System for verifying the accuracy of serially connected drug modules in a combinatorial drug delivery device

Abstract

In one aspect, the present invention provides a system for verifying the accuracy of a plurality of serially connected drug modules of a combinatorial drug delivery device, wherein each drug module comprises a drug reservoir for receiving a liquid drug, and the system comprises: a machine-readable code located on each drug module; application software on a user's mobile device, wherein the application software is configured to read the machine-readable code from a captured digital image of the serially connected drug modules, and the application software is configured to generate an activation code based on the machine-readable code and the sequence of the machine-readable codes; a transmitter on the user's mobile device configured to transmit the activation code; and a flow controller on the drug delivery device optionally operable to an active state to allow the flow of a liquid drug from the drug delivery device. A control unit on a drug delivery device having a computing processing unit and a receiver, wherein the computing processing unit has a memory associated with an authentication code stored thereon, the receiver is configured to receive an activation code transmitted by a transmitter, the computing processing unit is configured to compare the activation code with the authentication code, and if the authentication code matches the activation code, the computing processing unit is configured to cause the flow controller to operate in a used state to allow the flow of liquid drug from the drug delivery device.

Description

Technology Field

[0001] Combinational drug delivery devices and systems are illustrated and described below: U.S. Provisional Patent Application No. 62 / 670,266 (filed May 11, 2018); PCT Application No. PCT / US2019 / 031727 (filed May 10, 2019); PCT Application No. PCT / 2019 / 031762 (filed May 10, 2019); and PCT Application No. PCT / US2019 / 031791 (filed May 10, 2019). All of the aforementioned patents were filed by the same assignee as the present invention. As indicated in the aforementioned patent applications, drug modules of different liquid drugs may be provided in various combinations to provide different (individualized) drug combinations. The drug modules may be nested in series or in parallel on a tray or other base structure, i.e., connected. Alternatively, drug modules may be connected directly to each other in series (vertically and / or horizontally). U.S. Provisional Patent Application No. 62 / 670,266, PCT Application No. PCT / US2019 / 031727, PCT Application No. PCT / 2019 / 031762, and PCT Application No. PCT / US2019 / 031791 are incorporated herein by reference in their entirety. Background Technology

[0002] A combined system connected in series does not require separate tray components to achieve fluid connections, and thus has an advantage over nested designs in that it is more efficient in components and consequently in the supply chain.

[0003] In nested systems, the tray design can 'store' information regarding the precise configuration of modules through its unique design and tray layout. For example, the tray can provide a configuration (e.g., mechanical cooperation features, such as "lock and key" features) that ensures only the correct drug modules can be inserted into the tray's nest and that the correct drug modules are arranged in the correct order. This serves as a safety check when manufacturing drug modules for use. In contrast, serially connected systems do not have tray-type elements and therefore lack the capability for safety checks based on them.

[0004] Since it is impossible to prevent errors when tray-based mechanical means are connected in series, it is desirable to prevent the occurrence of medication errors by implementing other means to detect configuration errors in a serially connected system.

[0005] In one aspect, the present invention provides a system for verifying the accuracy of a plurality of serially connected drug modules of a combinatorial drug delivery device, wherein each drug module comprises a drug reservoir for receiving a liquid drug, and the system comprises: a machine-readable code located on each drug module; application software on a user's mobile device, wherein the application software is configured to read the machine-readable code from a captured digital image of the serially connected drug modules, and the application software is configured to generate an activation code based on the machine-readable code and the sequence of the machine-readable codes; a transmitter on the user's mobile device configured to transmit the activation code; and a flow controller on the drug delivery device, wherein the flow controller is optionally operable in an active state to allow the flow of a liquid drug from the drug delivery device. A control unit on a drug delivery device having a computing processing unit and a receiver, wherein the computing processing unit has a memory associated with an authentication code stored thereon, the receiver is configured to receive an activation code transmitted by a transmitter, the computing processing unit is configured to compare the activation code with the authentication code, and if the authentication code matches the activation code, the computing processing unit is configured to cause the flow controller to operate in a used state to allow the flow of liquid drug from the drug delivery device.

[0006] In a further aspect, the present invention provides a system for verifying the accuracy of a plurality of serially connected drug modules of a combinatorial drug delivery device, wherein each drug module comprises a drug reservoir for receiving a liquid drug, and the system comprises: a machine-readable code located on each drug module; application software on a user's mobile device, wherein the application software is configured to read the machine-readable code from a captured digital image of the serially connected drug modules, the application software is configured to generate an activation code based on the machine-readable code and the sequence of the machine-readable codes, the application software includes an application programming interface to call a remote server to obtain an authentication code associated with the drug delivery device, the application software is configured to compare the activation code and the authentication code, and if the authentication code and the activation code match, the application software generates an approval message; a transmitter on the user's mobile device configured to transmit the approval message; a flow controller on the drug delivery device, wherein the flow controller is optionally operable in an active state to allow the flow of a liquid drug from the drug delivery device; A control unit on a drug delivery device having a computing processing unit and a receiver, wherein the receiver is configured to receive an acknowledgment message transmitted by a transmitter, and based on the acknowledgment message, the computing processing unit is configured to cause the operation of a flow controller to a working state to allow the flow of liquid drug from the drug delivery device.

[0007] In a further aspect, the present invention provides a system for verifying the accuracy of a plurality of serially connected drug modules of a combinational drug delivery device, wherein each drug module comprises a drug reservoir for receiving a liquid drug, and the system comprises: a drug module machine-readable code located on each drug module; application software on a user's mobile device, wherein the application software is configured to read the drug module machine-readable code from a captured digital image of the serially connected drug modules and to read an auxiliary machine-readable code representing an authentication code, wherein the application software is configured to generate an activation code based on the sequence of the drug module machine-readable code and the drug module machine-readable code, wherein the application software is configured to compare the activation code and the authentication code, and if the authentication code and the activation code match, the application software generates an approval message; a transmitter on the user's mobile device configured to transmit the approval message; and a flow controller on the drug delivery device, wherein the flow controller is optionally operable in an active state to allow the flow of a liquid drug from the drug delivery device. A control unit on a drug delivery device having a computing processing unit and a receiver, wherein the receiver is configured to receive an acknowledgment message transmitted by a transmitter, and based on the acknowledgment message, the computing processing unit is configured to cause the operation of a flow controller to a working state to allow the flow of liquid drug from the drug delivery device.

