Drug delivery device with a needle guard mechanism in which the threshold of resistance to needle guard movement can be adjusted.

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 of related applications We claim priority to U.S. Provisional Patent Application No. 62 / 121,758, filed on 27 February 2015. All contents of this Provisional Patent Application are incorporated herein by reference.

[0002] Areas of disclosure This disclosure relates to a drug delivery device. More specifically, this disclosure relates to a drug delivery device having a needle guard mechanism having an interference mechanism in which a threshold of resistance force against movement of the needle guard that the patient or operator must overcome in order to exert the effect of needle insertion is adjustable. [Background technology]

[0003] Drugs, including, but not limited to, biological agents for the treatment of rheumatoid arthritis, psoriasis, dyslipidemia, osteoporosis, and other medical conditions, can be delivered to the subcutaneous, intramuscular, or intradermal space of a patient. Such drugs can be delivered by injection using drug delivery devices such as syringes, injectors, and auto-injectors.

[0004] Syringes and auto-injectors (syringes) are preferred for delivering many types of therapeutic drugs. One reason for this is that they are equipped with safety features that conventional syringes do not have. For example, it is desirable to protect against accidental needle sticks and unintended drug administration during handling of syringes.

[0005] Syringes can be transported with the needle shield in place. This needle shield acts as a seal to maintain the sterility of the injection needle and provides some protection against accidental needle sticks and unintended drug injections during syringe handling. However, the needle shield must be removed to enable drug delivery, thereby exposing the injection needle. During the injection process, the syringe must be handled with the needle shield not in place while the needle is positioned and the drug is being delivered, thus creating safety risks such as accidental needle sticks and unintended delivery before injection.

[0006] It is desirable in syringes to protect against the risks posed by exposed needles. As shown in Figure 1, many syringes are equipped with a retractable needle guard 52 that surrounds the injection needle 24, protecting against accidental needle sticks and unintended medication after the needle shield 29 has been removed. The needle guard 52 requires input to expose the injection needle 24. This input represents the user's intention to expose or attempt to insert the needle. If there is no input, the needle guard 52 remains extended, covering the needle 24.

[0007] The needle guard 24 can protect against unintended drug delivery by exposing the injection needle until a threshold input is reached and / or resisting the force attempting to insert it. Some prior art mechanisms have been developed to provide this resistance force. For example, as shown in Figure 1 (spring 60), many of these mechanisms use a spring to provide the resistance force. Other devices utilize an automatic needle insertion mechanism to provide the resistance force. However, the use of springs or automatic needle insertion mechanisms increases the complexity of the drug delivery device, adding further components to the device. In particular, automatic needle insertion mechanisms increase complexity and therefore can reduce the reliability of the syringe and increase the cost of the drug delivery device.

[0008] An automatic needle insertion mechanism provides energy for inserting a needle. Some of these mechanisms may use one or more springs (hereinafter referred to as springs). These springs provide potential energy for inserting the needle. Before being released, the spring stores potential energy. When the spring is compressed, the potential energy increases until it reaches a release threshold, and when it undergoes acceleration and / or deceleration, the potential energy is converted into kinetic energy. When a syringe with effective mass comes into contact with a spring that provides resistance, the kinetic energy determines the inertia as a function of the effective mass of the injection system and the velocity of the injection system of that effective mass. This inertia determines the speed and force of needle insertion. Therefore, the potential energy of the spring can be adjusted to provide the optimal speed and force of needle insertion. One of the advantages of an automatic needle insertion mechanism is that the needle insertion process can be optimized.

[0009] Therefore, there is a need for drug delivery devices that offer improved reliability, lower costs, and optimized needle insertion. [Overview of the project]

[0010] A drug delivery device comprising a housing for housing a drug storage container including a dose delivery member, wherein at least the insertion portion of the dose delivery member extends through an opening in the housing; and a needle guard movable relative to the housing between an extended position and a retracted position, wherein the insertion portion of the dose delivery member is surrounded by the needle guard in the extended position, and the insertion portion of the dose delivery member is at least partially exposed when the needle guard is in the retracted position; and while the dose delivery member is inserted into the body tissue of the injection site, the needle guard moves from the extended position to the retracted position. A drug delivery device comprising an interference mechanism for providing a selected threshold resistance force against the movement of a dose delivery member, the restraint mechanism comprising a first member attached to the surface inside the housing and a second member extending from the needle guard, the first member and the second member engaging with 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 toward the injection site during insertion of the dose delivery member, if the resistance force exceeds a selected threshold, causing the first member and the second member to slide past each other and move the needle guard to the retracted position.

[0011] Furthermore, the present invention provides a drug delivery device comprising a housing, a guard, and an interference mechanism, wherein the housing contains a drug storage container, the drug storage container includes a dosage delivery member that extends at least partially through an opening in the housing, the guard is movable relative to the housing between an extended position and a retracted position, the dosage delivery member is concealed by the guard in the extended position and exposed when the guard is in the retracted position, and the interference mechanism comprises a first member attached to the inner surface of the housing and a second member extending from the guard. A method comprising: providing a first member and a second member that engage with each other to hold the guard in an extended position; and pressing the guard against body tissue to insert a dose delivery member into body tissue at an injection site, wherein the interference mechanism provides a threshold resistance force against movement of the needle guard from the extended position, and when the threshold resistance force is exceeded, one of the first member and the second member moves to press, causing the guard to begin moving toward the housing to a retracted position and to slide past each other.

[0012] The same reference numeral is used in each drawing to identify the same or similar elements and structures of various embodiments. [Brief explanation of the drawing]

[0013] [Figure 1] This is a front view of a partial cross-section of a conventional drug delivery device. [Figure 2A] This is a front view of a partial cross-section of an embodiment of a drug delivery device relating to this disclosure. [Figure 2B] Figure 2B is a front view of a partial cross-section of the drug delivery device after needle insertion has been completed. [Figure 3A] This is a front view showing a cross-sectional view of an embodiment of the needle guard mechanism of a drug delivery device and an embodiment of the interference mechanism of the needle guard mechanism. [Figure 3B] Figure 3A is a cross-sectional view of the inside of the housing of a drug delivery device showing an embodiment of the cam element of the interference mechanism. [Figure 3C] Figure 3A is a cross-sectional view of the inside of the housing of a drug delivery device showing another embodiment of the cam element of the interference mechanism. [Figure 3D] Figure 3A is a perspective view of the needle guard showing an embodiment of the cam follower of the interference mechanism shown in Figure 3A. [Figure 4] This is a front view showing a cross-section of a needle guard mechanism of a drug delivery device, illustrating another embodiment of the interference mechanism. [Figure 5] This is a front view showing a cross-section of a needle guard mechanism of a drug delivery device, illustrating another embodiment of the interference mechanism. [Figure 6] This is a front view showing a cross-section of another embodiment of the needle guard mechanism of a drug delivery device and another embodiment of the interference mechanism of the needle guard mechanism. [Figure 7A] This is a cross-sectional view and a front view showing the operation of another embodiment of the needle guard mechanism and interference mechanism. [Figure 7B] This is a cross-sectional view and a front view showing the operation of another embodiment of the needle guard mechanism and interference mechanism. [Figure 8] This graph plots the force applied versus distance for a syringe equipped with a conventional manual spring-type needle insertion mechanism. [Figure 9] It is a graph plotting the acting force against the distance of a syringe equipped with a conventional automatic needle insertion mechanism. [Figure 10] It is a graph plotting the acting force against the distance of an embodiment of the drug delivery device of the present disclosure equipped with a needle guard having an interference mechanism.

