The invention relates to a control unit for a drug delivery device. Background of the Invention

Administering an injection is a process which presents a number of risks and challenges for users and healthcare professionals, both mental and physical. Injection devices typically fall into two categories - manual devices and auto-injectors. In a conventional manual device, a user must provide force to drive a medicament through a needle. This is typically done by some form of button / plunger that has to be continuously pressed during the injection. There are numerous disadvantages for the user from this approach. For example, if the user stops pressing the button / plunger, the injection will stop and may not deliver an intended dose to a patient. Further, the force required to push the button/plunger may be too high for the user (e.g., if the user is elderly). And, aligning the injection device, administering the injection and keeping the injection device still during the injection may require dexterity which some patients (e.g., elderly patients, children, arthritic patients, etc.) may not have.

Pen injectors or auto-injector devices aim to make self-injection easier for patients by providing the force for administering the injection by a spring. A trigger button or other mechanism may be used to activate the injection. Pen injectors or auto-injectors may be single-use or reusable devices.

Many patients hesitate injecting themselves because of fear of needles. In particular, patients flinch from inserting an injection needle into their skin while they readily accept administration by another person.

There remains a need for an improved control unit for a drug delivery device facilitating self administration. Summary of the Invention

It is an object of the present invention to provide an improved control unit for a drug delivery device and an improved drug delivery device.

The object is achieved by a control unit according to claim 1 and by a drug delivery device according to claim 6. Preferred embodiments of the invention are given in the dependent claims.

According to the invention a control unit for a drug delivery device with an injection needle is adapted to control movement of the injection needle from a retracted position, in which the injection needle is hidden within the drug delivery device, to an extended position, in which the injection needle protrudes from the drug delivery device, upon operation of a trigger, wherein the control unit is adapted to start the movement of the injection needle within a pre-determined time interval at a point in time, which is unpredictable for a human. Many patients hesitate injecting themselves because of fear of needles. In particular, patients flinch from inserting an injection needle into their skin while they accept administration by another person if they do not see the needle and cannot anticipate the exact moment of needle insertion. The control unit according to the invention uncouples the user action of operating the trigger from the exact moment of needle insertion thus mimicking administration by another person so that hesitant patients can learn to inject themselves. This reduces stress for the patients and improves compliance.

In an exemplary embodiment the control unit is adapted to determine the point in time for moving the needle from the retracted position to the extended position by a random or pseudo-random or chaotic process. This makes the exact point in time at least virtually unpredictable for a human.

In an exemplary embodiment the control unit is adapted to, upon operation of the trigger, wait for a first pre-determined time interval, e.g. 5 seconds, to elapse, and determine the point in time for moving the needle from the retracted position to the extended position within a subsequent second pre-determined interval, which may for example be 0 to 3 seconds. In an exemplary embodiment the control unit may also be adapted to control movement of the injection needle from the extended position to the retracted position after delivery of a dose of a drug contained in a syringe connected to the injection needle, i.e. needle retraction for providing post injection needle safety reducing the risk for needle stick injuries.

In an exemplary embodiment the control unit may also be adapted to control delivery of the drug contained in the syringe after having moved the injection needle from the retracted position to the extended position. The control unit may be applied in a drug delivery device for administering a drug, comprising:

- a case,

- an injection needle,

- a first drive adapted to move the injection needle from the retracted position, in which the injection needle is hidden within the case, to the extended position, in which the injection needle protrudes from the case through an orifice,

- the control unit connected to the first drive.

In an exemplary embodiment the drug delivery device may comprise a syringe defining a cavity arranged to contain a drug, wherein the injection needle is attachable to the syringe so as to be in fluid communication with the cavity.

In an exemplary embodiment the drug delivery device may comprise a second drive for causing displacement of a dose of the drug from the cavity. The second drive may also be controlled by the control unit.

In an exemplary embodiment the drug delivery device comprises a trigger arranged on the case and connected to the control unit for allowing manual operation by a user, e.g. a patient. In an exemplary embodiment the case of the drug delivery device is opaque preventing the user from seeing the needle prior to injection thus further reducing hesitation to apply the drug delivery device.

