Drug delivery device

Abstract

A drug delivery device includes a housing defining a casing having a proximal end and a distal end, a needle assembly disposed at least partially within the casing at the proximal end of the casing, a drive assembly disposed at least partially within the casing, and a damper mechanism disposed at least partially within the casing adjacent the distal end. The housing further defines a longitudinal axis extending between the proximal end and the distal end. The needle assembly includes a syringe containing a medicament and a needle or cannula. The drive assembly is operably coupled to the needle assembly to cause the medicament to pass through the needle or cannula. The damper mechanism is operably coupled to the drive assembly and the housing. Upon activation of the drive assembly, the damper mechanism exerts a torque on at least one component operably coupled to the drive assembly to dampen the action of the drive assembly.

Description

[0001] This application is a divisional application of the invention patent application with application number 201980064414.1, application date October 15, 2019, and invention title "Drug Delivery Device with Damping Mechanism". Technical Field

[0002] This disclosure generally relates to syringes, and more specifically to torque-driven syringes with damping mechanisms. Background Technology

[0003] Auto-injectors and on-body injectors offer several benefits in the delivery of medications and / or therapeutic agents. One of these benefits, compared to traditional delivery methods using, for example, conventional syringes, can be the ease of use.

[0004] Many syringe systems use helical spring structures to provide actuation energy for functions such as needle insertion and drug delivery. The use of springs can offer simplification benefits for user and device automation, but it can also have limitations. For example, there is a linear relationship between force and displacement in linear spring actuators. To provide sufficient energy for drug delivery at the end of the plunger stroke, excess energy may be input into the system as drug delivery begins.

[0005] Furthermore, when delivering higher viscosity drugs via an autoinjector, the required spring force may increase. A spring with a higher spring constant will transmit a greater force to the drug product and the main container for each stroke distance at the beginning of the stroke. In many autoinjectors, an air gap exists between the plunger face and the storage portion containing the drug before the drug is injected into the user. When the drug is to be administered, the spring pushes the plunger face toward the drug through the air gap. Because the plunger face exhibits very little resistance when passing through the air gap, and because of the greater force pushing the plunger, the plunger face may suddenly come into contact with the storage portion containing the drug. The patient may feel this excess energy as a “slap” or similar physical “impact” when the spring-driven plunger strikes the stopper of the main container storing the drug. Additionally, the user may also experience abrupt, recoil, and / or reaction forces when rotational motion begins due to a sudden change in acceleration. Such mechanical impacts can distract and / or interfere with the user of the syringe, and therefore may affect the appropriate dosage. Furthermore, the "slapping" and "impact" generated by excessive energy can potentially lead to catastrophic effects, such as shear loads causing rupture of the main container and damage to the pharmaceutical product. Additionally, high-force springs can generate undesirable high shear rates on pharmaceutical products.

[0006] Furthermore, due to variations in drug properties, patients may experience significant variations in injection time. These variations can be disruptive to users, who may perceive a problem with drug administration and therefore terminate the injection before receiving the full dose. Variations in injection time can be caused by significant changes in drug viscosity due to temperature changes, or significant changes in friction between components of the device (e.g., between the syringe and the stopper). Summary of the Invention

[0007] According to a first aspect, a drug delivery device includes a housing defining a shell having a proximal end and a distal end, a needle assembly at least partially disposed within the housing at the proximal end, a drive assembly at least partially disposed within the housing, and a damper mechanism at least partially disposed within the housing at the distal end. The housing further defines a longitudinal axis extending between the proximal and distal ends. The needle assembly includes a syringe containing a drug and a needle or cannula. The drive assembly is operatively coupled to the needle assembly to facilitate the passage of the drug through the needle or cannula. The damper mechanism is operatively coupled to the drive assembly and the housing. Upon activation of the drive assembly, the damper mechanism inhibits the action of the drive assembly. In some instances, the syringe may be constructed of a polymeric material. The drug may have a viscosity of less than about 10 cP at about 21 degrees Celsius.

[0008] In this respect, the damper mechanism includes a frame member, a damper member operatively coupled to the drive assembly, a chamber formed between a portion of the frame member and the damper member, and damper fluid disposed within the chamber. In some forms, the frame member may be integrally formed with the housing. When the drive assembly of the drug delivery device is activated, the frame member and the damper member rotate relative to each other, and the damper fluid applies opposing forces to at least one of the frame member and the damper member.

[0009] In some methods, the drug delivery device may further include an excess chamber fluidly coupled to the chamber. This excess chamber is adapted to receive excess damper fluid. Additionally, in some forms, the device may include a seal disposed near the chamber to retain the damper fluid within the chamber. In some aspects, the chamber is axially aligned with the longitudinal axis. In other methods, the chamber may be partially axially aligned with the longitudinal axis and may be partially laterally aligned with the longitudinal axis. In other methods, the chamber may be laterally aligned with the longitudinal axis.

[0010] In any of these examples, the drive assembly may include: a plunger assembly comprising a threaded plunger rod and a plunger face, a plunger rod guide coupled to the plunger assembly, and a torsion spring coupled to the plunger rod guide. The plunger face is disposed near the needle assembly and is movable along the longitudinal axis of the housing. The plunger rod guide guides the rotational movement of the plunger assembly and is operatively coupled to either the frame member or the damper member. The torsion spring applies a force to the plunger rod guide that causes it to rotate. The rotation of the plunger rod guide causes the plunger assembly to advance toward the proximal end of the housing to facilitate the passage of the medication through the needle assembly. The plunger assembly may additionally include a gap greater than about 10 mm between the threaded plunger rod and the plunger face. Further, the syringe may contain at least about 1 mL of medication with a viscosity of at least about 4 cP. Other examples are also possible.

[0011] Furthermore, in any of the foregoing examples, the damper mechanism may apply an opposing force to the drive assembly, or to at least one component operatively connected to the drive assembly.

[0012] According to another aspect, a damper mechanism for a drug delivery device includes a frame member, a damper member operatively coupled to a drive assembly of the drug delivery device, a chamber formed between a portion of the frame member and the damper member, and a damper fluid disposed within the chamber. When the drug delivery device is activated to administer a drug to a user, the frame member and the damper member rotate relative to each other, and the damper fluid applies opposing forces to at least one of the frame member and the damper member.

[0013] According to another aspect, an autoinjector includes: a housing defining a casing having a proximal end, a distal end, and a longitudinal axis extending between the proximal and distal ends of the casing; a needle assembly at least partially disposed within the housing at the proximal end; and a drive assembly at least partially disposed within the housing. The needle assembly includes a syringe containing a drug substance and a needle or cannula. The drive assembly is operatively coupled to the needle assembly to facilitate passage of the drug substance through the needle or cannula. The drive assembly includes a plunger assembly having a plunger rod and a plunger face disposed near the needle assembly and movable along the longitudinal axis of the housing. The syringe is adapted to contain at least about 1 mL of a drug substance with a viscosity of at least about 4 cP. The plunger rod and the plunger face have an initial gap greater than about 10 mm. Attached Figure Description

[0014] The above-mentioned needs are at least partially met by providing a torque-driven drug delivery device as described in the following specific embodiments, particularly studied in conjunction with the accompanying drawings, wherein:

[0015] Figure 1 A cross-sectional view of an exemplary torque-driven drug delivery device with a damper mechanism according to several different embodiments is shown;

[0016] Figure 2 Demonstrates various embodiments Figure 1 A close-up cross-sectional view of the damper mechanism of an exemplary drug delivery device;

[0017] Figure 3 A cross-sectional view of a second exemplary drug delivery device having a chamber for excess damper fluid according to several different embodiments is shown;

[0018] Figure 4 A cross-sectional view of a third exemplary drug delivery device having damper fluid disposed between disks of a damper mechanism, according to several different embodiments, is shown.

[0019] Figure 5 A cross-sectional view of a fourth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0020] Figures 6a and 6b show cross-sectional views of a fifth exemplary damper mechanism of a drug delivery device according to several different embodiments;

[0021] Figure 7 A cross-sectional view of a sixth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0022] Figure 8 A cross-sectional view of a seventh exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0023] Figures 9a-9c show cross-sectional views of an eighth exemplary damper mechanism of a drug delivery device according to several different embodiments;

[0024] Figure 10 A cross-sectional view of a ninth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0025] Figure 11 A cross-sectional view of a tenth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0026] Figure 12 A cross-sectional view of an eleventh exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0027] Figure 13A cross-sectional view of a twelfth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0028] Figure 14 A cross-sectional view of a thirteenth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0029] Figure 15 A cross-sectional view of a fourteenth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0030] Figure 16 A cross-sectional view of a fifteenth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0031] Figure 17 A cross-sectional view of a sixteenth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0032] Figure 18 A cross-sectional view of a seventeenth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0033] Figure 19 A cross-sectional view of an eighteenth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0034] Figure 20 A cross-sectional view of a nineteenth exemplary damper mechanism of a drug delivery device according to several different embodiments is shown;

[0035] Figure 21 The graphs depicting the change of shear stress with shear rate according to several different embodiments are shown.

[0036] Figure 22 A graph depicting the apparent viscosity as a function of shear rate according to several different embodiments is shown.

[0037] Figure 23 A perspective view of an exemplary drug delivery device with gaps between components, according to several different embodiments, is shown;

[0038] Figure 24 Illustrations show examples of the effect of damper mechanisms on drug delivery according to several different embodiments;

[0039] Figure 25 Illustrations show examples of the effects of damper mechanisms according to several different embodiments on drug delivery in low-friction environments;

[0040] Figure 26Illustrations show examples of the effects of damper mechanisms according to several different embodiments on drug expulsion in high-friction environments; and

[0041] Figure 27 Exemplary model calculations for a drug delivery device are shown according to several different embodiments.

