Devices and Methods for Delivering Therapeutic Fluids

Abstract

The therapeutic agent delivery system includes a therapeutic agent delivery assembly carried by a housing. The therapeutic agent delivery assembly includes a chamber having a passageway, a therapeutic agent transported in the passageway, and a needle in communication with the passageway. The therapeutic agent delivery assembly is translatable relative to the housing from a stowed configuration to a deployed configuration and from the deployed configuration to a retracted configuration. The system further includes a user input device configured to be actuated by a user, and actuation of the user input device translates the therapeutic agent delivery assembly from the stowed configuration to the deployed configuration. The system further includes a retraction mechanism that translates the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration.

Description

Technical Field

[0001] The present disclosure relates to methods and devices for parenteral / non - oral delivery of therapeutic agents. More specifically, the present disclosure relates to methods and devices for parenteral delivery of highly viscous therapeutic fluids (e.g., protein therapeutics). Background Art

[0002] Protein therapeutic drugs are a class of emerging drug therapies that can provide treatment for a variety of diseases, such as autoimmune diseases, cardiovascular diseases, diabetes, and cancer. A common delivery method for some protein therapeutic drugs (e.g., monoclonal antibodies) is by intravenous infusion, where a large volume of diluted solution is delivered over time. Intravenous infusions typically require the supervision of a doctor or nurse and are performed in a clinical setting. This can be inconvenient for patients, and thus efforts are underway to allow for the home delivery of protein therapeutic drugs. Ideally, protein therapeutic drug formulations can be administered using a syringe for subcutaneous delivery without the need for intravenous administration. Subcutaneous injections are typically performed by non - professionals, such as diabetics injecting insulin.

[0003] Transitioning the delivery of therapeutic protein formulations from intravenous delivery to injection devices such as syringes and pen injectors requires addressing the challenges associated with delivering high - concentration, high - molecular - weight molecules in a simple, reliable, and minimally painful manner for the patient. In this regard, while the volume of an intravenous infusion bag is typically 1 liter, the standard volume range of a syringe is from 0.3 milliliters to 25 milliliters. Thus, depending on the drug, to deliver the same amount of therapeutic protein, the concentration may have to be increased by 40 - fold or more. Moreover, for patient comfort and compliance, injection therapies are moving towards smaller needle diameters and faster delivery times.

[0004] The delivery of protein therapeutics is also challenging due to the high viscosities associated with such therapeutic formulations and the high forces required to drive such formulations through parenteral devices. For a variety of reasons, formulations with an absolute viscosity above 40 - 60 centipoise (cP) may be difficult to deliver through traditional spring - driven auto - injectors. Structurally, the spring used to deliver the pressure force occupies a relatively large amount of space and is fixed in a specific shape, which reduces the design flexibility for the delivery device. Secondly, auto - injectors are typically made of plastic components. However, a large amount of energy must be stored in the spring to reliably deliver a high - viscosity fluid. If not properly designed, this stored energy may cause damage to the plastic components due to creep, which tends to cause the plastic components to undergo permanent deformation under stress. Auto - injectors typically operate by using a spring to push an internal component containing the needle towards the outer edge of the syringe housing. The sound associated with the operation of a spring - based auto - injector may cause patient anxiety, which may reduce future compliance. The pressure - time profile generated by such spring - driven auto - injectors cannot be easily modified, which prevents the user from fine - tuning the pressure to meet their delivery needs.

[0005] There is a desire to provide a method and device by which a therapeutic fluid, particularly a high - viscosity fluid, can be self - administered within a reasonable time and using a limited injection space. These methods and devices can be used to deliver high - concentration proteins, high - viscosity pharmaceutical formulations, or other therapeutic fluids. Summary of the Invention

[0006] According to one embodiment of the present disclosure, a therapeutic agent delivery system includes a housing having a distal portion. The system also includes a therapeutic agent delivery assembly carried by the housing. The therapeutic agent delivery assembly includes a chamber having a passageway, a therapeutic agent transported in the passageway, and a needle in communication with the passageway. The therapeutic agent delivery assembly is translatable relative to the housing from a stowed configuration to a deployed configuration. In the deployed configuration, the needle extends at least partially distally from the distal portion of the housing. The therapeutic agent delivery assembly is also translatable relative to the housing from the deployed configuration to a retracted configuration. In the retracted configuration, the needle is disposed proximally relative to the distal portion of the housing. The system also includes a user input device configured to be actuated by a user, and actuation of the user input device causes the therapeutic agent delivery assembly to translate from the stowed configuration to the deployed configuration. The system also includes a retraction mechanism. The retraction mechanism includes a biasing element that can be reconfigured from a higher energy storage configuration to a lower energy storage configuration. The retraction mechanism also includes a release device coupled to the biasing element. The release device can be actuated to allow the biasing element to be reconfigured from the higher energy storage configuration to the lower energy storage configuration, and the biasing element thereby translates the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration.

[0007] According to another embodiment of the present disclosure, a therapeutic agent delivery system includes a housing having a distal portion. The system further includes a therapeutic agent delivery assembly carried by the housing. The therapeutic agent delivery assembly includes a chamber having a passageway, a therapeutic agent transported in the passageway, and a needle in communication with the passageway. The therapeutic agent delivery assembly is translatable relative to the housing from a stowed configuration to a deployed configuration. In the deployed configuration, the needle extends at least partially distally from the distal portion of the housing. The therapeutic agent delivery assembly is translatable relative to the housing from the deployed configuration to a retracted configuration. In the retracted configuration, the needle is disposed proximally relative to the distal portion of the housing. The system further includes a user input device configured to be actuated by a user. Actuation of the user input device causes the therapeutic agent delivery assembly to translate from the stowed configuration to the deployed configuration. The system further includes an electronics assembly configured to send a retraction signal and a retraction mechanism operatively coupled to the electronics assembly. The retraction mechanism includes a biasing element that can be reconfigured from a higher energy storage configuration to a lower energy storage configuration when the retraction mechanism receives the retraction signal from the electronics assembly. The biasing element thereby translates the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration.

