Drug delivery device having needle guard mechanism with tunable threshold of resistance to needle guard movement

Abstract

To provide a device, method, and system for drug delivery.SOLUTION: A drug delivery device includes: a casing 110 for housing a drug storage container, where a dose delivery member extends through an opening in the casing; a needle guard 152 movable relative to the casing between extended and retracted positions, the portion of the dose delivery member being surrounded by the needle guard in the extended position and the portion of the dose delivery member being exposed when the needle guard is in the retracted position; and an interference mechanism 154 for providing a selected threshold of resistance to movement of the needle guard from the extended position to the retracted position during insertion of the dose delivery member into body tissue at an injection site, the interference mechanism having a first member associated with a surface within the casing, and a second member extending from the needle guard. When the drug delivery device is pressed toward the injection site, the interference mechanism causes the first member and the second member to slide past one another to allow the needle guard to move into the retracted position.SELECTED DRAWING: Figure 2A

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS Priority is claimed to U.S. Provisional Patent Application No. 62 / 121,758, filed February 27, 2015, the entire contents of which are incorporated herein by reference.

[0002] Field of Disclosure The present disclosure relates to a drug delivery device, and more particularly to a drug delivery device with a needle guard mechanism having an interference feature that allows for an adjustable threshold of resistance to needle guard movement that must be overcome by a patient or operator to effect needle insertion. [Background technology]

[0003] Medication, including but not limited to biologics for treating rheumatoid arthritis, psoriasis, dyslipidemia, osteoporosis, and other conditions, may be delivered to the subcutaneous, intramuscular, or intradermal space of a patient. Drug delivery devices, such as syringes, injectors, and auto-injectors, may be used to deliver such medications by injection.

[0004] Injectors and auto-injectors (injectors) are preferred for the delivery of many types of therapeutic agents, in part because they incorporate safety features that traditional syringes do not, such as the desire to protect against inadvertent needle sticks and unintentional administration of medication during handling of the injector.

[0005] Syringes can be shipped with a needle shield in place. The needle shield acts as a seal to maintain the sterility of the injection needle and provides some protection against inadvertent needle sticks and unintended drug injection during handling of the syringe. However, the needle shield must be removed to allow drug delivery, thereby exposing the injection needle. The injection process requires handling of the syringe without the needle shield in place while positioning the needle and delivering the medication, presenting a safety risk of inadvertent needle sticks and unintended delivery prior to injection.

[0006] It is desirable in a syringe to provide protection against the risks posed by an exposed needle. As shown in FIG. 1, many syringes include a retractable needle guard 52 that surrounds the needle 24 to protect against inadvertent needle sticks and unintended medication administration after the needle shield 29 is removed. The needle guard 52 requires an input to expose the needle 24. This input represents the user's intent to expose or insert the needle for insertion. In the absence of an input, the needle guard 52 remains extended over the needle 24.

[0007] The needle guard 24 can protect against unintentional administration of medication by resisting forces attempting to expose and / or insert the injection needle until a threshold input is reached. Several prior art mechanisms have been developed to provide this resistance. For example, many of these mechanisms use springs to provide the resistance, as shown in FIG. 1 (spring 60). Other devices utilize automatic needle insertion mechanisms to provide the resistance. However, the use of springs or automatic needle insertion mechanisms increases the complexity of the drug delivery device and adds additional components to the device. In the case of automatic needle insertion mechanisms in particular, the increased complexity and therefore the potential for reduced syringe reliability and increased cost of the drug delivery device.

[0008] Automatic needle insertion mechanisms provide energy for inserting the injection needle. Some of these mechanisms may use one or more springs (hereafter springs). The springs provide potential energy for inserting the injection needle. Before being released, the springs store potential energy. When the springs are compressed, the potential energy increases until a release threshold is reached, and when they undergo acceleration and / or deceleration, the potential energy is converted into kinetic energy. When a syringe with an effective mass comes into contact with a spring with a resistive force, the kinetic energy determines the inertia as a function of the effective mass of the injection system and the velocity of the injection system at that effective mass. This inertia determines the speed and force of the needle insertion. Thus, the potential energy of the springs can be adjusted to provide an optimal speed and force of the needle insertion. One advantage of automatic needle insertion mechanisms is that the needle insertion process can be optimized.

[0009] Therefore, a drug delivery device with improved reliability, lower cost and optimized needle insertion is desired. Summary of the Invention

[0010] A drug delivery device, comprising: a housing for receiving a drug storage container including a dose delivery member, at least an insertion portion of the dose delivery member extending through an opening in the housing; a needle guard movable relative to the housing between an extended position and a retracted position, the insertion portion of the dose delivery member being surrounded by the needle guard in the extended position and the insertion portion of the dose delivery member being at least partially exposed when the needle guard is in the retracted position; and a needle guard movable relative to the housing between an extended position and a retracted position, the needle guard being movable relative to the housing between an extended position and a retracted position, the insertion portion of the dose delivery member being surrounded by the needle guard in the extended position and the insertion portion of the dose delivery member being at least partially exposed when the needle guard is in the retracted position; 1. A drug delivery device comprising: an interference mechanism for providing a selected threshold resistance to movement of the needle guard, the detent mechanism comprising a first member associated with a surface within the housing and a second member extending from the needle guard, the first and second members engaging each other to hold the needle guard in the extended position, and one of the first and second members moving when the drug delivery device is pressed towards an injection site during insertion of the dose delivery member toward the injection site if a selected threshold resistance force is exceeded to slide the first and second members past each other to move the needle guard to the retracted position.

[0011] Further, a method of administering a drug includes providing a delivery device comprising a housing, a guard and an interference mechanism, the housing enclosing a drug reservoir, the drug reservoir including a dose delivery member extending at least partially through an opening in the housing, the guard being movable relative to the housing between an extended position and a retracted position, the dose delivery member being concealed by the guard in the extended position and the dose delivery member being exposed when the guard is in the retracted position, the interference mechanism comprising a first member associated with a surface within the housing and a second member extending from the guard. and pressing the guard against body tissue at an injection site to insert the dosage delivery member into the body tissue, the interference mechanism providing a threshold resistance force against movement of the needle guard from the extended position, and one of the first and second members moving when the threshold resistance force is exceeded causing the guard to begin moving toward the housing to a retracted position and causing the first and second members to slide past each other.

[0012] The same reference numbers are used in the drawings to identify the same or similar elements and structures of the various embodiments. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a front view in partial cross-section of a prior art drug delivery device. [Figure 2A] 1 is a front view in partial section of an embodiment of a drug delivery device according to the present disclosure. [Figure 2B] FIG. 2C is a front view in partial section of the drug delivery device of FIG. 2B after completed needle insertion. [Figure 3A] 1A-1C are front views showing cross sections of an embodiment of a needle guard mechanism of a drug delivery device and an embodiment of an interference mechanism of the needle guard mechanism. [Figure 3B] 3B is a cross-sectional view of the interior of a housing of a drug delivery device showing an embodiment of a cam element of the interference mechanism shown in FIG. 3A. [Figure 3C] 3B is a cross-sectional view of the interior of a housing of a drug delivery device illustrating another embodiment of a cam element of the interference mechanism shown in FIG. 3A. [Figure 3D] FIG. 3B is a perspective view of the needle guard illustrating an embodiment of a cam follower of the interference mechanism shown in FIG. 3A. [Figure 4] FIG. 13 is a front view showing a cross section of a needle guard mechanism of a drug delivery device illustrating another embodiment of an interference mechanism. [Diagram 5] FIG. 13 is a front view showing a cross section of a needle guard mechanism of a drug delivery device illustrating another embodiment of an interference mechanism. [Figure 6] 13A-13C are front views showing cross sections of another embodiment of a needle guard mechanism of a drug delivery device and another embodiment of an interference mechanism of the needle guard mechanism. [Figure 7A] 13A-13C are front views showing a cross section of another embodiment of a needle guard mechanism and an interference mechanism and their operation. [Figure 7B] 13A-13C are front views showing a cross section of another embodiment of a needle guard mechanism and an interference mechanism and their operation. [Figure 8] 1 is a graph plotting force versus distance for a syringe with a conventional manual spring-loaded needle insertion mechanism. [Figure 9] 1 is a graph plotting force versus distance for a syringe with a conventional automatic needle insertion mechanism. [Figure 10] 13 is a graph plotting force versus distance for an embodiment of a drug delivery device of the present disclosure including a needle guard having an interference feature. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] overview Disclosed herein is a drug delivery device. In various embodiments, the drug delivery device comprises: a housing configured to carry a drug reservoir including a dose delivery member, the housing having an opening, such that at least an insert portion of the dose delivery member is configured to extend through the opening of the housing; a needle guard disposed proximate the opening and movable relative to the housing between an extended position and a retracted position, the insert portion of the dose delivery member being surrounded by the needle guard in the extended position and the insert portion of the dose delivery member being at least partially exposed when the needle guard is in the retracted position; and a needle guard for attaching the dose delivery member to an injection site. and an interference mechanism for providing a selected threshold resistance force against movement of the needle guard from the extended position to the retracted position during insertion into body tissue, the interference mechanism comprising a first member attached to a surface of the housing and a second member extending from the needle guard, the first and second members engaging each other to hold the needle guard in the extended position, and one of the first and second members moving when the drug delivery device is pressed towards an injection site during insertion of the dose delivery member if a selected threshold resistance force is exceeded causing the first and second members to slide past each other and move the needle guard to the retracted position.