Mode for Carrying Out the Invention

[0014] Overview Disclosed herein is a drug delivery device. In various embodiments, the drug delivery device is configured to carry a drug storage container including a dose delivery member, and is a housing having an opening, wherein at least an insertion portion of the dose delivery member is configured to extend through the opening of the housing, the housing; a needle guard disposed adjacent to the opening and movable relative to the housing between an extended position and a retracted position, wherein the insertion portion of the dose delivery member is surrounded by the needle guard in the extended position, and the insertion portion of the dose delivery member is at least partially exposed when the needle guard is in the retracted position, the needle guard; and an interference mechanism for applying a selected threshold resistance to the movement of the needle guard from the extended position to the retracted position while the dose delivery member is being inserted into the body tissue at the injection site, the interference mechanism comprising a first member associated with the surface of the housing and a second member extending from the needle guard, the first member and the second member engaging with each other to hold the needle guard in the extended position, and one of the first member and the second member moves when the drug delivery device is pressed toward the injection site during insertion of the dose delivery member, and when it exceeds the selected threshold resistance, it moves past each other and slides the first member and the second member to move the needle guard to the retracted position, the interference mechanism.

[0015] Further disclosed herein is a method for administering a drug. The method provides a delivery device comprising a housing, a needle guard, and an interference mechanism, wherein the housing houses a drug storage container, the drug storage container includes a dose delivery member extending at least partially through an opening in the housing, the needle guard is movable relative to the housing between an extended position and a retracted position, the dose delivery member is concealed by the needle guard in the extended position and exposed when the needle guard is in the retracted position, and the interference mechanism comprises a first member attached to a surface inside the housing and a second member extending from the needle guard. The first and second members engage with each other to provide, hold the needle guard in the extended position; and press the needle guard against the body tissue to insert the dose delivery member into the body tissue at the injection site, wherein the interference mechanism provides a threshold resistance force against movement of the needle guard from the extended position, and when the threshold resistance force is exceeded, one of the first and second members moves to press, causing the needle guard to begin moving toward the housing to the retracted position and to slide past the first and second members.

[0016] Further disclosed herein are a housing configured to house a drug storage container including a dose delivery member for delivering a dose of drug to a patient; a needle guard positioned adjacent to an opening in the housing for extending the dose delivery member, the needle guard being movable relative to the housing between an extended position for surrounding the dose delivery member and a retracted position for exposing the dose delivery member; and an interference mechanism providing a selected threshold resistance force that must be overcome to move the needle guard from the extended position to the retracted position, the interference mechanism being The drug delivery device comprises a first member attached to the surface of the housing and a second member attached to the needle guard, the first member and the second member being in contact with each other when the needle guard is in the extended position, and at least one of the first member and the second member is transported by the flexible arm such that when an axial force is applied that presses the needle guard from the extended position toward the retracted position, the flexible arm bends, causing the attached first member and / or second member to move radially away from the other, and the first member and the second member to slide past each other.

[0017] Detailed explanation Figure 2A shows an embodiment of the portable drug delivery device 100 according to the present disclosure. The device includes a needle guard mechanism 150 with an adjustable threshold for the resistance force to the movement of the needle guard 152, which is configured to exert and optimize the effects of needle insertion, speed, and force. The drug delivery device 100 can be configured as a single-use disposable syringe or as a reusable syringe for multiple uses. The drug delivery device 100 can be configured to deliver any suitable pharmaceutical or drug, including, for example, those having a viscosity that can take on a range of about 1 to 200 centipoise. Furthermore, the drug delivery device 100 can be configured as an auto-injector for self-administration, but such a device can also be used by a caregiver or a formally trained healthcare provider for injection. Referring to Figure 2A, the drug delivery device 100 of various embodiments may further include an elongated housing or external enclosure 110 that holds the drug storage device 120. The drug storage device 120 in various embodiments may comprise a main container 122, a stopper 126 movably positioned in an internal chamber 122c of the main container 122 for releasing the pharmaceutical or drug 128 contained therein, and a needle 124 (illustrated), a cannula, or other suitable dose delivery member or element capable of penetrating body tissue and administering the drug to the 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 can be attached to cover the needle 124 to maintain the needle in a sterile state before use of the drug delivery device 100. The drug storage device 120 may be pre-filled with one or more doses of pharmaceutical or drug 128.

[0018] In various embodiments, the inner surface 112 of the housing 110 is provided with one or more support members 114, and the drug storage device 120 can be fixedly held inside the outer housing 110 with at least the insertion portion of the injection needle 124 extending through an opening 110o defined at the distal end 110de of the housing 110.

[0019] Referring further to Figure 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 located within the housing 110 and, in some embodiments, may include a plunger 132 and a plunger drive spring 134 to propel the plunger 132 through to the main container 122 of the drug storage device 120 to inject or dispense the drug. The plunger 132 and plunger drive spring 134 may be configured such that one end of the spring 134 engages with the head member 138 of the plunger 132 and the other end of the spring 134 engages with the drive trigger mechanism 140, with the plunger 132 extending through the plunger drive spring 134. Before activating the injection drive mechanism 130, in some embodiments, the plunger 132 is positioned with the head member of the plunger 132 close to the opening 122o of the main container 122 of the drug storage device 120, with a 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 activated by the drive trigger mechanism 140, the plunger drive spring 134 extends, propelling the plunger 132 through the main container 122 of the drug storage device 120, driving the stopper 126 through the main container 122, and releasing the drug 128 through the injection needle 124.

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

[0021] Referring further to Figure 2A, the drive trigger mechanism 140 can be located within the housing 110 and may comprise an activation button 142 extending through an opening on the side of the housing 110, a plunger release arm 144 extending from the activation button 142, and a trigger spring 148 positioned between the plunger release arm 144 and the inner surface 112 of the housing 110. The activation button 142 allows the drive trigger mechanism 140 to be activated by a patient or other operator, thereby activating the injection drive mechanism 130. The plunger release arm 144 is movable between a plunger holding position and a plunger release position. In some embodiments, in the plunger holding position, the plunger release arm 144 holds the plunger 143 in place via a retainer 146. The retainer 146 may comprise a projection 146p on the plunger release arm 144 and a recess 146r formed on the side of the plunger 132. In the plunger release position, the plunger release arm 144 disengages the retaining projection 146p from the retaining recess 146r, thereby releasing the plunger 132 and allowing the plunger to be propelled by the plunger drive spring 134. The trigger spring 148 applies a force that maintains the plunger release arm 144 in the plunger holding position while the retaining projection 146p and recess 146r are engaged. When the activation button 142 is pressed, the plunger release arm 144 overcomes the force of the trigger spring 148 and moves from the plunger holding position to the plunger release position, thereby disengaging the retaining projection 146 and releasing the plunger 132.

