Patent Description:
A typical medicinal syringe includes a syringe assembly containing a fluid such as a medicament or drug product and a plunger rod coupled to the syringe assembly. The plunger rod may be coupled to a plunger disposed within a syringe barrel of the syringe assembly after the syringe is filled with fluid. The plunger may include internal threads that are sized to couple to external threads of a distal end of the plunger rod. When the distal end of the plunger rod is threaded to the plunger, the plunger rod is coupled to the syringe assembly. A force applied to the plunger rod can then drive the plunger through the syringe barrel to dispense the fluid contained within the syringe. The plunger rod includes a proximal rod end having a flange, which an operator may press with the operator's thumb while gripping the syringe barrel between two fingers. Syringe assemblies are sized to hold different quantities of fluid, and plunger rods may also be sized to match their syringe assembly counterpart. When coupling a plunger rod to a plunger, care must be taken to avoid applying excessive pressure that may prematurely expel fluid and/or compromise the Container Closure Integrity of the sealed prefilled syringe. In the prefilled syringe, the fill level of the fluid contained within the syringe barrel may differ within a batch of prefilled syringes, and thus the position of a plunger within a syringe barrel can also differ within the batch. As such, existing systems that couple plunger rods to prefilled syringes must be adaptable to accommodate for variations in fill level to prevent premature expulsion of the fluid.

A typical machine used for coupling plunger rods and syringe assemblies is fully automated and designed to perform a number of process steps, including loading the plunger rods and syringe assemblies to the machine, operating the machine, coupling the plunger rod to the plunger, and unloading the finished product from the machine. Fully automated technology is particularly useful for preparing large batches of <NUM> or more coupled plunger rod and syringe assemblies. To adjust the fully automated machine for assembling plunger rods and syringe assemblies of a different size, referred herein as the "changeover process," the machine must be partially disassembled, adjusted, and/or reassembled before operating. This changeover process often requires a skilled operator to manage the many components involved in the disassembly, adjustment and tooling, and reassembly of the machine, which can be a very time-intensive procedure. Moreover, the known machine has a large footprint and is generally non-portable once the machine is established in a processing laboratory. Using such a large-batch machine can be impractical for assembling small batches and easily assembly of syringe assemblies of different sizes. <CIT> discloses an apparatus for assembling the components of and filling syringes.

Any methods disclosed herein are not claimed and are mentioned for illustrative purposes only.

In accordance with a first exemplary aspect, a machine for coupling a plunger rod to a syringe assembly may include a selected carriage including a cradle having a seat portion sized to receive a syringe assembly and an aperture portion disposed above the seat portion and sized to receive a plunger rod. An actuating device may be operatively coupled to the selected carriage and adapted to move the cradle from a first position to a second position to couple the plunger rod to the syringe assembly. The selected carriage may be selected from separate and interchangeable first and second carriages, wherein the first carriage includes a cradle adapted to receive a syringe assembly of a first size and the second carriage including a cradle sized to receive a syringe assembly of a second size that is different from the first size.

In accordance with a second exemplary aspect, a method of using a machine to couple a plunger rod to a syringe assembly may include decoupling a second carriage from an actuating device and coupling a first carriage to the actuating device after decoupling the second carriage from actuating device, the first carriage including a movable first cradle adapted to receive a syringe assembly of a first size. Next, the method may include positioning a first syringe assembly onto the movable first cradle of the first carriage, the first syringe assembly including a distal end and a proximal end, a syringe barrel, and a plunger disposed within the syringe barrel. Then, the method may include positioning a first plunger rod onto the first cradle of the first carriage, the first plunger rod including a distal rod end and a proximal rod end and wherein the distal rod end is disposed above the proximal end of the first syringe assembly and is axially aligned with the plunger. Further, the method may include activating the actuating device coupled to the first carriage to move the first cradle from a first position to a second position, thereby applying a force to the first plunger rod causing the first plunger rod to become coupled to the first syringe assembly.

In accordance with a third exemplary aspect, a machine for coupling a plunger rod to a syringe assembly may include a carriage having a movable cradle including a seat portion sized to receive a syringe assembly and an aperture portion disposed above the seat portion sized to receive a plunger rod. An actuating device may be operatively coupled to the carriage and adapted to move the cradle from a first position to a second position to couple the plunger rod to the syringe assembly. The machine may further include an elongated pressure plate positioned adjacent to the carriage and defining an inlet and an outlet, the inlet being sized to receive a proximal end of the plunger rod and apply a downward force on the proximal end of the plunger rod as the plunger rod moves from the inlet to the outlet. A constant tension spring may be coupled to the pressure plate, the constant tension spring providing a downward force to the pressure plate such that the downward force is transferred to the plunger rod via the pressure plate as the cradle moves between the first position and the second position.

In accordance with a fourth exemplary aspect, a machine for coupling a plunger rod to a syringe assembly may include a carriage having a movable cradle including a seat portion sized to receive a syringe assembly and an aperture portion disposed above the seat portion sized to receive a plunger rod. The machine may include an actuating device operatively coupled to the carriage and adapted to move the cradle from a first position to a second position to couple the plunger rod to the syringe assembly. A pressure plate may be positioned adjacent to the carriage so that the cradle moves beneath the pressure plate when the cradle moves from the first position to the second position, the pressure plate adapted to apply a downward force to the plunger rod disposed in the aperture portion of the cradle when the cradle moves from the first position to the second position. The actuating device may include a lever operatively coupled to the carriage and adapted to be manipulated to index the cradle from the first position to the second position.

In accordance with a fifth exemplary aspect, a machine for coupling a plunger rod to a syringe assembly may include a carriage having a movable cradle including a seat portion sized to receive a syringe assembly and an aperture portion disposed above the seat portion sized to receive a plunger rod. An actuating device may be operatively coupled to the carriage and adapted to index the cradle from a first position to a second position only once upon an activation event for coupling the plunger rod to the syringe assembly.

In accordance with a sixth exemplary aspect, a method of using a machine to couple a plunger rod to a syringe assembly may include positioning a syringe assembly onto a movable cradle of a carriage, wherein the syringe assembly includes a distal end and a proximal end, a syringe barrel, and a plunger disposed within the syringe barrel at the proximal end of the syringe assembly. Next, the method may include positioning a plunger rod onto the cradle where the plunger rod may include a distal rod end and a proximal rod end and wherein the distal rod end of the plunger rod is disposed above the proximal end of the syringe assembly and is axially aligned with the plunger. The method may include activating an actuating device operatively connected to the carriage. Further, the method may include indexing the cradle from the first position to the second position only once in response to activating the actuating device, wherein a force may be applied to either or both of the syringe assembly and the plunger rod as the cradle indexes from the first position to the second position to couple the plunger rod to a plunger of the syringe assembly.

In accordance with a seventh exemplary aspect, a machine for coupling a plunger rod to a syringe assembly may include a carriage having a movable cradle including a seat portion sized to receive a syringe assembly and an aperture portion disposed above the seat portion sized to receive a plunger rod. An actuating device may be operatively coupled to the carriage and adapted to move the cradle from a first position to a second position to couple the plunger rod to the syringe assembly. Further, a friction element may be disposed adjacent to the carriage and below the pressure plate where the friction element may be adapted to engage a syringe barrel of the syringe assembly carried by the cradle as the cradle moves from the first position to the second position, thereby applying a rotational force to the syringe assembly and spin the syringe assembly relative to the plunger rod when the cradle moves from the first position to the second position.

In accordance with an eighth exemplary aspect, a method of using a machine to couple a plunger rod to a syringe assembly may include positioning a syringe assembly onto a movable cradle of a carriage, wherein the syringe assembly includes a distal end and a proximal end, a syringe barrel, and a plunger disposed within the syringe barrel at the proximal end of the syringe assembly. The method may include positioning a plunger rod onto the cradle, the plunger rod including a distal rod end and a proximal rod end and wherein the distal rod end of the plunger rod is disposed above the proximal end of the syringe assembly and is axially aligned with the plunger. Then, the method may include activating an actuating device operatively connected to the carriage to move the cradle from a first position to a second position, and rotating the syringe assembly relative to the plunger rod when the cradle moves between the first position and the second position, thereby causing a first threaded portion on the distal rod end of the plunger rod to become threadably coupled to a second threaded portion of the plunger of the syringe assembly.

