Abstract:
The invention relates to a dispense interface for use with a drug delivery device with an inner body and with a lockout element, wherein the lockout element is coupled to the inner body, wherein the lockout element is movable from a receptive condition to a locked condition, wherein in the receptive condition the dispense interface is attachable to the drug delivery device, wherein in the locked condition the dispense interface is not-attachable to the drug delivery device and wherein the lockout element is configured to move from the receptive condition to the locked condition when said dispense interface is attached to and detached from said drug delivery device. The invention solves the technical problem of reducing the risk of reuse of a dispense interface, after it has already been used with a drug delivery device.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application is a U.S. National Phase Application pursuant to 35 U.S.C. §371 of International Application No. PCT/EP2012/057685 filed Apr. 26, 2012, which claims priority to U.S. Provisional Patent Application No. 61/480,063, filed Apr. 28, 2011, and European Patent Application No. 11173271.5, filed Jul. 8, 2011. The entire disclosure contents of these applications are herewith incorporated by reference into the present application. 
     
    
     FIELD OF DISCLOSURE 
       [0002]    The present patent application relates to medical devices for delivering at least two drug agents from separate reservoirs. Such drug agents may comprise a first and a second medicament. The medical device includes a dose setting mechanism for delivering the drug agents automatically or manually by the user. 
         [0003]    The medical device can be an injector, for example a hand-held injector, especially a pen-type injector, that is an injector of the kind that provides for administration by injection of medicinal products from one or more multidose cartridges. In particular, the present invention relates to such injectors where a user may set the dose. 
         [0004]    The drug agents may be contained in two or more multiple dose reservoirs, containers or packages, each containing independent (single drug compound) or pre-mixed (co-formulated multiple drug compounds) drug agents. 
       BACKGROUND 
       [0005]    Certain disease states require treatment using one or more different medicaments. Some drug compounds need to be delivered in a specific relationship with each other in order to deliver the optimum therapeutic dose. The present patent application is of particular benefit where combination therapy is desirable, but not possible in a single formulation for reasons such as, but not limited to, stability, compromised therapeutic performance and toxicology. 
         [0006]    For example, in some cases it may be beneficial to treat a diabetic with a long acting insulin (also may be referred to as the first or primary medicament) along with a glucagon-like peptide-1 such as GLP-1 or GLP-1 analog (also may be referred to as the second drug or secondary medicament). 
         [0007]    Accordingly, there exists a need to provide devices for the delivery of two or more medicaments in a single injection or delivery step that is simple for the user to perform without complicated physical manipulations of the drug delivery device. The proposed drug delivery device provides separate storage containers or cartridge retainers for two or more active drug agents. These active drug agents are then combined and/or delivered to the patient during a single delivery procedure. These active agents may be administered together in a combined dose or alternatively, these active agents may be combined in a sequential manner, one after the other. 
       SUMMARY 
       [0008]    The drug delivery device also allows for the opportunity of varying the quantity of the medicaments. For example, one fluid quantity can be varied by changing the properties of the injection device (e.g., setting a user variable dose or changing the device&#39;s “fixed” dose). The second medicament quantity can be changed by manufacturing a variety of secondary drug containing packages with each variant containing a different volume and/or concentration of the second active agent. 
         [0009]    The drug delivery device may have a single dispense interface. This interface may be configured for fluid communication with a primary reservoir and with a secondary reservoir of medicament containing at least one drug agent. The drug dispense interface can be a type of outlet that allows the two or more medicaments to exit the system and be delivered to the patient. 
         [0010]    The combination of compounds from separate reservoirs can be delivered to the body via a double-ended needle assembly. This provides a combination drug injection system that, from a user&#39;s perspective, achieves drug delivery in a manner that closely matches the currently available injection devices that use standard needle assemblies. One possible delivery procedure may involve the following steps: 
         [0011]    1. Attach a dispense interface to a distal end of the electro-mechanical injection device. The dispense interface comprises a first and a second proximal needle. The first and second needles pierce a first reservoir containing a primary compound and a second reservoir containing a secondary compound, respectively. 
         [0012]    2. Attach a dose dispenser, such as a double-ended needle assembly, to a distal end of the dispense interface. In this manner, a proximal end of the needle assembly is in fluidic communication with both the primary compound and secondary compound. 
         [0013]    3. Dial up/set a desired dose of the primary compound from the injection device, for example, via a graphical user interface (GUI). 
         [0014]    4. After the user sets the dose of the primary compound, the micro-processor controlled control unit may determine or compute a dose of the secondary compound and preferably may determine or compute this second dose based on a previously stored therapeutic dose profile. It is this computed combination of medicaments that will then be injected by the user. The therapeutic dose profile may be user selectable. Alternatively, the user can dial or set a desired dose of the secondary compound. 
         [0015]    5. Optionally, after the second dose has been set, the device may be placed in an armed condition. The optional armed condition may be achieved by pressing and/or holding an “OK” or an “Arm” button on a control panel. The armed condition may be provided for a predefined period of time during which the device can be used to dispense the combined dose. 
         [0016]    6. Then, the user will insert or apply the distal end of the dose dispenser (e.g. a double ended needle assembly) into the desired injection site. The dose of the combination of the primary compound and the secondary compound (and potentially a third medicament) is administered by activating an injection user interface (e.g. an injection button). 
         [0017]    Both medicaments may be delivered via one injection needle or dose dispenser and in one injection step. This offers a convenient benefit to the user in terms of reduced user steps compared to administering two separate injections. 
         [0018]    Delivering one or more medicaments through a dose dispenser with a dispense interface can result in the contamination of the dispense interface with traces of each medicament. This contamination may prohibit reusing the dispense interface, for example after a certain time or after a predetermined number of usages, because the purity of the delivered medicaments cannot be guaranteed. Even a user who is conscious of this problem may inadvertently try to reuse a dispense interface because he may not remember and may find it difficult or impossible to determine by inspection whether a given dispense interface has in fact been used or not. 
         [0019]    It is therefore desirable to provide the dispense interface with a mechanism that prevents reuse of the dispense interface with a drug delivery device. This mechanism should be such that it is effective in its prevention of reuse as well as safe from manual manipulation by a user. 
         [0020]    The invention faces the technical problem of providing a dispense interface for use with a drug delivery device which is prevented of being reused after it has already been used with a drug delivery device. 
