. In the broadest sense, an active pharmaceutical ingredient ("API") is a chemical structure that has a biological effect on a human or animal. In pharmacology, a drug or medicament is used to treat, cure, prevent, or diagnose a disease, or to otherwise enhance physical or mental health. A drug or medicament can be used for a limited duration, or regularly for a chronic disorder.

[0027] As described below, a drug or medicament can 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 can include small molecules (having a molecular weight 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, i.e., 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 can be incorporated into a molecular delivery system (e.g., a vector, plasmid, or liposome). A mixture of one or more drugs is also contemplated.

[0028] A drug or medicament can be contained in a primary packaging or "drug container" suitable for use with a drug delivery device. The drug container can be, for example, a cartridge, syringe barrel, reservoir, or other rigid or flexible vessel that is configured to provide a suitable chamber for storing (e.g., short-term or long-term storage) 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., 1 day to at least 30 days). In some cases, the chamber can be designed to store the drug for about 1 month to about 2 years. Storage can occur at room temperature (e.g., about 20 °C) or at refrigerated temperature (e.g., from about -4 °C to about 4 °C). In some cases, the drug container can be or can include a dual-chamber cartridge that is 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), with one component stored in each chamber. In such cases, the two chambers of the dual-chamber cartridge can be configured to allow mixing between the two or more components before and / or during dispensing into a human or animal body. For example, the two chambers can be configured such that they are in fluid communication with each other (e.g., by means of a conduit between the two chambers) and allow the user to mix the two components when needed before dispensing. Alternatively or additionally, the two chambers can be configured to allow mixing when the components are dispensed into a human or animal body.

[0029] The drugs or medicaments accommodated in the drug delivery device described herein can be used for treating and / or preventing many different types of medical disorders. Examples of disorders include, for example, diabetes or diabetes-related complications (such as diabetic retinopathy), thromboembolic disorders (such as deep vein or pulmonary thromboembolism). Further examples of disorders are acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those described in the following manuals: such as the German Medical Practitioners' Drug Handbook (Rote Liste) 2014, for example, but not limited to, main group 12 (antidiabetic drugs) or 86 (oncological drugs); and the 15th edition of the Merck Index.

[0030] Examples of APIs for treating and / or preventing type 1 or type 2 diabetes or diabetes-related complications of type 1 or type 2 include insulin (such as human insulin, or human insulin analogues or derivatives); glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or their analogues or derivatives; dipeptidyl peptidase-4 (DPP4) inhibitors, or their pharmaceutically acceptable salts or solvates; or any mixture thereof. As used herein, the terms "analogue" and "derivative" refer to a polypeptide having a molecular structure that can be formally derived from the structure of a naturally occurring peptide (such as the structure of human insulin) by deletion and / or exchange 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 exchanged amino acid residues can be encoded 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 having a molecular structure that can be formally derived from the structure of a naturally occurring peptide (such as the structure of human insulin), wherein one or more organic substituents (such as fatty acids) are bound to one or more amino acids. Optionally, one or more amino acids present in the naturally occurring peptide may have been deleted and / or replaced by other amino acids (including non-encoded amino acids), or amino acids (including non-encoded amino acids) have been added to the naturally occurring peptide.

[0031] Examples of insulin analogs 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 proline at position B28 is replaced by Asp, Lys, Leu, Val or Ala and in which Lys at position B29 can be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0032] Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (insulin detemir, ); 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-γ-glutamyl)-des(B30) human insulin, B29-N-ω-carboxypentadecanoyl-γ-L-glutamyl-des(B30) human insulin (insulin degludec, ); B29-N-(N-lithocholyl-γ-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0033] Examples of GLP-1, GLP-1 analogs and GLP-1 receptor agonists are, for example, lixisenatide exenatide (Exendin-4, a 39-amino acid peptide produced by the salivary gland of the Gila monster), liraglutide semaglutide, taspoglutide, albiglutide dulaglutide rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211, CM-3, GLP-1 Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, 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, LY3298176 (Tirzepatide), SAR425899 (Bimagrumab), Exenatide-XTEN, and Glucagon-XTEN.