In accordance with a ninth exemplary aspect, a machine for coupling a plunger rod to a syringe assembly may include a carriage having a movable cradle including a seat portion sized to receive a syringe assembly and an aperture portion disposed above the seat portion sized to receive a plunger rod. The machine may include an actuating device operatively coupled to the carriage and adapted to index the cradle from a first position to a second position only once upon an activation event to couple the plunger rod to the syringe assembly. A pressure plate may be positioned adjacent to the carriage so that the cradle moves beneath the pressure plate when the cradle moves from the first position to the second position, the pressure plate adapted to apply a downward force to the plunger rod disposed in the aperture portion of the cradle when the cradle moves from the first position to the second position. The actuating device may include a servomotor and an operation switch for operatively controlling the servomotor, the servomotor coupled to the carriage to index the cradle via the carriage.

In accordance with a tenth exemplary aspect, a machine for coupling a plunger rod to a syringe assembly may include a base and a carriage attached to the base and movable relative to the base, the carriage including a movable cradle having a seat portion sized to receive a syringe assembly and an aperture portion disposed above the seat portion sized to receive a plunger rod. An actuating device may be coupled to the carriage and adapted to index the cradle from a first position to a second position. The machine may include a pressure plate supported by the base and positioned adjacent to the carriage so that the cradle moves beneath the pressure plate when the cradle moves from the first position to the second position, the pressure plate adapted to apply a downward force to the plunger rod disposed in the aperture portion of the cradle. The cradle may include a cradle axis that is coaxial with longitudinal axes of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed in the cradle, the cradle axis being disposed at an angle greater than zero degrees relative to vertical.

In accordance with an eleventh exemplary aspect, a machine for coupling a plunger rod to a syringe assembly may include a carriage having a movable cradle including a seat portion sized to receive a syringe assembly and an aperture portion disposed above the seat portion sized to receive a plunger rod, an actuating device operatively coupled to the carriage and adapted to move the cradle from a first position to a second position to couple the plunger rod to the syringe assembly, and
a pressure plate positioned adjacent to the carriage so that the cradle moves beneath the pressure plate when the cradle moves from the first position to the second position, the pressure plate adapted to apply a downward force to the plunger rod disposed in the aperture portion of the cradle when the cradle moves from the first position to the second position. The machine may include at least one of the following (a) through (e) aspects. In aspect (a), a constant tension spring may be operatively coupled to the pressure plate and the pressure plate may define an inlet portion adapted to receive a proximal end of the plunger rod when the cradle moves from the first position to the second position. The constant tension spring may provide the downward force to the plunger rod, applied via the pressure plate, when the cradle moves between the first position and the second position. In aspect (b), a friction element may be disposed adjacent to the carriage and below the pressure plate. The friction element may be adapted to engage a syringe barrel of the syringe assembly carried by the cradle as the cradle moves from the first position to the second position. The friction element may be adapted to apply a rotational force to the syringe barrel to spin the syringe assembly relative to the plunger rod when the cradle moves from the first position to the second position. In aspect(c), the actuating device may be operatively connected to the carriage and adapted to index the cradle between the first position and the second position in response to an activation event. In aspect (d), the cradle may include a cradle axis that is coaxial with longitudinal axes of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed in the cradle. The cradle axis may be disposed at an angle greater than zero degrees relative to vertical. Finally in aspect (e), the carriage may be selected from separate and interchangeable first and second carriages. The first carriage may include a cradle having a seat portion sized to receive a syringe assembly of a first size and the second carriage may include a cradle having a seat portion sized to receive a syringe assembly of a second size.

In accordance with a twelfth exemplary aspect, a method of using a machine to couple a plunger rod to a syringe assembly may include positioning a syringe assembly onto a movable cradle of a carriage, wherein the syringe assembly includes a distal end and a proximal end, a syringe barrel, and a plunger disposed within the syringe barrel at the proximal end of the syringe assembly. Next, the method may include positioning a plunger rod onto the cradle where the plunger rod may include a distal rod end and a proximal rod end and wherein the distal rod end of the plunger rod is disposed above the proximal end of the syringe assembly and is axially aligned with the plunger. The method may include activating an actuating device operatively connected to the carriage. Further, the method may include indexing the cradle from the first position to the second position more than once in response to activating the actuating device, wherein a force may be applied to either or both of the syringe assembly and the plunger rod as the cradle indexes from the first position to the second position to couple the plunger rod to a plunger of the syringe assembly.

In further accordance with any one or more of the foregoing first through twelfth aspects and methods, the machine for coupling a plunger rod and syringe assembly and method for using the machine may include any one or more of the following forms or method steps.

In a preferred form, the machine may include a selected pressure plate positioned above the cradle so that the cradle moves beneath the selected pressure plate when the cradle moves from the first position to the second position. The selected pressure plate may be adapted to apply a downward force to the plunger rod disposed in the aperture portion of the cradle when the cradle moves from the first position to the second position.

In a preferred form of the machine, the first carriage may include a first pressure plate coupled to the first carriage, and the second carriage may include a second pressure plate coupled to the second carriage, such that the selected pressure plate is coupled to the selected carriage.

In a preferred form, the machine may include a quick-change fastener and a table, the selected carriage may be removably coupled to the table by the quick-change fastener.

In a preferred form of the machine, the first carriage may include a first base and the second carriage may include a second base, and the actuating device may include a servomotor adapted to be operatively connected to the first and second bases.

In a preferred form, the machine may include a selected friction element disposed adjacent to the selected carriage. The selected friction element may be adapted to engage a syringe barrel of the syringe assembly carried by the cradle as the cradle moves from the first position to the second position. The friction element may be adapted to apply a rotational force to the syringe barrel to spin the syringe assembly relative to the plunger rod when the cradle moves from the first position to the second position.

In a preferred form of the machine, the first carriage may include a first guide plate coupled to the first carriage and carrying a first friction element and the second carriage may include a second guide plate coupled to the second carriage and carrying a second friction element such that the selected friction element is carried by a selected guide plate coupled to the selected carriage.

In a preferred form, the machine may include a selected constant tension spring operatively coupled to the selected pressure plate. The selected pressure plate defining an inlet portion may be adapted to receive a proximal end of the plunger rod when the cradle moves from the first position to the second position. The selected constant tension spring may provide the downward force to the plunger rod, applied via the selected pressure plate, when the cradle moves between the first position and the second position.

In a preferred form, the machine may include a servomotor and an operation switch for operatively controlling the servomotor, the servomotor coupled to the carriage to move the cradle via the carriage.

In a preferred form of the machine, the inlet may include a ramped surface positioned above the outlet relative to the carriage.

In a preferred form, the machine may include at least one guide post, the pressure plate slidably coupled to the at least one guide post in a direction parallel to a longitudinal axis of the carriage.

In a preferred form, the machine may include a threaded rod for adjustably mounting the pressure plate relative to the carriage such that the pressure plate is adjustable in the direction parallel to the longitudinal axis of the carriage to accommodate plunger rods at different heights.

In a preferred form, the machine may include a friction element disposed adjacent to the carriage and below the pressure plate. The friction element may be adapted to engage a syringe barrel of the syringe assembly carried by the cradle as the cradle moves from the first position to the second position. The friction element may be adapted to apply a rotational force to the syringe barrel to spin the syringe assembly relative to the plunger rod.

In a preferred form of the machine, the friction element may be immovably fixed relative to the cradle.

In a preferred form, the machine may include a guide plate and the friction element may be fixed to the guide plate.

In a preferred form of the machine, the friction element may be an elongated cord.

In a preferred form of the machine, the friction element may be an elastomeric material.

In a preferred form of the machine, the actuating device may be adapted to index the cradle between the first position and the second position in response to an activation event.

In a preferred form of the machine, the actuating device may index the cradle only once upon an activation event.

In a preferred form of the machine, the actuating device may index the cradle two or more times upon an activation event.

