Patent ID: 12201814

Identical elements, elements of the same kind and identically acting elements may be provided with the same reference numerals throughout the figures.

DETAILED DESCRIPTION

In the following, in conjunction with the drawings, several embodiments of cartridge assemblies with fixing features which are integrated into the cartridge holder of the assembly are disclosed. Before the specifics of the respective embodiments are disclosed, features which apply to all embodiments are discussed.FIGS.1A through1E,2A and2B,3A and3B, as well as4A through4C each illustrate one embodiment of a cartridge assembly300. The figure denoted with “A”, in each case shows a schematic perspective view of the cartridge assembly, where the remaining figure(s) show a schematic sectional view of the cartridge assembly, where only the distal region, i.e. the part of the assembly close to its distal end, is shown.

The cartridge assembly300comprises a cartridge301and a cartridge holder302. The cartridge301is arranged within a cartridge holding or retaining section303of the cartridge holder. The cartridge retaining section is expediently delimited by an inner wall304of the cartridge holder302, preferably circumferentially. The cartridge holder302has an opening305. The opening305is expediently a proximal opening. The proximal opening may provide access to the interior of the cartridge holder from the proximal end of the holder. Via the opening305, the cartridge301can be inserted into the cartridge holder. A dispensing end306of the cartridge may be inserted or introduced into the cartridge through the opening305. The opposite end of the cartridge holder is the distal end of the cartridge holder302, which may be that end which is arranged closest to the dispensing end306of the cartridge301. The distal end of the cartridge holder is preferably designed to retain the cartridge in the holder, e.g. by abutment, such that the cartridge may only leave the cartridge holder through the opening305. The axial extension of the cartridge holder is expediently chosen so as to cover at least 50%, preferably more than 60% or more than 70% such as more than 80% or more than 90% of the total length of the cartridge. The entire cartridge may be covered by the cartridge holder302as depicted in the embodiments.

The end of the cartridge opposite to the dispensing end306, i.e. the proximal end, is not illustrated explicitly in the figures. This end may be closed by a movable bung or stopper, which is likewise not explicitly illustrated. The bung or stopper may sealingly close a proximal opening of the cartridge. A drug307or medicament is contained in that region of the cartridge which is arranged between the dispensing end and the bung. Drug may be dispensed through the dispensing end306from the cartridge, if fluid communication between the interior of the cartridge and the exterior is provided and the bung is moved towards the dispensing end. The amount of drug307in the cartridge is preferably sufficient for a plurality of doses, where the size of the dose may be set by the user or may be fixed, e.g. by the design of the drive mechanism used to deliver the drug from the drug delivery device which comprises the cartridge.

The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.

As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may 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, double 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.

The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20° C.), or refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.

The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (anti-diabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.

Examples of APIs for the treatment and/or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue. The added and/or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as “insulin receptor ligands”. In particular, the term “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.

Examples of insulin 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, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

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

Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (LYXUMIA®), Exenatide (Exendin-4, BYETTA®, BYDUREON®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (VICTOZA®), Semaglutide, Taspoglutide, Albiglutide (SYNCRIA®), Dulaglutide (TRULICITY®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, 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, TT-401, BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten.

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

Examples of DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a polysulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a polysulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (SYNVISC®), a sodium hyaluronate.

The term “antibody”, as used herein, 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 polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).

The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full-length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are 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 (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region 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 within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining 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 certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.

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).

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.

Those of skill in the art will understand that modifications (additions and/or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