[0034] Examples of oligonucleotides are, for example, mipomersen sodium It is a cholesterol-reducing antisense therapeutic agent for treating familial hypercholesterolemia or RG012 for treating Alport syndrome.

[0035] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0036] Examples of hormones include pituitary hormones or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, gonadotropin), growth hormone (Somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0037] Examples of polysaccharides include glucosaminoglycane, hyaluronic acid, heparin, low molecular weight heparin or ultra-low molecular weight heparin or derivatives thereof, or sulfated polysaccharides (e.g., the polysulfated forms of the above polysaccharides), and / or their pharmaceutically acceptable salts. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 It is a sodium hyaluronate.

[0038] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen. The 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, the antibody has effector functions and can fix complement. In some embodiments, the antibody has a reduced or no ability to bind to Fc receptors. For example, the antibody can be an isotype or subtype, an antibody fragment, or a mutant that does not support binding to Fc receptors, e.g., it has a mutagenized or deleted Fc receptor-binding region. The term antibody also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTIs) and / or dual variable domain antibody-like binding proteins with cross-over binding domain orientation (CODV).

[0039] The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy chain and / or light chain polypeptide) that does not include the full-length antibody polypeptide but still includes at least a portion of the full-length antibody polypeptide that is capable of binding antigen. Antibody fragments can comprise a cleaved portion of the full-length antibody polypeptide, although the term is not limited to such cleaved 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, tetra-specific, and multispecific antibodies (e.g., diabodies, triabodies, tetra-bodies)), monovalent or multivalent antibody fragments (such as divalent, trivalent, tetravalent, and multivalent antibodies), minibodies, chelate recombinant antibodies, triabodies or diabodies, intracellular antibodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and antibodies containing VHHs. Other examples of antigen-binding antibody fragments are known in the art.

[0040] The term "complementary determining region" or "CDR" refers to short polypeptide sequences within the variable regions of both the heavy chain polypeptide and the light chain polypeptide that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to the amino acid sequences within the variable regions of both the heavy chain polypeptide and the light chain polypeptide that are not CDR sequences and are primarily responsible for maintaining the correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of some antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in the CDRs to interact with the antigen.

[0041] Examples of antibodies are anti-PCSK-9 mAb (e.g., Alirocumab), anti-IL-6 mAb (e.g., Sarilumab), and anti-IL-4 mAb (e.g., Dupilumab).

[0042] Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts.

[0043] Those skilled in the art will understand that various components of the APIs, formulations, devices, methods, systems, and embodiments described herein can be modified (added and / or removed) without departing from the full scope and spirit of the invention, and the invention encompasses such modifications and any and all equivalents thereof.

[0044] Example drug delivery devices can relate to needle-based injection systems as described in Table 1 of Section 5.2 of ISO 11608-1:2014(E). As described in ISO 11608-1:2014(E), needle-based injection systems can be broadly divided into multi-dose container systems and single-dose (with partial or full discharge) container systems. The container can be a replaceable container or an integrated non-replaceable container.

[0045] As further described in ISO 11608-1:2014(E), a multi-dose container system can relate to a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, and the size of the doses can be fixed or variable (preset by the user). Another multi-dose container system can relate to a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, and the size of the doses can be fixed or variable (preset by the user).

[0046] As further described in ISO 11608-1:2014(E), a single-dose container system can relate to 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 discharged (full discharge). In additional examples, each container holds a single dose, whereby a portion of the deliverable volume is discharged (partial discharge). As also described in ISO 11608-1:2014(E), a single-dose container system can relate to 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 discharged (full discharge). In additional examples, each container holds a single dose, whereby a portion of the deliverable volume is discharged (partial discharge).

[0047] The non-limiting exemplary embodiments of the present invention will now be described with reference to the accompanying drawings, in which:

[0048] Figure 1 shows a perspective view of a housing for a drug delivery device according to a first embodiment of the present invention;

[0049] Figure 2 shows a sectional view of the inside of the housing of Figure 1;

[0050] Figure 3 shows a perspective view of details of a housing for a drug delivery device according to a second embodiment of the present invention;

[0051] Figure 4 shows a section through the housing of Figure 3;

[0052] Figure 5 shows a side view of the housing of Figure 3;

[0053] Figure 6 shows a perspective view of a housing for a drug delivery device according to a third embodiment of the present invention;

[0054] Figure 7 shows a perspective view of the housing of Figure 6;

[0055] Figure 8 shows a sectional view of a housing for a drug delivery device according to a fourth embodiment of the present invention; and

[0056] Figure 9 shows a graph of the force applied by the extrusion bar against the axial travel of the cartridge.