[0015] Further disclosed herein is a method of administering a drug, comprising providing a delivery device comprising a housing, a needle guard and an interference mechanism, the housing containing a drug reservoir, the drug reservoir including a dose delivery member extending at least partially through an opening in the housing, the needle guard being movable relative to the housing between an extended position and a retracted position, the dose delivery member being concealed by the needle guard in the extended position and the dose delivery member being exposed when the needle guard is in the retracted position, the interference mechanism comprising a first member associated with a surface within the housing and a second member extending from the needle guard; The first and second members engage with each other to hold the needle guard in an extended position; and pressing the needle guard against body tissue to insert the dosage delivery member into the body tissue at an injection site, the interference mechanism providing a threshold resistance force against movement of the needle guard from the extended position, and one of the first and second members moving when the threshold resistance force is exceeded causing the needle guard to begin moving toward the housing to the retracted position and sliding the first and second members past each other.

[0016] Still further disclosed herein is a medical device comprising: a housing configured to carry a drug storage container including a dose delivery member for delivering a dose of a drug to a patient; a needle guard disposed proximate an opening in the housing for extending the dose delivery member, the needle guard being movable relative to the housing between an extended position to enclose the dose delivery member and a retracted position to expose the dose delivery member; and an interference mechanism providing a selected threshold resistive force that must be overcome to move the needle guard from the extended position to the retracted position, the interference mechanism comprising: A drug delivery device comprising a first member attached to a surface of the housing and a second member attached to the needle guard, the first member and second member contacting each other when the needle guard is in an extended position, and an interference mechanism, at least one of the first member and second member being carried by a flexible arm such that upon application of an axial force pressing the needle guard from the extended position toward the retracted position, the flexible arm deflects to move the attached first member and / or second member radially away from the other, causing the first member and second member to slide past each other.

[0017] Detailed Description FIG. 2A illustrates an embodiment of a portable drug delivery device 100 according to the present disclosure. The device includes a needle guard mechanism 150 with an adjustable threshold of resistance to movement of the needle guard 152 to effect and optimize needle insertion, speed, and force. The drug delivery device 100 can be configured as a single-use disposable syringe or a multiple-use reusable syringe. The drug delivery device 100 can be configured to deliver any suitable medicine or drug, including those having viscosities that can range, for example, from about 1 to 200 centipoise. Additionally, the drug delivery device 100 can be configured as an auto-injector for self-administration, although such devices can also be used to inject by a caregiver or a formally trained healthcare provider. Referring to FIG. 2A, the drug delivery device 100 of various embodiments can further include an elongated housing or external housing 110 that holds a drug storage device 120. The drug storage device 120 of various embodiments may comprise a primary container 122, a stopper 126 movably disposed in an interior chamber 122c of the primary container 122 for releasing a medicine or drug 128 contained therein, and an injection needle 124 (as shown), cannula or other suitable dose delivery member or element capable of penetrating body tissue and administering the drug to a patient's body. In some embodiments, the drug storage device 120 may comprise a conventional glass or plastic syringe or cartridge. A removable shield 129 may be placed over the injection needle 124 to keep it sterile prior to use of the drug delivery device 100. The drug storage device 120 may be pre-filled with one or more doses of medicine or drug 128.

[0018] In various embodiments, the inner surface 112 of the housing 110 has one or more support members 114 capable of fixedly holding the drug storage device 120 within the outer housing 110 with at least an insertion portion of the injection needle 124 extending through an opening 110o defined in the distal end 110de of the housing 110.

[0019] 2A, various embodiments of the drug delivery device 100 may further include an injection drive mechanism 130 and a drive trigger mechanism 140. The injection drive mechanism 130 may be disposed within the housing 110 and, in some embodiments, may include a plunger 132 and a plunger drive spring 134 to urge the plunger 132 through the primary reservoir 122 of the drug storage device 120 to inject or dispense a drug. The plunger 132 and plunger drive spring 134 may be configured such that the plunger 132 extends through the plunger drive spring 134 with one end of the spring 134 engaged with a head member 138 of the plunger 132 and the other end of the spring 134 engaged with the drive trigger mechanism 140. Prior to actuation of the injection drive mechanism 130, in some embodiments, the plunger 132 is positioned adjacent the opening 122o of the primary reservoir 122 of the drug storage device 120 with the spring 134 compressed between the head member 138 of the plunger 132 and the drive trigger mechanism 140. When the injection drive mechanism 130 is actuated by the drive trigger mechanism 140, the plunger drive spring 134 expands, propelling the plunger 132 through the primary reservoir 122 of the drug storage device 120 and driving the stopper 126 through the primary reservoir 122 to expel the drug 128 through the injection needle 124.

[0020] In other embodiments, the injection drive mechanism 130 of the drug delivery device 100 may comprise an electrical / mechanical mechanism (not shown) including one or more motors and / or solenoids and a drive train or power transmission device, or a mechanism that generates or releases a pressurized gas or liquid (not shown) to propel the plunger 132. Such injection drive mechanisms are known in the art. In further embodiments, the injection drive mechanism 130 may comprise a mechanical mechanism that generates or releases a pressurized gas or fluid (not shown) that acts directly on the stopper 126 to move it through the primary container 122 and release the drug 128 from the primary container through the injection needle 124. Such injection drive mechanisms are known in the art.

[0021] 2A, the actuation trigger mechanism 140 may be disposed within the housing 110 and may include an activation button 142 extending through an opening in a side of the housing 110, a plunger release arm 144 extending from the activation button 142, and a trigger spring 148 disposed between the plunger release arm 144 and the inner surface 112 of the housing 110. The activation button 142 allows the actuation trigger mechanism 140 to be actuated by a patient or other operator, thereby actuating the injection actuation mechanism 130. The plunger release arm 144 is movable between a plunger retention position and a plunger release position. In some embodiments, in the plunger retention position, the plunger release arm 144 holds the plunger 143 in place via a detent 146. The detent 146 may include a protrusion 146p on the plunger release arm 144 and a recess 146r formed in a side of the plunger 132. In the plunger release position, the plunger release arm 144 disengages the detent protrusion 146p from the detent recess 146r, thereby releasing the plunger 132 and allowing it to be driven by the plunger drive spring 134. The trigger spring 148 applies a force that maintains the plunger release arm 144 in the plunger retaining position with the detent protrusion 146p and recess 146r engaged. When the activation button 142 is pressed, the force of the trigger spring 148 is overcome and the plunger release arm 144 is moved from the plunger retaining position to the plunger release position, thereby disengaging the detent 146 and releasing the plunger 132.