In an exemplary embodiment the case may comprise a door for allowing insertion and removal of the syringe and needle. This allows for a reusable drug delivery device reducing resource consumption and costs as opposed to disposable drug delivery devices.

In an exemplary embodiment the first drive and/or the second drive comprise/comprises an electric motor. Furthermore, the first drive and/or the second drive may comprise gear such as a rack and a pinion driven by the electric motor allowing conversion of the motor's rotation to linear movement of the syringe, needle and/or a stopper within the syringe, if applicable. Depending on the geometry of the gear a pre-determined number of rotations of the motor results in a pre-determined linear movement of the needle, syringe and/or stopper.

In an exemplary embodiment the syringe may be arranged as a pen injector, which may typically be used for administering insulin. The pen injector may comprise an injector case, a drug cartridge containing the drug and having a stopper, a dose setting member, e.g. a dial, a pen drive mechanism, e.g. a spring for displacing the stopper within the cartridge and delivering the set dose and a pen trigger, e.g. a button for triggering the pen drive mechanism, wherein the second drive is arranged to operate the pen trigger. The pen injector is intended to be used independently which however makes the user see the needle and actively insert the needle into the skin. When using the pen injector in the drug delivery device with the control unit the user does neither see the needle prior to needle insertion nor can they predict the point in time at which the needle is moved to the extended position thus reducing the user's fear and allowing them to get used to self administration. If the user wants, they can start using the pen injector with the drug delivery device and then migrate to normal application once they got used to self administration. Application of a conventional pen injector in the drug delivery device reduces developing costs and effort for obtaining approval of the device by the

authorities. Typically, the dose to be delivered will be set prior to insertion of the pen injector into the case of the drug delivery device. In another exemplary embodiment the drug delivery device may be arranged as an auto-injector. In this case, a conventional syringe may be used, wherein the second drive is arranged to displace the stopper within the syringe. When using the auto- injector with the control unit the user does neither see the needle prior to needle insertion nor can they predict the point in time at which the needle is moved to the extended position thus reducing the user's fear and allowing them to get used to self administration.

In an exemplary embodiment a cap may be arranged to close the orifice in the case thus protecting the interior of the drug delivery device from staining.

In an exemplary embodiment a sensor unit may be arranged for detecting contact of the case at the orifice with a patient's skin and preventing operation of the trigger or making such operation ineffective otherwise. For example, an indicator light, e.g. red, may be arranged for indicating failure to correctly placing the drug delivery device against a patient's skin. The sensor unit may also be used to monitor maintenance of skin contact during drug delivery. If removal from skin is detected the drug delivery may be interrupted. This may also be indicated by the red light.

Another indicator light, for example a yellow light, may be arranged to indicate drug delivery in progress. An audio output and or yet another indicator light, e.g. a green light may be arranged to indicate the end of drug delivery.

The sensor unit may also be arranged to detect inappropriate injection sites such as blood vessels and scar tissue.

The sensor unit may be arranged to detect the distance between the injection site, e.g. the patient's skin and the needle tip and adjust the distance between the retracted position and the extended position accordingly, e.g. in case the drug delivery device is pressed hard against the skin such that the skin arches into the orifice. Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and

modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

Brief Description of the Drawings

The present invention will become more fully understood from the detailed description given hereinbelow and the accompanying drawings which are given by way of illustration only, and thus, are not limitive of the present invention, and wherein:

Figure 1 is a schematic view of a drug delivery device for administering a drug, with an injection needle in a retracted position,

Figure 2 is a schematic view of the drug delivery device with the injection

needle in an extended position,

Figure 3 is a schematic diagram depicting a sequence of operation controlled by a control unit of the drug delivery device, and

Figure 4 is a schematic view of another exemplary embodiment of a drug

delivery device for administering a drug.

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

Detailed Description of Preferred Embodiments

Figure 1 is a schematic view of a drug delivery device 2 for administering a drug D, with an injection needle 3 in a retracted position RP. Figure 2 is a schematic view of the drug delivery device 2 with the injection needle 3 in an extended position EP. The drug delivery device 2 comprises:

- a case 6 adapted to retain a syringe 5 defining a cavity 9 arranged to contain the drug D,

- an injection needle 3 attached to the syringe 5 so as to be in fluid communication with the cavity 9,

- a first drive 7 adapted to move the syringe 5 and the injection needle 3 from the retracted position RP, in which the injection needle 3 is hidden within the case 6, to the extended position EP (cf. fig. 2), in which the injection needle 3 protrudes from the case 6 through an orifice 8,

- a control unit 1 , connected to the first drive 7.