On the side of the dispensing end306, the interior of the cartridge which holds the drug or medicament307is sealingly closed by a septum308. The septum308may be retained at or fixed relative to a cartridge body340of the cartridge by means of a septum retainer309. The septum308is expediently pierceable, e.g. via a needle, which may provide fluid communication between the interior of the cartridge and the exterior. The septum retainer309may be formed by a cap, e.g. a metal cap, such as an aluminum cap. The metal cap may be connected via clamping or crimping to the cartridge body340. The body of the cartridge may be formed of glass. The body340may define the outer contour of the cartridge. In the region of the dispensing end306, where the needle should penetrate the septum, an opening is provided in the septum retainer308to allow the needle to pass through the region of the septum retainer. The cartridge301comprises a head portion310and a main body portion311. The head portion310is arranged on the side of the dispensing end306. The main body portion311may be arranged closer to the proximal end of the cartridge than the head portion310. Between the head portion310and the main body portion311a neck portion312may be arranged. The main body portion311may be that region, where the bung or stopper may travel. The main body portion has a tubular configuration. The neck portion312may have a reduced diameter, outer and/or inner diameter, as compared to the main body portion311. The head portion310has a reduced diameter, outer and/or inner diameter, as compared to the main body portion311. The neck portion312has a reduced diameter as compared to the main body portion and also with respect to the head portion310. The diameter may be the extension of the cartridge301in a direction perpendicular to the main longitudinal axis of the cartridge or the cartridge assembly which extends between the proximal end and the distal end. The neck portion may extend circumferentially. The entire cartridge301may be rotationally symmetric relative to the main longitudinal axis. The transition between the head portion310and the neck portion312may be formed via a comparatively steep surface, which is preferably less inclined relative to the radial direction than the surface which is provided between the neck portion312and the main body portion311. Accordingly, the transition between the neck portion312and the main body portion311may be less steep than the one between the head portion310and the neck portion312. Specifically, a cartridge surface313, which may delimit the head portion310proximally, may have an inclination relative to the radial direction which is less than the inclination of a shoulder surface314which delimits the main body portion distally. The cartridge surface may be formed by the septum retainer309or, alternatively by the cartridge body340. The septum retainer309may clamp the septum to the cartridge body. Thus, the septum retainer may extend from the distal end along the cartridge to a surface of the neck portion of the cartridge body facing away from the distal end of the cartridge and extending in the radial direction to clamp the septum308to the cartridge body. The cartridge may comprise or consist of the cartridge body340, the septum308, the septum retainer309, the drug or medicament307, and/or the bung (not explicitly illustrated).

The cartridge holder302comprises on that end opposite of the opening305and/or closest to the dispensing end306of the cartridge, i.e. its distal end, a distal end wall315. The distal end wall may extend circumferentially in a ring-like fashion. A proximal surface of the distal end wall315is arranged to abut the distal end face of the cartridge301. In this way, the cartridge301can be retained in the cartridge holder without moving distally relative to the cartridge holder302. The distal end wall315may define an opening316in the cartridge holder. The end wall may extend around the opening such that the opening is a central opening in the end wall. The opening may extend axially through the end wall315. The opening316may be provided such that a needle can be guided through the opening towards the cartridge, in particular towards the septum308.

The cartridge holder302may comprise a distal region317and a main body region318. The distal region317is arranged closest to the dispensing end of the cartridge and/or to the distal end wall315of the cartridge holder. The main body region318is arranged further away from the distal end or the distal end wall315and/or closer to the opening305than the distal region. As compared to the main body region the distal region may have a reduced outer diameter. The reduction may be determined by the reduced diameter of the head portion as compared to the diameter of the main body portion of the cartridge. The main body region318and the distal region may be connected by an inwardly directed shoulder region331. In the distal region a needle connector319, for example a thread may be arranged. Via the needle connector, a needle unit, for example a hub of a needle unit may be secured to the cartridge holder302. A needle retained in the needle hub may be guided through the opening316, pierce the septum308and provide fluid communication to the interior of the cartridge to dispense drug307or medicament from the cartridge301. The distal region317may be designed to receive the head portion310of the cartridge301in its interior. The main body region318may be designed to receive the main body portion311of the cartridge. On the side of the proximal end the cartridge holder may have a connection or interface region320. In that region, connection or interface features may be provided, which are configured to cooperate with corresponding features on a housing10to connect the cartridge assembly300to the housing to form a drug delivery device1(seeFIGS.5and6). The connection features may be designed for a threaded or bayonet connection between cartridge holder and housing. Preferably, the connection or interface features are coded to a housing which houses a drive mechanism designed for the drug or medicament contained in the cartridge of the cartridge assembly. The coding ensures that only a correct cartridge assembly can be assembled to the housing to form a drug delivery device. In this way, it can be guaranteed that the drug in the cartridge assembly is dispensed using a drive mechanism which is specifically designed to dispense the content of the cartridge. The drive mechanism may comprise a piston rod, which is arranged to drive the bung or stopper distally relative to the cartridge, if drug or medicament should be dispensed from the cartridge.

