Systems and methods for remotely processing data collected by a drug delivery device

Abstract

To provide systems and methods for processing sensor data collected by a drug delivery device with an external computing device.SOLUTION: A drug delivery device 302 includes a reservoir 312 and a delivery cannula having a proximal end 316 in fluid communication with the reservoir and a distal end 318 to be received within a patient. The drug delivery device further includes one or more sensors 360, 362, 364, 365 configured to generate sensor data representative of a condition and / or operational state of the drug delivery device, and a communication module 352 configured to transmit information to external computing devices 304, 306. The external computing devices may process the information received from the drug delivery device according to information stored in memories 422, 426 of the external computing devices to determine a condition or an operational state of the drug delivery device and generate instructional or informational prompts to be displayed to a user or patient.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS The benefit of priority is claimed from U.S. Provisional Patent Application No. 62 / 007,007, filed June 3, 2014, the entire contents of which are expressly incorporated herein by reference.

[0002] The present disclosure generally relates to systems and methods for use with drug delivery devices that process sensor data collected by the drug delivery devices to determine their condition and / or operating state and improve their usability for patients and other users. [Background technology]

[0003] Drugs can be administered through the use of drug delivery devices, such as autoinjectors or on-body injectors or syringes. These devices can replace older delivery systems that use syringe / vial combinations containing drugs or medications, or pre-filled syringes. Autoinjectors and on-body injectors can be used to automate the injection and delivery or administration process, thereby simplifying the process for certain patient populations or subgroups for whom, whether due to physiological or psychological disorders, the use of syringe / vial combinations or pre-filled syringe systems would be disadvantageous.

[0004] Even when using a drug delivery device such as an autoinjector, patients may experience difficulties during initial use of the drug delivery device after being prescribed a medication to be delivered or administered using the drug delivery device. For example, a user may be unsure whether to delay the injection after the drug delivery device is removed from refrigeration, such as in a refrigerator, and if so, how long to delay the injection. Furthermore, a user may be unsure whether the medication in the drug delivery device is the medication prescribed for them. Furthermore, a user may be unsure whether the medication has expired. Furthermore, a user may be unsure whether actions and their sequence are necessary to properly operate the drug delivery device.

[0005] Additionally, the condition and use of drug delivery devices is important to other parties, such as drug device manufacturers, pharmacies, healthcare providers, and insurers. For example, information about the status of drug delivery devices along the supply chain may be relevant to whether the drug delivery device is in working order for use with patients when it arrives. Information about the location of drug delivery devices along the supply chain may be relevant to manufacturers and pharmacies to ensure pharmacies have sufficient inventory to deliver to users. The adherence information mentioned above may be important to healthcare providers and insurers, as well as to patients, because adherence to a treatment regimen can directly impact the success of treatment.

[0006] To address some of the aforementioned difficulties, it is possible to provide a drug delivery device with one or more sensors to monitor the condition and use of the drug delivery device. However, analyzing, storing, communicating, and otherwise processing the sensor data collected by the one or more sensors may require the use of relatively expensive computer hardware, including a microprocessor, memory, an internet-accessible communication module, etc. Because the drug delivery device may be a disposable, single-use device, or may otherwise have a limited lifespan, it may be economically undesirable to incorporate such expensive computer hardware into the drug delivery device itself.

[0007] As described in further detail below, the present disclosure describes various systems and methods that embody advantageous alternatives to existing drug delivery systems and methods and that may address one or more of the difficulties or needs referenced above. Summary of the Invention

[0008] According to an aspect of the present disclosure, a system includes a drug delivery device and an external computing device. The drug delivery device may include a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for reception within a patient, one or more sensors configured to generate sensor data representative of at least one condition or operating state of the drug delivery device, and a first communications module coupled to the one or more sensors and configured to transmit the sensor data. The external computing device may include a second communications module configured to receive the sensor data from the first communications module, a processor coupled to the second communications module, and a memory coupled to the processor. The memory may store non-transitory computer-readable instructions that, when executed by the processor, cause the processor to determine at least one condition or operating state of the drug delivery device based on the sensor data.

[0009] According to another aspect of the present disclosure, a system includes a drug delivery device and an external computing device. The drug delivery device may include a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for reception within a patient, one or more sensors, a first communications module, and a first controller coupled to the one or more sensors and the first communications module. The first controller may be configured to determine at least one condition or operating state of the drug delivery device using the one or more sensors and control the first communications module to send a communication representing the condition or operating state of the drug delivery device. The external computing device may include the first communications module, a display device, a memory, and a second communications module configured to receive a communication from a second controller coupled to the display device, the memory, and the second communications module. The second controller may be configured to control the display device to display at least one of an instructional prompt or an informational prompt based on the communication from the first communications module.

[0010] According to yet another aspect of the present disclosure, a method of using a system including a drug delivery device and an external computing device is provided. The drug delivery device may include a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end received within a patient, one or more sensors configured to generate sensor data, and a first communications module. The external computing device may include a memory and a second communications module. The method may include (a) collecting sensor data using the drug delivery device, (b) transmitting the sensor data from the drug delivery device using the first communications module, (c) receiving the sensor data from the drug delivery device at the external computing device using the second communications module, and (d) determining, using the external computing device, at least one condition or operating state of the drug delivery device based on the sensor data.

[0011] According to yet another aspect of the present disclosure, a method of using a system including a drug delivery device and an external computing device is provided. The drug delivery device may include a reservoir and a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end received within a patient. The external computing device may include a memory. The method may include (a) determining at least one condition or operating state of the drug delivery device, (b) transmitting a communication from the drug delivery device representing the condition or operating state, (c) receiving the communication from the drug delivery device at the external computing device, and (d) processing the communication received from the drug delivery device according to information stored in the memory of the external computing device.

[0012] It is believed that the present disclosure will be more fully understood from the following description taken in conjunction with the accompanying drawings. Some of the figures may be simplified by the omission of selected elements for the purpose of more clearly showing other elements. Such omission of elements in some figures does not necessarily indicate the presence or absence of the particular element in any of the example embodiments, except as may be explicitly depicted in the corresponding written description. None of the drawings are necessarily to scale. [Brief explanation of the drawings]

[0013] [Figure 1] 1 is a schematic diagram of a drug delivery system in communication with one or more computing devices and one or more networks, according to an embodiment of the present disclosure. [Figure 2] FIG. 10 is a block diagram of a method of operating a drug delivery system according to another embodiment of the present disclosure. [Figure 3] 1 is a schematic diagram of a system including a drug delivery device, a local computing device, and a remote computing device interconnected by a communication link and a network. [Figure 4] 4 is a schematic diagram of a drug delivery device with an attachable control device that may be used in the interactive drug delivery system of FIG. 3. [Figure 5] 4 is a flow chart illustrating the operation of the drug delivery device according to FIG. 3. [Figure 6] 4 is a flow chart illustrating the operation of the interactive drug delivery system according to FIG. 3. [Figure 7] 10 is a simulated screenshot of a display screen of a local computing device according to a first state after removal of a drug delivery device from refrigeration. [Figure 8] 10 is a simulated screenshot of a display screen of a local computing device according to a second state before application of the apparatus. [Figure 9] 10 is a simulated screenshot of a display screen of a local computing device according to a third state after device application but before injection. [Figure 10] 10 is a simulated screenshot of a display screen of a local computing device according to a fourth state after injection but before completion. [Figure 11] 10 is a simulated screenshot of a display screen of a local computing device according to a fifth state after completion. [Figure 12] 4 is a flow chart illustrating the operation of a controller associated with the drug delivery device of the system of FIG. 3. [Figure 13] 4 is a flowchart illustrating the operation of a local computing device of the system of FIG. 3. [Figure 14] FIG. 10 is a flowchart illustrating the operation of a local computing device according to another embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0014] The present disclosure is directed to systems including drug delivery devices and methods for using drug delivery systems. Specifically, the systems and methods involve determining one or more conditions, which may be determined using one or more sensors in combination with one or more controllers. The sensors may rely on mechanical, electrical, or chemical sensing methods, and the controllers may be mechanical, electrical, or electromechanical. By way of example and not limitation, the conditions may relate to the operation of the drug delivery device or a condition of the drug delivery device. The systems and methods may use the condition determination to control the operation of the drug delivery device and / or communicate the condition determination to another device, such as a third-party server, which may collect, process, and / or further disseminate the condition determination received from a system including the drug delivery device, one or more sensors, and one or more controllers. Additionally or alternatively, the systems and methods may communicate the condition determination to a local computing device, such as a mobile computing device (e.g., a mobile phone).

[0015] A drug delivery system according to the present disclosure may include a drug delivery device having a reservoir (which may also be referred to as a primary container, e.g., a syringe, vial, or cartridge). The reservoir may contain a drug, which may also be referred to as a medicine or agent. The drug may be, but is not limited to, various biologics, such as peptides, peptibodies, or antibodies. The drug may be in fluid or liquid form, although the present disclosure is not limited to a particular state (e.g., it does not intend to distinguish between solutions, gels, or lyophilized formulations). The drug delivery device also includes a delivery cannula having a first end connected to or connectable in fluid communication with the reservoir and a second end inserted into the patient. As used herein, the term "delivery cannula" or "cannula" is defined herein to mean a tube that can be inserted into the body for delivery of a fluid. The cannula may include, by way of example and not limitation, a rigid or semi-rigid needle or a blunt cannula, or may be flexible. The cannula may be integrated with other elements of the drug delivery device, or the cannula may be separate from other elements of the drug delivery device until immediately prior to use. According to certain embodiments, the drug delivery device may further include an inserter for introducing the second end into the patient, although this is not required according to each embodiment of the present disclosure. The inserter may or may not be retracted within the device, thereby leaving the cannula within the patient.

[0016] In view of the foregoing description of drug delivery devices, the devices may be considered autoinjectors or on-body injectors, or injectors (reference to an injector is intended to also include reference to an injector to the extent a distinction is suggested). Autoinjectors may be single-use devices that administer a single dose during a single application of the device to the user's skin, but autoinjectors are not limited to single-use devices; they may also be multi-use devices. On-body injectors may be multi-use devices that administer multiple doses during one or more applications of the device to the user's skin, but on-body devices may also be used as single-use devices. Either autoinjectors or on-body injectors may have assemblies or subassemblies that are reusable, meaning that the assembly can be used and reused, for example, by refilling the reservoir, removing an empty reservoir and replacing it with a filled reservoir, or by changing the cannula.

[0017] As noted above, a system or method according to the present disclosure determines one or more conditions associated with a drug delivery device.

[0018] For example, the system or method may determine whether the drug delivery device is in one or more operational states (i.e., states associated with the operation of the drug delivery device to deliver a drug to a patient). A non-exhaustive list of general operational states may include: (i) a packaged / ready for distribution operational state; (ii) a packaged / distributed operational state; (iii) an unpackaged / ready for administration operational state; (iv) a sterility barrier removed operational state; (v) a device applied operational state; (vi) a cannula injected (or inserted) operational state; (vii) a drug delivery initiated operational state; (viii) a drug delivery completed operational state; and (ix) a device removed operational state. The system or method may determine specific operational states within each of the general operational states; for example, the system or method may determine whether the plunger has been moved from a first end of the bore (defining the drug reservoir) to a second end of the bore to determine whether the drug delivery device is in a “drug delivery completed” state.

[0019] Additionally, the system or method may determine whether the drug delivery device is in one or more condition states (i.e., states related to the condition of the drug delivery device that are not necessarily related to the operation of the drug delivery device to deliver a drug to a patient). A non-exhaustive list of condition states may include: (i) product age (e.g., relative to date of manufacture or expiration date), (ii) sterilization / contamination, (iii) temperature, (iv) temperature history, and (iv) orientation. The determination of a condition state may be considered as part of the determination of an operational state; for example, the determination of a temperature state may be considered as part of a "ready to administer" state. Alternatively, the operational state and the condition state may be determined separately.

[0020] These states may be determined through the use of one or more sensors. The sensor may be specific to the condition state being determined; for example, a thermocouple disposed adjacent to the reservoir may be used to determine the temperature state of the drug delivery device. The sensor may also be specific to the operating state being determined; for example, to determine the "sterility barrier removed" operating state, a switch may be coupled to the needle protection device to determine when the needle cap is removed, the switch opening when the needle cap is disposed on the second end of the cannula, and the switch closing when the needle protection device is not disposed on the second end of the cannula. Sensors may be used to determine both the condition state and the operating state; for example, a thermocouple may be used to determine the temperature condition state of the device (or more specifically, the drug) and / or a thermocouple may be used to determine the "ready to administer" operating state.

[0021] The system or method may use the determined condition to control operation of the drug delivery device. For example, the system may include a controller coupled to the sensor, and may be coupled to one or more of the above-mentioned drug delivery device assemblies or subassemblies, or to one or more additional assemblies or subassemblies of the drug delivery device. The controller may be structurally adapted, or (if electrical or electromechanical) programmed, to activate or inhibit these assemblies or subassemblies according to the determined condition. For example, the drug delivery device may include a lockout that limits or completely inhibits operation of the infusion device, and the controller may activate the lockout in a reversible manner when the temperature condition of the drug delivery device (and particularly the drug in the reservoir) is below a threshold condition or excessively above a threshold condition.

[0022] The system or method may communicate the determined status(ies) to another device or system, and this communication may be performed in conjunction with using the determined status(ies) to control the operation of the drug delivery device. For example, the system or method may communicate the determined status(ies) to a networked device using a communication link. In this sense, a networked device is intended to include any device that communicates with at least one other device over a communication link, and may include communication with devices such as a mobile device (e.g., a mobile phone or mobile computing device) using a Bluetooth® connection or a computing device using a Wi-Fi connection. The networked device may communicate the determined status to another computing device remote from the drug delivery system via a network including a networked device such as a server. According to certain embodiments of the present disclosure, the system communicates directly with the network (i.e., the system is a networked device without an intermediate networked device) or directly with a remote computing device such as a server (e.g., using a 3G antenna). The status information communicated over the network may then be used, for example, to determine whether a patient is compliant or whether a class of drug delivery devices is exhibiting a system anomaly. The state information may also be used in other ways.

[0023] The systems and methods may also include information related to the identification of a drug, a drug delivery device, or a user, and / or control of a drug delivery device pursuant to communication of this identification information. Identification information associated with a drug may include drug name, drug concentration, dosage information, lot or serial number, and manufacturing and / or expiration date. Identification information associated with a drug delivery device may include device type (e.g., autoinjector, on-body injector), lot or serial number, and manufacturing date. Identification information associated with a user may include patient name, demographic information, and patient subgroup information. This information may be referred to as "static" information, as opposed to the status information discussed above.

[0024] With regard to the communication of information, and particularly with regard to the identifying information discussed immediately above, it is understood that not all information will be useful, desirable, or even accessible to all different parties, for reasons of convenience, patient privacy, or data security concerns.

[0025] FIG. 1 illustrates a drug delivery system 100 according to an embodiment of the present disclosure. The drug delivery system 100 may be associated with a patient 102 who may use the drug delivery system 100 to inject a drug as part of a treatment regimen. The drug delivery system 100 may communicate with a computing device (e.g., a server) 104 via one or more intermediate computing devices and / or one or more networks. The server 104 may then communicate with the drug delivery system 100, the patient 102, and one or more computing devices (along with their associated parties) via one or more intermediate computing devices and / or one or more networks. As also shown in FIG. 1, the server 104 may communicate directly with the drug delivery system 100 using, for example, a 3G antenna.