A trigger 4, connected to the control unit 1 , is arranged on the case 6.

A second drive 10, connected to the control unit 1 , is arranged for causing displacement of a dose of the drug D from the cavity 9 of the syringe 5 through the needle 3.

The first drive 7 and/or the second drive 10 comprise/comprises respective electric motors 12.1 , 12.2, racks 13.1 , 13.2 and pinions 14.1 , 14.2 driven by the electric motor 12.1 , 12.2 allowing conversion of the motor's 12.1 , 12.2 rotation to linear movement.

The case 6 comprises a door 1 1 for allowing insertion and removal of the syringe 5 and needle 3.

In the embodiment of figures 1 and 2 the syringe 5 is arranged as a pen injector, which may typically be used for administering insulin. The pen injector 5 comprises an injector case 15 adapted to retain a drug cartridge 16 containing the drug D and having a stopper 17, a dose setting member 18, e.g. a dial, a pen drive mechanism 19, e.g. a spring for displacing the stopper 17 within the cartridge 16 and delivering the set dose and a pen trigger 20, e.g. a button for triggering the pen drive mechanism 19. The second drive 10 is arranged to operate the pen trigger 20.

The control unit 1 is adapted to control movement of the syringe 5 and the injection needle 3 from the retracted position RP (cf. fig. 1 ) to the extended position EP (cf. fig. 2) upon operation of the trigger 4, wherein the control unit 1 is adapted to start the movement of the injection needle 3 within a pre-determined time interval T ₂ at a point in time t _t , which is unpredictable for a human, for example by determining the point in time by a random or pseudo-random or chaotic process. Figure 3 is a schematic diagram depicting a sequence of operation controlled by the control unit 1 . At a trigger point to in time t the trigger 4 is operated which is detected by the control unit 1 . Upon operation of the trigger 4 the control unit waits for a first predetermined time interval Ti to elapse, e.g. by waiting for a timer or counter to run down. In an exemplary embodiment the first pre-determined time interval Ti may last between 0 s and 10 s, in particular between 3 s and 6 s, more particular 5 s. The point in time t _t for starting movement of the syringe 5 and needle 3 from the retracted position RP to the extended position EP is then determined within a subsequent second predetermined time interval T ₂ , which may for example be 3 s or even 30 s long. Within this second pre-determined time interval T ₂ , the point in time is determined by a random or pseudo-random or chaotic process such that it is unpredictable for a human.

A preferable embodiment provides that the first pre-determined time interval Ti and the second pre-determined time interval T ₂ are various in time. This is preferable, because at a beginning of a need for a pen injector, the uncoupling of the user decision of operating and the exact moment of needle insertion is more important than later, when the patient is more experienced. That means for example: At a first time, in which the first injection processes are performed, the first pre-determined time interval Ti may last 5 s. After performing some, i.e. 10, injection processes, the first pre-determined time interval Ti will be decreased. With this, a possible eagerness of an experienced patient can be reduced. At the same time, the second pre-determined time interval T ₂ will be increased respectively. With this a maximum process time will not be changed.

Additionally, the patient is allowed to adjust the first pre-determined time interval Ti and the second pre-determined time interval T ₂ by himself. For this, the control unit 1 implements selectable programs such as "Beginner", "Advancer" and "Expert" that are displayed on a display unit arranged on the pen injector. Alternatively, the control unit 1 implements a program, wherein the patient is allowed to adjust the pre-determined time intervals Ti and T ₂ directly. Thus the patient is able to decrease the pre-determined time intervals Ti and T ₂ stepwise so that when the patient is experienced the point in time of needle insertion meets the user action of operating the trigger. With other words: The first pre-determined time interval Ti=0 s. This allows the patient to adjust the time period for the required injection process according to his needs. The control unit 1 is also adapted to control delivery of the drug D contained in the syringe 5 after having moved the injection needle 3 from the retracted position RP to the extended position EP by operating the second drive 10. The rack 13.2 of the second drive operates the pen trigger 20 which in releases the pen drive mechanism 19. The pen drive mechanism 19 displaces the stopper 17 within the cartridge 16 and delivers the dose set by the dose setting member 18 prior to insertion of the syringe 5 (pen injector) into the case 6.