[0042] Those skilled in the art will understand that the elements in the figures are shown for simplicity and clarity and are not necessarily drawn to scale. For example, the size and / or relative position of some elements in the figures may be enlarged relative to other elements to aid in understanding the various embodiments of the invention. Furthermore, commonly used but easily understood elements that are available or necessary in commercially viable embodiments are generally not depicted to facilitate viewing these various embodiments with less obstruction. It will also be understood that certain actions and / or steps may be described or depicted in a specific sequence of occurrence, and those skilled in the art will understand that such specificity in sequence is not actually necessary. It will also be understood that the terms and expressions used herein have the ordinary technical meaning consistent with those of skill in the art as set forth above, except for the different specific meanings set forth herein. Detailed Implementation

[0043] Generally, according to these various embodiments, a torque-driven syringe includes a housing, a syringe assembly containing the medication to be injected into the user, and a rotatable actuation assembly that injects the medication into the user using a torsion spring. As the rotatable actuation assembly rotates to result in medication administration, a fluid damper is used to provide a more consistent drug delivery time between medications with varying viscosities and between medications that may exhibit viscosity changes based on different environmental variations (variable temperatures).

[0044] Furthermore, the damper mechanism reduces or eliminates the "slap" and "impact" that occur when the plunger face first contacts the medication and / or medication storage device during rotation of the actuation mechanism. The damper mechanism also reduces "sudden movement" or recoil upon release of the mechanism. Therefore, the user will not feel this sudden movement during medication delivery and can administer the medication comfortably and safely. Furthermore, the use of a high-turns torsion spring (discussed in further detail below) maintains a near-constant starting and ending torque compared to conventional springs and springs with fewer turns. As a result, a smaller autoinjector can be used, thus increasing overall user comfort. Additionally, the damper reduces and / or eliminates variations in injection time and minimizes the risk of device stoppage. The damper also provides design freedom to target optimal injection time for availability and can potentially eliminate the need for custom-designed devices for different medication volumes.

[0045] Now refer to the attached diagram, especially the reference... Figure 1 and Figure 2 An exemplary syringe 100 includes a housing 102 defining a shell, a needle assembly 110 at least partially disposed within the housing 102, a drive assembly 120 also at least partially disposed within the housing 102, and a damper mechanism 140 at least partially disposed within the housing 102. The housing 102 includes a proximal end 102a and a distal end 102b, and defines a longitudinal axis "L" extending between the proximal end 102a and the distal end 102b.

[0046] The needle assembly 110 is typically located at or near the proximal end 102a of the housing 102 and includes a syringe 112 containing the drug 113 and a needle or cannula 114. The needle assembly 110 may include any number of additional components, such as one or more sidewalls, openings allowing the drug 113 to pass through and reach the needle or cannula 114, a return spring, a shield member, a filter member, etc., but for brevity, these will not be discussed in detail. A portion of the syringe 112 may be opened to accommodate a portion of the drive assembly 120, which will be described in further detail below. The syringe 112 may have any desired shape and / or size to accommodate various amounts of drug 113. In some instances, the syringe 112 may be constructed from a polymeric material such as a cyclic olefin polymer (“COP”), a cyclic olefin copolymer (“COC”), or a glass material. Other examples are also possible.

[0047] The drive assembly 120 may include a nut 122, a trigger ring 124, a plunger rod guide 126, a plunger rod assembly 130, and a drive mechanism 136 in the form of a torsion spring or a power spring, positioned adjacent to the syringe barrel 112. Typically, a portion of the drive assembly 120 may be fixedly coupled to the housing 102 via various methods. In some arrangements, the nut 122 may be integrally formed with the housing 102 and may include a threaded opening 122a. The trigger ring 124 selectively engages with the nut 122 and is configured to move in an axial direction. In the example shown, the trigger ring 124 is in the form of a generally cylindrical ring, having a generally circular inner surface and any number of flanges, protrusions, and grooves disposed around and / or inside the circumference of the ring. The trigger ring 124 may be coupled to the housing 102 via various techniques.

[0048] The plunger rod guide 126 includes a rod-shaped portion 127 and a base portion 128 coupled to the rod-shaped portion. The plunger rod guide 126 includes an opening 126a that extends at least partially through the rod portion 127 and the base portion 128. The base portion 128 may have any number of protrusions or lugs extending therefrom to define a slidable engagement with the trigger ring 124.

[0049] The plunger rod assembly 130 includes a plunger rod 131 movable along the longitudinal axis L of the housing 102, a gasket 132, and a plunger 133. The plunger rod 131 has a threaded portion 131a that is threadedly engaged with a plunger rod guide 126 and a threaded opening 122a of a nut 122. The gasket 132 minimizes frictional losses between the rotating plunger rod 131 and the non-rotating plunger 133. In some methods, the gasket 132 can also be used to adjust the volume of the agent 113 by making the gasket 132 thicker or narrower. Therefore, the gasket 132 can be used to accommodate a range of fill volumes of agent 113 within the same device 100, thereby allowing for better control of the air gap between the bottom of the gasket 132 and the top of the plunger 133.

[0050] The rod portion 127 of the plunger rod guide 126 is coupled to the plunger rod assembly 130 via various methods, including, for example, via a splined connection or slotted arrangement that allows axial displacement of the plunger rod assembly 130 relative to the plunger rod guide 126. Thus, the plunger rod guide 126 guides the rotational movement of the plunger rod assembly 130. When driven by the drive mechanism 136, the threaded portion 131a of the plunger rod 131 and the corresponding threaded opening 122a of the nut 122 can have a pitch suitable for any desired drug delivery rate or force / torque combination. Relative rotation between the plunger rod 131 and the nut 122 causes the plunger rod 131 to advance axially toward the proximal end 102a of the housing 102. The plunger 133 has a top surface 133a disposed near the syringe barrel 112.

[0051] In the illustrated example, the drive mechanism 136 takes the form of a power spring or torsion spring 136, having an internal portion 136a connected via any known method to the rod portion 127 of the plunger rod guide 126 to apply torque to the plunger rod guide 126, causing the plunger rod guide 126 to rotate about axis L. In some examples, the torsion spring 136 may have a high number of turns to provide the appropriate rotational stroke required to expel the drug from the syringe barrel 112; however, other parameters of the spring design may affect its torque output, such as material properties and any applied heat treatment. The pre-forming of the torsion spring 136 may also affect its performance. As an example, in an autoinjector, a prestressed spring may be preferred because the prestressing process typically increases the spring's torque output by initially winding the spring in the opposite direction of the intended operating condition, resulting in permanent deformation of the steel strip. This deformation maximizes the stress in the material, leading to an increase in torque. This increase in torque is beneficial for minimizing the size and weight of the device.

[0052] In some examples, in a wound or loaded configuration, the torsion spring 136 may have approximately 1 to approximately 30 turns, and preferably approximately 12 turns. In some examples, due to a margin of approximately 20% at both ends of the working range, the total number of spring turns may be higher, potentially resulting in a range between approximately 1*1.4 = 1.4 and 30*1.4 = 42. The number of turns for the delivery mechanism is derived from the pitch and the required stroke length. As previously mentioned, a smaller pitch is preferred because it requires lower torque input and starting force. Therefore, the starting force will also be lower. If high axial force is not required, the pitch can be increased and fewer spring turns are needed, allowing for a smaller device. In some examples, the torsion spring 136 may have multiple initial or preloaded turns to have available torque. After the preloaded turns, the torsion spring 136 is further wound with working turns or turns used in the device during injection. As a non-limiting example, the torsion spring 136 may have approximately 2.5 preloaded turns and approximately 6 working turns. Therefore, the total number of turns during assembly is approximately 8.5. However, due to potentially large tolerances in the angular positioning of the spring terminals, the torsion spring 136 may have initial clearance before reaching a solid state, and thus may have approximately 10 turns in total. Devices with different drug volumes and viscosities may require different average torques from the torsion spring 136 if the same dosage is desired. The average torque output can be controlled by adjusting the width of the band used for the torsion spring 136 (e.g., the axial length of the torsion spring 136 when arranged in a device) and maintaining the same number of working turns. Doing so allows for the use of different springs with similar injection times for the same device construction, while allowing for variations in drug volume and / or viscosity.

[0053] In some instances, the energy (EFLOW) required to expel the drug 113 through the needle 114 is determined by any combination of drug volume, viscosity, needle flow path size, and target administration time. The energy (ESPRING) transmitted by the torsion spring 136 can be determined by any combination of the number of working turns (N) and the average spring torque during the working turns (T). The energy transmitted by the spring can be calculated using the following formula: ESPRING = 2*π*N*T. If there is no frictional loss in the system, the following relationship exists: EFLOW = ESPRING = 2*π*N*T. Therefore, the following relationship arises: EFLOW / (2*π) = N*T. In other words, in order to have sufficient energy in the torsion spring 136 to expel a given volume of a given drug through a given needle within a given time, the product (N*T) remains constant, and therefore a higher torque can be converted into fewer working turns.

[0054] The threaded interface between the plunger rod 131 and the nut 122 provides translation between the input torque and the output axial force of the torsion spring 136. By providing a torsion spring 136 with a high number of turns, a lower total torque and smaller variations in starting and ending torque are achieved compared to linear springs with comparable transmission specifications or other torsion springs with fewer turns and lower pitch. Furthermore, due to the increased number of turns, the threads of the plunger rod 131 and the nut 122 can have a smaller pitch while still achieving the same linear movement of the plunger rod assembly 130. If the pitch is smaller, a smaller input torque is required to provide the same output force as a high-pitch, high-torsion spring. Therefore, the high-turns (e.g., between about 1 and about 30 turns), low-torque system described herein allows for a reduced starting force, as the starting force is directly related to the input torque that must be used to drive the plunger rod assembly 130. Additionally, the reduced internal structural forces required to resist the torque from the torsion spring 136 during storage (e.g., before use) allow for a smaller syringe design and the use of less expensive raw materials. Furthermore, the threaded interface between the plunger rod 131 and the nut 122 allows the threaded plunger rod 131 to be adjusted to accommodate varying amounts of drug stored in the syringe 112. If necessary, the threaded plunger rod 131 can be initially installed in a lower position within the syringe 100 to minimize the volume of drug disposed in the syringe 112. This reduces the number of proprietary parts and simplifies variation management. The threaded plunger rod 131 can also be adjusted to various depths during manufacturing and / or assembly as needed.

[0055] The damper mechanism 140 is also at least partially disposed within the housing 102 at its distal end 102b. The damper mechanism 140 is operatively coupled to a portion of the drive assembly 120 (e.g., the plunger rod guide 126) and the housing 102. The damper mechanism 140 is used to suppress the effect of the torsion spring 136 on the drive assembly 120.