[0022] In other embodiments, the actuation trigger mechanism 140 may include an electrical / mechanical mechanism (not shown) including one or more switches, springs and / or sensors to activate the injection actuation mechanism 130. Such electrical / mechanical mechanisms are well known in the art.

[0023] 2A, the needle guard mechanism 150 of various embodiments includes a needle guard 152 movably disposed at the distal end 110de of the housing 110, and a detent or interference mechanism 154. The needle guard 152 can be biased to the position shown in FIG. 2A by a spring (not shown) similar to the spring 60 shown in FIG. 1. The interference mechanism 154 retracts and releases the needle guard 152 and holds the needle guard 152 in the extended position with an adjustable or selectable threshold resistance to the force of a patient or operator attempting to insert the injection needle 124 of the drug storage device 120 into body tissue, as shown in FIG. 2B, thereby optimizing the speed and force of needle insertion and preventing unintentional administration of medication after the needle shield 129 is removed.

[0024] The needle guard 152 in some embodiments can have a tubular configuration (extended position) that extends from the distal end 110de of the housing 110 and surrounds the insertion portion of the injection needle 124 to protect against inadvertent needle sticks. The needle guard 152 can be configured to be housed and retracted within the housing 110, as shown in FIG. 2B, or in other versions, can be configured to be retracted over the housing 110 (not shown).

[0025] The interference feature 154 in various embodiments can include a first member 1541 associated with the housing 110 and a second member 1542 associated with the needle guard 152. At least a portion of the first member 1541 and the second member 1542 engage with one another to hold the needle guard 152 in the extended position and provide a selected threshold resistance to movement or release of the needle guard 152. In some embodiments, one of the first member 1541 and the second member 1542 can be configured to move when an axial force applied to the drug delivery device 100 by a patient or operator pressing the drug delivery device 100 toward an injection site meets or exceeds a selected threshold resistance, such that the other of the first member 1541 and the second member 1542 slides past the other to release the needle guard 152 and pull the needle guard back toward the housing 110 to a retracted position for needle insertion, as shown in FIG. 2B.

[0026] 3A, in some embodiments, the interference mechanism 154 can include an over-center cam mechanism 254. The cam mechanism includes a fixed cam element 254c and one or more resiliently biased cam followers 254f. As shown in FIG. 3B, the fixed cam element 254c can include a circumferential bead 255 disposed on the inner surface 112 of the housing 110 proximate the opening 110o of the distal end 110de of the housing 110. The circumferential bead 255 can be continuous, as shown in FIG. 3B, or segmented, as shown in FIG. 3C. As shown in FIG. 3D, one or more of the resiliently biased cam followers 254f can include a flexible arm 256 extending from the proximal end 152pe of the needle guard 152 and a protrusion 257 disposed on the outwardly facing surface 152o of the flexible arm 256. As shown in FIG. 3A, one or more flexible arms 256 bias their corresponding protrusions 257 against a fixed circumferential bead cam element 255 (or multiple elements in a segmented embodiment).

[0027] 3A, the fixed cam element 254c of the housing 110 and the cam follower 254f of the needle guard 152 may be provided with curved (e.g., cammed or spherical) outer surfaces (e.g., profiles) to facilitate a sliding interaction during use of the drug delivery device 100. For example, when a user applies an axial force F p When a force is applied to the drug delivery device 100, a substantially equal and opposite axial force is applied to the needle guard 152, urging the needle guar 152 toward its retracted position. However, engagement of the cam element 254c with the cam follower 254f substantially prevents retraction until a selected threshold resistance force is overcome. That is, in the version of FIG. 3A, the threshold resistance force is equal to the force required to deflect the flexible arm 256 carrying the cam follower 254f away from the fixed cam element 254, thereby allowing the curved outer surface of the cam follower 254f to slide against and past the fixed cam element 254c. In FIG. 3A, the force applied by the user is F. pThis is shown as an axial force component F a and radial force component F r Thus, the axial force F applied by the user to overcome the threshold resistance force is p is the inherent resistive biasing force F of the flexible arm 256 b A radial force component F sufficient to overcome r The resistive biasing force F of the flexible arm 256 must be large enough to generate b depends primarily on the material comprising the arm 256 and the geometry of the arm 256 (eg, the length of the arm 256, the width of the arm 256, the thickness of the arm 256, the cross-sectional shape of the arm, etc.).

[0028] 4, various embodiments of the over-center cam mechanism 354 can include a circumferential bead 255 disposed on the inner surface 112 of the housing 110 as described above with respect to FIGS. 3A-3C, and one or more resiliently biased cam followers 356f configured as curvilinear grooves 357 formed in flexible arms 356 extending from the proximal end of the needle guard 152. The one or more flexible arms 356 bias their corresponding grooves 357 against the circumferential bead 255.

[0029] 5 illustrates one embodiment of an over-center cam mechanism, in which cam element 454c comprises a continuous or segmented circumferential groove 455 formed in inner surface 112 of housing 110 proximate opening 110o at distal end 110de of housing 110. In this embodiment, one or more flexible arms 256 bias their corresponding projections 257 against fixed circumferential groove 455.

[0030] 6, in a further embodiment, the needle guard 152 can be configured to retract over the exterior surface 113 of the housing 110. In such an embodiment, a fixed continuous or segmented circumferential bead 255 can be provided on the exterior surface 113 of the housing 110 and a protrusion 257 of a resiliently biased cam follower 254f can be provided on the interior surface 152i of the flexible arm 256.

[0031] 7A and 7B, in yet other embodiments, the needle guard 152 can include a fixed continuous or segmented circumferential bead 255 on its outer surface as described above, and the housing 110 can include one or more resiliently biased cam followers 254f including flexible arms 256 and protrusions 257.

[0032] The interference mechanism can be configured to provide a desired potential and kinetic energy as well as a desired inertia at the moment the needle contacts the body tissue. The force required to overcome the interference mechanism and the driven mass (device and patient / operator) represents the potential energy at the time of needle guard release. This potential energy, when subjected to acceleration / deceleration, is converted to kinetic energy as the interference mechanism releases the needle guard. When the needle contacts the resistant body tissue, the kinetic energy determines the speed and force of approach. By optimizing the potential and kinetic energy, the speed and force of needle insertion can be determined at the moment of needle contact. Thus, the patient experience is optimized to a level that can be comparable or better than an automatic needle insertion mechanism.

[0033] While each of the embodiments described above with reference to FIGS. 2A-7B include one or more resiliently biased cam followers relative to only one of the needle guard 152 (e.g., FIGS. 2A-6) or the housing 110 (e.g., FIGS. 7A-7B), other versions can include elements that are resiliently biased relative to both the needle guard 152 and the housing 110. For example, in one version, the housing 110 can include a plurality of segmented circumferential beads, each carried by a single flexible arm, and the needle guard 152 can include a corresponding number of cam followers, each carried by a single flexible arm. Of course, in other versions, the needle guard 152 can include a plurality of segmented circumferential beads, each carried by a single flexible arm, and the housing 110 can include a corresponding number of cam followers, each carried by a single flexible arm. In these alternative configurations, the flexible arms of the housing 110 and the needle guard 152 can be deflected simultaneously in response to forces attempting to overcome the resistance of the interference mechanism, thereby providing greater flexibility in patient-specific adjustment of the interference mechanism.

[0034] FIG. 8 is a graph plotting force versus distance for a syringe with a conventional manual spring-loaded needle insertion mechanism. Starting with zero time and force, the force can be observed to rise from about zero (although the residual force of the needle guard spring can be adjusted above zero to increase the starting force), and increases essentially linearly all the way until the needle emerges in the body tissue. In FIG. 8, the force to insert the needle is superimposed on the force of the needle guard spring. Thus, during needle insertion, the patient or operator is applying a force that overcomes both the force of the needle guard spring and the force to insert the needle into the body tissue. Once the needle approaches full insertion depth, a second mechanism appears to initiate automatic dosing. As shown in FIG. 8, this second mechanism appears with a sudden increase in the force. This indicates that the patient or operator can choose to provide further feedback and thus initiate dosing as a result of the increased force. However, dosing can continue without this further feedback to the patient or operator. This increase continues until a threshold force is reached and dosing is effected, at which point the force decreases with delivery.