Between the proximal end and the distal end of the cartridge holder302, preferably closer to the proximal end than to the distal end, a radially outwardly protruding step321or flange, may be provided. The step or flange321may extend over the entire circumference of the cartridge holder302. A proximal surface of the step321may be arranged to contact a distal surface of the housing when the cartridge assembly is connected to the housing. The connection region320may be covered by the housing, when the assembly has been connected to the housing. The main body region318and the distal region317may, however, protrude from the housing.

Furthermore, the cartridge holder301comprises at least one fixing feature322. As seen along the axial direction, the fixing feature322is provided between two interior regions of the cartridge holder, where one is adapted to receive and retain the head portion310and another one is adapted to receive and retain the main body portion311of the cartridge. The fixing feature322may extend in the region of the neck portion of the cartridge301. The fixing feature322protrudes radially from an inner wall of the cartridge holder301. Preferably, the fixing feature322reduces the inner diameter the cartridge holder such that in that region, the inner diameter is less than the outer diameter of the head portion of the cartridge.

Therefore, if the head portion of the cartridge should be guided axially past the fixing feature from the proximal opening, the fixing feature has to be deflected radially outwardly, e.g. displaced only radially. If the fixing feature is deflected, the head portion can pass the fixing feature. Preferably, the fixing feature is deflected by means of the head portion cooperating with a proximal surface of the fixing feature which may be oblique, i.e. neither perpendicular nor parallel, with respect to the main axis of the cartridge holder. After the head portion has passed the fixing feature, the fixing feature may move radially inward again, e.g. resiliently. The interior region of the cartridge holder which is designed to receive the head portion310may have a reduced diameter as compared to that region which receives the main body portion311.

The fixing feature322is formed integrally, e.g. by injection molding, with a section of the cartridge holder which defines an exterior surface or at least the outer contour of the cartridge holder. That is to say, if applicable the cartridge holder may be provided with a coating on the exterior surface whereas the outer contour may still be defined by the section of the cartridge holder the fixing feature is integrated into. InFIGS.1A through4A, an injection gate mark323is shown, which indicates the position where the fluid plastic compound is injected into a mold cavity which defines the shape of the cartridge holder. The injection gate mark323is positioned in the region of the distal end wall315of the cartridge holder, particularly on a distal face of the distal end wall.

The fixing feature322comprises a fixing surface324. The fixing surface324may be a distal surface of the fixing feature. Preferably, the fixing surface is radially oriented, i.e. it extends in the radial direction, and/or plane. The fixing surface324is arranged to abut or abuts a proximally facing surface of the cartridge, such as the cartridge surface313. Thus, the cartridge surface313and the fixing surface324are arranged to prevent that the cartridge is removed proximally from the cartridge holder through the opening305by mechanical cooperation with one another. Accordingly, removal of the cartridge from the holder through the opening305is prevented by means of the fixing feature322. The fixing feature322may be formed as a snap and/or clip feature. The angular extension of the fixing feature or the fixing surface may be less than or equal to one of the following values: 20°, 15°, 10°.

Furthermore, an outer wall of the cartridge holder is provided at the axial position of the fixing feature. Thus, the cartridge holder is closed at least in the region of the fixing feature. Accordingly, the fixing surface and/or the fixing feature cannot be accessed from the outside. This reduces the chances that the cartridge assembly can be tampered with.

In the following, some embodiments of cartridge holders with fixing features integrated into the cartridge holder are discussed in more detail. The embodiment depicted inFIGS.1A and1B, has one fixing feature322, in particular just one. Of course, a plurality of fixing features could be provided as well. Such an embodiment is shown inFIGS.2A and2Bwhich is very similar to the one ofFIGS.1A and1B.