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

[0023] Referring further to Figure 2A, the needle guard mechanism 150 in various embodiments comprises a needle guard 152 movably positioned at the distal end 110de of the housing 110, and a return or interference mechanism 154. The needle guard 152 can be biased to the position shown in Figure 2A by a spring (not shown) similar to the spring 60 shown in Figure 1. The interference mechanism 154 retracts and releases the needle guard 152 and holds the needle guard 152 in the extended position by an adjustable or selectable threshold resistance force against the force applied by a patient or operator attempting to insert the injection needle 124 of the drug storage device 120 into body tissue, as shown in Figure 2B. This optimizes the speed and force of needle insertion and prevents unintended drug delivery after the needle shield 129 is removed.

[0024] In some embodiments, the needle guard 152 may have a tubular structure (extended position) that surrounds the insertion portion of the injection needle 124 extending from the distal end 110de of the housing 110 to protect against accidental needle punctures. The needle guard 152 may be configured to be housed within the housing 110 and retracted, as shown in Figure 2B, or in other versions, to cover the housing 110 and be retracted (not shown).

[0025] The interference mechanism 154 in various embodiments may comprise a first member 1541 attached to the housing 110 and a second member 1542 attached to the needle guard 152. At least portions of the first member 1541 and the second member 1542 engage with each other to hold the needle guard 152 in the extended position and provide a selected threshold resistance force against the movement or release of the needle guard 152. In some embodiments, one of the first member 1541 and the second member 1542 may be configured to move when the axial force applied to the drug delivery device 100 by a patient or operator pressing the drug delivery device 100 toward the injection site matches or exceeds a selected threshold resistance force. This causes the other of the first member 1541 and the second member 1542 to slide past the other, releasing the needle guard 152 and pulling the needle guard toward the housing 110 toward the retracted position for needle insertion, as shown in Figure 2B.

[0026] Referring to Figure 3A, in some embodiments, the interference mechanism 154 may comprise an overcenter cam mechanism 254. This cam mechanism includes a fixed cam element 254c and one or more elastically biased cam followers 254f. As shown in Figure 3B, the fixed cam element 254c may comprise a circumferential bead 255 positioned on the inner surface 112 of the housing 110 adjacent to the opening 110o at the distal end 110de of the housing 110. The circumferential bead 255 may be continuous as shown in Figure 3B or divided as shown in Figure 3C. As shown in Figure 3D, one or more of the elastically biased cam followers 254f may comprise a flexible arm 256 extending from the proximal end 152pe of the needle guard 152, and a projection 257 positioned on the outward-facing surface 152o of the flexible arm 256. As shown in Figure 3A, one or more flexible arms 256 bias their corresponding projections 257 against a fixed cam element 255 (or multiple elements in a divided embodiment) of a circumferential bead.

[0027] Furthermore, as shown in Figure 3A, the fixed cam element 254c of the housing 110 and the cam follower 254f of the needle guard 152 are provided with curved (e.g., cammed or spherical) outer surfaces (e.g., profiles) to facilitate sliding interaction during use of the drug delivery device 100. For example, when the user applies an axial force F p When F is applied to the drug delivery device 100, approximately equal and opposite axial forces are applied to the needle guard 152, pushing the needle guar 152 toward its stowed position. However, the engagement of the cam element 254c and the cam follower 254f substantially prevents retraction until a selected threshold resistance force is overcome. That is, in the version of Figure 3A, the threshold resistance force is equal to the force required to deform the flexible arm 256 carrying the cam follower 254f toward the fixed cam element 254, thereby allowing the curved outer surface of the cam follower 254f to slide toward and beyond the fixed cam element 254c. In Figure 3A, the force applied by the user is F pThis is shown as, and this is the axial force component F in each cam follower 254f. a and radial force component F r The force is then applied to the fixed cam element 254c. Therefore, in order to overcome the resistance force of the threshold, the axial force F applied by the user is applied. p The inherent resistive biasing force F of the flexible arm 256 b A sufficient radial force component F to overcome it r It must be large enough to generate the resistive biasing force F of the flexible arm 256. b This primarily depends on the material constituting the arm 256 and the geometric shape of the arm 256 (for example, 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] Referring to Figure 4, various embodiments of the overcenter cam mechanism 354 may include a circumferential bead 255 positioned on the inner surface 112 of the housing 110 as previously described with respect to Figures 3A to 3C, and one or more elastically biased cam followers 356f configured as curved 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 with respect to the circumferential bead 255.

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

[0030] Referring to Figure 6, in a further embodiment, the needle guard 152 may be configured to cover and retract from the outer surface 113 of the housing 110. In such embodiments, a fixed continuous or segmented circumferential bead 255 may be provided on the outer surface 113 of the housing 110, and the projection 257 of the elastically biased cam follower 254f may be provided on the inner surface 152i of the flexible arm 256.

[0031] Referring to Figures 7A and 7B, in other embodiments, the needle guard 152 may have the fixed continuous or segmented circumferential bead 255 described above on its outer surface, and the housing 110 may have one or more elastically biased cam followers 254f including a flexible arm 256 and a projection 257.

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

[0033] Referring to Figures 2A to 7B, each of the embodiments described above includes one or more elastically biased cam followers relative to only one of the needle guard 152 (e.g., Figures 2A to 6) or the housing 110 (e.g., Figures 7A to 7B), while other versions may include elements elastically biased relative to both the needle guard 152 and the housing 110. For example, in one version, the housing 110 may include a plurality of segmented circumferential beads, each transported by a single flexible arm, and the needle guard 152 may include a corresponding number of cam followers, each transported by a single flexible arm. Naturally, in other versions, the needle guard 152 may include a plurality of segmented circumferential beads, each transported by a single flexible arm, and the housing 110 may include a corresponding number of cam followers, each transported by a single flexible arm. In these alternative configurations, the flexible arms of the housing 110 and the needle guard 152 can simultaneously deform in response to forces attempting to overcome the resistance of the interference mechanism, thereby providing greater flexibility when adjusting the interference mechanism to the patient's specific needs.

[0034] Figure 8 is a graph plotting the force versus distance for a syringe with a conventional manual spring-loaded needle insertion mechanism. Starting from zero time and force, the force can be observed to rise from approximately zero (although the initial force can be increased by adjusting the residual force of the needle guard spring to exceed zero) and increases essentially linearly all the way until the injection needle appears in the body tissue. In Figure 8, the force for inserting the injection 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 for inserting the injection needle into the body tissue. As the injection needle approaches full insertion depth, a second mechanism appears to initiate automatic drug delivery. As shown in Figure 8, this second mechanism appears with a rapid increase in the force. This indicates that it is possible to provide further feedback to the patient or operator and thus choose to initiate drug delivery as a result of the increased force. However, drug delivery can continue without applying this further feedback to the patient or operator. This increase continues until the threshold force is reached and the drug is administered, at which point the force decreases with delivery.