[0026] For example, the drug delivery system 100 is shown communicating with a mobile computing device 110 (e.g., a smartphone) via a first communication link 112 and with a computing device (e.g., a personal computer or dedicated hub) 114 via a second communication link 116. Both links 112, 116 may operate according to a short-range communication protocol, such as Bluetooth. The mobile computing device 110 may communicate with a cellular network 118 via a communication link 120, while the other computing device 114 may communicate with a hard-wired network (e.g., a local area network or a wide area network) 122 via a communication link 124. These networks 118, 122 may also communicate with the server 104.

[0027] The networks 118, 122 may facilitate communication between the server 104 and one or more parties associated with the patient 102, such as the patient's caregiver 130, support person 132, and healthcare provider 134, via their mobile computing devices (e.g., smartphones). The server 104 may also be in communication with one or more computing devices (e.g., servers) associated with one or more additional parties associated with the patient 102. For example, a health management system server 140, a payment server 142, a pharmacy server 144, a logistics provider server 146, and a government agency server 148 are shown in communication with the server 104 via the network 122. It will be understood that the networks 118, 122 may also be in communication with each other.

[0028] 2, possible methods of operating one or more computing devices in communication with a drug delivery system will now be discussed in terms of method 200. It will be understood that method 200 may be performed by a single computing device, such as server 104 shown in FIG. 1. Alternatively, the operations discussed with respect to FIG. 2 may be performed by multiple computing devices in combination with server 104, such as mobile device 110 or computing device 114.

[0029] Method 200 begins with a determination as to whether a report has been received from the drug delivery system at block 202. If a report has not been received, method 200 waits at block 202. If a report has been received as determined at block 202, method 200 proceeds to block 204.

[0030] In block 204, the reports received from the drug delivery system are used to update one or more records. In doing so, one or more computing devices adapted or programmed to perform method 200 may retrieve one or more records from storage in one or more memory storage devices, write the information received from the drug delivery device to the one or more records, and then store the one or more records in one or more memory storage devices. The one or more memory storage devices may be part of the one or more computing devices, may be separate from the one or more computing devices, or may include one or more of a memory storage device that is part of one or more computing devices and one or more memory storage devices that are separate from the one or more computing devices (i.e., the records are stored within the computing devices and in backup storage that is separate from the computing devices, possibly remote).

[0031] As mentioned above, reports may be used to update one or more records. For example, there may be one record per individual patient stored in a patient record database. The patient record may be used, for example, to track an individual patient's (e.g., patient 102) compliance with their regime(s). There may also be records related to the drug delivery systems used by individual patients stored in a drug delivery system database. The drug delivery system records may be used to store information about the drug delivery systems throughout their use. The drug delivery system records may be accessed by drug delivery system manufacturers or drug suppliers for quality control purposes (e.g., to monitor individual instances of drug delivery systems for failures or malfunctions caused by the drug delivery system, or to track the environmental condition history of one or more drug delivery systems for patterns that may assist in determining improvements in the design, packaging, shipping, or handling of the drug delivery systems). There may also be records related to drugs used in drug delivery systems stored in a drug database. This record may be used for quality control purposes in a manner similar to the drug delivery system records.

[0032] In addition to updating the record at block 204, a computing device adapted or programmed to perform method 200 may also be adapted or programmed to perform one or more actions based on information in the report received from the drug delivery system. For example, the computing device may be adapted or programmed to perform an action at block 206. This action may require not only the information received in the report and / or information previously stored in the record updated at block 204, but may also require additional information, such as from other patient records, drug system delivery records, and / or drug records. In this case, a determination may be made at block 208 that these other records need to be accessed, and a determination may be made at block 210 that the information has been obtained (e.g., by retrieving these other records from the patient, drug delivery system, and drug databases and retrieving information from these records once obtained). The action may then be performed at block 222.

[0033] As one example, one or more computing devices adapted or programmed to execute method 200 may be adapted or programmed to use information received in the report to create a patient adherence history, which tracks instance use of a drug delivery system by an individual patient for that patient's treatment regime to determine how well the patient has complied with that treatment regime, and this adherence history may be stored in the patient record. Additionally, the one or more computing devices may determine whether a pharmacy should be contacted to order the shipment of additional drug delivery devices for the individual patient, and may generate a communication to be sent to the pharmacy to order the shipment of additional drug delivery systems. Additionally, the one or more computing devices may determine whether a reminder should be sent to the patient via the mobile device 110, for example, to improve or assist the individual patient's adherence to the treatment regime, in which case the one or more computing devices may generate a communication to be sent to the patient or device user. Additionally, the one or more computing devices may determine that the operation of the drug delivery device should be modified, for example, due to a condition state received from the drug delivery device. For example, the one or more computing devices may determine that the drug delivery system should be locked to prevent its use, for example, due to the temperature history of the drug within the drug delivery system. In this case, the one or more computing devices may generate a communication in the form of, for example, a signal that is sent to the drug delivery system to lock a drug delivery device that is part of the drug delivery system. Other possible actions are discussed in detail below, but this discussion is for illustrative purposes only and is not intended to be limiting.

[0034] Depending on the actions taken in block 212, or even if it is determined in block 206 that no actions need to be taken, method 200 may proceed to blocks 214, 216, and 218, where a determination is made as to whether the computing device should contact other parties (block 214), interact with the patient (or user, if not the same as the patient) (block 216), or control a drug delivery device that is part of the drug delivery system (block 218). For example, as discussed above, the actions taken in block 212 may involve communication or generation of a signal that is sent to a third party, such as a pharmacy, the patient, or the drug delivery device. In such cases, one or more computing devices may perform the actions of blocks 220, 222, and 224 as determined by the determinations made in blocks 214, 216, and 218. Alternatively, one or more computing devices may perform the actions of blocks 220, 222, and 224 even if it is determined in block 206 that no actions need to be taken. For example, one or more computing devices may forward certain information to a third party 220 based solely on receipt of the information in a report from the drug delivery device, such that the one or more computing devices do not have to separately determine that an action should be taken with respect to the received information (i.e., the one or more computing devices act as relay stations for such information, and a communication is automatically sent based on the fact that the information was received). Receipt of information from the drug delivery device may also prompt a communication to be sent to the patient / user or control a signal sent to the drug delivery system without a separate determination that such action needs to be taken; a communication or control signal is sent simply because certain information and / or report was received from the drug delivery system.

[0035] Once the determinations at blocks 214, 216, and 218 have been made and the operations of blocks 220, 222, and 224 have been performed, method 200 may return to block 202 to await the next report. It will be appreciated that one or more computing devices may perform the operations of method 200 in parallel for each report received from different instances of the drug delivery system, or may perform the steps sequentially for each report. When performed in parallel, one or more computing devices may determine whether to perform an operation with respect to one report while one or more computing devices are interacting with another patient regarding information contained in the report received from that patient. Furthermore, the one or more computing devices performing method 200 need not be adapted or programmed to perform each of the operations described above in accordance with all embodiments of the one or more computing devices. For example, one of the one or more computing devices may be adapted or programmed to update each patient's record and determine whether patient interaction is necessary, while another of the one or more computing devices may be adapted or programmed to update each drug delivery device's record and determine that a control signal should be sent to the drug delivery device, while another of the one or more computing devices does not update any records but is adapted or programmed to, for example, access the patient record to determine whether a pharmacy needs to be contacted to order additional cases of the drug delivery system for the patient associated with the accessed patient record and generate a communication if ordering additional cases of the system is necessary.

[0036] It will be understood that the above method 200 only touches upon a small portion of the possible status and identification information that may be used to control and / or monitor a drug delivery system and that may be communicated between the drug delivery system and one or more computing devices, and how the information is used by the drug delivery system and one or more computing devices. Additional embodiments are possible in accordance with the present disclosure.

[0037] For example, a non-limiting matrix of status and identity information may include:

[0038] Condition Status Information: temperature Shock or vibration exposure light exposure Color and / or turbidity (associated with the drug) Orientation geographical location temporal information

[0039] Working status information: The device was removed from the packaging The device is removed from refrigeration (e.g., a refrigerator) Device / drug temperature is ready for administration Delivery started The device was applied to the patient The device was applied in the correct position / orientation on the patient The cannula is inserted into the patient and / or into the correct tissue Delivery is in progress Delivery completed An error occurred

[0040] Device Identification Information: Drug name or identity, concentration, and / or amount Confidential and / or anti-counterfeit information Patient prescription / treatment regime

[0041] Patient Identification Information: Point-of-care diagnosis for patients Self-analysis and measurement of progress Fingerprint, PIN, or other secure identification

[0042] This information may be communicated to other computing devices or otherwise used to control the drug delivery system or device being used, and an exemplary list of certain additional uses is included below: The following list and additional comments are intended to augment, not replace, the above discussion and are intended to be non-limiting.

[0043] As one example, the drug delivery system or one or more computing devices may make a determination regarding the authenticity of the drug and its compliance with manufacturing standards. Such a determination may be made by the drug delivery device, for example, at block 208 of method 200. The determination may be made based on the drug delivery device / drug's temperature, shock or vibration exposure, and / or light exposure (or history of one or more of these conditions), as well as the color and / or turbidity of the drug (as determined by optical inspection). This determination may result in control of the drug delivery device to either lock or unlock the device according to the determination made. See blocks 206-412 and 218, 224 of method 200.

[0044] As another example, the drug delivery system or one or more computing devices may make a determination as to whether a drug is appropriate for a patient. See blocks 206-212 of method 200. The determination may be made based on one or more of the device's items of patient identification information listed above, and may also result in control of the drug delivery device to either lock or unlock the device according to the determination made. See blocks 206-212 and 218, 224 of method 200.

[0045] As a further example, the drug delivery system or one or more computing devices may make a determination as to whether the dose was administered correctly. This determination may be made after determining that the drug is appropriate for the patient and / or that the drug is authentic (e.g., not counterfeit) and complies with manufacturing standards. See previous paragraph. The determination of whether the dose was administered correctly may depend on one or more of the types of operational status information listed above. This information may be used to update patient records, determine patient compliance or treatment progress, and may facilitate communication with a pharmacy regarding refills or communication with a payer (e.g., an insurance company) to approve payment for the drug delivery device. See blocks 204-214 of method 200 and servers 142, 144 of FIG. 1 .

[0046] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination regarding the operational status of the drug delivery device and generate instructional messages to guide the user through the actions necessary for proper use of the drug delivery device. The determination may be based on any of the operational status information listed above, and the generated instructions may be directed by the action that needs to be taken immediately after the operational status occurs. Implementing interactive instructions following changes in the status of the drug delivery device may help the user feel confident in administering the drug.

[0047] As a further alternative, the drug delivery system or one or more computing devices may use the information to determine that other people nearby are taking the same medication. See blocks 206-212 of method 200. This determination may be made based on the drug-identifying information and the patient-identifying information in combination with the geographic location information of the drug delivery system. This determination may facilitate communication with the patient regarding a local support network of people who have a similar condition and / or are taking a similar drug or medication (see blocks 216 and 222 of method 200), allowing the patient to receive support and encouragement from such a network. Alternatively, the determination may facilitate communication with a local support network(s) to provide support and encouragement to the patient (see blocks 214 and 220 of method 200). As a further alternative, the determination may facilitate a personalized intervention communication sent to the patient (see again blocks 216 and 222 of method 200).

[0048] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination of whether the patient is not complying with their treatment regimen. See blocks 206-212 of method 200. The determination may be based in part on drug identification information, such as the prescribed treatment regimen, in part on condition status information, such as the passage of time, and in part on operational status information, such as the drug delivery device being removed from the packaging but no additional operational status information being determined, reported, or received during the passage of time since the removal-from-package operational state. Based on this information, the drug delivery system and / or one or more computing devices may determine that an interaction with the patient should be generated, such as a notification being displayed or sent to the patient. See blocks 216 and 222 of method 200. Additionally, the drug delivery system and / or one or more computing devices may determine that a communication should be generated to be displayed or sent to a healthcare provider, caregiver, support person, and / or payer to encourage regime adherence. See blocks 214 and 220 of method 200.

[0049] As a further alternative, the drug delivery system or one or more computing devices may use the information to determine that the patient needs more medication (a refill). See blocks 206-212 of method 200. The determination may be based in part on drug identification information, such as a prescribed treatment regimen, and in part on operational status information, such as whether drug delivery has been completed. Based on this information, the one or more computing devices may generate a communication to be sent to a payer and / or pharmacy to request a prescription refill. See blocks 214, 220 of method 200.

[0050] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination that an injection was not performed correctly. See blocks 206-212 of method 200. The determination may be based, in part, on operational status information compared to information that may be collected and stored regarding conventional general levels of operation. Alternatively or additionally, a comparison between determined, reported, or received operational status information allows a determination that an injection was not performed correctly to be made. For example, determining, reporting, or receiving operational status information indicating drug delivery was completed without operational status information indicating that the device was initiated, that the device was applied to the patient, and / or that the cannula was inserted may indicate that the drug delivery device failed to perform correctly, was incomplete, or performed incorrectly.

[0051] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination that the patient's condition is improving. The determination may be based, in part, on patient-identifying information, such as point-of-care diagnostics (e.g., blood glucose tests or other tests) or self-analysis reports administered to the patient, and in part on determining, reporting, or receiving operational status information, such as that drug delivery has been completed. The determination may rely on overall trends as opposed to individual determinations or reports, as trends in data or reports are typically more indicative of an improvement in the patient's condition than individual case-by-case determinations of severe illness. Thus, information collected regarding the patient and the operational status of the drug delivery system / device may be combined in conjunction with treatment adherence history. This determination may result in personalized interventions being generated, which (e.g., encouraging messages and other forms of positive reinforcement) may increase persistence in treatment.

[0052] As a further alternative, the drug delivery system or one or more computing devices may use the information to determine the time of day (or week, month, etc.) when the patient typically takes their medication. This determination may be based, in part, on patient records in which time information is associated with operational status information related, for example, to the initiation of the drug delivery device or the completion of drug delivery. This determination may also depend on device identification information, such as a prescribed treatment regimen. Based on this determination, the one or more computing devices may generate a reminder communication, for example, sent to the mobile device 110, to notify the patient that it is nearly time to administer the patient's next dose. It may be beneficial to facilitate the patient's decision to take their medication at a specific time of day, week, month, etc., because the usefulness of reminders is enhanced when there is adequate access to and opportunity for use of the drug delivery device. Based on this determination, the one or more computing devices may also generate personalized interventions, such as encouraging messages used as positive reinforcement.

[0053] As a further alternative, the drug delivery system or one or more computing devices may use the information to determine where the patient typically takes their medication. This determination may be based, in part, on patient records in which geographic location information is associated with operational status information related, for example, to the initiation of the drug delivery device or the completion of drug delivery. This determination may also depend on device identification information, such as a prescribed treatment regimen. Based on this determination, the one or more computing devices may generate a reminder communication, for example, sent to the mobile device 110, to notify the patient that it is nearly time to administer their next dose when the patient is at or near a geographic location where the drug delivery system is typically used. It is beneficial to facilitate the patient's decision to take their medication when they are in their usual location to take their medication, because the usefulness of reminders is enhanced when there is reasonable access to and opportunity for use of the drug delivery device. Based on this determination, the one or more computing devices may also generate personalized interventions, such as encouraging messages used as positive reinforcement.

[0054] Of course, determinations regarding the usual time and location of use of the drug delivery device may be combined, and the one or more computing devices may generate a message only when the patient or user is at or near their usual location of use at or around the time they normally use the drug delivery device.