The fixing feature322protrudes radially from the inner wall304of the cartridge holder302. The fixing feature322is arranged in the interior of the distal region317of the cartridge holder302and, particularly, in the interior region of the cartridge holder where the needle connector319is provided on the exterior. As is apparent fromFIG.1Aand also fromFIG.1B, the distal end wall315which has a generally ring-like configuration, has an opening325. The opening325is radially oriented and interrupts the ring defined by the distal end wall315. The opening325extends radially outwardly from the opening316. The angular and radial position of the opening325may correspond to the one of the fixing feature322or the fixing surface324, where the opening is axially offset from the fixing feature, e.g. in the distal direction. Particularly, as seen from the distal end along the axis, the fixing surface may be visible from the distal end. The fixing surface may be framed radially and angularly by sidewalls which delimit the opening325. In the figures, the head portion310of the cartridge301is arranged between the opening325and the fixing surface324. The angular dimension and/or the radial dimension of the opening325may define, may correspond to or may be greater than the angular dimension and/or the radial dimension of the fixing surface and/or the fixing feature. Providing an opening in the region of the distal end facilitates molding of the cartridge holder with the integrated fixing feature with only minor modifications to the mold or molding tool as compared to a cartridge holder without fixing features. In a cartridge holder without a fixing feature, two core pins of different diameters may be used for producing the cartridge holder by injection molding, where one core pin defines the interior of the distal region and one core pin defines the interior of the main body region318of the cartridge holder. A short core pin may define the interior in the distal region and a long core pin may define the region of the interior in the main body region. The fixing feature322may be integrated right at the intersection or the boundary of the two different core pins of the injection molding tool. The opening325may be formed during the molding process and facilitates the molding of a cartridge holder with the fixing features322integrated into it. The opening325may be defined by a protrusion, e.g. of metal, on the short core pin.

In the region where the fixing feature is provided, e.g. the distal region317, the cartridge holder may be radially deformable. Thus, the inner diameter may be increased when the cartridge holder is exposed to a radially outwardly directed force. The capability of the cartridge holder to be radially deformed when exposed to a radially directed force may be increased in that angular section of the distal region317which overlaps angularly with the opening325. The fixing feature322is arranged in this region as it overlaps angularly with the opening. The fixing feature is expediently non-flexible and/or rigid, e.g. more rigid than the distal region317or the inner wall of the first region where the head portion of the cartridge is to be arranged. Thus, when an axial and/or radial force acts on the fixing feature, e.g. while the head portion is guided along and in contact with the fixing feature, the cartridge holder is widened on account of the rigidity of the fixing feature322. The fixing feature itself is not deformed or flexed or at least not significantly deformed as compared to that portion of the cartridge holder which is deformed, e.g. the distal region317or the shoulder region331. As the cartridge holder302is expediently of plastic, deformation of the fixing feature itself to a very limited degree cannot be avoided. However, in the proposed concept, it is the widening of the cartridge holder in a circumferentially closed region of the cartridge holder which is facilitates insertion of the cartridge into the cartridge holder. The cartridge holder is deformed when the cartridge is introduced into the cartridge holder. The region which is deformed expediently is a region which does not have flexible arms, tongues, or tab-like features. The fixing feature is used to transfer the insertion force of the cartridge to the cartridge holder in order to widen the cartridge holder laterally. The interior of the cartridge holder is widened in the region of mechanical contact between the cartridge and the cartridge holder, i.e. in the region in which the fixing feature is disposed, and preferably in axially and/or circumferentially adjacent regions. As opposed to deflecting distinct flexible arms, tongues, or tab-like features, widening the interior of the cartridge holder may provide a more stable fixation of the cartridge in the cartridge holder once the cartridge has been introduced into the cartridge holder. After the head portion310has passed the fixing feature322, the fixing feature is displaced inwardly again, e.g. on account of the deformation being an elastic deformation, and the cartridge surface313and the fixing surface324are arranged as depicted inFIG.1B. The fixing feature is preferably not or at least not significantly deformed during this process and, in particular, not axially deflected or pivoted.

As shown inFIG.1B, distally offset from the fixing surface324, a sloped surface326which rises radially along its extension in the distal direction, is arranged. By means of this surface, which is preferably arranged at the opposite side of the fixing surface or at least angularly offset from the fixing surface, a radial movement of the head portion310of the cartridge301may be achieved to a region overlapping radially with the fixing surface324. Thus, the sloped surface acts as a cartridge guiding feature during the assembling process of the cartridge assembly300. References to the sloped surface326may therefore be regarded as references to the cartridge guiding feature and vice versa. The radial overlap of the fixing surface324and the surface313of the cartridge301when the cartridge has reached its final position may be increased in this way. The sloped surface326may strengthen the stability of the securing of the cartridge in the cartridge holder, e.g. in case only one fixing feature is provided.

