Autoinjector with stall and end-point detection

Abstract

An autoinjector drug delivery device is described that is configured with stall and end-point detection algorithms that allow for variations in drug load, barrel, plunger, and other components. Upon stall or end-point detection, the autoinjector stops the expulsion process.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 587,421, filed November 16, 2017, the entire contents of which are expressly incorporated herein by reference.

[0002] The present disclosure relates to injection systems and devices, and more particularly to the operation of autoinjector devices. [Background technology]

[0003] Prefilled hypodermic syringes can be used for home use because they can be provided with the required dose of medication and are operated by simply advancing the syringe stopper. Aside from the cost of the particular medication used, prefilled syringes can be economical to manufacture.

[0004] Nevertheless, pre-filled syringes may have drawbacks. Specifically, many users may be afraid of the exposed injection needle or may feel that they are essentially unable to perform the injection. Due to the aversion to the exposed needle as well as the health and safety issues that may be involved, various types of injectors and other devices have been developed to hide the needle from the user and automate the injection process, in order to help users perform injections, ensure reliable delivery of medication, and ensure patient safety. Please refer to the following patents or patent applications, each of which is incorporated herein by reference in its entirety: U.S. Patent No. 8,052,645 and U.S. Patent No. 8,177,749; U.S. Patent Application Publication No. 2012 / 0101439; and PCT Publication No. WO 2012 / 145685.

[0005] Typically, three tasks may be performed when injecting a drug into a patient with a hypodermic syringe: 1) inserting the needle into the patient; 2) injecting the drug from the syringe into the patient; and 3) removing the needle after the injection is complete. For each task, the magnitude and direction of force applied to the syringe, as well as the location of the force, may differ from other tasks. For example, inserting the needle may require minimal force to be applied to the syringe for a very short period of time. In contrast, injecting the drug may require a greater force to be applied to the syringe plunger. This force may need to be applied for a relatively longer period of time. Furthermore, removing the needle may require a force to be applied in the opposite direction to needle insertion. These and other similar considerations may become relevant when the injection process is automated.

[0006] In addition to these mechanical considerations, the design of an autoinjector may need to consider ease of use. In particular, it may be desirable for the syringe's injection needle to be operatively hidden from the user's view. Preferably, this shielding is maintained before, during, and after the injection procedure. Furthermore, it may be desirable to limit syringe operation to only when the syringe is properly positioned for injection and / or when the proper sequence of operations is performed by the user.

[0007] When injecting a drug subcutaneously, a patient may desire a fast, yet smooth, and steady injection. The length the needle is placed within the patient is balanced with the sensation of the drug flow entering the subcutaneous space. In one form, a drug delivery device can determine that a dose of drug has been administered by moving the plunger rod from a start position to a fixed end position. However, such movement to the fixed position may leave some drug in the syringe if too gentle, or may shatter the glass of the syringe if too aggressive. Furthermore, if the plunger stalls midway through ejection before reaching the end position, the plunger rod may slip into or bypass the plunger in an attempt to reach the end position. Furthermore, stall detection becomes more difficult in a closed-loop feedback system that aims for a constant injection rate.

[0008] A plunger can stall due to a number of conditions. For example, manufacturing variations in everything from fill volume, to plunger mounting position, plunger configuration or its compression temperature, plunger or syringe siliconization, syringe tapering or shape, motor performance, battery performance affecting injection rate, etc. can cause variations in ejection rate throughout the injection process. Additionally, conditions such as drug temperature affecting drug viscosity, and localized heating of the motor windings causing degradation of engine performance can affect ejection rate. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] U.S. Patent No. 8,052,645 [Patent Document 2] U.S. Patent No. 8,177,749 [Patent Document 3] US Patent Application Publication No. 2012 / 0101439 [Patent Document 4] PCT International Publication No. 2012 / 145685 Pamphlet Summary of the Invention [Means for solving the problem]

[0010]

[0003] Described herein is a drug delivery device including a reservoir configured to contain a drug and having a first end and a second end, and a plunger disposed within the reservoir at the first end of the reservoir, the plunger being slidably movable within the reservoir. The device further includes a plunger rod configured to engage the plunger, a motor operatively coupled to the plunger rod and configured to drive the plunger rod to slide the plunger from one end of the reservoir to the second end of the reservoir, and an encoder coupled to the motor. The device further includes a controller configured to receive a signal from the encoder, determine based on the signal whether the plunger has stopped moving within the reservoir, and stop operation of the motor in response to determining that the plunger has stopped moving for a predetermined amount of time.

[0011] In various embodiments, the encoder may include a disk having one or more identifiable portions and an optical sensor configured to detect the identifiable portions and transmit a signal in response to the detection.

[0012] In various embodiments, the drug delivery device may further include a needle and a needle insertion mechanism, and the controller may be configured to retract the needle in response to determining that the plunger has stopped moving for a predetermined amount of time.

[0013] A method of operating a drug delivery device is described herein that includes receiving, at a controller, a signal from an encoder coupled to a motor of the drug delivery device, the motor operatively coupled to a plunger rod configured to engage and drive a plunger within a reservoir, determining, by the controller based on the signal, whether the plunger has stopped moving within the reservoir, and stopping operation of the motor by the controller in response to determining that the plunger has stopped moving for a predetermined amount of time.

[0014] In various embodiments, the method may further include detecting the distinguishable portion of the disc of the encoder with an optical sensor and transmitting a signal in response to the detection.

[0015] In various embodiments, the method may further include sampling, by the controller, the position of the plunger rod at set intervals by determining a current count of the signal.

[0016] In various embodiments, determining whether the plunger has stopped moving within the reservoir may include determining whether the signal indicates that the plunger has moved within the last predetermined number of samples. In a further embodiment, the method may further include comparing the current count to an expected endpoint count corresponding to the plunger being driven into the second end of the reservoir. In another further embodiment, the method may include modifying the predetermined number of samples in response to determining that the current count is less than the expected endpoint. In a further embodiment, the method may include determining that the plunger has stalled before being driven into the second end of the reservoir in response to determining that the current count is less than the expected endpoint.

[0017] In various embodiments, the method may further include retracting the needle of the drug delivery device with the needle insertion mechanism in response to the controller determining that the plunger has stopped moving for a predetermined amount of time.

[0018] It should be noted that although reference is made frequently herein to an autoinjector, in various embodiments the device may also be referred to as an injector. Reference to an autoinjector often relates to a patient administering a self-injection, although such an injection may also be administered by a healthcare provider. Similarly, use of the injector may be undertaken by either the patient or the healthcare provider.

[0019] The accompanying drawings illustrate embodiments in accordance with the present disclosure and are by way of example rather than limitation. [Brief explanation of the drawings]

[0020] [Figure 1] FIG. 1 is a side view of one embodiment of an autoinjector device including a cassette and autoinjector, showing the cassette before installation in the autoinjector. [Figure 2A] 2 is a front view of the autoinjector device of FIG. 1 showing the cassette installed in the autoinjector. FIG. [Figure 2B] 2 is a side view of a first side of the autoinjector device of FIG. 1 showing the cassette installed within the autoinjector. FIG. [Figure 2C] 2 is a rear view of the autoinjector device of FIG. 1 showing the cassette installed in the autoinjector. FIG. [Figure 2D] 2 is a side view of a second side of the autoinjector device of FIG. 1 showing the cassette installed within the autoinjector. FIG. [Figure 2E] 2 is an end view of a first end of the autoinjector of the autoinjector device of FIG. 1. FIG. [Figure 2F] FIG. 2 is an end view of a second end of the autoinjector of the autoinjector device of FIG. 1. [Figure 2G]FIG. 2 is a state diagram illustrating one embodiment of decision logic for controlling the skin sensor of the autoinjector device of FIG. 1. [Figure 2H] FIG. 1 is a cross-sectional side view of one embodiment of an autoinjector device showing a cassette installed within the autoinjector. [Figure 2I] FIG. 2 is a diagram of a motor and encoder for determining plunger travel distance of the autoinjector device of FIG. 1. [Figure 3] FIG. 10 is an exploded perspective view of an embodiment of a cassette. [Figure 4] FIG. 10 is a side cross-sectional view of one embodiment of a medication container that may be provided within the cassette. [Figure 5A] FIG. 10 is a top-down front perspective view of an embodiment of a cassette; [Figure 5B] FIG. 5B is a cross-sectional side view of the cassette of FIG. 5A. [Figure 5C] 5B is a cross-sectional side view of the cassette of FIG. 5A after a cassette cap of the cassette has been removed. [Figure 5D] FIG. 5D is a cross-sectional side view of the cassette of FIG. 5C showing the pre-filled drug containers of the cassette in the needle injection position. [Figure 6A] FIG. 10 is a bottom down front perspective view of an embodiment of the cassette showing the internal sleeve latching mechanism and the internal sleeve lock configuration; [Figure 6B] FIG. 6B is a bottom view of one embodiment of the outer housing of the cassette shown in FIG. 6A, showing certain elements of the inner sleeve latching mechanism and inner sleeve locking configuration. [Figure 7A] 1A and 1B are top and bottom front perspective views, respectively, of one embodiment of a cassette having a cassette identification feature; [Figure 7B] 1A and 1B are top and bottom front perspective views, respectively, of one embodiment of a cassette having a cassette identification feature; [Figure 8A] FIG. 10 is a bottom-down perspective view of a portion of a cassette showing one embodiment of a cassette identification mechanism. [Figure 8B]8B is a cross-sectional side view of the cassette of FIG. 8A being inserted into an autoinjector adapted to detect and decode the cassette identification feature contained in FIG. 8A. [Figure 9A] FIG. 10 is a bottom down perspective view of a portion of a cassette showing another embodiment of a cassette identification mechanism. [Figure 9B] 9B is a cross-sectional side view of the cassette of FIG. 9A being inserted into an autoinjector adapted to detect and decode the cassette identification feature contained in FIG. 9A. [Figure 10A] FIG. 10 is a bottom-down front perspective view of a portion of a cassette showing another embodiment of a cassette identification mechanism. [Figure 10B] 10B is a cross-sectional side view of the cassette of FIG. 10A being inserted into an autoinjector adapted to detect and decode the cassette identification feature contained in FIG. 10A. [Figure 11A] FIG. 10 is a bottom down perspective view of a portion of a cassette showing a further embodiment of a cassette identification feature. [Figure 11B] FIG. 10 is a bottom down perspective view of a portion of a cassette showing yet another embodiment of a cassette identification mechanism. [Figure 11C] FIG. 10 is a bottom down perspective view of a portion of a cassette showing yet another embodiment of a cassette identification mechanism. [Figure 11D] FIG. 10 is a bottom down perspective view of a portion of a cassette showing another embodiment of a cassette identification mechanism. [Figure 12] 1 is a flow chart illustrating one embodiment of a method for controlling the assembly of pre-filled drug containers (containing a variety of different drugs and / or fill levels), using a cassette identification mechanism to route assembled cassettes to appropriate packaging stations, and assembling different product lines on a single manufacturing line. [Figure 13] FIG. 1 is a bottom perspective view of the autoinjector of the autoinjector device or system showing the installation of the cassette into the autoinjector. [Figure 14]10 is a flow chart illustrating one embodiment of decision logic for forcing a user to perform steps in an injection process in a safe and reliable order. [Figure 15] 1 is a flowchart illustrating an endpoint and stall detection algorithm. [Figure 16] 1 is a graph showing the ejection process of an autoinjector device. DETAILED DESCRIPTION OF THE INVENTION

[0021] FIG. 1 illustrates one embodiment of an autoinjector system or device 100 that can be used to inject a dose of a medication (drug) into a patient. The injection is often self-administered by the patient (user). Alternatively, the drug can be administered by a healthcare provider. As shown, the autoinjection system or device 100 may include a removable cassette 200 and an autoinjector or injector 300. Various embodiments of the cassette 200 may be configured to contain a medication to be injected into a user by the autoinjector 300. In various other embodiments, the cassette 200 may be configured for use in training a user to operate the autoinjector 300 (a training cassette). The autoinjector 300 may be configured to automatically deliver an injection when activated by the user or other personnel. Various embodiments of the autoinjector 300 may have a cassette door 308 that can be configured to pivot between an open position and a closed position to allow insertion of the cassette 200 into the autoinjector 300. In some embodiments, the cassette door 308 may include a “cassette” icon (not shown) that indicates the insertion entry point for the cassette 200 .

[0022] 2A-2F collectively, various embodiments of autoinjector 300 may include a casing 302 having a handle portion 304 and a cassette receiving portion 306 aligned with the handle portion 304. To assist patients with dexterity challenges, the handle portion 304 of autoinjector casing 302 may define an ergonomically shaped handle 305 having a soft grip area 305S. Cassette receiving portion 306 includes cassette door 308 (FIGS. 2B and 2D), as described above. In the open position (FIG. 1), the cassette door receives cassette 200 and aligns it with the insertion and ejection drives, and in the closed position, aligns it with other structures and components of autoinjector 300. Cassette door 308 may include a "cassette" icon indicating the insertion entry point for cassette 200. The cassette-receiving portion 306 of the casing 302 may include windows 310A, 310B on its sides that align with the windows of the cassette 200 when the cassette door 308 is closed with the cassette 200 properly installed therein. In one or more embodiments, the windows 310A, 310B may be dual-layered. One or more lights (not shown) may be provided within the casing 302 to uniformly backlight the cassette window 212 ( FIG. 5A ) and the syringe 260 disposed within the internal sleeve 220 ( FIG. 5B ) of the cassette 200 so that a user can observe the injection cycle through the windows 310A, 310B of the autoinjector 300, i.e., the initial and final positions of the plunger stopper 264 of the syringe 260 ( FIG. 5B ) during the syringe's movement within the cassette 200 as well as during the syringe contents (hereinafter, “drug”) ejection process.