[0035] Figure 9 is a graph plotting the force versus distance of a conventional syringe with a conventional automatic needle insertion mechanism. Starting from zero time and force, the force can be observed to rise from approximately zero (in this case, the initial force can also be biased by adjusting the residual force of the resisting spring) and increases essentially linearly until the needle appears in the body tissue. In Figure 9, the force for inserting the needle is independent of the spring force of the needle guard. However, an inertial effect exists, which tends to be perceived as an additional force that must be overcome to keep the syringe in close contact with the body tissue. As the needle approaches the full insertion depth, the automatic mechanism continues to apply load to the drug container, pushing the previous volume through the needle. There is a residual force that overcomes during drug delivery to prevent the needle guard from stretching and covering the needle. This residual force may also cause the needle to tend to be pushed away from the body tissue.

[0036] Figure 10 is a graph plotting the force versus distance of an embodiment of the drug delivery device of the present disclosure equipped with a needle guard having an interference mechanism. Starting from zero time and force, the force required when the needle guard first makes contact with body tissue increases relatively rapidly. This increase represents the force that overcomes the resistive force provided by the interference mechanism. The magnitude of this force is selectively adjusted via the interference mechanism to adjust the inertia available when the release of the needle guard occurs, and thus the sensation of needle insertion can be tailored to the patient's preference. The adjustment can be made by adjusting one or more of the geometric shape, dimensions, and elastic modulus of the elements of the interference mechanism. Medication can be delivered manually (as preferred by some patients undergoing certain treatments) or automatically. In the case of automated medication delivery, the medication release (i.e., activation of the injection drive) can be performed separately, as shown in Figure 10, or simultaneously with the start of insertion so that needle insertion and medication delivery occur at the same time.

[0037] As can be seen from Figures 9 and 10, conventional syringes with automatic needle insertion mechanisms have a force that increases due to the deformation of the needle guard and the compression of the needle guard spring. Because the force to release the guard is generated over a relatively long distance, the patient or operator is not given a clear indication that the injection needle is approaching the working position. In a preferred embodiment, the force to release the guard (resistance force) is generated over a short distance, resulting in stronger feedback to the patient or operator. This indicates that the injection needle is approaching the needle insertion position. The duration of this working event can be adjusted via an interference mechanism of the needle guard mechanism to optimize the patient or operator's experience.

[0038] While a needle guard mechanism has been disclosed in this specification in relation to a portable drug delivery device, the needle guard mechanism may also be used in an on-body drug delivery device that includes a syringe and an automatic infusion device. This drug delivery device is worn on the patient's body.

[0039] The above description includes various systems and methods for use with drug delivery devices. It is clear that drug delivery devices or methods may further include the use of the medicinal products listed below. However, it should be noted that the following list should not be considered exhaustive or limited. The medicinal product is contained in a storage compartment. In some examples, the storage compartment is a main container that is filled or pre-filled for treatment using the medicinal product. The main container may be a cartridge or a pre-filled syringe.

[0040] For example, a drug delivery device, or more specifically, the storage section of a drug delivery device, may be filled 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 various pharmaceutical products such as erythropoiesis-stimulating agents (ESAs). These products may be in liquid or lyophilized form. ESAs are any molecules that stimulate erythropoiesis.ESA includes Epogen (registered trademark) (epoetin alfa), Aranesp (registered trademark) (darbepoetin alfa), Dynepo (registered trademark) (epoetin delta), Mircera (registered trademark) (methoxypolyethylene glycol-epoetin beta), Hematide (registered trademark), MRK-2578, INS-22, Retacrit (registered trademark) (epoetin zeta), and Neorec ormon) (registered trademark) (epoetin beta), Silapo (registered trademark) (epoetin zeta), Binocrit (registered trademark) (epoetin alpha), epoetin alpha hexal, Abseamed (registered trademark) (epoetin alpha), Ratioepo (registered trademark) (epoetin theta), Eporatio (registered trademark) (epoetin theta), Biopoin (registered trademark) (epoetin theta), epoe Epoetin alpha, epoetin beta, epoetin zeta, epoetin theta and epoetin delta, and the following patents or patent applications: U.S. No. 4,703,008; U.S. No. 5,441,868; U.S. No. 5,547,933; U.S. No. 5,618,698; U.S. No. 5,621,080; U.S. No. 5,756,349; U.S. No. 5,767,078; U.S. No. 5,773,569; U.S. No. 5,955,422; U.S. No. 5,986,047; U.S. No. 6,583, Examples include molecules or their variants or analogues as described in U.S. Patent No. 272; U.S. Patent No. 7,084,245; and U.S. Patent No. 7,271,689; and PCT applications WO91 / 05867; PCT applications WO95 / 05465; PCT applications WO96 / 40772; PCT applications WO00 / 24893; PCT applications WO01 / 81405; and PCT applications WO2007 / 136752, each of which is incorporated herein by reference in its entirety.