The distal offset (highlighted with “B” inFIG.1B) of the cartridge guiding feature326from the fixing feature, from the fixing surface324and/or from a radial free end of the fixing feature322may be greater than the thickness (highlighted with “A” inFIG.1B) of the septum308of the cartridge. This ensures that the septum retainer309is backed by the more rigid cartridge body340and preferably not by the septum, when the cartridge interacts with the fixing feature322to radially displace the feature outwardly in order to temporarily widen the interior of the cartridge holder. Thus, the force required to displace the feature322is not transferred to the septum. If the force were transferred to the septum, the risk that the septum retainer309, which may be a thin metal component, is deformed or the septum is damaged is considerably increased. This can be avoided by the distal offset between cartridge guiding feature326and the fixing surface324by more than the thickness of the septum308. The distal offset B is expediently less than the axial extension of the head portion310of the cartridge. In this way, the cartridge guiding feature may properly guide the cartridge301radially inwardly by cooperating with the head portion310.

In the region of the interior of the cartridge holder302between the cartridge guiding feature326and the fixing surface324, the inner diameter of the interior of the cartridge holder may be greater than in the region of the cartridge guiding feature and/or in a region distally offset from the cartridge guiding feature, if such a region is present which it may be or may not be. In the region of the interior of the cartridge holder between the cartridge guiding feature and the fixing surface the inner diameter may be greater than the inner diameter in the fixing feature region. In the region of the cartridge guiding feature326and/or distally with respect to the cartridge guiding feature, the inner diameter of the cartridge holder may be greater than the inner diameter in the fixing feature region, e.g. greater than or equal to the outer diameter of the head portion310.

In other words, the septum retainer or metal sleeve309has a distal section which surrounds the soft septum308, and a proximal section that surrounds the neck of the cartridge body or glass ampoule340. It is advantageous if the distal section of the septum retainer has moved past the fixing surface324before the distal section makes contact with the cartridge guiding feature or sloped surface326. In this way the radial overlapping of the metal sleeve309and the fixing surface is minimal during the period of assembly where the fixing surface could damage the metal sleeve309, and this overlapping is only increased when the fixing surface has moved past the distal section of the metal sleeve309and is applying radial pressure to the proximal section. As the proximal section is supported by a harder, e.g. glass like, material than the distal section it will not be damaged or indented. The final overlapping between the fixing surface and the cartridge surface at the end of assembling process is still high. The final overlap may be defined by the smaller inner diameter of the cartridge holder in the region of the sloped surface which marks the end of the sloped surface326.

When a cartridge holder302with an integrated fixing feature322was tested, it has been discovered, that the distal section of the septum retainer309dents badly unless the diameter prior to sloped surface326is sufficiently larger than the diameter after slope326so that the cartridge301can move away from the fixing feature with minimal, if any, interference in the distal section of the septum retainer and that this interference only increases after the fixing feature is pressing in the region of the septum retainer309where the head portion of the cartridge body, e.g. of glass, backs up/supports the septum retainer, which may be a thin and easily deformable metal component.

When the cartridge301has been assembled into the cartridge holder302, the fixing feature322may block proximal movement of the cartridge301relative to the holder302. The fixing feature, however, expediently does not exert a securing force, e.g. a distally or radially directed force, onto the cartridge regularly but only prevents removal of the cartridge from the cartridge holder. In this way, the force load onto the cartridge may be advantageously low.