[0055] While the foregoing has focused primarily on decisions made by the drug delivery system and / or one or more computing devices regarding a patient or the patient's use of the drug delivery device, decisions may also be made regarding the drug delivery device or drug before the drug delivery device is made available to the patient or user.

[0056] For example, the drug delivery system or one or more computing devices may use the information to make a determination as to whether delivery of a certain number of doses of a particular drug (e.g., an instance of a drug delivery device containing a particular drug) has arrived, for example, at a particular logistics or pharmacy location. This determination may be made based in part on the geographic location information and in part on the drug identification information. Based on this information, the one or more computing devices may generate a communication that is sent to a pharmacy or logistics provider (e.g., via a pharmacy or logistics provider server) to inform the pharmacy or logistics provider of the delivery of the drug delivery device. A pharmacy or logistics provider may use such smart drug delivery devices to simplify, for example, their logistics and inventory systems.

[0057] Along similar lines, the drug delivery system or one or more computing devices may use the information to make a determination that one or more of the drug delivery devices were damaged en route to a particular logistics or pharmacy location. This determination may be made based in part on geographic location information and in part on drug identification information. The determination may also be made in part on condition state information, such as temperature, shock / vibration exposure, light exposure, or drug color and / or turbidity (i.e., history established in the drug delivery device record or drug record), whether determined at a particular time or over a period of time. The determination may also or instead be based in part on product age related to the product's manufacturing date or expiration date. The determination may also or instead be based in part on operational state information, such as removal of a sterility barrier from the second end of the cannula of the drug delivery device. Based on this information, the one or more computing devices may generate a communication to be sent to a pharmacy or distributor (e.g., via a pharmacy or distributor server) to inform the pharmacy or distributor that the drug delivery device has been damaged or expired. The pharmacy or distributor may use such a smart drug delivery device to, for example, facilitate replacement of damaged or expired product at the distributor or pharmacy, preventing delays in patient treatment.

[0058] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination that the product is as described and not counterfeit. Such a determination may be based on drug identification information, such as the product's name, strength, and amount, as well as security and anti-counterfeiting measures associated with the drug. The determination made by the one or more computing devices may result in the generation of a communication, which may be sent to a government agency (e.g., customs / immigration officials) via a government agency server, to a logistics provider and / or pharmacy via their respective servers, and / or to the patient and caregiver via their personal mobile devices.

[0059] As a further alternative, certain decisions made by a drug delivery system and / or one or more computing devices operating in accordance with embodiments of the present disclosure may be used to operate a drug delivery device remotely (i.e., without a control device present in the same geographic location (e.g., room, building, or city) as the drug delivery device).

[0060] For example, the drug delivery system or one or more computing devices may use the information to make a determination that the device needs to be controlled to prevent inadvertent operation. The determination may be based in part on the drug identification information in combination with certain patient identification information, such as biometric information in the form of a fingerprint. If it is determined that an unauthorized party is attempting to use the drug delivery device, the one or more computing devices may generate a signal that is sent to the drug delivery system to lock the drug delivery device or to keep it locked until the drug delivery system is accessed by the patient or user for whom it is intended.

[0061] As a further alternative, the drug delivery system or one or more computing devices may use information to determine that a patient associated with the drug delivery device falls into a particular group or subgroup of patients or users who require or prefer a particular mode of drug delivery device operation. This determination may be made, in part, using information related to patient and drug identity. Based on this determination, the drug delivery system and / or one or more computing devices may generate a signal that personalizes the operation of the drug delivery device. For example, the drug delivery device may be personalized with respect to the sounds and / or lights used to notify the patient of various conditions or operating states according to a particular market segment or patient population associated with that patient. As one example, different sounds may be used for pediatric patients than for adult patients, louder sounds may be used for patients with hearing loss, and different lights or light sequences may be used for patients who are color-blind. Such control of the drug delivery device through the drug delivery system and / or one or more computing devices may reduce costs for drug delivery by allowing a single drug delivery device to be used that is tailored to the patient via software, rather than using multiple different drug delivery device types, each with different hardware from other types of drug delivery devices.

[0062] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination that the drug delivery device did not perform properly and generate a communication regarding that point in the manufacture of the drug delivery device. The manufacturer may then determine changes and / or improvements to enable proper administration of the drug, and if that is not followed or successful, can perform an inspection on the sensed information and relay the error.

[0063] As mentioned above, the drug delivery system and / or one or more computing devices in communication with the drug delivery system need not be adapted or programmed to perform all of the operations listed in FIG. 2 .

[0064] 3-14 illustrate additional embodiments of systems and methods in which some or all of the processing of sensor data or other information collected by the drug delivery device is performed by one or more computing devices external to the drug delivery device. Furthermore, the systems and methods of FIGS. 3-14 enable a user to interact with system components to address one or more difficulties experienced by a patient during initial use of the drug delivery device and / or during long-term use of the drug delivery device (e.g., in maintaining compliance with a treatment regimen). To achieve interactivity, the system may sense or determine different types of information about the drug delivery device, including operational status information (e.g., whether medication delivery is complete), condition information (e.g., temperature), and identification information (e.g., medication name). The drug delivery device may communicate this information to a local and / or remote computing device so that the local and / or remote computing device can provide this information and / or instructions to the user. Communication of information from the drug delivery device may be based, for example, on the type of information being communicated. The drug delivery device may then determine whether the user performed the correct actions in response to the information and / or instructions displayed on the local computing device and / or remote computing device, and this information may then be communicated to the local computing device and / or remote computing device for further processing.

[0065] 3-14 may have an associated controller (which may include a processor and memory) in communication with a first communication module (which may be a transmitter, a set of transmitters and receivers, or a transceiver), which may be connected via a communication link to a second communication module (which may be a receiver, a set of transmitters and receivers, or a transceiver) associated with a local computing device and / or a remote computing device (which may also include a controller having a processor and memory). The local computing device may be in communication with the remote computing device such that the drug delivery device (and more specifically, the controller associated with the drug delivery device) can communicate with the local computing device over the first communication link, and the local computing device can then communicate with the remote computing device over the second communication link.

[0066] While the drug delivery devices described below are configured as autoinjectors, in other embodiments, the drug delivery devices may be configured as on-body injection devices.

[0067] 3 illustrates an embodiment of a system 300 that includes a drug delivery device 302, a local computing device 304, and a remote computing device 306. While the system 300 includes both the local computing device 304 and the remote computing device 306, not all embodiments according to the present disclosure include both the local computing device 304 and the remote computing device 306.

[0068] The drug delivery device 302 may be in the form of an autoinjector and is therefore adapted for handheld use and application against the patient's skin. The drug delivery device 302 includes a housing 310 in which an assembly or structure is disposed that introduces a delivery cannula into the patient and forces a drug or agent from a reservoir 312 through the delivery cannula and into the patient. According to certain embodiments, the same assembly or structure that introduces the delivery cannula into the patient may also force a drug or agent from the reservoir through the delivery cannula and into the patient. The drug delivery device 302 may also include an assembly or structure that connects the delivery cannula to the reservoir, retracts the delivery cannula into the housing 310 through an opening in the housing 310 (not shown), or positions other structure that prevents contact with the delivery cannula when the delivery cannula is removed from the patient. Even additional assemblies and structures are possible. Accordingly, the specific embodiments of the drug delivery device 302 discussed below are by way of example and not limitation.

[0069] Thus, drug delivery device 302 includes a reservoir 312 and a delivery cannula 314 having a first end 316 (e.g., a proximal end) that may be connected to or fluidly connectable to reservoir 312, and a second end 318 (e.g., a distal end) that may be inserted into a patient. Delivery cannula 314 may be, for example, a rigid needle with a beveled edge that may be sized so that second end 318 of needle 314 is received under the skin to deliver a subcutaneous infusion of the agent in reservoir 312. First end 316 of needle 314 may be disposed through a wall 320 of reservoir 312 and thus may be fluidly connected to reservoir 312. Alternatively, the first end 316 of the needle 314 may be disposed partially through the wall 320 (which may be, for example, a resalable septum or stopper) such that the first end of the needle 314 is not fluidly connected until the second end 318 of the needle 314 is inserted into the patient. In such circumstances, the first end 316 of the needle 314 may be described as being fluidly connectable with the reservoir 312 in this manner, although it will be understood that there are other ways in which the first end 316 of the needle 314 may be fluidly connectable to the reservoir 312 but is not connected.

[0070] The drug delivery device 302 includes a shield 322 (e.g., a needle shield) that may be positioned to limit access to the second end 318 of the needle 314, at least after an injection is completed. According to certain embodiments, the shield 322 may have a biasing element 324 (such as a spring) that stretches the shield 322 from the housing 310 such that the distal end 326 of the shield 322 extends beyond the second end 318 of the needle 314 except when the shield 322 is disposed against the skin and insertion of the needle 314 is actuated. Indeed, according to certain embodiments of the drug delivery device 302, insertion of the needle 314 may be actuated by placing the distal end 326 of the shield 322 on or against the patient's skin.

[0071] The drug delivery device 302 may also include a lock 328 (e.g., a ratchet) coupled to the shield 322 and configured to limit or prevent movement of the shield 322 relative to the housing 310 of the drug delivery device 302, such that the distal end 326 of the shield 322 extends a sufficient distance from the housing 310 to limit or prevent contact with the second end 318 of the needle 314, for example, after the needle 314 is removed or released from the patient's skin. In some embodiments, the lock 328 may be coupled to a controller (e.g., the controller 350 described in more detail below) that can selectively activate or deactivate the lock 328 based on different types of information about the drug delivery device 302, including operational status information, condition information, and / or identification information, according to one or more of the methods described above. When the lock 328 is activated by the controller 350, the lock 328 may be configured to limit or prevent movement of the needle shield 322 relative to the housing 310. When the lock 328 is deactivated by the controller 350 , the lock 328 may be configured to allow movement of the needle shield 322 relative to the housing 310 .

[0072] The drug delivery device 302 also includes at least one driver 330, which may be used to insert the second end 318 of the needle 314 into the patient's skin and force the drug or agent from the reservoir 312 through the delivery cannula 314 and into the patient. According to certain embodiments, the driver 330 may include one or more springs. According to other embodiments, the driver 330 may include a source of pressurized gas or material in which a phase change occurs, such that the effused gas or phase-change material provides a motive force capable of pushing the drug into and from the reservoir 312. According to still other embodiments, the driver 330 may include an electromechanical system, for example, a prime mover, although such an electromechanical system may be more suitable for the on-body autoinjector or injector described above. Other embodiments of the driver 330 are also possible.

[0073] In one embodiment, the driver 330 may be coupled to a plunger 331 and / or a stopper 332 (e.g., a wall) disposed within the reservoir 312 to move the stopper 332 distally toward the delivery cannula 314. According to such an embodiment, the stopper 332 may be a stopper secured to a distal end of the plunger 331 and received within the bore 334. The plunger 331, in conjunction with the driver 330, may move the stopper 332 through the bore 334 along the longitudinal axis of the drug delivery device 302 from the proximal end of the bore 334 to the distal end of the bore 334, thereby forcing the medicament out of the reservoir 312.

[0074] In some embodiments, the driver 330 may also cooperate with the stopper 332 and / or the bore 334 to move the reservoir 312 relative to the housing 310 to move the second end 318 of the needle 314 relative to the housing 310 and into the patient. According to embodiments in which the driver 330 cooperates with the stopper 332, this may occur before the first end 316 of the needle 314 is in fluid communication with the reservoir 312. According to embodiments in which the driver cooperates with the bore 334, the driver may include one component (e.g., a first spring) that cooperates with the bore 334 to move the reservoir 312 and needle 314 relative to the housing 310, and a second component (e.g., a second spring) that cooperates with the stopper 332 to move the stopper 332 relative to the bore 334.

[0075] The drug delivery device 302 may also include a lock 335 coupled to the plunger 331 and configured to limit or prevent movement of the plunger 331 relative to the housing 310 of the drug delivery device 302 such that the stopper 332 cannot advance and release the medication from the reservoir 312 to the patient. In some embodiments, the lock 335 may be coupled to a controller (e.g., the controller 350 described in more detail below) that can selectively activate or deactivate the lock 335 based on different types of information about the drug delivery device 302, including operational status information, condition information, and / or identification information, according to one or more of the methods described above. When the lock 335 is activated by the controller 350, the lock 335 may be configured to limit or prevent movement of the plunger 331 relative to the housing 310. When the lock 335 is deactivated by the controller 350, the lock 335 may be configured to allow movement of the plunger 331 relative to the housing 310.

[0076] The driver 330 may be associated with an actuator 340. The actuator 340 may activate the driver 330, causing the driver 330 to insert the needle 314 and force the drug from the reservoir 312 through the needle 314 and into the patient. According to certain embodiments, the actuator 340 may be the needle shield 322, as described above. According to other embodiments, such as that illustrated in FIG. 3, the actuator 340 may be a button that can be manually depressed by a user or patient once the drug delivery device 302 is placed and positioned on or against the patient's skin. A lock 341 may be coupled to the actuator 340 and configured to limit or prevent movement of the actuator 340 so that the actuator 340 cannot be used to activate the driver 330. In some embodiments, the lock 341 may be coupled to a controller (e.g., the controller 350 described in more detail below) that can selectively activate or deactivate the lock 341 based on different types of information about the drug delivery device 302, including operational state information, condition information, and / or identification information, according to one or more of the methods described above. When the lock 341 is activated by the controller 350, the lock 341 may be configured to limit or prevent movement of the actuator 340 relative to the housing 310. When the lock 341 is deactivated by the controller 350, the lock 341 may be configured to allow movement of the actuator 340 relative to the housing 310.

[0077] The drug delivery device 302 may also include a removable sterility barrier 344 disposed around one or more of the distal end of the housing 310, the needle shield 322, and the second end 318 of the delivery cannula 314. The removable sterility barrier 344 may be removably attached to the distal end of the housing 310 as shown in FIG. 3 . In some embodiments, the removable sterility barrier 344 may form an interference or snap fit with the distal end of the housing 310. Frictional forces associated with the interference or snap fit can be overcome by manually pulling the removable sterility barrier 344 away from the housing 310. When attached to the drug delivery device 302, the removable sterility barrier 344 may reduce the risk of contamination of the delivery cannula 314 and other elements disposed within the drug delivery device 302.

[0078] Additionally, the drug delivery device 302 may include a heating element 346 coupled to the exterior of the reservoir 312 and configured to warm the medication within the reservoir 312, for example, by conductive heating. The heating element 346 may be coupled to the controller 350 such that the controller 350 can selectively activate or deactivate the heating element 346 based on different types of information about the drug delivery device 302, including operational status information, condition information, and / or identification information, according to one or more of the methods described above. In some embodiments, the heating element 346 may include a conductive coil disposed around the exterior of the reservoir 312. In other embodiments, the heating element may include a conductive coil disposed around the cannula 314. Alternatively, or in addition, a cooling element (not shown) may be coupled to the reservoir 312 and controllable by the controller 350 in a manner similar to the heating element 346.

[0079] The drug delivery device 302 may also include an output device 347 coupled to the housing 310 and configured to communicate information related to the drug delivery device 302 to a patient or user. The output device 347 may be coupled to the controller 350 such that the controller 350 can selectively activate or deactivate the output device 347 based on different types of information related to the drug delivery device 302, including operational status information, condition information, and / or identification information, according to one or more of the methods described above. The output device 347 may be any device suitable for conveying information to a patient or user, including a display (e.g., a liquid crystal display), a touch screen, a light source (e.g., a light emitting diode), a vibrator (e.g., an electromechanical vibrating element), a speaker, and / or an alarm, among other devices.