[0035] FIG. 9 is a graph plotting applied force versus distance for a prior art syringe with a conventional automatic needle insertion mechanism. Starting with zero time and force, the force can be observed to rise from about zero (again, the starting force can be biased by adjusting the residual force of the resisting spring) and increase essentially linearly until the needle appears in the body tissue. In FIG. 9, the force to insert the needle is independent of the needle guard spring force. However, inertial effects are present and thus tend to be perceived as an additional force to overcome to keep the syringe in intimate contact with the body tissue. Once the needle approaches full insertion depth, the automatic mechanism continues to load the drug container to push the pre-volume through the needle. There is a residual force that is overcome during drug delivery to prevent the needle guard from extending and covering the needle. This residual force may also tend to push the needle out of the body tissue.

[0036] FIG. 10 is a graph plotting the applied force versus distance for an embodiment of the drug delivery device of the present disclosure with a needle guard having an interference mechanism. Starting with zero time and force, there is a relatively steep rise in the force required when the needle guard first contacts the body tissue. This rise represents the force to overcome the resistance provided by the interference mechanism. The magnitude of this force can be selectively adjusted via the interference mechanism to adjust the inertia available when the release of the needle guard occurs, thus tailoring the needle insertion experience to the patient's preferences. The adjustment can be made by adjusting one or more of the geometry, dimensions and elastic modulus of the elements of the interference mechanism. Dosing can be manual (as some patients undergoing certain treatments prefer) or automatic. In the case of automatic dosing, the dosing release (i.e., activation of the injection driver) can be done separately as shown in FIG. 10, or can be done simultaneously with the insertion start so that needle insertion and dosing start are simultaneous.

[0037] As can be seen from Figures 9 and 10, a syringe with a conventional automatic needle insertion mechanism has a force that is increased by the deflection of the needle guard and the compression of the needle guard spring. The force to release the guard occurs over a relatively long distance, so the patient or operator does not get a clear indication that the needle is close to the actuation position. In a preferred embodiment, the force (resistance) to release the guard occurs over a short distance, resulting in a stronger feedback to the patient or operator, indicating that the needle is approaching the needle insertion position. The duration of this actuation event can be adjusted via an interference mechanism in the needle guard mechanism to optimize the patient or operator experience.

[0038] Although the needle guard mechanism is disclosed herein with respect to portable drug delivery devices, the needle guard mechanism may also be used in on-body drug delivery devices, including syringes and autoinjectors, which are worn on the body of a patient.

[0039] In the above description, various systems and methods for use with a drug delivery device are described. It is apparent that the drug delivery device or method may further include using a pharmaceutical agent as listed below. However, it is noted that the following list should not be considered all-inclusive or limiting. The pharmaceutical agent is contained in a reservoir. In some examples, the reservoir is a primary container that is filled or pre-filled for treatment with the pharmaceutical agent. The primary container may be a cartridge or a pre-filled syringe.

[0040] For example, the drug delivery device, or more specifically the reservoir of the drug delivery device, may be loaded with a colony stimulating factor, such as granulocyte colony stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neupogen® (filgrastim) and Neulasta® (pegfilgrastim). In various other embodiments, the drug delivery device may be used with a variety of pharmaceutical products, such as erythropoiesis stimulating agents (ESAs). These products may be in liquid or lyophilized form. An ESA is any molecule that stimulates red blood cell production.ESAs include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neoreccormon®, and DMARD. ormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin and the following patents or patent applications: U.S. Patent No. 4,703,008; U.S. Patent No. 5,441,868; U.S. Patent No. 5,547,933; U.S. Patent No. 5,618,698; U.S. Patent No. 5,621,080; U.S. Patent No. 5,756,349; U.S. Patent No. 5,767,078; U.S. Patent No. 5,773,569; U.S. Patent No. 5,955,422; U.S. Patent No. 5,986,047; U.S. Patent No. 6,583, 272; U.S. Patent No. 7,084,245; and U.S. Patent No. 7,271,689; as well as molecules or variants or analogs thereof as described in PCT Application No. WO91 / 05867; PCT Application No. WO95 / 05465; PCT Application No. WO96 / 40772; PCT Application No. WO00 / 24893; PCT Application No. WO01 / 81405; and PCT Application No. WO2007 / 136752, each of which patents or patent applications is incorporated herein by reference in its entirety.

[0041] The ESA can be an erythropoiesis stimulating protein. As used herein, "erythropoiesis stimulating protein" refers to any protein that directly or indirectly activates the erythropoietin receptor, for example by binding to the erythropoietin receptor and dimerizing it. Erythropoiesis stimulating proteins include erythropoietin and its variants, analogs or derivatives that bind to the erythropoietin receptor and activate the receptor; antibodies that bind to the erythropoietin receptor and activate the receptor; or peptides that bind to the erythropoietin receptor and activate the receptor. Erythropoiesis stimulating proteins include, but are not limited to, epoetin alpha, epoetin beta, epoetin delta, epoetin omega, epoetin iota, epoetin zeta and their analogs, pegylated erythropoietin, carbamylated erythropoietin, mimetic peptides (including EMP1 / hematide), and mimetic antibodies. Exemplary erythropoiesis stimulating proteins include erythropoietin, darbepoietin, erythropoietin agonist variants, and peptides or antibodies that bind to and activate the erythropoietin receptor (compounds disclosed in U.S. Publication Nos. 2003 / 0215444 and 2006 / 0040858, each of which is incorporated herein by reference in its entirety), as well as the following patents or patent applications: U.S. Pat. No. 4,703,008; U.S. Pat. No. 5,441,868; U.S. Pat. No. 5,547,933; U.S. Pat. No. 5,618,698; U.S. Pat. No. 5,621,080; U.S. Pat. No. 5,703,008 ... 756,349; U.S. Patent No. 5,767,078; U.S. Patent No. 5,773,569; U.S. Patent No. 5,955,422; U.S. Patent No. 5,830,851; U.S. Patent No. 5,856,298; U.S. Patent No. 5,986,047; U.S. Patent No. 6,030,086; U.S. Patent No. 6,310,078; U.S. Patent No. 6,391,633; U.S. Patent No. 6,583,272; U.S. Patent No. 6,586,398; U.S. Patent No. 6,900,292; U.S. Patent No. 6,750,369; U.S. Patent No. 7,030,226; U.S. Patent No. 7,084,245; and U.S. Patent No. 7,217,689; U.S. Publication No. 2002 / 0155998;U.S. Publication No. 2003 / 0077753;U.S. Publication No. 2003 / 0082749;U.S. Publication No. 2003 / 0143202;U.S. Publication No. 2004 / 0009902;U.S. Publication No. 2004 / 0071694;U.S. Publication No. 2004 / 0091961;U.S. Publication No. 2004 / 0143857;U.S. Publication No. 2004 / 0157293;U.S. Publication No. 2004 / 0175379;U.S. Publication No. 2004 / 0175824;U.S. Publication No. 2004 / 0229318;U.S. Publication No. 2004 / 0248815;U.S. Publication No. 2004 / 0266690;U.S. National Publication No. 2005 / 0019914; U.S. Publication No. 2005 / 0026834; U.S. Publication No. 2005 / 0096461; U.S. Publication No. 2005 / 0107297; U.S. Publication No. 2005 / 0107591; U.S. Publication No. 2005 / 0124045; U.S. Publication No. 2005 / 0124564; U.S. Publication No. 2005 / 0137329; U.S. Publication No. 2005 / 0142642; U.S. Publication No. 2005 / 0143292; U.S. Publication No. 2005 / 0153879; U.S. Publication No. 2005 / 0158822; U.S. Publication No. 2005 / 0158832; U.S. Publication No. 2005 / 0170457; U.S. Publication No. 2005 / 0181359; U.S. Publication No. 2005 / 0181482; U.S. Publication No. 2005 / 0192211; U.S. Publication No. 2005 / 0202538; U.S. Publication No. 2005 / 0227289; U.S. Publication No. 2005 / 0244409; U.S. Publication No. 2006 / 0088906; and U.S. Publication No. 2006 / 0111279; as well as PCT Publication No. WO91 / 05867; PCT Publication No. WO95 / 05465; PCT Publication No. WO99 / 66054; PCT Publication No. WO00 / 24893; CT Publication No. WO01 / 81405; PCT Publication No. WO00 / 61637; PCT Publication No. WO01 / 36489; PCT Publication No. WO02 / 014356; PCT Publication No. WO02 / 19963; PCT Publication No. WO02 / 20034; PCT Publication No. WO02 / 49673 PCT Publication No. WO02 / 085940; PCT Publication No. WO03 / 029291; PCT Publication No. WO2003 / 055526; PCT Publication No. WO2003 / 084477; PCT Publication No. WO2003 / 094858;PCT Publication No. WO2004 / 002424; PCT Publication No. WO2004 / 009627; PCT Publication No. WO2004 / 024761; PCT Publication No. WO2004 / 033651 ;PCT Publication No. WO2004 / 035603;PCT Publication No. WO2004 / 043382;PCT Publication No. WO2004 / 101600;PCT Publication No. WO2004 / 101606 ;PCT Publication No. WO2004 / 101611;PCT Publication No. WO2004 / 106373;PCT Publication No. WO2004 / 018667;PCT Publication No. WO2005 / 001025 PCT Publication No. WO2005 / 001136; PCT Publication No. WO2005 / 021579; PCT Publication No. WO2005 / 025606; PCT Publication No. WO2005 / 032460 PCT Publication No. WO2005 / 051327; PCT Publication No. WO2005 / 063808; PCT Publication No. WO2005 / 063809; PCT Publication No. WO2005 / 07045 No. 1; PCT Publication No. WO2005 / 081687; PCT Publication No. WO2005 / 084711; PCT Publication No. WO2005 / 103076; PCT Publication No. WO2005 / 10040 3; PCT Publication No. WO2005 / 092369; PCT Publication No. WO2006 / 50959; PCT Publication No. WO2006 / 02646; and PCT Publication No. WO2006 / 29094, each of which is incorporated herein by reference in its entirety.