[0008] According to yet another embodiment of the present disclosure, a therapeutic agent delivery system includes a housing having a distal portion. The system further includes a therapeutic agent delivery assembly carried by the housing. The therapeutic agent delivery assembly includes a chamber having a passageway, a therapeutic agent transported in the passageway, and a needle in communication with the passageway. The therapeutic agent delivery assembly is translatable relative to the housing from a stowed configuration to a deployed configuration. In the deployed configuration, the needle extends at least partially distally from the distal portion of the housing. The therapeutic agent delivery assembly is translatable relative to the housing from the deployed configuration to a retracted configuration. In the retracted configuration, the needle is disposed proximally relative to the distal portion of the housing. The system further includes a user input device configured to be actuated by a user, and actuation of the user input device causes the therapeutic agent delivery assembly to translate from the stowed configuration to the deployed configuration. The system further includes a retraction mechanism, and the retraction mechanism includes a biasing element that can be reconfigured from a higher energy storage configuration to a lower energy storage configuration. The retraction mechanism has a locked configuration and an unlocked configuration. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The above and other features and advantages of the present invention and the manner of realizing them will become more apparent and will be better understood by reference to the following description of embodiments of the invention in conjunction with the accompanying drawings, in the atta

[0010] In the drawings:

[0011] Figure 1 is a top perspective view of a therapeutic agent delivery system according to one embodiment of the present disclosure.

[0012] Figure 2 is Figure 1 a partial exploded view of the therapeutic agent delivery system of

[0013] Figure 3 is Figure 1 a longitudinal cross-sectional view of a therapeutic agent delivery system.

[0014] Figure 4 is Figure 1 a top perspective view of a proximal outer housing portion of a housing of a therapeutic agent delivery system.

[0015] Figure 5 is along Figure 4 a longitudinal cross-sectional view of the proximal outer housing portion along line 5-5 in

[0016] Figure 6 is Figure 1 a top perspective view of a proximal inner housing portion of a housing of a therapeutic agent delivery system.

[0017] Figure 7 is Figure 6 a bottom perspective view of the proximal inner housing portion.

[0018] Figure 8 is along Figure 6 a longitudinal cross-sectional view of the proximal inner housing portion along line 8-8 in

[0019] Figure 9 is Figure 1 a top perspective view of a distal housing portion of a housing of a therapeutic agent delivery system.

[0020] Figure 10 is Figure 9 a bottom perspective view of the distal housing portion.

[0021] Figure 11 is Figure 1 a top perspective view of a user input device support of a therapeutic agent delivery system.

[0022] Figure 12 is Figure 1 a top perspective view of a user input device of a therapeutic agent delivery system.

[0023] Figure 13 is Figure 1 a top perspective view of an input driver of a therapeutic agent delivery system.

[0024] Figure 14 is Figure 1 a bottom perspective view of a pressure generating actuator of a therapeutic agent delivery assembly of a therapeutic agent delivery system.

[0025] Figure 15 is Figure 14 a top perspective view of the pressure generating actuator.

[0026] Figure 16 isFigure 14 Partial exploded perspective view of the pressure generating actuator.

[0027] Figure 17 Is along Figure 15 Longitudinal cross-sectional view of the pressure generating actuator along line 17-17 in

[0028] Figure 18 Is Figure 1 Side view of the syringe assembly of the therapeutic agent delivery component of the therapeutic agent delivery system of

[0029] Figure 19 Is along Figure 18 Longitudinal cross-sectional view of the syringe assembly along line 19-19 in

[0030] Figure 20 Is Figure 1 Top perspective view of the retraction cap of the retraction mechanism of the therapeutic agent delivery system of

[0031] Figure 21 Is Figure 1 Top perspective view of the retraction base of the retraction mechanism of the therapeutic agent delivery system of

[0032] Figure 22 Is Figure 21 Bottom perspective view of the retraction base of

[0033] Figure 23 Is Figure 1 Schematic diagram of the electronic component assembly of the therapeutic agent delivery system of

[0034] Figure 24 Is Figure 23 Top perspective view of the electronic component assembly of

[0035] Figure 25 Is Figure 1 Side view of the retraction mechanism of the therapeutic agent delivery system of

[0036] Figure 26 Is in the initial or first configuration of Figure 1 Longitudinal cross-sectional view of the therapeutic agent delivery system of

[0037] Figure 27 Is in the first configuration of Figure 1 Enlarged top perspective view of the proximal portion of the therapeutic agent delivery system of ; several external components are shown in hidden lines to illustrate internal components.

[0038] Figure 28 Is a cross-sectional view of the therapeutic agent delivery system along Figure 27 Line 28-28 in through the input device driver and the reciprocating member of the pressure generating actuator when the user input device is actuated.

[0039] Figure 29 Is Figure 1 An enlarged top perspective view of the therapeutic agent delivery system when the deployment spring is extended and the therapeutic agent delivery assembly is moved distally relative to the housing; several external components are shown in hidden lines to show the internal components.

[0040] Figure 30 Is Figure 1 A partial longitudinal cross-sectional view of the therapeutic agent delivery system when the therapeutic agent delivery assembly is moved to the deployed configuration.

[0041] Figure 31 A longitudinal cross-sectional view of the reciprocating member of the pressure generating actuator rotating relative to the first mixing chamber and the second mixing chamber of the pressure generating actuator and thereby actuating the actuator.

[0042] Figure 32 A longitudinal cross-sectional view of the reciprocating member and the mixing piston of the pressure generating actuator in the deployed configuration.

[0043] Figure 33 Is Figure 1 A longitudinal cross-sectional view of the therapeutic agent delivery system when the syringe piston is moved in the syringe passage to expel the therapeutic agent from the needle.

[0044] Figure 34 Is of the Figure 25 Side view of the retraction mechanism in the initial or first configuration.

[0045] Figure 35 Is of the Figure 25 Top perspective view of the retraction mechanism in the first configuration.

[0046] Figure 36 Is Figure 25 Side view of the retraction mechanism during actuation.

[0047] Figure 37 Is Figure 25 Top perspective view of the retraction mechanism during actuation.

[0048] Figure 38 Is of the Figure 25 Side view of the retraction mechanism in the actuated configuration.

[0049] Figure 39 Is of the Figure 25 Top perspective view of the retraction mechanism in the actuated configuration.

[0050] Figure 40 Is of the Figure 1 Therapeutic agent delivery system with the needle in the retracted configuration, longitudinal cross-sectional view.

