EA044249B1 - DRUG DELIVERY DEVICE FOR ACCURATE DOSE DELIVERY - Google Patents

Description

Cross reference to related applications

This patent application claims the benefit of priority of the provisional patent application.

US No. 62/857,678, filed June 5, 2019; and US Provisional Patent Application No. 62/860,481, filed June 12, 2019; each of which is incorporated herein by reference in its entirety.

Field of technology

Aspects of the present disclosure relate to devices and methods for driving or configuring a dose delivery device, such as a syringe, to facilitate accurate dose delivery. More specifically, embodiments of the present disclosure relate to devices and methods for dispensing, storing, transporting, and/or delivering precise doses of a drug or other fluid.

Introduction

Finished dosage forms, which include flowable drug substances, can be delivered to patients in many ways, including by injection. In many cases, the accuracy and volumetric accuracy of the liquid dosage form are critical. For example, healthcare providers may be interested in ensuring that the approved or prescribed volume of a drug is consistently delivered to each patient requiring that drug. Additionally, an overdose or underdose of a drug in a patient, even a small amount, can have an undesirable (or even negative) clinical effect on the patient. In addition, some finished dosage forms are prescribed in small volumes (eg, less than 100 μl). At low volumes, human error in preparing and delivering the exact dose of drug substance for injection can affect the effectiveness of the drug in the patient and the subsequent clinical effect on the patient.

Additional aspects of fluid drug delivery can make it difficult to achieve the goal of accurately delivering a dose by injection. For example, in order to dispense the correct dose of a drug from a device (eg, a syringe), a corresponding, precise volume of that drug must be loaded into the device. Additionally, handling, storage, packaging, and/or transportation of refilled devices must not result in unintentional release of drug substance from the devices. Additionally, before administering the drug from the device, the device must be actuated, for example, to remove air bubbles and excess drug from inside the needle and barrel of the device. Incorrect actuation of the device may result in too much or too little drug being expelled from the device, which may also result in a decrease in the dose delivered to the patient, or may result in air bubbles being injected from the device into the patient.

This disclosure also addresses needs unmet by prior publications: WO 2018/232408, published December 20, 2018; WO 2018/224640 published December 13, 2018; and WO 2018/224644, published December 13, 2018. Additionally, at least some embodiments of the present disclosure include features that differ from those disclosed in WO 2019/118588, published June 20, 2019. Some features include itself, for example, a piston rod including one or more extensions extending distally from the actuation portion of the piston rod and having hook-like or staple-like portions received by the side openings of the flange element. The piston rod may include a journal having three or more sections, each of which has a different profile and/or cross-sectional shape. Additional features may include, for example, a flange member including a collar having one or more internal grooves for receiving hook or staple portions of one or more extensions, allowing the extensions to flex radially outward from a compressed configuration to an expanded configuration. The flange element may include an opening configured to receive each of three or more journal sections based on, for example, the rotational position of the piston rod relative to the flange element.

The flange member of the present disclosure may further include one or more movable ribs and/or one or more movable tabs for engaging the syringe body for connecting the flange member to the syringe body. For example, one or more movable ribs may be located proximally to the edge and side opening of the flange member for receiving the top flange of the syringe body. The movable ribs may move, deflect, and/or deform in response to receiving the top flange through the side opening and may be configured to apply a distally directed force to the top flange to secure the syringe body to the flange member. As a further example, one or more movable tabs may be located distal to the edge and side opening. The movable tabs may move, deflect, and/or deform in response to the flange member receiving the syringe body and may be configured to apply a radially directed force to the syringe body to secure the syringe body to the flange member. It should be understood that embodiments of the present disclosure include various other features shown

- 1 044249 and described here, which differ from the features disclosed in publication WO 2019/118588.

The essence of the invention

Drug delivery devices are disclosed herein. In one embodiment of the present disclosure, a drug delivery device includes a housing, a piston rod located partially within the housing, a projection extending from the piston rod, and a locking component on the housing. When the protrusion is in a first position relative to the locking component, the locking component limits the distal movement of the piston rod to a first stop point, and when the protrusion is in a second position relative to the locking component, the locking component limits the distal movement of the piston rod to a second stop point.

In some aspects of the present disclosure, the drug delivery device further includes a stopper located in the housing. Distal movement of the piston rod distally moves the stopper and the medicinal substance located in the housing between the stopper and the distal end of the housing. Distal movement of the piston rod to the first stopping point actuates the drug delivery device, and distal movement of the piston rod to the second stopping point dispenses a predetermined volume of drug from the distal end of the device.

In some aspects of the present disclosure, moving the protrusion from a first position to a second position involves rotating the piston rod relative to the locking component. In some aspects of the present disclosure, the drug delivery device further includes a cavity on a proximal side of the locking component, the cavity being configured to receive a portion of the protrusion. When the protrusion is in the second position relative to the locking component, the protrusion is located proximally from the cavity such that distal movement of the piston rod moves the protrusion into the cavity.

In some aspects of the present disclosure, the cavity is a first cavity, and the drug delivery device further includes a second cavity proximal to the blocking component, wherein the second cavity is configured to receive a portion of the protrusion. The first and second cavities are located on opposite sides of the central longitudinal axis of the drug delivery device. In some aspects of the present disclosure, the locking component includes a flange and is coupled to a proximal end portion of the housing, and a piston rod extends through an opening in the locking component. In some aspects of the present disclosure, the drug delivery device further includes an actuation portion at a proximal end portion of the piston rod, and a protrusion extends from the actuation portion.

In some aspects of the present disclosure, the actuation portion includes a substantially cylindrical shape having a diameter greater than the width of the rest of the piston rod. The protrusion extends from the side surface of the generally cylindrical shape, and the actuation portion further includes a thumb support at the proximal end of the actuation portion, and a ring on an outer surface on the side surface of the substantially cylindrical shape. In some aspects of the present disclosure, the drug delivery device further includes a proximal collar on the locking component, and the actuation portion is partially mounted within the proximal collar.

In some aspects of the present disclosure, the piston rod further includes a pair of extensions projecting distally from the actuation portion, and the locking component includes a pair of holes. A portion of each extension is configured to be received by one of a pair of holes at a first stopping point. In some aspects of the present disclosure, the locking component includes one or more recesses formed along a bottom wall of the locking component. A portion of each extension is configured to be received by one or more recesses upon distal movement of the piston rod relative to the locking component to allow distal movement of the piston rod to a second stopping point.

In some aspects of the present disclosure, the locking component includes a pair of internal grooves formed along a side wall of the locking component. A portion of each extension is configured to be received by at least one of a pair of internal grooves upon rotation of the piston rod relative to the locking component to expand the extensions radially outward from a compressed state to a weakened state. In some aspects of the present disclosure, the projection is a first projection, and the drug delivery device further includes a second projection extending from the piston rod in a direction opposite to the first projection. In some aspects of the present disclosure, the locking component is slidably coupled to the housing and includes a pair of internal ribs that are configured to engage an upper flange of the housing when the housing is slidably coupled to the locking component. A pair of internal ribs is configured to apply a distally directed force to

- 2 044249 upper flange.

In some aspects of the present disclosure, the locking component is slidably coupled to the body and includes a pair of movable tabs that are configured to engage the body sleeve when the body is slidably coupled to the locking component. The pair of movable legs are laterally deflectable after receiving the sleeve in the blocking component and are configured to apply a radially directed force to the sleeve. In some aspects of the present disclosure, the locking component further includes a pair of finger flanges. Each of the finger flanges includes a textured surface having a predetermined structure that enhances the grip of the locking component.

According to another embodiment of the present invention, a drug delivery device includes a housing, a piston rod having a distal end connected to a stopper within the housing, and a proximal end including a thumb rest actuator portion, a plurality of projections extending from the actuator portion , and a locking component located on the body, the locking component including a proximal collar. When the projections and the locking component are in the first configuration, the locking component limits the distal movement of the piston rod to the first stop point, and when the projections and the locking component are in the second configuration, the locking component limits the distal movement of the piston rod to the second stop point. The proximal collar is configured to receive the projections after distal movement of the piston rod when the projections are in the second configuration.

In some aspects of the present disclosure, the projections and the locking component are movable from a first configuration to a second configuration by rotating the actuation portion about a longitudinal axis relative to the locking component. In some aspects of the present disclosure, the difference between the first stopping point and the second stopping point is equivalent to the distance that the stopper must travel to push a given volume of the finished dosage form out of the distal end of the housing. In some aspects of the present disclosure, the plurality of projections includes two projections located symmetrically with respect to the actuation portion. In some aspects of the present disclosure, the locking component further includes a pair of finger flanges. In some aspects of the present disclosure, the drug delivery device is a pre-filled syringe.

In some aspects of the present disclosure, the drug delivery device may transition: (a) from a pre-operational state to an actuation state by longitudinally moving the piston rod until the piston rod reaches a first stopping point; (b) from the actuation state to the delivery state by rotating the piston rod relative to the locking component until the projections and the locking component are in a second configuration; and (c) from the delivered state to the used state by longitudinally moving the piston rod until the piston reaches a second stopping point. In some aspects of the present disclosure, the piston rod includes a journal located distal to the actuation portion, and the journal mates with an opening in the locking component to prevent proximal movement of the piston rod. In some aspects of the present disclosure, the neck is further mated to an opening in the locking component to prevent the drug delivery device from moving from a delivery state to an actuation state.

In a further embodiment of the present disclosure, the drug delivery device includes a housing, a piston rod including: a distal portion connected to a stopper within the housing; a proximal end including a substantially cylindrical actuation portion located outside the housing; and two projections extending from opposite sides of the actuation portion in a symmetrical configuration. The drug delivery device further includes a blocking component coupled to the housing, the blocking component including a collar configured to receive a distal portion of the actuation portion, and two cavities in the collar having proximally facing openings. Each cavity is configured to receive a distal portion of one of the two projections. The piston rod is longitudinally movable and rotatable about a longitudinal axis relative to the locking component. When the drug delivery device is in a pre-operational state, the projections and cavity openings are not longitudinally aligned, and when the drug delivery device is in a delivery state, the projections and cavity openings are longitudinally aligned. In some aspects of the present disclosure, the locking component further includes a finger flange, and the drug delivery device further includes a ribbed surface on a side surface of the actuation portion.

In a further embodiment of the present disclosure, a method of dispensing a substance from a drug delivery device having a piston rod and a housing is disclosed. The method includes steps in which the piston rod is advanced a predetermined distance into the housing until

- 3 044249 until the movement of the piston rod is resisted by the limiter, the piston rod is rotated around the longitudinal axis, and the piston rod is activated to distribute a given volume of the substance.

In some aspects of the present disclosure, the steps of advancing the piston rod and actuating the piston rod include the step of depressing the actuating portion of the piston rod. In some aspects of the present disclosure, the piston rod includes a projection, the stop includes a locking component coupled to the housing, and the locking component is adjacent to the projection to resist advancement of the piston rod.

In some aspects of the present disclosure, the step of rotating the piston rod includes the step of rotating the actuation portion of the piston rod relative to the locking component of the piston rod until a protrusion on the piston rod is longitudinally aligned with a cavity in the locking component. In some aspects of the present disclosure, the step of actuating the piston rod includes the step of pressing the actuating portion of the piston rod to advance the protrusion into the cavity.

In some aspects of the present disclosure, the method further includes advancing the protrusion into the cavity until the protrusion abuts the distal side of the cavity and a predetermined volume of material is dispensed when the protrusion abuts the distal side of the cavity.

In a further embodiment of the present disclosure, the drug delivery device includes a housing, a stopper located within the housing, and a sleeve having a proximal end and a distal end. The distal end is located inside the housing proximal to the stopper. The device includes a piston rod located at least partially inside the sleeve. When the stopper is in the ready position, distal advancement of one of (a) the sleeve only, (b) the piston rod only, or (c) both the sleeve and the piston rod together, relative to the housing, advances the stopper into the actuation position. When the stopper is in the actuation position, distal advancement of the other of (a) the sleeve only, (b) the piston rod only, or (c) both the sleeve and the piston rod together, relative to the body, advances the stopper to the dose end position.

In some aspects of the present disclosure, the drug delivery device further includes a removable locking component located between the proximal portion of the sleeve and the proximal end of the housing. The blocking component prevents distal advancement of the sleeve relative to the body. Distal advancement of the sleeve relative to the body after removal of the locking component advances the stopper into the actuation position. The locking component is a staple removably secured around at least a portion of the sleeve.

In some aspects of the present disclosure, the drug delivery device further includes a removable locking component that connects the piston rod to the sleeve. Distal advancement of both the sleeve and piston rod together relative to the body advances the stopper into the actuation position. Distal advancement of only the piston rod relative to the housing after removal of the locking component advances the stopper to the dose end position. At the end of the dose position, the proximal end of the piston rod is adjacent to the distal end of the sleeve so that any further distal movement of the piston rod relative to the housing is prevented. The removable locking component includes one of a pin, tab, or rod.

In some aspects of the present disclosure, the drug delivery device further includes a projection located on the piston rod and an internal projection located on the inner wall of the sleeve distal to the projection of the piston rod. Distal advancement of only the piston rod relative to the body advances the stopper into the actuation position and causes the protrusion of the piston rod to contact the inner protrusion of the sleeve. The distal advancement of both the piston rod and the sleeve relative to the body, after the protrusion of the piston rod contacts the inner protrusion of the sleeve, advances the stopper to the end of the dose position.

In some aspects of the present disclosure, a compressible protrusion is provided on the piston rod and an opening located on the inner wall of the sleeve proximal to the protrusion on the piston rod. Distal advancement of only the piston rod relative to the housing advances the stopper into the actuation position. Proximal withdrawal of the piston rod until the compressible protrusion of the piston rod engages the opening of the sleeve connects the sleeve to the piston rod. The distal advancement of both the piston rod and the sleeve coupled together relative to the body moves the stopper to the dose end position. In some aspects of the present disclosure, when the sleeve is coupled to a piston rod, the total length of the coupled sleeve and piston rod along a proximal-distal axis is greater than the length of the piston rod itself.

In some aspects of the present disclosure, the sleeve includes a finger flange. In some aspects of the present disclosure, the drug delivery device further includes a stop located at the proximal end of the housing. The limiter is made with

- 4 044249 the ability to block the distal advancement of the sleeve or piston rod when the stopper is in the end position.

In additional embodiments of the present disclosure, the drug delivery device includes a housing and a piston rod having a distal portion located within the housing and a proximal portion located outside the proximal end of the housing. The proximal part has a width greater than the width of the distal part. The device further includes an obstruction which, in an obstructive position relative to the piston rod, prevents distal advancement of the piston rod from the actuation position to the dose end position. Moving the obstacle from the obstructing position allows the piston rod to move distally to the dose end position.

In some aspects of the present disclosure, the drug delivery device further includes a collar attached to the proximal end portion of the housing. The collar surrounds the proximal portion of the piston rod. The drug delivery device further includes a collar extension extending radially inward from the collar. The proximal portion of the piston rod includes a channel into which a shoulder projection extends, the channel including a circular path and an axial dose end path. The obstacle contains a shoulder protrusion which, when positioned in the circular path of the channel, prevents the distal advancement of the piston rod to the dose end position. Moving the obstacle from the obstructing position involves torsion of the piston rod around the longitudinal axis to align the shoulder protrusion with the axial path of the end of the dose.

In some aspects of the present disclosure, the channel further includes an axial actuation path offset from the axial dose end path and connected to the axial dose end path in a circular manner. Distally moving the piston rod so that the shoulder protrusion moves along the axial actuation path advances the piston rod to the actuation position. In some aspects of the present disclosure, the collar further includes a finger flange.

In some aspects of the present disclosure, the proximal portion of the piston rod includes a projection extending radially outward. The drug delivery device further includes a rotatable alignment component located between the proximal portion of the piston rod and the housing. The alignment component includes a channel, wherein the channel is configured to receive a projection of the piston rod. The obstruction includes a channel wall that blocks the distal axial path of the piston rod protrusion when the piston rod is in the actuation position. Moving the obstruction from the obstructing position comprises rotating the alignment component to remove the channel wall from the distal axial path of the piston rod protrusion.

In some aspects of the present disclosure, the drug delivery device further includes a finger flange connected to the proximal end portion of the housing. The rotatable leveling component is located between the pin flange and the proximal portion of the piston rod. In some aspects of the present disclosure, the drug delivery device further includes a flange member located at the proximal end of the housing. The obstruction includes a removable cap which, when in an obstructive position relative to the piston rod, is located partially between the proximal portion of the piston rod and the flange member. In some aspects of the present disclosure, removal of the cap allows the proximal portion of the piston rod to be advanced to the dose end position. At the end of the dose position, the proximal part of the piston rod is in contact with the flange element. In some aspects of the present disclosure, a removable cap covers the proximal portion of the piston rod when in an obstructed position.

In some aspects of the present disclosure, the drug delivery device further includes a collar located between the proximal end of the housing and the proximal portion of the piston rod. The collar defines an opening configured to accommodate the proximal portion of the piston rod after distal advancement of the piston rod beyond the actuation position. The obstruction includes a tab extending radially outward from the proximal portion of the piston rod, the tab preventing the proximal portion of the piston rod from being installed in the bore of the collar. The depth of the collar hole coincides with the distance that the piston rod must move to distally advance to the end dose position.

In some aspects of the present disclosure, moving the obstruction from the obstructing position comprises either removing the tab or compressing the tab toward the proximal portion of the piston rod. In some aspects of the present disclosure, the tab is a first tab, and the obstruction further includes a second tab extending radially outward from the proximal portion of the piston rod in a direction opposite to the direction in which the first tab extends. In some aspects of the present disclosure, the obstacle includes a tab that, when in

- 5 044249 in an obstructive position, located between the housing and the proximal part of the piston rod.

The piston rod includes a geometry proximal to the tab, and this geometry cannot advance distally beyond the tab when the tab is in an obstructed position.

In some aspects of the present disclosure, moving the obstacle comprises removing the tab from the drug delivery device by pulling out the tab. In some aspects of the present disclosure, the drug delivery device further includes a flange member, with a portion of the tab located within a cavity of the flange member. In some aspects of the present disclosure, moving the obstacle comprises removing the tab from the drug delivery device by breaking the tab.

In some aspects of the present disclosure, the obstruction includes a flange member that, in an obstructive position, is located proximally from the proximal end of the housing between the proximal portion of the piston rod and the housing and is separated from the proximal end of the housing by a removable locking component. Removing the obstruction from the obstructing position involves removing the blocking component and moving the flange member distally toward the proximal end of the housing.

In some aspects of the present disclosure, the piston rod includes a projection extending radially outward. The obstruction includes a lever having an end that, in the obstructing position, is located distally from the protrusion and blocks distal movement of the protrusion and thereby distal movement of the piston rod. Moving the obstacle from the obstructing position comprises operating a lever to remove the end of the lever from its location distal to the protrusion. In some aspects of the present disclosure, distal advancement of the piston rod beyond the dose end position is prevented by contact between the proximal portion of the piston rod and the portion of the flange member coupled to the housing.

In additional embodiments of the present disclosure, the drug delivery device includes a housing and a sleeve attached to the housing. The sleeve includes a proximal end, a distal end, and an opening located in the circular wall of the sleeve. The drug delivery device further includes a piston rod extending through the sleeve, the piston rod including a distal end portion located within the housing and a radially extending projection. The piston rod can be advanced distally into the housing from a ready position to an actuating position. In the actuation position, the protrusion of the piston rod is located within the bore, and further distal movement of the piston rod is resisted by the contact between the protrusion and the wall of the bore. Pressure may be applied to the projection to overcome this resistance to further distally advance the piston rod.

In some aspects of the present disclosure, the opening in the sleeve is a second opening, and the sleeve further includes a first opening located in the circumferential wall of the sleeve proximal to the second opening, and a third opening located in the circumferential wall of the sleeve distal to the second opening. In the standby position, the protrusion of the piston rod is located in the first hole, and further distal movement of the piston rod is resisted by contact between the protrusion and the wall of the first hole. After further distal advancement of the piston rod beyond the actuation position, the protrusion of the piston rod is located in the third hole, and further distal advancement of the piston rod is prevented.

In some aspects of the present disclosure, the radially extending projection is a first projection, and the piston rod further includes a second radially extending projection opposite the first projection. Compressing the first and second projections toward each other when axial pressure is applied distally to the piston rod overcomes resistance to further distal advancement of the piston rod. In some aspects of the present disclosure, the proximal end of the sleeve includes a flared opening. Distal advancement of the piston rod from the ready position to the actuation position involves advancing the protrusion into the flared hole and through the sleeve, whereby the protrusion is clamped between the inside of the sleeve and the piston rod until the protrusion continues into the hole located in the circular sleeve wall. In some aspects of the present disclosure, the protrusion includes a distally tapering profile to assist in the distal advancement of the piston rod.

In further embodiments of the present disclosure, the drug delivery device includes a housing, a piston rod including a distal end portion located within the housing and a rotatable member, and a sleeve attached to the housing, the sleeve including a proximal opening, which can be advanced by the piston rod. Rotation of the rotatable element causes the piston rod to distally advance to the actuation position. When the piston rod is in the actuation position, further rotation of the rotating element is resisted.

In some aspects of the present disclosure, the rotatable element includes a cam lever. When the piston rod is in the actuation position, the piston rod can be pressed into the housing to distally advance the piston rod to the dose end position. In some aspects of the present disclosure, the drug delivery device further includes a collar located at a proximal end of the housing, the interior of the collar including a proximal threaded portion defining a proximal screw path. The rotatable element includes a proximal portion of the piston rod including a protrusion. The proximal portion of the piston rod can be rotated about the longitudinal axis to cause distal movement of the protrusion along the proximal helical path. When the protrusion reaches the end of the proximal threaded portion of the collar, the piston rod is in the actuation position.

In some aspects of the present disclosure, when the piston rod is in the actuation position, the piston rod may be pressed axially into the housing to distally advance the piston rod to a dose end position. In some aspects of the present disclosure, the interior portion of the collar further includes a distal threaded portion. The thread of the distal threaded portion forms a distal helical path offset from or opposite to the proximal helical path. Aligning the protrusion with the distal screw path places the piston rod in the actuation position. Rotating the proximal portion of the piston rod to cause the protrusion to move distally along the distal helical path causes the piston rod to move distally to the dose end position.

In further embodiments of the present disclosure, the drug delivery device includes a housing, a stopper located within the housing, and a first piston rod having a first proximal end portion and a first distal end portion narrower than the first proximal end portion. The first distal end portion has a first length. The drug delivery device further includes a second piston rod having a second proximal end portion and a second distal end portion narrower than the proximal end portion. The second distal end portion has a second length. The drug delivery device further includes a finger flange attached to the proximal end portion of the housing. The finger flange has a through hole aligned with the proximal hole of the housing. The through hole is configured to accommodate each of the first and second distal end portions without accommodating either the first or second proximal end portions. Sliding the first distal end portion through the through hole until the first proximal end portion abuts the pin flange pushes the stopper distally into the actuation position. Sliding the second distal end portion through the through hole until the second proximal end portion abuts the finger flange pushes the stopper distally into the dose end position.

In additional embodiments of the present disclosure, a method of assembling a drug delivery device includes the steps of connecting a housing to a locking component, wherein the locking component is a flanged member, and connecting a piston rod to the locking component such that the piston rod is located partially inside the housing in a pre-assembled state, and its proximal movement relative to the locking component was prevented. In a pre-assembled state, the piston rod is configured to move distally relative to the locking component to a first stopping point with a protrusion of the piston rod engaging the locking component, causing the medicament primer to be pushed out of the housing. When the protrusion engages the locking component, the locking component is configured to limit the distal movement of the piston rod to the first stopping point. The piston rod is further configured, while the piston rod is at the first stopping point, to rotate relative to the locking component to disengage the protrusion from the locking component and to move distally relative to the locking component to a second stopping point with the protrusion engaging the locking component, causing ejection delivery dose of medication from the body.

In some aspects of the present disclosure, the method further includes inserting the upper flange of the housing into the opening of the locking component, causing the locking component tab to deflect radially outward, and causing the locking component rib to deflect proximally. The tab applies a radially inward force to the housing, and the rib applies a distal force to the upper flange to secure the housing to the locking component. The method further includes inserting a piston rod extension into a side hole of the locking component to secure the piston rod to the locking component in a pre-assembled state. The piston rod is configured to deflect the extension radially inward in response to movement of the piston rod distally relative to the locking component to the first stopping point so that the extension is removed from the side opening. The extension is configured to move relative to the interior of the locking component as the piston rod rotates relative to the locking component to align the protrusion with the slot of the locking component. The extension bends radially outward within the locking component as the protrusion aligns with the slot. The extension is configured to continue into the recess along the interior of the locking component as the piston rod moves distally to the second stopping point.

Brief description of drawings

The accompanying drawings, which are incorporated into and form a part of this specification, illustrate various illustrative embodiments and, together with the description, serve to explain the principles of the disclosed embodiments. The drawings show various aspects of the present disclosure, and, where appropriate, reference numerals showing similar structures, components, materials, and/or elements in the different figures are designated as such. It is understood that various combinations of structures, components, and/or elements in various embodiments other than the combinations specifically shown are contemplated and are within the scope of the present disclosure.

Many embodiments are described and illustrated herein. The devices and methods described are not limited to any particular aspects and embodiments thereof, nor are they limited to any combinations and/or permutations of such aspects and/or embodiments. In addition, each of the aspects of the described inventions and/or embodiments thereof may be used alone or in combination with one or more other aspects of the described inventions and/or embodiments thereof. For brevity, some permutations and combinations are not separately described or illustrated here.

Fig. 1A-1E show an exemplary delivery device and components thereof according to some embodiments of the present disclosure.

Fig. 1F-2T show additional aspects and embodiments of the exemplary delivery device of FIG. 1A-1E.

Fig. 3A and 3B show an exemplary method of assembling the delivery device shown in FIG. 1A-1E, in accordance with aspects of the present disclosure.

Fig. 3C-3F show an exemplary method of assembling the embodiment of the delivery device shown in FIG. 1A-1E, in accordance with aspects of the present disclosure.

Fig. 4A-4F show an exemplary method of using the delivery device shown in FIG. 1A-1E, in accordance with aspects of the present disclosure.

Fig. 4G-4J show an exemplary method of using the delivery device embodiment shown in FIG. 1A-1E, in accordance with aspects of the present disclosure.

Fig. 4K-4S show illustrative aspects of piston rods for use in embodiments of the delivery device shown in FIG. 1A-1E.

Fig. 4T-4X show views of an illustrative piston rod neck and flange member opening in embodiments of the delivery device shown in FIG. 1A-1E.

Fig. 4Y-4Z show illustrative aspects of piston rods for use in embodiments of the delivery device shown in FIG. 1A-1E.

Fig. 5A-5C show another exemplary delivery device according to additional embodiments of the present disclosure.

Fig. 6A-6E show a further exemplary delivery device according to additional embodiments of the present disclosure.

Fig. 7A-7F show an exemplary method of using the delivery device shown in FIG. 6A-6E, in accordance with aspects of the present disclosure.

Fig. 8A-8E show a further exemplary delivery device according to embodiments of the present disclosure.

Fig. 8F and 8G show the locking component of the delivery device shown in FIG. 8A8E, according to embodiments of the present disclosure.

Fig. 9A-9E show an exemplary method of using the delivery device shown in FIG. 8A-8E, in accordance with aspects of the present disclosure.

Fig. 10A-10C show an exemplary method of assembling the delivery device shown in FIG. 8A-8E, in accordance with aspects of the present disclosure.

Fig. 10D-10G show another exemplary method of assembling the embodiment of the delivery device shown in FIG. 8A-8E, in accordance with aspects of the present disclosure.

Fig. The PA-HEs show an exemplary method of using the delivery device shown in FIG. 10D-10G, in accordance with aspects of the present disclosure.

Fig. 12A-12D show close-up views of aspects of the exemplary method shown in FIG. PA-HE.

Fig. 13A and 13B show a further exemplary delivery device and a method of assembling said delivery device according to additional embodiments of the present disclosure.

- 8 044249

Fig. 14A-14F show a method of using the delivery device shown in FIG. 12A and

12V.

Fig. 15A-15B, and 16A-16B show illustrative piston rod disks according to additional embodiments of the present disclosure.