[0057] In the drawings, the same elements, elements having the same function, or elements of the same kind may be provided with the same reference numerals.

[0058] As used herein, the terms "axial", "radial", or "circumferential" may be used relative to the main longitudinal axis 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).

[0059] "Distal" is used herein to indicate a direction, end, or surface that is arranged or to be arranged facing or pointing towards the dispensing end of the drug delivery device or its components and / or outwardly pointing, to be arranged away from or opposite to the proximal end. On the other hand, "proximal" is used to indicate a direction, end, or surface that is arranged or to be arranged away from or opposite to the dispensing end of the drug delivery device or its components and / or the distal end. The distal end may be the end closest to the dispensing end and / or the farthest from the proximal end, and the proximal end may be the end farthest from the dispensing end. The proximal surface may face away from the distal end and / or towards the proximal end. The distal surface may face the distal end and / or face away from the proximal end. For example, the dispensing end may be the needle end to which the needle unit is or is to be mounted to the device.

[0060] A first embodiment of the present invention is shown in FIGS. 1 and 2. These figures schematically show a housing element 1 for a drug delivery device. The housing element 1 comprises a proximal body portion 2 having a smaller diameter and a distal body portion 3 having a larger diameter compared to the proximal body portion 2. The proximal body portion 2 and the distal body portion 3 are connected by a flange-like wall extending substantially perpendicular to the longitudinal axis I. The distal body portion 3 has a circumferentially extending groove 4 which forms an engagement feature for axially constraining the housing 1 to another component of the drug delivery device, for example for axially constraining the housing element 1 to a cartridge holder (not shown in FIGS. 1 and 2).

[0061] The housing element 1 can be an inner housing or inner body of the drug delivery device, e.g., an inner component part that houses components of the drive mechanism and / or dose setting mechanism of the drug delivery device. As an alternative, the housing element 1 can be an outer housing or outer body of the drug delivery device, i.e., a housing that encloses all components of the drug delivery device.

[0062] As shown in FIGS. 1 and 2, the distal body portion 3 includes a hole 5. In an exemplary embodiment, the hole 5 is substantially rectangular and angled with respect to the longitudinal axis I of the housing 1. However, the shape and orientation of the hole 5 are not limited to the example shown. Additionally, there can be more than one hole 5, as shown in FIGS. 1 and 2.

[0063] FIG. 2 shows a partially cut-away view of the inner side of the distal body portion 3. On the inner side of the distal body portion 3, an extrusion strip 6 is provided adjacent to the hole 5. In other words, the extrusion strip 6 extends substantially radially inwards. As shown in FIG. 2, the extrusion strip 6 extends in a plane at an angle of approximately 15° with respect to the longitudinal axis I of the housing. The radially inwards edge of the extrusion strip 6 extends in a cylindrical surface parallel to the cylindrical distal body portion 3. In other words, the radially inwards edge is not tapered with respect to the distal body portion 3. Additionally, in an exemplary embodiment, the extrusion strip 6 has a substantially constant thickness of approximately 0.15 mm. For illustrative purposes, FIG. 2 shows an extrusion strip that is clearly thicker.

[0064] The inner space of the distal body portion 3 of the housing element 1 is for receiving the proximal end of a cartridge (not shown) during the assembly of the drug delivery device. The extrusion strip 6 is arranged such that the nominal outer diameter of the cartridge radially interferes with the extrusion strip 6. Thus, when the cartridge is assembled, the extrusion strip 6 folds / curls into the hole 5, maintaining axial and radial constraint of the cartridge under all tolerance conditions.