         [0021]    This object has been solved by a dispense interface for use with a drug delivery device with an inner body and with a lockout element, wherein the lockout element is coupled to the inner body, wherein the lockout element is movable from a receptive condition to a locked condition, wherein in the receptive condition the dispense interface is attachable to the drug delivery device, wherein in the locked condition the dispense interface is not-attachable to the drug delivery device and wherein the lockout element is configured to move from the receptive condition to the locked condition when said dispense interface is attached to and detached from said drug delivery device. 
         [0022]    The lockout element is arranged in its receptive condition such that it allows attachment of the dispense interface to the drug delivery device. However, the process of attaching the dispense interface to the drug delivery device mechanically moves the lockout element such that, once the dispense interface is detached and thereby is removed from the drug delivery device, the lockout element mechanically blocks a reattachment of the dispense interface to any drug delivery device. Therefore a reuse of the dispense interface is prevented and the risk of contamination from residual drug components within the dispense interface eliminated. 
         [0023]    According to an advantageous embodiment of the dispense interface, the lockout element is movable from the receptive condition to an activated condition, wherein in the activated condition the lockout element is configured to move automatically to the locked condition when said dispense interface is detached from said drug delivery device, and wherein the lockout element is configured to move from the receptive condition to the activated condition when said dispense interface is attached to said drug delivery device. This embodiment ensures in a particular safe and reliable manner the lockout element to move from the receptive condition to the locked condition, when said dispense interface is attached to and detached from said drug delivery device. 
         [0024]    Preferably, the lockout element has at least a spring element, which is strained in the receptive and/or the activated condition and at least partly relaxed in the locked condition. Accordingly, in the receptive and/or the activated condition the tensioned spring element stores energy, wherein in the locked condition the spring element stores less or no energy. In this configuration, the energy in the spring element is in a simple manner transformable into movement of the lockout element, especially an automatic movement to the locked condition. In particular, the spring element may effect an automatic movement of the lockout element from the activated to the locked condition. 
         [0025]    The spring element may be an integral part of the lockout element or a separate element, which is connected to the lockout element. Further, the spring element may comprise one or more spring arms, whereas the spring element preferably comprises two spring arms. 
         [0026]    It is further preferred, that the lockout element has at least a bearing section for bearing a distal portion of the drug delivery device, wherein in the receptive condition the bearing section is in an open position, in which it allows the distal portion of the drug delivery device to approach the inner body, and wherein in the locked condition the bearing section is in a blocking position, in which it prevents the distal portion of the drug delivery device to approach the inner body. 
         [0027]    Providing a lockout element with a bearing section for bearing a distal portion of the drug delivery device, allows the reattachment of the dispense interface to be prevented mechanically with a particularly simple constructive design of the lockout element. At the same time the mechanical blocking is reliable and therefore safely prevents the dispense interface from reattachment. The blocking function may be further improved by providing more than one bearing section, in particular two bearing sections for bearing two distal portions of the drug delivery device. 
         [0028]    According to a further embodiment of the dispense interface, the lockout element has at least a support section, wherein a support surface is provided on the inner body or an outer body, which is attached to the inner body, and wherein the lockout element is configured such that in the locked condition the support section is in engagement with the support surface so as to prevent the bearing section from being moved into the open position. 
         [0029]    Thereby, the bearing section may reliably be maintained in the blocking position once the lockout element has moved into the locked condition, thus safely preventing the dispense interface from being reattached to the drug delivery device after it has been used. In particular, this embodiment ensures the bearing section not to be moved from the blocking position back to the open position due to geometrical restrictions. The support section may be a surface portion or an edge portion of the lockout element. A further increased blocking safety may be achieved by providing a lockout element with two or more support sections and an outer body or respectively an inner body with two or more corresponding support surfaces. 
         [0030]    It is moreover preferred, that the bearing section is resiliently supported on the inner body by the spring element. Thereby, it is in a particularly simple manner possible to influence the strain condition of the spring element by attaching the dispense interface to a drug delivery device. 
         [0031]    Further to this, the lockout element may be configured such that when said dispense interface is attached to said drug delivery device, a distal portion of the drug delivery device acts on said bearing section such that said spring element is strained or further strained. 
         [0032]    Accordingly, by attaching the dispense interface to the drug delivery device the energy stored in the spring element is increased. This enables the lockout element to reliably change its condition. In particular, the lockout element may thereby be moved from the receptive condition to the activated condition. 
         [0033]    Moreover, the lockout element may be configured such that when said dispense interface is detached from said drug delivery device, a distal portion of the drug delivery device is retracted from said bearing section such that said spring element is at least partly relaxed and said bearing section is moved from the open to the blocking position. 
         [0034]    Thus, the energy stored in the spring element in the receptive and/or activated condition may in a simple and reliable manner effect the lockout element to move to the locked condition, in which the bearing section is in its blocking position. At the same time the detachment of the dispense interface may be supported by the relaxing process of the spring element. 
         [0035]    In a further preferred embodiment, the lockout element may have at least a release section with a shaped element, wherein the inner body has at least a retaining element, and wherein in the receptive condition the shaped element is in releasable engagement with the retaining element. Accordingly, the shaped element is in disengagement with the retaining element in the activated and/or the locked condition. 
         [0036]    Hereby, the shaped element corresponds to the retaining element, wherein the releasable engagement may preferably be configured as a positive fit. In particular, the shaped element may be formed as a recess and the retaining element may be formed as a protrusion and wherein in the releasable engagement the protrusion at least partly protrudes in the recess. 
         [0037]    By providing a lockout element with a release section, which comprises a shaped element, and an inner body with a retaining element, which corresponds to the shaped element, the lockout element may securely be held in the receptive condition. In particular, this enables to securely hold the spring element strained as long as the lockout element is in a receptive condition. This prevents the lockout element from being moved from the receptive to the locked condition unintentionally. Thus, it is thereby ensured that the dispense interface remains attachable as long as it has not been used. 
         [0038]    It is furthermore preferred, that the lockout element is configured such that when said dispense interface is attached to said drug delivery device, a distal portion of the drug delivery device acts on said bearing section such that said shaped element is released out of engagement with said retaining element. 
         [0039]    Thus, by attaching the dispense interface to the drug delivery device the shaped element may reliably released out of engagement with the retaining element. In this released condition the lockout element is in its activated condition, in which it moves automatically to the locked condition when the dispense interface is detached from the drug delivery device. 
         [0040]    Hence, in the released condition the spring element is no longer retained in its strained condition by the positive engagement of the shaped element and the retaining element. However, the spring element is further held in its strained condition by the distal portion of the drug delivery device acting on the bearing portion as long as the dispense interface is attached to the drug delivery device. As soon as the dispense interface is detached from the drug delivery device, the distal portion of the drug delivery device is retracted from the bearing portion, thus allowing the spring element, which is no longer held by the release section, to relax. 