[0041] ESAs can be erythropoiesis-stimulating proteins. As used herein, “erythropoiesis-stimulating protein” means any protein that directly or indirectly activates the erythropoietin receptor by binding to and dimerizing it, for example. Erythropoiesis-stimulating proteins include erythropoietin and its variants, analogs, or derivatives that bind to and activate the erythropoietin receptor; antibodies that bind to and activate the erythropoietin receptor; or peptides that bind to and activate the erythropoietin 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, darbepoetin, erythropoietin agonist variants, and peptides or antibodies that bind to and activate the erythropoietin receptor (including compounds published in U.S. Public Appeal No. 2003 / 0215444 and U.S. Public Appeal No. 2006 / 0040858, each of which is incorporated herein by whole reference), as well as the following patents or patent applications: U.S. No. 4,703,008; U.S. No. 5,441,868; U.S. No. 5,547,933; U.S. No. 5,618,698; U.S. No. 5,621,080; U.S. No. 5, U.S. Publication No. 756,349; U.S. Publication No. 5,767,078; U.S. Publication No. 5,773,569; U.S. Publication No. 5,955,422; U.S. Publication No. 5,830,851; U.S. Publication No. 5,856,298; U.S. Publication No. 5,986,047; U.S. Publication No. 6,030,086; U.S. Publication No. 6,310,078; U.S. Publication No. 6,391,633; U.S. Publication No. 6,583,272; U.S. Publication No. 6,586,398; U.S. Publication No. 6,900,292; U.S. Publication No. 6,750,369; U.S. Publication No. 7,030,226; U.S. Publication No. 7,084,245; and U.S. Publication No. 7,217,689; U.S. Publication No. 2002 / 0155998;U.S. Public Gazette No. 2003 / 0077753; U.S. Public Gazette No. 2003 / 0082749; U.S. Public Gazette No. 2003 / 0143202; U.S. Public Gazette No. 2004 / 0009902; U.S. Public Gazette No. 2004 / 0071694; U.S. Public Gazette No. 2004 / 0091961; U.S. Public Gazette No. 2004 / 0143857; U.S. Public Gazette No. 2004 / 0157293; U.S. Public Gazette No. 2004 / 0175379; U.S. Public Gazette No. 2004 / 0175824; U.S. Public Gazette No. 2004 / 0229318; U.S. Public Gazette No. 2004 / 0248815; U.S. Public Gazette No. 2004 / 0266690; U.S. National Gazette No. 2005 / 0019914; U.S. Gazette No. 2005 / 0026834; U.S. Gazette No. 2005 / 0096461; U.S. Gazette No. 2005 / 0107297; U.S. Gazette No. 2005 / 0107591; U.S. Gazette No. 2005 / 0124045; U.S. Gazette No. 2005 / 0124564; U.S. Gazette No. 2005 / 0137329; U.S. Gazette No. 2005 / 0142642; U.S. Gazette No. 2005 / 0143292; U.S. Gazette No. 2005 / 0153879; U.S. Gazette No. 2005 / 0158822; U.S. Gazette No. 2005 / 0158832; United States U.S. Public Gazette No. 2005 / 0170457; U.S. Public Gazette No. 2005 / 0181359; U.S. Public Gazette No. 2005 / 0181482; U.S. Public Gazette No. 2005 / 0192211; U.S. Public Gazette No. 2005 / 0202538; U.S. Public Gazette No. 2005 / 0227289; U.S. Public Gazette No. 2005 / 0244409; U.S. Public Gazette No. 2006 / 0088906; and U.S. Public Gazette No. 2006 / 0111279; and PCT Public Gazette No. WO91 / 05867; PCT Public Gazette No. WO95 / 05465; PCT Public Gazette No. WO99 / 66054; PCT Public Gazette No. WO00 / 24893; P 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 / 002417;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 This includes erythropoietin molecules, or their variants or analogues, as disclosed in PCT Publication No. 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 whole.

[0042] Other pharmaceutical products for use with drug delivery devices 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); Newpogen® (filgrastim, G-CSF, hu-MetG-CSF); and other biologics such as Nplate® (romiplostim); and small molecule drugs such as Sensipar® (cinacalcet). The drug delivery device may be used with therapeutic antibodies, polypeptides, proteins, or other chemicals such as iron, for example, fermoxytol, iron dextran, ferric glyconate, and iron sucrose. The pharmaceutical product may be in liquid form or reconstituted from a lyophilized form.

[0043] Certain exemplary proteins include the specific proteins (including their fusions, fragments, analogues, variants, or derivatives) listed below.

[0044] This publication includes, but is not limited to, fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies, as well as OPGL-specific antibodies, peptide bodies, and related proteins (also known as RANKL-specific antibodies, peptide bodies, etc.), including antibodies described in PCT Publication No. WO03 / 002713. With respect to OPGL-specific antibodies and antibody-related proteins, particularly proteins having sequences described in this publication, especially, but not limited to, OPGL-specific antibodies having the light chain of SEQ ID NO: 2 as shown in Figure 2 of this publication and / or the heavy chain of SEQ ID NO: 4 as shown in Figure 4 of this publication, the proteins designated in this publication as 9H7;18B2;2D8;2E11;16E1 and 22B3, the whole thereof is incorporated herein by reference, and each of these proteins is individually and specifically incorporated herein by reference as disclosed in the above publication;

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

[0046] IL-4 receptor-specific antibodies, peptide bodies, and related proteins, including those described in PCT Publication WO2005 / 047331, i.e., PCT Application PCT / US2004 / 03742 and U.S. Publication 2005 / 112694, that inhibit the effects mediated by the binding of IL-4 and / or IL-13 to their receptors. These publications, in particular with respect to IL-4 receptor-specific antibodies, especially those 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, are incorporated herein by reference in their entirety, and each of these antibodies, as disclosed in the above publications, is incorporated herein individually and specifically by reference in its entirety;

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

[0048] Ang2-specific antibodies, peptide bodies, and related proteins, including, but not limited to, those described in PCT Publication No. 03 / 057134 and U.S. Public Notice No. 2003 / 0229023. Each of these publications, in particular, contains, in part, a portion relating to sequences that include, in no particular limitation, 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), and such a portion is incorporated herein by reference. These Ang2-specific antibodies and peptide bodies include Ang2-specific antibodies and preparations such as those described in PCT Publication No. 2003 / 030833, and this PCT Publication, with respect to such products, particularly in the various permutations described in this publication, Ab526;Ab528;Ab531;Ab533;Ab535;Ab536;Ab537;Ab540;Ab543;Ab544;Ab545;Ab546;A5 With respect to 51;Ab553;Ab555;Ab558;Ab559;Ab565;AbF1AbFD;AbFE;AbFJ;AbFK;AbG1D4;AbGC1E8;AbH1C12;AblA1;AblF;AblK, AblP; and AblP, the whole is incorporated by reference, and each of these is incorporated individually and specifically by reference in its entirety, as disclosed in the above publication;

[0049] NGF-specific antibodies, peptide bodies, and related proteins, including, but not limited to, those described in U.S. Publication No. 2005 / 0074821 and U.S. Patent No. 6919426. These publications and patents are incorporated herein by reference in their entirety, particularly with respect to NGF-specific antibodies and related proteins. These NGF-specific antibodies and related proteins include, but not limited to, the NGF-specific antibodies designated as 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11 in the aforementioned publications and patents, each of which is incorporated herein by reference individually and specifically, in its entirety, as disclosed in the aforementioned publications;

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

[0051] IGF-1 receptor-specific antibodies, peptide bodies, and related proteins, such as those described in PCT Publication No. 06 / 069202. This publication, with respect to IGF-1 receptor-specific antibodies and related proteins, is incorporated herein by reference in its entirety. These IGF-1 receptor-specific antibodies and related proteins are described 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 This includes, but is not limited to, IGF-1 specific antibodies designated as 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, as well as derivatives thereof, each of which is incorporated separately and specifically herein by reference in its entirety, as disclosed in the above publication;