[0023] 2A, 2B, 2D, and 2F, autoinjector 300 may further include a user interface 312 and an audio speaker (not shown). User interface 312 (best shown in FIG. 2A) may be located in cassette-receiving portion 306 of casing 302 and provide various visual indicators. An audio speaker may be disposed within casing 302 and provide various audible indicators. The audio speaker may audibly communicate with the external environment through a speaker hole 314 formed in cassette-receiving portion 306 of casing 302. The visual and audible indicators produced by user interface 312 and audio speaker may inform the user when autoinjector 300 is ready for use, the progress of the injection process, completion of the injection, the occurrence of any errors, and other information. The autoinjector 300 may further include one or more of a set / mute switch 315, a speed select switch 316, a start button 307, and an eject button 317. The set / mute switch 315 (FIG. 2B) may be located in the cassette-receiving portion 306 of the casing 302. The mute switch 315 allows the user to turn all synthesized sounds, except error sounds, on and off and may be configured to respond in real time so that the sounds are immediately muted when the user begins the injection process and turns the mute switch off. The mute switch 315 may also be configured to slide toward a "mute" icon to mute the audio speaker. A light indicator may be provided to confirm the "mute" status. The speed select switch 316 (FIGS. 2A and 2B) may be located in the cassette-receiving portion 306 of the casing 302. The speed select switch 316 may be configured to allow the user to select from multiple preset drug delivery (excretion) rates to accommodate individual patient preferences. The speed select switch 316 may include three switch positions. Other embodiments of the speed select switch may include two switch positions or four or more switch positions. In still other embodiments, the speed select switch may be infinitely variable.In some embodiments, changing the position of the switch 316 before injection changes the drug output rate during injection, while changing the position of the rate select switch 316 during injection does not change the injection rate in real time. The autoinjector 300 may also include one or more demo cassettes to allow the user to experiment with different rates of drug delivery. The start button 307 may be located at the free end of the handle 305. The button 307 may include an indentation 307i (FIG. 2F) to optimize thumb placement on the button 307. The button 307 may be made of a translucent material that allows lighting effects to illuminate the button as a signal. The eject button 317 (FIG. 2D) may be located in the cassette-receiving portion 306 of the casing 302. The eject button 317 may include an indentation 317i to optimize finger placement on the button 317. In some embodiments, the eject button 317 may be controlled by the autoinjector's 300's microprocessor 350 (FIG. 2H), which can be programmed to eliminate accidental input during the injection process.

[0024] 2E, the cassette receiving portion 306 of the casing 302 and the cassette door 308 may form a proximal wall 318 of the autoinjector 300. The proximal wall 318 may be configured as a wide, flat, and stable base for easily placing the autoinjector 300 on a support surface after removal of the shield remover 240 (FIG. 5A) or when the autoinjector 300 does not contain a cassette 240. The portion of the proximal wall 318 formed by the cassette door 308 may include an aperture 308A sized and shaped to allow the shield remover 240 to be removed from the cassette 200 and ejected through the aperture 308A when the cassette 200 is installed within the autoinjector 300. The proximal wall of the autoinjector 300 may further include a target light 320. Target light 320 may be made to turn on when shield remover 240 is removed from cassette 200 and ejected through hole 308A, thereby providing a visual indication that shield remover 240 has been removed. When turned on, the target light assists the user in visualizing and selecting the injection site.

[0025] 2E , the autoinjector 300 may further include a capacitance-based skin sensor 380 (shown in dashed lines) or any other suitable skin sensor. The skin sensor 380 may be coupled to a microprocessor provided within the autoinjector 300, for example, to allow a signal or data to be transmitted to the microprocessor, such that the autoinjector 300 can determine when the proximal wall 318 of the autoinjector 300 has touched or is in contact with the skin without the need to apply downward pressure to the injection site area. The skin sensor 380 may also be configured to notify the user when skin contact is detected via audible and visual indicators generated by a speaker and a user interface. In some embodiments, the skin sensor 380 may include two pads or electrodes (not shown) located near the inner surface of or incorporated into the proximal wall 318 of the autoinjector 300. Bringing the proximal wall 318 into contact with the skin increases the capacitance signal of the electrodes. If the increase is sufficient, as determined by a microprocessor, which may be programmed with sensor decision logic, the electrode is activated. To determine whether skin contact has occurred, the microprocessor reads the capacitance of the electrode. The microprocessor then processes the capacitance information from both electrodes and determines that the proximal sidewall 318 has made adequate contact with the skin. In embodiments in which the electrode is located on the inside surface of the proximal sidewall 318, the electrode itself never touches the skin; only the plastic housing contacts the skin, with the electrode attached to the inside of the housing. Such a design accounts for the response of the housing material as well as the distance of the electrode from the skin (separated by the proximal sidewall 318) in a manner that computationally determines when the device is in contact with (or, indeed, very close to) the infusion site.

[0026] 2G is a state diagram illustrating decision logic for controlling the skin sensor 380 by the microprocessor of the autoinjector 300, according to one embodiment of the present disclosure. The process begins at 400, which indicates a reset of the autoinjector. The logic then proceeds to state 402, which indicates initialization of the skin sensor after a reset of the autoinjector. Once initialized, the logic proceeds to state 404, which indicates a "no contact" condition, where neither of the sensor's electrodes or only one of the sensor's electrodes detects that the proximal wall 318 has touched the skin. If both electrodes detect that the proximal wall 318 has touched the skin for less than a certain threshold time (e.g., 1 second), the logic proceeds to state 406, which indicates a "contact" condition. If either one of the electrodes detects that the proximal wall 318 has touched the skin, or if neither of the electrodes detects that the proximal wall 318 has touched the skin, the logic returns to state 404. However, if both electrodes detect that the proximal end wall 318 has touched the skin for a time equal to the threshold time (e.g., 1 second), the logic proceeds to state 408, which indicates a "contact okay" state. If one of the electrodes or neither electrode detects that the proximal end wall 318 has touched the skin, the logic proceeds to state 409. If both electrodes are touching the skin, the logic returns to "contact okay" state 408. If one electrode or neither electrode touches the skin for more than the threshold time (e.g., more than 1 second), the logic returns to state 404, which indicates a "no contact" state.

[0027] In a further approach, the autoinjector 300 can include multiple sensors 380, and the microprocessor 350 can analyze the capacitance measured by each sensor 380. In this embodiment, correct placement of the autoinjector 300 can be determined by a predetermined capacitance level of each sensor 380 over a predetermined amount of time. Furthermore, based on continuous readings or periodic sampling of the capacitance level of each sensor 380, the microprocessor 350 can determine whether the capacitance of one or more sensors 380 is decreasing, which may indicate that the user is tilting the injector 300. If the sensor 380 then falls below a threshold for a predetermined amount of time, the microprocessor 350 can then reorient the injector 300 according to the logic described above. This embodiment can assist the user in operating the autoinjector 300 with reduced errors due to nervousness, trembling, or restlessness.

[0028] As shown in FIGURE 2H, various embodiments of autoinjector 300 may include a chassis 301 disposed within a casing 302 for supporting a powered needle insertion drive 330, a powered drug ejection drive 340, a microprocessor 350, a battery 360 for powering drives 330, 340 and microprocessor 350, and a skin sensor 380. Casing 302 may define an ergonomically shaped handle portion 304 and a cassette receiving portion 306. Chassis 301 may include support surfaces 301s for supporting one or more cassettes 200 within autoinjector 300 and for aligning cassette 200, or a selected one of the one or more cassettes 200, with powered needle insertion drive 330 and powered drug ejection drive 340, respectively. A detector 370 may be provided on or within the cassette support surface 301s for detecting the presence of and / or information related to the cassette 200. The detector 370 may be coupled to the microprocessor 350 to enable transmission of signals or data to the microprocessor 350. The insertion drive 330 may include an insertion rack 332, an insertion drive motor 331, and an insertion drive gear train 333 for transmitting rotational motion of the insertion drive motor 331 to drive the rack 332. The insertion rack may include a tab arrangement including, for example, proximal and distal tabs 332p and 332d, respectively, that mates with the cassette 200. The ejection drive 340 may include an ejection drive motor 341, a plunger rod 342, a lead screw 343, and an ejection drive gear train 344. Plunger rod 342 may be driven by ejection drive motor 341 via lead screw 343 and ejection drive gear train 344 and may couple with plunger 264 of medication container 260 contained within cassette 200. Autoinjector 300 may be used to perform multiple injections.

[0029] With continued reference to FIG. 2H, the term microprocessor, as used herein, broadly refers to any controller, microcontroller, computer, or processor-based device having a processor, memory, and programmable input / output peripherals designed to control the operations of other components and devices. It is further understood to include common attached accessory devices that include memory, transceivers for communicating with other components and devices, and the like. These structural options are well known and understood in the art and need not be further described here. Microprocessor 350 may be configured to perform one or more of the steps, operations, and / or functions described herein (e.g., by using corresponding programming stored in memory, as will be appreciated by those skilled in the art). For example, microprocessor 350 of autoinjector 300 may be programmed with instructions that, when executed by microprocessor 350, enable control and monitoring of various operations and functions of autoinjector 300. For example, but not by way of limitation, microprocessor 350 may be programmed with instructions for controlling powered insertion and ejection drives 330, 340. These instructions may control and monitor each step of the injection cycle and process flow, thereby automating needle insertion, drug ejection, and needle retraction, and controlling the sequence of actions performed by the user to make the injection process and drug administration more reliable, accurate, and consistent. Microprocessor 350 may also be programmed with instructions to control audible and visual feedback to the user. An automatic power-on self-test verifies the operation and remaining battery charge of autoinjector 300.

[0030] In various other embodiments, the autoinjector 300 may include other types of needle insertion drives, drug ejection drives, and means for actuating and sequencing the drives. The insertion and ejection drives in such embodiments may be implemented as separate, distinct mechanisms, or may be combined into a single mechanism. The insertion and ejection drives in such embodiments may be powered by, but not limited to, a motor, a mechanical mechanism (e.g., a resilient member such as a spring), a gas pressure mechanism, a gas release mechanism, or any combination thereof. Various transmission mechanisms may be used to transmit power to the cassette to cause the drug injection. Additionally, the actuating and sequencing means may include various mechanical and electromechanical configurations and may be used in combination with or alone than the microprocessor described above. The autoinjector in such embodiments may be made reusable to perform multiple injections or may be designed for single, disposable use.

[0031] In one approach, the autoinjector 300 may include an encoder 346 coupled to the motor 341 and in communication with a microprocessor 350. The microprocessor 350 receives or queries a signal from the encoder 346 to determine the number of rotations of the motor 341 and thereby estimate the distance traveled by the plunger rod 342 and plunger 264 during the ejection process. The encoder 346 may take any suitable form. In the example shown in FIG. 2I, the encoder 346 includes a disk 348 having an identifiable portion 349 and an optical sensor 352. The disk 348 is coupled to and rotated by the motor 341, and the optical sensor 352 is configured to identify the identifiable portion 349 as it rotates within a detection field of the sensor 352. The identifiable portion 349 may be a window, a slit, a transparent portion, a translucent portion, or the like. If desired, the encoder 346 can illuminate the distinguishable portion 349 using a light source 354 so that the distinguishable portion 349 can be easily detected by the sensor 352 .

[0032] Referring now to FIG. 3 , various embodiments of the cassette 200 may include an outer housing 210, an inner sleeve 220, a drug container 260 for containing a drug, a cassette cap 240, a locking cap 230, and a cover 250. Such embodiments of the cassette 200 facilitate and enable simple injection of the drug using an auto-injector and can be made for single-use, disposable use. In various embodiments, the locking cap 230 and cover 250 of the cassette 200 may be configured to prevent removal of the drug container 260 from the cassette 200, thereby preventing needle protrusion before and after use of the cassette 200 and preventing the drug container 260 from being removed or replaced from the cassette 200. Additionally, the locking cap 230 and cover 250 protect the drug container 260 during delivery and transport. The cassette cap 240 of various embodiments may be configured to remove a needle shield 266 covering an injection needle associated with the drug container 260. In various other embodiments, the cassette cap 240 may also be configured to engage the outer housing 210 of the cassette 200 such that the cassette cap 240 cannot be rotated or turned, thereby preventing damage to the injection needle by the needle shield 266. Various embodiments of the inner sleeve 220 may be configured to position the drug container 260 within the cassette housing 210 in either a needle-hidden position or a needle-injection position during an injection cycle of the autoinjector. In various other embodiments, the outer housing 210 and inner sleeve 220 of the cassette 200 may include one or more locking features to protect the drug container 260 and prevent unintentional needle exposure or damage. Various other embodiments of the cassette 200 may include a cassette identification mechanism that interfaces with the autoinjector to communicate information regarding installation of the cassette 200 within the autoinjector and / or the cassette 200.