Fig. 17 shows an example piston rod and disk according to additional embodiments of the present disclosure.

Fig. 18A and 18B show an additional illustrative piston rod and disk according to additional embodiments of the present disclosure.

Fig. 19A and 19B show an exemplary rotary locking mechanism according to additional embodiments of the present disclosure.

Fig. 20 shows an exemplary piston rod latching device according to additional embodiments of the present disclosure.

Fig. 21 shows an exemplary piston rod with an impact device.

according to additional embodiments of the present disclosure.

Fig. 22 shows exemplary visual feedback devices according to some embodiments of the present disclosure.

Fig. 23A-23C show a further exemplary delivery device in accordance with aspects of the present disclosure.

Fig. 24A-24E show a further exemplary delivery device and a method of using said delivery device in accordance with aspects of the present disclosure.

Fig. 25A-25E show a further exemplary delivery device and a method of using said delivery device in accordance with aspects of the present disclosure.

Fig. 26A-26G show additional illustrative delivery devices and a method of using one such delivery device in accordance with aspects of the present disclosure.

Fig. 27A-27H show a further exemplary delivery device and a method of using said delivery device in accordance with aspects of the present disclosure.

Fig. 28A-28Z show additional illustrative delivery devices and methods of using said delivery devices in accordance with aspects of the present disclosure.

Fig. 29A-29C show a further exemplary delivery device and a method of using said delivery device in accordance with aspects of the present disclosure.

Fig. 30-31 show a further exemplary delivery device and a method of using said delivery device in accordance with aspects of the present disclosure.

Fig. 32-33 show a further exemplary delivery device and a method of using said delivery device in accordance with aspects of the present disclosure.

Fig. 34-40C show a further exemplary delivery device and a method of using said delivery device in accordance with aspects of the present disclosure.

Fig. 41A-41D show illustrative flange members according to additional embodiments of the present disclosure.

Many embodiments are described and illustrated herein. The present disclosure is not limited to any individual aspects and embodiments thereof, nor to any combinations and/or permutations of such aspects and/or embodiments. Each of the aspects of the present disclosure and/or their embodiments may be used alone or in combination with one or more other aspects of the present disclosure and/or their embodiments. For brevity, many of these combinations and permutations are not described separately here.

Detailed description

Embodiments of the present disclosure may be used in addition to and/or in combination with aspects of International Application No. PCT/US2018/065192, filed December 12, 2018, which is incorporated herein by reference in its entirety.

As used herein, the terms includes, contains, includes, includes, or any other variations thereof are intended to cover non-exclusive inclusion such that a process, method, article, or device that contains a list of elements includes not only those elements, but may also include other elements not explicitly listed or inherent in such a process, method, product, or device. The term illustrative is used in the sense of exemplary, not in the sense of ideal. It should be noted that an embodiment or implementation described herein as exemplary or illustrative should not be construed as preferable or advantageous, for example, compared to other embodiments or implementations; rather, they are intended to reflect or indicate that the embodiment(s) is/are one example and not an ideal. Additionally, the terms first, second, etc. here do not mean any order, quantity, or importance, but rather are used to distinguish an element, structure, stage, or process from others. Moreover, the terms one and some herein do not mean a limitation in quantity, but rather the presence of one or more of the elements mentioned. Additionally, the terms about, approximately, substantially, etc. used

- 9 044249 when describing a numerical value, means a deviation of +/-10% from this value, unless otherwise stated.

Embodiments of the present disclosure can be used with fluid-containing articles of any type, such as liquid drugs, liquid placebos, or other liquids that can be dispensed in dosage form. As used herein, the term drug substance may refer to a dosage substance including an active ingredient or ingredients, such as, for example, small or large molecules such as painkillers, steroids, or biologics. As used herein, the term biologic can refer to a large molecule (eg, larger than 15 kDa, larger than 30 kDa, larger than 50 kDa, larger than 75 kDa, or larger than 100 kDa) created in a living system, such as a cell. Biologics may include proteins (eg, antihues), nucleic acids, complex sugars, etc. Unlike small molecules, which have well-defined chemical structures, biologics can have very complex structures that cannot be easily quantified by laboratory methods. As used herein, the term finished dosage form may refer to a volume of drug substance dispensed into a primary packaging component for packaging, transportation, delivery, and/or administration to a patient.

The term primary packaging component refers to a packaging component for a finished dosage form, such as a drug container, that is designed and manufactured to be in direct physical contact with the drug substance being dispensed (see, for example, Guidance for Industry on Container Closure Systems for Packaging Human Drugs and Biologics, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, and Center for Biologics Evaluation and Research (May 1999, which is incorporated herein by reference). Examples of primary packaging components include pre-fill syringes, Luer locks, cartridges, and vials made of glass, plastic, other polymers or copolymers, and/or other materials.

As used herein, the terms distal and distal refer to a location (or part of a device) relatively closer to or in the direction of the patient's delivery site, and the terms proximal and proximal refer to a location (or part of a device) relatively closer to or in the direction of the user's an end opposite the distal location of the device portion.

As used herein, the term body, when used with reference to a portion of a device, may refer to a component of the device suitable for containing a volume of drug substance. The housing may include, for example, a barrel (such as a syringe barrel), tube, balloon, or other containing portion of the device. In some embodiments, the body may also include a distal end portion having a tip, a needle, a needle attachment point, and/or a distal cap.

Embodiments of the present disclosure can be used with products typically having low dosage volumes, such as, for example, ophthalmic dosage forms. In some embodiments, the devices of the present disclosure can be used with dosage forms comprising a large molecule, for example, with a molecular weight of 30 kDa or greater. In some embodiments, the devices of the present disclosure can be used with dosage forms that include a large molecule fragment. For example, in some embodiments, the devices of the present disclosure can be used with dosage forms that include an antigen-binding molecule. In some aspects, the antigen binding molecule may be an antibody or an antigen binding moiety. In some embodiments, the devices of the present disclosure may be suitable for use with finished dosage forms including ingredients such as, for example, aflibercept, alirocumab, abisipar pegol, bevacizumab, brolucizumab, conbercept, dupilumab, evolocumab, tocilizumab, certolizumab, abatacept , rituximab, infliximab, ranibizumab, sarilumab, adalimumab, anakinra, trastuzumab, pegfilgrastim, interferon beta-1a, insulin glargine (recombinant), epoetin alfa, dvrbepoetin, filgrastim, golimumab, etanercept, antigen binding fragments of any of the above, or combinations of such binding domains , such as bispecific anti-VEGF or angiopoietin-2, etc.

In some embodiments, the devices and aspects of the present disclosure can be used with any type of treatment for ocular diseases, including for the treatment of patients with diabetic eye disease, post-injection non-infectious endophthalmitis, neovascular (wet) age-related macular degeneration (AMD) ), macular edema after retinal vein occlusion (Retinal Vein Occlusion (RVO), diabetic macular edema (DME), and diabetic retinopathy (DR). In particular, large molecule and small molecule VEGF and/or ANG-2 blockers such as aflibercept, ranibizumab, bevacizumab, conbercept, ORT-302, RTH258 (brolucizumab), abisipar pegol (pegylated designed ankyrin repeating protein - DARPin)), RG7716, or their fragments at any concentration. Intravitreal (IVT) drug administration may

- 10 044249 be an effective treatment for such eye diseases (for example, macular degeneration, retinal vein occlusion, macular edema, retinopathy, etc.), however, IVT administration involves various tasks such as development of the finished dosage form, administration procedure and side effects. For example, ensuring accurate and proper delivery of small volumes (10-100 μL) requires precise design of container components. Accordingly, inaccuracies in dose delivery (eg, overdosing or underdosing) may result in unwanted side effects or loss of efficacy leading to unpredictable and variable clinical responses.

In some embodiments, the devices and aspects of the present disclosure can provide accurate dose delivery while also providing a container closure system to maintain the agent in a sterile, stable, and safe condition to increase the intended shelf life and effectiveness of the agent. IVT formulations are offered primarily in glass vials, but prefilled syringes provide more convenient administration by reducing the number of steps required to prepare a dose. Prepositioning the agent in the devices of the present disclosure can minimize the steps required to prepare a dose for delivery to a patient. Product development considerations may focus on the initial characterization of container components, compatibility of materials with the formulation, stability of the formulation, determination of fill volume, extractability/leaching, and terminal sterilization.

Additionally, careful selection of accessory components, such as disposable syringes and needles, and a detailed administration procedure that includes dosing instructions can ensure successful drug administration. Despite significant efforts to improve the finished dosage form and administration procedures, ocular safety concerns such as endophthalmitis, increased intraocular pressure, and the presence of floating silicone have been reported. The devices and aspects of the present disclosure may provide detailed administration procedures (eg, actuation instructions, dosing instructions, etc.) to ensure successful administration of the agent to a patient to minimize such ocular safety concerns. In some embodiments, the devices and aspects of the present disclosure may also be used for cosmetic applications or medical dermatology, such as for the treatment or diagnosis of allergic reactions.

In some embodiments, the devices and aspects of the present disclosure can be used to perform various ocular injection procedures, such as, for example, intraocular treatments and surgeries involving intravitreal injection of a finished dosage form. The devices and aspects of the present disclosure can be used to dispense finished dosage forms with variable protein concentration and/or viscosity, including, for example, finished dosage forms having a viscosity ranging from about 1 cP to about 10 cP, from about 2 cP to about 9 cps, about 3 cps to about 8 cps, about 4 cps to about 7 cps, or about 5 cps to about 6 cps. Finished dosage forms having other viscosities are also contemplated. Providing an accurate dose by the device of the present disclosure may be important due to possible variability in protein concentration or viscosity of the finished dosage form delivered to the patient. The devices and aspects of the present disclosure can be further used to dispense variable volumes and/or amounts of a finished dosage form, for example, volumes ranging from about 1 μL to about 200 μL, from about 10 μL to about 190 μL, from about 50 μL to about 150 µl, about 75 µl to about 125 µl, about 90 µl to about 110 µl, or about 100 µl. The devices of the present disclosure may be configured to require the application of a minimum force greater than a threshold to effect one or more procedures, such as, for example, device activation, dose delivery, and the like. By requiring the application of minimal force, the devices of the present disclosure can promote control over the administration of a consistent dosage of a finished dosage form and promote safety by minimizing inadvertent movement of device components, potentially reducing pain, discomfort, and harm to the patient.

For some drugs, particularly ophthalmic or other finished dosage forms, dosage accuracy may be especially important. However, it is also contemplated that embodiments of the present disclosure may be applicable to any other liquid products or to any other context for which precise methods of establishing and administering a guaranteed accurate dose or volume of delivery are preferred.

In some embodiments, devices of the present disclosure may be manufactured, packaged, filled, and/or otherwise prepared according to processes appropriate to the products (eg, finished dosage forms) of which they may be a part. For example, in some embodiments, devices of the present disclosure may be sterilized either before or after they are filled and/or packaged. For example, in some embodiments, devices of the present disclosure may be filled and packaged, such as in a blister pack, and/or may be terminally sterilized using any

- 11 044249 suitable method of the prior art. For example, devices of the present disclosure may be terminally sterilized using a chemical sterilization method, such as a method involving ethylene oxide or hydrogen peroxide (eg, vaporized hydrogen peroxide). In some embodiments, devices of the present disclosure may be terminally sterilized using methods described, for example, in International Application No. PCT/US2018/021013, filed March 6, 2018, which is incorporated herein by reference in its entirety.

Dose delivery devices available on the market, such as prefilled syringes or syringes for use with vials, do not adequately assist in accurately dispensing the required volume of drug, actuating the devices, expelling excess drug from the devices, and/or removing bubbles. air from devices. In dose delivery devices containing a small volume of drug substance, particularly (e.g., about 500 μL or less, about 300 μL or less, about 250 μL or less, about 200 μL or less, about 150 μL or less, about 100 μL or less, about 50 µl or less, about 25 µl or less, for example, between about 25 µl and about 50 µl, between about 50 µl and about 100 µl, between about 25 µl and about 100 µl, between about 50 µl and about 150 µl, between about 100 µl and about 250 µl, between about 100 µl and about 150 µl, between about 150 µl and about 250 µl, between about 200 µl and about 250 µl, between about 200 µl and about 500 µl, or between about 250 µl and about 500 µl), it may also be difficult to confirm the presence of the correct dose of drug in the device with the naked eye. There is currently a need in the dose delivery device market, and more specifically in the syringe market, for mechanisms that allow the user to precisely control the delivery of a small volume of drug from a syringe (e.g., prefilled or refillable/refillable syringe), actuate the syringe, remove bubbles air from the syringe, and/or confirm or ensure that the dose volume in the syringe is correct. Embodiments of the present disclosure may assist manufacturers, dosage form suppliers, healthcare professionals, and/or patients in accurately manufacturing, filling, or preparing a dosing device, actuating the device, removing air bubbles from the device, confirming a dose, and/or administering a dose from the device to the patient. In addition, embodiments of the present disclosure may help prevent or mitigate the effects of errors or deviations in the manufacture or use of devices, such as errors or deviations in the placement of dosage lines on devices, deviations in device geometry (for example, deviations in syringe neck geometry), deviations in the manufacturing tolerances of components, and/or deviations or errors in establishing the dosage line before delivery of the drug.

In some examples, embodiments of the present disclosure may particularly assist individuals who may have difficulty accurately and correctly setting doses. For example, embodiments of the present disclosure may assist elderly people, young children, or people with physical or mental disabilities in establishing accurate dosages.

Various embodiments of dose delivery devices, in particular syringes, are described herein. In some examples, embodiments or aspects of embodiments disclosed herein may be used in conjunction with existing syringe body parts to modify off-the-shelf products, which may reduce the time to develop and manufacture dose delivery devices. In other examples, embodiments or aspects of embodiments disclosed herein may be included in devices during manufacture. The syringes described herein may be pre-filled or may be refillable/refillable.

Embodiments of the present disclosure may include syringes having rotating portions, threaded portions, springs, gears, detents, channels, grooves, and the like, which may allow a user to precisely control the movement of actuating and dose delivery elements, such as pistons or stoppers. Such parts may be designed to reduce human error and/or increase accuracy.

In some embodiments, visualization devices, such as magnifiers, may be provided with, attached to, or located on delivery devices to help increase the visibility of dose measurement marks on the devices. It is contemplated that aspects of one embodiment (such as sleeves, channels, locking components, protrusions, retainers, threaded portions, grips, visual, tactile, or audible indicators, etc.) may be combined with aspects of one or more other embodiments implementation to create various combinations and permutations of features in one device.

In some embodiments, devices according to the present disclosure may be shown as including a single type of piston rod and piston or as including a general schematic representation of a piston rod and piston. For example, some devices according to the present disclosure may be shown or described as including, for example, a piston rod having a ball-terminating end that engages a stopper such that the piston rod and stopper can be secured together. It is contemplated that multiple and/or different configurations of piston rods and stoppers may be consistent with each of the embodiments disclosed herein. For example, in some cases, the aforementioned ball-terminated piston rod may be used with the embodiments disclosed herein. In some embodiments, the piston rod may not be attached to the stopper, but instead may be positioned near, adjacent to, or flush with the stopper such that pressure from the piston rod toward the stopper can push the stopper, but pull, twist, or no other movement of the piston rod could cause such pulling, twisting, or other movement of the stopper. As another example, in some embodiments, the piston rod may be attached to the stopper by threads, a clamp, or adhesive, or it may be integral with the stopper (e.g., it may be manufactured in the same mold as the stopper).

In some embodiments, devices of the present disclosure may include various cosmetic features appropriate to the intended users of the devices. For example, devices according to the present disclosure may be manufactured and marketed for use by pediatric patients, elderly patients, or patients with disabilities. In such cases, the devices of the present disclosure may include child-friendly colors, comic book images, or other cosmetic features attractive to children, or high-contrast colors, textured surfaces, or other features to facilitate identification and/or use. In some cases, devices according to the present disclosure may include inscriptions, markings, or other features designed so that they are easily recognized by intended users. For example, labels on a pediatric device or on a device for use by disabled or disabled persons or the elderly may have larger, more accessible markings that can be easily recognized and read by the user(s) of the device. In some embodiments, the inscriptions or markings may be raised, molded, or embossed.

With reference now to FIG. 1A-1E, views of the delivery device 1050 and its components are shown. The device 1050 includes a housing 1060 and a locking component in the form of a flange member 1070 with a proximal collar 1072 surrounding an opening 1073 (shown, for example, in FIG. 3B3E) through which a piston rod 1080 may extend into the housing 1060. The piston rod 1080 includes itself an actuator portion 1082 that may be actuated (e.g., pushed or rotated) to rotate the piston rod 1080 or to move the piston rod 1080 longitudinally into the housing 1060. The actuator portion 1082 may be configured to be installed (e.g., inserted or mounted) inside the proximal collar 1072.

The device 1050 may be, for example, an injection device, such as a syringe, for dispensing a predetermined volume of drug dosage. In some embodiments, device 1050 may be a pre-filled syringe. For example, the user may receive the assembled and packaged device 1050, ready for use, with some volume of drug dispensed already located between the stopper 1062 in the housing 1060 and the ejector end 1064 of the housing 1060. In some embodiments, an air bubble (not shown) may be is also located between the stopper 1062 and the ejector end 1064. In additional embodiments, the device 1050 may be a refillable syringe.

Housing 1060 may be any suitable housing configured to hold and eject a predetermined volume of drug substance being dispensed. In some embodiments, housing 1060 may have, for example, a hollow cylindrical portion. Housing 1060 may be configured to hold any suitable volume of drug dispensed for delivery to, for example, a patient and (together with other components of device 1050) push a predetermined portion of the held volume through, for example, ejector end 1064 during an actuation step and/or step delivery. In some embodiments, housing 1060 may be configured to hold and (together with other components of device 1050) eject a relatively small volume of drug dispensed (e.g., less than about 100 μL, e.g., less than about 80 μL, less than about 60 μL, less about 40 µl, less about 20 µl, less about 10 µl, about 95 µl, about 90 µl, about 85 µl, about 80 µl, about 75 µl, about 70 µl, about 65 µl, about 60 µl, about 55 µl, about 50 µl, about 45 µl, about 40 µl, about 35 µl, about 30 µl, about 25 µl, about 20 µl, about 15 µl, about 10 µl, or about 5 µl). The device 1050, along with its other components, may be further configured to minimize the residual volume of drug dispensed remaining in the housing 1060 after delivery of a predetermined small volume to a patient. In some embodiments, housing 1060 may be prefilled (eg, prior to completion of assembly, packaging, sterilization, and/or delivery of device 1050 to users). In some embodiments, the stopper 1062 may be configured to hold a predetermined volume of drug dispensed within the cavity of the housing 1060.

- 13 044249

The flange member 1070 may be of any suitable size and/or shape for use as a locking component in the delivery device 1050, to close, partially close, cover, or partially cover the end of the housing 1060 opposite the ejector end 1064, and/or to support and retain piston rod 1080 in place within housing 1060. In some embodiments, flange member 1070 may include a distal collar 1075 configured to engage housing 1060 and hold flange member 1070 in place relative to housing 1060. For example, distal collar 1075 may include including a lip 1071 that can slide under or relative to the housing flange 1061 to hold the flange member 1070 in place (eg, to slideably connect the flange member 1070 to the housing 1060). In alternative embodiments, the lip 1071 of the distal collar 1075 may be made of a flexible or semi-flexible material so that it can snap into place over the housing flange 1061. In additional embodiments, the distal collar 1075 or other portion of the flange member 1070 may be glued, molded, or attached to the body 1060, or may be frictionally engaged with the body 1060.

The flange member 1070 may be or may include a locking component; that is, part or all of the flange element 1070 may be configured to control the movement of the piston rod 1080 by blocking the movement of the piston rod 1080 when the piston rod 1080 is in certain configurations relative to the flange element 1070. For example, the flange element 1070 may be configured with the ability to control the rotational and longitudinal movement of the piston rod 1080, for example, through an opening 1073 (see, for example, FIGS. 3B-3E), which complements the size or shape of parts of the piston rod 1080 (for example, the journal 1084 and the actuation part 1082, and/or other parts of the piston rod 1080 shown in Fig. 3I and 3M). As described in more detail below, flange member 1070 may be formed from various materials having minimum strength and/or stiffness that may provide additional control of rotational or longitudinal movement of piston rod 1080. For example, flange member 1070 may be configured to resist proximal movement (or pulling back) the piston rod 1080 (for example, to prevent disassembly of the device 1050 by retracting the piston rod 1080) up to a predetermined force based at least in part on the material composition of the flange element 1070. It should be understood that the flange element 1070 can be configured in this manner such that the application of a force greater than a predetermined force may cause one or more of the flange member 1070 and the piston rod 1080 to collapse, rendering the device 1050 inoperable.

As a further example, flanged member 1070 may be configured to resist rotational movement of piston rod 1080 (e.g., to prevent unintended rotation) up to a predetermined force based at least in part on the material composition of flanged member 1070. Additionally and/or alternatively, flanged element 1070 may be configured to resist distal movement of piston rod 1080 to control the rate of dose delivery (eg, to prevent inadvertent delivery) based at least in part on the material composition of flange element 1070. Various other components of device 1050 other than flange element 1070 may include a material composition that provides frictional interaction to prevent disassembly of the device 1050, unintentional rotation of the piston rod 1080, and/or unintentional dose delivery.

A proximal shoulder 1072 of the flange member 1070 may be configured to receive a portion of the actuation portion 1082 of the piston rod 1080 while blocking the distal movement of the projections 1086 of the piston rod 1080 beyond a predetermined point until the piston rod 1080 is rotated to a specific position. As shown in FIG. 1A and 1B, collar 1072 may be cylindrical; in alternative embodiments, the collar 1072 may be of any suitable size or shape comparable to the actuation portion 1082. The collar 1072 may also include cavities, such as slots 1074, into which projections 1086 of the piston rod 1080 may be received. The slots 1074 may have proximally facing holes and may have a depth dimension parallel to the longitudinal axis of the device 1050. The number and configuration of the slots 1074 may correspond to the number and configuration of projections 1086 on the piston rod 1080. In some embodiments, the slots 1074 may be located around the perimeter of the collar 1072 in a radially symmetrical configuration . In additional embodiments, collar 1072 may include only one slot 1074. The depth of slots 1074 may correspond to the distance that piston rod 1080 must move to push stopper 1062 toward push end 1064 and dispense a predetermined volume of drug dispensed from the housing. 1060 through the ejector end 1064. Preferably, the predetermined volume of drug dispensed to be dispensed from the housing 1060 may be controlled during manufacture by, for example, selecting a specific depth of the slots 1074. In some embodiments, the device 1050 may be configured such that so that normal variations in the manufacture of other parts of the device 1050 (for example, the body 1060 or the piston rod 1080) do not

- 14 044249 could cause variations in the volume of drug dispensed to be dispensed from the housing 1060. As such, the target volume can be controlled simply by changes in the fabrication of the flange member 1070.

In some embodiments, the flange member 1070 may include one or more flanges 1076, which may be configured to assist a user in holding the device 1050 and/or ejecting the drug dispensed from the device 1050. In some embodiments, shown in FIGS. . 1A-1E, flange member 1070 may include two flanges 1076 opposed to each other and extending perpendicular to the longitudinal dimension of device 1050. In some embodiments, flange member 1070 may include other flange or flange arrangements, such as four flanges, or one circular flange extending radially outward from the central longitudinal axis of the device 1050. In some embodiments, the flange member 1070 may extend radially outward from the central longitudinal axis of the device 1050 beyond the circumference of the housing 1060. In such embodiments, the flange member 1070 may support the device 1050, when the device 1050 is placed on a surface, may prevent the device 1050 from rolling on a flat surface, and/or may allow the device 1050 to be easily gripped. In other additional embodiments, aspects of the locking component of the flange element 1070 (e.g., shoulder 1072) may be separate from the flange element 1070 such that the delivery device 1050 includes a separate flange member and a locking component.

The piston rod 1080 may generally be rotatable about a central longitudinal axis (eg, in one direction or both directions). In some embodiments, rotation of the piston rod 1080 may be accomplished by gripping and/or twisting the actuation portion 1082 relative to the flange member 1070 and/or housing 1060. In some embodiments, the projections 1086 may assist the user in gripping and/or twisting the actuation portion 1082 relative to flange member 1070 and/or body 1060 by providing additional surface area that a user can grip and/or push to twist actuation portion 1082. In some embodiments, only a portion or portions of piston rod 1080 (e.g., actuation portion 1082 and/or journal 1084) may be rotatable relative to flange member 1070 and/or body 1060. In some embodiments, piston rod 1080 may be rotatable relative to flange member 1070 in response to application of a predetermined torque force to actuation portion 1082. Flange member material composition 1070 may be determinant of a given torque force required to rotate the piston rod 1080 relative to the flange member 1070. For example, the flange member 1070 may be formed from various materials having a given stiffness that may generate frictional resistance to the piston rod 1080 to control the rotational movement of the piston rod 1080 up to a predetermined force (for example, to prevent unintentional rotation/accidental torsion of the piston rod 1080). Additionally, the material composition of the flange member 1070 may provide frictional tolerance to control the distal movement of the piston rod 1080 up to a predetermined force (eg, to prevent device 1050 from inadvertently delivering a dose).

The rod 1081 of the piston rod 1080 may have any thickness and cross-sectional shape suitable for installation in the body 1060 while maintaining strength. For example, in some embodiments, the rod 1081 may have a thickness along at least one dimension such that it can fit and slide into the housing 1060. Advantageously, such thickness may help prevent unwanted rocking of the piston rod 1080 relative to other components of the device 1050. In additional In embodiments, the rod 1081 may have a thinner thickness that still maintains strength (eg, does not bend, break, or deform during assembly and/or use of the device 1050). In some embodiments, portions of the rod 1081 may be configured to allow the piston rod 1080 to rotate relative to the flange member 1070, while other portions of the rod 1081 may be configured to prevent the piston rod 1080 from rotating relative to the flange member 1070 (see, for example, Fig. 3I-3Q).

The piston rod 1080 may also include a distal tip 1083 (see, for example, FIG. 1D) configured to push, attach to, or mate with the stopper 1062. The tip 1083 may be of any size or shape suitable to achieve this purpose. . In some embodiments, for example, the tip 1083 may be configured to engage the stopper 1062 through an opening in the stopper 1062. In additional embodiments, the tip 1083 may be shaped like a ball configured to fit into an opening of the stopper 1062. In other additional embodiments, , the tip 1083 may have a flat surface parallel to the proximal surface of the stopper 1062 and may be configured to push the stopper 1062 distally without being attached to the stopper 1062. In additional embodiments, the tip 1083 may have any shaped surface suitable for pushing the stopper

- 15 044249

1062 distally.

In some embodiments, the journal 1084 of the piston rod 1080 and the bore 1073 of the flange member 1070 may have complementary geometries that limit the range and direction in which the piston rod 1080 (or portion thereof) can rotate, depending on the particular longitudinal and/or rotational position of the piston rod 1080 relative to the flange element 1070. In some embodiments, the actuation portion 1082 of the piston rod 1080 and shoulder 1072 may also include complementary geometries that control the range and direction in which the piston rod 1080 can move relative to the flange element 1070. For example, the rotation and/or longitudinal movement of the piston rod 1080 may be limited based on the actuation, preparation, and/or dose delivery steps of the method of using the device 1050 (see, for example, the method described with respect to FIG. 3A3F, and an additional/alternative method described in relation to FIG. 3G and 3H) and the corresponding position of the piston rod 1080 relative to each step in such methods. For example, piston rod 1080 may be limited to extend proximally from flange member 1070 (e.g., when pulled out or pulled out) after assembly of device 1050. In addition, piston rod 1080 may be limited to rotate about its longitudinal axis before device 1050 will be in the powered state, and/or after the device 1050 is in the delivery state. Additionally, longitudinal movement of the piston rod 1080 in the proximal direction (for example, to retract the piston rod 1080) can be limited after the device 1050 is in the actuated and/or delivered state by complementary geometries of the piston rod journal 1084 1080 and the openings 1073 of the flange member 1070 and/or the actuation portion 1082 of the piston rod 1080 and the shoulder 1072 of the flange member 1070. Advantageously, this may prevent unwanted retraction of the piston rod in cases where the piston rod 1080 is not retained within the body 1060, such as by attachment to the stopper 1062. For example, in some embodiments, the piston rod 1080 may be configured to simply contact or abut the stopper 1062 such that proximal movement of the piston rod 1080 does not move the stopper 1062 proximally. In such cases, proximal movement of the piston rod 1080 can be prevented by the interaction between the complementary geometries of the piston rod 1080 and the flange element 1070. In addition, the interaction between the actuation portion 1082 of the piston rod 1080 and the shoulder 1072 of the flange element 1070 can limit the longitudinal movement of the piston rod 1080 in the distal direction. As an example, motor 1680 may be limited in distal movement after the driven state but before the delivered state.