After delivery of the dose of drug D the control unit 1 controls movement of the injection needle 3 from the extended position EP to the retracted position RP for providing post- injection needle safety.

Figure 4 is a schematic view of an alternative embodiment of the drug delivery device 2. The drug delivery device 2 of figure 4 is an auto-injector retaining a conventional syringe 5 with an attached or attachable injection needle 3 and a stopper 17 displaceable within the syringe cavity 9 instead of the pen injector of figures 1 and 2. In the embodiment of figure 4 the rack 13.2 of the second drive 10 is arranged as a plunger directly acting on the stopper 17.

The auto-injector may be reusable allowing replacement of the syringe 5 reducing costs and resource consumption. Alternatively, the auto-injector may be disposable without a replacement option thus reducing the risk for cross contamination.

In an exemplary embodiment the case 6 may be opaque so as to prevent a user from viewing the needle 3.

In an exemplary embodiment a cap may be arranged to close the orifice 8 in the case 6 thus protecting the interior of the drug delivery device 2 from staining. In an exemplary embodiment a sensor unit may be arranged for detecting contact of the case 6 at the orifice 8 with a patient's skin and preventing operation of the trigger 4 or making such operation ineffective otherwise. For example, an indicator light, e.g. red, may be arranged for indicating failure to correctly placing the drug delivery device 2 against a patient's skin. The sensor unit may also be used to monitor maintenance of skin contact during drug delivery. If removal from skin is detected the drug delivery may be interrupted. This may also be indicated by the red light.

Another indicator light, for example a yellow light, may be arranged to indicate drug delivery in progress. An audio output and or yet another indicator light, e.g. a green light may be arranged to indicate the end of drug delivery.

The sensor unit may also be arranged to detect inappropriate injection sites such as blood vessels and scar tissue.

The sensor unit may be arranged to detect the distance between the injection site, e.g. the patient's skin and the needle tip and adjust the distance between the retracted position and the extended position accordingly, e.g. in case the drug delivery device is pressed hard against the skin such that the skin arches into the orifice.

The term "drug" or "medicament", as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound, wherein in one embodiment the pharmaceutically active compound has a molecular weight up to 1500 Da and/or is a peptide, a proteine, a polysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or a fragment thereof, a hormone or an

oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound, wherein in a further embodiment the pharmaceutically active compound is useful for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism, acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever,

atherosclerosis and/or rheumatoid arthritis, wherein in a further embodiment the pharmaceutically active compound comprises at least one peptide for the treatment and/or prophylaxis of diabetes mellitus or

complications associated with diabetes mellitus such as diabetic retinopathy, wherein in a further embodiment the pharmaceutically active compound comprises at least one human insulin or a human insulin analogue or derivative, glucagon-like peptide (GLP-1 ) or an analogue or derivative thereof, or exendin-3 or exendin-4 or an analogue or derivative of exendin-3 or exendin-4. Insulin analogues are for example Gly(A21 ), Arg(B31 ), Arg(B32) human insulin; 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.

Insulin derivates 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-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; Β29-Ν-(ω- carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(u}-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1 -39), a peptide of the sequence H-His-Gly-

Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-G lu-Ala-Val-Arg-Leu-Phe- lle-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro- Pro-Ser-NH2. Exendin-4 derivatives are for example selected from the following list of compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1 -39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1 -39)-NH2,

des Pro36 Exendin-4(1 -39),

des Pro36 [Asp28] Exendin-4(1 -39),

des Pro36 [lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1 -39),

des Pro36 [Met(O)14, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1 -39),

des Pro36 [Trp(O2)25, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1 -39),

des Pro36 [Met(O)14 Trp(O2)25, lsoAsp28] Exendin-4(1 -39); or des Pro36 [Asp28] Exendin-4(1 -39),

des Pro36 [lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1 -39),

des Pro36 [Met(O)14, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1 -39),

des Pro36 [Trp(O2)25, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1 -39),