[0051] In all of the several views, corresponding reference numerals indicate corresponding parts. The examples set forth herein illustrate exemplary embodiments of the invention, and such examples should not be construed in any way as limiting the scope of the invention. Detailed Description

[0052] The present disclosure relates to systems, devices, and methods for parenteral delivery of therapeutic agents, such as highly viscous therapeutic fluids. Such systems and devices illustratively have a relatively compact profile.

[0053] 1. Drug / Therapeutic Agent

[0054] The systems and devices according to the present disclosure can carry a drug and facilitate delivery of the drug to a subject. The term "drug" refers to one or more therapeutic agents, including but not limited to insulin, insulin analogs (such as lispro insulin or insulin glargine), insulin derivatives, GLP-1 receptor agonists (such as dulaglutide or liraglutide), glucagon, glucagon analogs, glucagon derivatives, gastric inhibitory polypeptide (GIP), GIP analogs, GIP derivatives, combined GIP / GLP-1 agonists (such as tirzepatide), oxyntomodulin analogs, oxyntomodulin derivatives, therapeutic antibodies, and any therapeutic agent capable of being delivered by a device according to the present disclosure. The drug can be formulated with one or more excipients. The devices according to the present disclosure are generally operated by a patient, caregiver, or healthcare professional in the manner described herein to deliver the drug to a subject.

[0055] In certain embodiments, the therapeutic agent is a protein, such as a monoclonal antibody or some other protein useful therapeutically. In some embodiments, the concentration of the protein in the fluid can be from about 75 mg / mL to about 500 mg / mL. In certain embodiments, the concentration of the protein can be about 150 mg / mL, 200 mg / mL, 250 mg / mL, or higher. The drug can also contain a solvent or a non-solvent, such as water, a perfluoroalkane solvent, safflower oil, or benzyl benzoate.

[0056] The drug can be a fluid, more specifically a highly viscous fluid, and can have an absolute viscosity of from about 5 cP to about 1000 cP. In certain embodiments, the highly viscous fluid has an absolute viscosity of at least about 10 cP, 20 cP, 30 cP, 40 cP, 50 cP, 60 cP, or higher.

[0057] 2. Therapeutic Agent Delivery System

[0058] Figures 1-3Illustrated is a therapeutic agent delivery system 10 in accordance with one embodiment of the present disclosure. Illustratively, the therapeutic agent delivery system 10 generally includes the profile of an auto-injector pen, although other profiles may alternatively be used. Generally, the therapeutic agent delivery system 10 includes an elongate housing 12 along a longitudinal axis 14. The housing 12 carries a therapeutic agent delivery assembly 16. The therapeutic agent delivery assembly 16 includes a therapeutic agent 18 (see Figure 3 ) and a needle 20, and the therapeutic agent delivery assembly 16 is translatable relative to the housing 12 from a stowed configuration (as illustratively shown in Figures 1-3 , a configuration in which the needle 20 is fully located within the housing 12) to a deployed configuration (shown elsewhere—e.g., a configuration in which the needle 20 is at least partially exposed at a distal portion 22 of the housing 12 and configured to engage a subject and deliver the therapeutic agent to the subject). A proximal portion 24 of the therapeutic agent delivery system 10 includes a user input device 26 (illustratively, a depressible button) that is actuated to actuate the therapeutic agent delivery assembly 16 (i.e., move the needle 20 from the stowed configuration to the deployed configuration and deliver the therapeutic agent to the user). After actuation, the therapeutic agent delivery assembly 16 is translatable relative to the housing 12 from the deployed configuration to a retracted configuration (shown elsewhere—e.g., a configuration in which the needle 20 is fully located within the therapeutic agent delivery system 10). The therapeutic agent delivery system 10 includes a retraction mechanism 28 that translats the therapeutic agent delivery assembly 16 relative to the housing 12 from the deployed configuration to the retracted configuration. After reaching the retracted configuration, the therapeutic agent delivery assembly 16 is prohibited from translating to the deployed configuration (in other words, the system 10 is “locked”). These aspects, features, and components of the therapeutic agent delivery system 10 are described in more detail below.

[0059] Figure 4 and Figure 5 Illustrated is a proximal outer housing portion 30 of the housing 12. The proximal outer housing portion 30 includes a body 32 having a generally cylindrical shape. The body 32 includes an internal passageway 34 that carries other components of the therapeutic agent delivery system 10 described in more detail below. Adjacent to the internal passageway 34, an inner surface 36 of the proximal outer housing portion 30 includes translation features (illustratively, axially extending ridges 38) that facilitate translation of other components relative to the proximal outer housing portion 30.

[0060] Figures 6-8Shows the proximal inner housing portion 40 of the housing 12. The proximal inner housing portion 40 includes a body 42 having a generally cylindrical shape. The outer surface 44 of the body 42 includes translation features (illustratively, axially extending channels 46) that are coupled to the translation features of the proximal outer housing portion 30 (shown elsewhere - illustratively, axially extending ridges 38) to facilitate translation of the proximal inner housing portion 40 relative to the proximal outer housing portion 30. The body 42 also includes an internal passage 48 that houses other components of the therapeutic agent delivery system 10. Adjacent to the internal passage 48, the inner surface 50 of the proximal inner housing portion 40 includes actuation features (illustratively, two helically extending ramps 51, one of which is shown in Figure 8 ), which selectively engage the therapeutic agent delivery assembly 16 and facilitate its actuation. The inner surface 50 of the proximal inner housing portion 40 has translation features (illustratively, two pairs of axially extending ridges 52, one pair of which is shown in Figure 8 ), which facilitate translation of the therapeutic agent delivery assembly 16 relative to the proximal inner housing portion 40. The inner surface 50 also has a biasing platform (illustratively, a radially inwardly extending flange 54) as described in more detail below, which houses other components and facilitates translation of the therapeutic agent delivery assembly 16 from the deployed configuration to the retracted configuration.

[0061] Figure 9 and 10 Shows the distal housing portion 56 of the housing 12. The distal housing portion 56 includes a body 58 having a generally conical shape with an outwardly flared distal portion 60. The body 58 includes an internal passage 61 that houses the therapeutic agent delivery assembly 16 (shown elsewhere).