         [0041]    Furthermore, in the engagement condition of the shaped element and the retaining element, the release section of the lockout element may be in a strained condition. Consequently, by releasing the shaped element out of engagement with the retaining element, the release section may relax, thus maintaining or securing the released condition. 
         [0042]    It is moreover preferred, that the lockout element is attached to the inner body by a connecting element. The attachment of the lockout element to the inner body may thereby be safely maintained particularly in the locked condition. This prevents an inadvertent removal of the lockout element from the inner body and accordingly further reduces the risk of reattachment of the dispense interface after it has been used. 
         [0043]    The connecting element may be formed as an edge section, which is in engagement with a corresponding surface section of the inner body. Likewise the connection section may comprise a recess, through which a protrusion of the inner body at least partially protrudes. According to a further embodiment, the connection section may be formed by a connecting portion, which is engaged with an undercut of the inner body. In any of the mentioned embodiments of the connecting element, an at least partly positive fit with the inner body may be provided. 
         [0044]    The dispense interface may be produced cost effectively, in case the lockout element is formed as one piece. Preferably the lockout element may be formed from metal, particularly from a flat metal. Likewise the lockout element may be formed from plastic material, particularly from a flat plastic material. 
         [0045]    According to a further embodiment, the spring element and the release section adjoin the bearing section independently. This allows the spring element and the release section to be designed independently, whereby optimal use properties of the lockout element may be achieved. 
         [0046]    According to another embodiment, the release section adjoins the spring element and the bearing section is provided on the spring element. This embodiment allows the lockout element to be designed in a particularly simple manner and therefore be manufactured cost-effectively. 
         [0047]    It is especially advantageous if the support section is provided on the release section, whereby likewise a simple constructive design and therefore a cost-effective manufacturability may be ensured. 
         [0048]    The dispense interface is preferably configured to be used with a drug delivery device, in particular with a drug delivery device mentioned at the beginning, whereby the dispense interface is removably attached to the drug delivery device. By detaching the dispense interface from the drug delivery device, it may, due to the lockout element moving to the locked condition, not be reattached to the drug delivery device. The risk of contamination from residual drug components within the dispense interface is thus eliminated. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0049]    These as well as other advantages of various aspects of the present invention will become apparent to those of ordinary skill in the art by reading the following detailed description, with appropriate reference to the accompanying drawings, in which: 
           [0050]      FIG. 1  illustrates a perspective view of a delivery device with an end cap of the device removed; 
           [0051]      FIG. 2  illustrates a perspective view of the delivery device distal end showing the cartridge; 
           [0052]      FIG. 3  illustrates a perspective view of the delivery device illustrated in  FIG. 1  or  2  with one cartridge retainer in an open position; 
           [0053]      FIG. 4  illustrates a dispense interface and a dose dispenser that may be removably mounted on a distal end of the delivery device illustrated in  FIG. 1 ; 
           [0054]      FIG. 5  illustrates the dispense interface and the dose dispenser illustrated in  FIG. 4  mounted on a distal end of the delivery device illustrated in  FIG. 1 ; 
           [0055]      FIG. 6  illustrates one arrangement of a needle assembly that may be mounted on a distal end of the delivery device; 
           [0056]      FIG. 7  illustrates a perspective view of the dispense interface illustrated in  FIG. 4 ; 
           [0057]      FIG. 8  illustrates another perspective view of the dispense interface illustrated in  FIG. 4 ; 
           [0058]      FIG. 9  illustrates a cross-sectional view of the dispense interface illustrated in  FIG. 4 ; 
           [0059]      FIG. 10  illustrates an exploded view of the dispense interface illustrated in  FIG. 4 ; 
           [0060]      FIG. 11  illustrates a cross-sectional view of the dispense interface and needle assembly mounted onto a drug delivery device, such as the device illustrated in  FIG. 1 ; 
           [0061]      FIG. 12  illustrates a perspective view of the dispense interface with an inner body and a lockout element; 
           [0062]      FIG. 13  illustrates an exploded view of the dispense interface illustrated in  FIG. 12 ; 
           [0063]      FIG. 14  illustrates a perspective view of a lockout element according to a first embodiment; 
           [0064]      FIG. 15  illustrates a side view of a lockout element according to a first embodiment in a receptive condition coupled to an inner body of the dispense interface; 
           [0065]      FIG. 16  illustrates a side view of a lockout element according to a first embodiment in a locked condition coupled to an inner body of the dispense interface; 
           [0066]      FIG. 17  illustrates a perspective view of a lockout element according to a second embodiment in a receptive condition; 
           [0067]      FIG. 18  illustrates a side view of a lockout element according to a second embodiment in a receptive condition coupled to an inner body of the dispense interface; 
           [0068]      FIG. 19  illustrates a perspective view of a lockout element according to a second embodiment in an activated condition; 
           [0069]      FIG. 20  illustrates a side view of a lockout element according to a second embodiment in an activated condition coupled to an inner body of the dispense interface; 
           [0070]      FIG. 21  illustrates a perspective view of a lockout element according to a second embodiment in a locked condition; 
           [0071]      FIG. 22  illustrates a side view of a lockout element according to a second embodiment in a locked condition coupled to an inner body of the dispense interface; 
           [0072]      FIG. 23  illustrates a perspective view of a lockout element according to a third embodiment in a receptive condition coupled to an inner body of the dispense interface; 
           [0073]      FIG. 24  illustrates a side view of a lockout element according to a third embodiment in a receptive condition coupled to an inner body of the dispense interface; 
           [0074]      FIG. 25  illustrates a perspective view of a lockout element according to a third embodiment in an activated condition coupled to an inner body of the dispense interface; 
           [0075]      FIG. 26  illustrates a side view of a lockout element according to a third embodiment in an activated condition coupled to an inner body of the dispense interface; 
           [0076]      FIG. 27  illustrates a perspective view of a lockout element according to a third embodiment in a locked condition coupled to an inner body of the dispense interface; 
           [0077]      FIG. 28  illustrates a side view of a lockout element according to a third embodiment in a locked condition coupled to an inner body of the dispense interface. 
       
    
    
     DETAILED DESCRIPTION 
       [0078]    The drug delivery device illustrated in  FIG. 1  comprises a main body  14  that extends from a proximal end  16  to a distal end  15 . At the distal end  15 , a removable end cap or cover  18  is provided. This end cap  18  and the distal end  15  of the main body  14  work together to provide a snap fit or form fit connection so that once the cover  18  is slid onto the distal end  15  of the main body  14 , this frictional fit between the cap and the main body outer surface  20  prevents the cover from inadvertently falling off the main body. 