[0033] As shown in FIG. 4 , the medication container 260 may comprise a conventional glass or plastic syringe including a barrel 261 defining a fluid chamber 262. The fluid chamber 262 may be filled or pre-filled with a predetermined dose of medication 267 for treatment. The medication may have a viscosity that depends on the temperature of the product. The syringe 260 may further include an injection needle 265 removably or fixedly disposed at the proximal end of the barrel 261 and an outwardly extending flange 263 disposed at the distal end of the barrel 261. The injection needle 265 may communicate with the fluid chamber 262 to enable administration of the predetermined dose of medication 267 released from the fluid chamber 262 of the syringe barrel 261. The syringe 260 may further include a movable plunger stopper 264 disposed within the fluid chamber 262 of the barrel 261 for expelling the predetermined dose of medication 267 from the chamber 262 so that the predetermined dose of medication 267 may be dispensed through the injection needle 265. A protective needle shield 266 , for example made of a non-rigid material, may be provided to cover the infusion needle 265 .

[0034] In some embodiments, the drug contained within drug reservoir 260 may have a viscosity of about 19 centipoise at room temperature (20-25° C. [68-77° F.]).

[0035] In some embodiments, the drug contained within drug reservoir 260 may have a viscosity ranging from about 1 centipoise to about 320 centipoise at room temperature.

[0036] In some embodiments, the drug contained within drug reservoir 260 may have a viscosity ranging from about 5 centipoise to about 40 centipoise at room temperature.

[0037] In some embodiments, the drug contained within drug reservoir 260 may have a viscosity ranging from about 10 centipoise to about 35 centipoise at room temperature.

[0038] In some embodiments, the drug contained within drug reservoir 260 may have a viscosity in the range of about 15 centipoise to about 30 centipoise at room temperature.

[0039] In some embodiments, the drug contained within drug reservoir 260 may have a viscosity in the range of about 20 centipoise to about 25 centipoise at room temperature.

[0040] In some embodiments, the drug contained within drug reservoir 260 may have a viscosity ranging from about 16 centipoise to about 42 centipoise at room temperature.

[0041] In some embodiments, the drug contained within drug reservoir 260 may have a viscosity ranging from about 1 centipoise to about 29 centipoise at room temperature.

[0042] 5A-5D collectively, various embodiments of the outer housing 210 of the cassette 200 may include a top wall 210t, a bottom wall 210b, side walls 210s connecting the top wall 210t and the bottom wall 210b, respectively, a front or proximal end wall 210pe, and an open back or distal end 210de. The proximal end wall 210pe of the outer housing 210 may include an aperture 214 (FIGS. 5C and 5D) fabricated to removably receive the cassette cap 240. The outer housing 210 may be fabricated to retain the inner sleeve 220 within the outer housing 210 while allowing the inner sleeve 220 to slidably move freely within the outer housing 210 after removal of the cassette cap 240 (FIG. 5C). Some embodiments of the outer housing 210 may include an elongated opening or window 212 in each of its side walls 210s (FIG. 5A). The outer housing 210 of the cassette 200 may also include pins 215 (FIG. 5A) or any other suitable mechanical structure that prevents the cassette 200 from being inserted into the cassette door in the wrong direction and / or orientation. An "arrow" icon may be provided on the outer housing 210 (not shown) to indicate the proper direction and orientation for inserting the cassette into the cassette door.

[0043] 5A-5D, various embodiments of the inner sleeve 220 may each include a proximal end 222 and a distal end 224. The sleeve 220 may be sized and dimensioned to securely hold, directly or indirectly, a drug container 260 therein. The proximal end 222 of the inner sleeve 220 may define a bore 222a configured to allow an injection needle 265 of the drug container 260 to extend therethrough (FIG. 5C). The inner sleeve 220 may further include a drive post 268 that may be actuated by an insertion drive of an autoinjector during a needle insertion cycle of an injection cycle of the autoinjector. As seen in Figures 5C and 5D, the inner sleeve 220 can be driven through the outer housing 210 of the cassette 200 by an insertion drive of an autoinjector, during which the drug container 260 moves from a distal position within the outer housing 210 (Figure 5C) to a proximal position within the outer housing 210 (Figure 5D) and then back to the distal position. When the inner sleeve 220 is in the distal position (needle-hidden position) as shown in Figure 5C, the injection needle of the drug container 260 is housed within the outer housing 210 of the cassette 200 and hidden from the user's view. When the inner sleeve 220 is in the proximal position (needle-injection position) as shown in Figure 5D, the injection needle of the drug container 260 extends out through a hole 214 in the proximal wall 210pe of the outer housing 210 of the cassette 200 and through the autoinjector (not shown). Locking cap 230 closes open distal end 224 of inner sleeve 220, thereby securing drug container 260 within inner sleeve 220 so that drug container 260 moves with inner sleeve 220 as inner sleeve 220 is driven forward or backward through outer housing 210 by the autoinjector's insertion drive during the insertion cycle of autoinjector 300. Cover 250 closes open distal end 210de of outer housing 210 and encases inner sleeve 220 and drug container 260 within outer housing 210 of cassette 200, thereby preventing tampering with drug container 260 and providing a complete cosmetic appearance to cassette 200.Inner sleeve 220 may be made from a transparent rigid material, such as clear polycarbonate, to allow viewing of medication container 260 through window 212 in sidewall 210 s of outer housing 210 .

[0044] 6A and 6B collectively, various embodiments of the outer housing 210 of the cassette 200 may include a latching mechanism 280 that latches the drive post 268 of the inner sleeve 220 to retain the sleeve 220, and therefore the injection needle of the medication container, in a needle-hidden position, protecting the medication container and preventing accidental needle exposure to the user. As best shown in FIG. 6B , the latching mechanism 280 may include a pair of resilient, opposed latch arms 280a formed in the bottom wall 210b of the outer housing 210, or any other wall of the housing 210, that allows an insertion drive to engage the drive post 268 of the inner sleeve 220. The latching arms 280a may define a locking detent slot 280b ( FIG. 6B ) through which the drive post 268 of the inner sleeve 220 extends.

[0045] During assembly of cassette 200, inner sleeve 220, which houses the drug container, may be inserted into outer housing 210 such that drive posts 268 of inner sleeve 220 spread and slide between latch arms 280a of outer housing 210, and then enter and lock into detent slots 280b in latch arms 280a, as shown in FIGURE 6A. During the needle insertion cycle of the autoinjector, the insertion drive moves distal tab 332d proximally, thereby forcing latch arms 280a apart and releasing drive posts 268 of inner sleeve 220, thereby allowing the released inner sleeve 220 to move proximally and distally within cassette outer housing 210 via drive posts 268.

[0046] When released, the insertion drive can move the inner sleeve 220, and thus the drug container disposed therein, from the needle-hiding position to the needle-injecting position. Once the autoinjector's drug ejection cycle is complete, the insertion drive again moves the drive post 268, and thus the inner sleeve 220 containing the used drug container, to the needle-hiding position where the drive post 268 is again secured between the latch arms 280a of the latch mechanism 280.

[0047] Various other embodiments of the cassette may further include an internal sleeve locking arrangement 290 that prevents the internal sleeve 220 from unintentionally moving from its needle-hiding position within the external housing 210. The internal sleeve locking arrangement 290 may replace the latching mechanism 280 or may provide redundancy similar to the embodiment shown in Figures 6A-6B.

[0048] The addition of the internal sleeve locking configuration 290 provides redundancy and increases the reliability of the latching mechanism 280, for example, to protect the user from injury, protect the contents of the cassette, or prevent misuse. The internal sleeve locking configuration 290 provides improved resistance or locking against movement of the internal sleeve 220 during impacts, such as those caused by free fall, shipping, and / or handling. Furthermore, the internal sleeve locking configuration 290 improves absorption of impact energy to prevent damage to cassette components. Furthermore, the internal sleeve locking configuration 290 provides improved retention of the internal sleeve 220 in a needle-hidden position during removal of the needle shield to prevent exposure of the injection needle to the environment outside the external housing of the cassette 200. Additionally, the internal sleeve locking configuration 290 more accurately and repeatably positions the internal sleeve 220 in position for connection with an autoinjector.

[0049] 6B , various embodiments of the internal sleeve lock configuration 290 may further include one or more locking foot receiving slots 294 provided in the bottom wall 210 b of the cassette external housing 210 or any other wall of the housing that interfaces with the cantilever locking arms 292 of the internal sleeve 220. Each of the one or more locking foot receiving slots 294 may be provided at an end of a pair of elongated slots 282 that define the latch arms 280 a of the latch mechanism 280. Each of the locking foot receiving slots 294 functions to receive a corresponding one of the locking feet 292 f of the cantilever locking arms 292 to implement locking of the internal sleeve lock configuration 290.

[0050] In the embodiment described above, the internal sleeve locking configuration provides locking of the internal sleeve when the cantilever locking arm is in the unbiased state. In various other embodiments, the cantilever locking arm of the internal sleeve locking configuration can be made to provide locking of the internal sleeve in the biased, activated position. Such an embodiment may be desirable, for example, to hold the internal sleeve, and therefore the drug container, in a fixed position when desired. Furthermore, because the insertion motor drives the sleeve containing the drug container, the depth of the infusion needle can be controlled. This feature may be used in conjunction with the locking foot receiving slot and / or the cassette identification feature described below.

[0051] 7A and 7B collectively, various embodiments of cassette 200 may further include a cassette identification feature 410 that may be fabricated to communicate information about cassette 200 to an autoinjector. Cassette identification feature 410 may be located on the exterior surface of bottom wall 210bs of cassette outer housing 210 or any other portion of cassette 200 that can be detected and interpreted by an autoinjector. In some embodiments, the information communicated by cassette identification feature 410 may be in the form of a code. Specifically, cassette identification feature 410 may be fabricated to generate one of a number of different codes, each code corresponding to a particular characteristic of a particular cassette 200. The code allows an appropriately adapted autoinjector to determine the type of cassette 200 inserted into the autoinjector, i.e., whether the cassette is a training cassette (i.e., does not include a drug container or includes an empty drug container) or a drug cassette containing a drug container prefilled with a drug. Additionally, the code transmitted by cassette identification mechanism 410 can inform the autoinjector of the identity of the drug contained in the drug well and / or other cassette / drug container characteristics. Furthermore, the code may provide information that enables the autoinjector to determine whether cassette 200 was inserted into the autoinjector in the proper orientation. The autoinjector can be configured to automatically select an appropriate operating program and / or adjust its various operating parameters (e.g., by the aforementioned microprocessor) based on the information transmitted by cassette identification mechanism 410. For example, if the autoinjector detects the insertion of a training cassette, the autoinjector can automatically select a training program to train the user in using the autoinjector. In another example, if the autoinjector detects the insertion of a drug cassette containing a drug container prefilled with a particular drug, the autoinjector can automatically select the appropriate operating parameters for injecting that drug, such as the injection rate, needle insertion rate, pre- and post-injection wait times, needle insertion depth, temperature limits, etc.The available speed range may depend on the fill capacity of the drug container and the properties of the drug, such as viscosity. Automatic selection of its operating parameters by the autoinjector eliminates the need for the user to determine the appropriate operating parameters for a given drug and then manually enter them into the autoinjector.

[0052] As shown in FIG. 8A , various embodiments of the cassette identification mechanism 410 may include one or more protrusions or tabs 410t located on or within the bottom wall 210b of the cassette outer housing 210. The number and location of the tabs 410t may define a code, or at least a portion of a code, that indicates information about the cassette 200. As shown in FIG. 8B , the cassette identification mechanism 410 may further include a detector 370 that may be located on or within the cassette support surface 301s of the autoinjector 300 to detect the number and location of the tabs 410t when the cassette 200 engages the cassette support surface 301s when the autoinjector door 308 is closed. The detector 370 may be communicatively coupled to a microprocessor 350 housed within the autoinjector 300, thereby enabling the autoinjector 300 to detect the tabs 410t and obtain the code that indicates information about the cassette 200. In various embodiments, the detector 370 may include a plurality of conventional flush-mounted momentary pushbutton switches 372. The switches 372 may be positioned to engage corresponding ones of the tabs 410t. When the cassette 200 is supported on the cassette support surface 301s of the autoinjector 300, depending on the placement of the tabs 410t and the codes they represent, none, some, or all of the switches 372 may be activated by the tabs 410t of the cassette 200. Thus, the code defined by the tabs 410t and the information it represents about the cassette 200 may be communicated to the microprocessor 350 of the autoinjector 300 for decoding.

[0053] The tabs 410t can be distinguished from one another by their respective locations on or within the cassette housing 210. By utilizing the presence or absence of the tabs 410t, multiple combinations of codes can be created, with each code identifying a particular cassette 200 or cassette characteristic. While the cassette identification mechanism 410 shown in the embodiment of FIG. 8A includes three tabs 410t, various other embodiments of the cassette identification mechanism 410 may include more or fewer tabs to increase or decrease the number of available programming codes. In the embodiment shown in FIG. 8A, the presence and / or absence of one or more of the three tabs 410t provides up to eight possible different cassette identification codes that can be detected and decoded by the autoinjector 300. As previously mentioned, the information represented by each code may be used to define one of multiple programming instructions for the autoinjector 300 and / or to convey secondary information to the autoinjector 300, such as, but not limited to, verifying that the cassette 200 is an authorized OEM device and / or verifying proper insertion of the cassette 200 into the autoinjector 300.