[0042] Examples of other pharmaceutical products for use with the drug delivery device may include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab) and Prolia™ (denosumab); Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgrastim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-MetG-CSF), and other biologics such as Nplate® (romiplostim); small molecule drugs such as Sensipar® (cinacalcet). The drug delivery device may be used with therapeutic antibodies, polypeptides, proteins or other chemical agents such as iron, e.g., ferumoxytol, iron dextran, ferric glyconate and iron sucrose. The pharmaceutical product may be in liquid form or may be reconstituted from a lyophilized form.

[0043] Among certain exemplary proteins are the specific proteins described below (including fusions, fragments, analogs, variants or derivatives thereof).

[0044] OPGL-specific antibodies, such as fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies, peptibodies and related proteins, etc. (also referred to as RANKL-specific antibodies, peptibodies, etc.), including but not limited to the antibodies described in PCT Publication No. WO03 / 002713. This publication is incorporated herein in its entirety with respect to OPGL-specific antibodies and antibody-related proteins, particularly proteins having sequences described in this publication, particularly proteins designated in this publication as 9H7; 18B2; 2D8; 2E11; 16E1 and 22B3, including but not limited to OPGL-specific antibodies having a light chain of SEQ ID NO:2 as set forth in Figure 2 of this publication and / or a heavy chain of SEQ ID NO:4 as set forth in Figure 4 of this publication, each of which proteins is individually and specifically incorporated herein by reference in its entirety as disclosed in the above publication;

[0045] Myostatin-specific peptibodies, particularly myostatin binding proteins, peptibodies and related proteins, including those described in U.S. Publication No. 2004 / 0181033 and PCT Publication No. 2004 / 058988, which publications are incorporated by reference in their entireties, particularly in the portions relating to myostatin-specific peptibodies. The myostatin-specific peptibodies include, but are not limited to, the mTN8-19 family of peptibodies, including the family of SEQ ID NOs: 305-351, such as TN8-19-1 through TN8-19-40, TN8-19con1 and TN8-19con2; the mL2 family of peptibodies of SEQ ID NOs: 357-383; the mL15 family of SEQ ID NOs: 384-409; the mL17 family of SEQ ID NOs: 410-438; the mL20 family of SEQ ID NOs: 439-446; the mL21 family of SEQ ID NOs: 447-452; the mL24 family of SEQ ID NOs: 453-454; and the family of SEQ ID NOs: 615-631, each of which is individually and specifically incorporated by reference herein in its entirety as disclosed in the above publications;

[0046] IL-4 receptor-specific antibodies, peptibodies and related proteins, including those described in PCT Publication No. WO2005 / 047331, PCT Application No. PCT / US2004 / 03742 and U.S. Publication No. 2005 / 112694, which specifically inhibit effects mediated by the binding of IL-4 and / or IL-13 to the receptor. These publications are hereby incorporated by reference in their entirety, particularly in the portions relating to IL-4 receptor specific antibodies, particularly such antibodies described in these publications, particularly, but not limited to, those designated in the above publications as L1H1; L1H2; L1H3; L1H4; L1H5; L1H6; L1H7; L1H8; L1H9; L1H10; L1H11; L2H1; L2H2; L2H3; L2H4; L2H5; L2H6; L2H7; L2H8; L2H9; L2H10; L2H11; L2H12; L2H13; L2H14; L3H1; L4H1; L5H1; L6H1, each of which is individually and specifically incorporated by reference in its entirety as disclosed in the above publications;

[0047] Interleukin 1 receptor 1 ("IL1-R1") specific antibodies, peptibodies and related proteins, including but not limited to those described in U.S. Publication No. 2004 / 097712, which is incorporated herein by reference in its entirety in the portions relating to IL1-R1 specific binding proteins, particularly monoclonal antibodies, particularly but not limited to those designated in said publication as 15CA, 26F5, 27F2, 24E12 and 10H7, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in said publication;

[0048] Ang2-specific antibodies, peptibodies and related proteins, including but not limited to those described in PCT Publication No. 03 / 057134 and US Publication No. 2003 / 0229023. Each of these publications is incorporated by reference in its entirety herein, particularly in relation to the Ang2-specific antibodies and peptibodies described therein and which include, but are not limited to, sequences such as L1(N); L1(N)WT; L1(N)1KWT; 2xL1(N); 2xL1(N)WT; Con4(N), Con4(N)1KWT, 2xCon4(N)1K; L1C; L1C1K; 2xL1C; Con4C; Con4C1K; 2xCon4C1K; Con4-L1(N); Con4-L1C; TN-12-9(N); C17(N); TN8-8(N); TN8-14(N); Con1(N). These Ang2 specific antibodies, peptibodies and the like also include Ang2 specific antibodies and formulations such as those described in PCT Publication No. 2003 / 030833, which PCT Publication specifically discloses the same, in particular Ab526; Ab528; Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; Ab547; Ab548; Ab549; Ab550; Ab551; Ab552; Ab553; Ab554; Ab555; Ab556; Ab557; Ab558; Ab559; Ab560; Ab561; Ab562; Ab563; Ab564; Ab565; Ab566; Ab567; Ab568; Ab569; Ab570; Ab571; Ab572; Ab573; Ab574; Ab575; Ab576; Ab577; Ab578; Ab579; Ab580; Ab581; Ab582; Ab583; Ab584; Ab585; Ab586; Ab587; Ab588; Ab589; Ab590; Ab591; Ab592; Ab593; Ab594; Ab595; Ab596; Ab597; Ab598; Ab599; Ab590 ...1; Ab592; Ab593; Ab594; Ab595; Ab596; Ab597; Ab598; Ab599; Ab590; Ab591; Ab 51; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12; AblA1; AblF; AblK, AblP; and AblP are incorporated by reference in their entireties, each of which is individually and specifically incorporated by reference in its entirety as disclosed in the above publications;