[0052] Furthermore, non-limiting examples of anti-IGF-1R antibodies for use in the methods and configurations of the present invention include each and all of the following: (i) U.S. Public Notice No. 2006 / 0040358 (published February 23, 2006), U.S. Public Notice No. 2005 / 0008642 (published January 13, 2005), U.S. Public Notice No. 2004 / 0228859 (published November 18, 2004). As described in these publications, for example, include, but are not limited to, antibody 1A (DSMZ deposit number DSMACC2586), antibody 8 (DSMZ deposit number DSMACC2589), antibody 23 (DSMZ deposit number DSMACC2588), and antibody 18; (ii) PCT Bulletin No. 06 / 138729 (published December 28, 2006), PCT Bulletin No. 05 / 0169709 (published February 24, 2005), and Lu et al. (2004), J. Biol. Chem. 279:2856-2865. As described in these documents, the antibodies 2F8, A12 and IMC-A12 are included in no particular limit; (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. Public Notice No. 2005 / 0084906 (published April 21, 2005). This publication includes, but is 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 in this publication; (v) U.S. Public Notice No. 2005 / 0249728 (published November 10, 2005), U.S. Public Notice No. 2005 / 0186203 (published August 25, 2005), U.S. Public Notice No. 2004 / 0265307 (published December 30, 2004), and U.S. Public Notice No. 2003 / 0235582 (published December 25, 2003), as well as Maloney et al. (2003), Cancer Res. 63:5073-5083. This includes, but is not limited to, antibody EM164, surface-reconstituted EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2, and huEM164 v1.3, as described in these publications; (vi) U.S. Publication No. 7037498 (issued May 2, 2006), U.S. Public Notice No. 2005 / 0244408 (published November 30, 2005), and U.S. Public Notice No. 2004 / 0086503 (published May 6, 2004), as well as Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073, e.g., antibodies CP-751, 871. As described in these documents, this includes, but is not limited to, antibodies produced by hybridomas having ATCC acceptance numbers PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, and 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, respectively; (vii) U.S. Public Notice No. 2005 / 0136063 (published June 23, 2005) and U.S. Public Notice No. 2004 / 0018191 (published January 29, 2004). As described in these publications, the antibody 19D12, and non-limiting antibodies comprising the heavy chain encoded by polynucleotides in plasmid 15H12 / 19D12HCA(γ4) deposited under ATCC number PTA-5214 and the light chain encoded by polynucleotides in plasmid 15H12 / 19D12LCF(κ) deposited under ATCC number PTA-5220; (viii) U.S. Public Notice No. 2004 / 0202655 (published October 14, 2004). As described in this publication, the 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 are included without limitation, each and all of these, in whole, are incorporated herein by reference, particularly with respect to the antibodies, peptide bodies and related proteins that target the IGF-1 receptor;

[0053] B7-related protein 1 specific antibodies, peptide bodies, and related proteins ("B7RP-1", also referred to in the literature as B7H2, ICOSL, B7h, and CD275), in particular B7RP-specific fully human monoclonal IgG2 antibodies, in particular fully human IgG2 monoclonal antibodies that bind to the epitope in the first immunoglobulin-like domain of B7RP-1, in particular those that inhibit the interaction between B7RP-1 and its innate receptor ICOS, particularly in activated T cells, in all of the above, as disclosed in U.S. Public Appeal No. 2008 / 0166352 and PCT Publication No. WO07 / 011941. These publications, in whole, are incorporated herein by reference with respect to such antibodies and related proteins. Such antibodies and related proteins include, but are not limited to, the antibodies specified in the above publication as follows: 16H (containing the light chain variable sequence of SEQ ID NO: 1 and the heavy chain variable sequence of SEQ ID NO: 7); 5D (containing the light chain variable sequence of SEQ ID NO: 2 and the heavy chain variable sequence of SEQ ID NO: 9); 2H (containing the light chain variable sequence of SEQ ID NO: 3 and the heavy chain variable sequence of SEQ ID NO: 10); 43H (containing the light chain variable sequence of SEQ ID NO: 6 and the heavy chain variable sequence of SEQ ID NO: 14); 41H (containing the light chain variable sequence of SEQ ID NO: 5 and the heavy chain variable sequence of SEQ ID NO: 13); and 15H (containing 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 incorporated herein by reference in its entirety, as disclosed in the above publication;

[0054] In particular, IL-15 specific antibodies, peptide bodies, and related proteins, such as humanized monoclonal antibodies, as described in U.S. Patent Publication No. 2003 / 0138421; U.S. Patent Publication No. 2003 / 023586; and U.S. Patent Publication No. 2004 / 0071702; and U.S. Patent No. 7153507, respectively. These publications and patents, with respect to IL-15 specific antibodies and related proteins, are incorporated herein by reference in their entirety. These IL-15 specific antibodies and related proteins include, in particular, a HuMax IL-15 antibody and a peptide body, not limited to, an associated protein such as 146B7;

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

[0056] TALL-1 specific antibodies, peptide bodies and related proteins, as well as other TALL-specific antibodies, such as those described in U.S. Public Appeal No. 2003 / 0195156 and U.S. Public Appeal No. 2006 / 0135431. Each of these publications is incorporated herein by whole reference in its entirety with respect to TALL-1 binding proteins, particularly the molecules in Tables 4 and 5B, and each of these molecules is incorporated herein by whole reference individually and specifically, as disclosed in the above publications;

[0057] Thyroid hormone ("PTH")-specific antibodies, peptide bodies, and related proteins, such as those described in U.S. Patent No. 6,756,480. This patent, in particular with respect to proteins that bind to PTH, is incorporated herein by reference in its entirety;

[0058] Examples include thrombopoietin receptor ("TPO-R") specific antibodies, peptide bodies, and related proteins, such as those described in U.S. Patent No. 6,835,809. This patent, in particular with respect to proteins that bind to TPO-R, is incorporated herein by reference in its entirety;

[0059] Hepatocyte growth factor ("HGF")-specific antibodies, peptide bodies, and related proteins, etc. These HGF-specific antibodies, peptide bodies, and related proteins include those targeting the HGF / SF:cMet axis (HGF / SF:c-Met), such as the fully human monoclonal antibody that inactivates hepatocyte growth factor / dispersion (HGF / SF) described in U.S. Publication No. 2005 / 0118643 and PCT Publication No. WO2005 / 017107, huL2G7 described in U.S. Patent No. 7220410, and OA-5d5 described in U.S. Patent No. 5686292 and U.S. Patent No. 6468529 and PCT Publication No. WO96 / 38557, each of which is incorporated herein by reference in its entirety, particularly in its part relating to proteins that bind to HGF;

[0060] TRAIL-R2 specific antibodies, peptide bodies, and related proteins, such as those described in U.S. Patent No. 7,521,048. This patent, in particular with respect to proteins that bind to TRAIL-R2, is incorporated herein by reference in its entirety;

[0061] Activin A-specific antibodies, peptide bodies, and related proteins, etc., including, but not limited to, those described in U.S. Public Notice No. 2009 / 0234106. This publication, in particular with respect to proteins that bind to activin A, is incorporated herein by reference in its entirety;

[0062] TGF beta-specific antibodies, peptide bodies, and related proteins, etc., including, but not limited to, those described in U.S. Patent No. 6,803,453 and U.S. Publication No. 2007 / 0110747. Each of these patents and publications, in whole, is incorporated herein by reference, particularly in its part relating to proteins that bind to TGF beta;

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

[0064] c-Kit-specific antibodies, peptide bodies, and related proteins, etc., including, but not limited to, those described in U.S. Public Notice No. 2007 / 0253951. This publication, in particular with respect to proteins that bind to c-Kit and / or other stem cell factor receptors, is incorporated herein by reference in its entirety;