Once moved into the delivery state, the projections 1086 on the actuation portion 1082 may be longitudinally aligned with the slots 1074 of the collar 1072, allowing the piston rod 1080 to distally move to dispense a desired volume of drug from the housing 1060. As such, the piston rod 1080 may include a number and configuration of projections 1086 such that each projection 1086 can move distally into the slot 1074 when the piston rod 1080 is in a particular position (eg, delivery state). In some embodiments, one, two, three, or more projections 1086 may extend from the actuation portion 1082 in correspondence with one, two, three, or more slots 1074, respectively. For example, as shown, two projections 1086 may extend from the sides of the actuation portion 1082 in a radially symmetrical configuration (corresponding to two slots 1074 in collar 1072). In some embodiments, the radial symmetry of the multiple protrusions 1086 (and slots 1074) may preferably allow the protrusions 1086 to be installed in the slot 1074 in multiple configurations (eg, depending on whether the actuation portion 1082 rotates in one direction or another). In such embodiments, the actuation portion 1082 may rotate in one direction or another based on, for example, user preference, right-handedness or left-handedness, or other factors. In some embodiments, piston rod 1080 may not be pulled proximally or pulled back from housing 1060 (e.g., toward actuation portion 1082) after piston rod 1080 is in the actuated state and/or after the required volume of drug dispensed will be delivered from the device 1050 by pressing the piston rod 1080 into the housing 1060 (eg, due to the geometry of the neck 1084 and/or orifice 1073).

In some embodiments, device 1050 may be configured to facilitate its use and may include one or more devices that assist the user by providing tactile or visual feedback. For example, one, two, or more components of device 1050 may have contrasting colors or textures. In some embodiments, for example, flange member 1070 may have a different color than piston rod 1080. As a further example, one component of device 1050 may have two or more colors or textures. In some embodiments, for example,

- 16 044249 the actuation portion 1082 may include a first color on a distal portion of the actuation portion 1082 that is covered by the shoulder 1072 when the device 1050 is actuated, and a second color on the second portion of the actuation portion 1082 that moves adjacent the shoulder 1072 when the device 1050 is actuated to help indicate to the user that device 1050 is actuated correctly. As a further example, in some embodiments, flange member 1070 may provide a different tactile sensation than piston rod 1080 and/or body 1060. For example, flange member 1070 may be relatively rougher or smoother than piston rod 1080 and/or body 1060. or housing 1060. As another example, one or more components of device 1050 may have textures that assist in holding, gripping, identifying, or using device 1050. For example, flange member 1070 may have a slightly rough or raised texture to assist the user in gripping the flanges 1076, and/or to prevent the user's fingers from slipping off the flanges 1076 during use. In some embodiments, some or all of the flange member 1070 may have a smooth feel. As another example, the actuation portion 1082 of the piston rod 1080 may include a rough or raised texture to assist in gripping and rotating the piston rod 1080. For example, as shown in FIG. 1A-1I, 2A, 2B, and 3A-3H, the actuation portion 1082 may include circular fins on its side surface(s). The actuation portion 1082 may have any suitable number of ridges on its side surface(s) to provide texture. In additional embodiments, the actuation portion 1082 may not have any fins on its side surface(s).

In some embodiments, device 1050 or one or more components thereof may include colors, marks, or markers that may indicate the contents or state of device 1050, and/or that may direct or provide instructions to the user of device 1050. Examples include itself one or more marks for indicating the actuation position relative to the dose delivery position of the piston rod, one or more marks for indicating the directions in which to rotate or move the piston rod 1080, and/or one or more marks for indicating the amount of drug dispensed included in device 1050 (eg, line marks on housing 1060). The marks may be, for example, adhesive or printed on components of the device 1050, or may be embossed or molded as part of the components of the device 1050. In some embodiments, one or more textured marks (e.g., embossed or molded on the device 1050) may also serve as as a textured, rough, or raised surface to assist a user in gripping or using the device 1050. One or more exemplary markings may include words, numbers, pointers, and/or symbols (e.g., lines, padlocks, arrows, diagrams, and etc.).

In some embodiments, device 1050 may be configured to emit one or more sounds during use. For example, device 1050 may produce a clicking sound upon completion of the actuation step or upon rotation of the piston rod to a position suitable for dispensing a predetermined volume of drug dispensed. The clicking sound may be created through, for example, friction between two or more components (e.g., piston rod 1080 and flange member 1070), or a portion of one component contacting another portion (e.g., journal 1084 of piston rod 1080 contacting flange member bore 1073). element 1070). In some embodiments, device 1050 may include one or more detents or projections on adjacent surfaces of, e.g., piston rod 1080 and flange member 1070, which may produce a clicking sound upon contact with each other (e.g., wings 1089 on journal 1084, contacting the latches 1078 surrounding the hole 1073, as shown in Fig. 3R-3V). Such sounds may serve as audible feedback to indicate that the user has reached a particular milestone in using the device 1050.

In some embodiments, device 1050 may include additional features or components to control movement of piston rod 1080 relative to housing 1060. For example, as shown in FIG. 1F, flange member 1070 may include an opening 1079 through which a pin 1077 may pass. The pin 1077 may be configured to mate with an actuation portion 1082 of the piston rod 1080 (e.g., to slide into a hole (not shown) in the actuation portion 1082) such that when pin 1077 is inserted and engaged with actuation portion 1082, piston rod 1080 cannot move proximally or distally relative to housing 1060 and flange member 1070. In some embodiments, pin 1077 may also prevent rotational movement of piston rod 1080 relative to flange member element 1070. The pin 1077 may be inserted after the device (eg, device 1050 shown in FIGS. 1A and 1B) has been filled and assembled to prevent unwanted movement of the piston rod 1080 prior to use. In some embodiments,

- 17 044249 the pin 1077 may remain inserted during packaging, transportation, and delivery of the device 1050. Before using the device 1050, the pin 1077 may be removed or positioned so that it does not engage the actuation portion 1082.

As shown in FIG. 1G and 1H, in some embodiments, protrusion 1093 may be located at a distal portion of actuation portion 1082, which may be located within flange member 1070 after assembly of device 1050. An inner lip 1091 of flange member 1070 may extend beyond protrusion 1093 such that actuation portion 1082 cannot be pulled proximally from the flange member 1070. In some embodiments, one or both of the projection 1093 and the lip 1091 may be positioned circumferentially around the actuation portion 1082 such that the lip 1091 blocks the projection 1093 regardless of the rotational position of the actuation portion 1082 relative to flange member 1070. The protrusion 1093 and lip 1091 may have the rectangular cross-sectional profiles shown in FIG. 1G, the angled cross-sectional profiles shown in FIG. 1H, or any other suitable cross-section profiles. In some embodiments, the cross-sectional profile of protrusion 1093, lip 1091, or both may be selected to facilitate manufacturing (e.g., machining or shaping the shape of protrusion 1093 or lip 1091) or may be selected to facilitate assembly (e.g., insertion of piston rod 1080 in and partly through flange element 1070).

As shown in FIG. 1I, in some embodiments, the actuation portion 1082 may include one or more projections 1096 extending radially outward from the outer perimeter of the projection 1093. For example, the projection 1093 may include a pair of projections 1096 located around the projection 1093 in opposite locations relative to each other. . The protrusions 1096 may include various suitable sizes, shapes, and/or cross-sectional profiles. In some embodiments, the projections 1096 may be circular in shape with a rounded outer profile to facilitate movement of the projection 1093 within the flange member 1070.

In the present example, projections 1096 may be located along a side of projection 1093 that is longitudinally aligned with a corresponding side of the actuation portion 1082 including projections 1086. In other examples, projections 1096 may be located along a side of projection 1093 that is offset (e.g., not longitudinally aligned) with respect to the side of the protrusion 1093 including the protrusions 1086. The protrusions 1096 may be formed from a variety of flexible materials, including, for example, a polymer such as plastic, rubber, etc. It should be understood that the piston rod 1080 may include more and/or fewer projections 1096 on the projection 1093 or other portions of the actuation portion 1082 than are shown and described herein without departing from the scope of this disclosure.

Fig. 1J shows the distal end portion of the flange member 1070 including one or more recesses 1097 along the inner surface. The recesses 1097 may be configured to receive projections 1096 when the projection 1093 is received within the flange member 1070 and is positioned adjacent and/or in contact with the lip 1091. It should be understood that the lip 1091 may be configured to require the application of a hydrodynamic force to the piston rod 1080 to receive projections 1096 and protrusion 1093 distal from lip 1091 and in flange member 1070, whereby device 1050 is actuated and prevents retraction (e.g., proximal movement) of piston rod 1080 relative to flange member 1070. It should be understood that by preventing movement of piston rod stem 1080 after initial assembly into the flange member 1070, the device 1050 may be configured to prevent reuse of the device 1050 after initial use and/or to prevent the inadvertent suction of air forming bubbles within the device 1050. In the present example, the flange member 1070 may include a plurality of recesses 1097 located around the distal end portion in an annular array relative to each other. Multiple recesses 1097 may be spaced apart around the circumference of flange member 1070. In some embodiments, flange member 1070 may include recesses 1097 having variable sizes and/or shapes relative to each other.

As described in more detail below, a subset of the plurality of recesses 1097 may be configured to receive the projections 1096 and allow them to pass therethrough upon movement of the projection 1093 relative to the flange member 1070. A second subset of the plurality of recesses 1097 may be configured to receive the projections 1096 and not allow them to pass through. pass through it so that the protrusion 1093 is limited in further movement relative to the flange member 1070, as explained in more detail below.

For example, as shown in FIG. 1K, flange member 1070 includes a pair of flared recesses 1097a located around bore 1073 (with piston rod 1080 received therethrough) at opposite locations relative to each other (eg, at an angle of about 180° with respect to each other). The flange member 1070 further includes a pair of tapered recesses 1097b located around the opening 1073 at opposite locations relative to each other (eg, at an angle of about 180° with respect to each other). The recess 1097a may be positioned at an angle of about 90° relative to the adjacent recess 1097b along the circumference of the flange member 1070. The flared recesses 1097a may include a center wall transverse (e.g., perpendicular) to the longitudinal length of the flanges 1076, and side walls which are located at an angle to the central wall. The tapered recesses 1097b may include a center wall that is parallel to the longitudinal length of the flanges 1076 and side walls that are perpendicular to the center wall. It should be understood that the widened recesses 1097a may define a larger opening for receiving projections 1096 relative to the narrowed recesses 1097b. It should also be understood that the side walls of the recesses 1097a, 1097b may have a height that is parallel to the longitudinal length of the device 1050.

In the first configuration shown in FIG. 1K, piston rod 1080 is received through flange member 1070, and projection 1093 is oriented relative to bore 1073 such that projections 1096 are received within flared recesses 1097a. The angled side walls of the flared recesses 1097a may provide clearance to facilitate movement of the protrusions 1096 from the flared recesses 1097a in response to rotation of the piston rod 1080 relative to the flange member 1070. In this example, the protrusions 1096 may move along the angled side walls of the flared recesses 1097a, when the protrusion 1093 rotates relative to the hole 1073.

As can be seen in FIG. 1L, the projections 1096 may abut the inner surface of the flange member 1070 defining the opening 1073 when the projection 1093 is rotated. The projections 1096 may generate frictional interaction with the flange member 1070 as they move between adjacent recesses 1097. FIG. 1M shows a projection 1093 positioned relative to an opening 1073 with projections 1096 aligned with and received in the tapered recesses 1097b. In this example, the piston rod 1080 may be configured to generate audible and/or tactile feedback in response to the constricted recesses 1097b receiving the projections 1096. For example, a clicking or popping sound may be generated in response to the release of pressure applied to the internal projections 1096. surface of the flange member 1070 when the projections 1096 are received in the tapered recesses 1097b. Additionally and/or alternatively, audible feedback may be generated in response to the projections 1096 expanding and colliding with one or more walls defining the constricted recesses 1097b when received therein.

It should be understood that the frictional interaction between the projections 1096 and the flange member 1070 can be eliminated by receiving the projections 1096 within the tapered recesses 1097b. The side walls of the tapered recesses 1097b may provide a physical constraint that prevents further movement of the projections 1096. In this example, the piston rod 1080 may be secured relative to the flange member 1070 such that the projection 1093 cannot rotate further relative to the hole 1073 when the projections 1096 are received internally narrowed recesses 1097b.

As shown in FIG. 1N-1P, in some embodiments, the piston rod 1080 may additionally or alternatively include a projection 1085 on the rod 1081 that may be configured to engage an opening 1073 of the flange member 1070 such that the projection 1085 can only move distally through the opening 1073 The side 1092 of the hole 1073 may be angled to allow the distal passage of the projection 1085 and to block the proximal passage of the projection 1085 when the rod 1081 moves through the hole 1073. The projection 1085 and/or the side 1092 may have any suitable shape or configuration to achieve this goals. In some embodiments, the shape or configuration of the projection 1085 and/or side 1092 may be selected to facilitate manufacturing (eg, machining or shaping the shape of the projection 1085 and/or flange member 1070).

In other embodiments, flange member 1070 may include a movable arm 1071a seen in FIG. 1Q-1T. The movable arm 1071a may include a first end 1071b extending outwardly from the bead 1072 and a second end 1071c located within the bead 1072. The movable arm 1071a may be movable (eg, pivotable) about the rotation pin 1071d. The second end 1071c may be positioned within the opening 1073 such that the movable arm 1071a is configured to engage the protrusion 1085 after receiving the piston rod 1080 in the flange member 1070. Referring first to FIG. 1Q, the piston rod 1080 may be configured to actuate the device 1050 by moving the rod 1081 distally through the flange member 1070 until it encounters the movable arm 1071a.

As can be seen in FIG. 1R, the second end 1071c may abut the protrusion 1085 when the movable arm 1071a is in the obstructed position. The second end 1071c may be configured to inhibit movement of the piston rod 1080 relative to the flange member 1070 when the piston rod 1080 is in the actuation position. It should be understood that the distance between the second end 1071c and the projection 1085 may determine the actuation distance

- 19 044249 action for moving the piston rod 1080 to operate the device 1050. The movable arm 1071a may be configured to move (eg, rotate) relative to the shoulder 1072 and around the rotation pin 1071d to displace the second end 1071c from an obstructed position. The axis of rotation along which the rotation pin 1071d extends may be substantially perpendicular to the longitudinal axis along which the piston rod 1080 extends.

For example, as seen in FIG. 1S, the movable arm 1071a may be actuated in response to movement of the first end 1071b distally toward the flange 1076 and around the pin 1071d. In some embodiments, the first end 1071b may be actuated in response to a distally directed force applied thereto, for example, by the user of the device 1050. The second end 1071c may be moved proximally away from the flange 1076 and relative to the rotation pin 1071d in response to distally move the first end 1071b, causing the second end 1071c to disengage from the protrusion 1085.

Accordingly, as shown in FIG. 1T, the movable arm 1071a may allow the piston rod 1080 to be moved relative to the flange member 1070 until the projection 1085 engages a stop 1072a located at the distal end of the hole 1073. The stop 1072a may cause the piston rod 1080 to be positioned at the end position of the piston rod 1080. when the protrusion 1085 engages with it. It should be understood that the distance between the second end 1071c and the anvil 1072a may determine the dose delivery distance for moving the piston rod 1080 to dispense a controlled volume of substance from the device 1050.

As shown in FIG. 1U and 1V, in some embodiments, the actuation portion 1082 of the piston rod 1080 may additionally or alternatively include one or more extensions 1087 configured to mate with side openings 1094, 1095 in the collar 1072 of the flange member 1070. The extensions 1087 may extend distally from actuation portion 1082 and may have an angled or rounded distal portion configured to be pushed inward toward the central axis of the piston rod 1080 when the actuation portion 1082 is pushed distally into the collar 1072. The angled or rounded distal portion of each extension 1087 may include including a hook or staple portion 1087a. The extensions 1087 may further be made of a flexible material to allow them to be pushed into the bead 1072 and allow them to spring outward when they are no longer constrained by the side surface of the bead 1072. The side openings 1094, 1095 in the bead 1072 may be configured to receive a hook or staple portion. 1087a of the extension 1087 such that once the extension 1087 reaches the side hole 1094 or 1095, the hook or staple portion 1087a can spring outward into the side hole 1094 or 1095 and then prevent proximal movement of the piston rod 1080. The number of extensions 1087 may coincide with the number m side openings 1094 and side openings 1095 so that all extensions 1087 can be received in the corresponding side openings 1094 or 1095 simultaneously as the piston rod 1080 moves distally relative to the flange member 1070.

Specifically, the first side openings 1094 may be configured to receive hook or staple portions 1087a of the extensions 1087 after assembly of the device 1050 to prevent proximal movement of the piston rod 1080 once the piston rod 1080 is inserted into a ready-to-use position. When the hook or staple portion 1087a of each extension 1087 is received in the first side openings 1094, it may produce a clicking sound when it engages the collar 1072, thereby providing audible and/or tactile feedback indicating that the device is in the ready position. for use. In some embodiments, each of the first side openings 1094 may extend around a partial circumference of the collar 1072 such that the hook or staple portions 1087a of the extensions 1087 may be received in the side openings 1094 over a range of rotational positions of the piston rod 1080 relative to the flange member 1070. Second Side Openings 1095 may be configured to receive hook or staple portions 1087a of extensions 1087 when device 1050 is in a delivery configuration (eg, after actuation and additional rotation of actuation portion 1082 to align protrusions 1086 with slots 1074). In the embodiment shown in FIG. 1U and 1V, extensions 1087 are longitudinally aligned with projections 1086 and, as shown in FIG. 3C-3F, side openings 1095 are similarly longitudinally aligned with slots 1074 to allow actuation portion 1082 to be distally moved further into collar 1072 when the device is in a delivery configuration. It should be understood that the device may be placed in a delivery configuration in response to the application of a distally directed force to the actuation portion 1082 to overcome the engagement of the side openings 1094 with the extensions 1087, and a rotational force to overcome the frictional force between the interior of the collar 1072 and the extensions 1087. However, in other embodiments, it is contemplated that extensions 1087 and side openings 1094, 1095 may be in any suitable complementary configurations to assist in controlling proximal movement of the piston

- 20 044249 of the rod 1080.

In other embodiments, as shown in FIG. 1W, side openings 1094 may be positioned along collar 1072 in longitudinal alignment with side openings 1095. Device 1050 may be actuated by receiving hook or staple portions 1087a initially positioned proximally from side openings 1094 within side openings 1094. In some examples , feedback (e.g., tactile, audible, etc.) may be generated in response to receiving extensions 1087 within the side openings 1094. It should be understood that the proximal end of the collar 1072 may resist the distal movement of the piston rod 1080 relative to the flange member 1070 in response to the engagement of the hook or staple portions 1087a with the collar 1072 in the side openings 1094. Application of a distally directed force to the piston rod 1080 may cause the extensions 1087 to be released from the side openings 1094 and move distally through the collar 1072 before being received within the side openings 1095.

It should be understood that the distally directed force required to deflect the extensions 1087 inward and to release the hook or staple portions 1087a from the side openings 1094 may correspond to a minimum driving and hydrodynamic force. Accordingly, piston rod 1080 may be maintained in a constant radial orientation during the actuation and delivery phases of device 1050. In other embodiments, more and/or fewer side openings may be provided along the circumferential wall of collar 1072 longitudinally aligned with and/or offset (for example, not longitudinally aligned) relative to the side holes 1094, 1095.

As can be seen in FIG. 1X, flange member 1070 may alternatively include one or more internal projections 1095' instead of the side openings 1095 shown and described above. In this example, piston rod 1080 may be pre-installed into flange member 1070 with extensions 1087 (FIG. 1V) pressed into collar 1072 and positioned relatively proximal to side openings 1094. Device 1050 may be actuated by pushing piston rod 1080 distally through flange member 1070 until extensions 1087 are received within side openings 1094. In some examples, feedback (e.g., tactile, audible, etc.) may be generated in response to receiving extensions 1087 within side openings 1095. In additional embodiments, the side openings 1094 may be flared and/or the extensions 1087 may have a distally tapering profile to facilitate further distal advancement of the piston rod 1080 from the actuation position to the dose end position.

Further movement of the piston rod 1080 relative to the flange member 1070 may cause the extensions 1087 to flex radially inward toward each other, allowing the piston rod 1080 to move distally to deliver a dose from the device 1050. The piston rod 1080 may continue to move distally relative to the collar 1072 until until the hook or staple portions 1087a (FIG. 1V) collide with the inner projections 1095'. The internal projections 1095' may be configured to contact the extensions 1087 and secure the piston rod 1080 at the dose end position, and/or prevent further distal movement of the piston rod 1080 relative to the flange member 1070. Accordingly, further movement (e.g., proximal and/or distal ) of the piston rod 1080 relative to the flange member 1070 may be obstructed by internal projections 1095' engaging hook or staple portions 1087a within collar 1072. The internal projections 1095' may include complementary hook or staple portions that are configured to engage the hook or staple portions. staple-like portions 1087a or extensions 1087. It should be understood that the distance between the side openings 1094 and the internal projections 1095' may determine the dose delivery distance for dispensing a controlled volume of substance from the device 1050.

In other embodiments shown in FIGS. 2A-2C, flange member 1070 may include an attached sleeve 1072P extending from collar 1072. The attachment sleeve 1072P may have a circular cross-section defining an internal passage with an opening at each terminal end of the attached sleeve 1072P. The inner channel of the attached sleeve 1072P may extend through the longitudinal length of the attached sleeve 1072P and may be longitudinally aligned with the hole 1073 (FIG. 10) such that the corresponding longitudinal axis of the inner channel and the hole 1073 are coaxial with each other. The attachment sleeve 1072P may be configured to receive the rod 1081. In some embodiments, the attachment sleeve 1072P may be integral with the collar 1072, while in other embodiments, the attachment sleeve 1072P may be a separate element mounted to the flange member 1070.

The attachment sleeve 1072P may include a plurality of openings that are configured to receive the projection 1085. For example, the attachment sleeve 1072P may include a pair of proximal openings 1072Q and a pair of distal openings 1072R, longitudinally separated from each other by an offset distance. Additionally, two proximal ports 1072Q are located in

- 21 044249 in the same longitudinal position, and the two distal holes 1072R are located in the same longitudinal position. As described in more detail below, the longitudinal displacement between the proximal openings 1072Q and the distal openings 1072R may determine the dose delivery distance for moving the piston rod 1080 to dispense a controlled volume of substance from the device 1050. Alternatively, the longitudinal displacement between the openings 1072Q, 1072R may determine the actuation distance device 1050 such that the protrusion 1085 can be initially received within the proximal openings 1072Q during assembly of the device 1050 to prevent proximal retraction of the piston rod 1080. In this example, the dose delivery distance may correspond to a longitudinal offset between the distal end of the actuation portion 1082 and the bottom surface shoulder 1072 when protrusion 1085 is received within distal opening 1072R. Although not shown, it should be understood that an additional set of openings may be provided on the attached sleeve 1072P (e.g., proximal to the proximal openings 1072Q, distal to the proximal openings 1072Q, and/or distal to the distal openings 1072R) to further define the adduction distance. action and/or distance of dose delivery.

The proximal end of the attached sleeve 1072P may include an angled contact surface 1071P defining a proximal opening of the attached sleeve 1072P. The angled contact surface 1071P may be tapered radially inward toward the inner channel of the attached sleeve 1072P and configured to guide the rod 1081 and protrusion 1085 into the inner channel. In the illustrated example, protrusion 1085 may extend radially outward from shaft 1081 in opposite transverse directions and may be compressible and/or formed of flexible/deformable material such that protrusion 1085 is capable of retracting or deforming radially inward at and/or toward rod 1081 in response to a force applied to it. In other embodiments, the projection 1085 may be configured to at least partially deform the secured sleeve 1072P to facilitate movement of the projection 1085 toward and/or between the openings 1072Q, 1072R. In this example, the anchored sleeve 1072P may be formed from a flexible material configured to flex radially outward when a distally directed force is applied to the shaft 1081, thereby causing the protrusion 1085 to apply a radial force to the anchored sleeve 1072P.

Still with reference to FIG. 3A, the secured sleeve 1072P may be configured to receive a piston rod 1080 through an internal passage and allow the rod 1081 to pass through the shoulder 1072 to operate the device 1050. The protrusion 1085 may be received within the secured sleeve 1072P in response to an impact with an angled contact surface 1071P and compresses radially inward relative to the rod 1081 until the piston rod 1080 moves distally enough for the protrusion 1085 to be received by the proximal holes 1072Q. As shown in FIG. 2B, protrusion 1085 may be configured to expand radially outward (expand) when longitudinally aligned with proximal holes 1072Q to lock rod 1081 relative to flange member 1070. In this example, device 1050 may be in an actuated position to allow further movement of rod 1081 distal to the fixed sleeve 1072P and flange member 1070 could deliver a dose from the device 1050. Alternatively, the device 1050 could be pre-assembled with a projection 1085 received at the proximal openings 1072Q such that movement of the rod 1081 distal to the fixed sleeve 1072P could actuate the device 1050 until the projection 1085 is received within the distal openings 1072R.

As can be seen in FIG. 2C, while the protrusion 1085 is located within the proximal openings 1072Q, application of a distally directed force to the rod 1081 may cause the attached sleeve 1072P to compress (or deform) the protrusion 1085 radially inward, thereby allowing the rod 1081 to move distally relative to the attached sleeve 1072P. Alternatively, protrusion 1085 may be manually compressed (or deformed) by applying a radially inward force through proximal openings 1072Q. The protrusion 1085 can be moved distally through the internal channel of the attached sleeve 1072P and can be received by the distal openings 1072R. As the rod 1081 moves distally relative to the collar 1072, the device 1050 may transition from an actuation position to a dose end position where the projections 1085 are received within the distal openings 1072R, thereby delivering a dose.

It should be understood that the amount of dose delivered by the device 1050 can be controlled based on the longitudinal displacement distance between the proximal openings 1072Q and the distal openings 1072R. In some embodiments, the secured sleeve 1072P may include additional openings to receive the projection 1085 after actuation and delivery of a dose to prevent proximal retraction of the rod 1081 (eg, retraction of the piston rod 1080) relative to the flange element 1070. For example, the projection 1085 may be received within the proximal openings 1072Q during assembly of the device 1050 at the manufacturing stage such that the distal openings 1072R can determine the actuation position, and a third set of openings (not shown) distal to the distal opening 1072R can determine dose delivery position. Alternatively, the lower, inner surface of the flange element

1070 distal to the distal opening 1072R may determine the dose delivery position of the piston rod 1080.

In some embodiments shown in FIGS. 2D-2G, the flange member 1070 may include a movable sleeve 1072S extending distally and proximally from the collar 1072. The movable sleeve 1072S may have a circular cross-section defining an internal channel with an opening at each terminal end of the movable sleeve 1072S. The inner channel of the movable arm 1072S may extend through a longitudinal length of the movable arm 1072S. The movable sleeve 1072S may be configured to receive through the opening 1073, and the inner channel of the movable sleeve 1072S may be configured to receive a rod 1081. The movable sleeve 1072S may be secured relative to the collar 1072 when in a preassembled configuration and may be movable relative to the collar 1072 after engagement with piston rod 1080.

The movable arm 1072S may include a plurality of openings that are configured to receive the protrusion 1085. For example, the movable arm 1072S may include a proximal opening 1072U at the proximal end of the movable arm 1072S and a distal opening 1072T at the distal end of the movable arm 1072S. The proximal end of the movable arm 1072S may further include an angled contact surface 1071S defining a proximal opening of the movable arm 1072S. The angled contact surface 1071S may be tapered radially inward toward the inner channel of the movable arm 1072S and is configured to guide the rod 1081 and protrusion 1085 into the inner channel of the movable arm 1072S. In some embodiments, protrusion 1085 may extend radially outward from shaft 1081 in opposite directions and may be compressible such that protrusion 1085 is configured to compress toward and/or toward shaft 1081 in response to a force applied thereto.