[0049] and NGF-specific antibodies, peptibodies and related proteins, including, but not limited to, those described in U.S. Publication No. 2005 / 0074821 and U.S. Patent No. 6,919,426, which publications and patents are hereby incorporated by reference in their entireties in this regard, particularly with respect to NGF-specific antibodies and related proteins. These NGF-specific antibodies and related proteins include, but are not limited to, the NGF-specific antibodies designated in the above publications and patents as 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11, each of which is individually and specifically incorporated by reference in its entirety as disclosed in the above publications;

[0050] CD22-specific antibodies, peptibodies and related proteins, such as those described in U.S. Patent No. 5,789,554, which is incorporated herein by reference in its entirety with respect to CD22-specific antibodies and related proteins, particularly human CD22-specific antibodies, including but not limited to humanized and fully human antibodies. These humanized and fully human antibodies include, but are not limited to, humanized and fully human monoclonal antibodies, particularly human CD22-specific IgG antibodies, such as, for example, a dimer of human-mouse monoclonal hLL2 gamma chain disulfide-linked to human-mouse monoclonal hLL2 kappa chain, including, but not limited to, the human CD22-specific fully humanized antibody in epratuzumab, CAS Registry Number 501423-23-0;

[0051] IGF-1 receptor-specific antibodies, peptibodies and related proteins, such as those described in PCT Publication No. 06 / 069202, which is incorporated herein by reference in its entirety with respect to IGF-1 receptor-specific antibodies and related proteins. These IGF-1 receptor-specific antibodies and related proteins are referred to in the above publication as L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11, L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L30H30, L31H31, L32H32, L33H 33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1R binding fragments, and derivatives thereof, each of which is individually and specifically incorporated by reference in its entirety as disclosed in the above publications;

[0052] Additionally, non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the present invention include each and every one of those described below: (i) U.S. Publication No. 2006 / 0040358 (published February 23, 2006), U.S. Publication No. 2005 / 0008642 (published January 13, 2005), and U.S. Publication No. 2004 / 0228859 (published November 18, 2004), including, but not limited to, antibody 1A (DSMZ Accession No. D ... (ii) PCT Publication No. 06 / 138729 (published December 28, 2006), PCT Publication No. 05 / 0169709 (published February 24, 2005), and Lu et al. (2004), J. Biol. Chem. 279:2856-2865, including, but not limited to, antibodies 2F8, A12, and IMC-A12, as described in these documents; (iii) PCT Publication No. 07 / 012614 (published February 1, 2007), PCT Publication No. 07 / 000328 (published January 4, 2007), PCT Publication No. 06 / 013472 (published February 9, 2006), PCT Publication No. 05 / 058967 (published June 30, 2005) and PCT Publication No. 03 / 059951 (published July 24, 2003); (iv) U.S. Publication No. 2005 / 0084906, published April 21, 2005, including, but not limited to, antibody 7C10, chimeric antibody C7C10, antibody h7C10, antibody 7H2M, chimeric antibody *7C10, antibody GM607, humanized antibody 7C10 version 1, humanized antibody 7C10 version 2, humanized antibody 7C10 version 3, and antibody 7H2HM, as described therein; (v) U.S. Publication No. 2005 / 0249728 (published November 10, 2005), U.S. Publication No. 2005 / 0186203 (published August 25, 2005), U.S. Publication No. 2004 / 0265307 (published December 30, 2004) and U.S. Publication No. 2003 / 0235582 (published December 25, 2003), and Maloney et al. (2003), Cancer Res. 63:5073-5083, including, but not limited to, antibodies EM164, resurfaced EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2 and huEM164 v1.3, as described in these documents; (vi) U.S. Patent No. 7,037,498, issued May 2, 2006, U.S. Publication No. 2005 / 0244408, published November 30, 2005, and U.S. Publication No. 2004 / 0086503, published May 6, 2004, and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073, e.g., antibodies CP-751, 871. As described therein, including, but not limited to, antibodies produced by hybridomas having ATCC Accession Nos. PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, as well as antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2 and 4.17.3; (vii) U.S. Publication No. 2005 / 0136063, published June 23, 2005, and U.S. Publication No. 2004 / 0018191, published January 29, 2004, including, but not limited to, antibody 19D12, as described in these publications, and an antibody comprising a heavy chain encoded by a polynucleotide in plasmid 15H12 / 19D12HCA(γ4) deposited under ATCC No. PTA-5214 and a light chain encoded by a polynucleotide in plasmid 15H12 / 19D12LCF(κ) deposited under ATCC No. PTA-5220; (viii) U.S. Publication No. 2004 / 0202655 (published Oct. 14, 2004), including, but not limited to, antibodies PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2, PINT-12A3, PINT-12A4, and PINT-12A5, each and all of which are incorporated by reference herein in their entirety, particularly with respect to such antibodies, peptibodies, and related proteins that target the IGF-1 receptor;

[0053] B-7 related protein 1 specific antibodies, peptibodies, related proteins and the like ("B7RP-1", also referred to in the literature as B7H2, ICOSL, B7h and CD275), particularly B7RP specific fully human monoclonal IgG2 antibodies, particularly fully human IgG2 monoclonal antibodies that bind an epitope in the first immunoglobulin-like domain of B7RP-1, particularly those that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, particularly in activated T cells, particularly those disclosed in all of the above respects in U.S. Publication No. 2008 / 0166352 and PCT Publication No. WO07 / 011941, which are hereby incorporated by reference in their entireties with respect to such antibodies and related proteins. Such antibodies and related proteins include, but are not limited to, the antibodies designated in the above publications as follows: 16H (having harbored therein the light chain variable sequence of SEQ ID NO:1 and the heavy chain variable sequence of SEQ ID NO:7); 5D (having harbored therein the light chain variable sequence of SEQ ID NO:2 and the heavy chain variable sequence of SEQ ID NO:9); 2H (having harbored therein the light chain variable sequence of SEQ ID NO:3 and the heavy chain variable sequence of SEQ ID NO:10); 43H (having harbored therein the light chain variable sequence of SEQ ID NO:6 and the heavy chain variable sequence of SEQ ID NO:14); 41H (having harbored therein the light chain variable sequence of SEQ ID NO:5 and the heavy chain variable sequence of SEQ ID NO:13); and 15H (having harbored therein the light chain variable sequence of SEQ ID NO:4 and the heavy chain variable sequence of SEQ ID NO:12), each of which is individually and specifically incorporated by reference in its entirety as disclosed in the above publications;

[0054] IL-15 specific antibodies, such as humanized monoclonal antibodies, peptibodies and related proteins, in particular antibodies such as those described in U.S. Publication Nos. 2003 / 0138421; 2003 / 023586; and 2004 / 0071702; and U.S. Patent No. 7,153,507, each of which is incorporated herein by reference in its entirety with respect to IL-15 specific antibodies and related proteins. These IL-15 specific antibodies and related proteins include, in particular, peptibodies, including but not limited to, e.g., HuMaxIL-15 antibodies, and related proteins, such as, for example, 146B7;