         [0079]    The main body  14  contains a micro-processor control unit, an electro-mechanical drive train, and at least two medicament reservoirs. When the end cap or cover  18  is removed from the device  10  (as illustrated in  FIG. 1 ), a dispense interface  200  is mounted to the distal end  15  of the main body  14 , and a dose dispenser (e.g., a needle assembly) is attached to the interface. The drug delivery device  10  can be used to administer a computed dose of a second medicament (secondary drug compound) and a variable dose of a first medicament (primary drug compound) through a single needle assembly, such as a double ended needle assembly. 
         [0080]    The drive train may exert a pressure on the bung of each cartridge, respectively, in order to expel the doses of the first and second medicaments. For example, a piston rod may push the bung of a cartridge forward a pre-determined amount for a single dose of medicament. When the cartridge is empty, the piston rod is retracted completely inside the main body  14 , so that the empty cartridge can be removed and a new cartridge can be inserted. 
         [0081]    A control panel region  60  is provided near the proximal end of the main body  14 . Preferably, this control panel region  60  comprises a digital display  80  along with a plurality of human interface elements that can be manipulated by a user to set and inject a combined dose. In this arrangement, the control panel region comprises a first dose setting button  62 , a second dose setting button  64  and a third button  66  designated with the symbol “OK.” In addition, along the most proximal end of the main body, an injection button  74  is also provided (not visible in the perspective view of  FIG. 1 ). 
         [0082]    The cartridge holder  40  can be removably attached to the main body  14  and may contain at least two cartridge retainers  50  and  52 . Each retainer is configured so as to contain one medicament reservoir, such as a glass cartridge. Preferably, each cartridge contains a different medicament. 
         [0083]    In addition, at the distal end of the cartridge holder  40 , the drug delivery device illustrated in  FIG. 1  includes a dispense interface  200 . As will be described in relation to  FIG. 4 , in one arrangement, this dispense interface  200  includes a main outer body  212  that is removably attached to a distal end  42  of the cartridge housing  40 . As can be seen in  FIG. 1 , a distal end  214  of the dispense interface  200  preferably comprises a needle hub  216 . This needle hub  216  may be configured so as to allow a dose dispenser, such as a conventional pen type injection needle assembly, to be removably mounted to the drug delivery device  10 . 
         [0084]    Once the device is turned on, the digital display  80  shown in  FIG. 1  illuminates and provides the user certain device information, preferably information relating to the medicaments contained within the cartridge holder  40 . For example, the user is provided with certain information relating to both the primary medicament (Drug A) and the secondary medicament (Drug B). 
         [0085]    As shown in  FIG. 3 , the first and second cartridge retainers  50 ,  52  may be hinged cartridge retainers. These hinged retainers allow user access to the cartridges.  FIG. 3  illustrates a perspective view of the cartridge holder  40  illustrated in  FIG. 1  with the first hinged cartridge retainer  50  in an open position.  FIG. 3  illustrates how a user might access the first cartridge  90  by opening up the first retainer  50  and thereby having access to the first cartridge  90 . 
         [0086]    As mentioned above when discussing  FIG. 1 , a dispense interface  200  is coupled to the distal end of the cartridge holder  40 .  FIG. 4  illustrates a flat view of the dispense interface  200  unconnected to the distal end of the cartridge holder  40 . A dose dispenser or needle assembly that may be used with the interface  200  is also illustrated and is provided in a protective outer cap  420 . 
         [0087]    In  FIG. 5 , the dispense interface  200  illustrated in  FIG. 4  is shown coupled to the cartridge holder  40 . The axial attachment means between the dispense interface  200  and the cartridge holder  40  can be any known axial attachment means to those skilled in the art, including snap locks, snap fits, snap rings, keyed slots, and combinations of such connections. The connection or attachment between the dispense interface and the cartridge holder may also contain additional features (not shown), such as connectors, stops, splines, ribs, grooves, pips, clips and the like design features, that ensure that specific hubs are attachable only to matching drug delivery devices. Such additional features would prevent the insertion of a non-appropriate secondary cartridge to a non-matching injection device. 
         [0088]      FIG. 5  also illustrates the needle assembly  400  and protective cover  420  coupled to the distal end of the dispense interface  200  that may be screwed onto the needle hub of the interface  200 .  FIG. 6  illustrates a cross sectional view of the double ended needle assembly  402  mounted on the dispense interface  200  in  FIG. 5 . 
         [0089]    The needle assembly  400  illustrated in  FIG. 6  comprises a double ended needle  406  and a hub  401 . The double ended needle or cannula  406  is fixedly mounted in a needle hub  401 . This needle hub  401  comprises a circular disk shaped element which has along its periphery a circumferential depending sleeve  403 . Along an inner wall of this hub member  401 , a thread  404  is provided. This thread  404  allows the needle hub  401  to be screwed onto the dispense interface  200  which, in one preferred arrangement, is provided with a corresponding outer thread along a distal hub. At a center portion of the hub element  401  there is provided a protrusion  402 . This protrusion  402  projects from the hub in an opposite direction of the sleeve member. A double ended needle  406  is mounted centrally through the protrusion  402  and the needle hub  401 . This double ended needle  406  is mounted such that a first or distal piercing end  405  of the double ended needle forms an injecting part for piercing an injection site (e.g., the skin of a user). 
         [0090]    Similarly, a second or proximal piercing end  406  of the needle assembly  400  protrudes from an opposite side of the circular disc so that it is concentrically surrounded by the sleeve  403 . In one needle assembly arrangement, the second or proximal piercing end  406  may be shorter than the sleeve  403  so that this sleeve to some extent protects the pointed end of the back sleeve. The needle cover cap  420  illustrated in  FIGS. 4 and 5  provides a form fit around the outer surface  403  of the hub  401 . 
         [0091]    Referring now to  FIGS. 4 to 11 , one preferred arrangement of this interface  200  will now be discussed. In this one preferred arrangement, this interface  200  comprises: 
         [0092]    a. a main outer body  210 , 
         [0093]    b. an first inner body  220 , 
         [0094]    c. a second inner body  230 , 
         [0095]    d. a first piercing needle  240 , 
         [0096]    e. a second piercing needle  250 , 
         [0097]    f. a valve seal  260 , and 
         [0098]    g. a septum  270 . 