In a preferred form of the machine, the actuating device may include a lever for a user to manually index the cradle from the first position to the second position.

In a preferred form of the machine, the lever may be movably attached to a base of the carriage, and wherein the lever may be arranged to perform the activation event when the lever moves from a resting position to an activated position.

In a preferred form of the machine, the actuating device may include a motor-operated bracket disposed adjacent to the lever, the bracket may be adapted to move the lever between the resting position to the activated position.

In a preferred form of the machine, the actuating device may include a slidable bracket arranged to move the lever.

In a preferred form, the machine may include a pressure plate positioned adjacent to the carriage so that the cradle moves beneath the pressure plate when the cradle moves from the first position to the second position, the pressure plate adapted to apply a downward force to the plunger rod disposed in the aperture portion of the cradle when the cradle moves from the first position to the second position.

In a preferred form, the machine may include a two-hand anti-tie down operation switch arranged to perform the activation event.

In a preferred form of the machine, the actuating device may include a lever operatively coupled to the carriage, the lever arranged to be manually manipulated for performing the activation event.

In a preferred form of the machine, the seat portion of the cradle may include a first roller and a second roller separated by a gap. The first and second rollers of the seat portion may be adapted to engage the syringe barrel of the syringe assembly and retain the syringe barrel in the gap when carried by the cradle, the first and second rollers allowing for the syringe assembly to spin as the cradle indexes from the first position to the second position.

In a preferred form of the machine, each of the first and second rollers may include a rotational axis, the first roller being rotatable about the rotational axis of the first roller and the second roller being rotatable about the rotational axis of the second roller.

In a preferred form of the machine, the servomotor may be programmed to respond to an activation event to move the carriage, the activation event including triggering the operation switch.

In a preferred form of the machine, the servomotor may be programmed to index the cradle more than once in response to the activation event.

In a preferred form of the machine, the servomotor may be adapted to operatively couple to a different carriage.

In a preferred form of the machine, the cradle may include a cradle axis that is coaxial with longitudinal axes of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed in the cradle, the cradle axis being disposed at an angle greater than zero degrees relative to vertical.

In a preferred form of the machine, the carriage may include a rotational carousel with a rotational axis that is parallel to the cradle axis such that the rotational axis of the carriage is disposed at an angle greater than zero degrees relative to vertical.

In a preferred form of the machine, the base may include a bottom surface disposed at a first angle relative to horizontal, wherein the longitudinal axis of the cradle is offset from the vertical by the first angle.

In a preferred form, the machine may include a movable plunger rod base coupled to the carriage. The plunger rod base may be disposed above the cradle and may include an orifice sized to receive a flanged proximal end of the plunger rod, the orifice coaxially aligned with the aperture portion of the cradle. The plunger rod base may be movable with the cradle from the first position to the second position.

In a preferred form, the machine may include a holding cap having an outwardly extending tab arranged to extend into the orifice of the plunger rod base, the holding cap removably attached to the plunger rod base. The holding cap may be fixed relative to the carriage and is disposed in the orifice when the cradle is in the first position.

In a preferred form, the machine may include a selected movable plunger rod base coupled to the selected carriage.

In a preferred form of the machine, the plunger rod base may be selected from separate and interchangeable first and second plunger rod bases, the first plunger rod base including an orifice sized to receive a flanged plunger rod end of a first size and the second plunger rod base sized to receive a flanged plunger rod end of a second size that is different from the first size.

In a preferred form of the machine, the carriage may be rotationally disposed relative to the pressure plate.

In a preferred form of the machine, the carriage may include a plurality of cradles carried by the carriage.

In a preferred form, the machine may include an exit chute disposed adjacent to the carriage and at the second position of the cradle. The exit chute may be adapted to receive the plunger rod and syringe assembly from the cradle after the plunger rod is coupled to the syringe assembly.

In a preferred form, the first carriage may include a first exit chute coupled to the first carriage and the second carriage may include a second exit chute coupled to the second carriage such that the selected exit chute is coupled to the selected carriage.

In a preferred form of the machine, the exit chute may include a ramp, the ramp including a slot sized to receive the plunger rod and syringe assembly after the cradle moves to the second position.

In a preferred form, the method may include applying a downward force to the proximal rod end of the first plunger rod when the first cradle moves from the first position toward the second position.

In a preferred form, the method may include indexing the cradle from the first position to the second position two or more times in response to activating the actuating device.

In a preferred form, the method may include fastening the first carriage to a table by a quick-change fastener, wherein the table is connected to the actuating device.

In a preferred form of the method, decoupling the second carriage from the actuating device may include decoupling the quick-change fastener securing the second carriage to the table.

In a preferred form of the method, decoupling the second carriage from the actuating device may include decoupling a servomotor of the actuating device from a receiving member of the second carriage.

In a preferred form of the method, coupling the first carriage to the actuating device may include coupling a servomotor of the actuating device to a receiving member of the first carriage.

In a preferred form, the method may include, prior to decoupling the second carriage from the actuating device, positioning a second syringe assembly onto a second cradle of the second carriage, the second cradle adapted to receive the second syringe assembly of a second size, the second syringe assembly including a distal end and a proximal end, a syringe barrel, and a plunger disposed within the syringe barrel, wherein the second cradle of the second carriage is sized to receive a second syringe barrel of a second size. Further, the preferred form of the method may include positioning a second plunger rod onto the second cradle of the second carriage, the second plunger rod including a distal rod end and a proximal rod end and wherein the distal rod end is disposed above the proximal end of the second syringe assembly and is axially aligned with the plunger. In the preferred form, the method may include activating the actuating device coupled to the second carriage to move the second cradle from a first position to a second position, thereby applying a force to the second plunger rod causing the second plunger rod to become coupled to the second syringe assembly.

In a preferred form of the method, indexing the cradle may include rotating the carriage about a rotational axis of the carriage.

In a preferred form of the method, rotating the carriage may include rotating the carriage greater than zero degrees to index the cradle from the first position to the second position.

In a preferred form of the method, activating the actuating device may include moving a lever, wherein the lever causes the carriage to index the cradle from the first position to the second position.

In a preferred form of the method, activating the actuating device may include triggering an operation switch coupled to a servomotor, wherein the servomotor is arranged to slide a bracket to move the lever.

In a preferred form of the method, activating the actuating device may include triggering an operation switch coupled to a servomotor, wherein the servomotor is operatively coupled to the carriage.

In a preferred form, the method may include applying a downward force to the proximal rod end of the plunger rod when the cradle moves from the first position toward the second position.

In a preferred form of the method, applying a downward force to the proximal rod end of the plunger rod may include moving the plunger rod beneath a pressure plate positioned adjacent to the carriage when the cradle moves from the first position to the second position.

In a preferred form, the method may include applying a rotational force to the syringe barrel of the syringe assembly as the cradle moves from the first position to the second position.

In a preferred form of the method, applying the rotational force may include engaging the syringe assembly with a friction element disposed adjacent to the carriage when the cradle moves from the first position to the second position. The syringe assembly may be rotatable about a longitudinal axis of the cradle.

In a preferred form, the method may include rotating the carriage about a rotational axis of the carriage in a first direction to index the cradle from the first position to the second position.

In a preferred form of the method, rotating the syringe assembly may include rotating the syringe assembly in a direction opposite the first direction of the carriage, wherein the rotational axis of the carriage is parallel to the longitudinal axis of the cradle.

It is believed that the disclosure will be more fully understood from the following description taken in conjunction with the accompanying drawings. Some of the drawings may have been simplified by the omission of selected elements for the purpose of more clearly showing other elements. Such omissions of elements in some drawings are not necessarily indicative of the presence or absence of particular elements in any of the example embodiments, except as may be explicitly delineated in the corresponding written description. Also, none of the drawings is necessarily to scale.