[0008] Still in an additional aspect, the present invention provides a system for verifying the accuracy of a plurality of serially connected drug modules of a combinatorial drug delivery device, wherein each drug module comprises a drug reservoir for receiving a liquid drug, and the system comprises: a machine-readable code located on each drug module; application software on a user's mobile device, wherein the application software is configured to read the machine-readable code from a captured digital image of the serially connected drug modules, and the application software is configured to generate an activation code based on the machine-readable code and the sequence of the machine-readable codes; a transmitter on the user's mobile device configured to transmit the activation code; a remote server on which an authentication code associated with the drug delivery device is stored, wherein the remote server is configured to receive the activation code transmitted by the transmitter, and the remote server is configured to compare the activation code and the authentication code, and if the authentication code matches the activation code, the remote server is configured to generate an approval message and transmit the approval message, and upon receiving the approval message, the transmitter on the user's mobile device transmits the approval message; a flow controller on the drug delivery device, wherein the flow controller is optionally operable in an active state to allow the flow of liquid drug from the drug delivery device; A control unit on a drug delivery device having a computing processing unit and a receiver, wherein the receiver is configured to receive an acknowledgment message transmitted by a transmitter on a user's mobile device, and based on the acknowledgment message, the computing processing unit is configured to cause the operation of a flow controller to be in use to allow the flow of liquid drug from the drug delivery device.

[0009] These and other features of the present invention will be more easily understood through the detailed description and study of the attached drawings. Brief explanation of the drawing

[0010] FIGS. 1-15 illustrates various features of a system formed according to the present invention. Specific details for implementing the invention

[0011] Referring to FIG. 1, a system (10) available for verifying the accuracy of a plurality of serially connected drug modules (12) of a combinational drug delivery device (14) is illustrated. Each drug module (12) includes a drug reservoir (16) that contains a liquid drug (18). The drug reservoir (16) may be defined by a part of the drug module (12) or by a component inserted into the drug module (12), such as a vial. The combinational drug delivery device (14) may be formed according to any embodiment disclosed in any U.S. Provisional Patent Application No. 62 / 670,266, PCT Application No. PCT / US2019 / 031727, PCT Application No. PCT / 2019 / 031762, and PCT Application No. PCT / US2019 / 031791, including any aspect thereof. For the purpose of illustration, exemplary features of the combinational drug delivery device (14) are described herein. As recognized by those skilled in the art, the present invention is available by any combinational drug delivery device disclosed in any of the aforementioned patent applications and by any of its elements (e.g., system (10), drug module (12), method of connecting the drug module (12), flow controller (34), etc.).

[0012] As illustrated in FIG. 2, drug modules (12) are connected in series to define a single flow path to a drug delivery device (14) through a series of drug modules (12), through which liquid drug (18) can be drawn from each drug module (12). As illustrated in FIG. 2, inlet and outlet tubes (20, 22) may be provided in each drug module (12) to allow liquid drug (18) to be drawn continuously from each drug module (12). As illustrated in FIG. 3, inlet and outlet tubes (20, 22) may be formed continuously between drug reservoirs (16) so as to provide a length of tube that functions as both an outlet of one drug reservoir (16) and an inlet of the next drug reservoir (16). FIG. 2 illustrates six drug modules (12) (12A-12F). As understood by those skilled in the art, any amount of drug modules (12) may be used. A vent (13) can be provided at the end of the flow path (in the final drug module).

[0013] It should be noted that one or more bypass drug modules (12BY) may be required in series to accommodate one place but not to contain any liquid drug. As shown in FIG. 2a, the bypass drug module (12BY) may have a bypass tube (24) extending from its inlet to its outlet to enable flow through it without a drug reservoir. Alternatively, as shown in FIG. 3, the bypass tube (24) may be provided instead of one of the drug modules (12) to connect two components of the drug delivery device (14), such as two of the drug modules (12) or one of the drug modules (12) and the controller housing described below.

[0014] The liquid drugs (18) contained in the drug modules (12) may vary in type and concentration. The liquid drugs (18) in some modules (12) may be diluents without pharmaceutically or biologically active agents. The drug modules (12) may contain one or more solid components, which may be reconstituted by the flow of diluents within them to form liquid drugs. The ability of serially connected drug modules (12) to contain various drug types and concentrations enables the drug delivery device (14) to become a combinational drug delivery device (14) that provides a mixture of various liquid drugs. Liquid drugs (18) intended for a specific combination for a patient are prescribed by a physician. The present invention provides for the inclusion of specific drug modules (12) in the drug delivery device (14), as well as for the accuracy of the order of the drug modules (12). The order of the drug modules (14) may be significant and may possibly affect the efficacy of the finally produced combination.

[0015] The drug delivery device (14) preferably comprises a controller housing (26) connected to a drug module (12) connected in series. An outlet tube (22) of the first drug module (12A) (closest to the controller housing (26)) communicates with an inlet (28) formed in the controller housing (26) through which liquid drug (18) can flow from the drug module (12). A delivery tube (30) extends from the inlet (28) to deliver the liquid drug (18) through the controller housing (26) to the outlet (32). The tube or carrier is fixed to the outlet (32) so that the liquid drug (18) can be directed to a storage device (e.g., IV bag, injector) or a drug delivery device connected to a patient (e.g., butterfly needle).

[0016] A flow controller (34) is provided in the controller housing (26) and selectively controls the flow through the transfer tube (30). In one embodiment, the flow controller (34) may include an operable negative pressure source (36), such as a pump, provided in the controller housing (26) to draw liquid drug (18) from the inlet (28) through the transfer tube (30) (which may be discontinuous) and discharge the liquid drug (18) through the outlet (32). In a stationary state, the negative pressure source (36) does not generate negative pressure and therefore does not draw liquid drug (18). In a further embodiment, the flow controller (34) may include one or more adjustable valves (38), such as ball valves, provided in the controller housing (26), configured to selectively control the flow through the transfer tube (30), particularly configured to selectively adjust between an open and a closed state. By using the valve (38), a negative pressure source outside the controller housing (26) can be used, which is configured to apply negative pressure to the outlet (32) to draw out the liquid drug (18).

[0017] A control unit (40) including a computing processing unit (CPU) (42) may be provided in a controller housing (26). It is preferable that the flow controller (34) be electrically powered so as to be controlled by the CPU (42). For example, an electric motor or actuator having a switch configured to be controlled by the CPU (42) may be provided. The operation of the motor may cause the negative pressure source (30) to be activated (e.g., the pump is turned on), while the operation of the actuator may adjust the valve(s) (38) to an open state (e.g., the valve stem is rotated to an open state). The switch may be adjusted to an off position by the CPU (42) to turn off the motor or close the valve(s).

[0018] The drug modules (12) are expected to be connected in series when ready for use. Therefore, the drug modules (12) need to be assembled by the user or on behalf of the user. As a safety guarantee device, as shown in FIG. 4, to ensure that the drug modules (12) are properly contained and in the correct order in the drug delivery device (14), each drug module (12) could have a machine-readable code (44) corresponding to the liquid drug (18) applied thereto when the liquid drug (18) is loaded. The machine-readable code (44) is preferably permanently attached to the drug modules (12) to avoid separation of the machine-readable code (44) from the drug modules (12) during storage or transport (e.g., strong adhesive sticker, adhesive, etching, etc.). The machine-readable code (44) can be any format, including barcodes and QR codes. The machine-readable code (44) is arranged to specify the type of drug and possibly the concentration or strength of the drug. Liquid drugs (18) can be loaded into the drug module (12) at a manufacturing facility or pharmacy, and at the same time, a machine-readable code (44) can be attached. Care must be taken to apply the correct machine-readable code (44) to the drug module (12).