[0062] Figure 11 Shows the user input device support 62 of the therapeutic agent delivery system 10. The user input device support 62 is coupled to the proximal outer housing portion 30 (shown elsewhere) at the proximal portion 24 of the therapeutic agent delivery system 10. The user input device support 62 includes a body 64, and the body 64 has coupling features (illustratively, a plurality of snap connectors 66, one of which is shown in Figure 11 ) for coupling to the proximal outer housing portion 30. The body 64 includes an internal passage 68 that receives the user input device 26 (shown elsewhere). Adjacent to the internal passage 68, the inner surface 70 of the user input device support 62 has translation features (illustratively, a plurality of axially extending ridges 72, one of which is shown in Figure 11 ), which facilitate translation of the user input device 26 relative to the user input device support 62. In other embodiments, different arrangements of the user input device support 62 are possible.

[0063] Figure 12 shows the user input device 26 of the therapeutic agent delivery system 10. The user input device 26 includes translation features (illustratively, a plurality of axially extending channels 74, one of which is shown in Figure 12 ), for engaging with the translation features of the user input device support 62 (shown elsewhere - illustratively, a plurality of axially extending ridges 72) to facilitate translation of the user input device 26 relative to the user input device support 62 and the housing 12 (shown elsewhere). Adjacent to the translation features, the user input device 26 includes an exposed portion 76 that the user presses to translate the user input device 26 relative to the user input device support 62 and the housing 12. The user input device 26 also includes actuation features that facilitate actuation of the therapeutic agent delivery assembly 16 (shown elsewhere). Illustratively, the actuation features include two arms 78 disposed opposite the exposed portion 76. Each arm 78 includes an actuation surface (illustratively, a helically extending surface 80). The interaction of the arms 78 with other components of the therapeutic agent delivery system 10 is described in more detail below. In other embodiments, different arrangements of the user input device 26 are possible.

[0064] Figure 13 shows the input driver 82 of the therapeutic agent delivery system 10. The input driver 82 includes actuation features configured to interact with the actuation features of the user input device 26 (shown elsewhere). Illustratively, the actuation features of the input driver 82 include two partial flanges 84 and two openings 86 disposed between the partial flanges 84. Each partial flange 84 includes an actuation surface (illustratively, a rounded corner 88 adjacent to one of the openings 86) that engages one of the actuation surfaces 80 of the user input device 26 to facilitate rotation of the input driver 82 relative to the housing 12 (shown elsewhere) when translating the user input device 26 relative to the housing 12. Opposite the actuation features, the input driver 82 includes detachable coupling features (illustratively, a plurality of rungs 90 or radially outwardly extending L-shaped protrusions 90) that detachably couple the input driver 82 to the therapeutic agent delivery assembly 16 (shown elsewhere). In other embodiments, different arrangements of the input driver 82 are possible.

[0065] Figures 14-17Illustrated is a pressure generating actuator 92 of a therapeutic agent delivery assembly 16. Generally, the pressure generating actuator 92 is actuated by a user input device 26 via an input driver 82 (both shown elsewhere) to facilitate mixing of internally carried chemical reagents, which generates one or more pressurized fluids (e.g., one or more gases). Examples of suitable reagents and generated gases are provided below. As described in more detail below, the pressurized fluid is delivered to and facilitates movement of other components of the therapeutic agent delivery assembly 16.

[0066] The pressure generating actuator 92 includes a first mixing chamber 94 and a second mixing chamber 96, which are illustratively integrally formed with each other. The first mixing chamber 94 and the second mixing chamber 96 externally include translation features (illustratively, two axially extending ridges 98) for translatably coupling to translation features of a proximal inner housing portion 40 (shown elsewhere - illustratively, each axially extending ridge 98 is translatably received by a pair of axially extending ridges 52 of the proximal housing portion 40). Thus, the pressure generating actuator 92 is translatably carried by the proximal inner housing portion 40. At an outlet end portion 100, the mixing chambers 94, 96 include outlet coupling features (illustratively, an external threaded surface 102) for coupling to another component of the therapeutic agent delivery assembly 16. The outlet end portion 148 also includes an actuator outlet 104. The pressurized fluid is discharged from the pressure generating actuator 92 via the outlet 104.

[0067] The mixing chambers 94, 96 internally carry axially stacked actuator springs 108, mixing pistons 110, and a rotatable reciprocator 112. The rotatable reciprocator 112 includes a recess 114, and the recess 114 has detachable coupling features (illustratively, multiple rungs 116 or radially outwardly extending L-shaped protrusions 116) that engage detachable coupling features of the input driver 82 (illustratively, multiple rungs 90). The first mixing chamber 94 and the reciprocator 112 form a helical coupling for movably coupling to each other. Illustratively, the reciprocator 112 includes a helically extending ridge 118, and the first mixing chamber 94 includes a helically extending groove 120 that receives the ridge 118. The reciprocator 112 includes actuation features (illustratively, two radially outwardly extending fingers 122), which, as described in more detail below, engage and are driven by actuation features of the proximal inner housing portion 40 (shown elsewhere - illustratively, two helically extending ramps 51). The reciprocator 112 internally includes a first restraint feature (illustratively, eight radially inwardly extending tabs 124, four of which are shown in Figure 17 ). Illustratively, the reciprocator 112 also includes channels 126 disposed between adjacent tabs 124 (three of which are shown in Figure 17(shown in). The mixing piston 110 includes a second constraint feature structure (illustratively, eight radially outwardly extending tabs 128) that engages a first constraint feature structure of the reciprocating member 112. Initially and as Figure 19 shown, the first constraint feature structure engages the second constraint feature structure (illustratively, the radially inwardly extending tabs 124 of the reciprocating member 112 are angularly aligned and engaged with the radially outwardly extending tabs 128 of the mixing piston 110) to hold the mixing piston 110 in a position between the first mixing chamber 94 and the second mixing chamber 96. The mixing piston 110 thus keeps the reagents in the first mixing chamber 94 and the second mixing chamber 96 separated. Initially, the actuator spring 108 is also compressed against the mixing piston 110 within the second mixing chamber 96. In a subsequent configuration, as described in more detail below, the reciprocating member 112 rotates relative to the first mixing chamber 94 and the second mixing chamber 96 such that the first constraint feature structure disengages from the second constraint feature structure (illustratively, the radially inwardly extending tabs 124 of the reciprocating member 112 are angularly misaligned or angularly offset from the radially outwardly extending tabs 128 of the mixing piston 110, while the channel 126 is angularly aligned with the radially outwardly extending tabs 128 of the mixing piston 110). As a result, the actuator spring 108 extends and moves the mixing piston 110 into the reciprocating member 112 and the first mixing chamber 94, which allows the reagents in the first mixing chamber 94 and the second mixing chamber 96 to mix. The mixing of the reagents produces one or more pressurized fluids (e.g., one or more gases), and the pressurized fluid is delivered to other components of the therapeutic agent delivery assembly 16.