[0054] Various other embodiments of the tabs 410t of the cassette identification mechanism 410 may have different heights. In such embodiments, the autoinjector's push button switch 372 and microprocessor 350 may be fabricated to enable them to distinguish between tabs 410t of different heights, for example, but not by way of limitation, depending on how far the button (not shown) of the push button switch 372 is depressed into the switch 370 by the tabs 410t. An embodiment including both a low tab 410t and a high tab 410t may provide each possible tab position on the cassette outer housing 210, for example, in one of the following three possible states: Condition 1: Tab does not exist Condition 2: Low tab exists Condition 3: Tall tabs exist

[0055] If the cassette identification mechanism 410 includes, for example, up to three tabs 410t, each of which can be low or high, the autoinjector can detect up to 27 different tab states, increasing the number of possible codes.

[0056] As shown in Figure 9A, various other embodiments of the cassette identification mechanism 410 may include one or more indentations 410i disposed in the bottom wall 210b of the outer housing 210 of the cassette 200. As shown in Figure 1 IB, in such embodiments of the cassette identification mechanism 410, the sensing portion 370 of the autoinjector 300 may include a plurality of conventional pogo pin switches 374n for sensing the presence or absence of the indentations 410i. The encoding, sensing, decoding, and parameter control functions are generally the same as those described above with respect to the tab 410t.

[0057] Various other embodiments of the recesses 410i of the cassette identification feature 410 can have different depths. In such embodiments, to increase the number of different possible codes, the autoinjector's pogo pin switch 374 and microprocessor 350 can be made to allow them to distinguish between recesses of different depths depending on how far the pins 374p of the pogo pin switch 374 are pushed into the switch by the recesses.

[0058] In various further embodiments, the cassette identification feature 410 of the cassette may include a combination of the tab 410t and indentation 410i described above. Accordingly, the autoinjector of such an embodiment may be fabricated to include a corresponding push button switch 372 and pogo pin switch 374.

[0059] The code defined by the tabs 410t and / or indentations 410i of the cassette identification mechanism 410 conveys information about the cassette 200 to the autoinjector 300, which can then use this information to automatically adjust its programming, etc. For example, but not by way of limitation, one tab 410t or indentation 410i may define a code indicating that the cassette 200 contains a drug container filled with 1 mL of drug, while two tabs 410t or indentations 410i may define a code indicating that the cassette 200 contains a drug container filled with 0.5 mL of drug. Additional tabs 410t or indentations 410i within the same cassette identification mechanism may provide codes identifying the drug and / or drug characteristics. In another example, the code for a training cassette may include the presence of all possible tabs 410t and / or indentations 410i. In a further example, the absence of one of the tabs 410t and / or indentations 410i may define a code for a particular drug. Different combinations of the tabs 410t and / or indentations 410i can be used to distinguish between different drugs or to indicate the absence of a drug container for purposes of controlling autoinjector parameters.

[0060] As shown in Figure 10A, various other embodiments of the cassette identification mechanism 410 may include one or more flat conductive traces or strips 410s provided on the exterior surface of the bottom wall 210b of the outer housing 210. In such an embodiment of the cassette identification mechanism 410 as shown in Figure 10B, the sensing portion 370 of the autoinjector 300 may be fabricated with a pogo pin connector 376 that contacts the conductive strips 410s when the cassette 200 is inserted into the autoinjector 300. The conductive strips 410s may be molded into the exterior surface of the bottom wall 210b of the cassette, screen printed onto its surface, or comprise a separate component such as a flex cable material attached to its surface with a pressure-sensitive adhesive or any other suitable means.

[0061] In various embodiments, one or more conductive strips 410s can operate as cassette presence sensors, and each conductive strip 410s can operate to close an electrical circuit in the sensing unit 370 between two pogo pin connectors 376 when the cassette 200 is mounted on the support surface 301s of the autoinjector 300. In some embodiments, the conductive strips 410s can be fabricated to form a straight path (e.g., as shown in FIG. 10A ) to connect pogo pin connectors arranged side by side, or to form a serpentine path to connect pogo pin connectors that require a sawtooth or serpentine path for connection. In other embodiments, the conductive strips 410s can be fabricated to have a particular electrical resistance, capacitance, inductance, etc. that defines a code detectable via the electrical circuit of the sensing unit 370, which further communicates the code and therefore associated cassette information, such as drug, fill volume, infusion rate, etc., to the microprocessor 350 of the autoinjector 300.

[0062] 10A and 10B, various embodiments of the cassette identification mechanism 410 may combine one or more of the conductive strips 410s described above with one or more tabs 410t (and / or indentations 410i). In such embodiments of the cassette identification mechanism 410, the sensing portion 370 and microprocessor 350 of the autoinjector 300 may be fabricated with appropriate push button switches 372 and pogo pin switches 374 (and / or pogo pin connectors 376). However, it should be understood that the cassette identification mechanism 410 may include only one or more conductive strips 410s.

[0063] As shown in FIG. 11A, various other embodiments of the cassette identification mechanism 410 may include one or more magnets 410m embedded in the bottom wall 210b of the cassette outer housing 210 or provided on an exterior or interior surface of the bottom wall 210b of the cassette outer housing 210. In such embodiments of the cassette identification mechanism 410, the sensing portion 370 of the autoinjector 300 (e.g., FIGS. 8B-10B) may be fabricated as a magnetic resonance (MR) sensor or other magnetic detection sensor that is activated by one or more magnets when the cassette 200 is inserted into the autoinjector 300. The one or more magnets 410m should be of sufficient strength to activate the MR sensor. The magnet and MR sensor configuration may be used alone or in combination with any of the other aforementioned cassette identification mechanisms 410.

[0064] 11B, various further embodiments of the cassette identification mechanism 410 may include a radio frequency (RF) electromagnetic field (EMF) generating device 410rf, such as an RF identification (RFID) chip. The sensing portion 370 of the autoinjector 300 (e.g., FIGS. 8B-10B) may be fabricated as an EMF receiving device, such as an RFID chip reader, that is activated by the RF EMF device 410rf when the cassette 200 is inserted into the autoinjector 300. The RF EMF device 410rf may be molded into or attached to the bottom wall 210b of the cassette outer housing 210 or any other suitable portion of the cassette 200 that allows the RF EMF device 410rf to communicate with the sensing portion 370 of the autoinjector 300.

[0065] As shown in FIG. 11C, various other embodiments of the cassette identification mechanism 410 may include one or more optical-machine-readable (OMR) identifiers 410o. The one or more OMR identifiers 410o may include, but are not limited to, one or more barcode labels, one or more color-code labels, one or more other suitable OMR identifiers, or any combination thereof. OMR identifiers 410o embodied as barcode labels may include, but are not limited to, one-dimensional and two-dimensional matrix codes. The sensing unit 370 of the autoinjector 300 in such embodiments (e.g., FIGS. 8B-10B) may be fabricated as an optical scanner. The OMR identifier 410o may be provided on the exterior surface of the bottom wall 210b of the cassette's outer housing 210 or any other suitable portion or area of ​​the cassette 200 that can interface with the sensing unit 370 of the autoinjector 300.

[0066] The RF EMF device 410rf and one or more OMR identifier labels 410o may be applied to the cassette before or after it is assembled with the pre-filled drug container, allowing the RF EMF device 410rf and / or one or more OMR identifier labels 410o to include additional information or programming such as date of manufacture, place of manufacture, drug expiration date, drug temperature stabilization time to allow the drug to reach optimal temperature prior to injection, and confirmation to the autoinjector that the cassette 200 and drugs are OEM parts.

[0067] 11D, various other embodiments of the cassette identification mechanism 410 may include one or more magnets 410m, RF EMF emitter devices 410rf, one or more OMR identifiers 410o, and tabs 410t (and / or indentations 410i) described above, each defining a portion of the code provided by the mechanism 410. In such embodiments of the cassette identification mechanism, the autoinjector sensing portion 370 may be fabricated with appropriate switches, sensors, receivers, and / or scanners (e.g., FIGS. 8B-10B) to sense the corresponding cassette element of the cassette identification mechanism 410.

[0068] The cassette identification mechanism 410 may also be used to control aspects of the cassette manufacturing and packaging process. Figure 12 shows a flowchart illustrating one example of how a single production or manufacturing line can be used to assemble different product lines, using the cassette identification mechanism to control the assembly of pre-filled drug containers (containing a range of different drugs and / or fill levels) and then route the assembled cassettes to the appropriate packaging station. Block 500 represents a single manufacturing line, which may include a computer-controlled manufacturing system, and blocks 502, 504, 506, and 508 may represent four unassembled cassettes in the line, each with its own cassette identification mechanism configuration (1, 2, 3, or 4), such as a tab, indentation, etc. Each unassembled cassette 502, 504, 506, and 508 is assembled with a drug container having one of four different drugs (A, B, C, or D) that matches the cassette identification mechanism configuration (cassette ID configuration). In the embodiment shown in FIG. 12 , the manufacturing system may be programmed such that cassette ID configuration 1 identifies drug C, cassette ID configuration 2 identifies drug B, cassette ID configuration 3 identifies drug D, and cassette ID configuration 4 identifies drug A.

[0069] In block 510, the line's manufacturing system identifies the cassette ID configuration of each unassembled cassette 502, 504, 506, and 508. For each unassembled cassette 502, 504, 506, and 508, the system in block 512 uses the identified cassette ID to select a matching one of drug containers 514, 516, 518, and 519 prefilled with drugs A, B, C, and D, respectively, and assembles it with the unassembled cassette 502, 504, 506, and 508. Thus, in block 512, unassembled cassette 502 having cassette ID configuration 1 may be assembled with drug container 518 pre-filled with drug C to produce assembled cassette 522, unassembled cassette 504 having cassette ID configuration 2 may be assembled with drug container 516 pre-filled with drug B to produce assembled cassette 524, unassembled cassette 506 having cassette ID configuration 3 may be assembled with drug container 520 pre-filled with drug D to produce assembled cassette 526, and unassembled cassette 508 having cassette ID configuration 4 may be assembled with drug container 514 pre-filled with drug A to produce assembled cassette 528.

[0070] In block 530, the manufacturing system sorts assembled cassettes 522, 524, 526, and 528 using their cassette ID configurations 1, 2, 3, and 4, respectively, and places them into packages 532, 534, 536, and 538 for drugs C, B, D, and A, respectively.

[0071] 13 , autoinjector system 100 may be configured to force a user to perform the steps of the injection process in a safe and reliable order that simplifies operation of autoinjector system 100. Controlling the order of actions performed by the user can make the injection process more reliable. Thus, in various embodiments, autoinjector system 100 is configured to force or force a user to perform the following steps in order: insert cassette 200 into autoinjector 300; prepare autoinjector system 100 for injection; place autoinjector 300 on the skin and begin the injection process; and discard the used cassette 200 and store autoinjector 300 for future use. Performing these steps in order ensures reliability of the autoinjector system and safety for the user.

[0072] As noted above, various embodiments of autoinjector 300 and cassette 200 may include mechanical, electromechanical, and other structures that provide feedback signals to a microprocessor (not shown) of autoinjector 300. The microprocessor may be programmed with instructions (e.g., algorithms) that, when executed by the microprocessor, allow these signals to be evaluated by the microprocessor to enable autoinjector 300 to transition through discrete logic "states" where autoinjector system 100 is in a known configuration.

[0073] 13 in conjunction with the flowchart of FIG. 14, one embodiment of decision logic is described for controlling various functions of autoinjector system 100. The decision logic forces the user to perform the following steps in sequence: insert cassette 200 into autoinjector 300; prepare autoinjector system 100 for injection; place autoinjector 300 on the skin and begin the injection process; and discard the used cassette 200 and store autoinjector 300 for future use.

[0074] Inserting the cassette into the autoinjector Prior to use, in block 500 (off, door closed, no cassette), the autoinjector system 100 may be in a state in which the only active button is one for initiating cassette door opening (the eject button) and all other buttons are deactivated. This allows the autoinjector system 100 to respond to only one user action—pressing the eject button indicated by arrow 502—and ignore or disable all other actions. Once the cassette door 308 of the autoinjector 300 is opened in block 504, the user may insert the cassette 200 into the door. In various embodiments, the autoinjector 300 and cassette 200 may include specific structure to allow cassette 200 to be inserted only in the correct orientation, such as one or more pins 215 on the cassette 200 that interact with corresponding slots or pins 216 in the cassette door 308 of the autoinjector 300 to allow insertion only in the correct orientation and prevent insertion in orientations around the insertion axis (z-axis), as shown in FIG. 14 . The cassette 200 may also have a tapered or other structure that mates with the cassette door 308 of the autoinjector 300 to prevent rotation about the x-axis.

[0075] While waiting for the user to insert the cassette 200, the autoinjector 300 may transition to a known state (Waiting for Door Closed A) at block 506 where all other user actions other than closing the door, such as pressing the start and eject buttons, may be ignored.

[0076] This forces the user to either close the cassette door 308 with the cassette 200 present at arrow 508 and proceed with the injection process, or close the door without the cassette 200 at arrow 510 as the autoinjector system 100 transitions to a known state prior to block 500. If the user chooses not to perform the requested action, the autoinjector system 100 continues to remain in the same state (door open) at block 512.