Still with reference to FIG. 2D, the proximal end of the movable arm 1072S may be positioned adjacent the proximal end of the bead 1072, and the distal end of the movable arm 1072S may be located adjacent the distal end of the bead 1072 when in a preassembled position. The piston rod 1080 may be received through an internal passage of the movable sleeve 1072S with a rod 1081 extending through the shoulder 1072. The protrusion 1085 may be received within the distal opening 1072T so that the piston rod 1080 can be attached to the movable sleeve 1072S. The protrusion 1085 may be configured to extend from the distal opening 1072T and extend laterally outward in response to movement of the piston rod 1080 relative to the movable sleeve 1072S.

For example, as shown in FIG. 2E, application of a distally directed force to the actuation portion 1082 may cause the protrusion 1085 to compress radially inward, thereby allowing the rod 1081 to move distally relative to the movable sleeve 1072S. In this example, protrusion 1085 may extend from distal opening 1072T and expand upon distal movement from the distal end of movable arm 1072S. The device 1050 may transition from a preassembled state to an actuated state in response to distal movement of the rod 1081 relative to the shoulder 1072 until the actuation portion 1082 is adjacent to the proximal end of the movable arm 1072S. In this example, the device 1050 may be in an actuated state, and further movement of the rod 1081 relative to the shoulder 1072 may be prevented by the presence of a movable sleeve 1072S.

With reference now to FIG. 2F, piston rod 1080 may engage with movable sleeve 1072S in response to proximal movement of rod 1081 relative to collar 1072 until protrusion 1085 engages proximal opening 1072U. It should be understood that the protrusion 1085 may be in a compressed state when moving through the internal channel of the movable sleeve 1072S and may expand into the proximal opening 1072U after being longitudinally aligned therewith. In the case of protrusion 1085 engaged with proximal opening 1072U, distal movement of piston rod 1080 relative to flange member 1070 may allow simultaneous movement of movable arm 1072S relative to collar 1072. It should be understood that the total length of movable arm 1072S and piston rod 1080 may be greater than the longitudinal length of piston rod 1072. the 1080 rod itself.

As can be seen in FIG. 2G, the piston rod 1080 may be configured to move the movable arm 1072S through the channel of the flange member 1070 a predetermined distance until the actuation portion 1082 collides with the proximal end of the collar 1072. The piston rod 1080 may be configured to deliver a dose from the device 1050 in response to movement of the movable arm 1072S distally relative to the bead 1072. It should be understood that the dose delivered by the device 1050 can be controlled based on a predetermined distance between the actuation portion 1082 and the bead 1072 when the protrusion 1085 is received within the proximal opening 1072U. IN

- 23 044249 In some embodiments, the flange member 1070 may be configured to prevent proximal movement of the movable sleeve 1072S relative to the shoulder 1072 when the protrusion 1085 is received within the proximal opening 1072U. Although not shown, flange member 1070 may include one or more locking components configured to limit proximal retraction of movable sleeve 1072S from opening 1073.

In other embodiments shown in FIGS. 2H-2M, piston rod 1080 may include at least one projection 1085W located on actuation portion 1082. In this example, projection 1085W may be located on or adjacent to the distal end of actuation portion 1082 such that projection 1085W may be received within flange member 1070 in response to movement of piston rod 1080 into collar 1072.

As can be seen in FIG. 2K, the flange member 1070 may include one or more channels formed along the interior surface of the collar 1072. Specifically, the collar 1072 may include a first (proximal) helical channel 1071W formed along the interior of the collar 1072 and having a first curvature, and a second (distal) helical channel 1072W formed along the interior of the collar 1072 and having a curvature different from and/or opposite to the curvature of the first helical channel 1071W. For example, when viewed from the proximal end of the actuation portion 1082, the first helical channel 1071W may be concave, while the second helical channel 1072W may be convex when viewed from the same viewing point. Or, the first helical channel 1071W may be convex when viewed from the proximal end of the actuation portion 1082, while the second helical channel 1072W is concave from the same viewing point. Additionally, the second screw channel 1072W may be spaced longitudinally from the first screw channel 1071W. The first screw channel 1071W may be connected to the second screw channel 1072W intermediately, the third channel 1073W extending between them.

The third channel 1073W may extend substantially parallel to the longitudinal axis of the bead 1072. It should be understood that the size, shape, and/or orientations of one or more channels on the bead 1072 are merely examples, so that other suitable configurations may be provided without departing from the scope this disclosure. As described in detail below, a plurality of channels 1072 are configured to receive projection 1085W. In some embodiments, the first screw channel 1071W and the second screw channel 1072W may be threaded and configured to engage a corresponding component of the piston rod 1080 (eg, protrusion 1085W). Opposing rotational movements may be required to drive the protrusion 1085W through the first screw channel 1071W and the second screw channel 1072W. For example, a first rotational movement of the actuation portion (e.g., clockwise) may cause the protrusion 1085W to pass through the first screw channel 1071W, while an opposite rotational movement (e.g., counterclockwise) may cause the protrusion 1085W to pass through the second screw channel 1072W.

With reference to FIG. 2H, with piston rod 1080 in the ready position, protrusion 1085W may be received within collar 1072 in response to distal movement of actuation portion 1082 toward flange member 1070. As seen in FIG. 2I, protrusion 1085W may be received within the first screw passage 1071W and moved therethrough in response to rotation of the piston rod 1080 (e.g., in a first direction) relative to the flange member 1070. It should be understood that the piston rod 1080 may be configured to move axially in distal direction relative to the flange member 1070 when the piston rod 1080 rotates within the flange member 1070 due to the curvature of the first screw channel 1071W. For example, the piston rod 1080 may move a first distance determined by the configuration of the first screw channel 1071W before reaching the terminal end of the first screw channel 1071W. The first distance may correspond to the step of actuating the device 1050, such that the device 1050 can be at least partially actuated after the protrusion 1085W moves through the first screw channel 1071W.

With reference now to FIG. 2J, a protrusion 1085W may be located at the terminal end of the first helical channel 1071W and the proximal (eg, upper) end of the third channel 1073W. In some embodiments, piston rod 1080 may be subject to haptic feedback provided by the terminal end of first screw channel 1071W. The piston rod 1080 may be moved distally through the third channel 1073W to complete the actuation step of the device 1050, as shown in FIG. 2K. It should be understood that the first screw channel 1071W and the third channel 1073W may collectively determine the actuation distance of the device 1050 such that the piston rod 1080 will be in the actuation position when the protrusion 1085W moves through the third channel 1073W.

In the case of the projection 1085W received within the second screw channel 1072W, the piston rod 1080 may be rotated in a second direction (opposite the first direction) to transfer

- 24 044249 moves the piston rod 1080 distally a second distance, which is determined by the configuration of the second screw channel 1072W. The second distance may be less than, greater than, and/or substantially equal to the longitudinal dimension of the second screw channel 1072W depending on the specific application and need. The piston rod 1080 may be rotated in a second direction and moved a second distance to reach the terminal end of the second screw channel 1072W to deliver a dose from the device 1050. It will be understood that the second distance may correspond to a dose delivery step of the device 1050 such that the device 1050 can deliver the dose by moving the protrusion 1085W through the second screw channel 1072W and arriving at the dose end position.

In other embodiments shown in FIGS. 2L-2O, piston rod 1080 may include a projection, boss, and/or thread 1085X located on actuation portion 1082. In this example, threads 1085X may be located around the circumference of actuation portion 1082 and along the distal end such that thread 1085X could be received within flange member 1070 in response to movement of piston rod 1080 into collar 1072.

Flange member 1070 may further include a threaded portion 1072X disposed within bore 1073 and defining a helical path that is configured to receive threads 1085X. In this example, a threaded portion 1072X may be positioned along the proximal portion of the opening 1073 such that the distal portion of the opening 1073 may include an unthreaded portion 1071X. As described in more detail below, the threaded portion 1072X may determine a longitudinal distance corresponding to the actuation step of the device 1050, and the non-threaded portion 1071X may determine the distance corresponding to the dose delivery step of the device 1050.

For example, as seen in FIG. 2L, the actuation portion 1082 may be moved distally toward the flange member 1070 until the threads 1085X engage the distal end of the collar 1072. Rotation of the piston rod 1080 in a first direction (e.g., clockwise or counterclockwise) may cause the 1085X thread engages the 1072X threaded part. As shown in FIG. 2M, rotation of the piston rod 1080 may cause axial/longitudinal movement of the actuation portion 1082 into the collar 1072 as the thread 1085X moves along the helical path of the threaded portion 1072X. It should be understood that rotation and movement of thread 1085X through threaded portion 1072X can move device 1050 from a ready position (FIG. 2L) to an actuated position (FIG. 2N). With threads 1085X disengaged from threaded portion 1072X and positioned along unthreaded portion 1071X, device 1050 may be in an actuated position. In some examples, feedback (eg, tactile, audible, etc.) may be generated in response to thread 1085X exiting threaded portion 1072X and/or entering unthreaded portion 1071X.

In this example, as shown in FIG. 2O, the actuation portion 1082 may be moved distally relative to the flange member 1070 to deliver a dose from the device 1050 by applying a distally directed force to the actuation portion 1082. The thread 1085X may be moved through the distal portion of the opening 1073 when the thread 1085X is located within the non-threaded portion 1071X. The longitudinal length of the unthreaded portion 1071X, defined between the distal end of the threaded portion 1072X and the distal end of the orifice 1073, may control dose delivery of the device 1050. The device 1050 may complete dose delivery when the actuation portion 1082 engages the proximally facing and distal surface of the collar 1072, and the piston rod 1080 arrives at the end of the dose position.

Fig. 2P-2T show additional embodiments of a flange member that may be configured similar to the flange member 1070 shown and described above, except for the differences detailed herein. It should be understood that like reference numerals are used to identify like components, and the flange elements described below can be easily combined with one or more components of the device 1050 shown and described above.

For example, with reference first to FIG. 2P, the flange member 1070A may include one or more flanges 1076A that may be configured to assist a user in holding the device 1050 and/or ejecting a medicinal substance to be dispensed from the device 1050. The flanges 1076A may be further configured to allow the user to hold the device 1050 in a variety of hand/grip positions, locations, and/or orientations. As an illustrative example, the flanges 1076A may be configured such that the flange member 1070A can be held like a writing instrument (e.g., a pencil, pen, etc.) without the need for flanges 1076A, or may be configured according to the example shown in fig. 24A such that the flanges 1076A can abut one or more of the user's fingers. Flange member 1070A may include a pair of flanges 1076A extending radially outward from collar 1072 in opposite radial directions with respect to each other. The flanges 1076A may extend transversely from the collar 1072 (for example, the flanges 1076A may include an angled surface that is inclined radially inward in a distal direction) and may be configured to prevent a user's fingers from sliding off the flange member 1070A during using the 1050 device.

The flanges 1076A may be joined together to form a semicircular profile with a minimum radius relative to the collar 1072. Accordingly, the flanges 1076A may form a thin profile to facilitate visualization of the target treatment site at the distal end of the device 1050 (not shown) when using the device 1050 from a proximal perspective from the finger flange 1070A. It should be understood that flange member 1070A may include various other numbers and/or arrangements of flanges 1070A other than those shown and described herein without departing from the scope of this disclosure. In other embodiments, flanges 1076A may include various other suitable sizes and/or shapes.

The flange member 1070A may further include a distal collar 1075A extending distally from the collar 1072 and configured to engage the housing 1060 to hold the flange member 1070A in a stationary position relative to the housing 1060. The distal collar 1075A may be glued, molded, or attached to body 1060, or may engage with body 1060 through a friction fit. In this example, distal collar 1075A includes a longitudinal length that is generally less than the longitudinal length of collar 1072. In some embodiments, distal collar 1075A may be sized small enough to provide adequate alignment of housing 1060 for user grip and /or manipulated during use of the device 1050. Additionally, the distal collar 1075A may include a material composition that is similar to and/or different from the material composition of the collar 1072. For example, the distal shoulder 1075A may be formed from a flexible material such that the distal shoulder 1075A may be configured to flex radially outward when the housing 1060 is received into the flange member 1070A and to flex radially inward when the housing 1060 is fully received to facilitate connection to the snap-in fit (without destroying the distal collar 1075A). It should be understood that in other embodiments, flange member 1070A may not include distal collar 1075A at all.

In other embodiments shown in FIGS. 2Q, flange member 1070B may include a distal shoulder 1075B that is significantly longer than the distal shoulders 1075, 1075A shown and described above. For example, distal shoulder 1075B may be extended to a longitudinal length that is greater than the longitudinal length of shoulder 1072. In this example, distal shoulder 1075A may be large enough to surround a significant length of housing 1060. In this example, the outer surface of distal shoulder 1075B may provide contact a surface that is grasped and/or manipulated by the user during use of the device 1050. Additionally, the distal shoulder 1075B may include an extended diameter that is greater than the diameter of the body 1060 to provide increased surface area for gripping the flange member 1070B. In other words, the distal shoulder 1075B may have an extended size and/or shape to facilitate gripping and/or manipulation of the device 1050. In the present example, the distal shoulder 1075B may have a cylindrical shape with a convex outer surface when viewed from the outside of the flange member 1070B of the device.

Alternatively, as seen in FIG. 2R, the flange member 1070C may include a distal shoulder 1075C that is substantially similar to the distal shoulder 1075B and includes a longitudinal length that is greater than the longitudinal length of the shoulder 1072. In this example, the outer surface of the distal shoulder 1075C may be configured to provide contact a surface that is grasped and/or manipulated by the user during use of the device 1050. The distal shoulder 1075C may include a thin profile with a diameter that is larger than the diameter of the body 1060, such that the distal shoulder 1075C does not substantially increase the profile of the body 1060. In other words, the distal shoulder 1075C may have a size that is tapered relative to the distal shoulder 1075B. In some embodiments, the distal collar 1075C may include a terminal lip 1077C that extends radially outward at the distal end. The terminal lip 1077C may be configured to enhance gripping and/or manipulation of the distal collar 1075C. In the present example, the distal collar 1075C may have a flared shape with a concave outer surface when viewed from the outside of the flange member 1070C of the device.

In other embodiments shown in FIGS. 2S-2T, flange member 1070D may include a collar 1072D having a proximal lip 1074D. The proximal lip 1074D may define an irregular surface configured to mate with the piston rod 1080 when the actuation portion 1082 is received by the collar 1072D. For example, the proximal lip 1074D may include a pair of recessed surfaces 1075D located along opposite sides along the proximal lip 1074D. In other words, the recessed surfaces 1075D may be separated from each other by surfaces and/or portions of the proximal lip 1074D that are not recessed. In this example, recessed surfaces 1075D may be positioned adjacent to slots 1074 and may define a path for movement of piston rod 1080 relative to collar 1072D to actuate and deliver a dose from device 1050. In some embodiments, recessed surfaces 1075D may include a helical configuration (e.g., may be inclined distally) such that the recessed surfaces 1075D may be tapered distally between the first shoulder 1073D and the second shoulder

1076D.

In some embodiments, flange member 1070D may include visualization mechanisms, such as, for example, one or more marks or markers located on collar 1072D to provide instructions to the user of device 1050. For example, one or more marks (e.g., numbering ) may indicate the directions in which the piston rod 1080 should be rotated or moved relative to the flange member 1070D to actuate and deliver a dose from the device 1050. As an example, one or more marks may include markers that indicate a starting position (eg , 1), actuation position (eg, 2), and dose delivery position (eg, 3) of the projections 1086 relative to the proximal lip 1074D. Said one or more marks may be glued, printed, embossed, or molded onto the bead 1072D.

As described in more detail below, the flange member 1070D may be configured to allow movement of the piston rod 1080 in a single direction when actuating and delivering a dose from the device 1050. In illustrative use, the piston rod 1080 (not shown) may first be received through the flange element 1070D, and the actuation portion 1082 may be positioned against a shoulder 1072D with protrusions 1086 located along the first end of the recessed surfaces 1075D at marker 1 and opposite the slot 1074. Protrusions 1086 may only rotate in a single direction along the recessed surface 1075D toward marker 2 of - behind the first ledge 1073D, preventing the projections 1086 from moving in the opposite direction from the marker 2.

When the projections 1086 are received along the recessed surfaces 1075D at the marker 2, the second shoulder 1076D may further prevent the projections 1086 from moving past the slots 1074 and past the marker 3. It should be understood that the configuration of the proximal lip 1074D is illustrative, so that the flange member 1070D may include various other sizes, shapes, and/or configurations of the proximal lip 1074D and/or recessed surfaces 1075D other than those shown and described above to facilitate movement of the piston rod 1080 during use of the device 1050.

In other embodiments, components of the device 1050 may include one or more colored indicators in place of and/or in addition to the markers described above to provide instructions to the user of the device 1050. For example, the device 1050 may include colors, symbols (e.g. , arrows), etc., indicating the direction in which the piston rod 1080 should be rotated or moved relative to the flange member 1070D to actuate and deliver the dose. In one embodiment, the outer surface of the piston rod 1080 may be provided with different colors along different portions of the actuation portion 1082 to indicate the corresponding start position (e.g., green), actuation position (e.g., yellow), and dose delivery position (e.g., red ) of the piston rod 1080 relative to the collar 1072D. One or more color indicia may be printed or molded on the piston rod 1080. In other embodiments, various portions of the piston rod 1080 may include different textures instead of, or in addition to, the color indices described above to provide instructions to the user of the device 1050.

The components of device 1050 may be made from any suitable material, and each component may be made from the same material as the other components or from a different material. It should be understood that in some embodiments, one or more components of the device 1050 (e.g., flange member 1070, proximal shoulder 1072, piston rod 1080, actuation portion 1082, etc.) may be formed from a flexible material having sufficient flexibility to prevent destruction during bending. In some embodiments, one or more components of device 1050 may be rigid and may have strength sufficient to maintain shape and provide support. In other embodiments, one or more components of device 1050 (or at least a portion of a component) may have variable stiffness along the length or lateral width so that the component can have variable flexibility. In other further embodiments, one or more components of the device 1050 may have sufficient flexibility to prevent failure during bending, while also having sufficient rigidity and strength to maintain shape and provide support. In some embodiments, such features may further provide feedback to the user (e.g., tactile, audible, visual, etc.) when flexing and/or interacting with other components of the device 1050. For example, each of the housing 1060, flange member 1070, and piston rod 1080 may be made of a material including a polymer, such as plastic. In some embodiments, one or more of body 1060, flange member 1070, and piston rod 1080 may include multiple different materials (eg, glass, rubber, and/or plastic). In some embodiments, for example, the cylindrical body portion 1060 may be made of glass, plexiglass, or any other suitable polymer (e.g., cycloolefin polymer or cycloolefin copolymer) or other material, and the stopper 1062 may be made, for example, of plastic, rubber, or other polymer or copolymer. As a further example, flange member 1070 may include polypropylene homopolymer, ABS polymer (acrylonitrile, butadiene, and styrene), ABS-polycarbonate blend, and other suitable materials. In some embodiments, piston rod 1080 may include an ABS-polycarbonate compound. Such materials may provide better manufacturing tolerances (e.g., injection molding) of flange member 1070 and/or piston rod 1080 or provide improved reproducibility of said components of device 1050. As described in more detail above, in some embodiments, one or more components of device 1050 may be formed from a flexible and/or deformable composition of materials that provides better tolerances for bending or deformation of said components (e.g., without breaking) when actuating or delivering a dose from the device 1050.

In some embodiments, the portion of the housing 1060 configured to contain the medicinal substance being dispensed may be made of a transparent or translucent material. In some embodiments, flange member 1070 and piston rod 1080 may be made from the same, similar, or different materials, such as similar or different plastics (eg, having similar or different stiffnesses). In some embodiments, portions of the device 1050 may include resilient materials. For example, portions of the device 1050 may include rubber or plastic configured to allow a user to better grip the device 1050 or to create an airtight or sealed connection between two components of the device 1050 (eg, between the housing 1060 and the stopper 1062). In some embodiments, some portion or all of the piston rod 1080 (e.g., the actuation portion 1082 and/or extensions 1087, or alternatively the entire piston rod 1080) may be made of a material that has some flexibility, for example, to allow the extensions 1087 to bend. One or more of the materials listed above (eg, plastics, rubber, polymers, or copolymers) may have such characteristics. In some embodiments, some or all of the device 1050 may be suitable for sterilization, such as heat or chemical sterilization.

Fig. 2A and 2B show an exemplary method of assembling the delivery device shown in FIG. 1A-1E. Flange member 1070 may be assembled with housing 1060, as shown in FIG. 2A. Assembling flange member 1070 to body 1060 may include sliding, snapping, gluing, or securing the two components together. As shown in FIG. 2A, the flange member 1070 may be slid onto the housing 1060, for example, such that the lip 1071 of the flange member 1070 engages the housing flange 1061. The piston rod 1080 may be inserted through the assembled flange member 1070 and housing 1060 such that the distal end of the piston rod 1080 contacts the stopper 1062. The assembled device 1050 may then be in a configuration suitable for packaging, sterilization, and/or use.

Fig. 3C-3F show an exemplary method of assembling device 1050, in which actuation portion 1082 includes extensions 1087 and collar 1072 includes side openings 1094. In such an embodiment, piston rod 1080 may be inserted through flange member 1070 until the hook or staple portions of the extensions 1087 will not be received within the side openings 1094, at which point the assembled device 1050 may be in a configuration suitable for packaging, sterilization, and/or use. It should be understood that the side openings 1094 may be configured to prevent proximal retraction of the piston rod 1080 relative to the flange member 1070 after receiving the hook or staple portions of the extensions 1087. The side openings 1094 may function as a first lock when the device 1050 is in its initial state. assembly, to prevent disassembly of the 1050 device.

As described in more detail below (see FIGS. 4G-4J), the side openings 1095 may be configured to prevent proximal retraction of the piston rod 1080 after receiving the hook or staple portions of the extensions 1087. The side openings 1095 may function as a second lock, when the device 1050 is in a dose delivery state, to prevent the patient fluid from being withdrawn after the delivery of the drug/medicament has ended. It should be understood that the side openings 1094, 1095 may generate feedback indicating the relative position of the piston rod 1080 relative to the flange member 1070, such as, for example, audible feedback, tactile feedback, and the like. In some embodiments, device 1050 may include more and/or fewer side openings 1094, 1095 than shown and described herein to increase and/or decrease the number of locks on device 1050.

- 28 044249

In some embodiments, assembly of device 1050 may include prefilling housing 1060 prior to being combined with flange member 1070 and stopper 1062; for example, a predetermined amount of drug substance may be located in the housing 1060 between the stopper 1062 and the needle end 1064. In some embodiments, depending on anticipated changes in the designs of the components of the device 1050, an alternative order of assembly of the components of the device 1050 may be used. For example, in an embodiment (not shown), wherein the flange member 1070 is configured to be assembled to the body 1060 using a snap-fit contact surface, the piston rod 1080 may be first inserted through the flange member 1070, and the combined flange member 1070 and piston rod 1080 may be assembled with body 1060, for example, such that the flange member 1070 snaps over the proximal flange 1061 of the body 1060 and the piston rod 1080 is inserted into the body 1060.

Fig. 4A-4F show an exemplary method of using device 1050 in accordance with aspects of the present disclosure. In the pre-operational configuration shown in FIG. 4A, the device 1050 may retain a volume of medicinal substance between the stopper 1062 and the push end 1064. The actuation distance p may be between the protrusions 1086 and the proximal end of the proximal collar 1072, and the protrusions 1086 may not be aligned with the slots 1074. During the actuation step action shown in FIG. 4B, the piston rod 1080 may be moved longitudinally further into the housing 1060. For example, the user may press the actuation portion 1082 partially into the proximal shoulder 1072 of the flange member 1070. In some embodiments, the device 1050 may be held in an inverted position during this step to ensure that so that air trapped in housing 1060 can be pushed out through push end 1064 when stopper 1062 is pushed distally by piston rod 1080. In the pre-operational configuration of FIG. 4A and during the actuation step shown in FIG. 4B, rotation of the piston rod 1080 about the longitudinal axis of the syringe can be prevented due to the geometries of the hole 1073 in the flange member 1070 and the journal 1084 of the piston rod 1080 (shown in the upper cross section in FIG. 4B). As shown in FIG. 4B, the actuation step may be stopped when the projections 1086 of the piston rod 1080 abut the proximal end of the proximal shoulder 1072. After the actuation step is completed, the journal 1084 of the piston rod 1080 may be positioned longitudinally relative to the hole 1073 of the flange member 1070 such that it can now rotate relative to the flange member 1070. For example, after completion of the actuation step, a narrower portion of the neck 1084 may be located within the opening 1073 than when the device was in its pre-operational configuration.

As shown in FIG. 4D, device 1050 may be in a powered configuration. In the distribution preparation phase shown in FIG. 4E, the piston rod 1080 may be rotated about its longitudinal axis to align the projections 1086 with the slots 1074. To do this, the user may grip and twist the actuation portion 1082. In some embodiments, as described elsewhere, the actuation portion 1082 may be rotated to or another direction to align the projections 1086 and the slots 1074. In other embodiments, the actuation portion 1082 may be rotatable in only one direction. In some embodiments, once the projections 1086 are aligned with the slots 1074, further rotation of the piston rod 1080 relative to the flange member 1070 may be stopped, for example, by contact between the geometries of the journal 1084 and the hole 1073. Thus, the alignment of the projections 1086 and the slots 1074 may lock the device 1050 in a ready-to-distribute configuration. In some embodiments, rotation of the actuation portion 1082 may align the slotted projections 1086 with the first shelf support portion 107 and may allow the piston rod 1080 to remain longitudinally stationary relative to the flange member 1070 (e.g., no proximal or distal movement of the piston rod 1080 is caused by rotation of the actuation portion 1082 ). As shown in FIG. 4F, during the distribution step, the piston rod 1080 may be moved longitudinally further into the housing 1060. For example, the user may press the actuation portion 1082 distally into the proximal shoulder 1072 of the flange member 1070 so that the projections 1086 are moved into the slots 1074. Once the projections 1086 abut distal ends of the slots 1074, further distal movement of the piston rod 1080 is stopped. The dispensing step may ensure that a predetermined volume of medicinal substance within the housing 1060 is dispensed from the device 1050. In some embodiments, when the projections 1086 abut the distal ends of the slots 1074, the stopper 1062 does not bottom out or abut the interior of the ejector end 1064 in the housing 1060 Preferably, by ensuring that a predetermined volume of medicinal substance within the housing 1060 is dispensed from the device 1050 before the stopper 1062 can reach the bottom, any variations in the manufacture of the ejector end 1064 (for example, changing the exact size or shape of the ejector end 1064) are unlikely to occur. will affect the target volume of drug that is delivered from device 1050. Indeed, in some embodiments, the target volume of drug that is delivered

- 29 044249 from the device 1050 may not be affected by typical manufacturing variations of any component of the device 1050, in particular, any component other than the flange member 1070. Advantageously, this may allow different and larger tolerances to exist for variations in the manufacturing of some components of the device 1050 ( such as variations in the formation of the glass body 1060 or other glass components) that will not affect the target volume of drug to be delivered from the device 1050.

In some embodiments, after one or more steps in using the device 1050, the user may be prevented from re-executing a step and/or reversing one or more steps. For example, geometries of, e.g., piston rod journal 1084 and bore 1073 may prevent a user from being able to extend piston rod 1080 proximally (e.g., from housing 1060), rotate piston rod 1080 in advance (e.g., prior to the actuation step shown in FIG. 4C) , and/or excessively rotate the piston rod 1080 during the dispensing preparation step (eg, shown in FIG. 4E). In particular, FIG. 4G-4J show steps in using an embodiment of device 1050 having extensions 1087 on actuation portion 1082 and corresponding side openings 1094, 1095 in collar 1072 of flange member 1070. FIG. 4G and 4H show the device 1050 when the actuation portion 1082 is pushed distally into the collar 1072. Due to their angled distal portions, the extensions 1087 are pushed into the collar 1072. After the piston rod 1080 is rotated to the delivery position and further pushed the actuation portion 1082 distally into the collar 1072 to deliver a predetermined volume of drug from device 1050, extensions 1087 can be received into side openings 1095 (shown in FIGS. 4I and 4J), whereupon they limit proximal movement of piston rod 1080. Preferably, limiting proximal movement of piston rod 1080 can prevent inadvertent extracting material into device 1050 from, for example, a location to which a medicinal substance is being delivered. In some embodiments, device 1050 may include either side openings 1094 or side openings 1095. In other embodiments shown in FIGS. 4G-4J, device 1050 may include both side openings 1094 and side openings 1095.