[0056] Typically, to activate the device, the user presses the device 100 against their skin, thereby disengaging the trigger ring 124 from the nut 122 and / or the plunger rod guide 126. This disengagement allows the plunger rod guide 126 to rotate relative to the trigger ring 124. Because the torsion spring 136 is in a wound or compressed state, the torsion spring 136 will begin to unwrap, causing the plunger rod guide 126 to rotate. This rotation, in turn, causes the plunger rod 131 to rotate, which, due to the threaded interface between the plunger rod 131 and the nut 122, causes the plunger rod 131 and the plunger 133 to advance toward the proximal end 102a of the housing 102, thereby inserting the needle or cannula 114 and administering the medication 113. As a non-limiting example, U.S. Provisional Application No. 62 / 719,367, filed August 17, 2018, describes the activation process and components of the drive assembly in more detail, and the entire contents of that application are therefore incorporated herein by reference.

[0057] exist Figure 1 and Figure 2 In the illustrated example, the damper mechanism 140 includes a damper member 142, a frame member 150, a chamber 160 formed between a portion of the damper member 142 and the frame member 150, and a damper fluid 151 disposed within the chamber 160. The damper member 142 can be coupled to the plunger rod guide 126 via any number of methods (e.g., via friction fit or threaded engagement). The damper member 142 includes a body 143 having an inner surface 143a that defines a central opening or bore 144 to receive a portion of the plunger rod guide 126 and further includes an outer surface 143b. The damper member 142 further includes a wing-like portion 145, the inner surface 145a of which is positioned away from the body 143 and facing its outer surface 143b. A channel 146 is formed between the outer surface 143b of the body 143 and the inner surface 145a of the wing-like portion 145.

[0058] The frame member 150 is operatively coupled to the housing 102. For example, the frame member 150 may be in the form of a cylindrical member defining a body 152 and a connecting portion 153, which is coupled to the housing 102 by any number of methods, such as adhesive, threads, friction connection, etc. In some instances, the frame member 150 may be integrally formed with the distal end 102b of the housing 102.

[0059] The body 152 of the frame member 150 is adapted to be at least partially inserted into the channel 146 of the damper member 142. In the illustrated example, the frame member 150 further includes a flange 155 that engages (e.g., via a friction connection) with the inner surface 145a of the wing-like portion 145. The chamber 160 is defined by the body 152 of the frame member 150 and the body 143 of the damper member 140. In some examples, the housing 102 may further define the end faces of the chamber 160. The damper fluid 151 is disposed within this chamber 160.

[0060] As previously described, the relative rotation between the components of the damper mechanism 140 causes the damper fluid 151 to suppress this effect. Specifically, in this example, when the plunger rod guide 122 rotates, the damping member 140 rotates relative to the frame member 150. A torque from the torsion spring 136 exists between the damper member 142 and the frame 150, causing the system to accelerate from a standstill, thereby increasing the speed. During the relative rotation, the damper fluid 151 experiences shear stress due to the rotation of the damper member 142. Therefore, in the disclosed example, the damper fluid 151 applies an opposing reaction torque to the drive assembly 120, particularly to the plunger rod guide 126 of the drive assembly 120. The speed of the drive assembly 120 increases until the opposing damper torque has accumulated to the same level as the administered torque and reaches equilibrium. This balance occurs at specific speeds and torques and depends on many factors, such as the geometry of the damper mechanism 140, the fluid characteristics of the damper fluid 151, and the torque curve of the torsion spring 136. Other examples are also possible.

[0061] With this configuration, the damper mechanism 140 has a relatively simple design using a minimal number of parts, reducing assembly and component costs and complexity. The damper mechanism 140 can be easily assembled, filled, and tested on a separate assembly line before being inserted into the device 100. In some instances, a robust and stable damper mechanism 140 may also be of interest. Many parameters can affect the performance of the damper mechanism 140, and the stability of the damper mechanism 140 can be further increased by reducing the influence of these parameters. For example, and as previously mentioned, a damper fluid 151 with a low viscosity variation with temperature, exhibiting shear-thinning characteristics, can be selected. The shear stress in the damper fluid 151 is directly related to the damping torque. To obtain a relatively constant and predictable velocity at a given desired damping torque, it is desirable that changes in the input torque (and thus changes in shear stress) result in minimal changes in the shear rate. In some instances, and as... Figure 21The figure shown depicts the shear stress as a function of shear rate for damper fluid type "G," which is optimally achieved through a design that minimizes the shear rate (as a variation of shear rate y) at the lower end of the damper for a given input torque interval within this region. Note that... Figure 21 The curves provided and the values ​​shown therein are merely exemplary curves, and other curves may be used. Figure 22 The apparent viscosity of damper fluid type G is shown. The shear-thinning characteristic can be observed by the decrease in apparent viscosity with increasing shear rate.

[0062] Another parameter that may affect the robustness and stability of the damper mechanism includes the large clearance at the small diameter. The shear rate level is designed to be sized and influenced by the damper mechanism 140. The size of the clearance defining the chamber 160 affects the shear rate. Technical tolerances can have a minimal impact on the size of the chamber 160 while ensuring that the nominal size of the chamber 160 is as large as possible and that the chamber 160 is placed with the smallest possible diameter.

[0063] In addition, a brief reference Figure 23 The described damper mechanism 140 allows for a significant gap “C” (e.g., about 10 mm or more) between the plunger rod 131 and the plunger 133 without the risk of damage to the injection cartridge 112 or other components of the device 100 during its activation and impact between the plunger rod 131 and the plunger 133. These devices can be adapted to extrude at least about 1 ml of a pharmaceutical agent 113 having a viscosity of at least about 4 cP. Such a large gap advantageously reduces platform complexity, inventory variations, and / or process control. The damper mechanism 140 also provides a better user experience compared to devices without a damper mechanism, where the impact vibrations, sensations, and sounds can be startling to the user.

[0064] In some instances, it may be beneficial for a large portion of the damper component's surface to be in contact with the damper fluid. If, due to insufficient filling, the entire surface is not in contact with the damper fluid, the damping torque will be reduced. Therefore, Figure 3 An alternative damper mechanism 240 for drug delivery device 200, which is less sensitive to filling accuracy, is shown. It should be understood that drug delivery device 200 includes any number of similar parts and / or features similar to those of drug delivery device 100, and therefore includes those referenced. Figure 1 and Figure 2The similar two-digit suffixes used. Therefore, these components will not be discussed in substantial detail. In the drug delivery device 200, the damper member 242 includes a body 243 having an inner surface 243a that defines a central opening or hole 244 to receive a portion of the plunger rod guide 226 and further includes an outer surface 243b. The damper member 242 includes a wing-shaped portion 245 having an inner surface 245a and a notch 245b. The damper member 242 further defines a channel 246 between the outer surface 243b of the body 243 and the inner surface 245a of the wing-shaped portion 245, and further includes an end cap portion 247.

[0065] In this example, the frame member 250 is integrally formed as the end cap of the housing 202. The frame member includes a generally cylindrical protrusion 252 having an inner surface 252a and an outer surface 252b. The cylindrical protrusion 252 defines a lug 253 on the outer surface 252b. When the damper mechanism 240 is mounted to the drug delivery device 200, the cylindrical protrusion 252 is inserted into the channel 246. In this configuration, a notch 245b engages with the lug 253 to restrict relative axial movement between the damper member 242 and the frame member 250. Furthermore, the concentric cylinders are constrained to each other in the radial direction, so component tolerances have minimal impact on concentricity. However, relative rotation between the damper member 242 and the frame member 250 is still permitted. In this example, a U-shaped chamber 260 is formed between the protrusion 252, the body 243, and the end cap portion 247 to accommodate the damper fluid 251. In this configuration, the chamber is partially axially and partially laterally aligned with the longitudinal axis L. During construction, channel 246 further defines an excess chamber 248 to accommodate any excess damper fluid, which can be used to selectively adjust the resulting damping torque, or simply as an "overflow" area in case more fluid is unintentionally supplied than desired. In these examples, the damper mechanism 240 can be engaged with housing 202 and / or drive assembly 220 as needed. Furthermore, the damper mechanism 240 can be assembled to device 200 via an axial assembly process.

[0066] In some instances, it may be desirable to provide a sealed portion to ensure that the damper fluid remains within the desired chamber to maintain a constant damping torque. Such a seal can create resistance between the frame and the damper components, which in turn generates a drag torque. This may be undesirable during drug delivery because a larger power source (i.e., a torsion spring) may be required to overcome this additional resistance. Therefore, Figure 4An alternative drug delivery device 300 with an alternative damper mechanism 340 is shown, which allows for easy filling of damper fluid while preventing fluid leakage. The drug delivery device 300 includes any number of similar components and / or features similar to those of drug delivery devices 100 and 200, and therefore includes references. Figures 1 to 3 Similar two-digit suffixes are used. Therefore, these components will not be discussed in substantial detail. In the drug delivery device 300, the damper member 342 includes a body 343 and a disc portion 345 coupled to the body 343. The disc portion 345 defines a first surface 345a and includes any number of grooves 345b positioned along its length and terminating at an outer end 345c. The frame member 350 is also in the form of a generally cylindrical member having a generally disc-shaped base 352 that defines a first surface 352a and a sidewall portion 353 including a lug 353a. The disc-shaped base 352 further defines an opening 354.

[0067] In the illustrated example, any number of sealing members 347 are disposed within or near one or more recesses 345b of the damper member 342. For assembly of the damping mechanism, the disc damper member 342 is inserted into the opening 354 of the base 352, with its external end 345c engaging with the lug 353a of the sidewall portion 353. As a result, a chamber 360 is formed between the first surface 345a of the disc portion 345 and the first surface 352a of the base 352. In this example, the chamber 360 is configured laterally and sealed via the sealing members 347(s). Such a damper mechanism 340 can be assembled in the same power module without internal rotational clearance, thereby reducing and / or eliminating the risk of sudden movement of the device 300 during startup.