FIGS.1C through1Eshow additional views of the cartridge holder302.FIG.1Cshows a view from the distal end. As is immediately apparent, the angular dimension of the fixing feature322is less than the one of the opening325. The radial dimension of the fixing feature322or the fixing surface is less than the one of the opening325as well. FromFIG.1D, which shows the distal end as well but in a perspective view, it can be gathered that the cartridge holder, in particular the distal region317, is reinforced, i.e. has a higher wall strength or thickness, in a region which is angularly adjacent to the fixing feature322. A reinforcement section341extends circumferentially in the interior of the cartridge holder. The reinforcement section may axially overlap with the fixing feature. The reinforcement section341may be arranged distally offset from the fixing feature322alternatively or additionally. In the region of the interior of the cartridge holder which angularly overlaps with the fixing feature the reinforcement section is preferably interrupted to promote radial deformability of the cartridge holder when the head portion displaces the fixing feature322radially.

As seen from the opening325axially towards the fixing surface324, the wall thickness of the holder302may be less than the wall thickness in the reinforcement section341. The wall thickness of the cartridge holder301in the region of the fixing feature322and defined by the fixing feature may be greater than the one in the reinforcement section341. The fixing feature322may radially protrude over the reinforcement section341. The reinforcement section341is also depicted inFIG.1Ewhich shows a perspective sectional view of the cartridge holder302. In this figure, it is shown that the interior of the cartridge holder comprises a plurality of circumferentially disposed, preferably equally spaced, spacer features or cartridge support features342, e.g. ribs. The features342are axially oriented. The features342may be provided to radially support the cartridge, e.g. the main body portion311thereof, if the cartridge is retained in the cartridge holder. These features may be the only difference between a cartridge holder which receives cartridges with a smaller diameter and one which receives a cartridge with greater diameter. The cartridge holder for the larger diameter cartridge may, expediently, not have the cartridge support features342. Thus, the exterior dimensions of the cartridge holder may be the same although the exterior diameters of the cartridges retained in the cartridge holders are different.

As is apparent from the figures, e.g. fromFIG.1B, the needle connector319, e.g. a thread, is distally offset from the fixing feature322. Specifically, the region between the fixing feature and the cartridge guiding feature or sloped surface326may be free of the needle connector319. The needle connector may axially overlap with the cartridge guiding feature326or be provided distally offset from this feature326. Thus, the axial extension of the needle connector319may be less than in other cartridge holder designs. For example, the needle connector319may be restricted to a distal section of the distal region317of the cartridge holder, where between the needle connector319and the main body region a connector-free region is arranged. The axial extension of the connector-free region may be greater than 50% of the axial extension of the distal section with the needle connector. The axial extension of the distal section with the needle connector may be greater than the one of the connector-free region. As the cartridge holder in the region between the fixing feature322and the guiding feature326has a reduced wall thickness to increase the inner diameter of the cartridge holder302, e.g. in order to maintain a given outer contour or dimension of the cartridge holder302, providing an additional radial indentation on the exterior in this region, which would be required for the connector319, would increase the risk of damaging the cartridge holder in this region or even render it unmoldable. Thus, the shortened needle connector is advantageous.

Although the depicted embodiment shows only one fixing feature, a sloped surface may also be provided in case a plurality of fixing features is used. In the following embodiment, the sloped surface is not shown, however.

InFIGS.2A and2Ba cartridge holder302with two integrated fixing features322is shown. The fixing features322are oppositely disposed where each fixing feature has a fixing surface324which is arranged to abut the cartridge surface313, which may be formed flange-like. Two openings325are provided in the distal end wall315of the cartridge holder which interrupt the ring-like shape of the cartridge holder at positions which angularly and/or radially correspond to the position of the fixing surface324of the respective fixing feature. The respective opening325may be connected to the central opening316. As explained previously, this assists in integrating the fixing feature into the cartridge holder by injection molding which is particularly easy and a low-cost process, suitable for high volumes. The disclosure above regarding the opening therefore also applies for this embodiment. Still further, more than two fixing features could be provided as well. InFIG.2B, the needle connector overlaps axially with the fixing feature(s)322.