[0019] The specific liquid drug (18) (type, concentration) will be specified in the prescription. The drug module (12) will be manufactured to accommodate the specific liquid drug (18), and the number of drug modules (12) to be used will be at least equal to the number of drug components specified in the prescription. The drug module (12) may be delivered to the user or a location associated with the user as a kit for assembly together with the controller housing (26). Instructions regarding the assembly of the drug module (12) will be provided, including the order of the drug module (12), for example, a first location (closest to the controller housing (26)), a second location, etc.

[0020] When the drug module (12) is assembled with the controller housing (26) as a drug delivery device (14), the drug delivery device (14) must be prepared for use. To prepare the device, a digital image of a series of all drug modules (12) connected in series is captured by a digital camera or a device (46) equipped with a digital camera (smartphone, tablet, laptop, mobile phone), specifically including the machine-readable code (44) of all drug modules (12). The digital image can be captured by the device (46) under the control of the user (45) or through automated means, for example, the digital camera is arranged at the facility manufacturing the drug delivery device (14).

[0021] Preferably, the device (46) includes application software (48) configured to read a machine-readable code (44) to generate an activation code based on the contents and sequence of the machine-readable code (44). For example, the device (46) may be a mobile device, such as a smartphone, that includes a digital camera and has access to the application software (48). Any graphical user interface (GUI) is provided on the device (46) to enable an interface with the user. As understood by those skilled in the art, barcode and QR code recognition and reading software is known in the art and is available by the application software (48). The application software (48) may be stored as a set of instructions in a non-transient memory associated with the device (46). All or part of the application software (48) may be located outside the device (46) and may be called via a network as needed, as described below.

[0022] Alternatively, the device (46) may be connected to an auxiliary device or computer processing unit (47), which may be a remote server associated with application software (48). Here, digital images captured by the device (46) are transmitted to the auxiliary device or CPU (47) and read by the application software (48). The device (46) may be connected to the auxiliary device or CPU (47) via any network (49) (wired, wireless, internet, local area network (LAN), wide area network (WAN)). The auxiliary device or CPU (47) generates an activation code based on the reading of machine-readable code (44) from the captured images. The auxiliary device or CPU (47) may be associated with a non-transient memory (50) in which all or part of the application software (48) may be stored as an instruction set.

[0023] As illustrated in FIG. 4a, a combined alphanumeric data string CDS can be generated using the machine-readable code (44) of each drug module (12), and the individual data string DS of each drug module (12) are assembled together in the order of the drug modules (12) to generate an activation code.

[0024] The activation code may be used to compare with the authentication code to determine its accuracy. In one embodiment, the authentication code may be stored in a non-transient memory (41) associated with the CPU (42) in the controller housing (26). Application software (48) may be configured to transmit the generated activation code to the CPU (42) (e.g., via a transmitter (T1) on the device (46) and a receiver (R1) on the controller housing (26), and the CPU (42) performs a comparison to determine if they match. If they match, the CPU (42) can activate the flow controller (34) to deliver the liquid drug (18).

[0025] The transmitter (T1) and receiver (R1) may each be formed as a receiver and a transmitter. Any wireless network protocol, including but not limited to protocols taken from 802.11-compatible networks, Bluetooth networks, Cellular Digital Packet Data (CDPD) networks, High-Speed ​​Circuit Switched Data (HSCSD) networks, Packet Data Cellular (PDC-P) networks, General Packet Radio Service (GPRS) networks, 1x Radio Transmission Technology (1xRTT) networks, IrDA networks, Multichannel Multipoint Distribution Service (MMDS) networks, Local Multipoint Distribution Service (LMDS) networks, and Global Interoperability for Microwave Access (WiMAX) networks, may be used for wireless communication.

[0026] In an alternative embodiment, the application software (48) may be configured to call an auxiliary device or CPU (47) on the device (46), for example, via a network (49) using an application programming interface (API), to receive an authentication code from it. Alternatively, the device (46) may obtain an authentication code from another source, for example, from a machine-readable code provided in the drug module (12). Then, the application software (48) may compare the activation code on the device (46) with the authentication code. If they match, the application software (48) may generate an approval message, which is transmitted to the CPU (42), for example, using a transmitter (T1). The expected approval message may be stored in memory (41). If they match, the CPU (42) may operate the flow controller (34) to deliver the liquid drug (18). This embodiment eliminates the need for the authentication code to be stored in the controller housing (26).

[0027] In a further embodiment, the application software (48) may transmit an activation code to an auxiliary device or CPU (47) for comparison with an authentication code, for example, via a network (49) on the device (46). If they match, the auxiliary device or CPU (47) transmits an approval message to the application software (48), for example, via the network (49), and then the application software (48) transmits the approval message to the CPU (42), for example, using a transmitter (T1). The expected approval message may be stored in memory (41). If they match, the CPU (42) may operate the flow controller (34) to deliver the liquid drug (18). This embodiment eliminates the need for the authentication code to be stored in the controller housing (26).

[0028] The flow controller (34) may be provided to have a storage (i.e., non-use) state, for example, with one or more of the adjustable valves (38) in a closed position so as not to allow flow to the outlet (32) through the delivery tube (30). Additionally, or alternatively, in the storage state, the negative pressure source (36) is in a stopped state. When the activation code and the authentication code match, as described above, the CPU (42) may operate the flow controller (34) to cause the flow controller (34) to enter the use state. When the flow controller (34) is in the use state, delivery of the liquid drug (18) from the drug delivery device (14) can be achieved. In particular, one or more of the adjustable valves (38) may be adjusted to an open state to allow flow to the outlet (32) through the delivery tube (30). Additionally, the negative pressure source (36) can be operated, or alternatively, placed in an active state waiting to be operated (e.g., by a switch on the controller housing (26) and / or via application software (48) using the device (46).

[0029] As understood by a technician in the relevant technical field, the system (10) allows for various functionalities. For example, a user account may be established and stored in memory (50), for example, in the form of a database. Access to the user account may be granted by various entities, including a prescribing physician (P), a dispensing pharmacy (Ph), and / or manufacturing location(s) (M) that manufacture one or more components of the drug delivery device (14). If the user account is accessible via the network (49), the details of the prescription may be queried and / or updated as needed. Subsequently, this information may be used to select the liquid drug (18) used in the drug delivery device (14). The user (45) may access his / her account via the network (49) using a device (46), for example, a mobile device, and may rely on a GUI to access details as needed.