         [0099]    The main outer body  210  comprises a main body proximal end  212  and a main body distal end  214 . At the proximal end  212  of the outer body  210 , a connecting member is configured so as to allow the dispense interface  200  to be attached to the distal end of the cartridge holder  40 . Preferably, the connecting member is configured so as to allow the dispense interface  200  to be removably connected the cartridge holder  40 . In one preferred interface arrangement, the proximal end of the interface  200  is configured with an upwardly extending wall  218  having at least one recess. For example, as may be seen from  FIG. 8 , the upwardly extending wall  218  comprises at least a first recess  217  and a second recess  219 . 
         [0100]    Preferably, the first and the second recesses  217 ,  219  are positioned within this main outer body wall so as to cooperate with an outwardly protruding member located near the distal end of the cartridge housing  40  of the drug delivery device  10 . For example, this outwardly protruding member  48  of the cartridge housing may be seen in  FIGS. 4 and 5 . A second similar protruding member is provided on the opposite side of the cartridge housing. As such, when the interface  200  is axially slid over the distal end of the cartridge housing  40 , the outwardly protruding members will cooperate with the first and second recess  217 ,  219  to form an interference fit, form fit, or snap lock. Alternatively, and as those of skill in the art will recognize, any other similar connection mechanism that allows for the dispense interface and the cartridge housing  40  to be axially coupled could be used as well. 
         [0101]    The main outer body  210  and the distal end of the cartridge holder  40  act to form an axially engaging snap lock or snap fit arrangement that could be axially slid onto the distal end of the cartridge housing. In one alternative arrangement, the dispense interface  200  may be provided with a coding feature so as to prevent inadvertent dispense interface cross use. That is, the inner body of the hub could be geometrically configured so as to prevent an inadvertent cross use of one or more dispense interfaces. 
         [0102]    A mounting hub is provided at a distal end of the main outer body  210  of the dispense interface  200 . Such a mounting hub can be configured to be releasably connected to a needle assembly. As just one example, this connecting means  216  may comprise an outer thread that engages an inner thread provided along an inner wall surface of a needle hub of a needle assembly, such as the needle assembly  400  illustrated in  FIG. 6 . Alternative releasable connectors may also be provided such as a snap lock, a snap lock released through threads, a bayonet lock, a form fit, or other similar connection arrangements. 
         [0103]    The dispense interface  200  further comprises a first inner body  220 . Certain details of this inner body are illustrated in  FIG. 8-11 . Preferably, this first inner body  220  is coupled to an inner surface  215  of the extending wall  218  of the main outer body  210 . More preferably, this first inner body  220  is coupled by way of a rib and groove form fit arrangement to an inner surface of the outer body  210 . For example, as can be seen from  FIG. 9 , the extending wall  218  of the main outer body  210  is provided with a first rib  213   a  and a second rib  213   b.  This first rib  213   a  is also illustrated in  FIG. 10 . These ribs  213   a  and  213   b  are positioned along the inner surface  215  of the wall  218  of the outer body  210  and create a form fit or snap lock engagement with cooperating grooves  224   a  and  224   b  of the first inner body  220 . In a preferred arrangement, these cooperating grooves  224   a  and  224   b  are provided along an outer surface  222  of the first inner body  220 . 
         [0104]    In addition, as can be seen in  FIG. 8-10 , a proximal surface  226  near the proximal end of the first inner body  220  may be configured with at least a first proximally positioned piercing needle  240  comprising a proximal piercing end portion  244 . Similarly, the first inner body  220  is configured with a second proximally positioned piercing needle  250  comprising a proximally piercing end portion  254 . Both the first and second needles  240 ,  250  are rigidly mounted on the proximal surface  226  of the first inner body  220 . 
         [0105]    Preferably, this dispense interface  200  further comprises a valve arrangement. Such a valve arrangement could be constructed so as to prevent cross contamination of the first and second medicaments contained in the first and second reservoirs, respectively. A preferred valve arrangement may also be configured so as to prevent back flow and cross contamination of the first and second medicaments. 
         [0106]    In one preferred system, dispense interface  200  includes a valve arrangement in the form of a valve seal  260 . Such a valve seal  260  may be provided within a cavity  231  defined by the second inner body  230 , so as to form a holding chamber  280 . Preferably, cavity  231  resides along an upper surface of the second inner body  230 . This valve seal comprises an upper surface that defines both a first fluid groove  264  and second fluid groove  266 . For example,  FIG. 9  illustrates the position of the valve seal  260 , seated between the first inner body  220  and the second inner body  230 . During an injection step, this seal valve  260  helps to prevent the primary medicament in the first pathway from migrating to the secondary medicament in the second pathway, while also preventing the secondary medicament in the second pathway from migrating to the primary medicament in the first pathway. Preferably, this seal valve  260  comprises a first non-return valve  262  and a second non-return valve  268 . As such, the first non-return valve  262  prevents fluid transferring along the first fluid pathway  264 , for example a groove in the seal valve  260 , from returning back into this pathway  264 . Similarly, the second non-return valve  268  prevents fluid transferring along the second fluid pathway  266  from returning back into this pathway  266 . 
         [0107]    Together, the first and second grooves  264 ,  266  converge towards the non-return valves  262  and  268  respectively, to then provide for an output fluid path or a holding chamber  280 . This holding chamber  280  is defined by an inner chamber defined by a distal end of the second inner body both the first and the second non return valves  262 ,  268  along with a pierceable septum  270 . As illustrated, this pierceable septum  270  is positioned between a distal end portion of the second inner body  230  and an inner surface defined by the needle hub of the main outer body  210 . 
         [0108]    The holding chamber  280  terminates at an outlet port of the interface  200 . This outlet port  290  is preferably centrally located in the needle hub of the interface  200  and assists in maintaining the pierceable seal  270  in a stationary position. As such, when a double ended needle assembly is attached to the needle hub of the interface (such as the double ended needle illustrated in  FIG. 6 ), the output fluid path allows both medicaments to be in fluid communication with the attached needle assembly. 
         [0109]    The hub interface  200  further comprises a second inner body  230 . As can be seen from  FIG. 9 , this second inner body  230  has an upper surface that defines a recess, and the valve seal  260  is positioned within this recess. Therefore, when the interface  200  is assembled as shown in  FIG. 9 , the second inner body  230  will be positioned between a distal end of the outer body  210  and the first inner body  220 . Together, second inner body  230  and the main outer body hold the septum  270  in place. The distal end of the inner body  230  may also form a cavity or holding chamber that can be configured to be fluid communication with both the first groove  264  and the second groove  266  of the valve seal. 