[0065] One or more extrusion strips may be molded into the housing element 1 of the device, wherein one side of the extrusion strip 6 is adjacent to / coincides with the hole 5 through the side wall of the housing element 1 and is at least 3°, preferably 15°, relative to the longitudinal axis I of the housing element 1, such that when the cartridge is assembled, the extrusion strip 6 folds / curls into the hole 5, maintaining axial and radial restraint of the cartridge under all tolerance conditions. An example of such an embodiment including three extrusion strips 6 spaced 120° apart is shown in the exemplary embodiments of FIGS. 3 to 5. As can be seen, for example in FIG. 4, the distal body portion 3 may have a locally reduced wall thickness where the respective extrusion strip 6 joins the outer wall of the distal body portion 3. In addition, FIG. 4 shows a threaded interface 7 provided within the proximal body portion 2. The threaded interface may be adapted for engagement with a threaded piston rod or the like.

[0066] In FIG. 4, the cartridge is represented by two concentric circles D1 (outer diameter of the cartridge) and D2 (inner diameter of the cartridge). As can be seen, the extrusion strip 6 is designed to interfere with and deform the glass of the cartridge during the assembly of the mechanism.

[0067] Although the first and second embodiments shown in FIGS. 1 to 5 show a housing element 1 adapted to receive a 3 ml cartridge, at least one extrusion strip 6 according to the present disclosure may also be provided in a 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 of FIGS. 6 and 7. Although the diameter of the distal body portion 3 is the same as in the second embodiment of FIGS. 3 to 5, in the third embodiment, the outer diameter of the cartridge is much smaller. In FIG. 7, the reduced diameter of the cartridge is represented by the outer diameter D1 and the inner diameter D2 of the cartridge.

[0068] In this third embodiment, the distal body portion 3 is provided with two pairs of radially extending support walls 8 which are positioned 180° apart. An extrusion strip 6 is provided at the radially inward edge of each of the four support walls 8. When the cartridge is inserted into the housing element 1, the extrusion strip 6 interferes with the outer diameter of the cartridge and folds the extrusion strip 6 into the space between the inner edge of the support wall 8 and the distal body portion 3.

[0069] FIG. 8 shows a fourth embodiment of the present invention, wherein the housing element 1 is an inner body held within an outer body or housing 9. The inner housing element 1 is axially constrained within the outer body 9 by engagement of an inwardly extending flange of the outer body 9 with a groove 4 on the 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 driving mechanism but also serves as a cartridge holder. As an alternative, a separate cartridge holder may be provided to be connected to the housing element 1 and / or the outer body 9.

[0070] The inner housing element 1 has a threaded interface on the outside of the proximal body part 2 for engaging a dose dialing sleeve or a digital sleeve 10. Further, a spline interface provided on the inside of the proximal body part 2 engages and guides the drive 11 of the drug delivery device. Further, a threaded piston rod 12 is guided in the threaded interface 7. In the situation shown in Fig. 8, a cartridge 13 with a stopper 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 squeezing strip 6 deforms, thereby axially and radially confining the cartridge 13 within the inner housing element 1.

[0071] Fig. 9 is a graph comparing the force (dashed line) exerted by a tapered prior art rib and the force (solid line) exerted by the squeezing strip according to the present disclosure when the cartridge 13 is inserted into the housing element 1. While the tapered prior art rib results in a gradually increasing force applied to the cartridge, the force exerted by the squeezing strip according to the present disclosure on the cartridge is substantially constant. More specifically, after the initial engagement of the squeezing strip 6, at a relative travel of approximately 0.2 mm between the cartridge 13 and the squeezing strip 6, the force has risen to approximately 3 N. For the next 1.2 mm of travel, it only rises to just below 4 N. This is desirable as it can accommodate a tolerance of + / - 0.6 mm in the assembly height of the end face of the cartridge 13 relative to the housing element 1 while still applying 3 - 4 N to each squeezing strip 6. When the cartridge 13 is inserted, the squeezing strip 6 deforms and tends to fold away due to its angled geometry. Since the squeezing strip 6 is only 0.15 mm thick, this requires a lower assembly force and this assembly force does not change significantly as the cartridge is further axially inserted.

[0072] The low axial force for assembling the cartridge prevents breakage of the glass during assembly. Further, this maintains good dosing accuracy by preventing movement of the cartridge when attaching a needle (not shown), and when these squeezing strips 6 are used to hold the cartridge 13, improved shock test performance is shown, greatly reducing the occurrence of glass breakage.