Fig. 4K and 4O show in more detail exemplary aspects of the geometry of the journal 1084 that may help control movement of the piston rod 1080. For example, the most proximal portion a of the journal 1084 and rod 1081 (indicated by section d in FIG. 4K) may have the first cross-sectional shape shown in fig. 4L. This shape may allow the respective portions of the piston rod 1080 to move proximally/distally through an opening (eg, opening 1073) of the locking component (eg, flange member 1070), but may prevent the piston rod 1080 from rotating about its longitudinal axis. The narrow portion b of the neck 1084 may have a smaller cross-sectional shape as shown in FIG. 4M. This shape, when positioned in an opening (eg, opening 1073) of a locking component (eg, flange member 1070), may allow unidirectional or bidirectional rotation of piston rod 1080 about a longitudinal axis. It should be understood that the corresponding portion of the journal 1084 allowing transient rotation of the piston rod 1080 (e.g., at narrow portion b) may be configured with the smallest cross-sectional shape to provide more room for such movement relative to the cross-sectional shapes of other portions of the piston rod 1080. The third neck portion 1084 may have a larger cross-sectional shape as shown in FIG. 4N, which may directly correspond to the size and shape of an opening (eg, opening 1073) of a locking component (eg, flange member 1070). As such, proximal or distal movement of this portion of the journal 1084 through the opening 1073 may only be possible when the piston rod 1080 is in a particular rotational orientation relative to the flange member 1070. Moreover, the piston rod 1080 cannot rotate when the portion of the journal 1084 is positioned inside the bore 1073. This may ensure that, for example, the piston rod 1080 is in a desired position relative to the flange member 1070 (for example, when actuation is completed and part c is no longer located inside the bore 1073) before the piston rod 1080 can rotate. Together, the various cross-sectional shapes of the neck 1084 and the size and shape of the orifice 1073 may combine to create the specific sequence of movements of the piston rod 1080 required to actuate and deliver drug from the device 1050. In this example, the distal portion of the orifice 1073 may have the largest profile cross-section relative to the intermediate and/or proximal portion of the hole 1073 to accommodate variable geometries of the piston rod 1080 (eg, neck 1084, rod 1081, etc.).

In a further embodiment shown in FIG. 4O, the most proximal portion e of the neck 1084 and the majority portion h of the shaft 1081 may have the first cross-sectional shape shown in FIG. 4R. This shape may allow the respective portions of the piston rod 1080 to move proximally/distally through an opening (eg, opening 1073) of the locking component (eg, flange member 1070), but may prevent the piston rod 1080 from rotating about its longitudinal axis. The narrow part/necks of 1084 may have a smaller, winged (or swept)

- 30 044249 new) cross-sectional shape shown in Fig. 4Q (in a pre-rotational configuration relative to flange member 1070) and FIG. 4R (in a post-rotational configuration relative to flange member 1070). This winged shape, when positioned in an opening (e.g., opening 1073) of a locking component (e.g., flange member 1070), may allow unidirectional or bidirectional rotation of piston rod 1080 about a longitudinal axis and may limit or resist rearward rotation of piston rod 1080 in the opposite direction. after completion of rotation (as described below in relation to FIGS. 4T-4X). Portions g and l of the piston rod 1080 may have a large cross-sectional shape as shown in FIG. 4S, which may directly correspond to the size and shape of an opening (eg, opening 1073) of a locking component (eg, flange member 1070). As such, proximal or distal movement of these parts of the piston rod 1080 through the opening 1073 may only be possible when the piston rod 1080 is in a particular rotational orientation relative to the flange member 1070. Moreover, the piston rod 1080 cannot rotate when parts g or l piston rod 1080 are located within bore 1073. This may ensure that, for example, piston rod 1080 is in a desired position relative to flange member 1070 at certain stages during assembly and use of device 1050, allowing accurate assembly and use of device 1050. Additionally, a large the cross-sectional area of portions g and l may assist in preventing the piston rod from retracting when it cannot move proximally through the opening 1073 unless it is in a particular rotational position relative to the flange member 1070. For example, after rotating the piston rod 1080 from the actuated position into the delivery position, portion g of the piston rod 1080 may be unable to move through the hole 1073, thereby preventing retraction of the piston rod at this stage of use of the device 1050. Together, the various cross-sectional shapes of the piston rod 1080 and the size and shape of the hole 1073 may be combined to create a specific a sequence of movements of the piston rod 1080 necessary to assemble, actuate, and deliver the drug from the device 1050.

Fig. 4T-4X show in more detail the specific interactions between the wing portion of the neck 1084 and the hole 1073 in the flange member 1070. The flange member 1070 may include retainers 1078, either adjacent to or within the hole 1073, which may mate with the wings 1089 on the neck 1084 Fig. 4T shows a cross-section of journal 1084 within bore 1073 in a pre-rotation configuration (eg, after activation of device 1050 but before rotation of piston rod 1080 into delivery configuration relative to flange member 1070). Fig. 4U shows that when the piston rod 1080 rotates about the longitudinal axis, one of the wings 1089 may contact one of the detents 1078 (depending on the direction of rotation). As rotation continues, one of the detents 1078 may cause one of the wings 1089 to compress toward the rest of the neck 1084. After rotation has finished, one of the wings 1089 passes one of the detents 1078 and expands. This extension of the wing 1089 by the detent 1078 may provide audible click feedback and/or tactile feedback to indicate the end of rotation and may then prevent rearward rotation of the piston rod 1080 relative to the flange member 1070. The wings 1089 and detents 1078 may be configured with being able to interact in a similar manner regardless of whether the piston rod 1080 rotates in a clockwise or counterclockwise direction, thereby allowing bidirectional rotation of the piston rod 1080 to move the piston rod 1080 from an actuated position to a delivery position. As shown in more detail in FIG. 4X, each wing 1089 may be rounded to allow easy rotation in one direction, and the extension of the wing 1089 behind the detent 1078 may place the wing 1089 in a position relative to the detent 1078 in which it strongly resists or prevents rotation in the opposite direction. The latch 1078 may have any suitable contour configured to assist in unidirectional movement of the wing 1089 behind the latch 1078.

Preferably, the various configurations of piston rod 1080 described herein may provide the ability to model, mold, and/or manufacture one element (e.g., piston rod 1080) or two elements (e.g., piston rod 1080 and flange element 1070) to achieve several purposes - for example, controlling the required movement and assembly of the piston rod, reducing user error, preventing retraction of the piston rod, and minimizing the number of different parts that must be manufactured and handled to assemble the device 1050.

In some embodiments shown in FIGS. 4Y-4Z, device 1050 may include a pair of piston rods in one set, interchangeable with a single actuation portion 1082, or coupled to separate actuation portions 1082. For example, with reference first to FIG. 4Y, device 1050 may include a first piston rod 1080A that is substantially similar to the piston rod 1080 shown and described above, except for the differences detailed herein. The first 1080A piston rod may include eraser

- 31 044249 zhen 1081A, having a longitudinal length A defined between the distal end of the actuation part 1082 and the tip 1083A. As described in detail below, the longitudinal length A may define an actuation distance for moving the piston rod 1080A relative to the flange member 1070 to actuate the device 1050. The tip 1083A may have a flat and/or planar contact surface that may be configured to resist engagement. stopper 1062 when the first piston rod 1080A is received within the housing 1060.

With reference now to FIG. 4Z, device 1050 may further include a second piston rod 1080B that is substantially similar to piston rod 1080. Second piston rod 1080B may include a rod 1081B extending distally from the actuator portion 1082 and having a longitudinal length B defined between the distal end of the actuator parts 1082 and tip 1083B. Tip 1083B is substantially similar to tip 1083A described above. The longitudinal length B of the tip 1083B is relatively greater than the longitudinal length A of the rod 1081A and may determine the dose delivery distance for moving the piston rod 1080A relative to the flange member 1070 to deliver the dose from the device 1050.

The first piston rod 1080A may be configured to actuate the device 1050 in response to movement of the rod 1081A through the shoulder 1072 into the housing 1060 (see FIGS. 1A-1B). In this example, tip 1083A may contact and push stopper 1062 distally an actuation distance. It should be understood that the actuation distance of the device 1050 can be controlled based on the size of the longitudinal length A of the first piston rod 1080A. After actuating the device 1050, the first piston rod 1080A can be removed from the body 1060 and flange member 1070 without retracting the stopper 1062 due to the flattened contact surface of the tip 1083A. Accordingly, the stopper 1062 may remain in a fixed position relative to the housing 1060 after the first piston rod 1080A is retracted.

The second piston rod 1080B may be configured to deliver a dose from the device 1050 in response to movement of the rod 1081B through the collar 1072 into the housing 1060 (see FIGS. 1A-1B) after the actuation step described above using the rod 1081A. In this example, tip 1083B may contact and push stopper 1062 distally into the dose delivery distance. It should be understood that the dose delivery distance of the device 1050 can be controlled based on the size of the longitudinal length B of the second piston rod 1080B. The dose delivery distance may be substantially equal to the difference in length between rod 1081B and rod 1081A.

Fig. 5A-5C show another exemplary delivery device 1200 according to additional embodiments of the present disclosure. The device 1200 includes a housing 1220 and a flange member 1240 with a proximal shoulder 1242 in which an inner shoulder 1260 may be located. Together, the proximal shoulder 1242 and the inner shoulder 1260 may form a locking component for the device 1200. The piston rod 1280 may extend through the inner shoulder 1260 and a flange member 1240 into the housing 1060. The piston rod 1280 may have a longitudinal axis aligned with the central axis of the proximal shoulder 1242 and the inner shoulder 1260, and may have an actuating portion 1282 configured to be mounted (e.g., inserted or mounted) within the inner shoulder 1260.

The device 1200 may be, for example, an injection device, such as a syringe, for dispensing a predetermined volume of drug dosage. In general, device 1200 may have characteristics of size, capacity, material, preparation, assembly, manufacture, operation, or use that are the same as device 1050 or other delivery devices described herein. As with device 1050, device 1200 may be configured to facilitate use and may include one or more features that assist the user by providing tactile, audible, or visual feedback (e.g., using any of the features described herein in other places).

Housing 1220 may have any or all of the same characteristics, for example, housing 1060 of device 1050 or any syringe housing known in the art. For example, in some embodiments, housing 1220 may be prefilled or prefilled (e.g., filled or filled with medicinal substance prior to assembly, packaging, sterilization, and/or delivery of the device 1200 to users). In some embodiments, stopper 1222 may be configured to be inserted into housing 1220 and may be configured to retain a predetermined volume of medicinal substance to be dispensed within housing 1220 between stopper 1222 and ejector end 1224.

The flange member 1240 may be of any suitable size and/or shape to cover, partially cover, cover, or partially cover the end of the housing 1220 opposite the ejector end 1224, and/or to support and hold the piston rod 1280 in place within the housing 1220. In some In embodiments, the flange member 1240 may have some characteristics that are the same as the flange member 1070 of the device 1050. For example, the flange member 1240 may include a distal shoulder 1244 configured to engage the housing 1220 and hold the flange member 1240 in place relative to the body 1220.

- 32 044249 Pusa 1220. For example, the distal collar 1244 may include a lip 1245 that can slide over the body flange 1226 to hold the flange member 1240 in place. In alternative embodiments, the lip 1245 of the distal collar 1244 may be made of a flexible or semi-flexible material so that it can snap into place over the housing flange 1226. In additional embodiments, the distal collar 1244 or other portion of the flange member 1240 may be glued, molded, or attached to the body 1220, or may be frictionally engaged with the body 1220.

In some embodiments, flange member 1240 may include one or more flanges 1246 that may be configured to assist a user in holding device 1200 and/or ejecting drug dispensed from device 1200. In some embodiments shown in FIGS. 1A-1E, flange member 1240 may include two flanges 1246 opposed to each other and extending perpendicular to the longitudinal dimension of device 1200. In some embodiments, flange member 1240 may include other flange or flange arrangements, such as four flanges, or a single circular flange extending radially outward from the central longitudinal axis of the device 1200. In some embodiments, the flange member 1240 may extend radially outward from the central longitudinal axis beyond the circumference of the housing 1220. In such embodiments, the flange member 1240 may support the device 1200 when device 1220 is placed on a surface, may prevent device 1050 from rolling on a flat surface, and/or may allow device 1050 to be easily gripped.

In some embodiments, the flange member 1240 and inner shoulder 1260 may be configured to serve as a locking component in the device 1200, for example, by limiting and/or directing the rotational and longitudinal movement of the piston rod 1280. The proximal shoulder 1242 of the flange member 1240 may be configured to receive a portion of the inner bead 1260 while blocking distal movement of the projections 1262 until the inner bead 1260 is rotated in a particular direction. In turn, the inner collar 1260 may be configured to receive part or all of the actuation portion 1282 of the piston rod 1280. As shown in FIG. 5A-5C, proximal bead 1242, inner bead 1260, and actuation portion 1282 may all have substantially cylindrical shapes; in alternative embodiments, each of the proximal bead 1242, the inner bead 1260, and the actuation portion 1282 may have any suitable size or shape that allows the actuation portion 1282 to be mounted (e.g., inserted) within the inner bead 1260, and the inner bead 1260 to be mounted within the proximal collar 1242.

The piston rod 1280 and inner collar 1260 may be generally rotatable about a common central longitudinal axis (eg, in one direction or both directions). In addition, both the piston rod 1280 and the inner collar 1260 may be movable along the central longitudinal axis, for example, in a distal direction, to actuate the device 1200 and/or deliver a volume of medicinal substance from the distal end 1224 of the housing 1220. Actuation portion 1282 of the piston rod 1280 may include a distal geometry that, when the actuation portion 1282 moves distally into the inner shoulder 1260, mates with the inner shoulder 1260 to prevent proximal movement (e.g., retraction) of the piston rod 1280 from the inner shoulder 1260. For example, the actuation portion 1282 may include a wedge-shaped distal portion that, when it passes the distal portion of the inner bead 1260, expands distally from the inner bead 1260 such that the actuation portion 1282 can no longer move freely relative to the inner bead 1260.

The flange member 1240 may include cavities, such as slots 1248, into which projections 1262 of the inner bead 1260 can slide when the inner bead 1260 is rotated to a particular position. As with the slots 1074 of the device 1050, the slots 1248 may have a depth dimension parallel to the longitudinal axis of the device 1200, and the depth of the slots 1248 may correspond to the distance that the piston rod 1280 must move distally to push the stopper 1222 toward the ejector end 1224 and distribute a predetermined volume of medicinal substance dispensed from the housing 1220 through the ejector end 1224.

In some embodiments, device 1200 may have additional features. For example, in some embodiments, the journal of the piston rod 1280 may have a geometry complementary to the bore of the flange member 1240 that limits the range and direction in which the piston rod 1280 can rotate or move longitudinally, similar to the journal 1084 and bore 1073 of the device 1050. For example, the rotation and /or the longitudinal movement of the piston rod 1280 may be limited based on the actuation, preparation, and/or drug delivery steps during use of the device 1200. As another example, the piston rod 1280 may be prevented from extending or retracting from the device 1200 to any point during preparation or use of the 1200 device.

- 33 044249

In the contemplated use of the device 1200, the device 1200 may be filled with a predetermined volume of medicinal substance. The predetermined volume of drug substance may be greater than the volume of drug substance suitable for delivery to the patient. In some embodiments, device 1200 (eg, housing 1220) may contain both a predetermined volume of drug substance and an air bubble (not shown) that must be removed before delivery of the drug substance to the patient. In some embodiments, device 1200 may be a pre-filled syringe. To actuate the device 1200 (e.g., remove an air bubble, if present, and ensure that an appropriate volume of medicinal substance is delivered to the patient), the user may push the actuator portion 1282 of the piston rod 1280 into the inner collar 1260. The geometry of the actuator portion 1282 may interact with an inner shoulder 1260 (e.g., a distal wedge or clamp of the actuation portion 1282 may extend on the distal side of the inner shoulder 1260) to attach the actuation portion 1282 to and/or the inner shoulder 1260 and to prevent retraction of the piston rod 1280. At this point, device 1200 may be in a powered state. Then, the inner collar 1260 may be rotated about the longitudinal axis until the projections 1262 are longitudinally aligned with the slots 1248. At this point, the device 1200 may be in a delivery state. To deliver a predetermined volume of medicinal substance from the device 1200, the inner collar 1260, along with the actuation portion 1282 and the piston rod 1280, can then be moved distally until the projections 1262 abut the distal end of the slots 1248. Distance traversed by the piston rod 1280 at this point may push the stopper 1222 distally the distance required to dispense a predetermined volume of medicinal substance from the ejector end 1224 of the device 1200.

With reference now to FIG. 6A-6E show views of the delivery device 1300 and its components. The delivery device 1300 includes a locking component comprising a distal flange member 1340 and a proximal flange member 1360, a piston rod 1380, and a housing 1320. Each of the distal flange member 1340 and the proximal flange member 1360 includes flanges (1346 and 1366, respectively) . Optionally, the flanges 1366 of the proximal flange member 1360 may include a texture 1365. The distal flange member 1340 includes a channel 1341 that may allow sliding assembly of the distal flange member 1340 and the body 1320. The proximal flange member 1360 includes includes a staple 1364 which allows the proximal flange member 1360 and the distal flange member 1340 to be movably attached to each other such that they can still rotate relative to each other about the longitudinal axis of the delivery device 1300 (see, for example, FIGS. 6D and 6E). The proximal flange member 1360 includes brackets 1362 adjacent a central hole 1368 through which a piston rod 1380 may extend. The piston rod 1380 includes an actuation portion 1382, which may optionally include a texture 1381. The piston rod 1380 further includes a distal cervical mold 1384, a proximal cervical mold 1387, and a proximal restrictor 1386 having a cavity 1385, all of which are configured to mate with the distal flange member 1340 and the proximal flange member 1360 in a variety of configurations to enable controlled actuation and delivery of a predetermined volume of drug substances using the delivery device 1300. The piston rod 1380 further includes a distal tip 1383 at the distal end of the rod 1389, wherein the tip 1383 is configured to mate with the stopper 1322. The tip 1383 may have any suitable size, shape, and method of attaching to, attaching to, or pushing the stopper 1322. described with respect to, for example, the tip 1083 of the piston rod 1080. As with the rod 1081, the rod 1389 may be of any size and configuration suitable for installation within the housing 1320. In some embodiments, the rod 1389 may be configured to provide sufficient size (eg thickness), stability and/or rigidity to reduce the likelihood of unwanted bending, wobbling, or breaking.

Housing 1320 (shown in FIGS. 6D and 6E) may have any or all of the same characteristics as, for example, housing 1060 of device 1050 or any syringe housing known in the art. For example, in some embodiments, housing 1320 may be pre-filled or pre-filled. The stopper 1322 may be configured to be inserted into the housing 1320 and may be configured to hold a predetermined volume of medicinal substance to be dispensed within the housing 1320 between the stopper 1322 and the ejector end 1324.

The device 1300 may be, for example, an injection device, such as a syringe, for dispensing a predetermined volume of drug dosage. In general, device 1300 may have the same size, capacity, material, preparation, assembly, or manufacturing characteristics as device 1050, device 1200, or other delivery devices described herein. As with devices 1050 and 1200, delivery device 1300 may be configured to facilitate use and may include one or more features that assist the user by providing tactile, audible, or visual feedback (eg, textures). 1365, 1381, other textures, marks, colors, or tactile or audible feedback, or the use of any other features described elsewhere herein). As with devices 1050 and 1200, such features are optional, and one or more such features may be combined to facilitate use.

The proximal flange member 1360 and the distal flange member 1340 may be of any suitable size and/or shape for use as a locking component in the delivery device 1300 to cover, partially cover, cover, or partially cover the end of the housing 1320 opposite the ejector end 1324, and /or to support and hold the piston rod 1380 in place within the housing 1320. In some embodiments, proximal flange member 1360 and distal flange member 1340 may each include one or more flanges that may be configured to assist a user in holding device 1300 and/or in expelling the dispensed medicinal substance from the ejector end 1324. In some embodiments shown in FIGS. 6A-6E, each of the flange elements 1360, 1340 may include two flanges 1366, 1346, respectively, with the flanges in each pair of flanges opposing each other and extending perpendicular to the longitudinal dimension of the device 1300. In general, other flange or flange arrangements are possible. for example, one flange on each of the flange elements 1360, 1340. Each of the flange elements 1340, 1360 may extend radially outward from the central longitudinal axis of the device 1300 beyond the circumference of the housing 1320, for example, to support the device 1300 when the device 1300 is placed on a surface, preventing the device 1300 from rolling on a flat surface, and/or allowing the device 1300 to be easily grasped.

The flange members 1360 and 1340 may, in combination, define a central opening that is variable in size and/or shape depending on the relative position of the proximal flange member 1360 and the distal flange member 1340. For example, in the configuration shown in FIG. 6D, the proximal flange member 1360 and the distal flange member 1340 may combine to form an opening configured to allow distal passage of the distal neck portion 1384 of the piston rod 1380 but block passage of the proximal neck portion 1387. In the second configuration shown in FIG. 6E (e.g., when flanges 1346 and 1366 are aligned), the central opening defined by flange members 1360 and 1340 may be configured to allow distal passage of proximal neck portion 1387. Proximal stop 1386 may be of a size and shape that is too large to pass through through the central hole formed by flange elements 1360 and 1340 in any combination. In some embodiments, distal flange 1340 may be assembled with housing 1320 and piston rod 1380 such that distal flange 1340 is stationary relative to housing 1320 and cannot rotate relative to piston rod 1380. Proximal flange 1360 may, conversely, be assembled with distal flange 1340 (and body 1320) such that it is rotatable about a longitudinal axis relative to the distal flange 1340, body 1320, and piston rod 1380, which may extend through the central hole 1368. Specifically, the proximal flange 1360 may be rotatable relative to the distal flange 1340 from a first configuration in which flanges 1346, 1366 are offset from each other (see FIG. 6D) to a second configuration in which flanges 1346, 1366 overlap each other (see FIG. 6E). Those skilled in the art will appreciate that in alternative embodiments, the distal flange 1340 may be rotatable relative to other parts of the device 1300, while the proximal flange 1360 may be non-rotational. In other additional embodiments, both proximal flange 1360 and distal flange 1340 may be assembled with housing 1320 and piston rod 1380 such that they are both rotatable relative to other components of device 1300.

The staples 1362 of the proximal flange member 1360 may protrude and be biased toward the opening 1368. In a pre-service configuration (shown in FIG. 6D), the staples 1362 may be compressed by the piston rod 1380. They may be positioned on the proximal flange member 1360 such that after the piston rod 1380 is distally moved so that the distal neck shape 1384 passes through the opening 1368, they expand inwardly to abut the sides of the distal neck part 1384. Once the staples 1362 are expanded so that they can block the proximal movement of the piston rod 1380, for example, preventing retraction of the piston rod (see, for example, Fig. 7C). A cavity 1385 may be located on a proximal stop 1386 for each staple 1362 such that when the piston rod 1380 is moved distally into the housing 1320 to the fullest extent required, each staple 1362 can be installed in the cavity 1385.

Fig. 7A-7F show an exemplary method of using device 1300 in accordance with aspects of the present disclosure. In the pre-operational configuration shown in FIG. 7A, the device 1300 may hold a volume of medicinal substance between the stopper 1322 and the ejector end 1324. The flange members 1340 and 1360 may be in a pre-service configuration in which the flanges 1346, 1366 are offset from each other. The piston rod 1380, which may be adjacent to or may be assembled with a stopper 1322, may be partially inserted into the body 1320 through the flange members 1340, 1360. The proximal flange member 1360 may not be able to rotate about the longitudinal axis of the syringe due to the geometries of the piston rod 1380 and the flange element 1360. In the actuation step shown in FIG. 7B, the piston rod 1380 may be moved longitudinally further into the housing 1320 until distal movement is blocked by the proximal neck portion 1385 abutting the surface of the proximal flange member 1360. For example, the user may press the actuation portion 1382 toward the proximal flange member 1360. In some embodiments, device 1300 may be held in an inverted position during this step to ensure that air trapped in housing 1320 can be pushed out through push end 1324 when stopper 1322 is pushed distally by piston rod 1380. configuration, the distal neck portion 1384 may be located in the opening 1368 of the proximal flange member 1360. Additionally, as shown in FIG. 7C, after completion of the actuation step, the staples 1362 may be released from their compressed configuration so that they can expand inwardly and abut the side surface of the distal neck portion 1384. Because the distal neck portion 1384 may be comparatively narrower than the piston portion rod 1380 previously located in bore 1368, expansion of staples 1362 may prevent proximal movement (e.g., retraction) of piston rod 1380.

As shown in FIG. 7D, device 1300 may be in a powered configuration. In the distribution preparation phase shown in FIG. 7E, proximal flange member 1360 may be rotated about its longitudinal axis to align flanges 1366 and flanges 1346 and to change (eg, enlarge) the shape of the central opening formed by the combined openings of proximal flange member 1360 and distal flange member 1340. To do this, the user may grasp and twist the proximal flange element 1360.

In some embodiments, the proximal flange member may be rotated in one direction or another to align flanges 1366 and flanges 1346. In other embodiments, the proximal flange member 1360 may be rotatable in only one direction. In some embodiments, after the flanges 1366 and flanges 1346 are aligned (as shown, for example, in FIG. 7E), further rotation of the piston rod 1080 relative to the flange member 1070 can be stopped, for example, by a bracket 1362 adjacent to the flange 1346. Thus, device 1300 may be locked in a ready-to-distribute configuration. As shown in FIG. 7F, during the dispensing step, the piston rod 1380 may be moved longitudinally further into the housing 1320. For example, the user may push the actuation portion 1382 distally until each of the staples 1362 enters the cavity 1385 in the proximal stop 1386, and/or until until the proximal stop 1386 abuts the proximal surface of the proximal flange member 1360. The dispensing step may ensure that a predetermined volume of medicinal substance from within the housing 1320 is dispensed from the device 1300.

In some embodiments, after each subsequent step in using the device 1300, the user may be prevented from re-executing a step and/or reversing one or more steps. For example, the geometries of, for example, piston rod 1380 and the combined openings of proximal flange member 1360 and distal flange member 1340 may prevent a user from being able to pull piston rod 1380 proximally (e.g., from housing 1320), rotate piston rod 1380, or pre-rotate piston rod 1360 (e.g. , before the end of the actuation step shown in FIGS. 7B and 7C), and/or excessively rotate the flange member 1360 during the dispensing preparation step (eg, shown in FIG. 7E).

Fig. 8A-8G further show an exemplary device 1400 and its components. The delivery device 1400 includes a piston rod 1480, a locking component 1460, a flange member 1440, and a housing 1420. The piston rod 1480 includes an actuation portion 1482 and a projection 1484. The locking component 1460 may be a rotatable alignment component that is configured to partially or completely surround the piston rod 1480, and includes three connected channels 1462, 1464, 1468 configured to allow passage of the projection 1484. The flange element 1440 includes a proximal shoulder 1442 having a channel 1447 into which tabs 1461 can be slidably installed, a distal collar 1444 including a channel 1445 into which a flange 1421 of the housing 1420 can be mounted (e.g., slidably mounted), and flanges 1446.

Housing 1420 (shown in FIGS. 8D and 8E) may have any or all of the same characteristics as, for example, housing 1060 of device 1050 or any syringe housing known in the art. For example, in some embodiments, housing 1420 may be pre-filled or pre-filled. Stopper 1422 may be configured to be inserted into housing 1420 and may be configured to hold a predetermined volume of dispense.

- 36 044249 medicinal substance inside the housing 1420 between the stopper 1422 and the ejector end 1424.