[0065] OX40L-specific antibodies, peptide bodies, related proteins, etc., including, but not limited to, those described in U.S. Public Notice No. 2006 / 0002929. This publication, in particular with respect to proteins that bind to OX40L and / or other ligands of the OX40L receptor, is incorporated herein by reference in its entirety; 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, anti-CD22 monoclonal antibody); Betaseron® (Trademark) (Interferon Beta); Campath (Registered Trademark) (Alemtuzumab, anti-CD52 monoclonal antibody); Dinepo (Registered Trademark) (Epoetin Delta); Velcade (Registered Trademark) (Bortezomib); MLN0002 (Anti-α4β7mAb); MLN1202 (Anti-CCR2 chemokine receptor mAb); Enbrel (Registered Trademark) (Etanercept, TNF receptor / Fc fusion protein, TNF blocker); Eprex ( (Registered Trademark) (Epoetin Alpha); Erbitux (Registered Trademark) (Cetuximab, anti-EGFR / HER1 / c-ErbB-1); Genotropin (Registered Trademark) (Somatropin, human growth hormone); Herceptin (Registered Trademark) (Trastuzumab, anti-HER2 / neu(erbB2) receptor mAb); Humatrope (Registered Trademark) (Somatropin, human growth hormone); Humira ( Humira (registered trademark) (adalimumab); insulin solution; Infergen (registered trademark) (interferon-alphacon-1); Natrecor (registered trademark) (nesilitide; recombinant human B-type natriuretic peptide (hBNP); Kineret (registered trademark) (anakinra); Leukine (registered trademark) (salglamostim, rhuGM-CSF); Lympho Cide (registered trademark) (epratuzumab, anti-CD22mAb); Benlysta (trademark) (lymphostat B, belimumab, anti-BlySmAb);Metallyse (registered trademark) (tenecteplase, t-PA analog); Mircera (registered trademark) (methoxypolyethylene glycol-epoetin beta); Mylotarg (registered trademark) (gemtuzumab ozogamicin); Raptiva (registered trademark) (efalizumab); Cimzia (registered trademark) (certolizumab pegol, CDP870); Soliris (trademark) (eculizumab); Paxerizumab (anti-C5 complement); Numax (registered trademark) (MEDI-524); Lucentis (registered trademark) (ranibizumab); Panorex (registered trademark) (17-1A, edrecolomab); Trabio (registered trademark) (reldelimumab); Seracim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4); Osidem (registered trademark) (IDM-1); Ovalex (Ova Rex (Registered Trademark) (B43.13); Nuvion (Registered Trademark) (Vizilizumab); Cantuzumab Meltansine (huC242-DM1); Neorecolmon (Registered Trademark) (Epoetin Beta); Numega (Registered Trademark) (Operlbequin, Human Interleukin-11); Neulasta (Registered Trademark) (Peggylated Filgrastim, Peggylated G-CSF, Peggylated Hu-Met-G-CSF); Neupogen (Registered Trademark) (Filgrastim, G-CSF, Hu-MetG-CSF); Orthoclone OKT3 OKT3 (registered trademark) (muromonab-CD3, anti-CD3 monoclonal antibody), Procrit (registered trademark) (epoetin alfa); Remicade (registered trademark) (infliximab, anti-TNFα monoclonal antibody); Reopro (registered trademark) (absiximab, anti-GP1 / Ilia receptor monoclonal antibody); Actemra (registered trademark) (anti-IL6 receptor mAb); Avastin (registered trademark) (bevacizumab), HuMax-CD4 (zanorimumab); Rituxan (registered trademark) (rituximab, anti-CD20 mAb); Tarceva (registered trademark) (erlotinib);Roferon-A (registered trademark) (interferon alpha-2a); Simulect (registered trademark) (basiliximab); Prexige (registered trademark) (lumiracoxib); Synagis (registered trademark) (palivizumab); 146B7-CHO (anti-IL15 antibody, see U.S. Patent No. 7153507); Tysabri (registered trademark) (natalizumab, anti-α4 integrin mAb); Valort im)(Registered Trademark)(MDX-1303, anti-anthracran protective antigen mAb); ABthrax(Trademark); Vectibix(Registered Trademark)(Panitumumab); Xolair(Registered Trademark)(Omalizumab); ETI211(Anti-MRSAmAb); IL-1 trap (Extracellular domains of both the Fc portion of human IgG1 and the IL-1 receptor components (type I receptor and receptor accessory protein)); VEGF trap (Ig domain of VEGFR1 fused to the Fc of IgG1); Ze Zenapax (registered trademark) (daclizumab); Zenapax (registered trademark) (daclizumab, anti-IL-2RαmAb); Zevalin (registered trademark) (ibritumomab / tiuxetan), Zetia (ezetimibe), Orencia (registered trademark) (atacicept, TACI-Ig); anti-CD80 monoclonal antibody (galiximab); anti-CD23mAb (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 (saltumumab); M200 (boroxiximab, 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 mAb MDX-066 (CDA-1) and MDX-1388); anti-CD22dsFv-PE38 complex (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401);Adekatsumumb; Anti-CD30mAb (MDX-060); MDX-1333 (Anti-IFNAR); Anti-CD38mAb (HuMaxCD38); Anti-CD40LmAb; Anti-CriptomAb; Anti-CTGF Ifibrogen (FG-3019); Anti-CTLA4mAb; Anti-eotaxin1mAb (CAT-213); Anti-FGF8mAb; Anti-Gangri-Oshido GD2 ... GNOR GM2 mAb; Anti-GDF-8 HIT 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 (CN TO1275); Anti-IL13 mAb (CAT-354); Anti-IL2 RamAb (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-Mannos receptor / hCGβ mAb (MDX-1307); Anti-Methotrein dsFv-PE38 Complex (CAT-5001); anti-PD1 mAb (MDX-1106 (ONO-4538)); anti-PDGFRα antibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL receptor -2ヒトmAb (HGS-ETR2); anti-TWEAKmAb; anti-VEGFR / Flt-1mAb; anti-ZP3mAb (HuMax-ZP3); NVS antibody ♯1; ならびにNVS antibody ♯2などがある. ;

[0067] This may also include sclerostin antibodies, including, but not limited to, romosozumab, brosozumab, or BPS804 (Novartis). Furthermore, it may include therapeutic agents such as rilotumumab, bixalomer, trevananib, ganitumumab, conatumumab, motesanib diphosphate, brodalumab, vispiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX, or XGEVA. In addition, for example, U.S. Patent No. 8,030,547, U.S. Public Notice 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 Monoclonal antibodies (IgG) that bind to human protein-converting enzyme subtilisin / kexin type 9 (PCSK9), such as 55783, WO2012 / 0544438, WO2010 / 029513, WO2011 / 111007, WO2010 / 077854, WO2012 / 088313, WO2012 / 101251, WO2012 / 101252, WO2012 / 101253, WO2012 / 109530, and WO2001 / 031007, can be included in the drug delivery device.