A plunger rod assembly system for coupling a plunger rod to a prefilled syringe assembly is illustrated and described herein. <FIG> illustrate a first example plunger rod assembly machine <NUM> depicted in various stages of coupling a plunger rod <NUM> and a prefilled syringe assembly <NUM>. <FIG> illustrate various components of the machine <NUM> in more detail, and <FIG> and <FIG> illustrate an adaptive system to convert the non-automated machine <NUM> of <FIG> to a second example plunger rod assembly system that is semi-automated. A third example plunger rod assembly system is illustrated in <FIG> and may incorporate any or all of the various components of the previous illustrations to couple a plunger rod <NUM> to a syringe assembly <NUM>. The term "syringe assembly" <NUM> may refer to a prefilled syringe or an empty syringe.

In <FIG>, the first example of a plunger rod assembly system <NUM> for coupling a plunger rod <NUM> to a syringe assembly <NUM> is illustrated. The plunger rod assembly system <NUM> is a machine having a carriage <NUM> with a movable cradle <NUM> and an actuating device <NUM> operatively coupled to the carriage <NUM> and adapted to move the cradle <NUM> from a first position to a second position. The cradle <NUM> includes a seat portion <NUM> sized to receive the syringe assembly <NUM> and an aperture portion <NUM> disposed above the seat portion <NUM> and sized to receive the plunger rod <NUM>. Depicted in the illustrated example, the carriage <NUM> is a rotating carousel with a plurality of cradles <NUM> carried by the carriage <NUM> and disposed about the perimeter of the carousel <NUM>. For ease of reference, a single cradle <NUM> will be described as the carriage <NUM> rotates the cradle <NUM> between the first position and the second position. A "loaded cradle" <NUM> as used herein refers to the cradle <NUM> having the plunger rod <NUM> and syringe assembly <NUM> positioned thereon. While the machine <NUM> provides multiple cradles <NUM> in various positions, a "first position" P1 (seen in <FIG>) refers to the position where the plunger rod <NUM> and syringe assembly <NUM> are positioned onto the cradle <NUM> but are not yet coupled to each other. A "second position" P2 (seen in <FIG>) refers to any position of the loaded cradle <NUM> once the plunger rod <NUM> is coupled to the syringe assembly <NUM>. As used herein, a "coupled plunger rod syringe assembly" <NUM> refers to a final product where the plunger rod <NUM> is coupled to the syringe assembly <NUM>. The plunger rod <NUM> and the syringe assembly <NUM> may be loosely attached, removably secured to, or suitably fit onto the cradle <NUM>.

The function and operation of the machine <NUM> will be described when the cradle <NUM> is in three sequential positions: the first position P1, a position between the first position P1 and a second position P2, and the second position P2. The machine <NUM> is configured to couple the plunger rod <NUM> and the prefilled syringe assembly <NUM> by moving the cradle <NUM> from the first position P1 shown in <FIG>, through an intermediate position shown in <FIG>, and finally the second position P2 shown in <FIG> where the plunger rod <NUM> is coupled to the syringe assembly <NUM>. The actuating device <NUM> disposed within a base <NUM> of the machine <NUM> drives the rotation of the carriage <NUM> and the loaded cradle <NUM> about a rotational axis A of the carriage <NUM>. As the carriage <NUM> rotates, the loaded cradle <NUM> passes a guide assembly <NUM> attached to the base <NUM>. The guide assembly <NUM> includes a pre-force plunger unit <NUM> which is configured to apply a constant downward force to the plunger rod <NUM> as the plunger rod <NUM> engages a pressure plate <NUM>. Simultaneously, a friction element <NUM> (<FIG>) of the guide assembly <NUM> engages and applies a rotational force (e.g., a torque) to the syringe assembly <NUM> to spin the syringe assembly <NUM> relative to the plunger rod <NUM> as the loaded cradle <NUM> passes under the pressure plate <NUM>. The combination of the downward force applied by the pressure plate <NUM> and the rotational force applied by the friction element <NUM> effectively couples the plunger rod <NUM> to the syringe assembly <NUM> by the time the loaded cradle <NUM> reaches the second position P2. In <FIG>, the coupled plunger rod syringe assembly <NUM> is in the second position P2 adjacent to an exit chute <NUM> that receives the coupled plunger rod syringe assembly <NUM>. The cradle <NUM> is configured to release the coupled plunger rod syringe assembly <NUM> when the carriage <NUM> rotates again, and the cradle <NUM> is configured to deposit the coupled plunger rod syringe assembly <NUM> into the exit chute <NUM> as shown in <FIG>. The carriage <NUM> described herein may be controlled or operated by a rotary actuator, but other embodiments may include a linear actuator. For example, the carriage <NUM> may be replaced with a linear assembly line, such as a conveyor belt, where the cradle <NUM> is indexed linearly. The carriage <NUM> may include one or more movable cradles <NUM> that are coupled to a linear drive mechanism that moves the cradles <NUM> linearly. In this example, the guide assembly <NUM> may be positioned relative to the linear conveyor belt or other method of linear conveyance to interact with the movable cradles <NUM> to couple the plunger rod <NUM> to the syringe assembly18.

As shown in <FIG>, <FIG>, and <FIG>, the machine <NUM> is oriented at an angle when the base <NUM> of the machine <NUM> sits on a flat surface. As seen in <FIG>, the rotational axis A of the carriage <NUM> is disposed at an angle α relative to vertical V, and a bottom surface <NUM> of the base <NUM> is disposed at angle β relative to horizontal H. The rotational and/or longitudinal axis A of the carriage <NUM> is also parallel to a cradle axis B that is coaxial with longitudinal axes C of the plunger rod <NUM> and syringe assembly <NUM> when the plunger rod <NUM> and syringe assembly <NUM> are disposed in the cradle <NUM>. The cradle axis B and the rotational axis A are disposed at the angle α that is greater than zero degrees relative to vertical V. In one version, the angle α can be between <NUM> degree and <NUM> degrees, between <NUM> degrees and <NUM> degrees, between <NUM> degrees and <NUM> degrees, between <NUM> degrees and <NUM> degrees, between <NUM> degrees and <NUM> degrees, or any other suitable angle.

As mentioned earlier, the term "cradle" <NUM> refers to the structure that receives the plunger rod <NUM> and syringe assembly <NUM>. Each cradle <NUM> includes a seat portion <NUM> defined by a pair of rollers <NUM>, an orifice <NUM> of a plunger rod locating base <NUM>, and the aperture portion <NUM> defined by a plunger rod grip disk <NUM>. The rollers <NUM>, the plunger rod locating base <NUM>, and the plunger rod grip disk <NUM> are attached to the carriage <NUM> and are rotatable about the rotational axis A when the carriage <NUM> is actuated by the actuating device <NUM>. The locating base <NUM> includes a plurality of evenly spaced orifices <NUM> and the plunger rod grip disk <NUM> includes a plurality of evenly spaced apertures <NUM>. The locating base <NUM> and the grip disk <NUM> are spaced apart and positioned relative to the rollers <NUM> so that each cradle <NUM> is defined by one orifice <NUM>, one aperture <NUM>, and one seat portion <NUM> that are coaxial and arranged to receive a plunger rod <NUM> aligned with a syringe assembly <NUM>. Each roller <NUM> is rotatable about a pin <NUM> disposed through a central axis D of the roller <NUM>, and each pin <NUM> is secured to a bottom portion <NUM> of the carriage <NUM>. Each roller <NUM> is spaced away from an adjacent roller <NUM> a predetermined distance defining a gap G so that a syringe barrel <NUM> may fit within the seat portion <NUM> between and in engagement with two adjacent rollers <NUM>. First and second adjacent rollers <NUM> of the seat portion <NUM> are adapted to engage the syringe barrel <NUM> of the syringe assembly <NUM> and retain the syringe barrel <NUM> in the gap G when carried by the cradle <NUM>.