The delivery device 1400 may be, for example, an injection device, such as a syringe, for dispensing a predetermined volume of drug dosage. In general, delivery device 1400 may have size, capacity, material, preparation, assembly, or manufacturing characteristics that match those of device 1050, device 1200, device 1300, or other delivery devices disclosed herein. As with other devices disclosed herein, delivery device 1400 may be configured to facilitate use and may include one or more features that assist the user by providing tactile, audible, or visual feedback using any of the features described herein. in other places.

The locking component 1460 may have another suitable size or shape to assist in controlling the proximal and distal movement of the piston 1480 in the device 1400.

The flange member 1440 may be of any suitable size and shape to cover, partially cover, cover, or partially cover the end of the body 1420 opposite the ejector end 1424, and/or to support and retain the locking component 1460 and the piston rod 1480 relative to the body 1420. For example, the proximal shoulder 1442 and channel 1447 may be configured to retain the locking component 1460, and the distal shoulder 1444 and channel 1445 may be configured to support the flange 1421 of the housing 1420 such that the locking component 1460 is held stationary relative to the housing 1420. Additionally, the locking component 1460 may be configured to retain piston rod 1480 within housing 1420 and limit movement of piston rod 1480 relative to housing 1420. Flange member 1440 may include one or more flanges 1446 that may be configured to assist a user in holding device 1400 and/or or ejecting the medicinal substance to be dispensed from the ejector end 1424. In some embodiments shown in FIGS. 8A-8E, flange member 1440 may include two flanges 1446 opposed to each other. In general, other flange or flange arrangements are possible, such as one flange or three flanges. The flange member 1440 may extend radially outward from the central longitudinal axis of the device 1400 beyond the circumference of the housing 1400, for example, to support the device 1400 when the device 1400 is placed on a surface, prevent the device 1400 from rolling on a flat surface, and/or allow the device 1400 to be easily gripped.

The channels 1462, 1464, 1468 in the locking component 1460 together define a path along which the protrusion 1484 can move to allow controlled movement of the piston rod 1480. The first channel 1462 can allow the distal movement of the piston rod 1480 sufficient to operate the device 1400. The second channel 1464 may allow the piston rod to move between an actuated state and a delivered state. The channel 1464 may have a path requiring rotation of the piston rod 1480 about the longitudinal axis of the device 1400 (as opposed to distal movement of the piston rod 1480), so that the likelihood of accidental or unintentional movement of the piston rod 1480 into the delivery state can be reduced. The channel 1464 may provide a path of any suitable length (corresponding to any suitable angle of rotation of the piston rod 1480) to provide adequate separation of the driven state and the delivery state. The third channel 1468 may allow distal movement of the piston rod 1480 sufficient to dispense a predetermined volume of drug from the device 1400.

One or more of the channels 1462, 1464, 1468 may include one or more of the latches shown in FIG. 8F and 8G. For example, a cross section of the locking component 1460 in FIG. 8F shows the inside of a channel 1464 having a small detent 1491 located on one side. Fig. 8G shows two large clamps 1492, 1493 in channels 1462, 1464, respectively. Each detent may provide resistance to movement of the protrusion 1484 through channels 1462, 1464, and/or 1468 to provide audible feedback and/or to prevent inadvertent movement of the protrusion 1484. In some embodiments, the detents 1491, 1492, 1493 may be angled at one side to allow the projections 1484 to pass in one direction and not allow them to pass in the other direction. Retainers, such as the retainers shown in FIG. 8F and 8G may be suitable for inclusion in any device disclosed herein, as well as in device 1400.

Fig. 9A-9E show an exemplary method of using device 1400 in accordance with aspects of the present disclosure. In the pre-operational configuration shown in FIG. 9A, the device 1400 may retain a volume of medicinal substance between the stopper 1422 and the ejector end 1424. The piston rod 1480 may be partially inserted into the housing 1420 such that the protrusion 1484 of the piston rod 1480 is located at the proximal end portion of the channel 1462. During the actuation step, action shown in FIG. 9B, piston rod 1480 may be moved longitudinally further into housing 1420 until distal movement is blocked by abutment of projection 1484 to the distal end of channel 1462. For example, a user may push actuation portion 1482 distally through locking component 1460. In some embodiments, device 1400 may be held in an inverted position during this step to ensure that air trapped in housing 1420 can be expelled when stopper 1422 is pushed distally by piston rod 1480. In the actuated configuration shown in FIG. . 9C, a protrusion 1484 of the piston rod 1480 may be located at the first end of the channel 1464.

In the distribution preparation phase shown in FIG. 9D, the piston rod 1480 may be rotated about the longitudinal axis such that the protrusion 1484 moves from the first end of the channel 1464 to the second end of the channel 1464. For example, the user may grip and twist the actuation portion 1482 of the piston rod 1480. The device 1400 may then be configured ready for distribution, in which the protrusion 1484 is located at the proximal end of the channel 468. As shown in FIG. 9E, during the distribution step, the piston rod 1480 may be moved longitudinally further into the housing 1420. For example, the user may push the actuation portion 1482 distally until the projection 1484 abuts the distal end of the channel 468. The distribution step may ensure that a predetermined a volume of medicinal substance from within the housing 1420 is dispensed from the device 1400.

In some embodiments, after each subsequent step in using the device 1050, the user may be prevented from re-executing a step and/or reversing one or more steps. For example, geometries of, for example, piston rod 1480, protrusion 1484, and/or channels 1462, 1464, 1468 may prevent a user from being able to pull piston rod 1480 proximally (eg, from housing 1420).

Fig. 10A-10C show an exemplary method of assembling device 1400. As shown in FIG. 10A, flange member 1440 may be slidably assembled with housing 1420 such that flange 1421 is installed in channel 1445 and collar 1444 partially surrounds housing 1420. As shown in FIG. 10B, locking component 1460 may be slidably assembled with flange member 1440 such that tabs 1461 are located within channels 1447 and locking component 1460 abuts proximal collar 1442. As shown in FIG. 10C, piston rod 1480 may then be inserted into the combined locking component 1460, flange member 1440, and housing 1420 such that protrusion 1484 is located within bore 1462 of housing 1420.

Fig. 10D-10G, 11A-11E, and 12A-12D show a configuration and method of using the device 1400 and will not be described in more detail to avoid redundancy. Fig. 10D-10G show an alternative method of assembling device 1400, wherein blocking component 1460 includes an opening 1463 through which piston rod 1480 can be mounted. In this embodiment, channels within blocking component 1460 (e.g., channels 1462, 1468) can be closed proximally and a distal end to prevent retraction or excessive insertion of the piston rod 1480 relative to the body 1420. As shown in FIG. 10E, piston rod 1480 may be partially inserted into housing 1420, and flange member 1440 may be slidably assembled with housing 1420 such that flange 1421 is installed in channel 1445 and collar 1444 partially surrounds housing 1420. As shown in FIG. 10F, locking component 1460 may be assembled with piston rod 1480 such that protrusion 1484 is located within one of the channels in locking component 1460. As shown in FIG. 10G, the locking component 1460 may then be assembled with the flange member 1440 so that it is positioned in the channel 1447. The locking component may be attached to the flange member 1440 by any suitable method (e.g., using staples, adhesive, friction fit, dovetail joints). tail, etc.). Fig. 12A-12D show a close-up view of the protrusion 1484 moving through the channels of the blocking component 1460, according to the method of use shown in FIG. 11A-11E.

Fig. 13A and 13B show a further exemplary delivery device 1500 and a method for assembling said delivery device according to additional embodiments of the present disclosure. The device 1500 includes a piston rod 1580, a locking component in the form of a flange member 1540, and a housing 1520. To assemble the device 1500, the piston rod may be inserted into the housing 1520 (for example, as shown in FIG. 13A) so that it abuts or attached to a stopper 1522 in the housing 1520, and the flange member 1540 may be slidably assembled with the flange 1521, for example, by sliding a channel 1541 onto the flange 1521 of the housing 1520 (eg, as shown in FIG. 13B). The opening 1543 may allow the flange member 1540 to be assembled with the housing 1520 around the piston rod 1580. It is contemplated that alternative assembly methods may be possible depending on the size, shape, and design of each component of the device 1500.

The delivery device 1500 may be, for example, an injection device, such as a syringe, for dispensing a predetermined volume of drug dosage. In general, delivery device 1500 may have size, capacity, material, preparation, assembly, or manufacturing characteristics that match those of device 1050, device 1200, device 1300, or other delivery devices disclosed herein. As with other devices disclosed herein, delivery device 1500 may be configured to facilitate use and may include one or more features that assist the user by providing tactile, audible, or visual feedback using any symptoms described elsewhere here.

Fig. 14A-14F show an additional view of the device 1500 and a method of using the device 1500. As shown in FIG. 14A, the piston rod 1580 may include an actuation portion 1582, a proximal stop 1588, a proximal neck portion 1586, and a distal neck portion 1584. The body 1520 may have any or all of the same characteristics, for example, the body 1060 of the device 1050 or any syringe body. , known in the art. For example, in some embodiments, housing 1520 may be pre-filled or pre-filled. The stopper 1522 may be configured to be inserted into the housing 1520 and may be configured to hold a predetermined volume of medicinal substance to be dispensed within the housing 1520 between the stopper 1522 and the ejector end 1524.

The flange member 1540 may be of any suitable size and shape to partially cover, cover, or partially cover the end of the housing 1520 opposite the ejector end 1524 and/or to support and retain the piston rod 1580 in the housing 1520. The opening 1542 may be of a size and shape that configured to allow passage of the piston rod 1580 in two different configurations. The distal neck portion 1584 and the proximal neck portion 1586 may have similar shapes, but may be rotationally offset from each other (for example, such that after the distal neck portion 1584 passes through the opening 1542, the piston rod 1580 must be rotated about the longitudinal axis, to allow passage of the proximal cervical 1586). The distal neck portion 1584 may include, for example, a tapered distal side that may assist in orienting the piston rod 1580 so that the distal neck portion 1584 can pass through the opening 1542. This may facilitate, for example, an actuation step.

Fig. 14A shows a pre-operational configuration of the device 1500. In such a configuration, the device 1500 may retain a volume of medicinal substance between the stopper 1522 and the push end 1524. The piston rod 1580 may be partially inserted into the housing 1520 such that the distal neck portion 1584 is located proximal to the flange element 1540. In the actuation step shown in FIG. 14B, piston rod 1580 may be moved longitudinally further into housing 1520 until distal movement is blocked by abutment of proximal neck portion 1586 to opening 1542 (as shown in FIG. 14C). For example, the user may depress the actuation portion 1582 until the distal neck portion passes through the opening 1542. In some embodiments, the device 1500 may be held in an inverted position during this step to ensure that air trapped in the housing 1520 could be pushed out when the stopper 1522 is pushed distally by the piston rod 1580. In the actuated state shown in FIG. 14D, the proximal neck portion 1586 may be positioned against the surface of the flange member 1540.

In the distribution preparation phase shown in FIG. 14D, the piston rod 1580 may be rotated about its longitudinal axis such that the shape of the proximal neck portion 1586 is aligned with the opening 1542. For example, the user may grip and twist the actuation portion 1582 of the piston rod 1580. The device 1500 may then be in a dispensing-ready configuration. . As shown in FIG. 14E, during the distribution step, the piston rod 1580 may be moved longitudinally further into the housing 1520. For example, the user may push the actuation portion 1582 distally until the proximal stop 1588 abuts the surface of the flange member 1540. The distribution step may ensure that a predetermined volume of medicinal substance from within the housing 1520 is dispensed from the device 1500.

In some embodiments, after each subsequent step in using the device 1500, the user may be prevented from re-executing a step and/or reversing one or more steps. For example, the geometries of, for example, piston rod 1580, distal neck 1584, proximal neck 1586, and opening 1542 may mate with each other to prevent a user from retracting piston rod 1580 proximally (e.g., from housing 1520).

Additional embodiments of blocking components, dose control components, and the like will now be described. Fig. 15A-23C show illustrative piston rod disks according to additional embodiments of the present disclosure. For example, FIG. 15A shows a piston rod 1600 having an actuation portion 1610. The actuation portion 1610 may be shaped generally to match the flange member 1640. The piston rod 1600 may be rotatable relative to the flange member 1640 and/or the device body. The device may be in a configuration suitable for delivering the desired amount of drug when, for example, the shape of the piston rod 1610 is generally aligned with the shape 1640 (shown, for example, in the top view of FIG. 15A). As another example, FIG. 15B shows an actuation portion 1610' with a serrated side surface to facilitate rotation of the piston rod 1600' relative to the flange member 1640 and/or the rest of the syringe. Fig. 16A shows the actuation portion 1610'' with a ribbed side surface, also to facilitate rotation of the piston rod 1600. FIG. 16B shows an exemplary combination of actuation portion 1610'' with device 1500. Those skilled in the art will appreciate that any actuation portions or other features described herein may be combined with the devices described herein.

Fig. 17 shows an example piston rod and disk according to additional embodiments of the present disclosure. The actuation portion 1612 may be configured to fit into the collar 1642 of the flange member 1640' only in a specific configuration. The depth of the collar 1642 may correspond, for example, to the distance that the piston rod 1600 must travel to dispense a given volume of drug from the drug delivery device. In one embodiment, the actuation portion 1612 may be moved distally until it abuts the bead 1642, and then may be rotated until its shape matches the shape of the bead 1642 so that it can be pushed into collar 1642 during the distribution stage. Fig. 18A and 18B show an additional exemplary piston rod and disk that combine exemplary features that enable accurate dose delivery. The piston rod may include, for example, projections 1684 and 1682, each of which may be installed through the opening 1641' into the flange member 1680 in a particular configuration. Each of the projections 1684 and 1682 may correspond to a distance required to deliver a desired volume of medicinal substance from the device and/or to actuate the device. The actuation portion 1650 may include a raised portion 1652 that may assist a user in torsion of the piston rod relative to the flange member 1680.

Fig. 19A and 19B show a top view of flange member 1740 and piston rod 1720. Flange member 1740 and piston rod 1720 may have a cross-sectional shape that allows limited rotation of piston rod 1720 relative to flange member 1740 in a single direction. For example, flange member 1740 may have internal projections that may interact with the irregular cross-sectional shape of piston rod 1720 to resist the first portion of piston rod 1720 as it rotates past the internal projections and to stop the second portion of piston rod 1720 as it abuts the internal projections. protrusions

Fig. 20 shows an illustrative flange member 1750 with a recess 1760 having staples 1762. The piston rod actuator portion 1789 may be pushed distally into the recess 1760 until the staples 1762 overlap the actuator portion 1780 to hold the actuator portion 1780 in place and, for example, preventing the piston rod from retracting. The piston rod includes a distal projection 1781 and a proximal projection 1783, each of which is configured to be mounted through the opening 1764 when the piston rod is rotated to a particular position. The distal projection 1781 includes a tapered distal side that may assist in orienting the piston rod to a position required to advance the piston rod distally such that the distal projection 1781 extends through the opening 1764. This may facilitate, for example, an actuation step. In some embodiments, the height of the recess 1760 and/or the actuation portion 1780 may correspond to the height that the piston rod must travel to dispense a given volume of drug substance. Thus, the device can be actuated when adjacent to the proximal side of the recess 1760, and can deliver a predetermined volume of medicinal substance when the actuation portion 1780 is moved distally into the recess 1760.

Fig. 21 shows an exemplary device 1800 with a piston rod 1820 and a complementary flange member 1840. The piston rod 1820 may include, for example, projections 1844, 1846 having an angled or wedge-shaped shape corresponding to the shape of one or more holes 1842 in the flange member 1840. The wedge-shaped or angled shapes of the projections 1844, 1846 and holes 1842 may be sufficient to resist distal movement of the piston rod 1820 when the projection 1844 or 1846 is adjacent to the side surface of the hole 1842, but may be capable of moving one after the other if sufficient force is applied. The resistance provided by the abutment of the projections 1844, 1846 against the side surfaces of the holes 1842 may be sufficient to indicate to the user that a particular step in using the device 1800 has been completed. The user may then apply sufficient force to move the piston rod 1820 to overcome this resistance and proceed to to the next stage (for example, from the completed activation stage to the ready for delivery stage).

As has been described elsewhere, any of the devices disclosed herein may be combined with cues, audible feedback, and/or tactile feedback in the form of symbols (e.g., shown in FIG. 22 as lock and unlock symbols 1850, 1852 , chevrons 1856 on the triggering part 1854). The rotation of the piston rod may also be accompanied by a clicking sound.

Fig. 23A-23C show a further exemplary combination of components in a delivery device. For example, the piston rod actuator portion 1650 may include, for example, ribbed side surfaces and a raised portion 1652 to assist in torsion of the actuator portion. A device with these characteristics may include, for example, holes 1842 and corresponding angled projections 1844, 1846 (described in relation to FIG. 21).

Fig. 24A-24E show an additional exemplary delivery device 1900 and a method of using the device 1900. The device 1900 may include an actuation portion 1940 and a locking component 1980 shown on the piston rod 1920. The piston rod 1920 may be adjacent to a stopper 1912 in the housing 1910. The locking component 1980 may be rotatable relative to the piston rod 1920. In the pre-operational configuration shown in FIG. 24B, the locking component 1980 may be in a first position relative to the piston rod 1920 and the flange member 1960. During the actuation step shown in FIG. 24C, piston rod 1920 may be moved longitudinally further into housing 1910 until distal movement is blocked by abutment of locking component 1980 against recess 1962 in flange member 1960. For example, a user may push actuation portion 1940 distally toward flange member 1960. In the distribution preparation stage shown in FIG. 24D, the locking component 1980 may be rotated such that the smaller dimension of the locking component 1980 faces the flange member 1960. The recess 1962 may be curved to facilitate rotation of the locking component 1980. The distance between the locking component 1980 and the flange member 1960 after rotation of the locking component 1980 may correspond to the distance that the piston rod 1920 can move to dispense a predetermined volume of drug from the device 1900. As shown in FIG. 24E, during the distribution step, the piston rod 1920 may be moved longitudinally further into the housing 1910 until the rotated locking component 1980 abuts the flange member 1960 in a second position. For example, the user may push the actuation portion 1940 distally until the locking component abuts the flange member 1960. The dispensing step may ensure that a predetermined volume of medicinal substance from within the housing 1910 is dispensed from the device 1900.

Fig. 25A-25E show a further exemplary delivery device 2000 and a method of using the delivery device 2000. The piston rod 2080 of the device 2000 may include a thread 2100 corresponding to an internal thread (not shown) in the flange member 2062. As shown in FIG. 25A, the piston rod 2080 may be rotatable relative to other parts of the device 2000. The piston rod 2080 may also include a projection 2082 proximal to the threads 2100 (see, for example, FIG. 25B), which may correspond to an opening 2062 in the top member 2062 so that the piston rod 2080 must be in a particular configuration and position to allow the projection 2082 to pass into and/or through the flange member 2060. In the pre-operational configuration shown in FIG. 25C, threads 2100 and shoulder 2082 may be positioned proximally to flange member 2060. During the actuation step, piston rod 2080 may be rotated relative to the internal threads of flange member 2060 until threads 2100 pass through flange member 2060, and/ or the projection 2082 will not prevent further rotation or distal movement of the piston rod 2080. During the preparation stage for distribution, the projection 2082 may be moved toward the hole 2062. During the distribution stage, the projection 2082 may be moved through the hole 2062 to further advance the piston rod 2080 and to distribute a predetermined volume of medicinal substance from inside the body of the device 2000.

Fig. 26A-26E show a delivery device 2200 having additional options for dose control components. For example, device 2200 includes a piston rod 2280 with one or more staples 2284, each of which may be configured to slide distally into the channel 2242 of the flange member 2240 and, after sliding distally, resist proximal sliding out of the channel 2242 (e.g., to prevent or resistance to retraction of the piston rod 2280). The flange member 2240 may further have a second channel 2244 and a third channel 2246 through which each of the staples 2284 can slide during the pre-delivery and dose delivery steps as described above. Alternatively, as shown in FIG. 26B, channel 2242' may have an open proximal end through which protrusion 2284' may move to allow proximal and/or distal movement of piston rod 2280 relative to flange member 2240'. As shown in FIG. 26C, in a pre-service configuration, staples 2284 may be positioned proximally to channels 2242 of flange member 2240. During the actuation step, piston rod 2280 may be moved distally into device body 2200 until staples 2284 are moved into channels 2242 and will be adjacent to the distal end of the channels 2242. During the dispensing preparation phase, the piston rod 2280 may be rotated relative to the flange member 2240. During the distribution phase, the piston rod 2280 may be moved further distally into the body of the device 2200 to dispense a predetermined volume of drug substance from the device 2200 .

In other embodiments shown in FIGS. 26F-26G, flange element 2240'' can

- 41 044249 include one or more projections 2246'' located within the collar 2242''. In the present example, bead 2242'' may include a pair of projections 2246'' extending radially inwardly from the inner surface of bead 2242'' and in opposite directions relative to each other. For example, the projections 2246'' may be located at approximately 180 degrees to each other. It should be understood that flange member 2240'' may include more and/or fewer projections 2246'' than shown and described herein without departing from the scope of this disclosure. The flange member 2240'' may be configured to engage the piston rod 2080'' in response to the piston rod 2280'' receiving the projections 2246''.

As can be seen in FIG. 26G, piston rod 2280'' may include an actuation member 2284'' defined by a proximal end 2282'' and a distal end 2283''. The piston rod 2280'' may include a number of channels along opposite sides of the actuation element 2284'', such as, for example, a first channel 2286'', a second channel 2288'', and a third channel 2290'' located between the proximal end 2282' ' and the distal end 2283''. The first channel 2286'' is offset from the third channel 2290'' and is connected to the third channel 2290'' by a second channel 2288'' located between them. As described in detail below, the first channel 2286'' may determine the longitudinal and axial driving path of the piston rod 2280'', the second channel 2288'' may determine the circumferential path of the piston rod 2280'', and the third channel 2290'' may determine the longitudinal and axial path of the end of the dose. It should be understood that the opposite surface and/or side of the actuation element 2284'' (not shown) includes a substantially similar row of connected first channel 2286'', second channel 2288'', and third channel 2290'' seen in FIG. . 26G. In the present example, the first channel 2286'' and the third channel 2290'' may be aligned parallel to each other.

The first channels 2286'', the second channels 2288'', and the third channels 2290'' may be configured to receive at least one of a pair of projections 2246''. In the case of a piston rod 2280'' coupled to a flange member 2240'', projections 2246'' may extend into and slide through first passages 2286'', second passages 2288'', and third passages 2290'' for actuation and delivery. doses from device 2200 (FIG. 26A), as described in detail above. In some embodiments, the first channels 2286'' may have an open end at the proximal end 2282'' through which projections 2246'' can be received. In some embodiments, the first channels 2286" may have a closed proximal end, and the projections 2246" may be at least partially flexible and/or deformable such that the projections 2246" may be configured to flex radially outward as they reception at the proximal end of the first channels 2286''. In other embodiments, the first channels 2286'' may have an inclined, beveled, and/or tapered end to facilitate guiding the projections 2246'' towards the second channels 2288''. In this example, the inclined end may prevent retraction (eg, proximal movement) of the piston rod 2280'' relative to the flange member 2240''. The longitudinal length of the first channels 2286'' may define an axial actuation path (eg, amount or range of actuation) that is configured to facilitate proximal and/or distal movement of the piston rod 2280'' relative to the flange member 2240''. For example, projections 2246'' may be located at the proximal end of the first channels 2286'' and proximal to the second channels 2288'' when the device 2200 is in an assembled state. During the actuation step, the piston rod 2280'' may move distally relative to the flange member 2240'' until the projections 2246'' are located within the second channels 2288'' and at the distal end of the first channels 2286''. The second channels 2288'' may define the circular path of the piston rod 2280''.

In preparation for dispensing, the piston rod 2280'' may be rotated relative to the flange member 2240'' to move the projections 2246'' transversely along the circular path of the second channels 2288'' and towards the dose end path defined by the third channels 2290''. In some embodiments, piston rod 2280'' and/or flange member 2240'' may be configured to generate user feedback (e.g., tactile, audible, visual, etc.) when device 1050 is in a step preparation for distribution. During the distribution step, the piston rod 2280'' can be moved distally into the device body 2200 to distribute a controlled volume of substance by moving the projections 2246'' through the third channels 2290''. The longitudinal length of the third channels 2290'' may determine the dose delivery path (eg, dose amount). It should be understood that the axial actuation path (length of the first channels 2286'') may vary relative to the dose delivery path (length of the third channels 2290''). In other embodiments, piston rod 2280'' may include more and/or fewer passages along actuation member 2284'' (e.g., corresponding to the number of projections 2246'' on flange member 2240'') than shown and described herein, or may have various other relative channel configurations.

Fig. 27A-27H show an exemplary delivery device 2300 and a method of using the delivery device 2300. Actuator portion 2350 may also serve as a locking component of device 2300. Actuator portion 2350 may be slidably coupled to piston rod 2380 in two configurations via passage 2352. As shown in FIG. 27V, one side triggered

- 42 044249 part 2350 may include a channel 2354. The depth of the channel 2354 may correspond to the distance that the piston rod can move to dispense a predetermined volume of drug substance after activation of the device 2300. As shown in FIG. 27C and FIG. 27D, in a pre-operational configuration, the actuation portion 2350 may be assembled with the piston rod 2380 such that the flat side of the actuation portion 2350 faces the collar 2360 of the device 2300. During the actuation step, the actuation portion 2350 may be used to move the piston rod 2380 distally until the flat side 2356 of the actuation portion 2350 abuts the proximal side of the collar 2360. In preparation for the dose delivery step, the actuation portion 2350 may be removed from the piston rod 2380 and may be rotated or inverted and reassembled with the piston rod. 2380 so that channel 2354 faces collar 2360, as shown in FIG. 27F and 27G. During the dose delivery step, actuation portion 2350 may be used to push piston rod 2380 further distally until the proximal end of collar 2360 abuts the inner end of channel 2354. This movement of piston rod 2380 may be sufficient to dispense a predetermined dose of drug. from device 2300.

Fig. 28A-28C show an exemplary delivery device 2400 and a method of using the delivery device 2400. Delivery device 2400 may include features substantially similar to those shown and described above, such that like reference numerals are used to identify like components. As shown in FIG. 28A, the delivery device 2400 may include a removable bracket 2402 coupled to the housing 1060 at a position distal to the flange member 1070. The removable bracket 2402 may be an obstruction and/or locking component configured to prevent movement of the flange member 1070 relative to the housing 1060. The release clip 2402 is selectively removable such that the release clip 2402 is configured to disengage the housing 1060 in response to manual actuation of the release clip 2402.

As an illustrative example, release clip 2402 may have a housing that wraps around the outer portion of housing 1060 and is configured to selectively deform (e.g., collapse, rupture, etc.) upon application of force thereto to release release clip 2402 from the housing. 1060. In other examples, release clip 2402 may have a flexible body that is configured to flex in response to a radially outward force applied thereto, thereby disengaging release clip 2402 from body 1060. As a further example, release clip 2402 may have a housing that is configured to selectively transition between a closed configuration encapsulating the circumference of the housing 1060 and an open configuration allowing the housing 1060 to be removed from the release bracket body 2402. The release bracket 2402 may include various other suitable sizes, shapes, and/or or configurations other than those shown and described herein, without departing from the scope of this disclosure.

Delivery device 2400 may include a radial wall 1063 extending transversely outward from the exterior of housing 1060, thereby forming an obstruction along housing 1060. As seen in FIG. 28A, the radial wall 1063 may be configured to inhibit distal movement of the removable bracket 2402 along the housing 1060. In some embodiments, the radial wall 1063 may be a hinged component attached to the housing 1060, while in other embodiments, the radial wall 1063 may be formed integrally with housing 1060. Referring now to FIG. 28B, flange member 1070 and piston rod 1080 may be configured to move distally along housing 1060 to operate delivery device 2400 upon removal of release bracket 2402 from housing 1060. In this example, piston rod 1080 may remain stationary relative to flange member 1070, when the combined assembly of flange member 1070 and piston rod 1080 moves relative to housing 1060. In other embodiments, piston rod 1080 may remain stationary as flange member 1070 moves distally along housing 1060 to operate delivery device 2400. For example, at least a portion of the flange member 1070 may extend into the housing 1060 (eg, and past the stopper 1062) when the device 2400 is activated. In this example, the piston rod 1080 may be separately moved to deliver a dose from the delivery device 2400.