[0068] This may include tarimodine laharpalebeck or other oncolytic HSVs for the treatment of melanoma or other cancers. Examples of oncolytic HSVs include, but are not limited to, tarimodine laharpalebeck (US Patent Nos. 7,223,593 and 7,537,924); OncoVEXGALV / CD (US Patent 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] TIMP is also included. TIMP is an endogenous metalloproteinase tissue inhibitor (TIMP) that is 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 connective tissue degradation diseases 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 the DNA encoding TIMP-3 are disclosed in U.S. Patent No. 6,562,596, issued on May 13, 2003, and the disclosure of this patent is incorporated herein by reference. Descriptions of TIMP variants can be found in U.S. Patent Publication No. 2014 / 0274874 and PCT Publication No. WO2014 / 152012.

[0070] This includes 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 on these molecules can be found in PCT application WO2010 / 075238.

[0071] In addition, bispecific T cell engager antibodies (BiTe), such as blinotumomab, can be used in drug delivery devices. Alternatively, APJ macromolecule agonists, such as apelin or its analogues, can be included in drug delivery devices. Information regarding such molecules can be found in PCT Publication WO2014 / 099984.

[0072] In one embodiment, the pharmaceutical product contains a therapeutically effective amount of anti-thymocrine interstitial lymphocyte generating factor (TSLP) or a 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. Patents 7,982,016 and 8,232,372, and U.S. Patent Publication No. 2009 / 0186022. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in U.S. Patent 8,101,182. In a particularly preferred embodiment, the pharmaceutical product contains a therapeutically effective amount of anti-TSLP antibody designated as A5 in U.S. Patent 7,982,016.

[0073] While drug delivery devices, needle guard mechanisms, systems, methods, and their components have been described in reference to exemplary embodiments, they are not limited to such embodiments. Rather, the appended claims should be interpreted broadly to include other modifications and embodiments that can be made by those skilled in the art without departing from the effective and applicable scope of the equivalents of drug delivery devices, needle guard mechanisms, systems, methods, and their components.

Claims

1. A drug delivery device, A housing configured to accommodate a drug storage container including a dosage delivery member, having an opening, wherein at least the insertion portion of the dosage delivery member is configured to extend through the opening of the housing, A needle guard positioned adjacent to the opening and movable relative to the housing between an extended position and a retracted position, wherein the retracted position is close to the extended position, the insertion portion of the dosage delivery member is surrounded by the needle guard in the extended position, and the insertion portion of the dosage delivery member is at least partially exposed when the needle guard is in the retracted position, An interference mechanism for providing a selected threshold resistance force to the movement of the needle guard from the extended position to the retracted position while the dose delivery member is inserted into the body tissue of the injection site, the interference mechanism comprising a first member positioned radially inward of a portion of the inner surface of the housing near the first member and a second member extending from the needle guard, wherein the first member and the second member engage with each other to hold the needle guard in the extended position, and the first member moves relative to at least a portion of the housing when the resistance force exceeds the selected threshold force, allowing relative sliding between the first member and the second member when the needle guard is pressed toward the injection site so that the needle guard can be moved toward the retracted position and the dose delivery member can be inserted, and the interference mechanism The drug delivery device comprising the above-mentioned features.

2. The drug delivery device according to claim 1, wherein one of the first member and the second member is provided with a cam, and the other of the first member and the second member is provided with a cam follower.

3. The drug delivery device according to claim 2, wherein the cam follower is biased relative to the cam.

4. The drug delivery device according to any one of claims 2 to 3, wherein the cam follower comprises a flexible arm that applies a biasing force to the cam follower facing the cam.

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

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

7. The drug delivery device according to any one of claims 2 to 6, wherein the cam comprises a fixed continuous or segmented circumferential bead.

8. The drug delivery device according to any one of claims 2 to 5, wherein the cam is provided with a fixed groove.

9. The drug delivery device according to any one of claims 1 to 8, wherein the needle guard is at least partially inserted into the housing in the storage position.

10. The drug delivery device according to any one of claims 2 to 8, wherein the first member comprises the cam and the second member comprises the cam follower.

11. The drug delivery device according to any one of claims 2 to 8, wherein the first member comprises the cam follower and the second member comprises the cam.

12. The drug delivery device according to any one of claims 1 to 11, wherein the drug storage container comprises a syringe.

13. A drug delivery device according to any one of claims 1 to 12, further comprising: a drug storage container further comprising a stopper movably disposed within the drug storage container for releasing a drug; and an injection drive mechanism comprising a plunger acting on the stopper and an energy source that exerts force on the plunger to cause the plunger to act on the stopper and release the drug.

14. The drug delivery device according to any one of claims 1 to 13, wherein the dose delivery member comprises an injection needle or a cannula.

15. A drug delivery device according to any one of claims 1 to 14, further comprising a drug stored in the drug storage container, wherein the drug is selected from the group consisting of a TNF inhibitor, an antibody against a calcitonin gene-related peptide receptor, a colony-stimulating factor, a erythropoiesis stimulant, an apelin receptor agonist, an anti-thymocrine lymphocyte necrosis antibody, an anti-thymocrine lymphocyte necrosis receptor antibody, an antibody that binds to human protein-converting enzyme subtilisin / kexin type 9, and a tissue inhibitor of metalloproteinase.

16. The drug delivery device according to claim 1, wherein the first member is separate from the needle guard.

17. The drug delivery device according to claim 1, wherein the needle guard is configured to move relative to the first member when it moves to the storage position.

18. A drug delivery device, The longitudinal axis, A housing with an opening, A drug storage container comprising a proximal end, a distal end, and a dosage delivery member, wherein the dosage delivery member is positioned at the distal end of the drug storage container and has an insertion portion configured to extend through the opening of the housing during drug delivery, A needle guard positioned adjacent to the opening and movable relative to the housing between an extended position and a retracted position, wherein the retracted position is close to the extended position, the insertion portion of the dosage delivery member is surrounded by the needle guard in the extended position, and the insertion portion of the dosage delivery member is at least partially exposed when the needle guard is in the retracted position, A needle guard bias member configured to push the needle guard distally, wherein at least a portion of the needle guard bias member is distal to the proximal end of the drug storage container, An interference mechanism for providing a selected threshold resistance force to the movement of the needle guard from the extended position to the retracted position while the dose delivery member is inserted into the body tissue of the injection site, the interference mechanism comprising a first member extending from the inner surface of the housing toward the longitudinal axis and a second member extending from the needle guard, wherein the first member and the second member engage with each other to hold the needle guard in the extended position, and the first member moves relative to at least a portion of the housing when the resistance force exceeds the selected threshold force, allowing relative sliding between the first member and the second member when the needle guard is pressed toward the injection site so that the needle guard can be moved toward the retracted position and the dose delivery member can be inserted, and the interference mechanism The drug delivery device comprising the above-mentioned features.

19. The drug delivery device according to claim 18, wherein one of the first member and the second member is provided with a cam, and the other of the first member and the second member is provided with a cam follower.

20. The drug delivery device according to claim 18 or 19, wherein the needle guard is at least partially inserted into the housing in the storage position.

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