[0055] IFN gamma specific antibodies, peptibodies and related proteins, etc., particularly human IFN gamma specific antibodies, in particular fully human anti-IFN gamma antibodies, such as, for example, those described in U.S. Publication No. 2005 / 0004353. This publication discloses IFN gamma specific antibodies, in particular those described in, for example, U.S. Publication No. 1118; * ;1119;1121;and 1121 * With respect to the antibodies designated as above, the entire sequences of the heavy and light chains of each of these antibodies, as well as the sequences of the variable and complementarity determining regions of these heavy and light chains, respectively, are individually and specifically incorporated herein by reference in their entirety as disclosed in the above publications and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115. In addition, the descriptions of the properties of these antibodies set forth in the above publications are also incorporated herein by reference in their entirety. Specific antibodies, as disclosed in the above publications, include those having a heavy chain of SEQ ID NO: 17 and a light chain of SEQ ID NO: 18; those having a heavy chain variable region of SEQ ID NO: 6 and a light chain variable region of SEQ ID NO: 8; those having a heavy chain of SEQ ID NO: 19 and a light chain of SEQ ID NO: 20; those having a heavy chain variable region of SEQ ID NO: 10 and a light chain variable region of SEQ ID NO: 12; those having a heavy chain of SEQ ID NO: 32 and a light chain of SEQ ID NO: 20; those having a heavy chain variable region of SEQ ID NO: 30 and a light chain variable region of SEQ ID NO: 12; those having a heavy chain of SEQ ID NO: 21 and a light chain of SEQ ID NO: 22; those having a heavy chain variable region of SEQ ID NO: 14 and a light chain variable region of SEQ ID NO: 16; those having a heavy chain of SEQ ID NO: 21 and a light chain of SEQ ID NO: 33; and those having a heavy chain variable region of SEQ ID NO: 14 and a light chain variable region of SEQ ID NO: 31. A specific antibody contemplated is antibody 1119, disclosed in the above U.S. publication, which has the complete heavy chain of SEQ ID NO: 17 disclosed in that U.S. publication, and the complete light chain of SEQ ID NO: 18 disclosed in that U.S. publication;

[0056] TALL-1 specific antibodies, peptibodies and related proteins, and the like, as well as other TALL specific antibodies, such as those described in U.S. Publication Nos. 2003 / 0195156 and 2006 / 0135431, each of which is fully incorporated by reference in its entirety with respect to the TALL-1 binding proteins, particularly the molecules in Tables 4 and 5B, each of which is individually and specifically incorporated by reference in its entirety as disclosed in the above publications;

[0057] Thyroid hormone ("PTH") specific antibodies, peptibodies and related proteins, such as those described in U.S. Patent No. 6,756,480, which is incorporated herein by reference in its entirety, particularly in the portion relating to proteins that bind PTH;

[0058] Thrombopoietin receptor ("TPO-R") specific antibodies, peptibodies and related proteins, such as those described in U.S. Patent No. 6,835,809, which is incorporated herein by reference in its entirety, particularly in the portion relating to proteins that bind to TPO-R;

[0059] Hepatocyte growth factor ("HGF") specific antibodies, peptibodies and related proteins, including those that target the HGF / SF:cMet axis (HGF / SF:c-Met), such as the fully human monoclonal antibodies that neutralize hepatocyte growth factor / scatter (HGF / SF) described in U.S. Publication No. 2005 / 0118643 and PCT Publication No. WO2005 / 017107, huL2G7 described in U.S. Patent No. 7,220,410, and OA-5d5 described in U.S. Patent Nos. 5,686,292 and 6,468,529 and PCT Publication No. WO96 / 38557, each of which publications and patents are incorporated herein by reference in their entirety, particularly in the portions that relate to proteins that bind HGF;

[0060] TRAIL-R2 specific antibodies, peptibodies and related proteins, such as those described in U.S. Patent No. 7,521,048, which is incorporated herein by reference in its entirety, particularly in the portion relating to proteins that bind TRAIL-R2;

[0061] Activin A-specific antibodies, peptibodies and related proteins, including but not limited to those described in U.S. Publication No. 2009 / 0234106, which is incorporated herein by reference in its entirety, particularly in the portion relating to proteins that bind activin A;

[0062] TGF beta specific antibodies, peptibodies and related proteins, including but not limited to those described in U.S. Patent No. 6,803,453 and U.S. Publication No. 2007 / 0110747, each of which is incorporated by reference in its entirety herein, particularly in the portions relating to proteins that bind TGF beta;

[0063] Amyloid beta protein specific antibodies, peptibodies, related proteins, etc., including but not limited to those described in PCT Publication No. WO2006 / 081171, which is incorporated herein by reference in its entirety, particularly in the portion relating to proteins that bind to amyloid beta protein. One antibody contemplated is an antibody having a heavy chain variable region comprising SEQ ID NO:8 and a light chain variable region having SEQ ID NO:6, as described in the above publication;

[0064] c-Kit specific antibodies, peptibodies, related proteins, and the like, including but not limited to those described in U.S. Publication No. 2007 / 0253951, which is incorporated herein by reference in its entirety, particularly in the portion relating to proteins that bind c-Kit and / or other stem cell factor receptors;

[0065] OX40L-specific antibodies, peptibodies, related proteins, and the like, including but not limited to those described in U.S. Publication No. 2006 / 0002929, which is incorporated herein by reference in its entirety, particularly in the portion relating to proteins that bind OX40L and / or other ligands of the OX40L receptor; and

[0066] Other exemplary proteins. Such proteins include Activase® (alteplase, tPA); Aranesp® (darbepoetin alfa); Epogen® (epoetin alfa or erythropoietin); GLP-1, Avonex® (interferon beta-1a); Bexxar® (tositumomab, an anti-CD22 monoclonal antibody); Betaseron (registered trademark) trademark) (interferon beta); Campath® (alemtuzumab, an anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokine receptor mAb); Enbrel® (etanercept, a TNF receptor / Fc fusion protein, a TNF blocker); Eprex ( Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1); Genotropin® (somatropin, human growth hormone); Herceptin® (trastuzumab, anti-HER2 / neu(erbB2) receptor mAb); Humatrope® (somatropin, human growth hormone); Humira® Humira® (adalimumab); insulin solution; Infergen® (interferon alfacon-1); Natrecor® (nesiritide; recombinant human B-type natriuretic peptide (hBNP); Kineret® (anakinra); Leukine® (sargramostim, rhuGM-CSF); Lympho Cide® (epratuzumab, anti-CD22 mAb); Benlysta™ (Lymphostat B, belimumab, anti-BlyS mAb);Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin); Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP870); Soliris™ (eculizumab); Pexelizumab (anti-C5 complement); Numax® (MEDI-524); Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio® (lerdelimumab); Serasim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4); Osidem® (IDM-1); Ova Rex® (B43.13); Nuvion® (vigilizumab); cantuzumab mertansine (huC242-DM1); Neorecormon® (epoetin beta); Neumega® (oprelvekin, human interleukin-11); Neulasta® (pegylated filgrastim, pegylated G-CSF, pegylated hu-Met-G-CSF); Neupogen® (filgrastim, G-CSF, hu-MetG-CSF); Orthoclone OKT3 OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody), Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNFα monoclonal antibody); Reopro® (abciximab, anti-GPlIb / Ilia receptor monoclonal antibody); Actemra® (anti-IL6 receptor mAb); Avastin® (bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20 mAb); Tarceva® (erlotinib);Roferon-A®-(interferon alpha-2a); Simulect® (basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO (anti-IL15 antibody, see U.S. Patent No. 7,153,507); Tysabri® (natalizumab, an anti-α4 integrin mAb); Valort im)® (MDX-1303, an anti-anthrax protective antigen mAb); ABthrax®; Vectibix® (panitumumab); Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-1 Trap (the Fc portion of human IgG1 and the extracellular domains of both IL-1 receptor components (type I receptor and receptor accessory protein)); VEGF Trap (the Ig domain of VEGFR1 fused to the Fc of IgG1); Zet Zenapax® (daclizumab); Zenapax® (daclizumab, anti-IL-2Rα mAb); Zevalin® (ibritumomab tiuxetan), Zetia (ezetimibe), Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonal antibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist; CNTO148 (golimumab, anti-TNFα mAb); HGS-ETR1 (mapatumumab; human anti-TRAIL receptor-1 mAb); HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab); M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C. difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22dsFv-PE38 conjugate (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401);Adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333 (anti-IFNAR); anti-CD38 mAb (HuMaxCD38); anti-CD40L mAb; anti-Cripto mAb; anti-CTGF Idiopathic pulmonary fibrosis Phase I Fibrogen (FG-3019); anti-CTLA4 mAb; anti-eotaxin1 mAb (CAT-213); anti-FGF8 mAb; anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; anti-GDF-8 human mAb (MYO-029); anti-GM-CSF receptor mAb (CAM-3001); anti-HepC mAb (HuMaxHepC); anti-IFNα mAb (MEDI-545, MDX-1103); anti-IGF1R mAb; anti-IGF-1R mAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12 / IL23 mAb (CNTO1275); anti-IL13 mAb (CAT-354); anti-IL2R mAb (HuMax-TAC); anti-IL5 receptor mAb; anti-integrin receptor mAb (MDX-018, CNTO95); anti-IP10 Ulcerative colitis mAb (MDX-1100); anti-LLY antibody; BMS-66513; anti-mannose receptor / hCGβ mAb (MDX-1307); anti-Mesothelin dsFv-PE38 conjugate (CAT-5001); anti-PD1 mAb (MDX-1106 (ONO-4538)); anti-PDGFRα antibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL receptor-2 human mAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR / Flt-1 mAb; anti-ZP3 mAb (HuMax-ZP3); NVS antibody #1; and NVS antibody #2, etc.;