[0030] In the case of a drug delivery device (14) configured such that the receiver (R1) is also a transmitter, details of the drug administered by the drug delivery device (14) (time, date, confirmation of completion) can be transmitted via the network (49) to the relevant user account. A medical professional, such as a prescribing physician (P), can access this data to verify compliance with the administration regimen.

[0031] The system (10) also enables the provision of patient medical information available for determining a prescription. For example, information based on patient treatment can be uploaded to a user account and relied upon to determine a prescription. Results from testing various physiological parameters and / or biomarkers can be uploaded. This enables review by a prescribing physician (P) from a remote location, for example, and subsequent inquiry of the prescription by a pharmacy (Ph) and / or manufacturing facility (M) for prescription fulfillment. The kit of manufactured drug modules (12) and controller housings (26) can be delivered to the site of use for assembly by a user or an assistant. It is possible to deliver the kit to a facility that assembles the kit for the patient, such as a pharmacy (Ph), a doctor's office, etc.

[0032] Referring to FIG. 6-15, non-limiting examples of process flows of application software (48), including GUIs that can be presented on the device (46) at different stages of the process, are presented. Referring to FIG. 6, the available process flow (100) is shown starting from a homepage or splash screen (102). The process flow (100) continues to a package scanning subroutine having an initial screen (104) and an image reader or capture screen (106) (wherein a camera on the device (46) may be started) to read a machine-readable code on the packaging associated with the kit of the pre-assembled drug module (12). This subroutine allows verification of the authentication code associated with the packaged kit of the drug module (12). This subroutine may time out to return to the initial screen (104) to enable restart.

[0033] After the package scanning subroutine is successfully completed, an intermediate screen (108) is provided to allow the user to indicate the completion of the drug module (12) assembly. When the user indicates completion (e.g., by pressing button (110)), the drug module scanning subroutine is initiated to an image reader or capture screen (112), causing the camera of the device (46) to read or capture all machine-readable codes of the assembled drug module (12) in sequence. The application software (48) is configured to generate an activation code based on the machine-readable codes (including their contents and sequence). When an activation code is generated, the scan is considered successful (step (114)), as shown in the process flow (100). If the activation code is not successfully generated, for example, if the scan times out without capturing the appropriate data (as shown in screen (117)), the process flow of step (116) returns to the initial screen (104) and repeats the package scanning subroutine.

[0034] The application software (48) compares the generated activation code with the obtained authentication code to determine if a match exists. If so, it is determined that the drug modules (12) are in the appropriate and proper order, as indicated in step (118). This can start a screen (120) containing a list of drugs, dosages, and their order.

[0035] If there is no match between the activation code and the authentication code, the basis for the lack of match may be determined by the application software (48) and indicated as an error. For example, the application software (48) may determine that the appropriate drug module (12) exists but is in an incorrect order, as indicated in the error message (122). Alternatively, the application software (48) may determine that one or more of the drug modules (12) are incorrect, as indicated in the error message (124). Additionally, the application software (48) may determine that one or more of the drug modules (12) are missing and provide an incomplete order, as indicated in the error message (126). It is possible to return to the initial screen (104) and restart.

[0036] In one embodiment, any combinational drug delivery device disclosed herein may deliver two or more drugs for the benefit of a patient suffering from any wide range of diseases or conditions, e.g., cancer, autoimmune disorders, inflammatory disorders, cardiovascular diseases, or fibrotic disorders. In one embodiment, one or more of the drug modules (12) may contain a single drug. In one embodiment, one or more of the drug modules (12) may contain two or more co-formulated drugs. In one embodiment, one or more of the drug modules (12) may contain a drug in solid form (e.g., tablet, capsule, powder, lyophilized, spray-dried), which may be reconstituted by the flow of a diluent therein to form a liquid drug.

[0037] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are immune checkpoint inhibitors. In specific embodiments, immune checkpoint inhibitors are programmed death-1 ("PD-1") pathway inhibitors, cytotoxic T-lymphocyte-associated antigen 4 ("CTLA-4") antagonists, lymphocyte activation gene-3 ("LAG3") antagonists, CD80 antagonists, CD86 antagonists, T cell immunoglobulin and mucin domain ("Tim-3") antagonists, T cell immune receptor ("TIGIT") antagonists having Ig and ITIM domains, CD20 antagonists, CD96 antagonists, indoleamine 2,3-deoxygenase ("IDO1") antagonists, interferon gene stimulating factor ("STING") antagonists, GARP antagonists, CD40 antagonists, adenosine A2A receptor ("A2aR") antagonists, CEACAM1 (CD66a) antagonists, CEA antagonists, CD47 antagonists, receptor-associated immunoglobulin domains It is a protein-containing ("PVRIG") antagonist, tryptophan 2,3-deoxygenase ("TDO") antagonist, V-domain Ig inhibitor of T cell activation ("VISTA") antagonist, or killer-cell immunoglobulin-like receptor ("KIR") antagonist.

[0038] In one embodiment, the PD-1 pathway inhibitor is an anti-PD-1 antibody or its antigen-binding fragment. In a specific embodiment, the anti-PD-1 antibody is pembrolizumab (KEYTRUDA; MK-3475), pidilizumab (CT-011), nivolumab (OPDIVO; BMS-936558), PDR001, MEDI0680 (AMP-514), TSR-042, REGN2810, JS001, AMP-224 (GSK-2661380), PF-06801591, BGB-A317, BI 754091, or SHR-1210.

[0039] In one embodiment, the PD-1 pathway inhibitor is an anti-PD-L1 antibody or its antigen-binding fragment. In a specific embodiment, the anti-PD-L1 antibody is atezolizumab (TECENTRIQ; RG7446; MPDL3280A; RO5541267), durvalumab (MEDI4736), BMS-936559, avelumab (Bavencio), LY3300054, CX-072 (Proclaim-CX-072), FAZ053, KN035, or MDX-1105.

[0040] In one embodiment, the PD-1 pathway inhibitor is a small molecule drug. In a specific embodiment, the PD-1 pathway inhibitor is CA-170. In another embodiment, the PD-1 pathway inhibitor is a cell-based therapy. In one embodiment, the cell-based therapy is a MiHA-loaded PD-L1 / L2-silenced dendritic cell vaccine. In another embodiment, the cell-based therapy is anti-programmed apoptosis protein 1 antibody-expressing pluripotent killer T lymphocytes, auto-PD-1-targeted chimeric convertible receptor-modified T lymphocytes, or PD-1 knockout auto-T lymphocytes.

[0041] In one embodiment, the PD-1 pathway inhibitor is an anti-PD-L2 antibody or its antigen-binding fragment. In another embodiment, the anti-PD-L2 antibody is rHIgM12B7.