[0077] If, at arrow 508, the user inserts either a cassette 200 of unknown configuration and / or a used cassette 200 into the cassette door 308 and closes it, then, at block 516, the autoinjector system 100 detects this condition using, for example, the cassette identification mechanism described above, and does not allow the process to proceed to the next state. Thus, the user is forced to insert a valid cassette 200 (of known configuration and unused) in the correct orientation into the autoinjector 300 in order to proceed.

[0078] Equip the autoinjector system for injection Once the cassette door 308 of the autoinjector 300 is closed with a valid cassette 200, the autoinjector system 100 may transition to an active state (device activated) at block 514. The next step by the user in this configuration is to remove the cassette cap 240 at arrow 518. As noted above, in various embodiments, the autoinjector system 100 may be capable of detecting the presence or absence of the cassette cap 240 and may also be capable of monitoring the transition of the state of a cassette cap remover switch, which may be provided within the autoinjector 300, from present to absent. This transition may be used by the autoinjector system 100 to detect the removal of the cassette cap 240 by the user, causing the autoinjector system 100 to transition to the state of block 520 (cap off). This may force the user to either remove the cassette cap 240 at arrow 518 and continue the injection process, or abort the process by pressing the eject button at arrow 522, which will open the door at block 524 (Door Open A), allowing the cassette 200 to be removed, and returning the autoinjector system 100 to the last known state at block 506 (Door Close Wait A). If the user chooses not to perform the requested action, the autoinjector system 100 will continue to remain in the same state at block 515 (Cassette Sleep State).

[0079] To ensure that these actions are truly intended by the user and not initiated accidentally, the cassette cap removal and abort processes may require a commit action. Cassette cap removal may have a minimum pull force and direction so that the user or patient must intentionally hold and pull the cassette cap to remove the needle shield. In other words, there is a minimum removal force and direction for removal (pull straight down) so that the cassette cap cannot be accidentally removed through normal handling. For the abort process, this may be implemented by requiring the user to hold down the eject button at arrow 522 for a certain period of time before the ejection process begins.

[0080] Place it on the skin and start the injection process With a valid cassette 200 inserted into the autoinjector 300, the cassette cap 240 removed, and the autoinjector system 100 in the state of block 520 (cap off), at arrow 526, the user may place the autoinjector 300 over the injection site (skin). As noted above, various embodiments of the autoinjector 300 may include a skin sensor to enable the autoinjector system 100 to detect proximity to the injection site. Thus, the autoinjector system 100 may allow the user to proceed with the injection process only when the injection site is detected. As noted above, the microprocessor may be programmed with instructions that enable the microprocessor to indicate the presence of an injection site only when it detects a continuous positive signal from the skin sensor. This ensures that the user is engaged in the process and has stable contact with the injection site (ready to inject) to transition to the state of block 534. As described above, various embodiments of the cassette cap 240 may have a structure that prevents the cassette cap 240 from being reinserted into the cassette 200 once it has been removed, thereby preventing the user from reinserting the cassette cap 240 and returning to the previous state of block 514 (device activation).

[0081] This forces the user to either maintain the autoinjector 300 in stable contact with the injection site to proceed with the injection process at block 534, or abort the process by pressing the eject button at arrow 522, which allows the door to open and the cassette to be removed at block 524, returning the autoinjector system 100 to its last known state (Waiting for Door Closed A) after the door is opened at block 506. If a stable signal is not obtained at arrow 530, the autoinjector system 100 may continue to remain in the state of block 520 (Cap Off). If injection site contact is lost at any time, the autoinjector system 100 may return to the state of block 520 (Cap Off).

[0082] Once the above conditions are met and autoinjector system 100 is in the state of block 526 (ready to inject), the user activates an injection in this configuration at arrow 532. Upon initiation, autoinjector system 100 may recheck the cassette identification mechanism, skin sensor, etc. to confirm its expected configuration, and, if confirmed, may automatically perform the following steps, in order: needle injection and drug expulsion (injection progress) at block 536, (needle retract) at block 538, (injection complete) at block 540, (plunger retract) at block 542, and (automatically open door) at block 544, allowing cassette removal and disposal (door close wait B) at block 548. Immediately after the user initiates an injection, all other buttons and switches on autoinjector 300 may be disabled to prevent the user from accidentally activating any buttons during the injection process.

[0083] During the injection process, autoinjector system 100 continuously monitors the state of injection site contact at all times at block 564. The process may be terminated at any time if there is a loss of injection site contact for a predetermined period of time (e.g., the user intentionally removes autoinjector 300 from the injection site or adjusts its position in a manner that does not guarantee a reliable delivery process). Additionally, autoinjector system 100 may check for various mechanical errors during the injection process at block 560 (jammed needle error), block 562 (jammed plunger error), block 566 (needle retraction error), block 568 (device malfunction), and block 570 (cassette error).

[0084] If desired, the microprocessor 350 of the autoinjector 300 may be programmed with instructions that, when executed by the microprocessor 350, enable the autoinjector to control and monitor the insertion drive 330 inserting the needle 265 at two sequential speeds. More specifically, the microprocessor 350 may insert the needle 265 at a first, higher speed to begin the insertion process and at a second, lower speed at which momentum of the needle 265 and the components carrying the needle 265 eventually ceases to end the insertion process. In one example, the first speed is approximately 0.4 m / s and the second speed is approximately 0.2 m / s.

[0085] Monitoring the progress of the injection process Described herein is an autoinjector drug delivery device 300 configured with a stall and endpoint detection algorithm that tolerates the above-described variations in the drug 267 load, syringe or barrel 261, plunger 264, and other components of the autoinjector 300. The algorithm is effective in a variety of situations, configurations, and conditions. A stall or endpoint detected by the algorithm during an injection will cause the microprocessor 350 to stop the injection process, retract the plunger rod 342, and remove the needle 265 from the injection site.

[0086] The microprocessor 350 of the autoinjector 300 runs software that tracks the position of the plunger rod 342, such as by counting signals from the rotary encoder 342 with an optical sensor 352. The count starts at zero and has an expected end count, e.g., 2500 counts. The software samples the absolute position of the plunger rod 342 at set intervals, e.g., 5 mS. Using the counts and timing, an algorithm can determine whether the plunger rod 342 is simply slowing down or temporarily stalling, has stopped, or has reached the end of the barrel 261. Additionally, the microprocessor 350 can compare the readings to past samples, and the algorithm can be configured to use the past samples to provide an expected endpoint for determining when to stop the injection, when to retract the plunger rod 342, when to remove the needle 265, and when to terminate the injection process.

[0087] A flowchart of such an algorithm is shown in Figure 15. Generally, microprocessor 350 follows the logic of the algorithm to extract signal counts from encoder 346 and determine the position of plunger rod 342, and therefore plunger 264, during the injection process. By setting the value of the sample interval, the number of counts indicating movement, and the relationship between them, the algorithm allows microprocessor 350 to determine whether the plunger has stalled or reached an expected endpoint.

[0088] In block 600, the drug delivery process begins and the algorithm starts at count 0. After a predetermined interval (e.g., 5 mS), in block 602, the algorithm samples the injection location based on the rotary encoder 346 counts by the optical sensor 352. In block 604, the algorithm: One It is determined whether the sample indicates movement of the plunger rod 342. If there is movement, the algorithm returns to block 602 and performs another check of the plunger rod position. OneTake a sample. If there is no movement, then, in block 606, the algorithm determines whether a movement less than the count of the m signal detected by the encoder 346 has been detected within the last n samples. If the answer is no, the algorithm returns to block 602 and the plunger position is re-extracted. Alternatively, if the total movement within the last n samples is less than m, then, in block 608, the algorithm compares the total count number with the predicted end count x. If the total count number is not close to the end count x or is less than the end count x, the algorithm determines that the injection is incomplete and proceeds to block 610. In block 610, if the end count is not close, the "value < m within the last n samples" can be rechecked using different values of m and n. This is to confirm the stall during ejection due to the variations and conditions described above. If a stall is detected during ejection, in block 612, the motor is stopped and the algorithm ends. Otherwise, the algorithm continues to return to block 602 and re-extracts the plunger position. Returning to block 608, if the total count number is close to the end count x or greater than the end count x, the algorithm moves to block 614 and determines that the full dose of the drug 267 has been administered.

[0089] In this configuration, the selection of the value of n determines the sensitivity of the speed at which a stall is detected. For example, if a stall can be detected between [n and (n + 1)] samples when no movement is detected, a stall in an injection process having a duration between [(n * 5mS) and ((n + 1) * 5mS)] can be detected. The range of speeds (counts / second) at which the plunger moves when a stall is detected is obtained by [(1000 * m) / ((n + 1) * 5mS) and (1000 * m) / ((n) * 5mS)], where 1000 is the conversion factor 1000mS / S and 5mS is the sampling speed.

[0090]

Table 1

[0091] Applying the detection ranges shown in Table 1 to actual data from an injection operation of autoinjector device 300, as shown in FIG. 16, can reveal how effective the detection algorithm can be. As shown, the injection rate remains generally constant at approximately 225 counts / second for approximately 8.1 seconds until plunger 264 reaches the end of syringe barrel 261. The rate then steadily decreases until plunger 264 can no longer be pushed, which occurs just after 8.8 seconds. Plunger rod 342, which began to penetrate plunger 264 just before 9 seconds, stops again at 9.2 seconds. Further actuation of plunger rod 342 after 9.2 seconds could shatter the glass of syringe barrel 261. Ideally, the injection operation would fully push plunger 264 without penetrating plunger rod 342 into plunger 264. Therefore, in this example, ideal operation would stop at approximately 8.8 seconds. The graph shows the detection range for n=2 and m=1.

[0092] If desired, the microprocessor 350 can be further configured to maintain a generally constant ejection rate in order to continuously adjust the conditions or configuration of a particular injector 300. The algorithm first sets a current limit for a particular rate target based on the drug 267, the injector 300, user preferences, and combinations thereof. While the microprocessor 350 samples the position of the plunger rod 342 as described above, the microprocessor 350 compares the movement of the current sample with past samples to determine rate and change. If the rate exceeds the target, the current limit is adjusted lower. If the rate is below the target, the current limit is adjusted higher.

[0093] Discard the used cassette and store the autoinjector for future use. Once the injection process is complete and autoinjector system 100 reaches block 548 (Wait for Door Close B), the user is expected to remove and discard the used cassette 200 and close the cassette door 308 of the autoinjector 300 at arrow 550. To force the user to do this, autoinjector system 100 logic may be configured to prevent the user from closing the cassette door 308 of the autoinjector 300 with the cassette 200 present at block 548. If an attempt is made to close the door at arrow 552, autoinjector system 100 may detect the cassette 200 and immediately reopen the door at block 554. This may cause autoinjector system 100 to proceed to block 550 (OFF), forcing the user to close the cassette door 308 without the cassette 200 in order to store the autoinjector 300 for future use. If the user chooses not to perform the requested action, the autoinjector system 100 may continue to remain in the same state at block 556 (Door Open Sleep B).

[0094] Drug Information The above description describes various assemblies, devices, and methods for use with drug delivery devices. It should be clear that the assemblies, drug delivery devices, or methods can further include the use of drugs or agents as described below, and it should be noted that the following list should not be considered to be either all-inclusive or limiting. The drug or agent is contained within a reservoir. In some cases, the reservoir is a primary container that is either filled or pre-filled with a drug product or agent for treatment. The primary container may be a cartridge or a pre-filled syringe. As used herein, the term drug may be used interchangeably with other similar types of phrases and may refer to any type of pharmaceutical, therapeutic or non-therapeutic injectable, such as traditional and non-traditional medicines, functional foods, dietary supplements, prodrugs (e.g., compounds or molecules that are administered in an inactive or less active form but are cleaved / processed in the recipient to form an active drug), biologicals, bioactive compounds, bioactive molecules, bioactive agents, etc.

[0095] The drug container of the cassette may be filled or pre-filled with a pharmaceutical agent for treatment, such as an erythropoiesis-stimulating agent (ESA), which may be in liquid or lyophilized form. The ESA may be an erythropoiesis-stimulating protein. As used herein, "erythropoiesis-stimulating protein" refers to any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to the receptor and causing receptor dimerization. Erythropoiesis-stimulating proteins include erythropoietin and its variants, analogs, or derivatives that bind to and activate the erythropoietin receptor; antibodies that bind to and activate the erythropoietin receptor; or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis-stimulating proteins include, but are not limited to, epoetin alpha, epoetin beta, epoetin delta, epoetin omega, epoetin iota, epoetin zeta, and analogs thereof, PEGylated erythropoietin, carbamylated erythropoietin, mimetic peptides (including EMP1 / Hematide), and mimetic antibodies. Exemplary erythropoiesis-stimulating proteins include erythropoietin, darbepoietin, erythropoietin agonist variants, and peptides or antibodies that bind to and activate the erythropoietin receptor.

[0096] The term erythropoiesis-stimulating protein includes Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxy polyethylene glycol epoetin beta), Hematide™ (peginesatide), MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (erythropoiesis-stimulating protein), and erythropoiesis-stimulating protein (erythropoiesis-stimulating protein). Epoetin beta, epoetin zeta, epoetin theta, and epoetin delta.