des Pro36 [Met(O)14 Trp(O2)25, lsoAsp28] Exendin-4(1 -39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative; or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1 -39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1 -39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1 -39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1 -39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1 -39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1 -39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1 -39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1 -39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1 -39)-NH2, des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1 -39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1 -39)-(Lys)6-NH2, H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1 -39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1 -39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1 -39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1 -39)-NH2, des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1 -39)-(Lys)6-NH2, H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1 -39)-(Lys)6-NH2, H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1 -39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1 -39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1 -39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1 -39)- NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1 -39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1 -39)- (Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1 -39)- (Lys)6-NH2; or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists as listed in Rote Liste, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example 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, 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.

Antibodies are globular plasma proteins (-150 kDa) that are also known as

immunoglobulins which share a basic structure. As they have sugar chains added to amino acid residues, they are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a "Y"-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds between cysteine residues. Each heavy chain is about 440 amino acids long; each light chain is about 220 amino acids long. Heavy and light chains each contain intrachain disulfide bonds which stabilize their folding. Each chain is composed of structural domains called Ig domains. These domains contain about 70-1 10 amino acids and are classified into different categories (for example, variable or V, and constant or C) according to their size and function. They have a characteristic immunoglobulin fold in which two β sheets create a "sandwich" shape, held together by interactions between conserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ, and μ. The type of heavy chain present defines the isotype of antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.

Distinct heavy chains differ in size and composition; a and γ contain approximately 450 amino acids and δ approximately 500 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has two regions, the constant region (CH) and the variable region (V _H ). In one species, the constant region is essentially identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains γ, a and δ have a constant region composed of three tandem Ig domains, and a hinge region for added flexibility; heavy chains μ and ε have a constant region composed of four immunoglobulin domains. The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 1 10 amino acids long and is composed of a single Ig domain. In mammals, there are two types of immunoglobulin light chain denoted by λ and κ. A light chain has two successive domains: one constant domain (CL) and one variable domain (VL). The approximate length of a light chain is 21 1 to 217 amino acids. Each antibody contains two light chains that are always identical; only one type of light chain, K or λ, is present per antibody in mammals.

Although the general structure of all antibodies is very similar, the unique property of a given antibody is determined by the variable (V) regions, as detailed above. More specifically, variable loops, three each the light (VL) and three on the heavy (VH) chain, are responsible for binding to the antigen, i.e. for its antigen specificity. These loops are referred to as the Complementarity Determining Regions (CDRs). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chains, and not either alone, that determines the final antigen specificity. An "antibody fragment" contains at least one antigen binding fragment as defined above, and exhibits essentially the same function and specificity as the complete antibody of which the fragment is derived from. Limited proteolytic digestion with papain cleaves the Ig prototype into three fragments. Two identical amino terminal fragments, each containing one entire L chain and about half an H chain, are the antigen binding fragments (Fab). The third fragment, similar in size but containing the carboxyl terminal half of both heavy chains with their interchain disulfide bond, is the crystalizable fragment (Fc). The Fc contains carbohydrates, complement-binding, and FcR-binding sites. Limited pepsin digestion yields a single F(ab')2 fragment containing both Fab pieces and the hinge region, including the H-H interchain disulfide bond. F(ab')2 is divalent for antigen binding. The disulfide bond of F(ab')2 may be cleaved in order to obtain Fab'. Moreover, the variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv). Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCI or HBr salts. Basic salts are e.g. salts having a cation selected from alkali or alkaline, 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 described in "Remington's Pharmaceutical Sciences" 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Those of skill in the art will understand that modifications (additions and/or removals) of various components of the apparatuses, methods and/or 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. List of References

I control unit

2 drug delivery device

3 needle

4 trigger

5 syringe

6 case

7 first drive

8 orifice

9 cavity

10 second drive

I I door

12.1 motor

12.2 motor

13.1 rack

13.2 rack

14.1 pinion

14.2 pinion

15 injector case

16 drug cartridge

17 stopper

18 dose setting member

19 pen drive mechanism

20 pen trigger

D drug

EP extended position

RP retracted position

t time

to trigger point

Ti first pre-determined time interval

T ₂ second pre-determined time interval t _t point in time