[0042] In one embodiment, the PD-1 pathway inhibitor is a soluble PD-1 polypeptide. In a specific embodiment, the soluble PD-1 polypeptide is a fusion polypeptide. In some embodiments, the soluble PD-1 polypeptide comprises a ligand-binding fragment of the PD-1 extracellular domain. In another embodiment, the soluble PD-1 polypeptide comprises a ligand-binding fragment of the PD-1 extracellular domain. In yet another embodiment, the soluble PD-1 polypeptide further comprises an Fc domain.

[0043] In one embodiment, the immune checkpoint inhibitor is a CTLA-4 antagonist. In certain embodiments, the CTLA-4 antagonist is an anti-CTLA-4 antibody or its antigen-binding fragment. In some embodiments, the anti-CTLA-4 antibody is ipilimumab (YERVOY), tremelimumab (ticilimumab; CP-675,206), AGEN-1884, or ATOR-1015. In one embodiment, any combination drug delivery device disclosed herein comprises a CTLA-4 antagonist, e.g., ipilimumab (YERVOY), and a PD-1 pathway inhibitor, e.g., nivolumab (Opdivo) or pembrolizumab (Keytruda).

[0044] In one embodiment, the immune checkpoint inhibitor is an antagonist of LAG3. In a specific embodiment, the LAG3 antagonist is an anti-LAG3 antibody or its antigen-binding fragment. In a specific embodiment, the anti-LAG3 antibody is relatlimab (BMS-986016), MK-4280 (28G-10), REGN3767, GSK2831781, IMP731 (H5L7BW), BAP050, IMP-701 (LAG-5250), IMP321, TSR-033, LAG525, BI 754111, or FS-118. In one embodiment, any combination drug delivery device disclosed herein comprises a LAG3 antagonist, e.g., relatlimab or MK-4280, and a PD-1 pathway inhibitor, e.g., nivolumab (Opdivo) or pembrolizumab (Keytruda). In one embodiment, any combination drug delivery device disclosed herein comprises a LAG3 antagonist, e.g. relatlimab or MK-4280, and a CTLA-4 antagonist, e.g. ipilimumab (Yervoy). In one embodiment, any combination drug delivery device disclosed herein comprises a LAG3 antagonist, e.g. relatlimab or MK-4280, a CTLA-4 antagonist, e.g. ipilimumab (Yervoy), and a PD-1 pathway inhibitor, e.g. nivolumab (Opdivo) or pembrolizumab (Keytruda).

[0045] In one embodiment, the immune checkpoint inhibitor is a KIR antagonist. In certain embodiments, the KIR antagonist is an anti-KIR antibody or its antigen-binding fragment. In some embodiments, the anti-KIR antibody is ririlumab (1-7F9, BMS-986015, IPH 2101) or IPH4102.

[0046] In one embodiment, the immune checkpoint inhibitor is a TIGIT antagonist. In one embodiment, the TIGIT antagonist is an anti-TIGIT antibody or its antigen-binding fragment. In a specific embodiment, the anti-TIGIT antibody is BMS-986207, AB 154, COM902 (CGEN-15137), or OMP-313M32.

[0047] In one embodiment, the immune checkpoint inhibitor is a Tim-3 antagonist. In certain embodiments, the Tim-3 antagonist is an anti-Tim-3 antibody or its antigen-binding fragment. In some embodiments, the anti-Tim-3 antibody is TSR-022 or LY3321367.

[0048] In one embodiment, the immune checkpoint inhibitor is an IDO1 antagonist. In another embodiment, the IDO1 antagonist is indoxymod (NLG8189; 1-methyl- D -TRP), epacadostat (INCB-024360, INCB-24360), KHK2455, PF-06840003, naboximod (RG6078, GDC-0919, NLG919), BMS-986205 (F001287), or pyrrolidine-2,5-dione derivatives.

[0049] In one embodiment, the immune checkpoint inhibitor is a STING antagonist. In a specific embodiment, the STING antagonist is a 2' or 3'-mono-fluoro-substituted cyclic-di-nucleotide; a 2'3'-di-fluoro-substituted mixed-linked 2',5'-3',5' cyclic-di-nucleotide; a 2'-fluoro-substituted bis-3',5' cyclic-di-nucleotide; a 2',2"-diF-Rp,Rp,bis-3',5' cyclic-di-nucleotide; or a fluorinated cyclic-di-nucleotide.

[0050] In one embodiment, the immune checkpoint inhibitor is a CD20 antagonist. In some embodiments, the CD20 antagonist is an anti-CD20 antibody or its antigen-binding fragment. In one embodiment, the anti-CD20 antibody is rituximab (RITUXAN; IDEC-102; IDEC-C2B8), ABP 798, ofatumumab, or obinutuzumab.

[0051] In one embodiment, the immune checkpoint inhibitor is a CD80 antagonist. In a specific embodiment, the CD80 antagonist is an anti-CD80 antibody or its antigen-binding fragment. In one embodiment, the anti-CD80 antibody is galiximab or AV 1142742.

[0052] In one embodiment, the immune checkpoint inhibitor is a GARP antagonist. In some embodiments, the GARP antagonist is an anti-GARP antibody or its antigen-binding fragment. In a specific embodiment, the anti-GARP antibody is ARGX-115.

[0053] In one embodiment, the immune checkpoint inhibitor is a CD40 antagonist. In a specific embodiment, the CD40 antagonist is an anti-CD40 antibody against its antigen-binding fragment. In some embodiments, the anti-CD40 antibody is BMS3h-56, rucatumumab (HCD122 and CHIR-12.12), CHIR-5.9, or darsetuzumab (huS2C6, PRO 64553, RG 3636, SGN 14, SGN-40). In another embodiment, the CD40 antagonist is a soluble CD40 ligand (CD40-L). In one embodiment, the soluble CD40 ligand is a fusion polypeptide. In one embodiment, the soluble CD40 ligand is CD40-L / FC2 or monomeric CD40-L.

[0054] In one embodiment, the immune checkpoint inhibitor is an A2aR antagonist. In some embodiments, the A2aR antagonist is a small molecule. In certain embodiments, the A2aR antagonist is CPI-444, PBF-509, istradefilin (KW-6002), preradenant (SCH420814), tozadenant (SYN115), bipadenant (BIIB014), HTL-1071, ST1535, SCH412348, SCH442416, SCH58261, ZM241385, or AZD4635.

[0055] In one embodiment, the immune checkpoint inhibitor is a CEACAM1 antagonist. In some embodiments, the CEACAM1 antagonist is an anti-CEACAM1 antibody or its antigen-binding fragment. In one embodiment, the anti-CEACAM1 antibody is CM-24 (MK-6018).

[0056] In one embodiment, the immune checkpoint inhibitor is a CEA antagonist. In one embodiment, the CEA antagonist is an anti-CEA antibody or its antigen-binding fragment. In a specific embodiment, the anti-CEA antibody is sergutuzumab amunareukin (RG7813, RO-6895882) or RG7802 (RO6958688).