InFIGS.3A and3B, another embodiment of a cartridge holder with an integrated fixing feature322is shown. As shown inFIG.3A, the distal end wall315is ring-like and, preferably closed, i.e. no openings325interrupt the ring. The distal end wall315may encircle the opening316over the entire circumference. The distal region317of the cartridge holder comprises an opening327in a sidewall of the cartridge holder. The opening327extends radially through the entire sidewall of the cartridge holder from the outside to the inside. The opening327is in the proximal direction delimited by a surface, in particular by the fixing surface324. The opening327may be delimited by a region of that surface which does not abut the cartridge but rather continues the region which is arranged to abut the cartridge radially, preferably in a plane manner. The opening325may be delimited in the angular directions and/or the distal direction as well. The opening327may have a rectangular configuration as seen in top view. The opening327may be provided in the region of the needle connector319. Expediently it interrupts the connection feature, e.g. the thread of the needle connector. Two openings327may be provided, which may be arranged diametrically opposite relative to one another. The respective opening may be defined by a molding tool, which is arranged to abut one of the core pins used during molding, particularly the short core pin which defines that section of the cartridge holder where the head portion of the cartridge should be arranged in. Thus, during molding of the cartridge holder the fixing feature can be defined. The fixing surface324may have a region which protrudes radially into the interior of the cartridge holder and a section which delimits the opening327proximally. The fixing surface324may be a plane surface. This does apply for the previously discussed embodiments as well. There, however, the fixing surface originates at an inner wall of the cartridge holder and extends radially away from the inner surface. In the present embodiment, the fixing surface originates from an exterior surface and extends along the opening to the interior of the cartridge holder.

In the previously discussed embodiments, the cartridge holder was a unitary piece which could be injection-molded in its entirety, e.g. from plastic material.FIGS.4A through4Cillustrate an embodiment of the cartridge holder which has multiple parts. For example, the cartridge holder has two parts, a distal part328and a main body part329. The distal part328may define the distal region of the cartridge holder. Particularly, it comprises the needle connector319. The main body part329of the cartridge holder may comprise the integrated fixing feature322. The fixing feature322or a plurality of fixing features322with associated fixing surfaces may be integrated in the main body part, e.g. a distal end section thereof. The respective fixing feature may be a finger which axially and radially protrudes form an inner wall of the cartridge holder, e.g. the main body part. Thus, the fixing surface may be arranged at a distance from the inner wall of the cartridge holder. There may be a radial clearance between the fixing surface and the interior wall of the cartridge holder. The fixing feature may be flexed towards the interior wall into the clearance. The respective part may be unitary and/or injection molded. The parts328and329may be made of the same material or of different materials.

The distal part328and the main body part329are, preferably irreleasably and/or permanently, connected to one another, for example by means of a force-fit or a snap-fit connection. Connection features330are shown inFIG.4C. The features330may be resiliently connected to the distal part328. They may be oriented in the proximal direction. For securing the distal part to the main body part, a distally facing surface of the connection features may abut a proximally facing surface of the main body part, once the connection has been established. The features330may flex inwardly when the two parts328and329are assembled to one another and again outwardly to engage behind a flange of the main body part329, when having reached the final position. As depicted inFIG.4B, the distal part318abuts the fixing features322such that it is radially stabilized. Particularly, a radial outward movement of the fixing feature322is prevented. Accordingly, in this embodiment, the cartridge is preferably inserted into the main body part before the distal part is connected to the main body part. Then, the fixing fingers may still be flexible radially outwardly to a greater extent, as they are not supported radially by the distal part. However, afterwards the main body part and the distal part can be connected to one another and, thereafter, a radial outward movement which would be required to remove the cartridge from the cartridge holder is no longer possible. Thus, this assembly is particularly stable against removal of the cartridge from the cartridge holder. However, the expenditure for manufacturing this cartridge holder is increased, as it comprises multiple parts. The fixing feature322is still integrated into a section of the cartridge holder which defines the exterior or outer contour of the cartridge holder. A separate part is not needed. All parts of the cartridge holder in the depicted embodiment may be required for providing the functionalities of the cartridge holder which comprise protecting the cartridge and/or providing a needle connector.

As the fixing feature322interacts with the head portion in the depicted embodiments, cartridges with differently shaped main body portions may be secured in the cartridge holder easily, e.g. cartridges of different volumes, diameters and/or lengths. The head portions of the cartridges may be formed alike.

Cartridges of different volumes may have different lengths and/or different inner and/or outer diameters. The cartridge assembly may be a disposable item, which is, e.g. sold in the pharmacy. Different cartridges of the same or of different volumes may contain different drugs or drug formulations. Cartridges of a smaller volume may have a higher concentration of a drug.