[0068] In some embodiments, the pressure generating actuator 92 has a different structure. For example, suitable pressure generating actuators 92 include those described in the following documents: U.S. Patent No. 9,795,740 entitled "Chemical Power Device and Method for Injecting Highly Viscous Fluids in Particular"; U.S. Patent Application Publication No. US2020 / 0030537 entitled "Method and Apparatus for Delivering Fluids by Chemical Reaction"; International Publication No. WO2019 / 050791 entitled "System for Controlling Gas Generation within a Drug Delivery Device", the disclosures of which are hereby expressly incorporated by reference in their entirety.

[0069] Any suitable one or more chemical reagents can be used to generate one or more pressurized fluids in the pressure generating actuator 92 of the present disclosure. Examples of the generated gases include carbon dioxide gas, nitrogen gas, oxygen gas, chlorine gas, etc. Desirably, the generated gas is inert and non-flammable. The amount of gas required to facilitate the movement of other components of the therapeutic agent delivery assembly 16 may affect the type, amount, and concentration of each reagent used in the pressure generating actuator 92. The reagent can be in a dry form (e.g., powder form, tablet form) and / or in a liquid form.

[0070] In one exemplary embodiment, a bicarbonate (which may be in dry form) reacts with an acid (which may be in liquid form) to produce carbon dioxide gas in the pressure generating actuator 140. Examples of suitable bicarbonates include sodium bicarbonate, potassium bicarbonate, and ammonium bicarbonate. Other ingredients may also be present with the bicarbonate, such as diatomaceous earth. Examples of suitable acids include acetic acid, citric acid, potassium bitartrate, disodium pyrophosphate, and calcium dihydrogen phosphate. In one particular example, the bicarbonate is potassium bicarbonate and the acid is an aqueous solution of citric acid, which can react to produce carbon dioxide gas and a liquid mixture of water and dissolved potassium citrate.

[0071] In some embodiments, other reactions may be used. In one example, a metal carbonate such as copper carbonate or calcium carbonate is thermally decomposed in the pressure generating actuator 92 to produce carbon dioxide gas and the corresponding metal oxide. In another example, 2,2'-azobisisobutyronitrile (AIBN) is heated to produce nitrogen gas in the pressure generating actuator 92. In yet another example, an enzyme (such as yeast) reacts with sugar to produce carbon dioxide gas in the pressure generating actuator 92. Some substances readily sublime, changing from solid to gas. These substances include, but are not limited to, naphthalene and iodine. In yet another example, hydrogen peroxide is decomposed by a catalyst such as an enzyme (e.g., catalase) or manganese dioxide to produce oxygen gas in the pressure generating actuator 92. In yet another example, silver chloride decomposes upon exposure to light to generate gas in the pressure generating actuator 92. Suitable reagents, chemical agents, and reactions are further described in the above-incorporated U.S. Patent No. 9,795,740, U.S. Patent Application Publication No. US2020 / 0030537, and International Patent Application Publication No. WO2019 / 050791.

[0072] As briefly described above and again briefly referring to Figure 2 and 3 , the outlet 104 of the pressure generating actuator 92 may carry one or more absorbent materials 106. Such absorbent materials 106 can absorb excess liquid provided by mixing reagents within the pressure generating actuator 92. Suitable absorbent materials are further described in the above-incorporated U.S. Patent Application Publication No. US 2020 / 0030537.

[0073] Figure 18 and 19The syringe assembly 130 of the therapeutic agent delivery assembly 16 is shown. The syringe assembly 130 includes an inlet portion 132, and the inlet portion 132 includes an inlet coupling feature (illustratively, an internal threaded surface 134) that is coupled to an outlet coupling feature (shown elsewhere - illustratively, an external threaded surface 134) of the pressure generating actuator 92. The inlet portion 132 also includes an inlet 136 that receives pressurized fluid from the outlet 104 of the pressure generating actuator 92. The inlet portion 132 is coupled to a syringe chamber 138, and the syringe chamber 138 includes a syringe passageway 140 that receives pressurized fluid from the inlet portion 132. The syringe passageway 140 houses a syringe piston 142, and when the syringe passageway 140 receives pressurized fluid, the syringe piston 142 translates away from the inlet portion 132 and towards the outlet portion 144 of the syringe assembly 130. Illustratively and as described in further detail below, the syringe piston 142 carries a magnetic component 194 that may also be referred to as a target, which facilitates determining the position of the syringe piston 142 within the syringe passageway 140. The syringe passageway 140 also transports a therapeutic agent 18 (shown elsewhere - illustratively, 2.25 mL of therapeutic agent, although other volumes may alternatively be transported, including for example 0.5 mL, 1.0 mL, 3.0 mL, or 5 mL) between the syringe piston 142 and the outlet portion 144, more specifically the needle 20. Thus, translation of the syringe piston 142 within the syringe passageway 140 causes the needle 20 to expel the therapeutic agent therefrom. In other embodiments, different arrangements are possible. For example, the inlet portion 132 and the syringe chamber 138 may be integrally formed with each other, or the syringe assembly 130 may be replaced by another type of therapeutic agent container, such as a bellows or a bladder structure.