[0068] Go to Figure 5 The alternative damper mechanism 440 for the drug delivery device 400 includes features similar to those of the aforementioned damper mechanism 240. Therefore, these features have the same characteristics as... Figure 3 The similar two-digit suffix provided herein will therefore not be described in substantial detail. The damper mechanism 440 further includes a generally cylindrical extension 447a extending from the end cap portion 247, which mates with an inner cylinder 450a extending from the frame member 450. While relative rotation is still permitted when the frame member 450 is engaged with the damper member 442, the concentric engagement between the extension 447a and the inner cylinder 450a increases the alignment of the components, resulting in a smaller change in the dimensions of the chamber 460.

[0069] Turn Figure 6A , 6B , Figure 7 and Figure 8Alternative damper mechanisms are provided that effectively double the damping surface by forming two chambers containing damping fluid on multiple sides of the frame member. As a result, these damping mechanisms can produce approximately twice the damper torque compared to similar designs with a single chamber. Advantageously, these damper mechanisms can be made smaller than single-chamber designs if the same level of damping torque is required. These damping mechanisms include those referenced... Figures 1 to 5 The described features are similar, and therefore contain similar two-digit suffixes. Therefore, for the sake of brevity, some of these components may not be described in substantial detail.

[0070] like Figure 6A and Figure 6B As shown, the damper member 542 is generally U-shaped and defines a channel 546 between the inner sidewall 543a and the outer sidewall 543b. The damper member 542 may additionally include a lug 544 extending from the outer sidewall 543b and a flange 545 extending from the inner sidewall 543a. The frame member 550 includes a base portion 552, a first generally cylindrical projection 553, and a second generally cylindrical projection 554 carrying a notch 554a.

[0071] In operation, the flange 545 of the damper member 542 frictionally engages with the plunger rod guide 526 for rotatable connection to the plunger rod guide. The channel 546 is filled with damper fluid 551, and the frame member 550 is connected to the damper member 542 by inserting a first cylindrical protrusion 553 into the channel 546. In doing so, a notch 554a engages with a lug 544 to secure the damper member 542 to the frame member 550. Further, the first cylindrical protrusion 553 divides the channel 546 into a U-shaped chamber 560, whereby the damper fluid 551 surrounds and is thus positioned on both sides of the first protrusion 551.

[0072] Figure 7 Showing with Figure 6A and Figure 6B The described mechanism 540 is similar to the damper mechanism 640, but additionally includes a third generally cylindrical protrusion 655. This protrusion 655 engages with the inner wall 643a to form an additional channel 647 that serves as a fluid transport channel. Figure 8In this configuration, the components in the damper mechanism 740 are essentially reversed. In other words, the frame member 750 defines a channel 757 between the first sidewall 756 and the second sidewall 758, while still including a cylindrical protrusion 754 carrying a notch 754a. The damper member 742 includes a first protrusion 743, a second protrusion 744 carrying a lug 744a, and a third protrusion 745 carrying a flange 745a. A damper fluid 751 is disposed within the channel 757, and the first protrusion 743 is inserted therein to define a chamber 760 surrounding the first protrusion 743.

[0073] Figures 9A to 9C A similar damper mechanism 840 is shown, which allows for easy filling of damper fluid 851 into the channel 857 of the frame member 850. The damper member 842 is then applied, whereby the inclined protrusion 843 wedges into the damper fluid 851 and distributes the damper fluid into a single channel 860 between the first protrusion 843 and the first sidewall 856 and the second sidewall 858. In this example, the protrusion 844a engages with a notch 858a formed on the second sidewall 858. Similarly, in Figure 10 In the latter case, the components of the damper mechanism 940 are essentially reversed. In other words, like... Figure 6A , Figure 6B and Figure 7 The damper member 942 is generally U-shaped, defining a channel 946 between an inner sidewall 943a and an outer sidewall 943b. The damper member 942 further includes a second channel 947 extending from the outer sidewall 943b. The frame member 950 includes a base portion 952, a first protrusion 953, a second protrusion 954, and a third protrusion 956. Damper fluid 951 is inserted into the channel 946, and the first protrusion 953 is inserted into the channel 946 to define a chamber 960. In this example, the second protrusion 954 is inserted into the second channel 947.

[0074] Figure 11-20 Alternative damper mechanisms with a three-piece design are demonstrated. In these examples, the fluid path can be sealed and / or extended to ensure fluid is contained within the chamber or to allow for easy filling and assembly. Additionally, these components ensure concentricity between the damping surfaces. These damping mechanisms include reference... Figures 1 to 10 The described features are similar, and therefore contain similar two-digit suffixes. Therefore, for the sake of brevity, some of these components may not be described in substantial detail.

[0075] like Figure 11As shown, the damper mechanism 1040 includes a first damper member 1042, a frame member 1050, and a second damper member 1062. The first damper member 1042 can be coupled to a plunger rod guide (not shown) via any number of methods and includes a body 1043 having an inner surface 1043a, defining a central opening or hole 1044 to receive a portion of the plunger rod guide, and further defining an outer surface 1043b. The first damper member 1042 also includes a wing-like portion 1045, the inner surface 1045a of which is positioned away from the body 1043 and facing its outer surface 1043b. A channel 1046 is formed between the outer surface 1043b of the body 1043 and the inner surface 1045a of the wing-like portion 1045.

[0076] The second damper member 1062 is in the form of a generally cylindrical body 1063 having an inner surface 1063a and an outer surface 1063b. The second damper member 1062 includes a flange 1064 extending outward from the outer surface 1063b. The second damper member 1062 is adapted to be at least partially disposed within the channel 1046 and at least partially surround the body 1043 of the first damper member 1042 to form a concentric cylinder. In this configuration, a cavity 1060 is formed between the outer surface 1043b of the first damper member 1042 and the inner surface 1063a of the second damper member 1062. This cavity 1060 contains damper fluid 1051.

[0077] In this example, the frame member 1050 is integrally formed with the distal end 1002b of the housing 1002 and includes a base portion 1052 and a generally cylindrical protrusion 1053 extending from the base portion. In operation, the frame member 1050 is placed in or near the channel 1046 and can engage with the flange 1064 of the second damper member 1062 to hold the second damper member in place. The frame member 1050 may include any number of additional notches, lugs, etc., to selectively engage with the first damper member 1042 and / or the second damper member 1062. As a result, the chamber 1060 can be defined by the outer surface 1043b of the first damper member 1042, the inner surface 1063a of the second damper member 1062, and the base portion 1052 of the frame member 1050. Furthermore, the first damper member 1042, the second damper member 1062, and the frame member 1050 form three concentric cylinders, thereby restricting relative movement (except for relative rotation) between them. In some instances, the second damper member 1062 may be fixedly coupled to the frame member 1050 (which itself may be coupled to the housing 1002 and / or integrally formed with the housing) to ensure that the second damper member 1062 remains fixed while the first damper member 1042 rotates together with the plunger rod guide. Additionally, in some instances, the frame member 1050 may include a stop 1055 that engages with a groove 1045b on the wing-shaped portion 1045 of the first damper member 1042 to restrict relative axial movement.

[0078] Figure 12 The exemplary damper mechanism 1140 shown is similar to damper mechanism 1040 (and therefore, similar features include similar two-digit suffixes), but the placement of chamber 1160 and damper fluid 1151 differs. Specifically, chamber 1160 is defined by the inner surface 1145a of wing-shaped portion 1145, the outer surface 1163b of body 1163 of second damper member 1162, and the base portion 1152 of frame member 1150. In this example, frame member 1150 includes a protrusion 1153 that inserts into a channel 1164 defined by second damper member 1162 to secure frame member 1150 to second damper member 1162.

[0079] Figure 13 The exemplary damper mechanism 1240 shown is similar to damper mechanism 1140 (and therefore, similar features include similar two-digit suffixes), but differs in that the frame member 1250 includes a rotation-locking protrusion 1253 in the form of a pin, which engages with a cylinder or hole 1264 defined by the second damper member 1262. This restricts relative rotation between the frame member 1250 and the second damper member 1262.

[0080] Figure 14 The exemplary damper mechanism 1340 shown is similar to damper mechanism 1240 (and therefore, similar features include similar two-digit suffixes), but differs in that damper mechanism 1340 includes any number of sealing members to seal chamber 1360 to retain damper fluid 1351 therein. Specifically, frame member 1350 further includes resilient finger-like portions 1356 adapted to form a seal with the outer surface 1345b of the wing-like portion 1345 of the first damper member 1342. In this example, the wing-like portion 1345 has a generally conical or wedge-shaped shape to help properly position the resilient finger-like portion 1356 against its outer surface 1345b. Additionally, the first damper member 1342 abuts against the base portion 1352 of frame member 1350 as an additional seal in the form of a bump or stop 1343.

[0081] Figure 15 The exemplary damper mechanism 1440 shown is similar to the previously described three-piece damper mechanism (and therefore, similar features include similar two-digit suffixes), but can advantageously make the chamber 1460 easily filled with damper fluid 1451, and can further include any number of placement features to ensure proper alignment of the components during installation. Specifically, the protrusion 1453 formed by the base portion 1452 of the frame member 1450 may include a flange 1453a that facilitates proper placement of the first damper member 1442 against the frame member 1450. The outer surface 1443a of the first damper member 1442 abuts against the flange 1453a to ensure proper concentric arrangement of the frame member 1450 relative to the first damper member 1442, and further defines the chamber 1460 between the outer surface 1443a, the flange 1453a, and the protrusion 1453. Then, the chamber 1460 may be filled with damper fluid 1451, and a second damper member 1462 may be applied in the form of an assembled or press-fitted cap.

[0082] The second damper member 1462 includes a base portion 1463 that mates to define a channel 1466, a first protrusion 1464, and a second protrusion 1465. When the second damper member 1462 is installed, the first protrusion 1464 abuts against a protrusion 1453 of the frame member 1450, and the second protrusion 1465 further engages with a flange 1444 of the first damper member 1442. As a result, the protrusion 1453 of the base member 1450 engages with the flange 1444 of the first damper member 1442 to guide the placement of the second damper member 1462, thereby reducing and / or eliminating relative misalignment of these components. The second damper member 1462 also serves as a seal to close the chamber 1460.