The rollers <NUM> are arranged to loosely hold the syringe barrel <NUM> of the syringe assembly <NUM> when the syringe assembly <NUM> is attached to, or otherwise disposed on, the machine <NUM> in the first position P1, and to release the syringe barrel <NUM> when the cradle <NUM> moves toward the exit chute <NUM>. In the disclosed versions, the angled orientation of the carriage <NUM> enables the cradle <NUM> to hold the syringe barrel <NUM> while the cradle <NUM> moves from the first position P1 toward the second position P2. Additionally, the angled orientation of the machine <NUM> permits the cradle <NUM> to release the coupled plunger rod syringe assembly <NUM> into the exit chute <NUM> after the cradle <NUM> passes the second position P2. When the carriage <NUM> rotates again, the coupled plunger rod syringe assembly <NUM> is received by a slot <NUM> of the exit chute <NUM> and the coupled plunger rod syringe assembly <NUM> may slide down a ramp <NUM> where the coupled plunger rod syringe assembly <NUM> remains until removed. The slot <NUM> is sized to receive a particular size syringe assembly <NUM> so that the coupled plunger rod and syringe assembly <NUM> can easily slide down the ramp <NUM> for storage in the exit chute <NUM>. The ramp <NUM> may be sized and angled to hold a batch of coupled plunger rod syringe assemblies <NUM>.

The dimensions of the cradle <NUM> are based on the requirements of the syringe assembly <NUM> and plunger rod <NUM>. In particular, the seat portion <NUM> is sized to receive a specific type/size of syringe assembly <NUM> and the aperture portion <NUM> and orifice <NUM> of the cradle <NUM> are also sized to receive a specific type/shape of plunger rod <NUM>. In the illustrated example, the machine <NUM> is specifically designed to couple a plunger rod <NUM> and syringe assembly <NUM> of a particular size. In other embodiments, the machine <NUM> may be adjusted to accommodate different sizes of plunger rods <NUM> and syringe assemblies <NUM>. The machine <NUM> may be designed to accommodate one syringe assembly size, for example a <NUM> glass syringe assembly <NUM>. As such, the spacing between two adjacent rollers <NUM> is arranged so that the syringe assembly <NUM> having a <NUM> syringe barrel <NUM> may be loosely attached to the cradle <NUM>. Each aperture <NUM> of plunger rod grip disk <NUM> is designed to accommodate a particular shape of a plunger rod body <NUM> used with a <NUM> syringe assembly <NUM>. For a plunger rod <NUM> with an X-shaped cross-section, the aperture portion <NUM> may include a plurality of ridges to receive the plunger rod body <NUM> and to limit rotational, angular, and lateral movement of the plunger rod <NUM> relative to the axis C when the loaded cradle <NUM> moves from the first position P1 to the second position P2. The rollers <NUM>, on the other hand, are freely rotatable about the axis D and permit the syringe barrel <NUM> to rotate about the axis B of the cradle <NUM> when the friction element <NUM> contacts the syringe barrel <NUM>, as will be described in further detail below. The rollers <NUM>, the plunger rod grip disk <NUM>, and the plunger rod locating base <NUM> may be positioned to accommodate a specific height of a plunger rod body <NUM>.

The machine <NUM> is configured to accommodate a variety of different fill levels of a particular size syringe assembly <NUM> by interchangeable plunger rod locating bases <NUM> and <NUM>. Depicted in <FIG>, the plunger rod locating base <NUM> is selected from separate and interchangeable first and second plunger rod locating bases <NUM> and <NUM>. The first plunger rod locating base <NUM> includes the orifice <NUM> sized to receive a particular size proximal end <NUM> of a plunger rod <NUM> and the second plunger rod locating base <NUM> includes an orifice <NUM> sized to receive a different size proximal end <NUM> of a plunger rod <NUM>. The first plunger rod locating base <NUM> and corresponding plunger rod holding cap <NUM> shown in <FIG> and <FIG> may be interchanged with the different locating base <NUM> and associated holding cap <NUM> shown in <FIG> and <FIG>. The first and second plunger rod locating bases <NUM> and <NUM> may differ in height to accommodate different plunger rod heights, and they may have different orifice <NUM> and <NUM> sizes to accommodate two sizes of plunger rod proximal ends <NUM>. In the illustrated embodiment, the orifices <NUM> of the first locating base <NUM> are smaller in radius than the orifices <NUM> of the second locating base <NUM>. While not illustrated, the machine <NUM> may be configured to operate with any number of different plunger rod locating bases, and the machine <NUM> is not limited to the two embodiments described and illustrated herein.

Turning to <FIG> and <FIG>, the first plunger rod locating base <NUM> and holding cap <NUM> are removably attached to the machine <NUM>. The first plunger rod locating base <NUM> is coupled to the carriage <NUM> and is disposed above the plunger rod grip disk <NUM> so that the orifices <NUM> placed about the perimeter of the locating base <NUM> are coaxial with the apertures <NUM> of the grip disk <NUM>. Each orifice <NUM> is sized to receive a flanged proximal end <NUM> of the plunger rod <NUM> and provides sufficient clearance to permit the flanged proximal rod end <NUM> to fall through the orifice <NUM> when the cradle <NUM> moves from the first position P1 to the second position P2. The holding cap <NUM> is disposed on top of the locating base <NUM> and includes an outwardly extending tab <NUM> arranged to extend into the orifice <NUM> when the locating base <NUM> and holding cap <NUM> are attached to the machine <NUM>. Both the holding cap <NUM> and the plunger rod locating base <NUM> are removably attached to the machine <NUM> via a threaded fastener <NUM>. While the locating base <NUM> is movably coupled to the carriage <NUM> (such that the locating base <NUM> rotates with the carriage <NUM>), the holding cap <NUM> and the threaded fastener <NUM> are fixed to the machine <NUM> and do not rotate with the carriage <NUM> about the axis A. The holding cap <NUM> provides a holding function to the plunger rod <NUM> when the plunger rod <NUM> is first positioned onto the cradle <NUM>. As shown in <FIG> and <FIG>, the flanged proximal end <NUM> of the plunger rod <NUM> is received by the orifice <NUM> of the locating base <NUM> and sits against a portion <NUM> of the tab <NUM> that extends into the orifice <NUM>. The portion <NUM> of the tab <NUM> disposed in the orifice <NUM> holds the plunger rod <NUM> in suspension above the syringe assembly <NUM> positioned on the seat portion <NUM>. As the loaded cradle <NUM> moves from the first position P1, the locating base <NUM> rotates relative to the extending tab <NUM>, and the orifice <NUM> of the cradle <NUM> moves away from the portion <NUM> to release the plunger rod <NUM> therefrom. The flanged proximal end <NUM> of the plunger rod <NUM> drops below the orifice <NUM> of the locating base <NUM> and a distal end <NUM> of the plunger rod <NUM> contacts a plunger <NUM> disposed in the syringe barrel <NUM>, as shown in <FIG>.

<FIG> illustrates a first side 100a of the holding cap <NUM> associated with the first plunger rod locating base <NUM>, and <FIG> illustrates a second side 100b of the holding cap <NUM> associated with the second plunger rod locating base <NUM>. In each illustrated embodiment, the extending tab <NUM> of the holding cap <NUM> includes an asymmetrical contoured edge 101a and 101b which may be shaped according to variations in flanged ends <NUM> of different plunger rods <NUM>. Each side 100a and 100b of the holding cap <NUM> includes a particular mark or markings 102a and 102b associated with corresponding markings 103a and 103b on the plunger rod locating base <NUM> and <NUM>. The grip disk <NUM> also includes markings 105a and 105b that line up with the markings 102a and 102b to ensure alignment of the orifices <NUM> and <NUM> and the apertures <NUM> when assembling the cradles <NUM>. As shown in <FIG>, the markings 102a, 103a, and 105a may provide a visual indication that the plunger cap <NUM> is properly aligned with both the first plunger rod locating base <NUM> and the grip disk <NUM>. To replace the first plunger rod locating base <NUM> with the second plunger rod locating base <NUM>, a threaded fastener <NUM>, which includes a hand operated knurled knob, is removed from the machine <NUM> and the holding cap <NUM> and the first locating base <NUM> are removed. The second locating base <NUM> is placed onto the carriage <NUM> so that the markings 103b align with the corresponding markings 105b on the grip disk <NUM>. The holding cap <NUM> is flipped so that the second side 100b is facing away from the carriage <NUM> and then is placed on top of the second locating base <NUM> so that the markings 102b of the holding cap <NUM> align with the markings 103b of the second locating base <NUM> and the markings 105b of the grip disk <NUM>. When properly assembled, the extending tab <NUM> is disposed within the orifice <NUM> of the cradle <NUM> in the first position P1. In the illustrated embodiments, the machine <NUM> includes the plunge rod holding cap <NUM> and plunger rod locating bases <NUM> and <NUM> for suspending the plunger rod <NUM> above the syringe assembly <NUM> when loaded to the cradle <NUM> in the first position P1. In a different embodiment, the plunger rod <NUM> and syringe assembly <NUM> may be loaded together such that the plunger rod <NUM> is not held by the holding cap <NUM> and locating base <NUM> and <NUM>, and the distal end <NUM> may instead rest against the plunger <NUM> when the cradle <NUM> is in the first position P1. In this case, the locating base <NUM> and <NUM> and the holding cap <NUM> may be optionally attached to the machine <NUM> so that the cradle <NUM> is not defined by the orifice <NUM> and <NUM> of the locating base <NUM> and <NUM>.