[0057] In one embodiment, the immune checkpoint inhibitor is a CD47 antagonist. In some embodiments, the CD47 antagonist is an anti-CD47 antibody or its antigen-binding fragment. In certain embodiments, the anti-CD47 antibody is HuF9-G4, CC-90002, TTI-621, ALX148, NI-1701, NI-1801, SRF231, or Effi-DEM.

[0058] In one embodiment, the immune checkpoint inhibitor is a PVRIG antagonist. In a specific embodiment, the PVRIG antagonist is an anti-PVRIG antibody or its antigen-binding fragment. In one embodiment, the anti-PVRIG antibody is COM701 (CGEN-15029).

[0059] In one embodiment, the immune checkpoint inhibitor is a TDO antagonist. In one embodiment, the TDO antagonist is a 4-(indole-3-yl)-pyrazole derivative, a 3-indole-substituted derivative, or a 3-(indole-3-yl)-pyridine derivative. In another embodiment, the immune checkpoint inhibitor is a dual IDO and TDO antagonist. In one embodiment, the dual IDO and TDO antagonist is a small molecule.

[0060] In one embodiment, the immune checkpoint inhibitor is a VISTA antagonist. In some embodiments, the VISTA antagonist is CA-170 or JNJ-61610588.

[0061] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are immune checkpoint enhancers or stimulators.

[0062] In one embodiment, the immune checkpoint enhancer or stimulator is a CD28 agonist, a 4-1BB agonist, an OX40 agonist, a CD27 agonist, a CD80 agonist, a CD86 agonist, a CD40 agonist, an ICOS agonist, a CD70 agonist, or a GITR agonist.

[0063] In one embodiment, the immune checkpoint enhancer or stimulator is an OX40 agonist. In certain embodiments, the OX40 agonist is an anti-OX40 antibody or its antigen-binding fragment. In some embodiments, the anti-OX40 antibody is tabolixizumab (MEDI-0562), pogalizumab (MOXR0916, RG7888), GSK3174998, ATOR-1015, MEDI-6383, MEDI-6469, BMS 986178, PF-04518600, or RG7888 (MOXR0916). In another embodiment, the OX40 agonist is a cell-based therapy. In certain embodiments, the OX40 agonist is a GINAKIT cell (iC9-GD2-CD28-OX40-expressing T lymphocyte).

[0064] In one embodiment, the immune checkpoint enhancer or stimulator is a CD40 agonist. In some embodiments, the CD40 agonist is an anti-CD40 antibody or its antigen-binding fragment. In one embodiment, the anti-CD40 antibody is ADC-1013 (JNJ-64457107), RG7876 (RO-7009789), HuCD40-M2, APX005M (EPI-0050), or Chi Lob 7 / 4. In another embodiment, the CD40 agonist is a soluble CD40 ligand (CD40-L). In one embodiment, the soluble CD40 ligand is a fusion polypeptide. In a specific embodiment, the soluble CD40 ligand is a trimer CD40-L (AVREND®).

[0065] In one embodiment, the immune checkpoint enhancer or stimulator is a GITR agonist. In certain embodiments, the GITR agonist is an anti-GITR antibody or its antigen-binding fragment. In one embodiment, the anti-GITR antibody is BMS-986156, TRX518, GWN323, INCAGN01876, or MEDI1873. In one embodiment, the GITR agonist is a soluble GITR ligand (GITRL). In some embodiments, the soluble GITR ligand is a fusion polypeptide. In another embodiment, the GITR agonist is a cell-based therapy. In one embodiment, the cell-based therapy is an anti-CTLA4 mAb RNA / GITRL RNA-transfected autologous dendritic cell vaccine or a GITRL RNA-transfected autologous dendritic cell vaccine.

[0066] In one embodiment, the immune checkpoint enhancer or stimulator is a 4-1BB agonist. In some embodiments, the 4-1BB agonist is an anti-4-1BB antibody or its antigen-binding fragment. In one embodiment, the anti-4-1BB antibody is urelumab or PF-05082566.

[0067] In one embodiment, the immune checkpoint enhancer or stimulator is a CD80 agonist or a CD86 agonist. In some embodiments, the CD80 agonist or CD86 agonist is a soluble CD80 or CD86 ligand (CTLA-4). In certain embodiments, the soluble CD80 or CD86 ligand is a fusion polypeptide. In one embodiment, the CD80 or CD86 ligand is CTLA4-Ig (CTLA4-IgG4m, RG2077, or RG1046) or abatacept (ORENCIA, BMS-188667). In another embodiment, the CD80 agonist or CD86 agonist is a cell-based therapy. In one embodiment, the cell-based therapy is MGN1601 (allogeneic renal cell carcinoma vaccine).

[0068] In one embodiment, the immune checkpoint enhancer or stimulator is a CD28 agonist. In some embodiments, the CD28 agonist is an anti-CD28 antibody or its antigen-binding fragment. In a specific embodiment, the anti-CD28 antibody is TGN1412.

[0069] In one embodiment, the CD28 agonist is a cell-based therapy. In a specific embodiment, the cell-based therapy comprises JCAR015 (anti-CD19-CD28-zeta modified CAR CD3+ T lymphocytes); CD28CAR / CD137CAR-expressing T lymphocytes; allogeneic CD4+ memory Th1-like T cells / microparticle-conjugated anti-CD3 / anti-CD28; anti-CD19 / CD28 / CD3 zeta CAR gamma retrovirus vector-transduced autologous T lymphocytes KTE-C19; anti-CEA IgCD28TCR-transduced autologous T lymphocytes; anti-EGFRvIII CAR-transduced allogeneic T lymphocytes; autologous CD123CAR-CD28-CD3 zeta-EGFRt-expressing T lymphocytes; autologous CD171-specific CAR-CD28 zeta-4-1-BB-EGFRt-expressing T lymphocytes; Autologous CD19CAR-CD28-CD3Zetta-EGFRt-expressing Tcm-enhanced T cells; autologous PD-1-targeted chimeric conversion receptor-modified T lymphocytes (chimeras with CD28); CD19CAR-CD28-CD3Zetta-EGFRt-expressing Tcm-enhanced T lymphocytes; CD19CAR-CD28-CD3Zetta-EGFRt-expressing Tn / mem-enhanced T lymphocytes; CD19CAR-CD28Zetta-4-1BB-expressing allogeneic T lymphocytes; CD19CAR-CD3Zetta-4-1BB-CD28-expressing autologous T lymphocytes; CD28CAR / CD137CAR-expressing T lymphocytes; CD3 / CD28 co-stimulated vaccine-primed autologous T lymphocytes; or iC9-GD2-CD28-OX40-expressing T lymphocytes.

[0070] In one embodiment, the immune checkpoint enhancer or stimulator is a CD27 agonist. In a specific embodiment, the CD27 agonist is an anti-CD27 antibody or its antigen-binding fragment. In one embodiment, the anti-CD27 antibody is varlilumab (CDX-1127).