[0083] Figure 16 The exemplary damper mechanism 1540 shown is similar to the previously described three-piece damper mechanism (and therefore, similar features include similar two-digit suffixes), but includes alternative placement arrangements to ensure proper alignment of components during installation. The damper mechanism 1540 includes a first damper member 1542 having a wing-like portion 1545 defining a first surface 1545a, a lug 1545b, and a second surface or flange 1545c. A second damper member 1562 includes a cylinder or bore 1564 coupled to a rotation-locking protrusion 1553 carried by the body portion 1552 of the frame member 1550. The second damper member 1562 further includes a facing surface 1562a and a flange 1566. The first surface 1545 of the wing-shaped portion 1545 is adapted to abut against the flange 1566 of the second damper member 1562, and the second surface 1545c of the wing-shaped portion 1545 is adapted to abut against the facing surface 1562a of the second damper member 1562, thereby creating two contact points or mounting surfaces. This further ensures proper displacement of the damper mechanism 1540.

[0084] Figure 17 and Figure 18 Damper mechanisms 1640 and 1740 are shown that are similar to damper mechanisms 1240, 1340, 1440, and 1540 (and therefore, similar features include similar two-digit suffixes), but differ in that they use features of their respective frame members 1650 and 1750 as mounting surfaces. Specifically, in Figure 17In the first damper member 1642, a finger portion 1645 includes a first flange or surface 1645a, a second surface 1645b, a finger 1645c, and a protrusion 1645d extending from the finger 1645c. A frame member 1650 includes a base portion 1652 carrying a first protrusion 1653 that locks relative rotation and a second protrusion 1654 having an outer surface 1654a. The frame member 1650 further includes a lug 1656. A second damper member 1662 includes a first surface 1662a, a channel or hole 1664, and a flange 1666 defining the surface 1666a. The first protrusion 1653 of the frame member 1650 is inserted into the hole 1664 of the second damper member 1662 to prevent relative rotation between the two. Additionally, the surface 1666a of the flange 1666 of the second damper member 1662 abuts against the second protrusion 1654 of the frame member 1652. The first surface 1662a of the second damper member 1662 abuts against the first flange 1645a of the finger portion 1645 of the first damper member 1642, and the second surface 1645b of the finger portion 1645 of the first damper member 1642 abuts against the outer surface 1654a of the second protrusion 1654 of the frame member 1650. Furthermore, the fingers 1645c of the finger portion 1645 engage with the lugs 1656 of the frame member 1656. Therefore, multiple contact points or mounting surfaces are created between the first damper member 1642, the frame member 1650, and the second damper member 1662 to further ensure proper displacement of the damper mechanism 1640. Figure 18 In the middle, the damper mechanism 1740 includes... Figure 17 The damper mechanism 1640 shown has similar features, surfaces, and / or flanges, but the frame member 1750 additionally includes a protrusion 1753 that carries a lug 1753a that engages with a channel 1745a of the finger portion 1745 of the first damper member 1742.

[0085] Figure 19 and Figure 20 The exemplary damper mechanism shown is similar to the previously described damper mechanism (and therefore, similar features include a similar two-digit suffix), but includes an additional sealing component. Figure 19 As shown, the sealing member 1870 is operatively coupled (e.g., glued or otherwise secured) to the frame member 1850. The sealing member 1870 can be molded using any number of conventional methods and includes a plurality of resilient sealing fingers 1872. When a gap is formed between the frame member 1850 and the first damper member 1842 and / or the second damper member 1862, these fingers 1872 are at least partially inserted into the chamber 1860 to restrict the exit of damper fluid 1851 from the chamber 1860.

[0086] exist Figure 20 In this device, the resilient sealing fingers 1947 are carried by the finger portion 1945 of the first damper member 1945. These sealing fingers 1947 engage with the frame member 1950 to ensure that the damper fluid 1951 does not leak into the rest of the device 1900.

[0087] Turn Figures 24 to 26 In some instances, it may be advantageous to construct the syringe cartridge 112 using different materials. Delivery times can vary considerably due to the significant variation in friction between containers constructed from certain materials. Friction between the plunger and the syringe cartridge can cause large variations, especially when the syringe is made of a polymeric material. As mentioned above, the force required to expel the drug through the needle within a given time, directly related to the axial plunger velocity, varies with the drug's viscosity. For high-viscosity drugs (e.g., above 10-15 cP), the required force is higher, while for low-viscosity drugs, the required force is lower. This force also depends on the rate of drug expulsion. During administration, an equilibrium dosing rate is reached where the velocity-related resistance in the system matches the input torque from the power source. However, the range of frictional force variation in the system is constant and independent of the drug's viscosity. Therefore, in the case of low-viscosity drugs, the ratio between frictional force and drug expulsion force becomes higher. Furthermore, due to the anticipated large variability in the frictional force of the polymer syringe cartridge, the residual torque from the spring for drug expulsion may be too high or too low, resulting in dosing times that are too fast or too slow. This can lead to unacceptably high variations in dosing time, or even complete device failure.

[0088] The use of a damper mechanism addresses these inconsistencies by acting as a buffer against excess torque. The speed of the drug delivery mechanism is a result of mechanical equilibrium, where friction in the system, the torque required to expel the drug, and the torque acting on the mechanical damper equal the total input torque from the power source. Due to the non-constant torque, the damper torque and the added torque required to expel the drug become more dominant than friction; therefore, changes in friction will have a relatively small effect on the available torque for expulsion and thus a modest effect on speed. Typically, whenever resistance in the device increases (whether due to friction and component tolerances during drug delivery or due to higher drug viscosity), the speed in the device decreases. However, due to the speed dependence of the damper, even a small decrease in speed results in a decrease in the damping torque, which in turn releases the available torque to overcome the increased resistance.

[0089] like Figures 24 to 26As shown, variations between plunger friction, the torque required to expel the drug, and the torque absorbed by the damper are added to provide the nominal input torque requirement. Note that the torque contribution in the device is not limited to these provided terms. Because the damper dissipates a significant amount of torque, the spring size is larger than when no damper is used. The velocity-related term (i.e., T) damper and T drug It dissipates most of the energy in the device.

[0090] Since a small decrease in speed corresponds to a large decrease in damper torque (and vice versa), only a tiny change in the available torque for drug ejection is observed. This is in Figure 25 and Figure 26 The text shows that: Figure 25 In scenario 1, the frictional force is at the lower limit of the expected range, causing the magnitude of the viscous term to increase due to more available torque, where the damping term absorbs the maximum torque, while the torque available for drug expulsion increases only slightly. This results in only a slightly shorter dosing time. Conversely, in Figure 26 In scenario 2, the increased friction leads to a significant decrease in damper torque, while the available torque for drug expulsion decreases only slightly, resulting in only a slightly longer dosing time. In devices without a damper mechanism, a large percentage of the input torque is used to overcome friction in the system. The frictional change will be added directly to or subtracted from the available torque in the expulsion section. Therefore, higher fluctuations in dosing time are expected.

[0091] Go to Figure 27 Examples of high sensitivity are demonstrated through model calculations. The first two columns, A and B, show the dosing time range for the friction values ​​when using a mechanical damper mechanism. Due to the damper, the high-viscosity (column A) and low-viscosity (column B) drug variant devices exhibit narrower variations in dosing time. For variants without dampers (columns C and D), the variability of high-viscosity drug variants is similarly low. This is attributed to the higher proportion of the input torque spent on drug expulsion relative to the torque used to overcome constant friction. However, for low-viscosity drug variants without dampers (column D), the dosing time varies significantly with friction. In addition to the higher sensitivity of dosing time to friction variability, in terms of the device platform, any change in drug viscosity will significantly alter the input torque requirement without dampers. Therefore, a greater number of power springs will be required to obtain the desired operating time window. On the other hand, having a damper introduces a buffering effect, but at the cost of slightly larger springs.

[0092] Additionally, certain materials can affect these forces. For example, when using a glass syringe, the sliding force may be smaller and its variation smaller compared to a plastic syringe due to the silicification of the syringe barrel and stopper. When administering drugs with high viscosity, the flow resistance through the needle tends to be the largest contributor to the total injection time. However, when administering drugs with lower viscosity and smaller volume, the sliding force (and its relative variability) may be the largest contributor to the total force required in the system.

[0093] This configuration reduces the number of spring variations required in the autoinjector platform, improving dosing consistency for the user and reducing the risk of syringe damage. Because small variations in spring performance and / or drug viscosity can have a significant impact when using low-viscosity drugs, the damper mechanism described herein slows down all dosing times, thus requiring fewer spring variations. When using drugs with higher viscosity, especially when administering smaller volumes of drug products, the damper mechanism described herein has a greater impact on the plunger rod impact velocity. The damper mechanism reduces the plunger rod impact velocity to a safer level, reducing the risk of syringe damage. The damper mechanism described herein requires fewer parts, thus facilitating assembly and reducing costs. Furthermore, the described damper mechanism does not rely on surface friction and relatively complex motion mechanisms, further reducing system complexity.

[0094] The above description describes different components, devices, and methods for drug delivery systems. It should be understood that these components, drug delivery devices, or methods may further include the use of the pharmaceutical agents listed below; however, it should be noted that the following list should not be considered as including all pharmaceutical agents, nor should it be considered restrictive. The pharmaceutical agent will be contained in a reservoir. In some cases, the reservoir is a master container that is filled or prefilled with the pharmaceutical agent for treatment. This master container may be a cartridge or a prefilled syringe.

[0095] For example, a drug delivery device, or more specifically, its reservoir, may be filled with colony-stimulating factors, such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, those mentioned above. (Figurine) and (Pefilgrastim). In various other embodiments, the drug delivery device can be used with a variety of pharmaceutical products, such as erythropoiesis stimulants (ESAs), which can be in liquid or lyophilized form. ESAs are any molecules that stimulate erythropoiesis, such as... (Ibertin α), (Dabepostatin α) (Ibertinδ) (Methoxylated polyethylene glycol-Eberstein β) MRK-2578, INS-22 (Iberdinζ) (Ibertin β) (Iberdinζ) (Ebertin α), epoetinalfa Hexal, (Ibertin α), (Ibertinθ) (Ibertinθ) Iberine (θ), iperine α, iperine β, iperine ζ, iperine θ, and iperine δ, and the molecules or variants thereof disclosed in the following patents or patent applications: U.S. Patent Nos. 4,703,008; 5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078; 5,773,569; 5,955,422; 5,986,047; 6,583,272; 7,084,245; and 7,271,689; and PCT Publications WO 91 / 05867; WO 95 / 05465; WO 96 / 40772; WO00 / 24893; WO 01 / 81405 and WO Patent applications 2007 / 136752, each incorporated herein by reference in its entirety.