The guide assembly <NUM> in <FIG> and <FIG> includes the pre-force plunger unit <NUM> of the machine <NUM> attached to an infeed guide assembly <NUM>. The infeed guide assembly <NUM> includes a plurality of support rods <NUM> that connect a rod retaining guide <NUM>, a top infeed guide <NUM>, a guide plate <NUM>, a bottom infeed guide <NUM>, and a support base <NUM>. Generally, the rod retaining guide <NUM>, top infeed guide <NUM>, guide plate <NUM>, and bottom infeed guide <NUM> are contoured to partially surround and match the outer perimeter of the carriage <NUM>. The support base <NUM> is attached to the base <NUM> of the machine <NUM> and the supporting rods <NUM> support the remaining elements of the infeed guide assembly <NUM> and the pre-force plunger unit <NUM>. The top and bottom infeed guides <NUM> and <NUM> include cut-off ends <NUM> and <NUM>, respectively, to receive and guide the loaded cradle <NUM> and prevent jamming while the carriage <NUM> rotates. A syringe barrel guide <NUM> attached to the top infeed guide <NUM> assists the infeed guides <NUM> and <NUM> by providing a barrier to a proximal end <NUM> of the syringe assembly <NUM> as the loaded cradle <NUM> moves passed the guide assembly <NUM> to the second position P2. As shown in <FIG>, the syringe barrel guide <NUM> is an L-shaped bracket sized to receive and guide the proximal end <NUM> of the syringe assembly <NUM>.

A friction element <NUM> is illustrated in <FIG> fixed to an interior edge surface <NUM> of the guide plate <NUM> and disposed adjacent to the carriage <NUM> and below the pressure plate <NUM>. The friction element <NUM> is adapted to engage a syringe barrel <NUM> of the syringe assembly <NUM> attached to the cradle <NUM> when the cradle <NUM> moves from the first position P1 to the second position P2. The friction element <NUM> therefore applies a rotational force to the syringe barrel <NUM> to spin the syringe assembly <NUM> relative to the plunger rod <NUM>. In the illustrated example, the friction element <NUM> is an elongated cord that extends along the interior edge surface <NUM> of the guide plate <NUM> so that the friction element <NUM> remains in contact with the syringe barrel <NUM> as the syringe assembly <NUM> moves along at least a portion of its path from the first position P1 to the second position P2. When the cradle <NUM> moves from the first position P1 to the second position P2, the syringe assembly <NUM> passes the guide assembly <NUM> and engages the friction element <NUM> protruding from the interior edge surface <NUM> of the guide plate <NUM>. The friction element <NUM> contacts the syringe barrel <NUM> and causes the syringe barrel <NUM> and syringe assembly <NUM> to rotate about the longitudinal axis B of the cradle <NUM>. So configured, as the cradle <NUM> carries the syringe assembly <NUM> in a first direction, the friction element <NUM> engages the syringe barrel <NUM> and applies a rotational force to the syringe barrel <NUM>, causing the syringe barrel <NUM> to rotate between the rollers <NUM> of the cradle <NUM> in a direction opposite the first rotational direction of the carriage <NUM>. Meanwhile, the plunger rod <NUM> disposed in the aperture portion <NUM> of the cradle <NUM> does not rotate relative to the cradle <NUM> or the syringe assembly <NUM>, and instead receives a downward force from the pre-force plunger unit <NUM>.

In a preferred example, the pressure plate <NUM> of the pre-force plunger unit <NUM> applies a constant force (e.g., approximately 2N in some versions) to the plunger rod <NUM>, and the friction element <NUM> causes the syringe barrel <NUM> to rotate a maximum of four times to couple the plunger rod <NUM> and the syringe assembly <NUM>. The length of the friction element <NUM> may be determined based on the mating relationship between the plunger <NUM> of the syringe assembly <NUM> and the plunger rod <NUM>. For example, the plunger <NUM> may complete three rotations relative to the plunger rod <NUM> before the threaded distal end <NUM> of the plunger rod <NUM> adequately couples to the plunger <NUM>. If the friction element <NUM> causes the syringe assembly <NUM> to rotate more than necessary, the excessive rotational force applied to the syringe assembly <NUM> may detrimentally effect the plunger <NUM>, syringe barrel <NUM>, or some other component of the syringe assembly <NUM>. Thus, the length of the friction element <NUM> is based on a minimum number of rotations the syringe assembly <NUM> must take around the axis B to sufficiently couple the plunger <NUM> to the plunger rod <NUM> during a single index and without breaking. The friction element <NUM> may be an elastomeric material, such as silicon based rubber, gum rubber, latex, or other suitable material that would induce the syringe assembly <NUM> to spin relative to the cradle <NUM> when contacting the friction element <NUM>. In another embodiment, the friction element <NUM> may be disposed on the rollers <NUM> rather than on the interior edge surface <NUM> of the guide plate <NUM>. In this example, the guide plate <NUM> may be positioned so that a portion of the guide plate <NUM> contacts the friction element <NUM> disposed on the rollers <NUM>, causing the rollers <NUM> to spin the syringe assembly <NUM> when the cradle <NUM> moves passed the guide assembly <NUM>.

In <FIG> and <FIG>, the pre-force plunger unit <NUM> includes a base plate <NUM> attached to the rod retaining guide <NUM>, the pressure plate <NUM>, a constant tension spring <NUM> coupled to the pressure plate <NUM>, and first and second guide posts <NUM>. The elongated pressure plate <NUM> is positioned adjacent to the carriage <NUM> so that the cradle <NUM> moves beneath the pressure plate <NUM> when the cradle <NUM> moves from the first position P1 to the second position P2. In other words, the carriage <NUM> is rotationally disposed relative to the pressure plate <NUM>. The pressure plate <NUM> is adapted to apply a downward force to the plunger rod <NUM> disposed in the aperture portion <NUM> of the cradle <NUM>. In particular, the pressure plate <NUM> defines an inlet <NUM> (seen in <FIG>) and an outlet <NUM> where the inlet <NUM> is sized to receive the proximal end <NUM> of the plunger rod <NUM> and apply a downward force onto the proximal rod end <NUM> of the plunger rod <NUM> as the plunger rod <NUM> moves from the inlet <NUM> to the outlet <NUM>. The constant tension spring <NUM> is coupled to the pressure plate <NUM> and provides the downward force to the plunger rod <NUM> via the pressure plate <NUM> as the cradle <NUM> moves between the first position P1 and the second position P2. The pressure plate <NUM> is elongated with a ramped surface <NUM> at the inlet <NUM> to receive the proximal rod end <NUM> without colliding with the body <NUM> of the plunger rod <NUM>.

