State indicator and drug delivery device with a state indicator and a method for manufacturing a drug delivery device

Abstract

The present disclosure relates to a state indicator designed for indicating at least three states (S1 to Sn) of a drug delivery device and formed as a single indicator for indicating a respective state (S1 to Sn) at least before injection, during injection and after injection.

Claims

1. A state indicator comprising: an outer housing structure which is designed for indicating a number of states of a drug delivery device, wherein the state indicator is formed as a single indicator configured to indicate a current state of the drug delivery device selected from at least three states based on respective marks located on a movable component of the drug delivery device, the at least three states comprising: a pre-injection state before an injection, an injection state during the injection when the injection is being performed, and a post-injection state when the injection is completed, and wherein the state indicator is formed as at least one of a visual indicator, an optical indicator, or an electronic indicator.

2. The state indicator according to claim 1, wherein the state indicator is designed as an add-on device which can be attached to and removed from the drug delivery device.

3. The state indicator according to claim 2, wherein the add-on device comprises at least the electronic indicator and connecting elements extending from the electronic indicator of the add-on device and forming clamping arms.

4. The state indicator according to claim 2, wherein the add-on device comprises at least the visual indicator, the visual indicator comprising a light source with an integrated position or distance sensor.

5. A drug delivery device comprising: a housing; a container with a needle; a piston rod movable with respect to the container; a needle shroud relatively movable with respect to the housing; and a state indicator comprising an outer housing structure which is designed for indicating a number of states of the drug delivery device, wherein the state indicator is formed as a single indicator configured to indicate a current state of the drug delivery device selected from at least three states based on respective marks located on a movable component of the drug delivery device, the at least three states comprising: a pre-injection state before an injection, an injection state during the injection when the injection is being performed, and a post-injection state when the injection is completed, and wherein the state indicator is formed as at least one of a visual indicator, an optical indicator, or an electronic indicator.

6. The drug delivery device according to claim 5, wherein the housing comprises a drug window.

7. The drug delivery device according to claim 5, wherein the state indicator is associated with the needle shroud to indicate the at least three states depending on at least one of different needle shroud positions or different piston rod positions.

8. The drug delivery device according to claim 5, wherein the state indicator is designed at least as the visual indicator, the visual indicator being formed by a window in the housing through which at least one mark of the piston rod and/or of the needle shroud is visible in different states of the drug delivery device.

9. The drug delivery device according to claim 5, wherein at least one of the piston rod or the needle shroud is marked with at least one of a profile, a color mark, or a print mark.

10. The drug delivery device according to claim 9, wherein the at least one of the profile, the color mark, or the print mark is arranged on an outer surface of at least one of the piston rod or the needle shroud, the outer surface being directed towards the housing.

11. The drug delivery device according to claim 5, wherein the state indicator is configured as an add-on device which is removably mountable to the housing.

12. The drug delivery device according to claim 5, wherein the needle shroud and the piston rod are coaxially arranged and axially moveable relative to each other and relative to the housing.

13. The drug delivery device according to claim 5, wherein the state indicator comprises a window proximal to the container within the housing.

14. The drug delivery device according to claim 5, wherein: at least one of the piston rod or the needle shroud is marked with at least one of a profile, a color mark, or a print mark, the state indicator comprises a window proximal to the container within the housing, and the at least one of the profile, the color mark, or the print mark is positionable relative to the window.

15. The drug delivery device according to claim 5, wherein both the piston rod and the needle shroud are marked with at least one of a profile or a mark, and wherein the needle shroud and the piston rod are aligned relative to each other such that the at least one of the profile and the mark are aligned relative to each other.

16. The drug delivery device according to claim 5, wherein the container is prefilled with a drug.

17. The drug delivery device according to claim 5, wherein the state indicator comprises a sensor configured to read data through the housing.

18. The drug delivery device according to claim 17, wherein the sensor comprises an infrared camera.

19. A method of using a drug delivery device, the method comprising: arranging a state indicator within or on the drug delivery device, wherein the state indicator is formed as a single indicator configured to indicate a current state of the drug delivery device selected from at least three states based on respective marks located on a movable component of the drug delivery device, the at least three states comprising: a pre-injection state before an injection, an injection state during the injection when the injection is being performed, and a post-injection state when the injection is completed, and wherein the state indicator is formed as at least one of a visual indicator, an optical indicator, or an electronic indicator; and operating the drug delivery device in the pre-injection state to initiate the injection.