[0096] ESA can be an erythropoietin-stimulating protein. As used herein, "erythropoietin-stimulating protein" means any protein that directly or indirectly causes activation of the erythropoietin receptor (e.g., by binding to and causing dimerization of the receptor). Erythropoietin-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. Erythropoietin-stimulating proteins include, but are not limited to, epoetin α, epoetin β, epoetin δ, epoetin ω, epoetin ι, epoetin ζ and their analogs, pegylated erythropoietin, carbamylated erythropoietin, mimic peptides (including EMP1 / hematide), and mimic antibodies. Exemplary erythropoietin-stimulating proteins include: erythropoietin, dabepoetin, erythropoietin agonist variants, and peptides or antibodies that bind to and activate the erythropoietin receptor (and include compounds reported in U.S. Publications 2003 / 0215444 and 2006 / 0040858, the disclosures of which are incorporated herein by reference in their entirety), as well as erythropoietin molecules or variants or analogs thereof as disclosed in U.S. Patent Nos. 4,703,008; 5,444. 1,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078; 5,773,569; 5,955,422; 5,830,851; 5,856,298; 5,986,047; 6,030,086; 6,310,078; 6,391,633; 6,583,272; 6,586,398; 6,900,292; 6,750,369; 7,030,2 26; 7,084,245; and 7,217,689; U.S. Publication Nos. 2002 / 0155998; 2003 / 0077753; 2003 / 0082749; 2003 / 0143202; 2004 / 0009902; 2004 / 0071694; 2004 / 0091961; 2004 / 0143857; 2004 / 0157293; 2004 / 0175379; 2004 / 0175824; 2004 / 022931 8; 2004 / 0248815; 2004 / 0266690; 2005 / 0019914; 2005 / 0026834; 2005 / 0096461; 2005 / 0107297; 2005 / 0107591; 2005 / 0124045; 2005 / 0124564; 2005 / 0137329; 2005 / 0142642; 2005 / 0143292; 2005 / 0153879; 2005 / 0158822;2005 / 0158832; 2005 / 0170457; 2005 / 0181359; 2005 / 0181482; 2005 / 0192211; 2005 / 0202538; 2005 / 0227289; 2005 / 0244409; 2006 / 0088906; and 2006 / 0111279; and PCT Publication No. WO 91 / 05867; WO 95 / 05465; WO 99 / 66054; WO 00 / 24893; WO 01 / 81405; WO 00 / 61637; WO 01 / 36489; WO 02 / 014356; WO 02 / 19963; WO 02 / 20034; WO 02 / 49673; WO 02 / 085940; WO 03 / 029291; WO 2003 / 055526; WO 2003 / 084477; WO 2003 / 094858; WO 2004 / 002417; WO 2004 / 002424; WO 2004 / 009627; WO 2004 / 024761; WO 2004 / 033651; WO2004 / 035603; WO 2004 / 043382; WO 2004 / 101600; WO 2004 / 101606; WO 2004 / 101611;WO2004 / 106373;WO 2004 / 018667; WO 2005 / 001025; WO 2005 / 001136; WO 2005 / 021579; WO2005 / 025606; WO 2005 / 032460; WO 2005 / 051327; WO 2005 / 063808; WO 2005 / 063809; WO2005 / 070451; WO 2005 / 081687; WO 2005 / 084711; WO 2005 / 103076; WO 2005 / 100403; WO2005 / 092369; WO 2006 / 50959; WO 2006 / 02646; and WO Patents 2006 / 29094, each incorporated herein by reference in its entirety.

[0097] Examples of other pharmaceutical products used in conjunction with this device may include, but are not limited to, antibodies, for example (panitumab), Xgeva TM (Dinosem and Prolia) TM (denosamab); other biological agents, such as (Etanercept, TNF receptor / Fc fusion protein, TNF blocker) (Pefilgrastim, polyethylene glycol-modified filgrastim, polyethylene glycol-modified G-CSF, polyethylene glycol-modified hu-Met-G-CSF) (Fegristatin, G-CSF, hu-MetG-CSF) and (romiplostim); small molecule drugs, such as (Cinacalcet). This device can also be used with therapeutic antibodies, peptides, proteins, or other chemicals such as iron, for example, ferrumoxytol, dextran iron, ferrous gluconate, and ferrous sucrose. The pharmaceutical product can be in liquid form or can be reconstituted from a lyophilized form.

[0098] The specific illustrative protein is the particular protein described below, including its fusions, fragments, analogs, variants, or derivatives:

[0099] OPGL-specific antibodies, peptides, and related proteins (also known as RANKL-specific antibodies, peptides, etc.), including fully humanized OPGL-specific antibodies and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies, including but not limited to antibodies described in PCT Publication No. WO 03 / 002713 (which is incorporated herein by reference in its entirety) concerning OPGL-specific antibodies and antibody-related proteins, particularly those having the sequences listed therein, particularly but not limited to those specified therein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, including those having the sequences such as Figure 2 The light chain of sequence identification number 2 shown and / or as Figure 4 The OPGL-specific antibodies of the heavy chain of sequence identification number 4 shown herein are each individually and specifically incorporated herein by reference in their entirety as disclosed in the foregoing disclosure;

[0100] Myostatin-binding proteins, peptides, and related proteins, including myostatin-specific peptides, particularly those described in U.S. Publication No. 2004 / 0181033 and PCT Publication No. WO 2004 / 058988 (which are incorporated herein by reference in their entirety), especially in the sections relating to myostatin-specific peptides, including but not limited to peptides of the mTN8-19 family, including those with sequence identification numbers 305-351, including TN8-19-1 to TN8-19-40, TN8-19 con1, and TN8-19 con2; the mL2 family of sequence numbers 357-383, the mL15 family of sequence numbers 384-409, the mL17 family of sequence numbers 410-438, the mL20 family of sequence numbers 439-446, the mL21 family of sequence numbers 447-452, the mL24 family of sequence numbers 453-454, and those of sequence numbers 615-631, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the foregoing disclosures;

[0101] IL-4 receptor-specific antibodies, peptides, and related proteins, particularly those that inhibit activity mediated by the binding of IL-4 and / or IL-13 to the receptor, including those described, particularly in the sections relating to IL-4 receptor-specific antibodies, in PCT Publication No. WO 2005 / 047331 or PCT Application No. PCT / US2004 / 37242 and US Publication No. 2005 / 112694 (which are incorporated herein by reference in their entirety), especially those antibodies as described therein, particularly but not limited to those specified therein: L1H1; L1H2; L1H3; L1H4; L1H5; L1H6; L1H 7; 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 herein by reference in its entirety as disclosed in the foregoing disclosure;

[0102] Interleukin-1 receptor 1 (“IL1-R1”) specific antibodies, peptides, 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, with regard to the portion relating to IL1-R1 specific binding proteins), particularly monoclonal antibodies, especially but not limited to those specified therein: 15CA, 26F5, 27F2, 24E12, and 10H7, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the foregoing disclosure;

[0103] Ang2-specific antibodies, peptides, and related proteins, including but not limited to those described in PCT Publication No. WO 03 / 057134 and US Publication No. 2003 / 0229023 (each of which is incorporated herein by reference in its entirety), particularly in the sections relating to Ang2-specific antibodies and peptides, especially those having the sequences described therein and including but not limited to: L1(N); L1(N)WT; L1(N)1K WT; 2xL1(N); 2xL1(N)WT; Con4(N), Con4(N)1K WT, 2xCon4(N)1K; L1C; L1C 1K; 2xL1C; Con4C; Con4C 1K; 2xCon4C 1K; Con4-L1(N); Con4-L1C; TN-12-9(N); C17(N); TN8-8(N); TN8-14(N); Con 1(N); also includes anti-Ang 2 antibodies and formulations, such as those described in PCT Publication No. WO 2003 / 030833 (which is incorporated herein by reference in its entirety), particularly Ab526; Ab528; Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1; AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12; AblA1; AblF; AblK; AblP; and AblP; each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the foregoing publications;

[0104] NGF-specific antibodies, peptides, 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 (the aspects of these patents, particularly those relating to NGF-specific antibodies and related proteins, are incorporated herein by reference in their entirety), including, in particular, those NGF-specific antibodies designated as 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the foregoing disclosures;

[0105] CD22-specific antibodies, peptides, and related proteins, such as those described in U.S. Patent No. 5,789,554 (the aspects of that patent relating to CD22-specific antibodies and related proteins are incorporated herein by reference in their entirety), particularly human CD22-specific antibodies, such as, but not limited to, humanized and fully human antibodies, including but not limited to humanized and fully human monoclonal antibodies, particularly including but not limited to human CD22-specific IgG antibodies, such as dimers like human-mouse monoclonal hLL2γ-chain linked to human-mouse monoclonal hLL2κ chain by disulfide, including but not limited to, human CD22-specific fully humanized antibodies such as epazuzumab, CAS Registry No. 501423-23-0;

[0106] IGF-1 receptor-specific antibodies, peptides, and related proteins, such as those described in PCT Publication No. WO 06 / 069202 (the aspect of that patent concerning IGF-1 receptor-specific antibodies and related proteins is incorporated herein by reference in its entirety), including but not limited to those specified therein 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, L28H19, etc. 28. IGF-1 specific antibodies against L29H29, L30H30, L31H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, and L52H52, as well as IGF-1R binding fragments and their derivatives, each of which is incorporated herein by reference in its entirety, as disclosed in the foregoing disclosures;

[0107] In non-limiting examples of anti-IGF-1R antibodies used in the methods and compositions of the present invention, there are also each and all of the following antibodies:

[0108] (i) U.S. Publications Nos. 2006 / 0040358 (published on February 23, 2006), 2005 / 0008642 (published on January 13, 2005), and 2004 / 0228859 (published on November 18, 2004), including but not limited to, for example, antibodies 1A (DSMZ accession number DSM ACC 2586), 8 (DSMZ accession number DSM ACC 2589), 23 (DSMZ accession number DSMMACC 2588) and 18 described therein;