[0080] The drug delivery device 302 may also include an input device 348 coupled to the housing 310 and configured to allow a user or patient to input information (e.g., password information) for use by the control device 350. In some embodiments, the input device 348, the output device 347, and even the fingerprint sensor 365 may be a single device, such as a touchscreen. In other embodiments, the input device 348, such as a keyboard or buttons, may be a separate device from the output device 347.

[0081] As shown in FIG. 3 , the reservoir 312, the biasing element 324, the locks 328, 335, 341, the plunger 331, the stopper 332, the driver 330, and the heating element 346 are disposed within a housing 310 along with at least a portion of the delivery cannula 314. Also disposed within the housing 310 are a controller 350, a communication module 352 (e.g., a wireless transmitter), and at least one sensor or switch. According to the embodiment shown in FIG. 3 , four sensors are included: a temperature sensor 360, a skin sensor 362, at least one orientation sensor 364, and a fingerprint sensor 365. The sensors 360, 362, 364, and 365 may each generate sensor data (e.g., raw or unprocessed data) associated with a respective measured characteristic or aspect of the drug delivery device 302. The sensor data may represent at least one of a condition or operating state of the drug delivery device 302. Additionally, the drug delivery device 302 includes a switch 366. The controller 350 is coupled to the communication module 352, the locks 328, 335, 341, the sensors 360, 362, 364, 365, the heating element 346, the fingerprint sensor 365, the output device 347, the input device 348, and the switch 366. The controller 350 may be configured to process sensor data generated by the sensors 360, 362, 364, and 365 and determine the condition and / or operating state of the drug delivery device 302. The controller 350, the communication module 352, one or more of the sensors 360, 362, 364, 365, and the switch 366 may be implemented together as a single module, or each component may be manufactured separately and combined once the components are disposed within the housing 310. According to certain embodiments, each electrical component may be integrated with the structure of device 302 associated with the electrical component (e.g., sensors 362, 364 may be integrated with shield 322). In some embodiments, controller 350, communications module 352, one or more of sensors 360, 362, 364, 365, and / or switch 366 may be packaged together within removable sterility barrier 344.

[0082] Controller 350 may include at least one processor 370 (e.g., a microprocessor) and memory 372 (e.g., random access memory (RAM), non-volatile memory such as a hard disk, flash memory, removable memory, non-removable memory, etc.). Controller 350 may also include or be coupled to a power source, such as a battery. Processor 370 may be programmed to perform the operations that controller 350 is adapted to perform, and memory 372 may include one or more non-transitory, readable, tangible memories having executable computer-readable, non-transitory instructions stored thereon that, when executed by at least one processor 370, cause at least one processor 370 to perform the operations that controller 350 is adapted to perform. Alternatively, controller 350 may include other circuitry that performs the operations that controller 350 is adapted to perform.

[0083] The memory 372 may store the identifying information discussed above. The identifying information may be stored in the memory 372 prior to commencing execution of any of the methods discussed above. The identifying information may include, by way of example and not limitation, a unique identifier, the name of the drug, the dosage, the expiration date, and information regarding the identity of the patient to whom the drug is prescribed. Using this information, the controller 350 or a local computing device (e.g., a smartphone) may make a determination regarding the patient to whom the drug is about to be administered and provide appropriate informational and / or instructional prompts. As an alternative to the memory 372, the identifying information may be included in a QR code label or radio frequency identification tag associated with the drug delivery device 302.

[0084] The communication module 352 may be any of several different communication modules used to communicate with a local computing device (e.g., a smartphone) and / or a remote computing device (e.g., a server operated by the device manufacturer). According to one embodiment, the communication module 352 may be a Bluetooth and / or Bluetooth low energy module mounted with the controller 350. The communication module 352 is used to transmit information from the drug delivery device 302 to the local computing device 304. Alternatively, other wireless protocols may be used by the communication module 352, such as radio frequency identification (RFID), Zigbee, Wi-Fi, near field communication (NFC), etc. In practice, communications may be transmitted along hard-wired connections rather than using the electromagnetic (EM) spectrum. As defined herein, communications transmitted and / or received between the module 352, the local computing device, and / or the remote computing device may be in the form of, for example, hard-wired or EM signals, or patterns of such signals.

[0085] The temperature sensor 360 may be disposed in proximity to the reservoir 312 so as to be able to determine the temperature of the drug within the reservoir 312. Alternatively, the temperature sensor 360 may simply be disposed within the housing 310 so as to be able to generally determine the approximate temperature of the drug within the reservoir 312 and the drug delivery device 302. According to an embodiment, the temperature sensor 360 may be an internal temperature sensor 360 attached to the processor 370.

[0086] A skin sensor 362 may be attached to or associated with the shield 322 to determine when the drug delivery device 302 is disposed on or against the patient's skin. According to one embodiment, the skin sensor 362 is a pressure sensor. According to other embodiments, the skin sensor 362 may be a capacitance sensor, a resistance sensor, or an inductance sensor. The skin sensor 362 or the switch 366 (attached to or associated with the actuator 340) may be used to determine when the drug delivery device 302 has been activated or actuated, depending on the design and operation of the drug delivery device 302 used to actuate the drive unit 330, in accordance with the above discussion. Even when the shield 322 is not used as the actual actuator, the signal from the skin sensor 360 may be used to determine when the drug delivery device 302 has been activated, the basic premise being that movement of the shield 322 is necessarily related to the actuation of the device 302.

[0087] As shown, orientation sensors 364, of which there may be at least two, may be associated with the shield 322 (or that portion of the housing 310 adjacent to the shield 322) and the controller 350 (which may be disposed from the shield 322 to the other end of the drug delivery device 302 or housing 310, as shown). The orientation sensors 364 may be, for example, magnetometers. Specifically, the orientation sensor 364 associated with the controller 350 may be an integrated magnetometer. The orientation sensors 364 may be used to determine the orientation of the drug delivery device 302 (specifically, the housing 310) relative to the injection site (or more specifically, relative to the placement of the drug delivery device 302 on or against the patient's skin).

[0088] It will be understood that the arrangement of the components of the drug delivery device 302 within the housing 310 is but one embodiment of the present disclosure. For example, Figure 4 illustrates a second embodiment of the drug delivery device 302 in which certain components of the drug delivery device 302 are disposed outside the drug delivery device 302.

[0089] According to this embodiment, the drug delivery device 302 may include a housing 310, a reservoir 312, a needle 314, a shield 322, a biasing element 324, a lock 328, a driver 330, and a button 340. Additionally, sensors 362, 364, and a switch 366 may be disposed within the housing 310. A separate module 400 is provided within the housing 402 in which the control unit 350, the communication module 352, and the built-in temperature and orientation sensors 360, 364 are disposed. The fingerprint sensor 365, the output device 347, and the input device 348 may be disposed on the outside of the module 130 to allow a user or patient to interact with them. In some embodiments, the communication module 352 may be disposed within the housing 310 rather than within the module 400.

[0090] The module 400 may be adapted to be attached to the exterior surface 404 of the housing 310; for example, the module 400 may have an annular or C-shaped configuration with a central aperture sized so that the end 406 of the drug delivery device 302 can be disposed within the aperture and the module 400 can be secured in place by a mating configuration. According to certain embodiments, the module 400 may be movable relative to the drug delivery device 302 such that movement of the module 400 relative to the housing 310 (e.g., by depressing the button 340) can activate the autoinjector; in this case, the switch 366 may actually be located within the housing 402 of the module 400. According to other embodiments, the housing 310 and the exterior surface 404 of the module 400 may have cooperating couplings. As a further alternative, fasteners, whether reversible or irreversible, may be provided on the housing 310 or the module 400 that cooperate with other features of the housing 310 or the module 400 to attach or secure the module 400 to the housing 310. One example of such a fastener may be a set screw on the module 400 that cooperates with a recess on the surface 404 of the housing 310 .

[0091] The exterior surface 404 of the housing 310 may also have one or more contacts 408 that mate with contacts 410 on the exterior surface 412 of the housing 402 of the module 400. The mating contacts 408, 410 couple the sensors 362, 364, locks 328, 335, 341, heating element 346, and switch 366 in the drug delivery device 302 to the controller 350 in the module 400 (i.e., according to certain embodiments described above in which the module 352 is also disposed in the housing 310, the sensors 362, 364, locks 328, 335, 341, heating element 346, and switch 366 can be coupled to the controller 350 or the communication module 352). The contacts 408, 410 may contact one another, or the contacts may mate without physically contacting one another, in which case the contacts 408, 410 may be provided below the surfaces 404, 412 of the housings 310, 402.

[0092] Separating the controller 350, communications module 352, and other components into module 400 may allow module 400 to be used with multiple instances of drug delivery device 302. In doing so, module 400 may be considered the reusable portion of the drug delivery device 302 / module 400 combination (which may be referred to as drug delivery device 302 for purposes of this disclosure), while drug delivery device 302 may be considered the disposable portion of the drug delivery device 302. By separating more expensive components into the reusable module 400 and less expensive components (including certain sensors) into the disposable drug delivery device 302, the overall cost of the autoinjector may be optimized. The arrangement of components within module 400 and drug delivery device 302 may also facilitate manufacturing and sterilization of drug delivery device 302 and module 400.

[0093] 3, the local computing device 304 may be in the form of at least one computing device including at least one processor 420 (e.g., a microprocessor) and memory 422 (e.g., random access memory (RAM), non-volatile memory, e.g., a hard disk, flash memory, removable memory, non-removable memory, etc.). The at least one processor 420 and memory 422 may be integrated into a controller 423 of the local computing device 304 and / or configured separately. Similarly, the remote computing device 306 may be in the form of at least one computing device including at least one processor 424 (e.g., a microprocessor) and memory 426 (e.g., random access memory (RAM), non-volatile memory, e.g., a hard disk, flash memory, removable memory, non-removable memory, etc.). The at least one processor 424 and memory 426 may be integrated into a controller 427 of the local computing device 304 and / or configured separately. The processors 422, 424 may be programmed to perform the operations described below with respect to the methods of Figures 6, 13, and 14, and the memories 422, 426 may include one or more non-transitory computer-readable tangible memories having computer-executable instructions stored thereon (e.g., in the form of a custom mobile application, or an application for short integers, or other software modules), which, when executed by the processors 422, 424, may cause the processors 422, 424 to perform the operations described below with respect to the methods of Figures 6, 13, and 14. Alternatively, the local computing device 304 and the remote computing device 306 may include other circuitry that performs the operations described below with respect to the methods of Figures 6, 13, and 14.

[0094] Indeed, according to certain embodiments of the present disclosure, the local computing device 304 may perform the operations of Figures 6, 13, and 14 independently of the remote computing device 306. According to other embodiments, the local computing device 304 may perform certain of the operations of Figures 6, 13, and 14, while the remote computing device 306 performs other of the operations of Figures 6, 13, and 14. For example, according to certain embodiments, the processor(s) 420 may control components of the local computing device 304 that enable communications with the controller 350 and / or a user, but may not make decisions regarding the content of these communications; decisions regarding the content of these communications are made by the remote computing device 306.

[0095] According to the illustrated embodiment, the local computing device 304 is a mobile computing device (e.g., a smartphone, a smart watch, a tablet computer, etc.), while the remote computing device 306 is a server. In some embodiments, the local computing device 304 can include nearly any computing device capable of processing data and synchronizing with and communicating with the drug delivery device 302, such as, for example, a smart wearable device, a personal computer, a laptop computer, a smart television, a smart appliance, a smart automobile, a networked computer, etc. According to other embodiments, the local computing device 304 may be a dedicated device such as a hub or gateway that can establish a communications link with the communications module 352 and potentially with the remote computing device 306, where communication with the remote computing device 306 is necessary or desirable.

[0096] 6, 13, and 14, the local computing device 304 may further include a communication module 430 for wirelessly communicating with the communication module 352 of the drug delivery device 302, for example, by using a Bluetooth / Bluetooth Low Energy protocol. Alternatively, other wireless protocols may be used by the communication module 352, such as radio frequency identification (RFID), Zigbee, Wi-Fi, near field communication (NFC), cellular, and others. The local computing device 304 may also include a display device 432 used to communicate instructions to a user. The local computing device 304 may include other output devices for communicating with a user other than the display device 432, such as a speaker 434. The speaker 434 may be controlled by the processor(s) 420 to provide instructions in audible form that are displayed in written form on the display device 432.

[0097] The local computing device 304 may also include one or more communications modules, which may be the same as or different from the communications module 430, that may be used to communicate with one or more networks 440, 442. For example, the network 440 may be a wireless radio frequency network, such as a cellular mobile device network, while the network 442 may be a network of computing devices, such as the Internet. As illustrated in FIG. 6, the networks 440, 442 may be in communication with each other such that the local computing device 304 can communicate with the remote computing device 306 over the network 440, the network 442, or a combination of the networks 440, 442. The remote computing device 424 may include a communications module 436 for receiving communications from the networks 440, 442.

[0098] While the terms "local" and "remote" are used to describe the local computing device 304 and the remote computing device 306, these terms are not selected to require a particular spatial or geographic distance between the devices 304, 306. Instead, these terms are used to suggest relative proximity to the user and the fact that the remote computing device 306 need not be in the same physical location as the user and the drug delivery device 302. According to certain embodiments, it is possible, and even likely, that the remote computing device 306 may be located in a different geographic location than the user and the drug delivery device 302, e.g., a different city, state, or country.

[0099] The local computing device 304 and the remote computing device 306 are each separate or remote from the drug delivery device 302 and therefore may each be considered an “external computing device” with respect to the drug delivery device 302 .

[0100] Before describing the interaction and communication of information between the drug delivery device 302, the local computing device 304, and the remote computing device 306, a method 500 for implementing the drug delivery device 302 will be described with reference to FIG. 5. The method 500 begins at block 502 with the removal of the drug delivery device 302 from refrigeration, such as a refrigerator. Because the medication in the reservoir 312 is cold, it may be desirable to delay use for a period of time after the drug delivery device 302 is removed from refrigeration at block 504 to allow the device 302 and medication to warm. Warming the device 302 and medication may improve the operation of the device 302 and / or the performance and reliability of medication delivery. Alternatively, warming the device 302 and medication may minimize discomfort associated with delivering medication when cold. In any event, after the delay at block 504, the method 500 continues to block 506. While this description applies to removing an autoinjector from refrigeration, it is clear that the method may equally well apply if the device is too warm when removed from refrigeration.

[0101] At block 506, packaging is removed from around the drug delivery device 302. For example, a removable, disposable covering may be disposed over the second end 318 of the needle 314 during storage to maintain sterility and prevent accidental contact. This covering, and any other packaging that limits or prevents use of the device (e.g., an external safety lock), may be removed by the user prior to deployment and activation of the device. Once the packaging is removed at block 506, the drug delivery device 302 is applied to the patient's skin at block 508. The drug delivery device 302 is then positioned in a specific orientation relative to the patient's body at block 510.

[0102] With the drug delivery device 302 on or against the skin and in the correct position, the user is ready to activate the drug delivery device 302 at block 512. For example, the user may depress the button 340 or press the drug delivery device 302 toward the skin, causing relative movement between the housing 310 and the shield 322 of the drug delivery device 302, which activates the device. Once the drug delivery device 302 has been activated, the user waits for delivery to be completed at block 514.