20. The method of claim 19, wherein arranging the state indicator within or on the drug delivery device comprises removably attaching the state indicator to the drug delivery device.

21. The method of claim 19, wherein operating the drug delivery device in the injection state to initiate the injection comprises operating the drug delivery device such that the state indicator indicates the injection state during the injection and then indicates the post-injection state when the injection is completed.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The present disclosure will become more fully understood from the detailed description given below and the accompanying drawings, which are given by way of illustration only, and do not limit the present disclosure, and wherein:

(2) FIG. 1A to 1B is a schematic perspective view of an exemplary embodiment of a drug delivery device comprising a housing and a cap assembly,

(3) FIG. 1C is a schematic perspective view of an exemplary embodiment of a drug delivery device comprising a movable component,

(4) FIG. 2 is a schematic perspective view of an exemplary embodiment of a housing of the drug delivery device,

(5) FIG. 3 is a schematic perspective view of an exemplary embodiment of a piston rod of the drug delivery device,

(6) FIG. 4 is a schematic perspective view of an exemplary embodiment of a needle shroud of the drug delivery device,

(7) FIG. 5 is a schematic side view of a cut-out of an exemplary embodiment of the drug delivery device in different states,

(8) FIG. 6 is a schematic view of different marks assigned to the different states of the drug delivery device,

(9) FIG. 7 is a schematic view of a mark represented by a print onto a needle shroud and assigned to pre-injection state of the drug delivery device,

(10) FIG. 8 is a schematic view of a mark represented by a print onto a needle shroud and assigned to post-injection state of the drug delivery device, and

(11) FIGS. 9, 10 are schematic perspective views of an exemplary embodiment of a stand-alone unit which may be removably attached to the drug delivery device.

(12) Corresponding parts are marked with the same reference symbols in all figures.

DETAILED DESCRIPTION

(13) According to some embodiments of the present disclosure, an exemplary drug delivery device 10 is shown in FIGS. 1A & 1B. Device 10, as described above, is configured to inject a medicament into a patient's body. Device 10 includes a housing 10.2 which typically contains a container 10.3 or a reservoir containing the medicament to be injected (e.g., a syringe) and the components required to facilitate one or more steps of the delivery process. Device 10 can also include a cap assembly 16 that can be detachably mounted to the housing 10.2. Typically a user must remove cap assembly 16 from housing 10.2 before device 10 can be operated.

(14) As shown, housing 10.2 is substantially cylindrical and has a substantially constant diameter along the longitudinal axis X. The housing 10.2 has a distal region 20 and a proximal region 21. The term “distal” refers to a location that is relatively closer to a site of injection, and the term “proximal” refers to a location that is relatively further away from the injection site.

(15) Device 10 can also include as a moveable component 10.1 at least one of a needle sleeve or shroud 13 and a piston rod 14 and a syringe carrier 15. The sleeve 13 is coupled to housing 10.2 to permit movement of sleeve 13 relative to housing 10.2. For example, sleeve 13 can move in a longitudinal direction parallel to longitudinal axis X. Specifically, movement of sleeve 13 in a proximal direction can permit a needle 10.4 to extend from distal region 20 of housing 10.2. The piston rod 14 comprises a piston 14.1 which is axially displaceable in the container 10.3.

(16) Insertion of needle 10.4 can occur via several mechanisms. For example, needle 10.4 may be fixedly located relative to housing 10.2 and initially be located within an extended needle sleeve 13. Proximal movement of sleeve 13 by placing a distal end of sleeve 13 against a patient's body and moving housing 10.2 in a distal direction will uncover the distal end of needle 10.4. Such relative movement allows the distal end of needle 10.4 to extend into the patient's body. Such insertion is termed “manual” insertion as needle 10.4 is manually inserted via the patient's manual movement of housing 10.2 relative to sleeve 13.