[0071] In one embodiment, the immune checkpoint enhancer or stimulator is a CD70 agonist. In some embodiments, the CD70 agonist is an anti-CD70 antibody or its antigen-binding fragment. In one embodiment, the anti-CD70 antibody is ARGX-110.

[0072] In one embodiment, the immune checkpoint enhancer or stimulator is an ICOS agonist. In certain embodiments, the ICOS agonist is an anti-ICOS antibody or its antigen-binding fragment. In some embodiments, the anti-ICOS antibody is BMS986226, MEDI-570, GSK3359609, or JTX-2011. In other embodiments, the ICOS agonist is a soluble ICOS ligand. In some embodiments, the soluble ICOS ligand is a fusion polypeptide. In one embodiment, the soluble ICOS ligand is AMG 750.

[0073] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are an anti-CD73 antibody or its antigen-binding fragment. In a specific embodiment, the anti-CD73 antibody is MEDI9447.

[0074] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are TLR9 agonists. In one embodiment, the TLR9 agonist is agatolimod sodium.

[0075] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are cytokines. In certain embodiments, the cytokine is a chemokine, interferon, interleukin, lymphokine, or a member of the tumor necrosis factor family. In some embodiments, the cytokine is IL-2, IL-15, or interferon-gamma.

[0076] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are TGF-β antagonists. In some embodiments, the TGF-β antagonists are presolimumab (GC-1008); NIS793; IMC-TR1 (LY3022859); ISTH0036; travedersen (AP 12009); recombinant transforming growth factor-beta-2; autoimmune HPV-16 / 18 E6 / E7-specific TGF-beta-resistant T lymphocytes; or TGF-beta-resistant LMP-specific cytotoxic T lymphocytes.

[0077] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are iNOS antagonists. In some embodiments, the iNOS antagonist is N-acetyle-cysteine ​​(NAC), aminoguanidine, L-nitroarginine methyl ester, or S,S-1,4-phenylene-bis(1,2-ethandiyl)bis-isothiourea.

[0078] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are SHP-1 antagonists.

[0079] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are colony-stimulating factor 1 receptor ("CSF1R") antagonists. In certain embodiments, the CSF1R antagonist is an anti-CSF1R antibody or its antigen-binding fragment. In some embodiments, the anti-CSF1R antibody is emactuzumab.

[0080] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are agonists of TNF family members. In some embodiments, the agonists of TNF family members are ATOR 1016, ABBV-621, or adalimumab.

[0081] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are interleukin-2 (IL-2), e.g., aldesleukin. Preferably, IL-2 or conjugated IL-2 (e.g., pegylated), e.g., bempegaldehydesleukin, is modified to selectively activate T-effector cells relative to T-regulatory cells ("T-eff IL-2"). In one embodiment, any combination drug delivery device disclosed herein comprises modified IL-2, e.g., bempegaldehydesleukin, which selectively activates T-effector cells relative to T-regulatory cells, and a PD-1 pathway inhibitor, e.g., nivolumab (Opdivo) or pembrolizumab (Keytruda). In one embodiment, any combination drug delivery device disclosed herein comprises a modified IL-2, e.g., bempegaldehydeleukin, which selectively activates T-effector cells relative to T-regulatory cells, and a LAG3 antagonist, e.g., relatlimab or MK-4280. In one embodiment, any combination drug delivery device disclosed herein comprises a modified IL-2, e.g., bempegaldehydeleukin, which selectively activates T-effector cells relative to T-regulatory cells, and a PD-1 pathway inhibitor, e.g., nivolumab (Opdivo) or pembrolizumab (Keytruda), and a LAG3 antagonist, e.g., relatlimab or MK-4280. In one embodiment, any combination drug delivery device disclosed herein comprises a modified IL-2, e.g., bempegaldehydeleukin, which selectively activates T-effector cells relative to T-regulatory cells, and a CTLA-4 antagonist, e.g., ipilimumab (Yervoy). In one embodiment, any combination drug delivery device disclosed herein comprises a modified IL-2, e.g., bempegaldehydeleukin, which selectively activates T-effector cells relative to T-regulatory cells, a PD-1 pathway inhibitor, e.g., nivolumab (Opdivo) or pembrolizumab (Keytruda), and a CTLA-4 antagonist, e.g., ipilimumab (Yervoy).In one embodiment, any combination drug delivery device disclosed herein comprises a modified IL-2, e.g., bempegaldehydeleukin, which selectively activates T-effector cells relative to T-regulatory cells, a CTLA-4 antagonist, e.g., ipilimumab (Yervoy), and a LAG3 antagonist, e.g., relatlimab or MK-4280. In one embodiment, any combination drug delivery device disclosed herein comprises a modified IL-2, e.g., bempegaldehydeleukin, which selectively activates T-effector cells relative to T-regulatory cells, a PD-1 pathway inhibitor, e.g., nivolumab (Opdivo) or pembrolizumab (Keytruda), a CTLA-4 antagonist, e.g., ipilimumab (Yervoy), and a LAG3 antagonist, e.g., relatlimab or MK-4280.

[0082] In one embodiment, one or more of the drugs of any combination drug delivery device disclosed herein are CD160 (NK1) agonists. In a specific embodiment, the CD160 (NK1) agonist is an anti-CD160 antibody or its antigen-binding fragment. In one embodiment, the anti-CD160 antibody is BY55.

[0083] In one embodiment, one or more of the drug modules (12) may contain a soluble CTLA-4 polypeptide that may be useful for treating, for example, T-cell-mediated autoimmune disorders, such as rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, graft-versus-host disease, and transplant rejection. In one embodiment, the soluble CTLA-4 polypeptide is abatacept (Orencia), velatacept (NULOJIX), RG2077, or RG-1046. In a specific embodiment, one or more of the drug modules (12) of the combinational drug delivery device described herein contain a soluble CTLA-4 polypeptide, for example, abatacept (Orencia), and a Bruton tyrosine kinase inhibitor, for example, branebrutinib. In a specific embodiment, one or more drug modules (12) of the combinational drug delivery device described herein comprise a soluble CTLA-4 polypeptide, e.g., abatacept (Orencia), and a tyrosine kinase-2 inhibitor, e.g., BMS-986165. In a specific embodiment, one or more drug modules (12) of the combinational drug delivery device described herein comprise a soluble CTLA-4 polypeptide, e.g., abatacept (Orencia), and interleukin-2 (IL-2) or "T-reg IL-2" that selectively activates T-regulatory cells relative to T-effector cells, e.g., BMS-986326 and NKTR-358.