[0103] Completion of drug delivery by the drug delivery device 302 may be communicated to the user in several different ways. For example, the drug delivery device 302 may have a window in the side of the housing 310 that allows visualization of the reservoir 312, and in particular the movement of the stopper 332 along the bore 334 in the reservoir 312. Alternatively, the drug delivery device 302 may include a sound-emitting device, such as a ratchet or clicker, that activates when drug delivery is complete. Once delivery is complete, the drug delivery device 302 may be removed and discarded at block 516.

[0104] As mentioned above, a user (who may be a patient or, alternatively, a healthcare provider) may have difficulty with any or all of the steps of method 500. For example, the user may be unsure whether to delay use (block 504) or how long to delay use. Alternatively, the user may not apply the device 302 against the skin (block 508), or the drug delivery device 302 may be improperly positioned (block 510). The user may be unsure how to determine when delivery is complete (block 514) and therefore administer less than the full dose. The user may confuse the order of the steps outlined in method 500, or may simply forget or decide not to perform any of the steps of method 500.

[0105] Referring to Figure 6, a method 600 is provided for limiting the likelihood that a user will fail to perform steps of method 500 using interactive drug delivery system 300. While method 600 describes the operation of the overall system 300, further methods that may be performed by the controller 350 of drug delivery device 302, the local computing device 304, and / or the remote computing device 306 are provided in Figures 12 and 13. Method 600 will also be discussed with reference to the simulated screenshots of Figures 7-11.

[0106] Method 600 begins at block 602, where the system 300 determines that the drug delivery device 302 has been removed from refrigeration. Specifically, the temperature sensor 360 is used to determine that a temperature change has occurred with respect to the drug delivery device 302, specifically an increase in temperature. This change in temperature is communicated from the drug delivery device 302 to the local computing device 304, which is running software, such as a mobile application, that enables this information to be received from the drug delivery device 302 and used to generate a series of instructions and information prompts for a user that are displayed on the display 432 of the local computing device 304, as illustrated in FIGS. 7-11 . According to certain embodiments, the local computing device may control the display 432 to display instructions or information prompts not only according to the received communication, but also according to information stored on or received by the local computing device 304 (i.e., other than the communication). According to method 600, a first instructional prompt may be displayed by the local computing device 304 at block 604, where the user will wait before continuing with operation of the device (see FIG. 7 ).

[0107] The method 600 then remains at block 606 where the temperature sensor 360 is monitored to determine whether the temperature of the drug delivery device 302 has risen above a desired threshold (i.e., T1). If the temperature has not risen above the threshold, the system 300 continues monitoring the temperature at block 606. Otherwise, the method 600 continues to block 608 where a further instructional prompt may be displayed by the local computing device 304 that the user may continue operating the drug delivery device 302 (see FIG. 8 ).

[0108] The method 600 may then remain at blocks 610, 612 where additional instructional prompts are displayed by the local computing device 304 to instruct the user to remove any packaging (e.g., a needle cover) and apply the drug delivery device 302 to the patient's skin. The system 300 then monitors the skin sensor 362 to determine whether the drug delivery device 302 has been applied to the skin at block 614. If the drug delivery device 302 has not been applied, the method 600 remains at block 614; if the drug delivery device 302 has been applied, the method 600 continues to block 616.

[0109] At block 616, a further instructional prompt may be displayed by the local computing device 304 that the user should position the drug delivery device 302 on the skin. For example, it may be desirable for the drug delivery device 302 to be positioned on the skin so that the needle 314 enters the skin at the correct angle, or perpendicular to the skin. The system 300 may monitor the orientation of the device using the orientation sensor 364 at block 618, and a further instructional prompt may be displayed by the local computing device 304 to the user to reposition the device 302 relative to the skin at block 620. See FIG. 9 . If the system determines that the position of the drug delivery device 302 is acceptable, the method may proceed to block 622.

[0110] At block 622, an instructional prompt may be displayed by the local computing device 304 that the user should activate the drug delivery device 302. The system 300 may then monitor the switch 366 to determine that the user has activated the button 340 before continuing to block 626. At block 626, an instructional prompt may be displayed by the local computing device 304 that the user should wait for completion of drug delivery. See FIG. 10 . Also at block 626, the local computing device 304 may display an informational prompt informing the user that a predetermined amount of drug has been delivered. See also FIG. 10 . This informational prompt may depend on a determination made based on, for example, an additional sensor monitoring the movement of the stopper 332 within the hole 334 of the reservoir 312. Alternatively, the informational prompt may be based on an estimate of the completion state based on time-measured tests performed using other instances of the drug delivery device 302 in which drug was delivered or administered.

[0111] At the same time, the system 300 may continue to monitor the orientation sensor 364 at block 628 to determine that the drug delivery device 302 remains in the proper position relative to the patient's skin. An instructional prompt to reposition the drug delivery device 302 may be displayed at block 630 by the local computing device 304 in addition to or instead of the informational prompt displayed at block 626. The system 300 also determines whether drug delivery is complete at block 632, which determination may be made, for example, based on monitoring a sensor associated with the stopper 332, or based, for example, on an inference based on timed tests. In fact, the determinations made at blocks 628 and 632 may be combined with the instructional prompt displayed at block 630 that occurs only if it is desirable to reposition the autoinjector and delivery is not complete.

[0112] If the system 300 determines that drug delivery is complete, the method 600 continues to block 634, in which an informational prompt (see FIG. 11) may be displayed by the local computing device 304 that delivery is complete and the device may be removed and discarded, and block 636, in which a report of completion of drug delivery by the user using the drug delivery device 302 is provided, for example, to the remote computing device 306.

[0113] As discussed above, the method 600 describes the operation of the overall system 300. However, the operation of the overall system 300 can also be described in terms of operations performed by the drug delivery device 302 and the local computing device 304. The individual operations of each device 302, 304, and the cooperation between the devices 302, 304, will now be described with reference to Figures 12 and 13. It should be noted that in an alternative embodiment, some or all of the operations performed by the local computing device 304 with respect to Figure 13 may be performed by the remote computing device 306.

[0114] 12, a method 700 is provided with respect to the operation of the controller 350. The method 700 begins at block 702, where the controller 350 monitors the temperature sensor 360 to determine whether the drug delivery device 302 has been removed from refrigeration. When the controller 350 determines that the temperature has increased corresponding to the presumed removal from refrigeration, the controller 350 controls the communication module 352 to send a communication (in the form of a signal) to the local computing device 304 at block 704 that the autoinjector 304 has been removed from refrigeration.

[0115] 13 , a method 800 implemented by the local computing device 304 begins at block 802 pursuant to receiving a communication sent by the drug delivery device 302 (more specifically, the communication module 352) by the local computing device 304 (more specifically, the communication module 430) that the drug delivery device 302 has been removed from refrigeration. The method 800 continues at block 804, in which the processor 420 of the controller 423 controls the display device 432 to display an instructional prompt to the user instructing the user to wait before using the drug delivery device 302. Before displaying the instructional prompt at block 804, the processor 420 of the controller 423 may process (e.g., compare) the communication received from the drug delivery device 302 at block 802 using or according to information stored in the memory 422 of the local computing device 304 to determine whether the sensed temperature is acceptable for the patient to use the drug delivery device 302. An instructional prompt may be displayed at block 804 in response to determining that the sensed temperature is unacceptable for the patient to use the drug delivery device 302. Subsequently, at block 806, the local computing device 304 (more specifically, the processor 420) may monitor the module 430 for subsequent communication from the drug delivery device 302.

[0116] 12 , the method 700 continues at block 706, where the controller 350 monitors the temperature sensor 360 to determine when the temperature sensed by the temperature sensor 360 exceeds a threshold temperature. When the controller 350 determines that the sensed temperature exceeds the threshold temperature, the controller 350 controls the communication module 352 to send a communication to the local computing device 304 that the temperature has been reached, at block 708. In some embodiments, the controller 350 may control the communication module 352 to send a communication representing the temperature of the drug delivery device 302, and upon receipt, the controller 423 of the local computing device 304 may compare the sensed temperature to information stored in the memory 422 of the local computing device 304 (e.g., threshold temperature information indicating a minimum temperature or temperature range) to determine whether the sensed temperature is acceptable for use of the drug delivery device 302 by the patient.

[0117] 13 , the method 800 remains at block 808 where the processor 420 controls the display device 432 to display an informational prompt instructing the user that the temperature of the drug delivery device 302 is now suitable or acceptable for use. The method 800 continues at blocks 810 and 812 where the processor 420 controls the display device 432 to display an instructional prompt to the user that the user should remove any packaging and apply the drug delivery device 302 to the patient's skin. The method 800 then remains at block 814 to monitor the communication link for the next communication from the drug delivery device 302.

[0118] In some embodiments, the controller 350 may evaluate the temperature history of the drug delivery device 302 to determine the range and duration of temperatures experienced by the drug delivery device 302 in the past and determine whether the temperature history renders the drug delivery device 302 or its medication unacceptable for use. If so, the controller 350 may control the communication module 352 to send a communication to the local computing device 304 that the temperature history of the drug delivery device 302 renders the drug delivery device 302 unsuitable for use, and the controller 423 of the local computing device 304 controls the display 423 to display an informational prompt instructing the patient not to use the device. In some embodiments, the evaluation of the temperature history may be performed by the controller 423 of the local computing device 304 by comparing the temperature history received from the drug delivery device 302 with information stored in the memory 422 of the local computing device 304 to determine whether the temperature history is acceptable for use by the patient.

[0119] The method 700 then remains at block 710 of FIG. 12 where the controller 350 monitors the skin sensor 362 to determine whether the drug delivery device 302 has been applied to the patient's skin. When the controller 350 determines that the drug delivery device 302 has been applied to the patient's skin, the controller 350 controls the communication module 352 to send a communication to the local computing device 304 at block 712 that the drug delivery device 302 has been applied.

[0120] 13 is received, the method 800 continues to block 816, where the processor 420 controls the display device 432 to display an instructional prompt instructing the user or patient that the drug delivery device 302 should be adjusted relative to the patient's skin. The instructional prompt may include an example of the appropriate manner in which the device should be positioned relative to the patient's skin. To generate the instructional prompt at block 816, the processor 420 may process (e.g., compare) the communication received from the drug delivery device 302 at block 814 with or according to information stored in the memory 422 of the local computing device 304.

[0121] The method 800 may then continue to block 818, where the processor 420 monitors the communication link for any error communication received from the drug delivery device 302 regarding the device's position and / or orientation (see blocks 714, 716 of method 700 of FIG. 12 ), and, if an error communication is received, controls the display device 432 to display an instructional prompt to the user in block 820. The error communication may include an indication of the type of position and / or orientation error occurring, such that the displayed instructional prompt can be tailored to provide specific guidance (e.g., "Tilt right" or "Tilt left," etc.). To generate the instructional prompt in block 820, the processor 420 may process (e.g., compare) the error communication received from the drug delivery device 302 in block 818 with or in accordance with information stored in the memory 422 of the local computing device 304. The method 800 further continues at block 822, where the processor 420 monitors the communication link for further communications from the drug delivery device 302 and cycles between blocks 818, 822 until such further communications are received.

[0122] 12 , the controller 350 monitors the orientation sensor 364 at this point to determine whether the drug delivery device 302 is properly oriented, at block 714. If the device 302 is not positioned correctly, the controller 350 transmits one or more error communications, at block 716, and when the device 302 is correctly positioned, the controller 350 controls the communications module 352 to transmit a communication that the device is positioned, at block 718. In some embodiments, the controller 350 may control the communications module 352 to transmit a communication indicative of the orientation of the delivery device 302, and upon receipt, the controller 423 of the local computing device 304 may compare the sensed orientation with information stored in the memory 422 of the local computing device 304 to determine whether the sensed orientation is acceptable for a patient to use the drug delivery device 302 to deliver a medication thereto.

[0123] 13 , the method 800 continues at block 824 where the processor 420 controls the display device 432 to display an instructional prompt to the user to activate the drug delivery device 302 and begin drug delivery. To generate the instructional prompt at block 822, the processor 420 may process (e.g., compare) the communication received from the drug delivery device 302 at block 822 with or according to information stored in the memory 422 of the local computing device 304. The method 800 then continues to block 826 where the processor 420 monitors the communication link for the next communication from the drug delivery device 302.

[0124] 12 at block 720, the controller 350 monitors the switch 366 to determine whether the button 340 has been depressed or other action has been taken to activate the drug delivery device 302. If the controller 350 receives a signal from the switch that the button 340 has been depressed, for example, the controller 350 controls the communication module 352 to send a communication to the local computing device 304 that the device has been activated, as shown in block 722.

[0125] 13, upon receiving a communication that the device has been activated, the method 800 remains at block 828 where the processor 420 controls the display device 432 to display an informational prompt to the user that an infusion has begun. To generate the instructional prompt at block 828, the processor 420 may process (e.g., compare) the communication received from the drug delivery device 302 at block 826 with or according to information stored in the memory 422 of the local computing device 304.

[0126] Method 800 may continue at blocks 830, 832, where processor 420 monitors the communication link for any error communications regarding the device's location (block 830) and controls display device 432 to display an instructional prompt to the user to reposition the device (block 832). See also blocks 724 and 726 of method 700 of Figure 12. Method 800 further continues at block 834, where processor 420 monitors the communication link for further communications from drug delivery device 302. While shown as separate blocks, it will be understood that the operations of blocks 830 and 834 may be combined into a single block.

[0127] The method 800 repeats blocks 828, 830, 834 (and block 832, when circumstances require) until such communication is received. It will be appreciated that during the repeat loop of block 828, the processor 420 may control the display device 432 to provide informational prompts to the user reflecting progress toward delivery of the drug from the drug delivery device 302. Thus, the repetition of block 828 is not intended to indicate that the same informational prompts will be repeatedly displayed to the user, although repeated display may occur according to certain embodiments.

[0128] Returning to method 700 of Figure 12, the controller 350 continues to monitor the orientation sensor 364 at block 724 (and, if necessary, sends an error communication at block 726) until the controller 350 determines that the injection is complete at block 728. While these operations are illustrated as separate blocks in Figure 12, the operations of blocks 724 and 728 may be combined. When the controller 350 determines that the injection is complete at block 728, the controller 350 controls the communication module 352 to send a delivery completion communication to the local computing device 304 at block 730.

[0129] It will be appreciated that the determination made at block 728 may be made based on monitoring signals received from one or more sensors associated with reservoir 312, as described above. Alternatively, the determination at block 728 may be made based on a timer set according to an estimate of the time required to fully expel the drug from reservoir 312 according to a previously performed time trial. According to other embodiments, controller 312 may not make the determination that delivery is complete, but rather this determination may be made by local computing device 304 based, for example, on receiving a communication that the device has been activated, a timer monitored or managed by processor 420, and an estimate of the time required to fully expel the drug from reservoir 312 according to a previously performed time trial.

[0130] However, according to the illustrated embodiment, the delivery completion communication is sent to the local computing device 304 and the method 800 continues at blocks 834, 836 of Figure 13 with the local computing device 304 receiving the communication (block 834) and the processor 420 controlling the display device 432 to display an informational prompt to the user that delivery is complete and / or an instructional prompt to safely discard the drug delivery device 302. The processor 420 may then format and send to the remote computing device 306 a report at block 838 regarding operation of the device 302 indicating completion of drug delivery to the patient.

[0131] While the structure and operation of an embodiment of system 300 according to the present disclosure has been discussed above, it will be understood that further variations of the present system 300 and methods of operation thereof may be described.