(17) Another form of insertion is “automated,” whereby needle 10.4 moves relative to housing 10.2. Such insertion can be triggered by movement of sleeve 13 or by another form of activation, such as, for example, a button 22. As shown in FIGS. 1A & 1B, button 22 is located at a proximal end of housing 10.2. However, in other embodiments, button 22 could be located on a side of housing 10.2.

(18) Other manual or automated features can include drug injection or needle retraction, or both. Injection is the process by which a bung or piston 14.1 is moved from a proximal location within a container 10.3 to a more distal location within the container 10.3 in order to force a medicament from the container 10.3 through needle 10.4. The needle 10.4 is configured as a needle assembly with a needle 10.4 comprising a needle hub which is attachable to the container 10.3.

(19) In other embodiments, the device 10 may comprise a drug window 60 in the housing 10.2. The drug window 60 allows a view on the container 10.3. The drug window 60 extends in the longitudinal direction and may have a length similar to the length of the container 10.3. In some embodiments, the device 10 may comprise two opposing drug windows 60 in the housing 10.2. The drug windows 60 may be configured as a recess or aperture in the housing 10.2. Alternatively, the drug window 60 may be configured as a transparent area in the housing 10.2.

(20) In another form, the container 10.3 may be configured as a prefilled syringe with a needle attached to it. The container 10.3 may be arranged within the syringe carrier 15.

(21) In some embodiments, a drive spring (not shown) is under compression before device 10 is activated. A proximal end of the drive spring can be fixed within proximal region 21 of housing 10.2, and a distal end of the drive spring can be configured to apply a compressive force to a proximal surface of piston 14.1.

(22) Following activation, at least part of the energy stored in the drive spring can be applied to the proximal surface of piston 14.1. This compressive force can act on piston 14.1 to move it in a distal direction. Such distal movement acts to compress the liquid medicament within the container 10.3, forcing it out of needle 10.4.

(23) Following injection, needle 10.4 can be retracted within sleeve 13 or housing 10.2. Retraction can occur when sleeve 13 moves distally as a user removes device 10 from a patient's body. This can occur as needle 10.4 remains fixedly located relative to housing 10.2. Once a distal end of sleeve 13 has moved past a distal end of needle 10.4, and needle 10.4 is covered, sleeve 13 can be locked. Such locking can include locking any proximal movement of sleeve 13 relative to housing 10.2.

(24) Another form of needle retraction can occur if needle 10.4 is moved relative to housing 10.2. Such movement can occur if the syringe within housing 10.2 is moved in a proximal direction relative to housing 10.2. This proximal movement can be achieved by using a retraction spring (not shown), located in distal region 20. A compressed retraction spring, when activated, can supply sufficient force to the syringe to move it in a proximal direction. Following sufficient retraction, any relative movement between needle 10.4 and housing 10.2 can be locked with a locking mechanism. In addition, button 22 or other components of device 10 can be locked as required.

(25) The drug delivery device 10 can comprise a state indicator 12 for indicating at least three states S1 to Sn of the drug delivery device 10. The state indicator 12 is formed as a single indicator for indicating a respective state S1 to Sn of the drug delivery device 10 at least before injection, during injection and after injection. In an exemplary embodiment, the state indicator 12 is formed as a window in the housing 10.2 through which different movable components 10.1 or part of these components 10.1, e.g. at least one of the needle sleeve 13 and piston rod 14, are visible at the various states S1 to Sn.

(26) FIG. 1C shows a schematic perspective view of an exemplary embodiment of a drug delivery device 1. The drug delivery device 1 comprises at least one movable component 1.1. The component 1.1 is relatively movable with respect to a housing 1.2 of the drug delivery device 1.

(27) The drug delivery device 1 may be configured as a pre-filled, disposable injection pen or as an autoinjector comprising the housing 1.2 receiving the movable component 1.1 and at least a container 1.3 to which a needle 1.4 may be fixed. The needle 1.4 may be protected by an inner needle cap and an outer needle cap, e.g. a so called needle shield (not illustrated).

(28) The drug delivery device 1 comprises a state indicator 2 for indicating at least three states S1 to Sn of the drug delivery device 1. The state indicator 2 is formed as a single indicator for indicating a respective state S1 to Sn of the drug delivery device 1 at least before injection, during injection and after injection.