With flange member 1070 moved from a proximal position (FIG. 28A) to a distal position (FIG. 28B), the delivery device 2400 may be in an actuated position. It should be understood that the housing 1060 may be configured to limit the movement of the flange member 1070 based on the location of the radial wall 1063 to a certain distance, which may correspond to the actuation distance of the delivery device 2400. Accordingly, the actuation distance of the delivery device 2400 can be controlled by adjusting the range of movement of the flange member 1070 along the housing 1060.

As can be seen in FIG. 28C, the piston rod 1080 can be moved distally relative to the core

- 43 044249 thrust 1060 in response to the application of a distally directed force to actuation portion 1082. In this example, rod 1081 may move relative to flange member 1070, thereby causing stopper 1062 to move within housing 1060 to deliver a dose. It should be understood that the range over which the piston rod 1080 moves relative to the flange member 1070 may determine the dose delivery distance of the delivery device 2400. The dose delivery distance can be controlled based on the gap formed between the collar 1072 and the actuation portion 1082.

In other embodiments shown in FIGS. 28D-28F, delivery device 2400 may further include a locking component, such as, for example, a release rod 2404 coupled to flange member 1070. Referring specifically to FIG. 28D, the removable rod 2404 may be received through the proximal end of the collar 1072, for example, through one or more transverse apertures (not shown) formed through the collar 1072. The removable rod 2404 may be configured to inhibit movement of the piston rod 1080 relative to the flange member 1070. for example, to prevent the actuation portion 1082 from being received in the collar 1072. The release rod 2404 may be selectively removable and configured to disengage the collar 1072 upon manual actuation of the release rod 2404. It should be understood that the delivery device 2400 may include various other locking components in addition to and/or instead of the removable rod 2404, such as, for example, a pin, tab, rod, and the like.

For example, with reference now to FIG. 28E, flange member 1070 and piston rod 1080 (e.g., rod 1081 and actuation portion 1082) may be configured to move distally along housing 1060 to actuate delivery device 2400 in response to removal of release clip 2402 from housing 1060. Piston rod 1080 may remain stationary relative to the flange member 1070 as the flange member 1070 and piston rod 1080 assembly moves relative to the housing 1060. In the case of the flange member 1070 moved from a proximal position (FIG. 28D) to a distal position (FIG. 28E), delivery device 2400 may be in the actuation position. It should be understood that the housing 1060 may be configured to limit the movement of the flange member 1070 based on the location of the radial wall 1063 along the housing 1060 to a certain distance, which may correspond to the actuation distance of the delivery device 2400.

As can be seen in FIG. 28F, the removable rod 2404 may be disengaged from the collar 1072 so that it no longer interferes with the movement of the piston rod 1080 distally relative to the flange member 1070. The actuation portion 1082 may be moved into the collar 1072 to move the rod 1081 and the stopper 1062 within the housing 1060 for delivery doses. The range over which the piston rod 1080 moves relative to the flange member 1070 may determine the dose delivery distance of the delivery device 2400.

In other embodiments shown in FIGS. 28G-28I, the release bracket 2402 may be eliminated entirely so that the delivery device 2400 may include a single obstructing and/or locking component, i.e., a rod 2404. In this example, the flange member 1070 may be stationary relative to the housing 1060 In the case of an actuator portion 1082 located proximal to the rod 2404, the delivery device 2400 may be actuated in response to distal movement of the piston rod 1080 toward the flange member 1070 prior to impact with the rod 2404. It should be understood that the flange member 1070 and/or or rod 2404 may be configured to inhibit distal movement of the piston rod 1080 relative to them in the absence of a distally directed force being applied thereto. In other examples, delivery device 2400 may include a locking component located between actuation portion 1082 and rod 2404 (e.g., release clip 2402) to prevent distal movement of piston rod 1080.

Accordingly, the actuation distance of the delivery device 2400 may be determined by the distance between the distal end of the actuation portion 1082 and the shaft 2404 when the delivery device 2400 is in an assembled, pre-actuated state (FIG. 28G). In the case of the actuation portion 1082 contacting the rod 2404, as shown in FIG. 28H, the delivery device 2400 may be in a powered state. The rod 2404 may be removed from the collar 1072 to thereby allow the piston rod 1080 to further move distally relative to the flange member 1070. As shown in FIG. 28I, a dose may be delivered from the delivery device 2400 in response to the bead 1072 receiving the actuation portion 1082. It should be understood that the longitudinal displacement of the distal end of the actuation portion 1082 and the inner surface of the bead 1072 may be determinative of the dose delivery distance. Accordingly, the range (eg, dose delivery distance) over which the piston rod 1080 moves relative to the flange member 1070 may determine the volume of dose delivered by the delivery device 2400.

In other embodiments shown in FIGS. 28J-28L, the delivery device 2400 may include an attached staple 2406 attached to the housing 1060 at a location relatively distal from the removable staple 2402. The attached staple 2406 may be obstructive and/or

- 44 044249 a locking component positioned in contact with the detachable bracket 2402 such that the attached staple 2406 is configured to prevent movement of the detachable staple 2402 along the housing 1060. In the case of a flange member 1070 located proximally from the detachable staple 2402, the attached staple 2406 may be further configured to prevent movement of the flange member 1070 when the removable bracket 2402 is positioned therebetween.

With reference now to FIG. 28K, the flange member 1070 may be configured to move distally along the housing 1060 to operate the delivery device 2400 upon removal of the release bracket 2402 from the housing 1060. In this example, the piston rod 1080 may remain stationary relative to the flange member 1070 when the piston assembly is removed from the housing 1060. rod 1080 and flange member 1070 moves toward the secured staple 2406. With flange member 1070 moved from a proximal position (FIG. 28J) to a distal position (FIG. 28K) in contact with the attached staple 2406, the delivery device 2400 may be in activation position. It should be understood that the housing 1060 may be configured to limit the movement of the flange member 1070 to a certain distance, which may correspond to the actuation distance of the delivery device 2400.

As can be seen in FIG. 28L, the piston rod 1080 may be moved distally relative to the housing 1060 in response to the application of a distally directed force to the actuation portion 1082. The rod 1081 may be moved relative to the flange member 1070 causing the stopper 1062 to move within the housing 1060 to deliver a dose. It should be understood that the range over which the piston rod 1080 moves relative to the flange member 1070 may determine the dose delivery distance of the delivery device 2400. The dose delivery distance may be controlled based on the position of the secured bracket 2406 along the body 1060.

In additional embodiments, delivery device 2400 may include a sleeve 2408 extending distally from flange member 1070, as shown in FIG. 28M. The sleeve 2408 may be attached to the distal end of the flange member 1070 and/or may be integral with the flange member 1070, thereby forming a single structure. Sleeve 2408 may be located within housing 1060 and may include a distal end 2410. Sleeve 2408 may define a lumen that is configured to receive rod 1081 when piston rod 1080 is coupled to flange member 1070. As described in more detail below, sleeve 2408 may be configured to move within the lumen of housing 1060 in response to movement of flange member 1070 along the exterior of housing 1060.

The sleeve 2408 may further include a locking component, such as, for example, a second projection 2412 formed along the inner surface of the sleeve 2408 such that the second projection 2412 extends at least partially into the lumen defined by the sleeve 2408. In this embodiment, the second a protrusion 2412 is located relatively proximally from the distal end 2410. In other embodiments, the sleeve 2408 may include various other suitable locking components in place of the second protrusion 2412, such as, for example, an opening configured to receive the protrusion 1085.

With reference specifically to FIG. 28M, protrusion 1085 may extend radially outward from shaft 1081 and be positioned proximally relative to second protrusion 2412 when piston rod 1080 is received through flange member 1070 and sleeve 2408. To operate delivery device 2400, piston rod 1080 may be moved distally relative to flange member 1070 and sleeve 2408 until protrusion 1085 contacts second protrusion 2412. It should be understood that the range over which piston rod 1080 moves relative to sleeve 2408 may determine the actuation distance of delivery device 2400. The actuation distance can be controlled based on the position of the protrusion 1085 and the second protrusion 2412 relative to each other.

With protrusion 1085 in contact with second protrusion 2412 and the distal end of the actuation portion of logic processor 108 received against the inner surface of collar 1072, piston rod 1080 may be coupled to sleeve 2408 and delivery device 2400 may be in the actuated state shown in fig. 28N. The actuation portion 1082 may be fully received within the collar 1072, and the rod 1081 may be locked to the sleeve 2408. Accordingly, further movement of the piston rod 1080 may cause the flange member 1070 and sleeve 2408 to move relative to the housing 1060. For example, as seen in FIG. 280, piston rod 1080 and flange member 1070 may be moved distally relative to housing 1060 in response to the application of a distally directed force to actuation portion 1082. Rod 1081 may be movable relative to housing 1060 causing stopper 1062 to move within housing 1060 to deliver a dose.

The distal end 2410 may move toward the ejector end 1064 as the piston rod 1080 and flange member 1070 move distally until it encounters the attached bracket 2406. It should be understood that the range over which the piston rod 1080 and flange member 1070 move may determine the distance dose delivery device 2400 delivery.

- 45 044249

The dose delivery distance may be controlled based on the position of the secured bracket 2406 along the body 1060.

In other embodiments shown in FIGS. 28P-28Q, the delivery device 2400 may include an obstruction and/or locking component in the form of a tear tab 2420. The tear tab 2420 may include a housing 2422 having a circular cross-section defining a central opening 2424. The housing 2422 may be formed from various flexible materials including, for example, plastic, rubber, etc. As described in more detail below, the tear tab 2420 may be frangible and/or deformable in response to the application of force to the housing 2422. The tear tab 2420 may further include a gripping member 2426 extending outwardly from the housing 2422 and configured to facilitate manual engagement. operation of the tear tab 2420. As seen in FIG. 28P, the grip member 2426 may be integrally formed with the housing 2422 such that the application of a radially outward force (e.g., a pulling force) to the grip member 2426 may cause the housing 2422 to deform (e.g., rupture, collapse, etc.). ), as shown in Fig. 28Q.

With reference now to FIG. 28R, a tear-off tab 2420 may be attached to a flange member 1070 along the proximal end of the collar 1072. A tear-off tab 2420 may be positioned over the shoulder 1072 such that the flange member 1070 is separated from the actuation portion 1082 by a tear-off tab 2420 disposed therebetween. The rod 1081 may be received through the central hole 2424 into the bead 1072 when the body 2422 is attached to the bead 1072. The tear tab 2420 may be configured to prevent movement of the actuation portion 1082 into the bead 1072. The thickness and/or width of the body 2422 may be of a size such that such that the diameter of the center hole 2424 is less than the diameter of the actuation portion 1082 to block passage of the actuation portion 1082 through the tear tab 2420.

Delivery device 2400 may be actuated in response to distal movement of piston rod 1080 relative to flange member 1070 until it engages housing 2422, as shown in FIG. 28S. It should be understood that the range over which the piston rod 1080 moves relative to the flange member 1070 may correspond to the actuation distance of the delivery device 2400. The actuation distance may be controlled based on the thickness of the housing 2422, by which the relative distance between the actuation portion 1082 and the shoulder 1072 is varied. In the case of the actuation portion 1082 contacting the housing 2422, the gripping member 2426 may be actuated to remove (e.g., break) , tearing, pulling, etc.) of the tear tab 2420 from the collar 1072. In this example, the housing 2422 can be deformed (see FIG. 28Q) and disengaged from the flange member 1070, allowing the piston rod 1080 to further move distally relative to flange element 1070.

As can be seen in FIG. 28T, the actuation portion 1082 may be received within the collar 1072 in response to the application of a distally directed force to the actuation portion 1082. The rod 1081 may be movable relative to the housing 1060 causing the stopper 1062 to move within the housing 1060 to deliver a dose. It should be understood that the range over which the piston rod 1080 moves relative to the collar 1072 may correspond to the dose delivery distance of the delivery device 2400. The dose delivery distance may be controlled based on the thickness of the tear tab 2420, by which the relative distance between the actuation portion 1082 and the distal (e.g., lower) end of the bead 1072 is varied.

In additional embodiments shown in FIGS. 28U-28X, the delivery device 2400 may include a removable cap 2430 coupled to the piston rod 1080. The removable cap 2430 may include a housing 2432 defining a cavity 2434 that is configured to receive at least a portion of the piston rod 1080 (e.g., triggered part 1082). The removable cap 2430 may include an opening along the bottom (e.g., distal) wall of the housing 2432 to receive the rod 1081. In some embodiments, the removable cap 2430 may be attached to the actuation portion 1082, while in other embodiments, the housing 2432 may be directly connected to the rod 1081. The removable cap 2430 may be an obstacle and/or locking component configured to increase the cross-sectional profile of the actuation portion 1082 to prevent movement of the piston rod 1080 relative to the flange member 1070 and, more specifically, to prevent movement of the actuation portion 1082 to collar 1072.

With reference now to FIG. 28V, the piston rod 1080 may be configured to move distally relative to the flange member 1070 to actuate the delivery device 2400 until the bottom wall of the housing 2432 collides with the proximal end of the collar 1072. The removable cap 2430 may prevent the actuation portion 1082 from being internally received. shoulder 1072 due to the fact that at least a portion of the housing 2432 is located between the actuation portion 1082 and the shoulder 1072. In the case of the piston rod 1080 moved from a proximal position (Fig. 28U) to a distal position (Fig. 28V), when the housing 2432 contacts shoulder - 46 044249 com 1072, the delivery device 2400 may be in the actuation position. It should be understood that the range over which the piston rod 1080 moves relative to the flange member 1070 may correspond to the actuation distance of the delivery device 2400. The actuation distance may be controlled based on the size of the removable cap 2430 and/or the position of the removable cap 2430 relative to the piston rod 1080. For example, in other embodiments, the bottom wall of the housing 2432 may be attached to a proximal portion of the rod 1081 located relatively distally from the actuation portion 1082 In this example, the actuation distance of the delivery device 2400 may be reduced relative to the actuation distance shown and described herein because the housing 2432 may be located in close proximity to the shoulder 1072. Accordingly, the piston rod 1080 may need to be moved a shorter distance so that the removable cap 2430 collides with the collar 1072.

As can be seen in FIG. 28X, the removable cap 2430 may be detached from the piston rod 1080 so that the actuation portion 1082 can be removed from the housing 2432. The piston rod 1080 may be moved distally relative to the housing 1060 and received within the collar 1072 in response to the application of a distally directed force to the actuation portion 1082 The rod 1081 can move relative to the flange member 1070, causing the stopper 1062 to move within the housing 1060 to deliver a dose. It should be understood that the range over which the piston rod 1080 moves relative to the flange member 1070 may correspond to the dose delivery distance of the delivery device 2400. The dose delivery distance can be controlled based on the attachment of the removable cap 2430 relative to the actuation portion 1082 and/or the rod 1081, as described above. Additionally, the depth of the bead 1072 may be determinant of the dose delivery distance, such that the size of the bead 1072 may be adjusted accordingly to produce various suitable dose delivery distances.

For example, attaching the removable cap 2430 such that the distal wall of the removable cap 2430 is flush with the distal end of the actuation portion 1082 may increase the relative actuation distance of the delivery device 2400 by providing a greater distance between the removable cap 2430 and the collar 1072. Accordingly, the position attaching the release cap 2430 may correspond to a shorter dose delivery distance after the actuation portion 1082 is moved into the collar 1072 after removal of the release cap 2430. Alternatively, attaching the release cap 2430 such that the distal wall of the release cap 2430 is located distal to the distal end of the release portion 1082 may reduce the relative actuation distance, thereby providing a greater dose delivery distance, since the actuation portion 1082 may require additional longitudinal movement to be fully received within the bead 1072. It should be understood that the size and/or shape of the removable cap 2430 may be varied to accommodate different positions attachments described above.

In some embodiments shown in FIGS. 28W-28Z, the delivery device 2400 may include one or more tabs 2440 attached to the piston rod 1080, such as along the actuation portion 1082, the rod 1081, and/or various other parts of the piston rod 1080. In this example, the delivery device 2400 includes a pair of tabs 2440 extending radially outward from a distal end of the actuation portion 1082. The tabs 2440 may be an obstacle and/or locking component configured to increase the cross-sectional profile of the actuation portion 1082 to prevent movement of the piston rod 1080 relative to the flange member 1070 and more specifically, to prevent the actuation portion 1082 from moving into the collar 1072. In some embodiments, the tabs 2440 may be selectively removable from the actuation portion 1082 when force is applied thereto. In other embodiments, the tabs 2440 may be compressible and configured to be pushed into the actuation portion 1082 in response to force being applied thereto. In either example, tabs 2440 may be configured to move the actuation portion 1082 from an expanded profile (FIGS. 28W-28Y) to a compressed profile (FIG. 28Z).

With reference now to FIG. 28Y, the piston rod 1080 may be configured to move distally relative to the flange member 1070 to actuate the delivery device 2400 until the tabs 2440 engage the proximal end of the collar 1072. The tabs 2440 may prevent the collar 1072 from receiving the actuation portion 1082. B With the piston rod 1080 moved from a proximal position (FIG. 28W) to a distal position (FIG. 28Y), when the tabs 2440 contact the collar 1072, the delivery device 2400 may be in the actuation position. It should be understood that the range over which the piston rod 1080 moves relative to the flange member 1070 may correspond to the actuation distance of the delivery device 2400.

The actuation distance may be controlled based on the size (e.g., thickness, width, height, etc.) of the tabs 2440 and/or the position of the tabs 2440 relative to the piston rod

- 47 044249

1080. For example, in other embodiments, a pair of tabs 2440 may be attached to the intermediate and/or proximal portion of the actuation portion 1082 or, alternatively, along the shaft

1081. In this example, the actuation distance of the delivery device 2400 may be increased and/or decreased, respectively, relative to the actuation distance shown and described here.

As can be seen in FIG. 28Z, the tabs 2440 may be pressed against the actuation portion 1082 by the collar 1072 applying an inward pushing force (or alternatively may be disengaged from the actuation portion 1082 by applying an outward pulling force, a rotating latch force, or the like) such that the actuation portion 1082 could form a profile of a smaller cross-section. The piston rod 1080 may be moved distally relative to the housing 1060 and received within the collar 1072 in response to the application of a distally directed force to the actuation portion 1082. The rod 1081 may be moved relative to the flange member 1070 causing the stopper 1062 to move within the housing 1060 to deliver a dose. It should be understood that the range over which the piston rod 1080 moves relative to the flange member 1070 may correspond to the dose delivery distance of the delivery device 2400. As described above, the dose delivery distance can be controlled based on the position of the tabs 2440 relative to the actuation portion 1082, the size (eg, longitudinal depth) of the bead 1072, and the like. For example, a relative position of the tabs 2440 that increases the actuation distance of the delivery device 2400 may correspond to a shorter dose delivery distance, and a position of the tabs 2440 that corresponds to a reduced actuation distance may provide a greater dose delivery distance. In other examples, piston rod 1080 may include a second set of tabs (not shown) along actuation portion 1082 that may determine a dose delivery distance based on the relative position of these tabs relative to tabs 2440.

Fig. 29A-29C show an exemplary delivery device 2500 and a method of using the delivery device 2500. Delivery device 2500 may include features substantially similar to those shown and described above, such that like reference numerals are used to identify like components. As shown in FIG. 29A, delivery device 2500 may include a piston rod 2580 including a first actuation portion 2502, a second actuation portion 2504, and a cam lever 2510. The first actuation portion 2502 may be coupled to the second actuation portion 2504 by one or more arms 2506. In this example, , a pair of arms 2506 may be attached to a first actuation portion 2502 along a first end of the arms 2506, and the arms 2506 may be further coupled to a second actuation portion 2504 at a second end of the arms 2506 that is opposite the first end. The second actuation portion 2504 may be a rotatable member including a proximal end 2505 and an opposing distal end having a connection 2508. A pair of arms 2506 may be coupled to the distal end of the second actuation portion 2504 at a connection 2508.

It should be understood that when in the ready position shown in FIG. 29A, the second actuation portion 2504 may be oriented such that the connection 2508 is positioned proximate the first actuation portion 2502 relative to the proximal end 2505. The proximal end 1088 of the rod 1081 may be positioned adjacent the connection 2508 at the distal end of the second actuation portion 2504. For example, the proximal end 1088 may be in contact with and/or may be adjacent to the distal end of the second actuation portion 2504. In some embodiments, the shaft 1081 may extend through the center of the first actuation portion 2502 and/or may be positioned adjacent the first actuation portion 2502. The second actuation portion 2504 may be configured to move relative to the first actuation portion 2502 and about the connection 2508. The cam lever 2510 may be coupled to the second actuation portion 2504 at the connection 2508 and is configured to move (e.g., rotate, rotate, offset, etc. ) a second actuator portion 2504 relative to the first actuator portion 2502. Accordingly, it should be understood that the second actuator portion 2504 may be configured to move the rod 1081 relative to the housing 1060 in response to movement by the cam lever 2510 of the second actuator portion 2504 relative to the first actuator portion 2502.

For example, with reference to FIG. 29A, the cam arm 2510 may be actuated by rotating the cam arm 2510 about the connection 2508, which causes the second actuation portion 2504 to rotate about the connection 2508. The proximal end 2505 may be moved toward the first actuation portion 2502 in response to the rotation of the second actuation portion. 2504 around the connection 2508. In this example, the proximal end 2505 may be moved toward the first actuation portion 2502. In the case of the proximal end 2505 moved from the proximal position (Fig. 29A) to the distal position (Fig. 29B), the proximal end 1088 may be pushed distally, thereby moving the rod 1081 relative to the housing 1060 to actuate the delivery device 2500. In other words, the rotation of the cam arm 2510 and/or the second actuation portion 2504 relative to the first actuation portion 2502 may

- 48 044249 actuate the delivery device 2500 by applying a distal force to the rod 1081.

It should be understood that the distance of movement of the proximal end 2505 toward the first actuation portion 2502 may correspond to the distance of actuation of the delivery device 2500. In other words, the actuation distance of the delivery device 2500 may be controlled by the longitudinal length of the second actuation portion 2504 between the proximal end 1505 and the connection 2508. In some embodiments, the first actuation portion 2502, the arms 2506, and/or the cam arm 2510 may inhibit further rotation the second actuation portion 2504 after the piston rod 2580 has moved from the ready position (FIG. 29A) to the actuating position (FIG. 29B).

As can be seen in FIG. 29C, piston rod 2580 may be moved distally relative to housing 1060 in response to application of a distally directed force to first actuation portion 2502 and second actuation portion 2504. In this example, cam lever 2510 may be depressed (e.g., pushed and/or pulled) distally. to move the first actuation portion 2502 and the second actuation portion 2504 toward the flange member 1070 until they engage the proximal end of the bead 1072. The rod 1081 may move relative to the bead 1072, thereby causing the stopper 1062 to move within the housing 1060 to deliver a dose. It should be understood that the range of movement of the piston rod 2580 relative to the flange member 1070 may correspond to the dose delivery distance of the delivery device 2500. The dose delivery distance may be controlled based on the clearance formed between the shoulder 1072 and the cam arm 2510.

Fig. 30-31 show an exemplary delivery device 2600 that may include features substantially similar to those shown and described above such that like reference numerals are used to identify like components. The delivery device 2600 may include a flange member 2670, a piston rod 2680, and a housing 1220. The flange member 2670 may include a tapered collar 2672 having a variable size and/or shape between a distal end and a proximal end. In this example, the tapered collar 2672 may have a larger cross-sectional profile (e.g., diameter) along the distal end adjacent the flanges 1076 than at the proximal end adjacent the slots 1074. The tapered collar 2672 may be configured to minimize the overall profile and/or or the weight of the delivery device 2600 by minimizing the configuration of the flange element 2670. In some embodiments, the flanges 1076A may have a reduced length to provide better control and maneuverability of the flange element 2670.

The piston rod 2680 may include an actuation portion 2682 having a cross-sectional profile (e.g., diameter) that is relatively smaller than the tapered collar 2672 to facilitate acceptance thereof of the actuation portion 2682. Accordingly, the actuation portion 2682 may be similarly configured to minimize the overall profile and/or weight of the delivery device 2600 by minimizing the configuration of the actuation portion 2682. Additionally, the piston rod 2680 may not include a textured and/or ribbed surface along the actuation portion 2682 to simplify the appearance of the piston rod 2680.

With reference specifically to FIG. 30, the actuation portion 2682 may further include a proximal end having an outer ring 2687, an inner surface 2688, and one or more holes 2689 defined through the inner surface 2688. In this example, the inner surface 2688 may be located within the outer ring 2687 and may have an angled profile that slopes radially inward toward one or more openings 2689. The inner surface 2688 may be configured to define a contact surface for actuating the piston rod 2680 (e.g., applying a distally directed force to the actuation portion 2682 with a finger user). Although piston rod 2680 is shown as including a pair of holes 2689, it should be understood that in other embodiments more and/or fewer holes 2689 may be provided on the inner surface 2688.

In some embodiments, as shown in FIG. 31, piston rod 2680 may include an outer ring 2687' having a width that defines an outer surface located around the inner surface 2688. For example, the outer surface of the outer ring 2687' may be angled inwardly toward the inner surface 2688 and the holes. 2689 and/or may be transversely directed relative to the inner surface 2688. In the present example, the outer ring 2687' defines a flat outer surface that is substantially perpendicular to the longitudinal length of the actuation portion 2682. The increased width of the outer ring 2687' may provide additional contact surface area for the user device 1050 when actuating the piston rod 2680. It should be understood that the width of the outer ring 2687' may be greater and/or less than the width of the outer ring 2687' shown and described herein without departing from the scope of this disclosure.

Fig. 32-33 show an exemplary piston rod 2780, which may include

- 49 044249 features substantially similar to those of the piston rod 1080 shown and described above, such that like reference numerals are used to identify like components. The piston rod 2780 may include an actuation portion 2782 having a proximal end defined by an outer ring 2787, an inner ring 2788, and one or more holes 2789. In this example, the inner ring 2788 may be located within the outer ring 2787 and may sense at least at least one hole 2789. The outer ring 2787 may further define at least one hole 2789 located radially outward from the inner ring 2788. The one or more holes 2789 may minimize the overall weight of the piston rod 2780, increase the moldability of the piston rod 2780 by providing nominal wall thickness of the actuation part 2782, etc. Additionally, the actuation portion 2782 may include a transverse shoulder 2786 extending across the width of the distal end and aligned with the projections 1086. The transverse edge 2786 may branch one or more openings 2789 defined by an outer ring 2787 and an inner ring 2788. The transverse edge 2786 may be collinear. with projections 1086 to provide visual alignment and/or identification of projections 1086 to the user of piston rod 2780.

As can be seen in FIG. 33, in the case of a piston rod 2780 received within a flange member 1070 and a housing 1220, the transverse edge 2786 may be configured to improve identification of movement of the piston rod 2780 relative to the flange member 1070 from a perspective proximal to the device 1200. For example, the transverse shoulder 2786 may facilitate identifying the relative position of the projections 1086 relative to the slots 1074 from a perspective proximal to the actuation portion 2782 during use of the device 1200. In some embodiments, the piston rod 2780 may not include a textured and/or ribbed surface along the actuation portion 2782 to simplify appearance piston rod 2780.

Fig. 34 shows another example delivery device 2800 according to one example of this disclosure. Delivery device 2800 may include features substantially similar to those of delivery device 1050 and delivery device 1200 shown and described above, such that like reference numerals are used to identify like components. The delivery device 2800 may include a flange member 2870, a piston rod 2880, and a housing 1220. The flange member 2870 may have a collar 2872 and a pair of flanges 2876 extending transversely outward from the collar 2872. The collar 2872 may have a tapered profile, for example, relative to the collar 1072. Additionally, the flanges 2876 may have a reduced length relative to the flanges 1076. Accordingly, the flange element 2870 of the present example may have a generally tapered profile. Flange member 2870 may further include a lip 2871 that may slide under or receive housing flange 1226 (FIG. 35). The lip 2871 may be configured to hold the flange member 2870 in place by slidingly connecting the flange member 2870 to the housing 1220. As described in more detail below, the lip 2871 may be made of a flexible or semi-flexible material configured to form a snap-fit connection to the flange 1226 buildings.