The pressure plate <NUM> is slidably coupled to the first and second guide posts <NUM>, enabling the pressure plate <NUM> to move along the posts <NUM> in a direction parallel to the rotational axis A. The guide posts <NUM> are disposed through first and second apertures of the pressure plate <NUM> and adjustably mount the pressure plate <NUM> relative to the carriage <NUM> such that the pressure plate <NUM> is adjustable to accommodate plunger rods <NUM> and plungers <NUM> disposed at different heights. The tension spring <NUM> is disposed through a third aperture of the pressure plate <NUM> and is fixed to the top surface <NUM> of the pressure plate <NUM> so that a constant force, e.g. <NUM> N, is always applied to the plunger rod <NUM>. That is, as the plunger rod <NUM> moves from the first position P1 to the second position P2, the proximal rod end <NUM> of the plunger rod <NUM> exerts an upward force on the pressure plate <NUM> that may slightly lift the pressure plate <NUM>. But the tension spring <NUM> ensures that a sufficient non-zero force is applied to the plunger rod <NUM> to positively influence coupling of the plunger rod <NUM> to the plunger <NUM>. A threaded rod <NUM> is disposed through a bore in the base plate <NUM> and is adapted to engage a bottom surface <NUM> of the pressure plate <NUM> to adjust the height of the pressure plate <NUM> along the guide posts <NUM>.

The pressure plate <NUM> may be adjusted to accommodate for different fill levels of the syringes assemblies <NUM>, which correlate to the different positions of the plunger <NUM> within the syringe barrel <NUM>. For example, it may be desirable to fill a syringe assembly <NUM> above the syringe assembly capacity marked by a fill line, causing the plunger <NUM> to be situated at position higher than the fill line at a distal end <NUM> of the syringe assembly <NUM>. In another example, it may be desirable to fill the syringe assembly <NUM> below the syringe assembly capacity fill line, thereby causing the plunger <NUM> to be situated at a position lower than the fill line. To accommodate for a different fill level or plunger rod height, the position of the pressure plate <NUM> relative to the cradle <NUM> may be adjusted by rotating the threaded rod <NUM> in the clockwise direction or counterclockwise to raise or lower the pressure plate <NUM>, respectively. A ruler <NUM> can be attached to the guide assembly <NUM> and remains stationary relative to the pressure plate <NUM> when the pressure plate <NUM> moves. The ruler <NUM> can be used to measure the distance the pressure plate <NUM> must be adjusted to accommodate for standard fill levels. For example, a syringe assembly <NUM> having a <NUM> volume capability may be filled to a fill level below or above a <NUM> fill line. The fill level determined by measured rulings on the syringe barrel <NUM> may indicate by how much the position of the pressure plate <NUM> may need to be adjusted outside the standard fill levels. The machine <NUM> and systems disclosed herein may be configured to operate with any number of different syringe assemblies <NUM>, and are not limited to the <NUM> and <NUM> sizes described herein.

According to the present disclosure, the machine <NUM> is configured to index the cradle <NUM> to couple the plunger rod <NUM> to the syringe assembly <NUM>. In a single indexed rotation, the distal end <NUM> of the plunger rod <NUM> can threadably couple to internal threads of the plunger <NUM> disposed in the proximal end <NUM> of the syringe assembly <NUM>. For example, the loaded cradle <NUM> moves the plunger rod <NUM> to engage the pressure plate <NUM> while the friction element <NUM> engages the syringe barrel <NUM> to spin the syringe assembly <NUM>. The combination of the downward force applied to the plunger rod <NUM> by the pressure plate <NUM> and the rotational force applied to the syringe assembly <NUM> induced by the friction element <NUM> permits the threaded distal end <NUM> of the plunger rod <NUM> to couple to the threaded surface of the plunger <NUM>. In some versions, the machine may not include the pressure plate <NUM> at all and in such versions, coupling of the plunger rod <NUM> to the plunger <NUM> can be effected solely by the friction element <NUM> imparting a rotational force on the syringe barrel <NUM>. In yet other versions, the machine <NUM> may not include a friction element <NUM> at all, and in those versions, coupling of the plunger rod <NUM> to the plunger <NUM> can be effected solely by applying a downward force to the plunger rod <NUM> with the pressure plate <NUM>. In the latter configuration, the plunger rod <NUM> may not need to be threaded into the plunger <NUM>, but rather simply friction fitted.

The machine <NUM> is arranged or programmed to index the cradle <NUM> such that the loaded cradle <NUM> moves between the first position P1 and the second position P2 in one movement of the carriage <NUM>. The actuating device <NUM>, which is operatively connected to the carriage <NUM>, is adapted to index the cradle <NUM> so that the plunger rod <NUM> and syringe assembly <NUM> are coupled in less than three seconds. Each index of the cradle <NUM> may include rotating the carriage <NUM> approximately one third of a complete <NUM> degrees rotation, such as <NUM> degrees about the rotational axis A. For example, the cradle <NUM> in the first position P1 may be rotated about the axis A of the carriage <NUM> approximately <NUM> degrees relative to the first position P1 to reach the second position P2. Depending on the position of the guide assembly <NUM> and size of the carriage <NUM>, the carriage <NUM> may be configured to index the cradle <NUM> in rotations less than <NUM> degrees about the axis A. In this way, the machine <NUM> limits instances of user-error or repetitive starting and stopping a continuously run machine. The machine <NUM> is configured to couple one plunger rod <NUM> to one syringe assembly <NUM> at a time.

The actuating device <NUM> may be arranged or programmed to index the cradle <NUM> via the carriage <NUM> only once upon an activation event. An activation event may be, for example, manually manipulating a lever <NUM> of the actuating device <NUM> or triggering a switch. One pull of the lever <NUM>, for example, activates a servomotor or other mechanically-driven system of the actuating device <NUM> to index the cradle <NUM> between the first position P1 and the second position P2. The actuating device <NUM> may be further programmed so that the carriage <NUM> will not rotate until the lever <NUM> is pulled again or when some other activation event occurs. In other embodiments, the machine <NUM> may be actuated using another suitable mechanism other than the lever <NUM>.

The lever <NUM> of the non-automated machine <NUM> illustrated in <FIG> is operatively coupled to the carriage <NUM> and adapted to index the cradle <NUM> between the first position P1 and the second position P2. The lever <NUM> is movably attached to the base <NUM> and disposed within a slot <NUM>. When the lever <NUM> is pulled from a resting position to a left-most end of the slot <NUM>, the carriage <NUM> rotates until the lever <NUM> returns to its initial resting position in the slot <NUM>. The lever <NUM> may be coupled to a mechanically-operated device or electrically-powered drive mechanism housed in the base <NUM> that converts the motion of the lever <NUM> to rotational motion of the carriage <NUM>. In another embodiment, the actuating device <NUM> may be arranged or programmed to index the cradle <NUM> more than once upon the activation event. For example, the slot <NUM> of the lever <NUM> may be marked to indicate where the lever <NUM> can be pulled index the cradle <NUM> a certain number of times. For example, when the lever <NUM> is pulled to a first activated position, the cradle <NUM> indexes once; and when the lever <NUM> is pulled to a further second activated position along the slot <NUM>, the cradle <NUM> indexes twice.

<FIG> and <FIG> illustrate an adaptive system <NUM> to convert the non-automated machine <NUM> of <FIG> into a semi-automated plunger rod assembly system <NUM>. <FIG> illustrates the adaptive system <NUM> and <FIG> depicts the machine <NUM> of <FIG> stationed on an actuating platform <NUM> of the adaptive system <NUM>. The actuating platform <NUM> receives and secures the base <NUM> of the machine <NUM> to a table <NUM>. A rigid member <NUM> is movably attached to the table <NUM> and extends vertically from the table <NUM> through a semi-circular bracket <NUM>. The rigid member <NUM> carries the semi-circular bracket <NUM>, which is adapted to smoothly glide on the surface of the table <NUM>, when the rigid member <NUM> is actuated to move the lever <NUM>. As shown in <FIG>, the rigid member <NUM> is positioned adjacent to the lever <NUM> of the machine <NUM> when the lever <NUM> is in the resting or non-activated position. The semi-circular bracket <NUM> is shaped to match the contoured perimeter of the base <NUM>. A servomotor <NUM> attached to the table <NUM> is operatively connected to the rigid member <NUM> via wiring disposed beneath the table <NUM>. First and second two hand anti-tie down operation switches <NUM> are secured to opposite sides of the table <NUM> and are positioned to permit an operator to trigger the operation switches <NUM> simultaneously. The operation switches <NUM> are coupled to the servomotor <NUM> and are configured to trigger the servomotor <NUM> only when the switches <NUM> are pressed simultaneously. In operation, the servomotor <NUM> actuates the rigid member <NUM> to engage the lever <NUM> of the machine <NUM> and move the lever <NUM> within the slot <NUM>. The rigid member <NUM> moves in an arc-shaped path to engage the lever <NUM> until the lever <NUM> reaches the left-most end of the slot <NUM>. The servomotor <NUM> may be programmed to move the rigid member <NUM> only once when both operating switches <NUM> are triggered to index the cradle <NUM>. In another embodiment, the servomotor <NUM> may be programmed to index more than once if desired. In this case, a control panel coupled to the activation switches <NUM> and the servomotor <NUM> may be configured to either index the cradle <NUM> more than once when a control panel switch is activated.