         [0110]    Axially sliding the main outer body  210  over the distal end of the drug delivery device attaches the dispense interface  200  to the multi-use device. In this manner, a fluid communication may be created between the first needle  240  and the second needle  250  with the primary medicament of the first cartridge and the secondary medicament of the second cartridge, respectively. 
         [0111]      FIG. 11  illustrates the dispense interface  200  after it has been mounted onto the distal end  42  of the cartridge holder  40  of the drug delivery device  10  illustrated in  FIG. 1 . A double ended needle  400  is also mounted to the distal end of this interface. The cartridge holder  40  is illustrated as having a first cartridge containing a first medicament and a second cartridge containing a second medicament. 
         [0112]    When the interface  200  is first mounted over the distal end of the cartridge holder  40 , the proximal piercing end  244  of the first piercing needle  240  pierces the septum of the first cartridge  90  and thereby resides in fluid communication with the primary medicament  92  of the first cartridge  90 . A distal end of the first piercing needle  240  will also be in fluid communication with a first fluid path groove  264  defined by the valve seal  260 . 
         [0113]    Similarly, the proximal piercing end  254  of the second piercing needle  250  pierces the septum of the second cartridge  100  and thereby resides in fluid communication with the secondary medicament  102  of the second cartridge  100 . A distal end of this second piercing needle  250  will also be in fluid communication with a second fluid path groove  266  defined by the valve seal  260 . 
         [0114]      FIG. 11  illustrates a preferred arrangement of such a dispense interface  200  that is coupled to a distal end  15  of the main body  14  of drug delivery device  10 . Preferably, such a dispense interface  200  is removably coupled to the cartridge holder  40  of the drug delivery device  10 . 
         [0115]    As illustrated in  FIG. 11 , the dispense interface  200  is coupled to the distal end of a cartridge housing  40 . This cartridge holder  40  is illustrated as containing the first cartridge  90  containing the primary medicament  92  and the second cartridge  100  containing the secondary medicament  102 . Once coupled to the cartridge housing  40 , the dispense interface  200  essentially provides a mechanism for providing a fluid communication path from the first and second cartridges  90 ,  100  to the common holding chamber  280 . This holding chamber  280  is illustrated as being in fluid communication with a dose dispenser. Here, as illustrated, this dose dispenser comprises the double ended needle assembly  400 . As illustrated, the proximal end of the double ended needle assembly is in fluid communication with the chamber  280 . 
         [0116]    In one preferred arrangement, the dispense interface is configured so that it attaches to the main body in only one orientation, that is it is fitted only one way round. As such as illustrated in  FIG. 11 , once the dispense interface  200  is attached to the cartridge holder  40 , the primary needle  240  can only be used for fluid communication with the primary medicament  92  of the first cartridge  90  and the interface  200  would be prevented from being reattached to the holder  40  so that the primary needle  240  could now be used for fluid communication with the secondary medicament  102  of the second cartridge  100 . Such a one way around connecting mechanism may help to reduce potential cross contamination between the two medicaments  92  and  102 . 
         [0117]    Embodiments of a dispense interface with a lockout element and an inner body will be described in detail hereinafter. 
         [0118]      FIGS. 12 and 13  show a dispense interface  1200 . As may be seen from  FIG. 12  and the exploded view in  FIG. 13 , the dispense interface  1200  may comprise an outer body  1210  and in inner body  2000 . The inner body  2000  may be seated within an interior space defined by the outer main body  1210 . Preferably, it is the inner body  2000  of the dispense interface  1200  that is configured to be coupled to a distal end of a drug delivery device while also being securely positioned within an interior space defined by the outer body  1210 . The dispense interface  1200  may further comprise a manifold  2300 . 
         [0119]    As may be further be seen from  FIGS. 12 and 13  the dispense interface  2000  also comprises a lockout element in the form of a lockout spring  2600 . One reason that a lockout element  2600  may be incorporated into a dispense interface  1200 , is to ensure that once the dispense interface  1200  is removed from the drug delivery device, the dispense interface  1200  cannot be re-attached and used a second time. Preventing re-attachment tends to ensure that medicament is not allowed to reside in the dispense interface  1200  indefinitely and contaminate the drug delivered to the patient. 
         [0120]      FIG. 14  shows a first embodiment of a lockout element  6600  according to the invention, and  FIGS. 15 and 16  show and a dispense interface  6605  comprising a lockout element  6600  according to the invention. 
         [0121]    Specifically,  FIG. 14  illustrates a perspective view of a lockout element  6600  in the form of a platform spring. The lockout element  6600  is formed as one piece from a flexible material such as a suitable plastic material or a suitable metal material. The lockout element  6600  comprises a bearing section  6602  in the form of a platform, which provides the lockout functionality of the lockout element  6600 . Thus the bearing section  6602  in the form of a platform is configured to bear a distal portion of a drug delivery device, to which the dispense interface  6605  may be attached. 
         [0122]    Further to this, the lockout element  6600  comprises release sections  6604  and  6606 , which adjoin the bearing section  6602  on opposite sides. Thereby, shaped elements  6608  and  6610  are formed on the release sections  6604  and  6606 . The shaped elements  6608  and  6610  are formed as recesses, which may be engaged with corresponding retaining elements  6612  and  6614  of the inner body  6607 . The retaining elements  6612  and  6614  may be formed as protrusions as shown in  FIGS. 15 and 16 . 
         [0123]    At the free end of the release sections  6604  and  6606  support sections  6616  and  6618  are provided, which may engage support surfaces  6620  and  6622  of the outer body  6609 , as illustrated in  FIG. 16 . 
         [0124]    The lockout element  6600  also comprises two spring elements  6624  and  6626 , which adjoin the bearing section  6602  on opposite sides of the lockout element  6600  independent of the release sections  6604  and  6606 . The spring elements  6624  and  6626  are formed as spring arms with each at least one curved section. Here, the spring element  6626  has a first curved section  6628  and a second curved section  6630  and the spring element  6618  has a first curved section  6632  and a second curved section  6634 . At the free ends of the spring elements  6624  and  6626  connecting elements  6636  and  6638  are formed as edges, which engage corresponding surfaces  6640  and  6642  of the outer body  6609 . Thereby the lockout element  6600  is securely connected to the outer body  6609  of the dispense interface  6605 . 