[0132] For example, while the foregoing suggests that communications (other than error communications) include some identifying information (e.g., a delivery completion communication) that makes each unique, this need not be the case according to all embodiments. For example, the local computing device 304 may simply wait for the next non-error communication to be received from the drug delivery device 302, and based on the receipt of a further non-error communication, the local computing device may move to the next operation of the method 800. As such, all of the non-error communications may become indistinguishable from one another.

[0133] As a further example, in addition to the information transmitted from the drug delivery device 302 to the local computing device 304 described above, the drug delivery device 302 may include identifying information about the drug and / or device 302 in memory 372. This identifying information may be transmitted to the local computing device 304 before or simultaneously with the controller 350 controlling the communications module 352 to transmit the initial “device removal” communication of block 704 of FIG. 12 , or along with the report that occurs in block 636 of FIG. 6 . The information may include, by way of example and not limitation, a unique identifier, the name of the drug, the dosage, and the expiration date. Alternatively, this information may be included on a QR code label or radio frequency identification tag associated with the drug delivery device 302, and the local computing device processor 420 may control the display device 432 to display instructional prompts to the user to obtain this information using the local computing device 304. In any event, the method 800 of FIG. 13 may include, if the local computing device 304 determines that the drug product is not appropriate for use by the user because, for example, the drug is incorrect, the dosage is incorrect, or the expiration date has passed, displaying informational prompts and even instructional prompts to the user based on this information.

[0134] Along similar lines, the identification information may include information regarding the identity of the patient to whom the drug is prescribed. Using this information, the local computing device 304 may make a determination regarding the patient to whom the drug is about to be administered and provide appropriate informational and / or instructional prompts. In combination with the drug identification information discussed above, the local computing device 304 may use this information to address the five correctnesses in administering a medication: right patient, right drug, right dosage, right time, and right route.

[0135] The local computing device 304 may also operate to display information prompts in the form of reminders to adhere to a prescribed treatment regimen. Indeed, the remote computing device 306 may interact with and / or control one or more local computing devices 304 that display the reminder information prompts. The remote computing device 306 may control the timing and / or content of the displayed reminder information prompts based on information received from one or more local computing devices 304. For example, if one or more local computing devices 304 evidence a particular type of use or behavior pattern on the part of these users, the remote computing device 306 may determine that one or another message is most appropriate for (e.g., most effective for) the user and may control the timing and / or content of the reminder information prompts accordingly. Other information prompts that may be displayed on a local computing device may include personal infusion history or general educational material regarding the patient's efficacy expectations for a prescribed treatment regimen.

[0136] By processing communications from the drug delivery device 302 on the local computing device 304 according to method 800, the data processing and / or storage burden on the drug delivery device 302 may be reduced. Furthermore, the drug delivery device 302 may not need to have a display device to provide informational and / or instructional prompts to the patient or user. Thus, method 800 allows for the use of relatively simple and / or inexpensive computer hardware-equipped drug delivery device 302, which may be desirable from an economic standpoint, particularly if the drug delivery device 302 is a disposable, single-use device, or otherwise has a limited lifespan.

[0137] To further reduce the data processing and / or storage burden on the drug delivery device 302, the drug delivery device 302 may transmit sensor data (e.g., raw or unprocessed data) from one or more of the sensors 360, 362, 364, and 365 to the local computing device 304 and / or the remote computing device 306 without processing the sensor data or with very minimal processing of the sensor data before its transmission. Thus, in such embodiments, the local computing device 304 and / or the remote computing device 306, as opposed to the drug delivery device 302, may process the sensor data to determine the condition and / or operating state of the drug delivery device 302. In addition to transmitting the sensor data to the local computing device 304 and / or the remote computing device 306, the drug delivery device 302 may not need to process the sensor data. This configuration may free the drug delivery device 302 from having to include a controller 350, a processor 370, and / or a memory 372, thereby reducing the cost and complexity of the drug delivery device 302. In such an embodiment, the only computer-related electronics onboard the drug delivery device 302 may be the sensors 360 , 362 , 364 , and 365 and the communications module 430 .

[0138] An example of a method, designated by the numeral 900, in which the local computing device 304, as opposed to the drug delivery device 302, has sensor data to determine at least one of the condition and / or operating state of the drug delivery device 302, will now be described with reference to FIG. 14. In some embodiments, some or all of the steps of the method 900 may be performed by the remote computing device 306 instead of the local computing device 304. The method 900 begins at block 902 by the local computing device 304 receiving sensor data at its communications module 430, generated by the temperature sensor 360 and transmitted from the communications module 352 of the drug delivery device 302. Next, at block 904, the sensor data received at block 902 may be processed (e.g., analyzed) by the processor 420 of the local computing device 304 according to information stored in the memory 422 of the local computing device 304 to determine the temperature or temperature history of the drug delivery device 302.

[0139] The method 900 then continues to block 906, where the processor 430 compares the temperature or temperature history determined in block 904 with information stored in memory 422 to determine whether the temperature or temperature history is acceptable for the patient to use the drug delivery device 302. In some embodiments, the processor 430 may compare the temperature to a threshold temperature and determine that the temperature is acceptable only if the temperature exceeds the threshold temperature. In embodiments where the temperature history is evaluated, the processor 430 may compare the temperature history to an acceptable temperature range to determine whether the drug delivery device 302 has previously been outside of the acceptable temperature range, and for how long.

[0140] In response to a determination at block 906 that the temperature or temperature history is unacceptable, the processor 430 may control the display device 432 to display an instructional prompt to the user at block 907 instructing the user to wait before using the drug delivery device 302 (or, for example, to not use the drug delivery device at all if the temperature history is unacceptable), after which the method 900 may return to block 902. In response to a determination at block 906 that the temperature or temperature history is acceptable, the processor 430 may control the display device 432 to display an instructional prompt at blocks 908, 910, and 912, respectively, instructing the user that the temperature or temperature history of the drug delivery device 302 is acceptable for use, to remove any packaging from the drug delivery device, and to apply the drug delivery device 302 to the patient's skin.

[0141] The method 900 then continues to block 914, in which the local computing device 304 receives at its communication module 430 sensor data generated by the skin sensor 362 and transmitted from the communication module 352 of the drug delivery device 302. The sensor data received at block 914 may then be processed (e.g., analyzed) by the processor 420 of the local computing device 304 in accordance with information stored in the memory 422 of the local computing device 304 to determine whether the drug delivery device 302 has been placed on or against the patient's skin at block 916. In response to a determination at block 916 that the drug delivery device 302 has not been applied to the patient's skin, the method 900 may return to block 912. In response to a determination at block 916 that the drug delivery device 302 has been applied to the patient's skin, the processor 430 may control the display device 432 to display an instructional prompt instructing the user to correctly or properly orient the drug delivery device 302 relative to the patient's skin at block 917.

[0142] The method 900 then continues to block 918, where the local computing device 304 receives at its communications module 430 the sensor data generated by the orientation sensor 364 and transmitted from the communications module 352 of the drug delivery device 302. Then, at block 920, the sensor data received at block 918 may be processed (e.g., analyzed) by the processor 420 of the local computing device 304 according to information stored in the memory 422 of the local computing device 304 to determine the orientation of the drug delivery device 304. The method 900 then continues to block 922, where the processor 430 compares the orientation determined at block 904 with the information stored in the memory 422 to determine whether the orientation of the drug delivery device relative to the patient's skin is acceptable. In response to determining at block 922 that the drug delivery device 302 is not properly oriented relative to the patient's skin, the processor 430 may control the display device 432 to display an instructional prompt instructing the user to reposition or reorient the drug delivery device 302 at block 924, after which the method 900 may return to block 918. In response to determining at block 922 that the drug delivery device 302 is properly oriented relative to the patient's skin, the processor 430 may control the display device 432 to display an instructional prompt instructing the user to actuate the drug delivery device 302 to deliver medication to the patient at block 926. In some embodiments, the drug delivery device 302 may be actuated by manually depressing the actuator 340.

[0143] The method 900 then continues to block 928, in which the local computing device 304 receives at its communication module 430 the sensor data generated by the switch 366 and transmitted from the communication module 352 of the drug delivery device 302. The sensor data received at block 928 may then be processed (e.g., analyzed) by the processor 420 of the local computing device 304 according to information stored in the memory 422 of the local computing device 304 to determine whether the drug delivery device 304 has been activated, at block 930. In response to a determination at block 930 that the drug delivery device 302 has not been activated, the method 900 may return to block 928. In response to a determination at block 930 that the drug delivery device 302 has been activated, the processor 430 may control the display device 432 to display an instructional prompt instructing the user to wait for completion of delivery of the medication from the reservoir to the patient, at block 932.

[0144] The method 900 then continues to block 934, where the local computing device 304 receives at its communications module 430 the sensor data generated by the orientation sensor 364 and transmitted from the communications module 352 of the drug delivery device 302. Then, at block 936, the sensor data received at block 934 may be processed (e.g., analyzed) by the processor 420 of the local computing device 304 according to information stored in the memory 422 of the local computing device 304 to determine the orientation of the drug delivery device 304. The method 900 then continues to block 938, where the processor 430 compares the orientation determined at block 904 with the information stored in the memory 422 to determine whether the orientation of the drug delivery device relative to the patient's skin is acceptable. In response to determining at block 938 that the drug delivery device 302 is not properly oriented relative to the patient's skin, the processor 430 may control the display device 432 to display an instructional prompt instructing the user to reposition or reorient the drug delivery device 302 at block 940, after which the method 900 may return to block 934. In response to determining at block 938 that the drug delivery device 302 is properly oriented relative to the patient's skin, the processor 430 may control the display device 432 to display an instructional prompt instructing the user to wait for completion of delivery of the medication from the reservoir 312 to the patient at block 941.

[0145] The method 900 then continues to block 942, where the local computing device 304 receives sensor data at its communication module 430, generated by a medication fluid level sensor (not shown) associated with the reservoir 312 and transmitted from the communication module 352 of the drug delivery device 302. The sensor data received at block 942 may then be processed (e.g., analyzed) by the processor 420 of the local computing device 304 in accordance with information stored in the memory 422 of the local computing device 304 to determine whether delivery of medication from the reservoir 312 to the patient is complete, at block 944. In some embodiments, the determination of completion of medication delivery may not be based on sensor data received from the drug delivery device 302, but instead on a timer monitored or managed by the processor 420 and an estimate of the time required to completely expel the medication from the reservoir 312 according to a previously conducted time trial.

[0146] In response to a determination at block 944 that delivery of the drug from the reservoir 312 to the patient is not complete, the processor 430 may control the display device 432 to display an instructional prompt instructing the user to wait for completion of delivery of the drug from the reservoir 312 to the patient at block 946, after which the method 900 may return to block 942. In response to a determination at block 944 that the drug delivery device 302 is properly oriented with respect to the patient's skin, the processor 430 may control the display device 432 to display an instructional prompt instructing the user to discard the drug delivery device 302 at block 948.

[0147] The method 900 may then proceed to block 950, where the processor 420 controls the communication module 430 to generate a report indicating completion of delivery of the medication to the patient and transmit the report to another external computing device (e.g., the remote computing device 306) and / or the drug delivery device 302.

[0148] The above description describes various sensors and sensor systems that can be used in combination with a drug delivery device to detect the condition and / or operating state of the drug delivery device. Additional or alternative sensors and sensor systems can also be incorporated into the drug delivery devices described above, including any combination of the sensors and sensor systems disclosed in co-pending international patent application entitled "Drug Delivery System and Method of Use," Attorney Docket No. 32263 / 48365A, which is incorporated herein by reference in its entirety.

[0149] The above description describes various systems and methods for use with a drug delivery device. The system, drug delivery device, or method may further include the use of the agents listed below, although it should be clear that none of the following lists should be considered all-inclusive or limiting. The agent is stored in a reservoir. In some cases, the reservoir is a primary container that is either filled or pre-filled with the agent for treatment. The primary container may be a cartridge or a pre-filled syringe.

[0150] For example, the drug delivery device, or more specifically the reservoir of the device, may be loaded with a colony-stimulating factor, such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neupogen® (filgrastim) and Neulasta® (pegfilgrastim). In various other embodiments, the drug delivery device may be used in conjunction with various pharmaceutical products, such as erythropoiesis-stimulating agents (ESAs), which may be in liquid or lyophilized form. ESAs are any molecules that promote erythropoiesis, such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxypolyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin alpha ... and epoetin zeta, epoetin theta, and epoetin delta, as well as molecules or variants or analogs thereof disclosed in the following patents or patent applications, each of which is incorporated herein by reference in its entirety: U.S. Pat. Nos. 4,703,008, 5,441,868, 5,547,933, 5,618,698, 5,621,080, 5,756,349, 5,756,349, and 5,762,112. Nos. 6,778, 5,773,569, 5,955,422, 5,986,047, 6,583,272, 7,084,245, and 7,271,689, and PCT Publication Nos. WO91 / 05867, WO95 / 05465, WO96 / 40772, WO00 / 24893, WO01 / 81405, and WO2007 / 136752.

[0151] The ESA may also be an erythropoiesis-stimulating protein. As used herein, "erythropoiesis-stimulating protein" refers to any protein that directly or indirectly activates the erythropoietin receptor, for example, by binding to the erythropoietin receptor and inducing its 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 (as well as compounds reported in U.S. Patent Publication Nos. 2003 / 0215444 and 2006 / 0040858, the disclosures of each of which are incorporated herein by reference in their entireties), and erythropoietin molecules or variants or analogs thereof disclosed in the following patents or patent applications, each of which is incorporated herein by reference in its entirety: U.S. Patent Nos. 4,703,008, 5,441,86 ... No. 5,547,933, No. 5,618,698, No. 5,621,080, No. 5,756,349, No. 5,767,078, No. 5,773 ,569, No.5,955,422, No.5,830,851, No.5,856,298, No.5,986,047, No.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 7,217,689; U.S. Patent Publication No. 2002 / 0155998,Same No. 2003 / 0077753, No. 2003 / 0082749, No. 2003 / 0143202, No. 2004 / 0009902 No. 2004 / 0071694, No. 2004 / 0091961, No. 2004 / 0143857, No. 2004 / 01572 No. 93, No. 2004 / 0175379, No. 2004 / 0175824, No. 2004 / 0229318, No. 2004 / 024 No. 8815, No. 2004 / 0266690, No. 2005 / 0019914, No. 2005 / 0026834, No. 2005 / 0 No. 096461, No. 2005 / 0107297, No. 2005 / 0107591, No. 2005 / 0124045, No. 2005 / 0124564, No. 2005 / 0137329, No. 2005 / 0142642, No. 2005 / 0143292, No. 20 No. 05 / 0153879, No. 2005 / 0158822, No. 2005 / 0158832, No. 2005 / 0170457, No. 2005 / 0181359, 2005 / 0181482, 2005 / 0192211, 2005 / 0202538, See PCT Publication Nos. 2005 / 0227289, 2005 / 0244409, 2006 / 0088906, and 2006 / 0111279, as well as PCT Publication Nos. WO91 / 05867, WO95 / 05465, WO99 / 66054, WO00 / 24893, WO01 / 81405, WO00 / 61637, WO01 / 36489, WO02 / 014356, WO02 / 19963, WO02 / 20034, WO02 / 49673, WO02 / 085940, WO 03 / 029291, WO2003 / 055526, WO2003 / 084477, WO2003 / 094858, WO2004 / 002417, WO2004 / 002424, WO2004 / 009627, WO2004 / 02 4761, WO2004 / 033651, WO2004 / 035603, WO2004 / 043382, WO2004 / 101600, WO2004 / 101606, WO2004 / 101611, WO2004 / 106373,WO2004 / 018667, WO2005 / 001025, WO2005 / 001136, WO2005 / 021579, WO2005 / 025606, WO2005 / 032460, WO2005 / 051327, WO2005 / 063808, WO2005 / 063809 , WO2005 / 070451, WO2005 / 081687, WO2005 / 084711, WO2005 / 103076, WO2005 / 100403, WO2005 / 092369, WO2006 / 50959, WO2006 / 02646, and WO2006 / 29094.