[0097] The term erythropoiesis stimulating protein further includes molecules or variants or analogs disclosed in the following patents or patent applications, the contents of each of which are incorporated herein by reference in their entirety: U.S. Pat. No. 4,703,008; U.S. Pat. No. 5,441,868; U.S. Pat. No. 5,547,933; U.S. Pat. No. 5,618,698; U.S. Pat. No. 5,621,080; U.S. Pat. No. 5,756,349; U.S. Pat. No. 5,767,078; U.S. Pat. No. 5,773,569; U.S. Pat. No. 5,830,851. , U.S. Patent Nos. 5,856,298, 5,955,422, 5,986,047, 6,030,086, 6,310,078, 6,391,633, 6,583,272, 6,586,398, 6,900,292, 6,750,369, 7,030,226, 7,084,245, and 7,271,689 Publication No. 2002 / 0155998, Publication No. 2003 / 0077753, Publication No. 2003 / 0082749, Publication No. 2003 / 0143202, Publication No. 2003 / 0215444, Publication No. 2004 / 0009902, Publication No. 2004 / 0071694, Publication No. 2004 / 0091961, Publication No. 2004 / 0143857, Publication No. 200 4 / 0157293, U.S. Patent Application Publication No. 2004 / 0175379, U.S. Patent Application Publication No. 2004 / 0175824, U.S. Patent Application Publication No. 2004 / 0229318, U.S. Patent Application Publication No. 2004 / 0248815, U.S. Patent Application Publication No. 2004 / 0266690, U.S. Patent Application Publication No. 2005 / 0019914, U.S. Patent Application Publication No. 2005 / 0026834, U.S. Patent Application Publication No. 2005 / 0096461, U.S. Patent Application Publication No. 2005 / 0107297,U.S. Patent Application Publication No. 2005 / 0107591, U.S. Patent Application Publication No. 2005 / 0124045, U.S. Patent Application Publication No. 2005 / 0124564, U.S. Patent Application Publication No. 2005 / 0137329, U.S. Patent Application Publication No. 2005 / 0142642, U.S. Patent Application Publication No. 2005 / 0143292, U.S. Patent Application Publication No. 2005 / 0153879, U.S. Patent Application Publication No. 2005 / 0158822, U.S. Patent Application Publication No. 2005 / 0158832, U.S. Patent Application Publication No. 2005 Nos. 2005 / 0170457, 2005 / 0181359, 2005 / 0181482, 2005 / 0192211, 2005 / 0202538, 2005 / 0227289, 2005 / 0244409, 2006 / 0040858, 2006 / 0088906, and 2006 / 0111279 , as well as PCT Publication Nos. WO 91 / 05867, WO 95 / 05465, WO 96 / 40772, 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 / 4 9673 pamphlet, WO 02 / 085940 pamphlet, WO 03 / 029291 pamphlet, WO 2003 / 055526 pamphlet, WO 2003 / 084477 pamphlet, WO 2003 / 094858 pamphlet, WO 2004 / 002417 pamphlet, WO 2004 / 002424 pamphlet, WO 2004 / 009627 pamphlet, WO 2004 / 024761 pamphlet, WO 2004 / 033651 pamphlet,WO 2004 / 035603, WO 2004 / 043382, WO 2004 / 101600, WO 2004 / 101606, WO 2004 / 101611, WO 2004 / 106373, WO 2004 / 018667, WO 2005 / 001025, WO 2005 / 001136, WO 2005 / 021579, WO 2005 / 025606, WO 2005 / 032460, WO 2005 / 0 No. 51327, WO 2005 / 063808, WO 2005 / 063809, WO 2005 / 070451, WO 2005 / 081687, WO 2005 / 084711, WO 2005 / 103076, WO 2005 / 100403, WO 2005 / 092369, WO 2006 / 50959, WO 2006 / 02646, WO 2006 / 29094, and WO 2007 / 136752.

[0098] Alternatively, the drug containers of the cassettes may also be filled or pre-filled with other products for therapy. Examples of other pharmaceuticals that may be used include biologics (e.g., therapeutic substances such as Enbrel® (etanercept, a TNF receptor / Fc fusion protein, a TNF inhibitor); anti-TNF antibodies such as adalimumab, infliximab, certolizumab pegol, and golimumab; anti-IL-12 antibodies such as ustekinumab, other Fc fusions such as CTL4A:Fc, also known as abacept; Neulasta® (pegylated Therapeutic agents may include, but are not limited to, other small molecule drugs, therapeutic antibodies, polypeptides, proteins, or other chemicals such as iron (e.g., ferumoxytol, iron dextran, ferric glyconate, and ferric iron oxide). Therapeutic agents may be in liquid form or reconstituted from a lyophilized form.

[0099] Among certain exemplary proteins that may be used within the drug reservoir of the cassette are antibodies, peptibodies, PEGylated proteins, polypeptides, and related proteins (including fusions, fragments, analogs, variants, or derivatives thereof), such as proteins that specifically bind to OPGL; IL-4 receptor; interleukin 1-receptor 1 ("IL1-R1"); angiopoietin-2 (Ang2); NGF; CD22; IGF-1; B-7-related protein 1 (B7RP1); IL-15; IL-17 receptor A; IFN gamma; TALL-1; parathyroid hormone ("PTH"); thrombopoietin receptor ("TPO-R"); hepatocyte growth factor ("HGF"); TRAIL-R2; activin A; TGF-β; amyloid-β; c-Kit; α4β7; and IL-23, or one of its subunits; and other therapeutic proteins.

[0100] The drug container of the cassette may also be loaded or pre-loaded for therapeutic use with OPGL-specific antibodies (also referred to as RANKL-specific antibodies, peptibodies, etc.), peptibodies, and related proteins, including those having the sequences described in PCT Publication WO 03 / 002713, specifically but not limited to those shown in the publications (9H7, 18B2, 2D8, 2E11, 16E1, and 22B3), including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies, including OPGL-specific antibodies having the light chain of SEQ ID NO: 2 set forth in Figure 2 of PCT Publication WO 03 / 002713 and / or the heavy chain of SEQ ID NO: 4 set forth in Figure 4 of PCT Publication WO 03 / 002713, each of which is individually and specifically incorporated herein by reference in its entirety.

[0101] The drug containers of the cassettes also contain TN8-19-1 through TN8-19-40, TN8-19 con1, and TN8-19 con2, as disclosed in U.S. Patent Application Publication No. 2004 / 0181033 and PCT Publication No. WO 2004 / 058988, each of which is individually and specifically incorporated herein by reference in its entirety. Peptibodies of the mTN8-19 family, including those of SEQ ID NOs: 305-351, including con2; the mL2 family of SEQ ID NOs: 357-383 in the above publication, the mL15 family of SEQ ID NOs: 384-409 in the above publication, the mL17 family of SEQ ID NOs: 410-438 in the above publication, the mL20 family of SEQ ID NOs: 439-446 in the above publication, the mL21 family of SEQ ID NOs: 447-452 in the above publication, the mL24 family of SEQ ID NOs: 453-454 in the above publication, and the peptibodies of SEQ ID NOs: 615-631 in the above publication, in particular those described in the above publications, which are incorporated herein by reference in their entirety, particularly in part with respect to myostatin-specific peptibodies, may be loaded or preloaded for therapeutic use.

[0102] The drug containers of the cassettes may also contain L1H1, L1H2, L1H3, L1H4, L1H5, L1H6, L1H7, L1H8, L1H9, L1H10, L1H11, L2H1, L2H2, L2H3, L2H4, L2H5, L2H6, L2H7, L2H8, L2H9, L2H10, L2H11, L2H12, L2H13, L2H14, L2H15, L2H16, L2H17, L2H18, L2H19, L2H20, L2H21, L2H22, L2H23, L2H24, L2H25, L2H26, L2H27, L2H28, L2H29, L2H30, L2H31, L2H32, L2H33, L2H34, L2H35, L2H36, L2H37, L2H38, L2H40, L2H41, L2H42, L2H43, L2H44, L2H45, L2H46, L2H47, L2H48, L2H50, L2H51, L2H52, L2H53, L2H54, L2H55, L2H56, L2H57, L2H58, L2H6, L2H60, L2H61, L2H62, L2H63, L2H64, L2H65, L2H66, L2H67, L2H68, L2H69, L2H70, L2H71, L2H72, L2H73, L2H74, L2H75, L2H76, L2H77, L2H IL-4 receptor-specific antibodies, including, but not limited to, IL-4 receptor-specific antibodies, particularly those described in the above publications, particularly those that inhibit activities mediated by IL-4 and / or IL-13 binding to the receptor, including, but not limited to, IL-4 receptor-specific antibodies, L2H12, L2H13, L2H14, L3H1, L4H1, L5H1, L6H1, and the like, particularly those that inhibit activities mediated by IL-4 and / or IL-13 binding to the receptor, including, but not limited to, IL-4 receptor-specific antibodies, peptibodies, and related proteins, may be loaded or preloaded for therapeutic use.

[0103] The drug reservoirs of the cassette may also be therapeutically loaded or pre-loaded with interleukin-1-receptor-1 ("IL1-R1")-specific antibodies, peptibodies, and related proteins, including but not limited to those set forth in U.S. Patent Application Publication No. 2004 / 097712 A1, namely, 15CA, 26F5, 27F2, 24E12, and 10H7, each of which is individually and specifically incorporated herein by reference in its entirety, in part, with particular reference to IL1-R1-specific binding proteins, particularly monoclonal antibodies, and the like.

[0104] The drug reservoirs of the cassettes may also contain 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, as disclosed in the following publications, each of which is individually and specifically incorporated herein by reference in its entirety: Ang2-specific antibodies and peptibodies, including, but not limited to, Ang2-specific antibodies and peptibodies, such as Ang2-1K, Con4-L1(N), Con4-L1C, TN-12-9(N), C17(N), TN8-8(N), TN8-14(N), and Con1(N), particularly those described in PCT Publication No. WO 03 / 057134 and U.S. Patent Application Publication No. 2003 / 0229023, each of which is incorporated herein by reference in its entirety, and particularly those described in the following publications: Ab526, Ab528, Ab531, Ab533, Ab535, Ab536, Ab537, Ab538, Ab540, Ab541, Ab542, Ab543, Ab544, Ab545, Ab546, Ab547, Ab548, Ab549, Ab550, Ab551, Ab552, Ab553, Ab554, Ab555, Ab556, Ab557, Ab558, Ab559, Ab560, Ab561, Ab562, Ab563, Ab564, Ab565, Ab566, Ab567, Ab568, Ab569, Ab570, Ab571, Ab572, Ab573, Ab574, Ab575, Ab576, Ab577, Ab578, Ab579, Ab580, Ab581, Ab582, Ab583, Ab584, Ab585, Ab586, Ab587, Ab588, Ab589, Ab590, Ab591, Ab592, Ab593, Ab594, Ab595, Ab596, Ab597, Ab598, Ab599, Ab599, Ab5 Ang2-specific antibodies, peptibodies, and related proteins, including anti-Ang2 antibodies and formulations such as those described in PCT Publication WO 2003 / 030833, the entire contents of which are incorporated herein by reference, may be loaded or preloaded for therapeutic use.

[0105] The drug reservoirs of the cassette may also be therapeutically loaded or pre-loaded with NGF-specific antibodies, peptibodies, and related proteins, etc., as disclosed in U.S. Patent Application Publication No. 2005 / 0074821 and U.S. Patent No. 6,919,426, each of which is individually and specifically incorporated herein by reference in its entirety, particularly those described in the above publications, which are incorporated herein by reference in their entireties, with respect to NGF-specific antibodies and related proteins, including, but not limited to, the NGF-specific antibodies 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11 set forth therein.

[0106] The drug reservoirs of the cassette may also be therapeutically loaded or pre-loaded with CD22-specific antibodies, peptibodies, and related proteins, including, but not limited to, humanized and fully human monoclonal antibodies, particularly human CD22-specific IgG antibodies, such as, for example, a dimer of human-mouse monoclonal hLL2 gamma chain disulfide linked to a human-mouse monoclonal hLL2 kappa chain, including, but not limited to, the human CD22-specific fully humanized antibody of epratuzumab (CAS Registry Number 501423-23-0), and specifically human CD22-specific antibodies, such as those described in U.S. Pat. No. 5,789,554, the entire contents of which are incorporated herein by reference, with respect to CD22-specific antibodies and related proteins.

[0107] The drug container of the cassette also contains IGF-1 specific antibodies L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L1H11, L1H12, L1H13, L1H14, L1H15, L1H16, L1H17, L1H18, L1H19, L1H20, L1H21, L1H22, L1H23, L1H24, L1H25, L1H26, L1H27, L1H28, L1H29, L1H30, L1H31, L1H32, L1H33, L1H40, L1H41, L1H42, L1H43, L1H44, L1H45, L1H46, L1H47, L1H , L11H11, L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H 21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L30H30, L31H31, L32 IGF-1 receptor-specific antibodies, peptibodies, and related proteins, including but not limited to H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1R-binding fragments and derivatives thereof, such as those described in the above publications, which are incorporated by reference herein in their entireties, with respect to IGF-1 receptor-specific antibodies and related proteins, may be loaded or preloaded for therapeutic use.