         [0125]      FIG. 15  illustrates a dispense interface  6605  comprising a platform spring lockout element  6600  in the receptive condition. In this illustrated arrangement, the platform lockout element  6600  is held in a strained state on assembly. Thus, the spring arms  6624  and  6626  are in a strained condition and the shaped elements  6608  and  6610  of the release sections  6604  and  6606  are in engagement with the retaining elements  6612  and  6614 . Further, the bearing section  6602  is in an open position, in which the dispense interface  6605  is attachable to a drug delivery device. 
         [0126]    Upon fitting the dispense interface  6605  to the distal end of a drug delivery device, a distal portion of the drug delivery device acts on the bearing section  6602 , whereby the shaped elements  6608  and  6610  are released out of engagement with the retaining elements  6612  and  6614 . The lockout element  6600  is thus moved into an activated condition. In this activated condition the spring elements  6624  and  6626  remain strained by the distal portion of the drug delivery device acting on the bearing section  6602  as long as the dispense interface remains attached to the drug delivery device. 
         [0127]    When the dispense interface  6605  is detached from the drug delivery device, the distal portion of the drug delivery device is retracted from the bearing section  6602 . Since in this condition the shaped elements  6608  and  6610  are released out of engagement with the retaining elements  6612  and  6614 , the spring elements  6624  and  6626  are enabled to relax. The lockout element  6600  is thereby moved into the locked condition, which is illustrated in  FIG. 16 . 
         [0128]    In the locked condition of the lockout element  6600  the bearing section  6602  is moved to a blocking position, in which the release sections  6604  and  6606  with their support sections  6616  and  6618  are in engagement with support surfaces  6620  and  6622 . By this engagement the bearing section  6602  is prevented from being moved from the blocking position back into the open position, thus the lockout element  6600  is prevented from being moved back to the receptive condition. This ensures that the dispense interface  6605  is not reattached to a drug delivery device after it has been used. 
         [0129]      FIGS. 17 ,  19  and  21  show a second embodiment of a lockout element  6800  according to the invention, and  FIGS. 18 ,  20  and  22  show a dispense interface  6805  comprising a lockout element  6800  according to the invention. 
         [0130]    As illustrated in  FIG. 17 , the lockout element  6800  is formed as a lockout spring as one piece from a flexible material such as a suitable plastic material or a suitable metal material. 
         [0131]    The lockout element  6800  comprises spring elements  6802  and  6804 , which are formed as spring arms and which are pivotably positioned near to a center portion  6806  of the locking member  6800 . The center portion  6806  of the locking member  6800  further comprises connecting elements  6808  and  6810  in the form of recesses, which engage a non-return clip or a protrusion  6812  provided along the external surface of the inner body  6807  of the dispense interface  6805 , as illustrated in  FIG. 18 . Thereby the lockout element  6800  is securely connected to the inner body  6807 . 
         [0132]    The spring elements  6802  and  6804  further comprise bearing sections  6814  and  6816  for bearing a distal portion of a drug delivery device. Thus the bearing sections  6814  and  6816  provide the lockout functionality of the lockout element  6800 . 
         [0133]    Furthermore, the lockout element  6800  comprises release sections  6818  and  6820 , which adjoin the bearing sections  6814  and  6816 . Thereby, shaped elements  6822  and  6824  are formed on the release sections  6818  and  6820 . The shaped elements  6822  and  6824  are formed as recesses, which may be engaged with corresponding retaining elements  6826  and  6828  of the inner body  6807 , whereas the retaining elements  6826  and  6828  may be formed as protrusions as shown in  FIGS. 18 ,  20  and  22 . 
         [0134]    At the free end of the release sections  6818  and  6820  support sections  6830  and  6832  are provided, which may engage support surfaces  6834  and  6836  of the outer body  6809 , as illustrated in  FIG. 22 . 
         [0135]      FIGS. 17 and 18  illustrate the lockout element  6800  in a receptive condition, in which the dispense interface  6805  is attachable to a drug delivery device. As can be seen from  FIG. 18  particularly, in the receptive condition, the spring elements  6802  and  6804  of the locking element  6800  reside slightly above the top surface of the inner body  6807  with the connecting element  6808  engaged with the non-return clip  6812 . In this position, the spring elements  6802  and  6804  are strained in a proximal direction and the bearing sections  6814  and  6816  are in their open position. However, the shaped elements  6822  and  6824  of the release sections  6818  and  6820  are engaged with the retaining elements  6826  and  6828  of the inner body  6807  and thereby prevent the spring elements to relax. Thus, the bearing sections are also prevented from moving to the blocking position. 
         [0136]      FIGS. 19 and 20  illustrate a side view of locking member  6800  within the dispense interface  6805  in the activated condition, wherein  FIG. 20  shows the locking member  6800  connected to the inner body  6807 . To activate the locking member  6800 , the distal end of the drug delivery device is inserted into the dispense interface  6805  and a distal portion of the drug delivery device will act on the bearing sections  6814  and  6816  provided on the spring elements  6802  and  6804 . Thereby the shaped elements  6822  and  6824  are released out of engagement with the retaining elements  6626  and  6628 . The lockout element  6800  is thus moved into an activated condition. In this activated condition the spring elements  6802  and  6804  remain strained by the distal portion of the drug delivery device acting on the bearing sections  6814  and  6816  as long as the dispense interface remains attached to the drug delivery device. 
         [0137]      FIG. 21  illustrates a perspective view of the lockout element  6800  in a locked condition and  FIG. 22  illustrates this lockout element  6800  within the dispense interface  6805  in the locked condition. The lockout element  6800  moves from the activated to the locked condition when the dispense interface  6805  is detached from the drug delivery device. Thereby the distal portion of the drug delivery device is retracted from the bearing sections  6814  and  6816 . Since in this condition the shaped elements  6822  and  6824  are released out of engagement with the retaining elements  6826  and  6828 , the spring elements  6802  and  6804  are enabled to relax. The lockout element  6800  is thereby moved into the locked condition, which is illustrated in  FIG. 22 . 
         [0138]    In the locked condition of the lockout element  6800  the bearing sections  6814  and  6816  are moved to a blocking position, in which the support sections  6830  and  6832  are in engagement with support surfaces  6834  and  6836  of the outer body  6809 . By this engagement the bearing sections  6814  and  6816  are prevented from being moved from the blocking position back into the open position, thus the lockout element  6800  is prevented from being moved back to the receptive condition. This ensures that the dispense interface  6805  is not reattached to a drug delivery device after it has been used. 
         [0139]      FIGS. 23 to 28  show a third embodiment of a dispense interface  7005  comprising a lockout element  7000  according to the invention. 