(29) The state indicator 2 is designed as a single indicator. The single indicator is designed in an exemplary embodiment as a visual indicator 2.1. The visual indicator 2.1 comprises at least a window 1.2.1 in the housing 1.2. The window 1.2.1 may be configured as a transparent area or as an aperture in the housing 1.2. In an exemplary embodiment, the drug delivery device 1 may comprise two opposing windows 1.2.1 in the housing 1.2.

(30) The drug delivery device 1 comprises further a drug window 6. The drug window 6 is formed for example as a longitudinal recess, an aperture or a transparent area in the housing 1.2. In an exemplary embodiment, the drug delivery device 1 comprises two opposing drug windows 6 in the housing 1.2. The drug window/s 6 allow/s a view on the container 1.3, in particular on the drug in the container 1.3.

(31) In an exemplary embodiment, the drug window 6 has larger dimensions than the window 1.2.1. For example, the drug window 6 extends in a longitudinal direction and its length is larger than its width.

(32) The drug window 6 or each of the drug windows 6 is/are spaced apart to the state indicator 2. In particular, the drug window 6 is spaced apart to the window 1.2.1 in the housing 1.2. In more detail, the drug window 6 or each of the drug windows 6 is/are spaced apart to the state indicator 2, in particular to the window 1.2.1 in longitudinal direction as well as angularly. The window 1.2.1 has for example a round shape.

(33) The movable component 1.1 may be designed as a needle shroud 3 which is movably received within the housing 1.2 and with respect to the housing 1.2.

(34) The state indicator 2, in particular the visual indicator 2.1, is associated with the needle shroud 3 to produce the at least three state indications depending on different needle shroud positions.

(35) In particular, the visual indicator 2.1 indicates a first status S1 when the needle shroud 3 is in an expanded position before injection (shown in FIGS. 1 and 5), a second status S2 when the needle shroud 3 is in an unexpanded position during injection (shown in FIG. 5) and a third status S3 when the needle shroud 3 is an expanded position after injection (shown in FIG. 5).

(36) The respective state S1 to Sn is displayed through the window 1.2.1 arranged within the housing 1.2. The respective state S1 to Sn may be represented by mark M1 to Mn printed or laser marked spirally around an outer circumference of the movable component 1.1. The mark M1 to Mn may be printed as numbers, icons, bars, holes, colored symbols or the like.

(37) Additionally or alternatively, the movable component 1.1 may be designed as a piston rod 4 and/or a piston 4.1 which are movably received within the container 1.3 and with respect to the container 1.3.

(38) In a further exemplary embodiment, hence, the state indicator 2, in particular the visual indicator 2.1, is associated with the needle shroud 3 and/or the piston rod 4 and/or the piston 4 to produce the at least three state indications depending on different needle shroud/piston/piston rod positions.

(39) FIG. 2 shows a schematic perspective view of an exemplary embodiment of a housing 1.2 of the drug delivery device 1. The window 1.2.1 is a transparent part of the housing 1.2 permeable for visible light and may have dimensions enabling displaying exactly one mark M1 to Mn provided by the needle shroud 3, the piston 4.1 and/or the piston rod 4. For example, the window 1.2.1 is configured as an aperture.

(40) FIG. 3 shows a schematic perspective view of an exemplary embodiment of a piston rod 4 of the drug delivery device 1. The piston rod 4 comprises different mark M3, M4 which are associated with at least two states S3 to S4.

(41) In particular, mark M3 is associated with the state S3 which represent that the drug delivery device 1 is in an injection state. For example a colored outer surface of the piston rod 4 is visible through the window 1.2.1 of housing 1.2 during injection.

(42) The mark M4 is associated with the state S4 which represent that the injection of the drug delivery device 1 is completed. For example another colored outer surface of the piston rod 4 or a symbol or a print on the piston rod 4 is visible through the window 1.2.1 of housing 1.2 at the end of injection.

(43) FIG. 4 shows a schematic perspective view of an exemplary embodiment of a needle shroud 3 of the drug delivery device 1. The needle shroud 3 comprises different marks M1, M2 and M5 which are associated with at least two states S1, S2, S5.