[0109] (ii) PCT publications WO 06 / 138729 (published on December 28, 2006) and WO 05 / 016970 (published on 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 therein;

[0110] (iii) PCT Publications WO 07 / 012614 (published on February 1, 2007), WO 07 / 000328 (published on January 4, 2007), WO 06 / 013472 (published on February 9, 2006), WO 05 / 058967 (published on June 30, 2005) and WO03 / 059951 (published on July 24, 2003);

[0111] (iv) U.S. Publication No. 2005 / 0084906 (published on April 21, 2005), including but not limited to antibody 7C10, chimeric antibody C7C10, antibody h7C10, antibody 7H2M, chimeric antibody *7C10, antibody GM 607, humanized antibody 7C10 variant 1, humanized antibody 7C10 variant 2, humanized antibody 7C10 variant 3 and antibody 7H2HM as described herein;

[0112] (v) U.S. Publications Nos. 2005 / 0249728 (published November 10, 2005), 2005 / 0186203 (published August 25, 2005), 2004 / 0265307 (published December 30, 2004) and 2003 / 0235582 (published December 25, 2003) and Maloney et al. (2003), Cancer Res. 63:5073-5083, including but not limited to the antibody EM164, surface-remodeled EM164, humanized EM164, huEM164v1.0, huEM164v1.1, huEM164v1.2 and huEM164v1.3 as described;

[0113] (vi) U.S. Patent Nos. 7,037,498 (published May 2, 2006), 2005 / 0244408 (published November 30, 2005) and 2004 / 0086503 (published May 6, 2004), and Cohen et al. (2005), Clinical Cancer Res. 11:2063-2073, such as antibody CP-751,871, including but not limited to each antibody produced by hybridomas having ATCC accession numbers PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793 as described herein, and antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3;

[0114] (vii) U.S. Publications 2005 / 0136063 (published June 23, 2005) and 2004 / 0018191 (published January 29, 2004), including but not limited to antibody 19D12 as described therein and the following antibodies comprising a heavy chain encoded by a polynucleotide in plasmid 15H12 / 19D12 HCA(γ4) (deposited at ATCC with the number PTA-5214) and a light chain encoded by a polynucleotide in plasmid 15H12 / 19D12 LCF(κ) (deposited at ATCC with the number PTA-5220); and

[0115] (viii) U.S. Publication No. 2004 / 0202655 (published on October 14, 2004), including but not limited to 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 as described herein; each of these and all aspects relating particularly to the aforementioned antibodies, peptides, and related proteins targeting the IGF-1 receptor are incorporated herein by reference in their entirety;

[0116] B-7-related protein 1 specific antibodies, peptides, and related proteins (“B7RP-1”, also referred to in the literature as B7H2, ICOSL, B7h, and CD275), particularly B7RP-specific fully human monoclonal IgG2 antibodies, especially fully human IgG2 monoclonal antibodies that bind to epitopes in the first immunoglobulin-like domain of B7RP-1, and especially those that inhibit the interaction of B7RP-1 with its natural receptor ICOS on activated T cells, particularly in all of the foregoing aspects, US Publication No. 2008 / 0166352 and PCT Publication No. WO Those disclosed in 07 / 011941 (the aspects of the aforementioned disclosure concerning such antibodies and related proteins are incorporated herein by reference in their entirety), including but not limited to the antibodies specified therein: 16H (having light chain variable sequences and heavy chain variable sequences, respectively, sequence identification numbers 1 and 7); 5D (having light chain variable sequences and heavy chain variable sequences, respectively, sequence identification numbers 2 and 9); 2H (having light chain variable sequences and heavy chain variable sequences, respectively, sequence identification numbers 3 and 10); 43H (having light chain variable sequences and heavy chain variable sequences, respectively, sequence identification numbers 6 and 14); 41H (having light chain variable sequences and heavy chain variable sequences, respectively, sequence identification numbers 5 and 13); and 15H (having light chain variable sequences and heavy chain variable sequences, respectively, sequence identification numbers 4 and 12), each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the foregoing disclosure;

[0117] IL-15 specific antibodies, peptides, and related proteins, such as, in particular, humanized monoclonal antibodies, especially those disclosed in U.S. Publications 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), including peptides, particularly including, but not limited to, HuMax IL-15 antibodies and related proteins, such as 146B7;

[0118] IFNγ-specific antibodies, peptides, and related proteins, especially human IFNγ-specific antibodies, particularly fully human anti-IFNγ antibodies, such as those described in U.S. Publication No. 2005 / 0004353 (which is incorporated herein by reference in its entirety), particularly those antibodies referred to as 1118; 1118*; 1119; 1121; and 1121*. The complete sequences of the heavy and light chains of each of these antibodies, as well as the sequences of their heavy and light chain variable and complementarity-determining regions, are each incorporated herein by reference in their entirety as disclosed in the aforementioned publications and in Thakur et al. (1999), Mol. Immunol. [Molecular Immunology] 36:1107-1115. Furthermore, descriptions of the properties of these antibodies provided in the aforementioned publications are also incorporated herein by reference in their entirety. Specific antibodies include those having a heavy chain with sequence identification number 17 and a light chain with sequence identification number 18; those having a heavy chain variable region with sequence identification number 6 and a light chain variable region with sequence identification number 8; those having a heavy chain with sequence identification number 19 and a light chain with sequence identification number 20; those having a heavy chain variable region with sequence identification number 10 and a light chain variable region with sequence identification number 12; those having a heavy chain with sequence identification number 32 and a light chain with sequence identification number 20; those having a heavy chain variable region with sequence identification number 30 and a light chain variable region with sequence identification number 12; those having a heavy chain sequence with sequence identification number 21 and a light chain sequence with sequence identification number 22; those having a heavy chain variable region with sequence identification number 14 and a light chain variable region with sequence identification number 16; those having a heavy chain with sequence identification number 21 and a light chain with sequence identification number 33; and those having a heavy chain variable region with sequence identification number 14 and a light chain variable region with sequence identification number 31, as disclosed in the above disclosures. The envisioned specific antibody is antibody 1119, which is as disclosed in the aforementioned U.S. publication and has a complete heavy chain as disclosed therein with sequence identification number 17 and a complete light chain as disclosed therein with sequence identification number 18.

[0119] TALL-1 specific antibodies, peptides and related proteins, and other TALL-specific binding proteins, such as those described in U.S. Publications 2003 / 0195156 and 2006 / 0135431 (each aspect of these patents relating to TALL-1 binding proteins is incorporated herein by reference in its entirety), particularly the molecules in Tables 4 and 5B, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the foregoing disclosures;

[0120] Parathyroid hormone (“PTH”) specific antibodies, peptides and related proteins, such as those described in U.S. Patent No. 6,756,480 (which is incorporated herein by reference in its entirety, and in particular in the portion relating to proteins that bind to PTH);

[0121] Thrombopoietin receptor (“TPO-R”) specific antibodies, peptides and related proteins, such as those described in U.S. Patent No. 6,835,809 (which is incorporated herein by reference in its entirety, and particularly in the portion relating to proteins that bind to TPO-R);

[0122] Hepatocyte growth factor (“HGF”) specific antibodies, peptides, and related proteins, including those targeting the HGF / SF:cMet axis (HGF / SF:c-Met), such as the fully human monoclonal antibody that neutralizes hepatocyte growth factor / dispersant (HGF / SF) as described in U.S. Patent Publication No. 2005 / 0118643 and PCT Publication No. WO 2005 / 017107, huL2G7 as described in U.S. Patent No. 7,220,410, and OA-5d5 as described in U.S. Patent Nos. 5,686,292 and 6,468,529 and PCT Publication No. WO 96 / 38557, each of which is incorporated herein by reference in its entirety, and in particular in the portion relating to proteins that bind HGF;

[0123] TRAIL-R2 specific antibodies, peptides, related proteins, etc., such as those described in U.S. Patent No. 7,521,048 (which is incorporated herein by reference in its entirety, and particularly in the portion relating to proteins that bind to TRAIL-R2);

[0124] Activin A-specific antibodies, peptides, 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, and particularly in respect of the portion relating to proteins that bind to activin A);

[0125] TGF-β specific antibodies, peptides, 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 is incorporated herein by reference in its entirety, and in particular in the portion relating to proteins that bind TGF-β);

[0126] Amyloid-β protein-specific antibodies, peptides, related proteins, etc., including but not limited to those described in PCT Publication No. WO2006 / 081171 (that patent is incorporated herein by reference in its entirety, particularly the portion relating to proteins that bind amyloid-β protein). One contemplated antibody is one having a heavy chain variable region containing sequence identification number 8 and a light chain variable region containing sequence identification number 6, as disclosed in the aforementioned publication.