         [0140]    As illustrated in the perspective views in  FIGS. 23 ,  25  and  27 , the lockout element  7000  is formed as a lockout spring as one piece from a flexible material such as a suitable plastic material or a suitable metal material. 
         [0141]    The lockout element  7000  comprises a spring element  7002 , which is formed as a spring arm and is pivotably positioned near a center portion  7004  of the locking member  7000 . The center portion  7004  of the locking member  7000  further comprises a connecting element  7006  in the form of a material portion, which is engaged in an undercut provided on the inner body  7007  of the dispense interface  7005 , as illustrated in  FIGS. 24 ,  26  and  28 . Thereby the lockout element  7000  is securely connected to the inner body  7007 . 
         [0142]    The spring element  7002  further comprises bearing sections  7008  and  7010  for bearing a distal portion of a drug delivery device. Thus, the bearing sections  7008  and  7010  provide the lockout functionality of the lockout element  7000 . 
         [0143]    Furthermore, the lockout element  7000  comprises a release section  7012 , which adjoins the spring element  7002 . Thereby, a shaped element  7014  is formed on the release section  7012 . The shaped element  7014  is formed as a recess, which may be engaged with a corresponding retaining element  7016  of the inner body  7007 , whereas the retaining element  7016  may be formed as a protrusion as shown in  FIGS. 23 to 28 . At the free end of the release section  7014  a support section  7018  is provided, which may engage a support surface  7020  of the outer body  7009 , as illustrated in  FIG. 28 . 
         [0144]      FIGS. 23 and 24  illustrate the lockout element  7000  in a receptive condition, in which the dispense interface  7005  is attachable to a drug delivery device. As can be seen from  FIG. 24  particularly, in the receptive condition, the spring element  7002  of the locking element  7000  resides slightly above the center portion  7006  with the connecting element  7006  engaged with an undercut of the inner body  7007 . 
         [0145]    In this position, the spring element  7002  is strained in a proximal direction and the bearing sections  7008  and  7010  are in their open position. However, the shaped element  7014  of the release section  7012  is engaged with the retaining element  7016  of the inner body  7007  and thereby prevents the spring element  7002  to relax. Thus, the bearing sections  7008  and  7010  are also prevented from moving to the blocking position. 
         [0146]      FIGS. 25 and 26  illustrate the locking member  7000  within the dispense interface  7005  in the activated condition. To activate this locking member  7000 , the distal end of the drug delivery device is inserted into the dispense interface  7005  and a distal portion of the drug delivery device will act on the bearing sections  7008  and  7010  provided on the spring element  7002 . Thereby the shaped element  7014  is released out of engagement with the retaining element  7016 . The lockout element  7000  is thus moved into an activated condition. In this activated condition the spring element  7002  remains strained by the distal portion of the drug delivery device acting on the bearing sections  7008  and  7010  as long as the dispense interface  7005  remains attached to the drug delivery device. 
         [0147]      FIGS. 27 and 28  illustrate the lockout element  7000  within the dispense interface  7005  in the locked condition. The lockout element  7000  moves from the activated to the locked condition when the dispense interface  7005  is detached from the drug delivery device. Thereby the distal portion of the drug delivery device is retracted from the bearing sections  7008  and  7010 . Since in this condition the shaped element  7014  is released out of engagement with the retaining element  7016 , the spring element  7002  is enabled to relax. The lockout element  7000  is thereby moved into the locked condition, which is illustrated in  FIGS. 27 and 28 . 
         [0148]    In the locked condition of the lockout element  7000  the bearing sections  7008  and  7010  are in a blocking position, in which the release section  7012  with its support section  7018  is in engagement with support surface  7020  of the outer body  7009 . By this engagement the bearing sections  7008  and  7010  are prevented from being moved from the blocking position back into the open position, thus the lockout element  7000  is prevented from being moved back to the receptive condition. This ensures that the dispense interface  7005  is not reattached to a drug delivery device after it has been used. 
         [0149]    The term “drug” or “medicament”, as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound, 
         [0150]    wherein in one embodiment the pharmaceutically active compound has a molecular weight up to 1500 Da and/or is a peptide, a protein, 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, 
         [0151]    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, 
         [0152]    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, 
         [0153]    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 exedin-3 or exedin-4 or an analogue or derivative of exedin-3 or exedin-4. 
         [0154]    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. 
         [0155]    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 LysB28 ProB29 human insulin; B28-N-palmitoyl-LysB28 ProB29 human insulin; B30-N-myristoyl-ThrB29 LysB30 human insulin; B30-N-palmitoyl-ThrB29 LysB30 human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyhepta-decanoyl) human insulin. 
         [0156]    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-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2. 
         [0157]    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 [Asp28] Exendin-4 (1-39),   des Pro36 [IsoAsp28] Exendin-4 (1-39),   des Pro36 [Met(O)14, Asp28] Exendin-4 (1-39),   des Pro36 [Met(O)14, IsoAsp28] Exendin-4 (1-39),   des Pro36 [Trp(O2)25, Asp28] Exendin-4 (1-39),   des Pro36 [Trp(O2)25, IsoAsp28] 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, IsoAsp28] Exendin-4 (1-39); or   des Pro36 [Asp28] Exendin-4 (1-39),   des Pro36 [IsoAsp28] Exendin-4 (1-39),   des Pro36 [Met(O)14, Asp28] Exendin-4 (1-39),   des Pro36 [Met(O)14, IsoAsp28] Exendin-4 (1-39),   des Pro36 [Trp(O2)25, Asp28] Exendin-4 (1-39),   des Pro36 [Trp(O2)25, IsoAsp28] 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, IsoAsp28] 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
   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 0 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 Exedin-4 derivative.
   
 
         [0204]    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. 
         [0205]    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. 
         [0206]    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. 
         [0207]    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 70-110 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. 
         [0208]    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. 
         [0209]    Distinct heavy chains differ in size and composition; α 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 (VH). 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, α 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 110 amino acids long and is composed of a single Ig domain. 
         [0210]    In mammals, there are two types of immunoglobulin light chain denoted by λ and ε. A light chain has two successive domains: one constant domain (CL) and one variable domain (VL). The approximate length of a light chain is 211 to 217 amino acids. Each antibody contains two light chains that are always identical; only one type of light chain, κ or λ, is present per antibody in mammals. 
         [0211]    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. 
         [0212]    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). 
         [0213]    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 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&#39;s Pharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology. 
         [0214]    Pharmaceutically acceptable solvates are for example hydrates.