[0108] Also among the non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the present invention are each of those described below. (i) antibodies described in U.S. Patent Application Publication No. 2006 / 0040358 (published February 23, 2006), U.S. Patent Application Publication No. 2005 / 0008642 (published January 13, 2005), and U.S. Patent Application Publication No. 2004 / 0228859 (published November 18, 2004), including, but not limited to, antibody 1A (DSMZ Accession No. DSM ACC 2586), antibody 8 (DSMZ Accession No. DSM ACC 2589), antibody 23 (DSMZ Accession No. DSM ACC 2588), and antibody 18; (ii) antibodies described in PCT Publication No. WO 06 / 138729 (published December 28, 2006) and PCT Publication No. WO 05 / 016970 (published February 24, 2005), and by Lu et al. al.(2004), J. Biol. Chem.279:2856-2865, (iii) antibodies described in PCT Publication No. WO 07 / 012614 (published February 1, 2007), PCT Publication No. WO 07 / 000328 (published January 4, 2007), PCT Publication No. WO 06 / 013472 (published February 9, 2006), PCT Publication No. WO 05 / 058967 (published June 30, 2005), and PCT Publication No. WO 03 / 059951 (published July 24, 2003); (iv) antibodies described in U.S. Patent Application Publication No. 2005 / 0084906 (published April 21, 2005). (v) U.S. Patent Application Publication No. 2005 / 0249728 (published November 10, 2005), U.S. Patent Application Publication No. 2005 / 0186203 (published August 25, 2005), U.S. Patent Application Publication No. 2004 / 0265307 (published December 30, 2004), and U.S. Patent Application Publication No. 2003 / 0235582 (published December 25, 2003), and Maloney (vi) antibodies including, but not limited to, antibody EM164, resurfaced EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2, and huEM164 v1.3, as described in U.S. Pat. No. 7,037,498 (issued May 2, 2006), U.S. Patent Application Publication No. 2005 / 0244408 (published November 30, 2005), and U.S. Patent Application Publication No. 2004 / 0086503 (published May 6, 2004), and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-73, ATCC accession numbers PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, and antibody 2.(vii) antibody 19D12, described in U.S. Patent Application Publication No. 2005 / 0136063 (published June 23, 2005) and U.S. Patent Application Publication No. 2004 / 0018191 (published January 29, 2004), including, but not limited to, each of the antibodies produced by hybridomas having the sequences 15H12 / 19D12 HCA(γ4), which has been deposited with the ATCC under accession number PTA-5214, and the heavy chain encoded by the polynucleotide of plasmid 15H12 / 19D12 HCA(γ4), which has been deposited with the ATCC under accession number PTA-5220. and (viii) antibodies including, but not limited to, antibodies PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2, PINT-12A3, PINT-12A4, and PINT-12A5, which are described in U.S. Patent Application Publication No. 2004 / 0202655 (published October 14, 2004), each of which is incorporated by reference in its entirety, with respect to the aforementioned antibodies, peptibodies, and related proteins that specifically target the IGF-1 receptor.

[0109] The drug container of the cassette may also contain B-7 related protein 1-specific antibodies, peptibodies, related proteins, and the like ("B7RP-1," also referred to in the literature as B7H2, ICOSL, B7h, and CD275), particularly B7RP-specific fully human monoclonal IgG2 antibodies, particularly fully human IgG2 monoclonal antibodies that bind to an epitope in the first immunoglobulin-like domain of B7RP-1, particularly those that inhibit the interaction of B7RP-1 with ICOS, the natural receptor for B7RP-1, particularly on activated T cells, and particularly 16H (within which are light and heavy chain variable region sequences SEQ ID NO:1 and SEQ ID NO:7, respectively), 5D (within which are light and heavy chain variable region sequences SEQ ID NO:2 and SEQ ID NO:3, respectively), as disclosed in the following U.S. publications, each of which is individually and specifically incorporated herein by reference in its entirety: 9), 2H (having therein light chain variable region sequences and heavy chain variable region sequences, SEQ ID NO:3 and SEQ ID NO:10, respectively), 43H (having therein light chain variable region sequences and heavy chain variable region sequences, SEQ ID NO:6 and SEQ ID NO:14, respectively), 41H (having therein light chain variable region sequences and heavy chain variable region sequences, SEQ ID NO:5 and SEQ ID NO:13, respectively), and 15H (having therein light chain variable region sequences and heavy chain variable region sequences, SEQ ID NO:4 and SEQ ID NO:12, respectively). Such antibodies and related proteins may be loaded or preloaded for therapeutic use, including, but not limited to, the antibodies set forth in the following publications: U.S. Patent Application Publication No. 2008 / 0166352 and PCT Publication No. WO 07 / 011941, each of which is incorporated by reference in its entirety:

[0110] The drug reservoirs of the cassette may also be therapeutically loaded or pre-loaded with IL-15 specific antibodies, peptibodies, and related proteins, particularly antibodies, particularly humanized monoclonal antibodies, such as those disclosed in U.S. Patent Application Publication Nos. 2003 / 0138421, 2003 / 023586, and 2004 / 0071702, and U.S. Patent Application Publication No. 7,153,507, each of which is incorporated herein by reference in its entirety for IL-15 specific antibodies and related proteins, including, inter alia, peptibodies, including, but not limited to, HuMax IL-15 antibody and related proteins, such as 146B7.

[0111] The drug reservoir of the cassette may also be therapeutically loaded or preloaded with a pharmaceutical composition comprising an antagonistic human monoclonal antibody against human IL-17 receptor A. The properties, cloning, and preparation of IL-17 receptor A are described in U.S. Patent No. 6,072,033, issued June 6, 2000, which is incorporated by reference in its entirety. The amino acid sequence of human IL-17RA is set forth in SEQ ID NO: 10 (GenBank Accession No. NM014339) of U.S. Patent No. 6,072,033. Such antibodies may include those disclosed in WO 2008 / 054603, which is incorporated by reference in its entirety, or those claimed in U.S. Patent No. 7,767,206 and U.S. Patent Application No. 11 / 906,094, issued August 3, 2010, which are incorporated by reference in their entireties.

[0112] The drug reservoirs of the cassettes may also be loaded or preloaded for therapy with IFNγ-specific antibodies, peptibodies, and related proteins, particularly human IFNγ-specific antibodies, particularly fully human anti-IFNγ antibodies, such as those described in the following patent publications: U.S. Patent Application Publication No. 2005 / 0004353, the entire sequences of which are incorporated herein by reference in their entireties for the antibodies designated 1118, 1118*, 1119, 1121, and 1121*. The entire sequences of the heavy and light chains of each of these antibodies, as well as the sequences of their heavy and light chain variable regions and complementarity-determining regions, are individually and specifically incorporated herein by reference in their entireties, as disclosed in the aforementioned U.S. publications and Thakur et al., Mol. Immunol. 36:1107-1115 (1999), respectively. Additionally, the descriptions of the properties of these antibodies provided in the above publications are also incorporated herein by reference in their entireties. Specific antibodies include those having a heavy chain of SEQ ID NO: 17 and a light chain of SEQ ID NO: 18, those having a heavy chain variable region of SEQ ID NO: 6 and a light chain variable region of SEQ ID NO: 8, those having a heavy chain of SEQ ID NO: 19 and a light chain of SEQ ID NO: 20, those having a heavy chain variable region of SEQ ID NO: 10 and a light chain variable region of SEQ ID NO: 12, those having a heavy chain of SEQ ID NO: 32 and a light chain of SEQ ID NO: 20, those having a heavy chain variable region of SEQ ID NO: 30 and a light chain variable region of SEQ ID NO: 12, those having a heavy chain sequence of SEQ ID NO: 21 and a light chain sequence of SEQ ID NO: 22, those having a heavy chain variable region of SEQ ID NO: 14 and a light chain variable region of SEQ ID NO: 16, those having a heavy chain of SEQ ID NO: 21 and a light chain of SEQ ID NO: 33, and those having a heavy chain variable region of SEQ ID NO: 14 and a light chain variable region of SEQ ID NO: 31, as disclosed in the aforementioned U.S. publication. Specific antibodies contemplated include antibody 1119, disclosed in the aforementioned U.S. Patent Application Publication, having the complete heavy chain of SEQ ID NO: 17 and the complete light chain of SEQ ID NO: 18, as disclosed in the aforementioned U.S. Patent Application Publication;

[0113] The drug containers of the cassette may also be loaded or preloaded for therapeutic use with TALL-1 binding proteins, such as TALL-1 specific antibodies, peptibodies, and related proteins, as disclosed in the following U.S. publications, each of which is individually and specifically incorporated herein by reference in its entirety, particularly those described in U.S. Patent Application Publication Nos. 2003 / 0195156 and 2006 / 0135431, each of which is incorporated herein by reference in its entirety with respect to the molecules in Tables 4 and 5B of the above publications:

[0114] The drug reservoirs of the cassette may also be therapeutically loaded or preloaded with PTH-specific antibodies, peptibodies, and related proteins, such as those described in U.S. Pat. No. 6,756,480, which is incorporated herein by reference in its entirety, with particular reference to proteins that bind PTH.

[0115] The drug reservoirs of the cassette may also be therapeutically loaded or preloaded with TPO-R specific antibodies, peptibodies, and related proteins, such as those described in U.S. Pat. No. 6,835,809, which is incorporated herein by reference in its entirety, with particular reference in part to proteins that bind to TPO-R.

[0116] The drug reservoirs of the cassette may also be therapeutically loaded or preloaded with hepatocyte growth factor ("HGF")-specific antibodies, peptibodies, and related proteins, including those that target the HGF / SF:c-Met axis (HGF / SF:c-Met), such as fully human monoclonal antibodies that neutralize hepatocyte growth factor / scatter (HGF / SF), as described in U.S. Patent Application 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 by reference in its entirety with particular reference to proteins that bind HGF.

[0117] TRAIL-R2 specific antibodies, peptibodies, related proteins, etc., such as those described in U.S. Pat. No. 7,521,048, which is incorporated herein by reference in its entirety, with particular reference to proteins that bind to TRAIL-R2, may be loaded or preloaded for therapeutic use.

[0118] The drug reservoir of the cassette may also be therapeutically loaded or preloaded with activin A-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Application Publication No. 2009 / 0234106, the entire contents of which are incorporated herein by reference, with particular reference to proteins that bind to activin A.

[0119] The drug reservoirs of the cassette may also be therapeutically loaded or preloaded with TGF-β specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Pat. No. 6,803,453 and U.S. Patent Application Publication No. 2007 / 0110747, each of which is incorporated by reference in its entirety, with particular reference in part to proteins that bind to TGF-β.

[0120] The drug reservoir of the cassette may also be therapeutically loaded or preloaded with amyloid beta protein-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in PCT Publication WO 2006 / 081171, which is incorporated herein by reference in its entirety, with particular reference in part to proteins that bind to amyloid beta protein. One contemplated antibody is the antibody disclosed in the above publication having a heavy chain variable region comprising SEQ ID NO:8 and a light chain variable region having SEQ ID NO:6.

[0121] The drug reservoirs of the cassettes may also be therapeutically loaded or pre-loaded with c-Kit-specific antibodies, peptibodies, related proteins, and the like, including, but not limited to, those described in U.S. Patent Application Publication No. 2007 / 0253951, which is incorporated herein by reference in its entirety, with particular reference in part to proteins that bind c-Kit and / or other stem cell factor receptors.

[0122] The drug reservoirs of the cassette may also be therapeutically loaded or pre-loaded with OX40L-specific antibodies, peptibodies, related proteins, and the like, including, but not limited to, those described in U.S. Patent Application Publication No. 11 / 068,289, which is incorporated herein by reference in its entirety, with particular reference in part to proteins that bind to OX40L and / or other ligands of the OX40L receptor.