(44) In particular, mark M1 is associated with the state S1 which represent that the drug delivery device 1 is in a pre-injection or initial state. For example a colored outer surface of the needle shroud 3 or a symbol or a print on the needle shroud 3 is visible through the window 1.2.1 of housing 1.2 before injection.

(45) The mark M2 is associated with the state S2 which represents that the drug delivery device 1 is in an injection state or in a final state. For example, another colored outer surface of the needle shroud 3 or a hole within the needle shroud 3 or a symbol or a print on the needle shroud 3 is visible through the window 1.2.1 of the housing 1.2 during or after injection. In particular, through the hole within the needle shroud 3 one of the marks M3, M4 of the piston rod 4 is visible.

(46) The mark M5 is associated with the state S5 which represents that the drug delivery device 1 is in a post-injection or final state. For example another colored outer surface of the needle shroud 3 or a hole within the needle shroud 3 or a symbol or a print on the needle shroud 3 is visible through the window 1.2.1 of the housing 1.2 in the post-injection state, in particular when the needle shroud 3 is finally locked to prevent a re-using.

(47) FIG. 5 shows a schematic side view of a cut-out of an exemplary embodiment of the drug delivery device 1 in different states S1 to S3, in particular in status S1 before injection, in status S2 during injection and in status S3 when the injection is completed. The drug delivery device 1 comprises a rear housing part 1.5. The needle shroud 3 is movably received within the housing part 1.5 as best seen from the sequence of views.

(48) In status S1, the mark M1 of the needle shroud 3 is visible through the window 1.2.1 of the housing 1.2 before injection.

(49) In status S2, the mark M2 of the needle shroud 3 is designed as an aperture within the needle shroud 3 so that the mark M3 of the piston rod 4 is visible through the window 1.2.1 of the housing 1.2 during injection.

(50) In status S3, the mark M2 of the needle shroud 3 is designed as an aperture within the needle shroud 3 so that the mark M4 of the piston rod 4 or the mark M5 of the needle shroud 3 is visible through the window 1.2.1 of the housing 1.2 at the end of injection before the needle shroud 3 is locked or after injection (post-injection) when the needle shroud 3 is locked against re-using of the drug delivery device 1.

(51) FIG. 6 shows a schematic view of different marks M1 to Mn assigned to the different states S1 to Sn of the drug delivery device 1.

(52) The mark M1 is for example a print on an outer surface of the needle shroud 3 representing that the drug delivery device 1 is a pre-injection status S1.

(53) The marks M2 and M3 are examples for a coloured movable component 1.1, e.g. for a partially coloured needle shroud 3 or a partially coloured piston rod 4 representing that the drug delivery device 1 is in a start status S2 before injection or in an injection status S3 during injection.

(54) The mark M4 is an example for a coloured movable component 1.1, e.g. for a partially coloured needle shroud 3 or a partially coloured piston rod 4 representing that the injection of the drug delivery device 1 is completed. For example, once the piston 4.1 has reached a distal end of the container 1.3, it is ensured by the mark M4 that indication to the user that injection of the product is completed is given only once the product is substantially expelled from the container 1.3.

(55) The mark M5 is for example a print on an outer surface of the needle shroud 3 representing that the drug delivery device 1 is in a post-injection status S5 in which the needle shroud 3 is for example locked.

(56) FIGS. 7 and 8 show further schematic views of other possible marks M1, M5 represented by a print onto the needle shroud 3 and assigned to pre-injection state S1 or post-injection state S5 of the drug delivery device 1. The marks M1, M5 are visible through the window 1.2.1 of the housing 1.2.

(57) FIG. 9 shows a schematic perspective view of an embodiment of a stand-alone unit 5 as an example for an electronic indicator 2.2 which may be removably attached to the drug delivery device 1. According to this embodiment an additional part is necessary. The stand-alone unit 5 may be designed as a clip which may be removably attached to the housing 1.2 of the drug delivery device 1. Alternatively, the stand-alone unit 5 may comprise force-fit or form-fit connecting elements 5.1 to removably attach the unit 5 onto the housing 1.2 or another holder to hold the device 5 onto the housing 1.2.