[0152] Examples of other pharmaceutical products for use with the device include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab), and Prolia™ (denosumab); other biologics such as Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF inhibitor), Neulasta® (pegfilgrastim, pegylated filgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-Met-G-CSF), and Nplate® (romiplostim); and small molecule drugs such as Sensipar® (cinacalcet). The device may also be used with therapeutic antibodies, polypeptides, proteins, or other chemicals such as iron, e.g., ferumoxytol, iron dextran, ferric gluconate, and iron sucrose. The pharmaceutical product may be reconstituted from a liquid form or a lyophilized form.

[0153] Among examples of particular proteins are the specific proteins described below, including fusions, fragments, analogs, variants, or derivatives thereof.

[0154] and OPGL-specific antibodies (also referred to as RANKL-specific antibodies, peptibodies, etc.), including OPGL-specific antibodies having either a light chain of SEQ ID NO:2 set forth in Figure 2 of the following publications and / or a heavy chain of SEQ ID NO:4 set forth in Figure 4 of the following publications, each of which is individually and specifically incorporated by reference in its entirety as disclosed in the following publications:

[0155] Specifically with reference in part to myostatin-specific peptibodies, including but not limited to the mTN8-19 family of peptibodies, including those in SEQ ID NOS: 305-351, TN8-19-1 to TN8-19-40, TN8-19 con1, and TN8-19 con2, i.e., peptibodies of the mL2 family of SEQ ID NOS: 357-383, the mL15 family of SEQ ID NOS: 384-409, the mL17 family of SEQ ID NOS: 410-438, the mL20 family of SEQ ID NOS: 439-446, the mL21 family of SEQ ID NOS: 447-452, the mL24 family of SEQ ID NOS: 453-454, and myostatin-binding proteins, peptibodies, and related proteins, including those of SEQ ID NOS: 615-631, in particular the myostatin-specific peptibodies described in U.S. Patent Publication No. 2004 / 0181033 and PCT Publication No. WO2004 / 058988, which are incorporated by reference in their entireties;

[0156] 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, L2H39, L2H40, L2H41, L2H42, L2H43, L2H44, L2H45, L2H46, L2H47, L2H48, L2H49, L2H50, L2H51, L2H52, L2H53, L2H54, L2H55, L2H56, L2H57, L2H58, L2H59, L2H60, L2H61, L2H62, L2H63, L2H64, L2H65, L2H66, L2H67, L2H68, L2H69, L2H70, L2H71, L2H72, L2H73, L2H74, L2H75, L2H76, L2H77, L and IL-4 receptor-specific antibodies, peptibodies, and related proteins, which specifically inhibit activities mediated by binding to IL-4 and / or IL-13 receptors, including, but not limited to, L2H11, L2H12, L2H13, L2H14, L3H1, L4H1, L5H1, and L6H1, including those described in PCT Publication No. WO2005 / 047331 or PCT Application No. PCT / US2004 / 37242 and U.S. Patent Publication No. 2005 / 112694, which are incorporated herein by reference in their entireties;

[0157] Interleukin 1-receptor 1 ("IL1-R1")-specific antibodies, peptibodies, and related proteins, including but not limited to those described in U.S. Patent Publication No. 2004 / 097712, which is incorporated herein by reference in its entirety, particularly with respect to IL1-R1-specific binding proteins, monoclonal antibodies, including but not limited to those set forth in the following publications: 15CA, 26F5, 27F2, 24E12, and 10H7, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the following publications:

[0158] Each of the following publications is individually and specifically incorporated herein by reference in its entirety as if it were disclosed in the following publications, particularly those with sequences described in the following publications, particularly in relation to Ang2-specific antibodies and peptibodies, etc.: L1(N), L1(N)WT, L1(N)1K WT, 2xL1(N), 2xL1(N)WT, Con4(N), Con4(N)1K WT, 2xCon4(N)1K, L1C, L1C 1K, 2xL1C, Con4C, Con4C 1K, 2xCon4C 1K, Con4-L1(N), Con4-L1C, TN-12-9(N), C17(N), TN8-8(N), TN8-14(N), Con1(N), including, but not limited to, those described in PCT Publication No. WO03 / 057134 and U.S. Patent Publication No. 2003 / 0229023, which are incorporated by reference in their entireties, and in part with respect to Ang2-specific antibodies and peptibodies, etc., particularly Ab526, Ab528, Ab531, Ab533, Ab534, and various permutations thereof, as described in the following publications: Ang2-specific antibodies, peptibodies, and related proteins, including anti-Ang2 antibodies and formulations such as those described in PCT Publication No. WO 2003 / 030833, wherein Ab5, Ab536, Ab537, Ab540, Ab543, Ab544, Ab545, Ab546, A551, Ab553, Ab555, Ab558, Ab559, Ab565, AbF1, AbFD, AbFE, AbFJ, AbFK, AbG1D4, AbGC1E8, AbH1C12, AblA1, AblF, AblK, AblP, and AblP are described in PCT Publication No. WO 2003 / 030833, which is incorporated herein by reference in its entirety;

[0159] With respect to NGF-specific antibodies and related proteins, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the following publications, specifically including, but not limited to, the NGF-specific antibodies 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11 set forth in the following publications, NGF-specific antibodies, peptibodies, and related proteins, including, but not limited to, those described in U.S. Patent 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:

[0160] Humanized and fully human antibodies, including, but not limited to, humanized and fully human monoclonal antibodies, particularly human CD22-specific IgG antibodies, such as, for example, a dimer of a 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), including, but not limited to, humanized and fully human antibodies, particularly human CD22-specific antibodies, peptibodies, and related proteins, such as those described in U.S. Pat. No. 5,789,554, which is incorporated herein by reference in its entirety with respect to CD22-specific antibodies and related proteins;

[0161] IGF-1 specific antibodies L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11, L12H12, L1H13, L1H14, L1H15, L1H16, L1H17, L1H18, L1H19, L1H20, L1H21, L1H22, L1H23, L1H24, L1H25, L1H26, L1H27, L1H28, L1H29, L1H30, L1H31, L1H32, L1H33, L1H34, L1H35, L1H36, L1H37, L1H38, L1H39, L1H40, L1H41, L1H42, L1H 3H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21, L22H22, L2 3H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L30H30, L31H31, L32H32, L33 IGF-1 receptor-specific antibodies, peptibodies, and related proteins, including, but not limited to, H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1 R-binding fragments and derivatives thereof, such as those described in PCT Publication No. WO 06 / 069202, which is incorporated by reference in its entirety with respect to IGF-1 receptor-specific antibodies and related proteins;

[0162] Also among the non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the present invention are each and every one of those described below. (i) U.S. Patent Publication Nos. 2006 / 0040358 (published February 23, 2006), 2005 / 0008642 (published January 13, 2005), and 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, as described in the following patent publications: (ii) antibodies, including but not limited to, 2F8, A12, and IMC-A12, described in PCT Publication Nos. WO 06 / 138729 (published December 28, 2006) and WO 05 / 016970 (published February 24, 2005), and Lu et al. (2004), J. Biol. Chem. 279:2856-2865; (iii) PCT Publication Nos. WO07 / 012614 (published February 1, 2007), WO07 / 000328 (published January 4, 2007), WO06 / 013472 (published February 9, 2006), WO05 / 058967 (published June 30, 2005), and WO03 / 059951 (published July 24, 2003); (iv) antibodies described in the following patent publications, including, but not limited to, antibody 7C10, chimeric antibody C7C10, antibody h7C10, antibody 7H2M, chimeric antibody *7C10, antibody GM607, humanized antibody 7C10 version 1, humanized antibody 7C10 version 2, humanized antibody 7C10 version 3, and antibody 7H2HM: U.S. Patent Publication No. 2005 / 0084906 (published April 21, 2005); (v) antibodies described in U.S. Patent Publication Nos. 2005 / 0249728 (published November 10, 2005), 2005 / 0186203 (published August 25, 2005), 2004 / 0265307 (published December 30, 2004), and 2003 / 0235582 (published December 25, 2003), including, but not limited to, EM164, resurfaced EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2, and huEM164 v1.3; and Maloney et al. (2003), Cancer Res. 63:5073-5083; (vi) U.S. Patent No. 7,037,498 (issued May 2, 2006); U.S. Patent Publication Nos. 2005 / 0244408 (published November 30, 2005) and 2004 / 0086503 (published May 6, 2004); and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073, such as antibody CP-751,871, including, but not limited to, each of the antibodies produced by hybridomas having ATCC Accession Nos. PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, and antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3, as set forth in (vii) U.S. Patent Publication Nos. 2005 / 0136063 (published June 23, 2005) and 2004 / 0018191 (published January 29, 2004), including, but not limited to, antibody 19D12, described in the following patent publications: U.S. Patent Publication Nos. 2005 / 0136063 (published June 23, 2005) and 2004 / 0018191 (published January 29, 2004); and antibodies comprising a heavy chain encoded by the polynucleotide of plasmid 15H12 / 19D12 HCA(γ4), deposited with the ATCC under accession number PTA-5214, and a light chain encoded by the polynucleotide of plasmid 15H12 / 19D12 LCF(κ), deposited with the ATCC under accession number PTA-5220; (viii) U.S. Patent Publication No. 2004 / 0202655 (published October 14, 2004), including, but not limited to, the antibodies PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2, PINT-12A3, PINT-12A4, and PINT-12A5, which are each and every incorporated by reference herein in their entireties with respect to the foregoing antibodies, peptibodies, and related proteins that specifically target the IGF-1 receptor;

[0163] 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 antibodies set forth in the following patent publications, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the aforementioned publications: 16H (in which the light chain variable region sequence and heavy chain variable region sequence are SEQ ID NO: 1 and SEQ ID NO: 7, respectively), 5D (in which the light chain variable region sequence and heavy chain variable region sequence are SEQ ID NO: 1 and SEQ ID NO: 7, respectively), and and 15H (having light chain variable region sequences SEQ ID NO:4 and SEQ ID NO:12, respectively). In all of the foregoing respects, those disclosed in U.S. Patent Publication No. 2008 / 0166352 and PCT Publication No. WO07 / 011941, which are incorporated by reference herein in their entireties, with respect to such antibodies and related proteins, including, but not limited to, 2H (having light chain variable region sequences SEQ ID NO:5 and SEQ ID NO:13, respectively), 2H (having light chain variable region sequences SEQ ID NO:6 and SEQ ID NO:14, respectively), 2H (having light chain variable region sequences SEQ ID NO:7 and SEQ ID NO:10, respectively), 43H (having light chain variable region sequences SEQ ID NO:8 and SEQ ID NO:11, respectively), 41H (having light chain variable region sequences SEQ ID NO:9 and SEQ ID NO:11, respectively), and 15H (having light chain variable region sequences SEQ ID NO:12 and SEQ ID NO:13, respectively).

[0164] In particular, antibodies, particularly IL-15 specific antibodies, peptibodies, and related proteins, such as humanized monoclonal antibodies, such as those disclosed in U.S. Patent Publication Nos. 2003 / 0138421, 2003 / 023586, and 2004 / 0071702, and U.S. Patent No. 7,153,507, each of which is incorporated herein by reference in its entirety for IL-15 specific antibodies and related proteins, including, but not limited to, HuMax IL-15 antibodies such as 146B7 and related proteins, including peptibodies;

[0165] In particular, 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, e.g., the antibodies designated 1118, 1118*, 1119, 1121, and 1121*, U.S. Patent Publication No. 2005 / 0004353, which is incorporated herein by reference in its entirety with respect to IFNγ-specific antibodies. 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 each individually and specifically incorporated herein by reference in their entirety as disclosed in the aforementioned publications and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115. Additionally, the descriptions of the properties of these antibodies provided in the aforementioned publications are also incorporated herein by reference in their entirety. As disclosed in the aforementioned publications, 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. Specific antibodies contemplated include antibody 1119, as disclosed in the aforementioned U.S. publication, having the complete heavy chain of SEQ ID NO: 17 as disclosed in the aforementioned U.S. publication, and the complete light chain of SEQ ID NO: 18 as disclosed in the aforementioned U.S. publication;

[0166] TALL-1 specific antibodies, peptibodies, and related proteins, such as those described in U.S. Patent Publication Nos. 2003 / 0195156 and 2006 / 0135431, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the following publications, and other TALL specific binding proteins, each of which is incorporated herein by reference in its entirety with respect to TALL-1 binding proteins, particularly the molecules in Tables 4 and 5B:

[0167] Parathyroid hormone ("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, particularly with respect to proteins that partially bind PTH;

[0168] thrombopoietin receptor ("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, particularly with respect to proteins that partially bind to TPO-R;

[0169] 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), described in U.S. Patent Publication No. 2005 / 0118643 and PCT Publication No. WO2005 / 017107, huL2G7, described in U.S. Patent No. 7,220,410, and OA-5d5, described in U.S. Patent Nos. 5,686,292 and 6,468,529 and PCT Publication No. WO96 / 38557, each of which is incorporated by reference in its entirety, particularly with respect to proteins that partially bind HGF;

[0170] 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, particularly with respect to proteins that partially bind TRAIL-R2;

[0171] Activin A-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Publication No. 2009 / 0234106, which is incorporated herein by reference in its entirety, particularly with respect to proteins that partially bind activin A;

[0172] TGF-β specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent No. 6,803,453 and U.S. Patent Publication No. 2007 / 0110747, each of which is incorporated herein by reference in its entirety, particularly with respect to proteins that partially bind TGF-β;

[0173] Amyloid β protein-specific antibodies, peptibodies, related proteins, and the like, including, but not limited to, those described in PCT Publication No. WO2006 / 081171, which is incorporated herein by reference in its entirety, particularly with respect to proteins that partially bind to amyloid β protein. One contemplated antibody is an antibody having a heavy chain variable region comprising SEQ ID NO:8 and a light chain variable region having SEQ ID NO:6, as disclosed in the aforementioned publication;

[0174] c-Kit-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Publication No. 2007 / 0253951, which is incorporated herein by reference in its entirety, particularly with respect to proteins that bind, in part, to c-Kit and / or other stem cell factor receptors;

[0175] OX40L-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Publication No. 2006 / 0002929, which is incorporated herein by reference in its entirety, particularly with respect to proteins that bind, in part, to OX40L and / or other ligands of the OX40 receptor;

[0176] Activase® (alteplase, tPA), Aranesp® (darbepoetin alfa), Epogen® (epoetin alfa, or erythropoietin), GLP-1, Avonex® (interferon beta-1a), Bexxar® (tositumomab, an anti-CD22 monoclonal antibody), Betaseron® (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 inhibitor), 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), Benlysta™ (lymphostat B, belimumab, anti-BlyS)mAb), Metalyse® (tenecteplase, t-PA analog), Mircera® (methoxypolyethylene glycol-epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP870), Soliris™ (eculizumab), pexelizumab (anti-complement C5), Numax® (MEDI-524), Lucentis® (ranibizumab), Panorex® (17-1A, edrecolomab), 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, pegylated G-CSF, pegylated hu-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 domain of both IL-1 receptor components (type I receptor and receptor accessory protein)), VEGF trap (the domain of VEGFR1 fused to IgG1 Fc), Zenapax® (daclizumab), Zenapax® (daclizumab, anti-IL-2Rα mAb), Zevalin® (ibritumomab tiuxetan), Zetia® (ezetimibe), Orencia® (atacicept, TACI-Ig), anti-CD80 monoclonal antibody (galiximab), anti-CD23 mAb (lumiliximab), BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist), CNTO148 (golimumab, anti-TNFα mAb), HGS-ETR1 (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-CD30mAb (MDX-060), MDX-1333 (anti-IFNAR), anti-CD38 mAb (HuMax CD38), anti-CD40L mAb, anti-Cripto mAb, anti-CTGF idiopathic pulmonary fibrosis stage 1 fibrogen (FG-3019), anti-CTLA4 mAb, anti-eotaxin-1 mAb (CAT-213), anti-FGF8 mAb, anti-ganglioside GD2 mAb, anti-ganglioside GM2 mAb, anti-GDF-8 human mAb (MYO-029), anti-GM-CSF receptor mAb (CAM-3001), anti-HepC mAb (HuMax HepC), anti-IFNα mAb (MEDI-545, MDX-1103), anti-IGF1R mAb, anti-IGF-1R mAb (HuMax-Inflam), anti-IL12 mAb (ABT-874), anti-IL12 / IL23 mAb (CNTO1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-integrin receptor mAb (MDX-018, CNTO95), anti-IP10 ulcerative colitis mAb (MDX-1100), anti-LLY antibody, BMS-66513, anti-mannose receptor / hCGβ mAb (MDX-1307), anti-mesothelin dsFv-PE38 conjugate (CAT-5001), anti-PD1 mAb (MDX-1106(ONO-4538)), anti-PDGFRα antibody (IMC-3G3), anti-TGFβ Other exemplary proteins include mAb (GC-1008), anti-TRAIL receptor-2 human mAb (HGS-ETR2), anti-TWEAK mAb, anti-VEGFR / Flt-1 mAb, anti-ZP3 mAb (HuMax-ZP3), NVS antibody no. 1, and NVS antibody no. 2.