[0074] Figure 20 The retraction cap 148 of the retraction mechanism 28 (shown elsewhere) is shown. Illustratively, the retraction cap 148 includes a body 150 having a generally cylindrical shape, and the body 150 includes an internal passageway 152. The proximal portion 154 of the body 150 carries coupling features (illustratively, a plurality of snap connectors 156) for coupling the retraction cap 148 to the proximal inner housing portion 40 (shown elsewhere). The proximal portion 154 of the body 150 also carries a biasing platform (illustratively, a radially inwardly extending flange 158) that, as described in more detail below, engages a spring (shown elsewhere) to facilitate reconfiguring the system 10 from the deployed configuration to the retracted configuration. The distal portion 160 of the body 150 carries detachable coupling features (illustratively, a plurality of rungs 162 or radially outwardly extending protrusions 162, two of which are in Figure 20As shown (elsewhere), the coupling feature removably couples the retraction cap 148 to another component of the retraction mechanism 28, which is described in more detail below. The distal portion 160 of the body 150 also has a retraction feature (illustratively, an axially extending post 164), which, as described in more detail below, engages another component of the retraction mechanism 28 to facilitate reconfiguring the system 10 from the deployed configuration to the retracted configuration.

[0075] Figure 21 and Figure 22 The retraction base 166 of the retraction mechanism 28 (shown elsewhere) is shown. Illustratively, the retraction base 166 includes a body 168 having a generally annular shape, and the body 168 includes an internal passage 170. The proximal portion 172 of the body 168 includes a recess 174, and the recess 174 has a detachable coupling feature (illustratively, a plurality of rungs 176 or radially inwardly extending L-shaped protrusions 176), which engages the detachable coupling feature (shown elsewhere - illustratively, a plurality of rungs 162) of the retraction cap 148. The recess 174 also includes a biasing platform (illustratively, a proximally facing surface 178), which, as described in more detail below, engages the same spring (shown elsewhere) as the retraction cap 148. The recess 174 also includes an opening 180 that extends from the proximal portion 172 to the opposite distal portion 182. The opening 180 is elongated in the circumferential or angular direction 184. As described in more detail below, the opening 180 receives the retraction feature (shown elsewhere - illustratively, an axially extending post 164) of the retraction cap 148. Illustratively, the post 164 extends through the opening 180, and the post 164 is movable within the opening 180 in the angular direction 184. The distal portion 182 of the body 168 also includes a mounting surface (illustratively, a radially outwardly facing surface 186), which, as described in more detail below, carries another component of the retraction mechanism 28.

[0076] Figure 23 and 24Shows the electronic component assembly 188 of the therapeutic agent delivery system 10. The electronic component assembly 188 includes an electronic controller 190 that is operably coupled to a power source 192 (illustratively, a battery) and receives power therefrom. The controller 190 is also operably coupled to a sensor 194. The sensor 194 can send a sensor signal to the controller 190 in response to sensing various types of inputs. For example, the sensor 194 can be configured to determine the position of the syringe piston 142 within the syringe chamber 138 (both shown elsewhere - e.g., to determine whether the syringe piston 142 has moved toward the syringe outlet portion 144, indicating that the therapeutic agent has been discharged from the needle 20). More specifically, the sensor 194 can be a Hall effect sensor configured to sense a magnetic component 146 (shown elsewhere) carried by the syringe piston 142. As another example, the sensor 194 can be an optical sensor or a vibration sensor. As yet another example, the sensor 194 and / or the target 146 can be configured to sense a sensor signal and send the sensor signal to the controller 190 when the user input device 26 (shown elsewhere) is actuated.

[0077] Specifically referring to Figure 23 , the controller 190 is also operably coupled to a release device 196 of a retraction mechanism 28 (shown elsewhere). The controller 190 can send a retraction signal to the release device 196 (e.g., upon receiving a sensor signal, or after the sensor 194 senses that the user input device 26 has been actuated for a predetermined period of time) to actuate the release device 196. The retraction mechanism 28 can thereby reconfigure the system 10 from an extended configuration to a retracted configuration. More details of the release device 196 are described below.

[0078] Figure 25 Shows the retraction mechanism 28, including a wire / thread element 198 that illustratively forms the release device 196. The wire 198 extends around the outward-facing surface 186 of the retraction base 166 and loops around a post 164 of the retraction cap 148. The wire 198 can contract or otherwise pull the post 164 such that the post 164 slides within an opening 180 of the retraction base 166. The retraction cap 148 thereby rotates relative to the retraction base 166, which disengages the detachable coupling features (shown elsewhere - illustratively, rungs 162 and 172) of the retraction cap 148 and the retraction base 166. As described in more detail below, this action allows a spring (shown elsewhere) carried between the retraction cap 148 and the retraction base 166 to expand and urge the retraction cap 148 and the retraction base 166 apart. This action in turn reconfigures the system 10 from an extended configuration to a retracted configuration.

[0079] Illustratively, the wire 198 can include one or more shape memory materials that contract when heated. For example, the wire 198 can include a shape memory alloy such as Nitinol, and the controller 190 can provide a retraction signal as an electric current to the wire 198, thereby heating and contracting the wire 198. Alternatively, these components can take other forms. For example, the controller 190 can provide a retraction signal to a separate heating element (not shown), and the heating element can provide thermal energy to the wire 198, thereby causing the wire 198 to contract.

[0080] Illustratively, the actuation of the therapeutic agent delivery system 10 is as follows. Referring to Figure 26 , the therapeutic agent delivery system 10 is shown in an initial or first configuration. In the first configuration, the therapeutic agent delivery assembly 16 is set to a stowed configuration (illustratively, a configuration in which the needle 20 is fully located within the housing 12).

[0081] Referring to Figure 27 , the user input device 26 and the input driver 82 are shown in a first configuration. In this configuration, the user input device 26 can be actuated by the user to actuate the therapeutic agent delivery system 10. More specifically, the user input device 26 can be pressed and translated relative to the housing 12 in a direction D1 (e.g., can be substantially parallel to the longitudinal axis 14 (i.e., parallel ±5 degrees)). This action causes the actuation surface 80 of the user input device 26 (one of which is shown in Figure 27 ) to engage with the actuation surface 88 of the input driver 82 (one of which is shown in Figure 27 ). The user input device 26 thereby causes the input driver 82 to rotate in the direction D2. As shown in Figure 28 , this action in turn causes the rung 90 of the input driver 82 to begin sliding on the rung 116 of the reciprocator 112 and then disengage from the rung 116.