The piston rod 2880 may include an actuation portion 2882 having one or more projections 1086 along a proximal end and one or more extensions 1087 along a distal end. The actuation portion 2882 may have a diameter that is generally smaller than the diameter of the actuation portion 1082 shown and described above. Accordingly, it should be understood that the piston rod 2880 and flange member 2870 may collectively form a tapered profile relative to the piston rod 1080 and flange member 1070 assembly. By providing a reduced profile, the delivery device 2800 may be configured to provide a user with improved control and maneuverability of the piston rod rod 2880 and flange member 2870 during use of delivery device 2800.

In this embodiment, the projections 1086 may have a curvature configured to improve the grip, comfort, and/or ergonomics of the piston rod 2880 for the user of the delivery device 2800. The curvature of the projections 1086 may have a concave outer configuration that tapers inward along the distal portion of the projections. The proximal end of the actuation portion 2882 may further include a first ring 2887, an opening 2888, and a second ring 2889 located distal to the first ring 2887. The first ring 2887 may define a proximal contact surface of the actuation portion 2882, and the opening 2888 may be located at the center of the first ring 2887. The proximal contact surface defined by the first ring 2887 may be angled to the opening 2888 such that the proximal end of the actuation portion 2882 may be inclined radially inward. In some embodiments, the first ring 2887 may be configured to facilitate actuation of the piston rod 2880 by defining a pin support to receive a user's finger. The hole 2888 may be configured to maintain the nominal wall thickness of the actuation portion 2882 to facilitate molding of the piston rod 2880 during the manufacturing process of the delivery device 2800. 2888 bores can further minimize the overall weight of the piston rod

- 50 044249

2880.

With reference still to FIG. 34, a second ring 2889 may extend radially outward from an outer surface of the actuation portion 2882 and is positioned adjacent the first ring 2887. The second ring 2889 may be configured to form a gripping element along the actuation portion 2882 to enhance control of the piston rod 2880, such as when the piston rod is rotating. rod 2880. The first ring 2887 may have a larger diameter than the actuation portion 2882 such that the pin support formed by the first ring 2887 may have a larger cross-sectional profile than the actuation portion 2882. In some embodiments, the second ring 2889 may include a diameter greater than the diameter of the actuation portion 2882 and substantially similar to the diameter of the first ring 2887.

The piston rod 2880 may not include a textured and/or ribbed surface along the actuation portion 2882 to simplify the appearance of the piston rod 2880.

As can be seen in FIG. 35, the actuation portion 2882 may be configured to have a predetermined length C between the distal end of the protrusion 1086 and the hook or staple portion 1087a of the extensions 1087. In some embodiments, the predetermined length C may be sized according to the type and/or size of the syringe cap used with delivery device 2800 (eg, Ompi Alba ITC, Ompi Alba OVS, Gerresheimer TELC, silicone-free syringes, etc.). For example, the predetermined length C may be increased and/or decreased according to the requirement of a smaller and/or larger filling volume, respectively, determined based on the syringe cap. Additionally, a predetermined length C may be configured to provide full travel of the piston rod 2880 in the flange member 2870 to ensure that the delivery device 2800 delivers a full dose. The predetermined length C may be further configured to provide one of a variety of suitable dose delivery distances for the delivery device 2800. Flange member 2870 may include additional features and/or components configured to provide full stroke of piston rod 2880.

For example, with reference now to FIG. 36, the flange member 2870 may include one or more recesses 2875 formed along a proximally facing and distally facing (bottom) surface of the bead 2872. The recess 2875 may be configured to define a recessed surface in the bottom surface of the bead 2872. The recess 2875 may be configured with the ability to facilitate the reception of the piston rod 2880 into the flange element 2870 to ensure full stroke. In other words, the recess 2875 may provide increased space and/or clearance within the collar 2872 to receive one or more components of the piston rod 2880, such as, for example, a hook or staple portion 1087a of the extensions 1087.

In the present example, delivery device 2800 may be configured to deliver a full dose upon contact of a pair of projections 1086 with the distal end (bottom) of slots 1074. A pair of extensions 1087 may be positioned adjacent to (but not in contact with) the bottom surface of collar 2872 when the projections 1086 contact the distal end of the slots 1074. Specifically, in some embodiments, the extensions 1087 may be positioned proximal to the bottom surface of the collar 2872 such that the extensions 1087 do not contact that bottom surface when the piston rod 2880 bottoms out, and/or when the full dose has been delivered from the delivery device 2800. By forming a recess along the bottom surface of collar 2872, recess 2875 may allow actuation portion 2882 to move distally relative to collar 2872 to complete the full stroke of piston rod 2880 without engagement or contact of extensions 1087 with the bottom surface of collar 2872. In some embodiments, extensions 1087 may flex inwardly. toward the recess 2875 upon engagement of the hook or staple portions 1087a with the bottom surface of the bead 2872, whereby the hook or staple portions 1087a are guided into the recess 2875. It should be understood that the enlarged space defined by the recess 2875 may allow the extensions 1087 to contact the bottom the surface of the collar 2872 does not interfere with the completion of the full stroke of the piston rod 2880 and/or delivery of the full dose.

With reference still to FIG. 36, the flange member 2870 may further include one or more ribs 2874 configured to engage the housing flange 1226 when the housing 1220 is coupled to the flange member 2870. The one or more ribs 2874 may be positioned adjacent to the lip 2871, such as distally from the bottom surface of collar 2872 and proximally from lip 2871. In some embodiments, ribs 2874 may extend radially inward from the inner side wall of flange member 2870, while in other embodiments, ribs 2874 may extend outward from the inner top wall of flange member 2870 In the present example, the ribs 2874 may extend radially inward at an angle relative to the inner side wall of the flange member 2870. It should be understood that the ribs 2874 may be located and/or may extend from various other suitable locations and at various other suitable angles within the flange member 2870 for coupling with housing flange 1226.

- 51 044249

In this embodiment, the ribs 2874 may be formed from a flexible and/or semi-flexible material (e.g., plastic, rubber, etc.) and configured to engage the housing flange 1226 after receiving the housing 1220 within the flange member 2870. As As an illustrative example, the ribs 2874 may be configured to flex and/or bend proximally toward the bottom surface of the collar 2872 in response to the lip 2871 receiving the housing flange 1226. The ribs 2874 may be configured to attach the housing flange 1226 to the flange member 2870 by applying a distally directed force thereto. Accordingly, the ribs 2874 may maintain position (e.g., longitudinal, rotational, etc.) of the housing 1220 relative to the flange member 2870 by engaging the upper/proximal surface of the housing flange 1226 when the lip 2871 engages the lower surface of the housing flange 1226. In other embodiments, more and/or fewer ribs 2874 may be provided to prevent movement of the housing flange 1226 and/or housing 1220 relative to the flange member 2870.

With reference now to FIG. 37, flange member 2870 may include a textured and/or structured contact surface 2878 along the lower, distally facing surface of flanges 2876. Textured contact surface 2878 may include one or more projections, recesses, and/or various other features defining at least one of a variety of structures to improve the grip, control, and/or ergonomics of the flange member 2870. In this example, the textured contact surface 2878 includes a plurality of semicircular projections of varying sizes. As shown in FIG. 37, each contact surface 2878 may be concave when viewed from the radial center of the flange 2876. However, in alternative embodiments, one or more contact surfaces 2878 may be convex when viewed from the radial center of the flange 2876. As described in more detail below, the textured contact surface surface 2878 may include various other structures, elements, and/or structures along the bottom surface (see FIGS. 41A-41D) of flanges 2876. Flange member 2870 may further include a pair of movable tabs 2877 adjacent lip 2871 and along opposite sides of the opening 1073. The movable legs 2877 may be formed from a flexible and/or semi-flexible material and may be configured to move relative to the collar 2872 and/or flanges 2876 in response to a force applied thereto (eg, by the housing 1220).

Each movable tab 2877 may define an opening 2873 located between the movable tab 2877 and the flange 2876. Accordingly, the movable tabs 2877 may be separated from the flanges 2876 by an opening 2873 formed therebetween. The holes 2873 may provide clearance and/or spacing to accommodate lateral movement of the movable legs 2877 upon application of a radially outward force. For example, the movable tabs 2877 may be deflected radially outward toward the flanges 2876 in response to the flange member 2870 receiving the housing 1220 through the opening 1073, thereby changing the size and/or shape of the holes 2873. In this example, the movable tabs 2877 may flex outwardly. from the opening 1073 until the housing flange 1226 is received by the lip 2871. The movable legs 2877 may be configured to bend inward toward the housing 1220 to return to their original configuration after the lip 2871 has fully accepted the housing flange 1226. In some embodiments, the movable tabs 2877 may flex toward the housing 1220 to a substantially original configuration such that the movable tabs 2877 can remain at least partially pressed against the housing 1220 to prevent movement of the housing 1220 relative to the flange member 2870 and provide continuous applying pressure to the housing 1220 to prevent slippage.

With reference still to FIG. 37, the movable tabs 2877 may be configured to apply a radially inward force to the housing 1220 (e.g., radially inwardly displacing material), thereby forming a snap-fit connection between the flange member 2870 and the housing 1220. Additionally, the movable tabs 2877 may support housing 1220 in a stable and fixed position relative to flanged member 2870, thereby connecting flanged member 2870 to housing 1220. It should be understood that openings 2873 may be provided between movable tabs 2877 and flanges 2876 to reduce the force required to couple housing 1220 to flanged member element 2870. For example, the holes 2873 may be configured to reduce the force required to snap the housing 1220 into the flange element 2870 to a minimum force ranging from about 15 N to about 25 N, compared to a design that does not include the holes 2873 .

Fig. 38A-40C show an exemplary method of using the delivery device 2800. As can be seen in FIG. 38A, delivery device 2800 may be preassembled with a distal actuation portion 2882 received within collar 2872 and extensions 1087 received internally and coupled to openings 1094. In the case of extensions 1087 coupled to collar 2872 through openings 1094, it will be understood that flange member 2870 may prevent proximal retraction of actuation portion 2882. Accordingly, piston rod 2880 may be prevented from detaching from flange member 2870. In this example, delivery device 2800 may be

- 52 044249 is actuated by distal movement of the piston rod 2880 into the flange element 2870.

As can be seen in FIG. 38B, the actuation portion 2882 may be moved distally relative to the flange member 2870 until the projections 1086 engage the proximal end of the collar 2872. The piston rod 2880 may complete the process of actuating the delivery device 2800 after the projections engage and/or abut the collar. 2872. It should be understood that the range over which the piston rod 2880 moves distally relative to the flange member 2870 may correspond to the actuation distance of the delivery device 2800. The actuation distance may be controlled based on the longitudinal length of the projections 1086 and/or extensions 1087, whereby the relative distance between the proximal end of the shoulder 2872 and the distal end of the projections 1086 is varied.

As shown in FIG. 38C, flange member 2870 may be rotated relative to piston rod 2880, or vice versa, to move projections 1086 relative to collar 2872 until they are radially and longitudinally aligned with slots 1074. Referring to FIG. 39A-39B, extensions 1087 may contact the inner surface 2872A of collar 2872 as piston rod 2880 rotates relative to flange member 2870. As seen in FIG. 39D, in the case of a hook or staple portion 1087a contacting the inner surface 2872A, the extensions 1087 may be deflected radially inward by the collar 2872 until the piston rod 2880 is rotated until the extensions 1087 are aligned with the internal grooves 2879 of the flange member 2870. The internal grooves 2879 may detect recesses formed along the inner surface 2872A. As can be seen in FIG. 39C and fig. 39E, the internal grooves 2879 may be configured to receive extensions 1087. It should be understood that the bead 2872 may have a larger diameter along the internal grooves 2879 than along the internal surface 2872A such that the extensions 1087 are configured to expand radially outward from a compressed configuration (FIG. 39A-39B and Fig. 39D) into an expanded configuration (Fig. 39C and Fig. 39E) when the extensions 1087 move in radial alignment with the internal grooves 2879.

In other words, the extensions 1087 may become weakened when received within the internal grooves 2879 due to the additional space provided by the internal grooves 2879, as shown in FIG. 39E. In some examples, feedback (e.g., tactile, audible, etc.) may be generated in response to receiving extensions 1087 within internal grooves 2879. Delivery device 2800 may be positioned in a dose delivery state such that further adjustment the action of the piston rod 2880 could ensure delivery of the dose. In some embodiments, flange member 2870 may be configured to generate user feedback (e.g., tactile, audible, etc.) upon rotation of piston rod 2880 relative to flange member 2870 to actuate delivery device 2800.

As described in detail above and as seen in FIG. 40A-40C, the opening 1073 may have a semicircular shape with one or more edges 2873 extending into the opening 1073. In the case of a piston rod 2880 coupled to a flange member 2870, a rod 1280 may be received through the opening 1073. The rod 1280 may include a rounded a side wall 2884 that is configured to engage one or more edges 2873 when the piston rod 2880 rotates relative to the shoulder 2872. For example, the rounded side wall 2884 may define a semicircular end along the rod 1280 that may contact the edges 2873 when the piston rod 2880 moves from the actuation position (FIG. 38B) to the dose delivery position (FIG. 38C). As described in detail above (FIGS. 4K-4X), it should be understood that the rod 1280 may have various suitable shapes and/or configurations to facilitate movement (e.g., rotation) of the piston rod 2880 relative to the flange member 2870.

With reference now to FIG. 38D, in the case of projections 1086 aligned with slots 1074, the actuation portion 2880 may be moved distally relative to the collar 2872 to terminate the full stroke of the piston rod 2880 in response to the application of a distally directed force to the actuation portion 2882. In this example, the rod 1280 may be moved relative to flange member 2870, thereby causing stopper 1222 to move within housing 1220 to deliver the dose. In this example, the projections 1086 may be received within the slots 1074, and the second ring 2889 may be located proximate the proximal end of the bead 2872. In other words, in some embodiments, the second ring 2889 does not contact the proximal end of the bead 2872. Additionally, as described in more detail above, the recesses 2875 may receive extensions 1087 (FIG. 36) upon completion of the full stroke of the piston rod 2880. It should be understood that the range over which the piston rod 2880 moves relative to the flange member 2870 may determine the dose delivery distance of the delivery device 2800. The dose delivery distance may be controlled based on the longitudinal length of the projections 1086 relative to the actuation portion 2882 and/or the depth of the slots 1074 relative to the collar 2872.

As can be seen in FIG. 41A-41D, delivery device 2800 may include various other

- 53 044249 flange elements 2870 having at least one of a plurality of textured contact surfaces on the flanges 2876. As a merely illustrative example, as seen in FIG. 41A, an alternative illustrative flange member 2870A may include a textured contact surface 2878A on the flanges 2876 comprising a plurality of circular projections and/or recesses arranged in an annular array relative to each other. As can be seen in FIG. 41B, another exemplary flange member 2870B may include a textured contact surface 2878B including a decorative design, such as a snowflake, on each flange 2876. FIG. 41C shows an exemplary flange member 2870C including a textured contact surface 2878C on flanges 2876 comprising a plurality of circular projections and/or recesses arranged in an irregular pattern with respect to each other.

As a further example, with reference now to FIG. 41D, the flange member 2870D may include a textured contact surface 2878D comprising a plurality of diamond-shaped projections and/or apertures arranged in a grid arrangement along the flanges 2876. It should be understood that the various textured contact surfaces shown and described herein may be configured improve the grip, control, aesthetic properties and/or ergonomics of the flange element. It should also be understood that the textured contact surfaces shown and described herein are merely illustrative, so that various other suitable structures, textures, and/or features may be provided on the flange members without departing from the scope of this disclosure.

Components of the devices described herein may be designed and/or manufactured by one or more methods. In some embodiments, for example, components of the devices described herein (e.g., device 1050, device 1200, device 1300, device 1400, device 2400, device 2500, device 2600, device 2800, etc.) may be suitable for manufacture through, for example, injection molding, 3D printing, or machining. In one embodiment, for example, components of device 1050 may be particularly suitable for injection molding. For example, in some existing devices, molding is not suitable for high volume production, leading to the use of 3D printing. In some embodiments, because manufacturing tolerances may be tighter with molding technologies than with 3D printing technologies, devices formed by 3D printing will not have the same level of accuracy as devices formed by molding. Accuracy may be particularly important for devices of the present disclosure, for example, devices used for intravitreal injections in volumes of 100 μl or less.

Accordingly, it should be understood that the devices of the present disclosure described herein may be configured to store predetermined volumes of drug that may be suitable for intravitreal (IVT) injections, such as, for example, 100 μl or less. In some embodiments, the devices described herein may be designed to inject certain volumes into the vitreous body based on the intended use of the device in a particular procedure. For example, the devices of the present disclosure may be configured to store a volume of intravitreal drug from about 65 μl to about 75 μl for high-dose aflibercept procedures; from about 95 µl to about 105 µl for Mini Trap procedures; or from about 5 μl to about 15 μl for retrolethal fibroplasia (Retinopathy of Prematurity - ROP).

The devices of the present disclosure may further be configured to store relatively large volumes of intravitreal injection preparation based on the degree of myopia, for example, about 3 ml, 4 ml, or more. Additionally, the devices described herein can be designed to inject large volumes of intravitreal drug based on the intended procedure, for example, from about 3 ml to about 6 ml of silicone or tamponade gas after vitrectomy. It should be understood that the devices of the present disclosure may be configured to inject various other volumes of intravitreal drug relative to other procedures, such as procedures for the treatment of diabetic eye disease, post-injection non-infectious endophthalmitis, neovascular (wet) age-related macular degeneration (AMD), post-occlusion macular edema retinal vein disease (RVO), diabetic macular edema (DME), and diabetic retinopathy (DR).

The devices of the present disclosure are configured to provide accurate measurements when delivering large volumes of intravitreal drugs with high accuracy by minimizing the incidence of user error in incorrectly setting the dose line. As described in detail above, various designs and configurations of one or more components of the devices described herein (e.g., piston rod, flange member, etc.) can provide dose accuracy by controlling the actuation distance and dose delivery distance of the device, thereby eliminating user definition of device parameters in each respective configuration.

The features listed above have been described in the context of specific embodiments.

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Claims (19)

However, as those skilled in the art will appreciate, features and aspects of each embodiment may be combined, added to other embodiments, subtracted from an embodiment, etc., in any manner suitable to assist in controlled preparation and/or or drug delivery. Aspects of the embodiments disclosed herein are described with respect to actuating drug delivery devices and removing excess air bubbles from within drug delivery devices, and some embodiments disclosed herein are described as specific types of drug delivery devices (eg, prefilled syringes ). Aspects of the present disclosure may also be used and/or found in other types of drug delivery devices (eg, refillable syringes, pipettes, etc.). For example, devices having features of the present disclosure may provide a more precise means for transferring a volume of drug or other fluid from one container to another, for example, from a vial to a syringe. The precision in fluid transfer provided by the embodiments disclosed herein can reduce or minimize unwanted overflow and/or reduce drug loss. While a number of embodiments are presented herein, it is contemplated that multiple variations of such embodiments and combinations of elements from one or more embodiments are possible that are within the scope of the present disclosure. Moreover, those skilled in the art will appreciate that the concept on which this disclosure is based can be readily used as a basis for the design of other devices, methods, and systems to achieve some of the objectives of the present disclosure. CLAIM 1. Device (2800) for drug delivery, containing: body (1220); a piston rod (2880) including a proximal end portion (2882) and a distal end portion (1280) located partially within the housing (1220), the proximal end portion (2882) having a diameter greater than the diameter of the distal end portion (1280) ); a protrusion (1086) extending from the outer surface of the proximal end portion (2882) of the piston rod (2880); and a locking component (2870) connected to the proximal end portion of the housing (1220), wherein the locking component (2870) is a flange member that includes a channel with an open distal end (1073) and a slot (1074) with a closed distal end, wherein when the protrusion (1086) is in a first position relative to the locking component (2870), the protrusion (1086) is not aligned with the slot (1074) and the locking component (2870) limits the distal movement of the piston rod (2880) through the open distal end (1073) to the first stopping point and when the projection (1086) is in a second position relative to the locking component (2870), the projection (1086) is aligned with the slot (1074) and the locking component (2870) restricts the distal movement of the piston rod (2880) through the open distal end (1073) of the second stopping point when the protrusion (1086) abuts the closed distal end of the slot (1074). 2. Device (2880) for drug delivery according to claim 1, additionally containing: a stopper (1222) located in the housing (1220), wherein distal movement of the piston rod (2880) distally moves the stopper (1222); and a drug substance located in the housing (1220) between the stopper (1222) and the distal end of the housing (1220), wherein distal movement of the piston rod (2880) to the first stopping point operates the drug delivery device (2800), and distal movement of the piston rod the rod (2880) to the second stopping point dispenses a predetermined volume of drug from the distal end of the drug delivery device (2800). 3. The drug delivery device (2800) of claim 1, wherein moving the protrusion (1086) from the first position to the second position includes twisting the piston rod (2880) relative to the locking component (2870) such that the protrusion (1086) was located outside the blocking component (2870) when in the second position. 4. Drug delivery device (2800) according to claim 1, in which: a slot (1074) is located on the proximal side of the locking component (2870), the slot (1074) being sized and configured to receive the distal end of the protrusion (1086) such that the proximal end of the protrusion (1086) is located outside the slot (1074 ) when the distal end is received within the slot (1074), wherein, when the protrusion (1086) is in a second position relative to the locking component (2870), the distal end of the protrusion (1086) is located proximally from the slot and disengaged from the proximal side of the locking component (2870). component (2870) such that distal movement of the piston rod (2880) moves the distal end of the projection (1086) into the slot (1074). 5. The drug delivery device (2800) of claim 4, wherein the slot (1074) is the first slot (1074) and the protrusion (1086) is the first protrusion (1086), and further comprising: a second slot (1074) on the proximal side of the locking component (2870), the second slot (1074) being sized and configured to receive a second projection (1086) extending from an outer surface of the proximal end portion (2882) of the piston rod (2880) , wherein the first and second slots (1074) are located on opposite sides of the central longitudinal axis of the drug delivery device (2800). 6. The drug delivery device (2800) of claim 4, wherein when the protrusion (1086) is in the first position relative to the locking component (2870), the proximal side engages the distal end of the protrusion (1086) and limits the distal movement of the piston rod ( 2880) first stopping point; and when the protrusion (1086) is in a second position relative to the locking component (2870), the distal end of the protrusion (1086) is aligned with the slot (1074) and disengaged from the proximal side. 7. The drug delivery device (2800) of claim 6, wherein the piston rod (2880) further includes a pair of extensions (1087) protruding distally from the proximal end portion (2882) and the locking component (2870) includes a pair of holes (1094); and wherein a portion of each extension (1087) is configured to be received by one of the pair of holes (1094) before moving the piston rod (2880) to the first stopping point to limit proximal movement of the piston rod (2880) relative to the locking component (2870). 8. The drug delivery device (2800) of claim 7, wherein the blocking component (2870) includes one or more recesses (2875) formed along a bottom wall of the blocking component (2870); and wherein a portion of each extension (1087) is configured to be received by one or more recesses (2875) upon distal movement of the piston rod (2880) relative to the locking component (2870) to allow distal movement of the piston rod (2880) to the second stopping point. 9. The drug delivery device (2800) of claim 7, wherein the blocking component (2870) includes a pair of internal grooves (2879) formed along a side wall of the blocking component (2870); and wherein a portion of each extension (1087) is configured to be received by at least one of a pair of internal grooves (2879) upon rotation of the piston rod (2880) relative to the locking component (2870) to expand the extensions (1087) radially outward from a compressed state to a relaxed state . 10. The drug delivery device (2800) of claim 1, wherein the locking component (2870) is slidably coupled to the housing (1220) and includes a cavity and a pair of ribs (2874) that extend into the cavity in which the housing (1220) includes an upper flange (1226), and a pair of ribs (2874) is configured to engage the upper flange (1226) received in the cavity; and wherein a pair of internal ribs (2874) are configured to apply a distally directed force to the upper flange (1226). 11. The drug delivery device (2800) of claim 1, wherein the locking component (2870) is slidably coupled to the housing (1220) and includes a pair of movable tabs (2877) that are configured to engage the housing (1220). ); and wherein a pair of movable legs (2877) are lateral deflectable after receiving the housing (1220) in the locking component (2870) and are configured to apply a radially inward force to the housing (1220). 12. Device (2800) for drug delivery, containing: body (1220); a piston rod (2880) having a distal end (1280) contacting a stopper (1222) within the housing (1220), and a proximal end including an actuation portion (2882) with a thumb support (2887); a plurality of projections (1086) extending from the thumb support (2887) and along the actuation portion (2882); and a locking component (2870) located on the housing (1220), the locking component (2870) including a proximal collar (2872) having a proximally facing surface, a channel with an open distal end (1073), and a plurality of slots (1074) extending beyond the proximally facing surface, each of the plurality of slots (1074) including a closed distal end; wherein, when the projections (1086) and the slots (1074) are in a first configuration relative to each other, the piston rod (2880) is configured to move toward the locking component (2870) until the proximally facing surface abuts the plurality of projections (1086), and the locking component (2870) will not restrict the distal movement of the piston rod (2880) through the open distal end (1073) to the first stopping point, wherein, in the first configuration, the plurality of projections (1086) are not aligned with the plurality of slots (1074), and yet, when the projections (1086) and slots (1074) are in the second configuration, the proximally facing surface is separated from the plurality of projections (1086), and the piston rod (2880) is movable relative to the locking component (2870) until the locking component (2870) will limit the distal movement of the piston rod (2880) through the open distal end (1073) to the second stopping point, wherein in the second configuration the slots (1074) are aligned with the projections (1086) and configured to receive the projections (1086) until each of the projections is abutted to the closed distal end of the slots (1074). 13. The drug delivery device (2800) of claim 12, wherein the projections (1086) and slots (1074) are movable from the first stopping point to the second stopping point by rotating the actuation portion (2882) about a longitudinal axis relative to the locking component (2870), and movement of the piston rod (2880) relative to the locking component (2870); and wherein, when the projections (1086) and the slots (1074) are at the second stopping point, the projections (1086) and the slots (1074) cannot be rotated. 14. The drug delivery device (2800) of claim 12, wherein the longitudinal difference between the first stopping point and the second stopping point is equivalent to the distance that the stopper (1222) must travel to push a given volume of the finished dosage form from the distal end of the housing (1220) , wherein this distance is determined by the depth of the slots (1074) from the proximally facing surface of the locking component (2870), and in which the piston rod (2880) is prevented from moving from the second stopping point to the first stopping point. 15. Drug delivery device (2800) according to claim 12, wherein the drug delivery device (2800) is configured to transition: (a) from the pre-operational state to the actuation state by longitudinally moving the piston rod (2880) until the piston rod (2880) reaches the first stopping point; (b) from the actuation state to the delivery state by rotating the piston rod (2880) relative to the locking component (2870) until the projections (1086) and the locking component (2870) are in a second configuration; and (c) from the delivered state to the used state by longitudinally moving the piston rod (2880) until the piston rod (2880) reaches the second stopping point, and wherein the drug delivery device (2800) cannot change from the used state to delivery state, from the delivery state to the activation state, or from the activation state to the pre-operational state. 16. The drug delivery device (2800) of claim 15, wherein the piston rod (2880) includes a neck (1084) disposed distal to the actuation portion (2882), wherein the neck (1084) mates with an opening at the open distal end (1073) in the locking component (2870) to prevent proximal movement of the piston rod (2880). 17. The drug delivery device (2800) of claim 16, wherein the neck (1084) is further mated with an opening at the open distal end (1073) in the locking component (2870) to prevent movement of the drug delivery device (2800) from the delivery state into a state of activation. 18. The drug delivery device (2800) of claim 12, wherein when the piston rod (2880) is at the second stopping point, the stopper (1222) does not contact the distal end of the housing (1220). 19. Device (2800) for drug delivery, containing: body (1220); a piston rod (2880) extending along a longitudinal axis, including a distal end portion (1280) contacting a stopper (1222) within the housing (1220); a proximal end including a generally cylindrical actuation portion (2882) and a thumb rest (2887) located proximally within the generally cylindrical actuation portion (2882); and two projections (1086) extending from opposite sides of the actuation portion (2882) in a symmetrical configuration, with the distal facing surfaces of the two projections (1086) positioned