(58) In particular, the connecting elements 5.1 are formed as arms extending form the electronic indicator 2.2. The arms are flexible and form clamping arms which engage and clamp the stand-alone unit 5 to the drug delivery device 1. The clamp arms are lengthened and biased radially to retain the stand-alone unit 5

(59) The stand-alone unit 5 may comprise a display unit 5.2 for indicating different states Sn of the drug delivery device 1.

(60) Alternatively the stand-alone unit 5 may be structured as an optical unit, e.g. as an optical glass, for example as a magnifying glass with zoom function to enlarge marks, symbols or profiles provided on the drug delivery device 1.

(61) FIG. 10 shows another exemplary embodiment for a stand-alone unit 5 which may be designed as an optical indicator 2.3. The optical indicator 2.3 comprises at least one light source as a mark M1 to Mn. For example the light source is a light emitting diode wherein only one light emitting diode may be represented different states S1 to Sn of the drug delivery device 1. Alternatively, the optical indicator 2.3 comprises a number of light sources wherein each of them is associated with one of the different states S1 to Sn.

(62) The terms “drug” or “medicament” are used herein to describe one or more pharmaceutically active compounds. As described below, a drug or medicament can include at least one small or large molecule, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Exemplary pharmaceutically active compounds may include small molecules; 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 of these drugs are also contemplated.

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

(64) 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 vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more pharmaceutically active compounds. 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 a drug formulation (e.g., a drug and a diluent, or two different types of 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 of the drug or medicament 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.

(65) The drug delivery devices and drugs described herein can be used for the treatment and/or prophylaxis of many different types of disorders. Exemplary 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 exemplary disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.

(66) Exemplary drugs for the treatment and/or prophylaxis of diabetes mellitus or complications associated with 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 term “derivative” refers to any substance which is sufficiently structurally similar to the original substance so as to have substantially similar functionality or activity (e.g., therapeutic effectiveness).

(67) Exemplary insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; 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.

(68) Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin; 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—(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example: Lixisenatide/AVE0010/ZP10/Lyxumia, Exenatide/Exendin-4/Byetta/Bydureon/ITCA 650/AC-2993 (a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide/Victoza, Semaglutide, Taspoglutide, Syncria/Albiglutide, Dulaglutide, rExendin-4, CJC-10.234-PC, PB-1023, TTP-054, Langlenatide/HM-10.2260C, 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.

(69) An exemplary oligonucleotide is, for example: mipomersen/Kynamro, a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia.

(70) Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

(71) Exemplary 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.

(72) Exemplary 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 poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20/Synvisc, a sodium hyaluronate.

(73) 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′).sub.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.

(74) 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 disclosure 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, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), 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.

(75) 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.

(76) Exemplary antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

(77) The compounds described herein may be used in pharmaceutical formulations comprising (a) the compound(s) or pharmaceutically acceptable salts thereof, and (b) a pharmaceutically acceptable carrier. The compounds may also be used in pharmaceutical formulations that include one or more other active pharmaceutical ingredients or in pharmaceutical formulations in which the present compound or a pharmaceutically acceptable salt thereof is the only active ingredient. Accordingly, the pharmaceutical formulations of the present disclosure encompass any formulation made by admixing a compound described herein and a pharmaceutically acceptable carrier.

(78) Pharmaceutically acceptable salts of any drug described herein are also contemplated for use in drug delivery devices. Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g. salts having a cation selected from an alkali or alkaline earth metal, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharmaceutically acceptable salts are known to those of skill in the arts.

(79) Pharmaceutically acceptable solvates are for example hydrates or alkanolates such as methanolates or ethanolates.

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

LIST OF REFERENCES

(81) 1, 10 drug delivery device 1.1, 10.1 movable component 1.2, 10.2 housing 1.2.1, 10.2.1 window 1.3, 10.3 container 1.4, 10.4 needle 1.5 housing part 2, 12 state indicator 2.1 visual indicator 2.2 electronic indicator 2.3 optical indicator 3, 13 needle shroud 4, 14 piston rod 4.1, 14.1 piston 5 stand-alone unit 5.1 connecting element 5.2 display unit 6, 60 drug window 15 syringe carrier 16 cap assembly 20 distal region 21 proximal region 22 button M1 to Mn mark S1 to Sn status X longitudinal axis