[0082] As shown in Figure 29 , the compression spring 200 disposed between the input driver 82 and the reciprocator 112 is relatively unconstrained when the input driver 82 and the reciprocator 112 disengage. Thus, the compression spring 200 extends and pushes the therapeutic agent delivery assembly 16 (shown elsewhere) distally relative to the housing 12. As shown in Figure 30 , the therapeutic agent delivery assembly 16 thereby moves from the stowed configuration to the deployed configuration (illustratively, the deployed configuration is a configuration in which the needle 20 is partially exposed at the distal portion 22 of the housing 12 and is configured to engage with a subject and deliver a drug to the subject). Illustratively, the needle 20 translates from the stowed configuration to the deployed configuration in a direction D3 that is substantially parallel to the longitudinal axis 14 (i.e., parallel ±5 degrees).

[0083] Referring again to Figure 29, distal translation of the therapeutic agent delivery assembly 16 relative to the housing 12 also causes the radially outwardly extending fingers 122 of the reciprocator 112 (one of the fingers is shown in Figure 29 ) to engage and slide on the helically extending ramp 51 (one of the ramps is shown in Figure 29 ). This engagement causes the reciprocator 112 to rotate relative to the mixing chambers 94, 96 of the pressure generating actuator 92 (illustratively, about an axis substantially parallel to the longitudinal axis 14 (i.e., parallel ±5 degrees)), which actuates the pressure generating actuator 92. More specifically and as shown in Figure 31 , rotating the reciprocator 112 relative to the first mixing chamber 94 and the second mixing chamber 96 causes the radially inwardly extending tab 124 of the reciprocator 112 to be angularly misaligned with the radially outwardly extending tab 128 of the mixing piston 110, and causes the radial channel 126 of the reciprocator 112 to be angularly aligned with the radially outwardly extending tab 128 of the mixing piston 110. Accordingly, the actuator spring 108 is relatively unconstrained, and as shown in Figure 32 , the actuator spring 108 extends and translates the mixing piston 110 into the reciprocator 112 and the first mixing chamber 94. The reagents in the first mixing chamber 94 and the second mixing chamber 96 then mix and react to provide a pressurized gas, which the pressure generating actuator 92 delivers from the actuator outlet 104.

[0084] Referring to Figure 33 , the pressure generating actuator 92 delivers the pressurized gas to the syringe passage 140, thereby causing the syringe piston 142 to translate distally in the syringe passage 140. Accordingly, the syringe piston 142 pushes the therapeutic fluid distally to the needle 20, and the needle 20 discharges the therapeutic fluid and delivers the therapeutic fluid to the subject. When delivering the therapeutic fluid to the subject, as shown in Figure 34 and 35 , the retraction mechanism 28 remains in its initial or first configuration. More specifically, the retraction cap 148 is fixed to the retraction base 166 via detachable coupling features (illustratively, a plurality of rungs 162 and 176 - see Figure 35 ), and the compression spring 202 is carried between the retraction cap 148 and the retraction base 166 in a higher energy storage configuration (i.e., a loaded or compressed configuration). After delivering the therapeutic fluid to the subject (illustratively, determined by sensing with a sensor 194 that the magnetic member 146 and the syringe piston 142 are disposed near the outlet portion 144 of the syringe assembly 130 - all shown elsewhere), the electronic component assembly 188 (shown elsewhere) actuates the retraction mechanism 28. More specifically, the electronic component assembly 188 passes an electric current through the wire 198 to heat the wire 198 and as shown in Figure 36 and 37As a result, wire 198 contracts. Wire 198 thereby pulls and slides post 164 of retraction cap 148 within opening 180 of retraction base 166, which causes retraction cap 148 to rotate relative to retraction base 166 about longitudinal axis 14. During this rotation, the coupling feature structures (illustratively, multiple rungs 162) of retraction cap 148 disengage from the coupling feature structures (illustratively, multiple rungs 176) of retraction base 166. As Figure 38 and 39 shown, spring 202 is then relatively unconstrained, and spring 202 releases stored energy to reconfigure from a higher energy storage configuration to a lower energy storage configuration (i.e., spring 202 extends). Spring 202 thereby urges retraction cap 148 away from retraction base 166, as Figure 40 shown, which causes proximal inner housing portion 40, pressure generating actuator 92, and syringe assembly 130 to translate proximally relative to proximal outer housing portion 30. This action causes needle 20 to translate from the deployed configuration to the retracted configuration. Illustratively, therapeutic agent delivery system 10 cannot be actuated again (i.e., therapeutic agent delivery system 10 can be "locked"), and therapeutic agent delivery system 10 can be discarded.

[0085] Although the present invention has been described with an exemplary design, the present invention may be further modified within the spirit and scope of this disclosure. Accordingly, this application is intended to cover any variations, uses, or adaptations of the present invention using its general principles. Moreover, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and fall within the limits of the appended claims.

Claims

1. A therapeutic agent delivery system, comprising: a housing having a distal portion; a therapeutic agent delivery assembly carried by the housing, the therapeutic agent delivery assembly comprising: a chamber including a passage configured to transport a therapeutic agent; a needle in communication with the passage; the therapeutic agent delivery assembly being translatable relative to the housing from a storage configuration to a deployed configuration, in which the needle extends at least partially distally from the distal portion of the housing, and the therapeutic agent delivery assembly being translatable relative to the housing from the deployed configuration to a retracted configuration, in which the needle is disposed proximally closer to the distal portion of the housing; a user input device configured to be actuated by a user, actuation of the user input device translating the therapeutic agent delivery assembly from the storage configuration to the deployed configuration; a retraction mechanism, the retraction mechanism comprising: a biasing element configurable from a higher energy storage configuration to a lower energy storage configuration; an electronic component assembly configured to send a retraction signal; and a release device coupled to the biasing element, the release device being actuable to allow the biasing element to configure from the higher energy storage configuration to the lower energy storage configuration, the biasing element thereby translating the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration, wherein the release device includes a wire, and the wire contracts in response to the retraction signal, thereby actuating the release device.

2. The therapeutic agent delivery system according to claim 1, wherein, The biasing element includes a compression spring, the higher energy storage configuration being a compressed configuration and the lower energy storage configuration being an extended configuration.