[0073] Reference numerals

[0074] 1 (inner) housing element

[0075] 2 proximal body part

[0076] 3 distal body part

[0077] 4 engagement groove

[0078] 5 hole

[0079] 6 squeezing strip

[0080] 7 threaded interface

[0081] 8 walls

[0082] 9 Outer body (housing)

[0083] 10 Digital sleeve

[0084] 11 Driver

[0085] 12 Piston rod

[0086] 13 Cartridge

[0087] 14 Piston

[0088] D1 Cartridge outer diameter

[0089] D2 Cartridge inner diameter

[0090] I Longitudinal axis

Claims

1. A housing element for a drug delivery device, the housing element including a longitudinal axis (I) and defining an internal 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, wherein the housing element includes engagement features (4) for axially constraining the housing element to a cartridge holder (9) of the drug delivery device. Characterized in that the housing element further includes at least one squeezing strip (6) projecting radially inwards into the internal space, wherein the at least one squeezing strip (6) is at an angle of at least 3° relative to the longitudinal axis (I) of the housing element, such that when the cartridge (13) is introduced into the internal space, the at least one squeezing strip (6) folds radially outwards.

2. The housing element according to claim 1, wherein the at least one squeezing strip (6) is at an angle of at least 5° relative to the longitudinal axis (I) of the housing element.

3. The housing element according to claim 1 or 2, wherein the housing element has at least one lateral hole (5), and wherein the at least one squeezing strip (6) is located adjacent to and / or aligned with the at least one lateral hole (5), such that when the cartridge (13) is introduced into the internal space, the at least one squeezing strip (6) folds into the at least one lateral hole (5).

4. The housing element according to claim 1 or 2, wherein the housing element includes three squeezing strips (6) spaced 120°.

5. The housing element according to claim 1 or 2, wherein the housing element has at least one support structure (8) extending radially inwards into the internal space, thereby reducing the diameter for receiving the cartridge (13) of the drug delivery device, and wherein the at least one squeezing strip (6) is located on the at least one support structure (8), such that when the cartridge (13) is introduced into the internal space, the at least one squeezing strip (6) folds radially outwards.

6. The housing element according to claim 5, wherein the at least one support structure (8) includes two pairs of radially inwards projecting walls (8), and wherein one squeezing strip (6) is positioned on each of the four walls (8).

7. The housing element according to claim 6, wherein the two pairs of radially inwards projecting walls (8) are spaced 180°.

8. The housing element according to claim 1 or 2, wherein the at least one squeezing strip (6) has a thickness of at least 0.1 mm.

9. The housing element according to claim 1 or 2, wherein the housing element has a locally reduced wall thickness at the location where the at least one squeezing strip (6) engages the housing element.

10. The housing element according to claim 1 or 2, wherein the housing element comprises an internal thread (7) for engaging a threaded piston rod (12) of the drug delivery device, and / or wherein the housing element comprises an external thread for engaging a dose selection sleeve (10) of the drug delivery device, and / or wherein the housing element comprises internal axially extending splines for engaging a drive sleeve (11) of the drug delivery device.

11. The housing element according to claim 1 or 2, wherein the housing element comprises: a distal body portion (3) having a larger diameter for receiving at least a portion of a cartridge (13) of the drug delivery device; and a proximal body portion (2) having a smaller diameter than the distal body portion (3) for receiving components (10, 11) of the drive mechanism of the drug delivery device, wherein the distal body portion (3) and the proximal body portion (2) are connected to each other by a radially extending flange wall.

12. The housing element according to claim 1 or 2, wherein the engaging feature (4) is a circumferentially extending bead or groove (4) provided on an 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, a cartridge (13) containing a medicament, a drive mechanism for driving a piston (14) in the cartridge (13), and an external body (9) axially constrained to the housing element (1) by the engaging feature (4).

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

15. The drug delivery device according to any one of claims 13 or 14, wherein the cartridge (13) has a nominal outer diameter (D1) that radially interferes with the at least one squeezing strip (6) when the cartridge (13) is introduced into the internal space of the housing element.

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