Claims

Claim 1 A system for verifying the accuracy of multiple serially connected drug modules of a combinatorial drug delivery device, wherein each drug module includes a drug reservoir for receiving a liquid drug, and the system comprises the following: a machine-readable code located on each drug module; application software on a user's mobile device, wherein the application software is configured to read the machine-readable code from a captured digital image of the serially connected drug modules, and the application software is configured to generate an activation code based on the machine-readable code and the sequence of the machine-readable codes; a transmitter on the user's mobile device configured to transmit the activation code; and a flow controller on the drug delivery device, wherein the flow controller is optionally operable to an active state to allow the flow of a liquid drug from the drug delivery device. A control unit on a drug delivery device having a computing processing unit and a receiver, wherein the computing processing unit has a memory associated with an authentication code stored thereon, the receiver is configured to receive an activation code transmitted by a transmitter, the computing processing unit is configured to compare the activation code with the authentication code, and if the authentication code matches the activation code, the computing processing unit is configured to cause the flow controller to operate in a used state to allow the flow of liquid drug from the drug delivery device. Claim 2 A system according to claim 1, wherein the machine-readable code is selected from one or more of the group consisting of QR codes and barcodes. Claim 3 A system according to claim 1, wherein application software generates a data string for serially connected drug modules based on its respective machine-readable code, and the generated data strings are assembled together based on the order of the serially connected drug modules to generate an alphanumeric data string combined as an activation code. Claim 4 A system according to paragraph 3, wherein each machine-readable code indicates the type of drug contained in the drug reservoir of each drug module. Claim 5 A system according to paragraph 4, wherein each machine-readable code indicates the concentration of a drug contained in the reservoir of each drug module. Claim 6 A system for verifying the accuracy of multiple serially connected drug modules of a combinatorial drug delivery device, wherein each drug module includes a drug reservoir for receiving a liquid drug, and the system comprises the following: a machine-readable code located on each drug module; application software on a user's mobile device, wherein the application software is configured to read the machine-readable code from a captured digital image of the serially connected drug modules, the application software is configured to generate an activation code based on the machine-readable code and the sequence of the machine-readable codes, the application software includes an application programming interface to call a remote server to obtain an authentication code associated with the drug delivery device, the application software is configured to compare the activation code and the authentication code, and if the authentication code and the activation code match, the application software generates an approval message; a transmitter on the user's mobile device configured to transmit the approval message; and a flow controller on the drug delivery device, wherein the flow controller is optionally operable in an active state to allow the flow of liquid drug from the drug delivery device. A control unit on a drug delivery device having a computing processing unit and a receiver, wherein the receiver is configured to receive an acknowledgment message transmitted by a transmitter, and based on the acknowledgment message, the computing processing unit is configured to cause the operation of a flow controller to a working state to allow the flow of liquid drug from the drug delivery device. Claim 7 A system according to paragraph 6 in which the machine-readable code is selected from one or more of the group consisting of QR codes and barcodes. Claim 8 A system according to claim 6, wherein application software generates a data string for serially connected drug modules based on its respective machine-readable code, and the generated data strings are assembled together based on the order of the serially connected drug modules to generate an alphanumeric data string combined as an activation code. Claim 9 A system according to claim 8, wherein each machine-readable code indicates the type of drug contained in the drug reservoir of each drug module. Claim 10 A system according to claim 9, wherein each machine-readable code indicates the concentration of a drug contained in the reservoir of each drug module. Claim 11 A system for verifying the accuracy of multiple serially connected drug modules of a combinatorial drug delivery device, wherein each drug module includes a drug reservoir for receiving liquid drugs, and the system comprises: a drug module machine-readable code located on each drug module; application software on a user's mobile device, wherein the application software is configured to read the drug module machine-readable code from a captured digital image of the serially connected drug modules and to read an auxiliary machine-readable code representing an authentication code, wherein the application software is configured to generate an activation code based on the sequence of the drug module machine-readable code and the drug module machine-readable code, wherein the application software is configured to compare the activation code and the authentication code, and if the authentication code and the activation code match, the application software generates an approval message; a transmitter on the user's mobile device configured to transmit the approval message; and a flow controller on the drug delivery device, wherein the flow controller is optionally operable in an active state to allow the flow of liquid drugs from the drug delivery device. A control unit on a drug delivery device having a computing processing unit and a receiver, wherein the receiver is configured to receive an acknowledgment message transmitted by a transmitter, and based on the acknowledgment message, the computing processing unit is configured to cause the operation of a flow controller to a working state to allow the flow of liquid drug from the drug delivery device. Claim 12 A system according to claim 11 in which the machine-readable code and the auxiliary machine-readable code are selected from one or more of the group consisting of QR codes and barcodes. Claim 13 A system according to claim 11, wherein application software generates a data string for serially connected drug modules based on its respective machine-readable code, and the generated data strings are assembled together based on the order of the serially connected drug modules to generate an alphanumeric data string combined as an activation code. Claim 14 A system according to paragraph 13 in which each machine-readable code indicates the type of drug contained in the drug reservoir of each drug module. Claim 15 A system according to paragraph 14, wherein each machine-readable code indicates the concentration of a drug contained in the reservoir of each drug module. Claim 16 A system for verifying the accuracy of multiple serially connected drug modules of a combinatorial drug delivery device, wherein each drug module includes a drug reservoir for receiving liquid drugs, and the system comprises the following: a machine-readable code located on each drug module; application software on a user's mobile device, wherein the application software is configured to read the machine-readable code from a captured digital image of the serially connected drug modules, and the application software is configured to generate an activation code based on the machine-readable code and the sequence of the machine-readable codes; a transmitter on the user's mobile device configured to transmit the activation code; a remote server on which an authentication code associated with the drug delivery device is stored, wherein the remote server is configured to receive the activation code transmitted by the transmitter, and the remote server is configured to compare the activation code and the authentication code, and if the authentication code matches the activation code, the remote server is configured to generate an approval message and transmit the approval message, and upon receipt of the approval message, the transmitter on the user's mobile device transmits the approval message; a flow controller on the drug delivery device, wherein the flow controller is optionally in a state of use to allow the flow of liquid drugs from the drug delivery device Operable; and a control unit on a drug delivery device having a computing processing unit and a receiver, wherein the receiver is configured to receive an acknowledgment message transmitted by a transmitter on a user's mobile device, and based on the acknowledgment message, the computing processing unit is configured to cause the operation of a flow controller to be in use to allow the flow of liquid drug from the drug delivery device. Claim 17 A system in which, in paragraph 16, the machine-readable code is selected from one or more of the group consisting of QR codes and barcodes. Claim 18 A system according to claim 16, wherein application software generates a data string for serially connected drug modules based on its respective machine-readable code, and the generated data strings are assembled together based on the order of the serially connected drug modules to generate an alphanumeric data string combined as an activation code. Claim 19 A system according to paragraph 18 in which each machine-readable code indicates the type of drug contained in the drug reservoir of each drug module. Claim 20 A system according to paragraph 19, wherein each machine-readable code indicates the concentration of a drug contained in the reservoir of each drug module.

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