[0177] Sclerostin antibodies may also be included, such as, but not limited to, romosozumab, brosozumab, or BPS804 (Novartis). Further therapeutic agents may be included, such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX, or XGEVA. Further, see, for example, U.S. Patent No. 8,030,547, U.S. Patent Publication No. 2013 / 0064825, WO 2008 / 057457, WO 2008 / 057458, WO 2008 / 057459, WO 2008 / 063382, WO 2008 / 133647, WO 2009 / 100297, WO 2009 / 100318, WO 2011 / 037791, WO 2011 / 053759, WO 2011 / 053783, WO 2008 / 125623, WO 2011 / 072263, WO 2009 Monoclonal antibodies (IgG) that bind to human proprotein convertase subtilisin / kexin type 9 (PCSK9) may also be included in the device, as described in US Pat. Nos. 2012 / 055783, 2012 / 0544438, 2010 / 029513, 2011 / 111007, 2010 / 077854, 2012 / 088313, 2012 / 101251, 2012 / 101252, 2012 / 101253, 2012 / 109530, and 2001 / 031007.

[0178] Talimogene laherparepvec or other oncolytic HSVs for the treatment of melanoma or other cancers can also be included. Examples of oncolytic HSVs include, but are not limited to, talimogene laherparepvec (U.S. Patent Nos. 7,223,593 and 7,537,924), OncoVEXGALV / CD (U.S. Patent No. 7,981,669), OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143), G207, 1716, NV1020, NV12023, NV1034, and NV1042 (Vargehes et al. (2002), Cancer Gene Ther., 9(12):967-978).

[0179] TIMPs are also included. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) and are important in many natural processes. TIMP-3 is expressed by various cells or / and present in the extracellular matrix, inhibits all major cartilage-degrading metalloproteinases, and may play a role in many connective tissue degrading diseases, including rheumatoid arthritis and osteoarthritis, as well as in cancer and cardiovascular conditions. The amino acid sequence of TIMP-3 and the nucleic acid sequence of DNA encoding TIMP-3 are disclosed in U.S. Patent No. 6,562,596, issued May 13, 2003, the disclosure of which is incorporated herein by reference. Descriptions of TIMP mutations can be found in U.S. Patent Publication No. 2014 / 0274874 and PCT Publication No. WO2014 / 152012.

[0180] Also included are antagonistic antibodies of the human calcitonin gene-related peptide (CGRP) receptor, and bispecific antibody molecules that target the CGRP receptor and other headache targets. Further information regarding these molecules can be found in PCT Application No. WO2010 / 075238.

[0181] Additionally, bispecific T cell-inducing antibodies (BiTe), such as brinotumomab, can be used in the device. Alternatively, APJ macromolecular agonists, such as apelin or analogs thereof, can be included in the device. Information related to such molecules can be found in PCT Publication No. WO2014 / 099984.

[0182] In certain embodiments, the agent comprises a therapeutically effective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptor antibody. Examples of anti-TSLP antibodies that may be used in such embodiments include, but are not limited to, those described in U.S. Patent Nos. 7,982,016 and 8,232,372, and U.S. Patent Publication No. 2009 / 0186022. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in U.S. Patent No. 8,101,182. In a particularly preferred embodiment, the agent comprises a therapeutically effective amount of the anti-TSLP antibody designated A5 in U.S. Patent No. 7,982,016.

[0183] It should be noted that the configurations of the various embodiments of the drug delivery devices and drug delivery systems described herein are exemplary only. While only a few embodiments of the drug delivery devices and drug delivery systems are detailed in this disclosure, those skilled in the art who review this disclosure will readily understand that many modifications (e.g., changes in the size, dimensions, structure, shape, and proportions of various elements, parameter values, mounting arrangements, material use, orientation, etc.) are possible without significantly departing from the novel teachings and advantages of the subject matter of the present disclosure. For example, any combination of one or more of the sensors and / or controllable elements described herein may be incorporated into one or more of the drug delivery systems and drug delivery devices described herein. Also, the order or sequence of any process or method steps described herein may be changed or rearranged in any combination according to alternative embodiments. Furthermore, any combination of one or more of the elements of one or more of the claims set forth at the end of this disclosure is possible.

[0184] While the preceding text sets forth detailed descriptions of different embodiments of the present invention, it should be understood that the legal scope of the present invention is defined by the terms of the claims set forth at the end of this patent. The detailed description is intended to be merely exemplary and does not describe every possible embodiment of the present invention, as describing every possible embodiment would be impractical, if not impossible. Numerous alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent that still falls within the scope of the claims defining the present invention.

[0185] It should be understood that unless a term is expressly defined in this patent using the sentence "As used herein, the term '______' is herein defined to mean ..." or similar language, no term is intended to limit the meaning of the term, either explicitly or by implication, beyond its plain or conventional meaning, and such term should not be construed as limiting in scope based on any statement made in any part of this patent (other than the terminology in the claims). To the extent that any term recited in a claim at the end of this patent is referenced herein in a manner consistent with a single meaning, that is done for purposes of clarity so as not to confuse the reader, and such claim term is not intended to be limited by implication or otherwise limited to a single meaning. Finally, unless a claim element is defined by reciting the word "means" and a function without any recitation of structure, the scope of any claim element is not intended to be construed based on application of 35 U.S.C. § 112, paragraph 6.

Claims

1. In the system, 1. An on-body drug delivery device comprising: Storage section, a stopper movably disposed within the reservoir; a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for reception within a patient; a plurality of sensors including a first sensor configured to detect contact with the patient's skin and a second sensor configured to monitor movement of a stopper within the reservoir; a first communication module; a first controller coupled to the plurality of sensors and the first communication module, determining whether the on-body drug delivery device is in contact with the patient's skin using the first sensor; determining at least one of a condition or operating state of the on-body drug delivery device using one or more of the plurality of sensors; a first control device configured to control the first communication module to transmit a communication indicative of at least one of the condition or the operating state of the on-body drug delivery device when the on-body drug delivery device is in contact with the patient's skin; an external computing device, a second communication module configured to receive the communication from the first communication module; display device, memory, and a second control device coupled to the display device, the memory, and the second communication module, an external computing device comprising a second control unit configured to, after processing the communication received from the on-body drug delivery device according to information stored in the memory of the external computing device, control the display device to display at least one of instructional or informational prompts regarding use of the on-body drug delivery device to deliver a drug to the patient based on the communication from the first communication module, at least after delivering the drug to the patient using the on-body drug delivery device; At least one of the instructional or informational prompts includes an amount of the drug to be delivered to the patient determined based at least in part on information from the second sensor configured to monitor movement of a stopper within the reservoir.

2. The first control device uses one or more of the plurality of sensors to determining the temperature or temperature history of the on-body drug delivery device; determining an orientation of the on-body drug delivery device; determining whether the patient or user has activated the on-body drug delivery device; determining whether delivery of the drug from the reservoir to the patient is complete; and The first control device controls the first communication module, a communication representative of at least one of the temperature or the temperature history of the on-body drug delivery device; a communication representative of contact between the on-body drug delivery device and the skin of the patient; a communication indicative of an orientation of the on-body drug delivery device; a communication indicating that the on-body drug delivery device has been activated by the patient or user; a communication indicating completion of delivery of medication from the reservoir to the patient; and further configured to transmit at least one of: The second control device comparing the temperature or the temperature history of the on-body drug delivery device with information stored in the memory of the external computing device to determine whether the temperature or the temperature history of the on-body drug delivery device is acceptable, and in response to determining that the on-body drug delivery device has an acceptable temperature or acceptable temperature history, controlling the display device to display an instructional prompt instructing a user or patient to place the on-body drug delivery device on or against the patient's skin; in response to determining that the on-body drug delivery device is in contact with the patient's skin, controlling the display device to display an instructional prompt instructing the patient or user to properly orient the on-body drug delivery device relative to the patient's skin; responsive to determining that the orientation of the on-body drug delivery device is acceptable, controlling the display device to display an instructional prompt instructing the patient or user to activate the on-body drug delivery device; in response to determining that the on-body drug delivery device has been activated by the patient or user, controlling the display device to display an instructional prompt instructing the patient or user to wait for completion of delivery of medication from the reservoir to the patient; in response to determining that the delivery of the medication from the reservoir to the patient is completed, controlling the display device to display an instructional prompt instructing the patient or user to discard the on-body drug delivery device; The system of claim 1 , configured to perform at least one of the following:

3. 3. The system of claim 1, wherein the plurality of sensors comprises a temperature sensor configured to detect a temperature of the medication in the reservoir, and the first sensor includes at least one of a pressure sensor, a capacitance sensor, a resistance sensor, or an inductance sensor.

4. The system of claim 3 , wherein the first sensor is mounted on a needle shield disposed around the distal end of the delivery cannula.

5. 5. The system of claim 1, wherein the reservoir contains a drug selected from the group consisting of a TNF inhibitor, an antibody against calcitonin gene-related peptide receptor, a granulocyte colony-stimulating factor, an erythropoiesis-stimulating agent, an apelin receptor agonist, an antibody against proprotein convertase subtilisin / kexin type 9 (PCSK9), and a tissue inhibitor of metalloproteinase.

6. 1. A method of operating a system comprising an on-body drug delivery device and an external computing device, wherein the on-body drug delivery device comprises a reservoir, a stopper movably disposed within the reservoir, a plurality of sensors including a first sensor configured to detect contact with a patient's skin and a second sensor configured to monitor movement of the stopper within the reservoir, and a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end received within the patient, the external computing device comprising a memory, the method comprising: a processor of the on-body drug delivery device determining whether the on-body drug delivery device is in contact with the skin of the patient based on an output from the first sensor; a processor of the on-body drug delivery device determining at least one of a condition or an operating state of the drug delivery device; if a determination is made that the on-body drug delivery device is in contact with the skin of the patient, a processor of the on-body drug delivery device transmitting a communication from the on-body drug delivery device representing at least one of the condition or the operating state; a processor of the external computing device receiving the communication from the on-body drug delivery device at the external computing device; a processor of the external computing device processing the communication received from the on-body drug delivery device according to information stored in the memory of the external computing device; a processor of the external computing device, based on the communication received from the on-body drug delivery device, displaying at least one of an instructional prompt or an informational prompt regarding use of the on-body drug delivery device to deliver a drug to the patient at least after delivering the drug to the patient using the on-body drug delivery device; wherein at least one of the instructional or informational prompts includes an amount of the drug to be delivered to the patient determined based at least in part on information from the second sensor configured to monitor movement of a stopper within the reservoir.

7. 7. The method of claim 6, further comprising the processor of the external computing device displaying at least one of the instruction prompt or information prompt according to (i) the communication received from the on-body drug delivery device and (ii) the information stored in the memory of the external computing device.

8. The determining of the at least one of the condition or the operating state of the on-body drug delivery device using one or more of the plurality of sensors includes: a processor of the on-body drug delivery device determining a temperature or temperature history of the on-body drug delivery device; a processor of the on-body drug delivery device determining an orientation of the on-body drug delivery device; a processor of the on-body drug delivery device determining whether the on-body drug delivery device has been activated by the patient or user; a processor of the on-body drug delivery device determining whether delivery of the drug from the reservoir to the patient is complete; 8. The method of claim 6 or 7, comprising at least one of:

9. a processor of the external computing device comparing the temperature or the temperature history of the on-body drug delivery device with the information stored in the memory of the external computing device to determine whether the temperature or the temperature history of the on-body drug delivery device is acceptable; 9. The method of claim 8, further comprising: in response to a processor of the external computing device determining that the on-body drug delivery device has an acceptable temperature or acceptable temperature history, displaying an instruction prompt instructing the patient or user to place the on-body drug delivery device on or in contact with the patient's skin.

10. 10. The method of claim 8 or 9, wherein the processor of the external computing device, in response to determining that the on-body drug delivery device is in contact with the patient's skin, displays an instruction prompt instructing the patient or user to correctly orient the on-body drug delivery device relative to the patient's skin.

11. a processor of the external computing device comparing the orientation of the on-body drug delivery device with the information stored in the memory of the external computing device to determine whether the orientation of the on-body drug delivery device relative to the patient's skin is acceptable; 11. The method of claim 8, further comprising: displaying an instruction prompt to the patient or user to activate the on-body drug delivery device in response to the processor of the external computing device determining that the orientation of the on-body drug delivery device is acceptable.

12. 12. The method of claim 8, further comprising the processor of the external computing device, in response to determining that the on-body drug delivery device has been activated by the patient or user, displaying an instruction prompt instructing the patient or user to wait for completion of delivery of the medication from the reservoir to the patient.

13. 13. The method of claim 8, further comprising the processor of the external computing device, in response to determining that the delivery of the medication from the reservoir to the patient is complete, displaying an instruction prompt instructing the patient or user to discard the on-body drug delivery device.

14. The method of any one of claims 6 to 13, wherein the reservoir contains a drug, and the drug is selected from the group consisting of a TNF inhibitor, an antibody against calcitonin gene-related peptide receptor, a granulocyte colony-stimulating factor, an erythropoiesis-stimulating agent, an apelin receptor agonist, an antibody against proprotein convertase subtilisin / kexin type 9 (PCSK9), and a tissue inhibitor of metalloproteinase.

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