3. The therapeutic agent delivery system according to claim 1, wherein, The wire is operatively coupled to the electronic component assembly, the retraction signal includes an electric current, and wherein the release device is actuated by contracting upon receipt of the electric current.

4. The therapeutic agent delivery system according to any one of claims 1-3, wherein, The electronic component assembly includes a sensor configured to sense the discharge of the therapeutic agent from the needle, and the electronic component assembly is configured to send a retraction signal when the sensor senses the discharge of the therapeutic agent from the needle.

5. The therapeutic agent delivery system according to any one of claims 1-3, wherein, The release device includes: a retraction base; and a retraction cap carried by the retraction base, the biasing element being carried between the retraction base and the retraction cap.

6. The therapeutic agent delivery system according to claim 5, wherein, The retraction cap is rotatable relative to the retraction base to actuate the retraction mechanism.

7. The therapeutic agent delivery system according to claim 5, wherein, The retraction cap includes a post coupled to the wire, and when actuated, the wire moves the post to disengage the retraction cap from the retraction base.

8. The therapeutic agent delivery system according to claim 7, wherein, The retraction base includes an opening configured to receive the post, wherein the post is movable within the opening.

9. The therapeutic agent delivery system according to any one of claims 1-3, wherein, The housing further includes: an outer housing; and an inner housing translatably carried within the outer housing, the inner housing translatably carrying the therapeutic agent delivery assembly; wherein the therapeutic agent delivery assembly translates relative to the inner housing and the outer housing when translating from the storage configuration to the deployed configuration, and the therapeutic agent delivery assembly, together with the inner housing, translates relative to the outer housing from the deployed configuration to the retracted configuration.

10. A therapeutic agent delivery system, comprising: a housing having a distal portion; A therapeutic agent delivery assembly carried by the housing, the therapeutic agent delivery assembly comprising: A chamber including a passage configured to transport a therapeutic agent; A needle in communication with the passage; The therapeutic agent delivery assembly is translatable relative to the housing from a storage configuration to a deployed configuration in which the needle extends at least partially distally from a distal portion of the housing, and the therapeutic agent delivery assembly is translatable relative to the housing from the deployed configuration to a retracted configuration in which the needle is disposed proximally closer to the distal portion of the housing; A user input device configured to be actuated by a user, actuation of the user input device translating the therapeutic agent delivery assembly from the storage configuration to the deployed configuration; An electronic component assembly configured to send a retraction signal; and A retraction mechanism operably coupled to the electronic component assembly, the retraction mechanism including a biasing element that can be reconfigured from a higher energy storage configuration to a lower energy storage configuration when the retraction mechanism receives the retraction signal from the electronic component assembly, the biasing element thereby translating the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration, wherein the retraction mechanism further includes a wire that contracts when the retraction mechanism receives the retraction signal, the wire contracting to cause the biasing element to be reconfigured from the higher energy storage configuration to the lower energy storage configuration.

11. The therapeutic agent delivery system according to claim 10, wherein, The electronic component assembly includes a sensor configured to sense the discharge of the therapeutic agent from the needle, and the electronic component assembly is configured to send a retraction signal when the sensor senses the discharge of the therapeutic agent from the needle.

12. The therapeutic agent delivery system according to any one of claims 10-11, wherein, The retraction mechanism further includes: A retraction base; and A retraction cap carried by the retraction base, the biasing element being carried between the retraction base and the retraction cap.

13. The therapeutic agent delivery system according to claim 12, wherein, The retraction cap includes a retraction structure coupled to the wire, and when actuated, the wire moves the retraction structure to disengage the retraction cap from the retraction base.

14. The therapeutic agent delivery system according to claim 12, wherein, The retraction cap is rotatable relative to the retraction base to reconfigure the biasing element from the higher energy storage configuration to the lower energy storage configuration.

15. The therapeutic agent delivery system according to claim 10, wherein, The biasing element includes a compression spring, the higher energy storage configuration being a compressed configuration and the lower energy storage configuration being an extended configuration.

16. A therapeutic agent delivery system, comprising: A housing having a distal portion; A therapeutic agent delivery assembly carried by the housing, the therapeutic agent delivery assembly comprising: A chamber including a passage; A therapeutic agent transported in the passage; A needle in communication with the passage; The therapeutic agent delivery assembly is translatable relative to the housing from a storage configuration to a deployed configuration in which the needle extends at least partially distally from a distal portion of the housing, and the therapeutic agent delivery assembly is translatable relative to the housing from the deployed configuration to a retracted configuration in which the needle is disposed proximally closer to the distal portion of the housing; A user input device configured to be actuated by a user, actuation of the user input device translating the therapeutic agent delivery assembly from the stowed configuration to the deployed configuration; A retraction mechanism including a biasing element configurable from a higher energy storage configuration to a lower energy storage configuration, the retraction mechanism having: A locked configuration in which the biasing element is held in the higher energy storage configuration; and An unlocked configuration in which the biasing element is allowed to configure from the higher energy storage configuration to the lower energy storage configuration, the biasing element thereby translating the therapeutic agent delivery assembly from the deployed configuration to the retracted configuration; Wherein the retraction mechanism further includes a wire configured to contract to configure the retraction mechanism from the locked configuration to the unlocked configuration.

17. The therapeutic agent delivery system according to claim 16, wherein, The wire includes one or more shape memory materials that contract upon receipt of thermal energy.

18. The therapeutic agent delivery system according to any one of claims 16-17, wherein, The retraction mechanism further includes: A retraction base; and A retraction cap carried by the retraction base, the biasing element being carried between the retraction base and the retraction cap, and the retraction cap being rotatable relative to the retraction base to configure the retraction mechanism from the locked configuration to the unlocked configuration.

19. The therapeutic agent delivery system according to claim 18, wherein, The retraction cap includes a post coupled to the wire, and when actuated, the wire moves the post to disengage the retraction cap from the retraction base.

20. The therapeutic agent delivery system of claim 16, further comprising an electronics component assembly including a sensor configured to sense the discharge of the therapeutic agent from the needle, the electronics component assembly configured to send a retraction signal when the sensor senses the discharge of the therapeutic agent from the needle, and wherein when the retraction signal is received from the electronics component assembly, the retraction mechanism configures from the locked configuration to the unlocked configuration.

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