[0067] Sclerostin antibodies, including but not limited to romosozumab, brosozumab, or BPS804 (Novartis), may also be included. Additionally, therapeutic agents such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, bizupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX, or XGEVA may be included. In addition, see, for example, U.S. Patent No. 8,030,547, U.S. Publication No. 2013 / 0064825, WO2008 / 057457, WO2008 / 057458, WO2008 / 057459, WO2008 / 063382, WO2008 / 133647, WO2009 / 100297, WO2009 / 100318, WO2011 / 037791, WO2011 / 053759, WO2011 / 053783, WO2008 / 125623, WO2011 / 072263, WO2009 / 0 The drug delivery device may comprise a monoclonal antibody (IgG) that binds to human protein convertase subtilisin / kexin type 9 (PCSK9), such as WO2012 / 101251, WO2012 / 101252, WO2012 / 101253, WO2012 / 109530, and WO2001 / 031007.

[0068] Talimogene laherparepvec or another oncolytic HSV for the treatment of melanoma or other cancers may also be included. Examples of oncolytic HSV include, but are not limited to, Talimogene laherparepvec (U.S. Pat. Nos. 7,223,593 and 7,537,924); OncoVEXGALV / CD (U.S. Pat. No. 7,981,669); OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143); G207,1716; NV1020; NV12023; NV1034 and NV1042 (Vargehes et al. (2002), Cancer Gene Ther., 9(12):967-978).

[0069] Also included are TIMPs. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) that are important in many natural processes. TIMP-3 is expressed by various cells and is present in the extracellular matrix. It inhibits all major cartilage-degrading metalloproteinases and may be involved in many degradative diseases of connective tissue, such as rheumatoid arthritis and osteoarthritis, as well as cancer and cardiovascular diseases. The amino acid sequence of TIMP-3 and the nucleic acid sequence of DNA encoding TIMP-3 are disclosed in U.S. Patent No. 6,562,596, issued May 13, 2003, the disclosure of which is incorporated herein by reference. Descriptions of TIMP variants can be found in U.S. Publication No. 2014 / 0274874 and PCT Publication No. WO2014 / 152012.

[0070] Also included are antibodies that antagonize the human calcitonin gene-related peptide (CGRP) receptor, as well as bispecific antibody molecules that target the CGRP receptor and other headache-causing targets. Further information regarding these molecules can be found in PCT Application No. WO2010 / 075238.

[0071] In addition, bispecific T cell engager antibodies (BiTe), such as Blinotumomab, can be used in the drug delivery device. Alternatively, APJ large molecule agonists, such as apelin or analogs thereof, can be included in the drug delivery device. Information regarding such molecules can be found in PCT Publication No. WO2014 / 099984.

[0072] In certain embodiments, the medicament comprises a therapeutically effective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptor antibody. Examples of anti-TSLP antibodies that may be used in such embodiments include, but are not limited to, those described in U.S. Patent Nos. 7,982,016 and 8,232,372, and U.S. Publication No. 2009 / 0186022. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in U.S. Patent No. 8,101,182. In a particularly preferred embodiment, the medicament comprises a therapeutically effective amount of an anti-TSLP antibody designated A5 in U.S. Patent No. 7,982,016.

[0073] Although the drug delivery devices, needle guard mechanisms, systems, methods and elements thereof have been described with respect to exemplary embodiments, they are not limited to such embodiments, but rather the appended claims should be construed broadly to include other variations and embodiments thereof that may be made by those skilled in the art without departing from the scope and applicability of the equivalents of the drug delivery devices, needle guard mechanisms, systems, methods and elements thereof.

Claims

1. 1. A drug delivery device comprising: a housing configured to carry a drug reservoir including a dose delivery member, the housing having an opening, such that at least an insertion portion of the dose delivery member is configured to extend through the opening of the housing; a needle guard disposed adjacent the opening and movable relative to the housing between an extended position and a retracted position, the insertion portion of the dose delivery member being surrounded by the needle guard in the extended position and the insertion portion of the dose delivery member being at least partially exposed when the needle guard is in the retracted position; an interference mechanism for providing a selected threshold resistance to movement of the needle guard from the extended position to the retracted position during insertion of the dose delivery member into body tissue at an injection site, the interference mechanism comprising a first member associated with an inner surface of the housing and a second member extending from the needle guard, the first member and the second member engaging each other to hold the needle guard in the extended position, and one of the first member and the second member moving when the drug delivery device is pressed towards the injection site during insertion of the dose delivery member if the selected threshold resistance force is exceeded, causing the first member and the second member to slide over each other and move the needle guard to the retracted position; The drug delivery device comprising:

2. 10. The drug delivery device of claim 1, wherein one of the first member and the second member comprises a cam and the other of the first member and the second member comprises a cam follower.

3. The drug delivery device of claim 2 , wherein the cam follower is biased against the cam.

4. 4. A drug delivery device according to claim 2, wherein the cam follower comprises a flexible arm that applies a biasing force to the cam follower against the cam.

5. 5. The drug delivery device of claim 4, wherein the cam follower further comprises a protrusion disposed at or adjacent a free end of the flexible arm.

6. 5. The drug delivery device of claim 4, wherein the cam follower further comprises a groove disposed at or adjacent a free end of the flexible arm.

7. 7. A drug delivery device according to claim 2, wherein the cam comprises a fixed continuous or segmented circumferential bead.

8. A drug delivery device according to claim 2 , wherein the cam comprises a fixed groove.

9. The drug delivery device of claim 1 , wherein the needle guard is at least partially recessed into the housing in the retracted position.

10. 10. A drug delivery device according to claim 2, wherein the first member comprises the cam member and the second member comprises the cam follower member.

11. 10. A drug delivery device according to any one of claims 2 to 9, wherein the first member comprises the cam follower member and the second member comprises the cam member.

12. 12. The drug delivery device of claim 1, wherein the drug reservoir comprises a syringe.

13. 13. The drug delivery device of claim 1, further comprising an injection drive mechanism including a plunger acting on the stopper and an energy source for exerting a force on the plunger to cause the plunger to act on the stopper and release the drug, the drug storage container further comprising a stopper movably disposed within the drug storage container for releasing the drug.

14. 14. A drug delivery device according to any preceding claim, wherein the dose delivery member comprises an injection needle or a cannula.

15. 15. The drug delivery device of claim 1, further comprising a drug stored in the drug storage container, the drug being selected from the group consisting of TNF inhibitors, antibodies against calcitonin gene-related peptide receptors, colony-stimulating factors, erythropoietin stimulators, apelin receptor agonists, anti-thymic stromal lymphopoietin antibodies, anti-thymic stromal lymphopoietin receptor antibodies, antibodies that bind to human protein convertase subtilisin / kexin type 9, and tissue inhibitors of metalloproteases.

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