If the drug is insulin or an insulin derivative, for example, the cartridge of a smaller volume may have a concentration which is more than 2 times, e.g. 3 times, the concentration of drug in the larger volume cartridge. The drug or medicament in the larger volume cartridge may be formed by the same active pharmaceutical ingredient. Differences in the content between the cartridges may be, preferably only, in the concentrations of the drug within the liquid, i.e. in the specific formulation of the drug. For example, a 3 mL cartridge may comprise 300 IU (IU: International Unit), e.g. of insulin, whereas the 1.5 mL cartridge may comprise 450 IU, which, taking into account the lower volume, corresponds to three times the concentration of drug in the 3 mL cartridge.

The head portion310of the cartridge301in the proposed cartridge assembly300can be tightly fitted within the interior region of the cartridge holder between the distal end wall315and the fixing surface324. That is to say, the cartridge may be in permanent contact with the fixing surface and an inner surface of the distal end wall. Then, the cartridge cannot move axially relative to the cartridge holder. Alternatively, there may be a remaining axial play or slackness between the head portion and the cartridge holder, which allows axial movement between the cartridge and the holder. Preferably, the play is less than or equal to one of the following values: 2 mm, 1 mm, 0.9 mm, 0.8 mm, 0.7 mm, 0.6 mm, 0.5 mm, 0.4 mm, 0.3 mm.

FIGS.5and6schematically illustrate embodiments of a drug delivery device suitable to be used in conjunction with the disclosed cartridge assembly.FIG.5shows the device1in a condition where a cap120is attached and covers the cartridge assembly300. InFIG.6the cap has been removed. The cartridge assembly300is, expediently releasably, connected to a main body or housing10of the drug delivery device1as depicted inFIG.6. The housing expediently defines the outer contour of the device and may be formed sleeve-like. A needle unit can be connected to the needle connector319in order to dispense drug or medicament from the device1. A dose setting member70is movably retained in the housing10and can be manipulated by the user to set a dose. For example, it can be rotated relative to the housing to set a dose. The device may be a variable dose device, where the size of the dose is not predetermine by the design of the drive mechanism retained in the housing but rather may be changed by the user. InFIG.6, a dose set condition of the drug delivery device is illustrated, where the numeral depicted in window230is changed as compared toFIG.5such that it illustrates the size of the currently set dose. The device may be designed such that, during dose setting, the dose setting member70is displaced proximally relative to the housing10. Alternatively, the dose setting member may stay in the same axial position independently of the set dose. From the position depicted inFIG.6, a dispensing action may be initiated, expediently by moving or exerting a force in the distal direction onto the dose setting member70or a dose dispensing member provided in a proximal end section of the drug delivery device1. To dispense the dose, the bung is displaced distally relative to the cartridge, e.g. by a piston rod of the device (not explicitly shown). In the interior of the housing a cartridge bias member may be arranged (not explicitly shown) such as a spring washer or a resilient cushion, e.g. of rubber. The bias member may bias the cartridge distally into contact with a proximal surface of the cartridge holder, e.g. the inner surface of the distal end wall315. The bias member may abut the cartridge, e.g. the cartridge body, directly, e.g. the proximal end thereof to transfer its load onto the cartridge, or indirectly via a rigid spacer component.

The scope of protection is not limited to the examples given herein above. Any invention disclosed herein is embodied in each novel characteristic and each combination of characteristics, which particularly includes every combination of any features which are stated in the claims, even if this feature or this combination of features is not explicitly stated in the claims or in the examples.

REFERENCE NUMERALS

300cartridge assembly301cartridge302cartridge holder303cartridge retaining section304inner wall305opening306dispensing end307drug/medicament308septum309septum retainer310head portion311main body portion312neck portion313cartridge surface314shoulder surface315distal end wall316opening317distal region318main body region319needle connector320connection region321step322fixing feature323injection gate mark324fixing surface325opening326surface327opening328distal part329main body part330connection feature331shoulder region340cartridge body341reinforcement section342cartridge support feature1drug delivery device120cap70dose setting member10housing230windowA thicknessB distance