[0123] The cassette drug reservoir may also contain Activase® (alteplase, tPA), Aranesp® (darbepoetin alfa), Epogen® (epoetin alfa, or erythropoietin), Avonex® (interferon beta-1a), Bexxar® (tositumomab, an anti-CD22 monoclonal antibody), Betaseron® (interferon-beta), Campath® (alemtuzumab, an anti-CD52 monoclonal antibody), Dynepo® (epoetin delta), Velcade® (bortezomib), MLN0002 (anti-alpha4beta7 mAb), MLN1202 (anti-CCR2 chemokine receptor mAb), Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Eprex® (epoetin alfa), Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1), Genotropin® (somatropin, human growth hormone), Herceptin® (trastuzumab, anti-HER2 / neu(erbB2) receptor mAb), Humatopeptide® (anti-HER2 / neu(erbB2) receptor mAb), Rope® (somatropin, human growth hormone), Humira® (adalimumab), insulin in solution, Infergen® (interferon Alfacon-1), Natrecor® (nesiritide, recombinant human B-type natriuretic peptide (hBNP), Kineret® (anakinra), Leukine® (sargamostim, rhuGM-CSF), LymphoCide® (epratuzumab, anti-CD22 mAb), Lymphostat B® (belimumab, anti-BlySmAb), Metalyse® (tenecteplase, t-PA analog), Mircera® (methoxypolyethylene glycol-epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP870), Soliris™ (eculizumab), pexelizumab (anti-complement C5), MEDI-524 (Numax®), Lucentis® (ranibizumab), 17-1A (edrecolomab, Panorex®), Trabio® (lerdelimumab), TheraCim hR3 (nimotuzumab), Omnitarg (pertuzumab, 2C4), Osidem® (IDM-1), OvaRex® (B43.13), Nuvion® (vigilizumab), cantuzumab mertansine (huC242-DM1), NeoRecormon® (epoetin beta), Neumega® (oprelvekin, human interleukin-11), Neulasta® (pegylated filgastrim, pegG-CSF, peghu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-Met-G-CSF), Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody), Procrit® (epoetin alfa), Remicade® (infliximab, anti-TNFα monoclonal antibody), Reopro® (abciximab, anti-GP 1Ib / Ilia receptor monoclonal antibody), Actemra® (anti-IL6 receptor mAb), Avastin® (bevacizumab), HuMax-CD4 (zanolimumab), Rituxan® (rituximab, anti-CD20mAb), Tarceva® (erlotinib), Roferon-A® (interferon alpha-2a), Simulect® (basiliximab), Prexige® (lumiracoxib), Synagis® (palivizumab), 146B7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507), Tysabri® (natalizumab, anti-alpha4 integrin mAb), Valortim® (MDX-1303, anti-anthrax protective antigen mAb), ABthrax™, Vectibix® (panitumumab), Xolair® (omalizumab), ETI211 (anti-MRSA mAb), IL-1 Trap (the Fc portion of human IgG1 and the extracellular domains of both IL-1 receptor components (type I receptor and receptor accessory protein)), VEGF Trap (the Ig domain of VEGFR1 fused to IgG1 Fc), Zenapax® (daclizumab), Zenapax® (daclizumab, anti-IL-2Rα mAb), Zevalin® (ibritumomab tiuxetan), Zetia® (ezetimibe), atacicept (TACI-Ig), anti-CD80 monoclonal antibody (mAb) (galiximab), anti-CD23 mAb (lumiliximab), BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist), CNTO148 (golimumab, anti-TNFα mAb), HGS-ETR1 (mapatuzumab, human anti-TRAIL receptor-1 mAb), HuMax-CD20 (ocrelizumab, anti-CD20 human mAb), HuMax-EGFR (zalutumumab), M200 (volociximab, anti-α5β1 integrin mAb), MDX-010 (ipilimumab, anti-CTLA-4 mAb, and VEGFR-1 (IMC-18F1), anti-BR3 mAb, anti-C. difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388), anti-CD22 dsFv-PE38 conjugate (CAT-3888 and CAT-8015), anti-CD25 mAb (HuMax-TAC), anti-CD3 mAb (NI-0401), adecatumumab, anti-CD30 mAb (MDX-060), MDX-1333 (anti-IFNAR), anti-CD38mAb (HuMax CD38), anti-CD40L mAb, anti-Cripto mAb, anti-CTGF idiopathic pulmonary fibrosis stage 1 fibrogen (FG-3019), anti-CTLA4 mAb, anti-eotactic-signal 1 mAb (CAT-213), anti-FGF8 mAb, anti-GD2 mAb, anti-GM2 mAb, anti-GDF-8 receptor 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 (CNTO1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-Ig receptor mAb (MDX-018, CNTO95), anti-IP10 ulcerative colitis mAb (MDX-1100), anti-LLY antibody, BMS-66513, anti-Mannos receptor / hCGβ mAb (MDX-1307), anti-Methotrexone dsFv-PE38 complex (CAT-5001), anti-PD1 mAb (MDX-1106 (ONO-4538)), anti-PDGFRα antibody (IMC-3G3), anti-TGFβ mAb (GC-1008), anti-TRAIL receptor-2 ヒトmAb (HGS-ETR2), anti-TWEAK mAb, anti-VEGFR / Flt-1 mAb, anti-ZP3Other exemplary proteins may be loaded or preloaded for therapy, including, but not limited to, sclerostin antibodies such as, but not limited to, mAb (HuMax-ZP3), NVS Antibody No. 1, and NVS Antibody No. 2, romosozumab, brosozumab, or BPS804 (Novartis). Therapeutic agents such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, romosozumab, NPLATE, PROLIA, VECTIBIX, or XGEVA may also be included. Additionally, the AI ​​can include a monoclonal antibody (IgG) that binds to human proprotein convertase subtilisin / kexin type 9 (PCSK9), and is described, for example, in U.S. Pat. No. 8,030,547, U.S. Patent Application No. 13 / 469,032, WO 2008 / 057457, WO 2008 / 057458, WO 2008 / 057459, WO 2008 / 063382, WO 2008 / 133647, WO 2009 / 100297, WO 2009 / 100318, WO 2011 / 037791, WO 2011 / 053759, WO 2012 / 053759, WO 2013 / 053759, WO 2014 / 053759, WO 2015 / 053759, WO 2016 / 053759, WO 2017 / 053759, WO 2018 / 053759, WO 2019 ... WO 2011 / 053783, WO 2008 / 125623, WO 2011 / 072263, WO 2009 / 055783, WO 2012 / 0544438, WO 2010 / 029513, WO 2011 / 111007, WO 2010 / 077854, WO 2012 / 088313, WO 2012 / 101251, WO 2012 / 101252, WO 2012 / 101253, WO 2012 / 109530, and WO 2001 / 031007.

[0124] The drug reservoir of the cassette may also be therapeutically loaded or preloaded with antibodies including, but not limited to, those that recognize any one or combination of the above proteins and / or proteins including, but not limited to, the following antigens: CD2, CD3, CD4, CD8, CD11a, CD14, CD18, CD20, CD22, CD23, CD25, CD33, CD40, CD44, CD52, CD80 (B7.1), CD86 (B7.2), CD147, IL-1α, IL-1β, IL-2, IL-3, IL-7, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-19, IL-21, IL-18, IL-19, IL-22, IL-19, IL-23, IL-19, IL-19, IL-24, IL-19, IL-19, IL-19, IL-25, IL-19, IL-19, IL-26, IL-19, IL-19, IL-27, IL-19, IL-19, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33, IL-34, IL-35, IL-19, IL-19, IL-19, IL-19, IL-19, IL-19, IL-19, IL-21, IL-19, IL-19, IL-19, IL-19, IL-1 8, IL-10, IL-2 receptor, IL-4 receptor, IL-6 receptor, IL-13 receptor, IL-18 receptor subunit, FGL2, PDGF-β and its analogs (see U.S. Pat. Nos. 5,272,064 and 5,149,792), VEGF, TGF, TGF-β2, TGF-β1, EGF receptor (see U.S. Pat. No. 6,235,883), VEGF receptor, hepatocyte growth factor, osteoprotegerin ligand, IFN-gamma, B lymphocyte stimulating factor (also known as BlyS, BAFF, THANK, TALL-1, and zTNF4; Do and Chen-Kiang (2002), Cytokine Growth Factor Rev.13(1):19-25), C5 complement, IgE, tumor antigen CA125, tumor antigen MUC1, PEM antigen, LCG (a gene product expressed in association with lung cancer), HER-2, tumor-associated glycoprotein TAG-72, SK-1 antigen, tumor-associated epitopes present at elevated levels in the serum of patients with colon and / or pancreatic cancer, cancer-associated epitopes or proteins expressed in breast, colon, squamous cell, prostate, pancreatic, lung and / or kidney cancer cells, and / or melanoma, glioma, or neuroblastoma cells, the necrotic core of tumors, integrin α4β7, integrin VLA-4, B2 integrin, TRAIL receptors 1, 2, 3, and 4, RANK, RANK ligand, TNF-α, the adhesion molecule VAP-1, epithelial cell adhesion molecule (EpCAM), intercellular adhesion molecule-3 (ICAM-3), leukointegrin adhesins adhesin), platelet glycoprotein gpIIb / IIIa, cardiac myosin heavy chain, parathyroid hormone, rNAPc2 (factor VIIa-tissue factor inhibitor), MHCI, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), tumor necrosis factor (TNF), CTLA-4 (cytotoxic T lymphocyte-associated antigen), Fc-gamma-1 receptor, HLA-DR10 beta, HLA-DR antigen, L-selectin, respiratory syncytial virus, human immunodeficiency virus (HIV), hepatitis B virus (HBV), Streptococcus mutans, and Staphylococcus aureus.

[0125] Additional examples of known antibodies that may be housed in the drug reservoirs of the cassette include adalimumab, bevacizumab, infliximab, abciximab, alemtuzumab, bapineuzumab, basiliximab, belimumab, briakinumab, canakinumab, certolizumab pegol, cetuximab, conatumumab, denosumab, eculizumab, gemtuzumab ozogamicin, golimumab, ibritumomab tiuxetan, and labetuzumab. These may include, but are not limited to, rifabutinib, mapatuzumab, matuzumab, mepolizumab, motavizumab, muromonab-CD3, natalizumab, nimotuzumab, ofatumumab, omalizumab, oregovomab, palivizumab, panitumumab, pemtumomab, pertuzumab, ranibizumab, rituximab, lovelizumab, tocilizumab, tositumomab, trastuzumab, ustekinumab, zalutumumab, and zanolimumab.

[0126] Although the autoinjector system, cassette, and autoinjector have been described in terms of exemplary embodiments, they are not limited to the exemplary embodiments. Rather, the appended claims should be construed broadly to include other variations and embodiments thereof that may be made by those skilled in the art without departing from the scope of the autoinjector system, cassette, and autoinjector, and equivalents of their elements.

Claims

1. a reservoir configured to contain a drug, the reservoir having a first end and a second end; a plunger disposed within the reservoir at the first end thereof, the plunger being slidably movable within the reservoir; a plunger rod configured to engage the plunger; a motor operatively coupled to the plunger rod and configured to drive the plunger rod to slide the plunger from the first end of the reservoir to the second end of the reservoir; an encoder operatively coupled to the motor; a controller, (i) receiving a signal from the encoder; (ii) determining whether the plunger has stopped moving within the reservoir based on one sample of the signal count, the controller taking samples of the signal count at set intervals by determining a current count of the received signal, the count of the signal indicating an amount of movement of the plunger rod; (iii) if the plunger has stopped moving, determining whether the movement of the plunger in the most recent predetermined number n of samples of the signal is less than a threshold (m), or if the plunger has not stopped moving, the controller takes another sample of the count of the signal; (iv) if the plunger movement in the most recent n samples is less than m, comparing the signal count to an expected end count corresponding to the plunger being driven to the second end of the reservoir to determine whether the full dose of the drug has been administered, or if the plunger movement in the most recent n samples is greater than m, the controller takes another sample of the signal count; (v) stopping operation of the motor in response to determining that the movement in the most recent n samples is less than m and that the signal count is near an expected end count. a controller configured to:

1. A drug delivery device comprising:

2. 10. The drug delivery device of claim 1, wherein the encoder includes a disk having one or more identifiable portions and an optical sensor configured to detect the identifiable portions and transmit a signal in response to the detection.

3. 2. The drug delivery device of claim 1, wherein the controller configured to determine whether the plunger has stopped moving comprises the controller determining whether the signal indicates that the plunger has moved within the most recent n samples.

4. the controller modifying n in response to determining that the signal count is less than the expected end count; or (i) determining that the plunger is stalled in response to determining that the count is less than the expected end count; and (ii) ceasing operation of the motor in response to determining that the plunger has stalled.

5. 2. The drug delivery device of claim 1, wherein the controller is configured to determine that the plunger is stalled in response to determining that the current count is less than the expected end count.

6. 6. The drug delivery device of claim 1, further comprising a needle and a needle insertion mechanism, wherein the controller is configured to retract the needle in response to determining that the plunger has stopped moving for the predetermined amount of time.

7. A drug delivery device according to any one of claims 1 to 6, comprising an autoinjector.

8. The drug delivery device of any one of claims 1 to 7, further comprising a drug in the reservoir, the drug comprising etanercept.

9. 1. A method of operating a drug delivery device, comprising: receiving, in a controller, a signal from an encoder coupled to a motor of the drug delivery device, the motor operatively coupled to a plunger rod configured to engage and drive a plunger in a reservoir; determining by the controller whether the plunger has stopped moving within the reservoir based on one sample of the signal count received from the encoder coupled to the motor of the drug delivery device, the motor being operatively coupled to the plunger rod configured to engage and drive the plunger within the reservoir, the controller taking samples of the signal count at set intervals by determining a current count of the received signal, the count of the signal indicating an amount of movement of the plunger rod; if the plunger has stopped moving, the controller determines whether the movement of the plunger in the most recent predetermined number n of samples of the signal is less than a threshold (m), or if the plunger has not stopped moving, the controller takes another sample of the count of the signal; if the plunger movement in the most recent n samples is less than m, the controller compares the signal count to an expected end count corresponding to the plunger being driven to the second end of the reservoir to determine whether the full dose of the drug has been administered, or if the plunger movement in the most recent n samples is greater than m, the controller takes another sample of the signal count; the controller ceasing operation of the motor in response to determining that the movement in the most recent n samples is less than m and that the signal count is near an expected end count; A method comprising:

10. disposing an optical sensor to detect a discernible portion of the disc of said encoder (346); configuring the optical sensor to transmit a signal in response to the detection; The method of claim 9 further comprising:

11. 10. The method of claim 9, further comprising programming the controller to determine whether the signal indicates that the plunger has moved within the most recent n samples.

12. modifying n in response to determining that the signal count is less than the expected end count; or (i) in response to determining that the count is less than the expected end count, determining that the plunger is stalled before being driven into the second end of the reservoir; and (ii) ceasing operation of the motor in response to determining that the plunger has stalled; The method of claim 9 , further comprising programming the controller to perform at least one of the following:

13. 10. The method of claim 9, further comprising, in response to determining that the current count is less than the expected end count, determining that the plunger is stalled before being driven into the second end of the reservoir.

14. 14. The method of any one of claims 9 to 13, further comprising programming the controller to operate a needle insertion mechanism to retract a needle of the drug delivery device in response to determining that the plunger has stopped moving for the predetermined amount of time.

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