[0127] c-Kit specific antibodies, peptides, related proteins, etc., 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 to c-Kit and / or other stem cell factor receptors);

[0128] OX40L-specific antibodies, peptides, related proteins, etc., including but not limited to those described in U.S. Publication No. 2006 / 0002929 (which is incorporated herein by reference in its entirety, particularly the portion relating to proteins that bind to OX40L and / or other ligands of the OX40 receptor); and

[0129] Other exemplary proteins, including (Alteplase, tPA); (Dabepostatin α); (Eberferone α, or erythropoietin); GLP-1, (Interferon β-1a); (Tosimomab, an anti-CD22 monoclonal antibody); (Interferon-β); (Alemtuzumab, anti-CD52 monoclonal antibody); (Ibertinδ); (Bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokine receptor mAb); (Etanercept, TNF receptor / Fc fusion protein, TNF blocker); (Ibertin α); (Cetuximab, anti-EGFR / HER1 / c-ErbB-1); (Growth hormone, human growth hormone); (Trastuzumab, anti-HER2 / neu(erbB2) receptor mAb); (Growth hormone, human growth hormone); (Adalimumab); Insulin in solution; (interferon alfacon-1); (nesiritide; recombinant human B-type natriuretic peptide (hBNP); (anaretin); (Shagstine, rhuGM-CSF); (Epazolizumab, anti-CD22mAb); Benlysta TM (lymphostat B, belizumab, anti-BlyS mAb); (Tennexase, t-PA analogue); (Methoxylated polyethylene glycol-Eberstein β); (Gitocilizumab ozomicin); (Efalizumab); (Cetuzumab, CDP 870); Soliris TM (Ikulizumab); Pexizumab (anti-C5 complement); (MEDI-524); (Lanibizumab); (17-1A, Izodacone); (lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4); (IDM-1); (B43.13); (Vesizumab); mocantuzumab mertansine (huC242-DM1); (Ibertin β); (Aupre interleukin, human interleukin-11); (Polyethylene glycol-modified filgrastim, polyethylene glycol-modified G-CSF, polyethylene glycol-modified hu-Met-G-CSF); (Fegrostin, G-CSF, hu-MetG-CSF); (Moromab-CD3, anti-CD3 monoclonal antibody); (Ibertin α); (Infliximab, anti-TNFα monoclonal antibody); (Abciximab, anti-GP lIb / Ilia receptor monoclonal antibody); (Anti-IL6 receptor mAb); (Bevacizumab), HuMax-CD4 (zanolimumab); (Rituximab, anti-CD20 mAb); (Erlotinib); (Interferon α-2a); (Bariximab); (Romexicob); (palizumab); 146B7-CHO (anti-IL15 antibody, see US Patent No. 7,153,507); (Natazumab, anti-α4 integrin mAb); (MDX-1303, protective antigen mAb against Bacillus anthracis); ABthrax TM ; (Panitumumab); (Omalizumab); ETI211 (anti-MRSA mAb); IL-1 trap (extracellular domain of the Fc portion of human IgG1 and IL-1 receptor components (type I receptor and receptor accessory protein); VEGF trap (Ig domain of VEGFR1 fused to IgG1 Fc). (Dalizumab); (Dalizumab, anti-IL-2RαmAb); (Imozolomide); (Ezetimibe); (Acecept, TACI-Ig); Anti-CD80 monoclonal antibody (galiximab); Anti-CD23 mAb (ruximab); BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist); CNTO 148 (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 (iplimumab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-Clostridium difficile toxin A and toxin BC mAb MDX-066 (CDA-1 and MDX-1388); anti-CD22 dsFv-PE38 conjugates (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 (HuMax CD38); anti-CD40L mAb; anti-Cripto mAb; anti-CTGF fibrinogen for stage I idiopathic pulmonary fibrosis (FG-3019); anti-CTLA4 mAb; anti-eosinophil chemotactic factor 1 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 (HuMax HepC); 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 (CNTO 1275); Anti-IL13 mAb (CAT-354); Anti-IL2Ra mAb (HuMax-TAC); Anti-IL5 receptor mAb; Anti-integrin receptor mAb (MDX-018, CNTO 95); 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.

[0130] It may also contain sclerosing protein antibodies, such as, but not limited to, romosozumab, blosozumab, or BPS 804 (Novartis). It may further contain therapeutic agents, such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib, brodalumab, vidupiprant, panitumab, denosumab, NPLATE, PROLIA, VECTIBIX, or XGEVA. Additionally, the device may contain a monoclonal antibody (IgG) that binds to the human proprotein convertase subtilisin / Kexin type 9 (PCSK9). This PCSK9-specific antibody includes, but is not limited to, those disclosed in the following patents or patent applications. (evolocumab) and (alirocumab) and its molecules, variants, analogs, or derivatives: US Patent No. 8,030,547, US Publication No. 2013 / 0064825, WO 2008 / 057457, WO 2008 / 057458, WO 2008 / 057459, WO 2008 / 063382, WO 2008 / 133647, WO 2009 / 100297, WO 2009 / 100318, WO2011 / 037791, WO 2011 / 053759, WO 2011 / 053783, WO 2008 / 125623, WO 2011 / 072263, WO2009 / 055783, WO 2012 / 0544438, WO WO 2010 / 029513, WO 2011 / 111007, WO 2010 / 077854, WO2012 / 088313, WO 2012 / 101251, WO 2012 / 101252, WO 2012 / 101253, WO 2012 / 109530 and WO2001 / 031007, these patents or patent applications are incorporated herein by reference in their entirety for all purposes.

[0131] It may also include talimogen (talimogenelaherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers. Examples of oncolytic HSVs include, but are not limited to, talimogen (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).

[0132] It also includes TIMP. TIMP is an endogenous tissue metalloproteinase inhibitor (TIMP) and is important in many natural processes. TIMP-3 is expressed by various cells or present in the extracellular matrix; it inhibits all major cartilage-degrading metalloproteases and can play a role in many degenerative diseases of connective tissue, including 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 May 13, 2003, the disclosure of which is incorporated herein by reference. Descriptions of TIMP mutations can be found in U.S. Publication No. 2014 / 0274874 and PCT Publication No. WO 2014 / 152012.

[0133] It also includes antagonistic antibodies against the human calcitonin gene-related peptide (CGRP) receptor and bispecific antibody molecules targeting the CGRP receptor and other headache targets. Further information about these molecules can be found in PCT application number WO2010 / 075238.

[0134] In addition, a bispecific T-cell conjugate can be used in this device. Antibodies, for example (Bonatumab). Alternatively, the device may contain a macromolecular agonist of APJ, such as apelinide or an analogue thereof. Information on such molecules can be found in PCT Publication No. WO 2014 / 099984.

[0135] In some embodiments, the agent comprises a therapeutically effective amount of an anti-thymocyte 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 agent comprises a therapeutically effective amount of an anti-TSLP antibody designated A5 in U.S. Patent No. 7,982,016.

[0136] Although drug delivery devices, methods, and components thereof have been described with reference to exemplary embodiments, they are not limited thereto. The detailed description is to be interpreted as exemplary only and does not describe every possible embodiment of the invention, as it would be impractical to describe every possible embodiment if possible. Many alternative embodiments may be implemented using current technology or technology developed after the date of this patent application, and these embodiments still fall within the scope of the claims defining the invention. For example, components described herein with reference to certain types of drug delivery devices (such as portable syringe drug delivery devices or other types of drug delivery devices) may also be used in other types of drug delivery devices (such as auto-injector drug delivery devices).

[0137] Those skilled in the art will understand that various modifications, alterations, and combinations can be made to the embodiments described above without departing from the scope of the invention, and such modifications, alterations, and combinations can be considered to be within the scope of the inventive concept.

Claims

1. A drug delivery device, comprising: The housing defines a shell having a proximal end, a distal end, and a longitudinal axis extending between the proximal end and the distal end of the shell; A needle assembly, which is at least partially disposed within the housing at the proximal end of the housing, the needle assembly including a syringe containing a drug and a needle or cannula; A drive assembly, which is at least partially disposed within the housing and operatively coupled to the needle assembly to facilitate the passage of the drug through the needle or cannula; as well as A damper mechanism, at least partially disposed within the housing and adjacent to the distal end of the housing, is operatively coupled to the drive assembly, wherein, upon activation of the drive assembly, the damper mechanism applies torque to the drive assembly to suppress the action of the drive assembly.

2. The drug delivery device as claimed in claim 1, wherein, The damper mechanism includes: Frame components; A damper component operably connected to the drive assembly; The cavity formed between a portion of the frame member and the damper member; and The damper fluid is disposed in the chamber, which is formed between the frame member and the damper member; When the drive assembly of the drug delivery device is activated, the damper member rotates relative to the frame member, and the damper fluid applies opposing forces to at least one of the frame member and the damper member.

3. The drug delivery device as claimed in claim 2, wherein, The frame component is integrally formed with the shell.

4. The drug delivery device of claim 2 or 3, further comprising an excess chamber fluidly coupled to the chamber, the excess chamber being adapted to receive excess damper fluid.

5. The drug delivery device of claim 2 or 3, further comprising a seal disposed near the chamber to retain the damper fluid within the chamber.

6. The drug delivery device as claimed in claim 2 or 3, wherein, The chamber: (a) Aligned with the longitudinal axis; (b) Partially aligned with the longitudinal axis axially and partially aligned with the longitudinal axis laterally; or (c) Aligned with the horizontal axis of the vertical axis.

7. The drug delivery device as claimed in claim 2 or 3, wherein, The driver component includes: A plunger assembly including a threaded plunger rod and a plunger face disposed near the needle assembly and movable along the longitudinal axis of the housing; A plunger rod guide, coupled to the plunger assembly to guide the rotational movement of the plunger assembly, the plunger rod guide being further operably coupled to either the frame member or the damper member; and A torsion spring is coupled to the plunger rod guide to apply a force to the plunger rod guide that causes it to rotate, wherein the rotation of the plunger rod guide causes the plunger assembly to advance toward the proximal end of the housing to facilitate the passage of the drug through the needle assembly.

8. The drug delivery device as claimed in claim 7, wherein, The plunger assembly includes a gap of more than 10 mm between the threaded plunger rod and the plunger face, wherein the syringe is adapted to contain at least 1 mL of a drug with a viscosity of at least 4 cP.

9. The drug delivery device of claim 7, wherein the damper member of the damper mechanism is operatively coupled to the plunger rod guide of the drive assembly.

10. The drug delivery device according to claim 2 or 3, wherein when the frame member and the damper member rotate relative to each other, the magnitude of the torque applied by the damper mechanism is related to the magnitude of the shear stress in the damper fluid.

11. The drug delivery device according to any one of claims 1-3, wherein the syringe is filled or pre-filled with a drug, and wherein the drug comprises evolocumab.

12. The drug delivery device as claimed in claim 1, wherein, The damper mechanism applies the torque to the plunger rod guide.

13. The drug delivery device as claimed in claim 4, wherein, The excess damper fluid is configured to selectively regulate the torque applied by the damper mechanism.

14. The drug delivery device as claimed in claim 2, wherein, The damper component includes a body and a wing-shaped portion, the wing-shaped portion being positioned away from the body to define a channel between the body and the wing-shaped portion.

15. The drug delivery device of claim 14, wherein, The body of the damper component includes an inner surface defining a central opening, wherein the central opening is configured to receive at least a portion of the drive assembly.

16. The drug delivery device as claimed in claim 14 or 15, wherein, The channel is configured to receive at least a portion of the frame components.

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