The adaptive system <NUM> of <FIG> and <FIG> illustrates a plunger rod assembly system capable of converting the non-automated plunger rod assembly system <NUM> into a semi-automated system using the existing machine <NUM> of <FIG>. In the following <FIG>, a semi-automated plunger rod assembly system <NUM> is illustrated in accordance with another embodiment of the present disclosure. The plunger rod assembly system <NUM> is similar to the machine <NUM> described above, except that the system <NUM> is semi-automated and includes a different actuating device <NUM>. Elements of the system <NUM> in <FIG> which are similar to the elements of the machine <NUM> are designated by the same reference numeral, incremented by <NUM>. A description of many of these elements is abbreviated or even eliminated in the interest of brevity.

The plunger rod assembly system <NUM> of <FIG> includes a machine <NUM> and exit chute <NUM> secured to a removable base plate <NUM>. The base plate <NUM> is removably attached to a table <NUM> by a plurality of quick-change fasteners <NUM>. An actuating device <NUM> is operatively coupled to a carriage <NUM> and adapted to index a cradle <NUM> carried by the carriage <NUM> from a first position P1 to a second position P2 to couple a plunger rod <NUM> to a syringe assembly <NUM>. The plunger rod <NUM> and the syringe assembly <NUM> are not shown with the plunger rod assembly system <NUM>, but may be positioned or attached to the machine <NUM> in the same or similar manner as described and illustrated in the previous figures. The actuating device <NUM> includes a servomotor <NUM> and first and second operation switches <NUM> for operatively controlling the servomotor <NUM>. The servomotor <NUM>, shown in <FIG>, is attached to the table <NUM> and positioned below the machine <NUM> so that the servomotor <NUM> can directly connect to the carriage <NUM>.

To changeover to a different size syringe assembly <NUM>, the carriage <NUM> may be selected from separate and interchangeable first and second carriages. The system <NUM> is configured to permit an operator to easily remove the selected carriage <NUM> and/or machine <NUM> from the servomotor <NUM>, which is removably coupled or attached to the table <NUM>, and replace the selected carriage <NUM> with a first carriage capable of receiving a different size syringe assembly <NUM>. The first carriage <NUM> includes a cradle <NUM> having a seat portion <NUM> sized to receive a syringe assembly <NUM> of a first size, such as <NUM> syringe, and the second carriage includes a cradle having a seat portion sized to receive a syringe assembly of a second size, such as <NUM> syringe. The servomotor <NUM> of the actuating device <NUM> is adapted to couple to a base portion <NUM> of the first carriage <NUM> and a base portion of the second carriage. For example, the servomotor <NUM> may include a spline shaft <NUM> or other suitable device extending into a receiving member <NUM> disposed in the base portion <NUM> of the carriage <NUM>. The receiving member <NUM> of both the first carriage <NUM> and the second carriage is adapted to couple with the spline shaft <NUM> of the servomotor <NUM> when the base <NUM> of the machine <NUM> is attached to the table <NUM>. The machine <NUM> and exit chute <NUM> may be interchangeable with a second machine and second exit chute. Each machine <NUM> may include an attached guide assembly <NUM> and pre-force plunger unit <NUM> adapted to interact with the carriage <NUM> as described above in connection with the machine <NUM> of <FIG>.

For example, selected carriage <NUM> may be chosen by the operator based on the size of the syringe assembly <NUM> to be assembled. Each selected carriage <NUM> may correspond to a selected pressure plate <NUM>, a selected friction element <NUM>, and a selected guide plate <NUM>. The first carriage <NUM> includes a first pressure plate <NUM> coupled to the carriage <NUM>, and the second carriage includes a second pressure plate coupled to the second carriage. The first carriage <NUM> includes a first guide plate <NUM> coupled to the first carriage <NUM> and carrying a first friction element <NUM>, and the second carriage includes a second guide plate coupled to the second carriage and carrying a second friction element. Accordingly, the selected pressure plate <NUM> is coupled to the selected carriage <NUM>, and the selected friction element <NUM> is carried by a selected guide plate <NUM> coupled to the selected carriage <NUM>.

According to a preferred method of using the plunger rod assembly system <NUM> and <NUM>, the method may include positioning a syringe assembly <NUM> onto a cradle <NUM> and <NUM> of a carriage <NUM> and <NUM>, where the cradle <NUM> and <NUM> of the carriage <NUM> and <NUM> is sized to receive a syringe assembly <NUM> of a specific size. The syringe assembly <NUM> includes a distal end <NUM> and a proximal end <NUM>, a syringe barrel <NUM>, and a plunger <NUM> disposed within the syringe barrel <NUM>. A plunger rod <NUM> is positioned onto the cradle <NUM> and <NUM> of the carriage <NUM> and <NUM>, where the plunger rod <NUM> includes a distal rod end <NUM> and a proximal rod end <NUM> where the distal rod end <NUM> is disposed above the proximal end <NUM> of the syringe assembly <NUM> and is axially aligned with the plunger <NUM>. After both the plunger rod <NUM> and the first syringe assembly <NUM> are positioned onto the cradle <NUM> and <NUM>, the method includes activating the actuating device <NUM> and <NUM> coupled to the carriage <NUM> and <NUM> to move the cradle <NUM> and <NUM> from a position P1 to a second position P2, thereby applying a force to the plunger rod <NUM> causing the plunger rod <NUM> to become coupled to the syringe assembly <NUM>.

Activating the actuating device <NUM> and <NUM> includes rotating the carriage <NUM> and <NUM> so that the cradle <NUM> and <NUM> indexes from the first position P1 to the second position P2, where the syringe assembly <NUM> and the plunger rod <NUM> are positioned onto the cradle <NUM> and <NUM> in the first position P1 and the plunger rod <NUM> is coupled to the syringe assembly <NUM> in the second position P2. Further, the method includes rotating the carriage <NUM> and <NUM> about the axis A. When the cradle <NUM> and <NUM> is between the first and second positions P1 and P2, the method includes applying a downward force to the proximal rod end <NUM> of the plunger rod <NUM> when the cradle <NUM> and <NUM> moves from the first position P1 toward the second position P2. Applying a downward force to the proximal end <NUM> of the plunger rod <NUM> includes moving the plunger rod <NUM> beneath a pressure plate <NUM> and <NUM> positioned adjacent to the carriage <NUM> and <NUM> when the cradle <NUM> and <NUM> moves from the first position P1 to the second position P2. Further, the method includes applying a rotational force to a syringe barrel <NUM> of the syringe assembly <NUM> as the cradle <NUM> and <NUM> moves from the first position P1 to the second position P2. Applying the rotational force includes engaging the syringe assembly <NUM> with a friction element <NUM> and <NUM> disposed adjacent to the carriage <NUM> and <NUM> when the cradle <NUM> and <NUM> moves from the first position P1 and the second position P2. As the carriage <NUM> and <NUM> rotates in a first direction, rotating the syringe assembly <NUM> includes engaging the syringe barrel <NUM> with the friction element <NUM> and <NUM> and rotating the syringe assembly <NUM> in a direction opposite the first direction of rotation of the carriage <NUM> and <NUM>.

To changeover the machine <NUM> and <NUM> in the second and third plunger rod assembly systems <NUM> and <NUM> of <FIG>, the method further includes decoupling a carriage, e.g. a second carriage, from the actuating device <NUM> and <NUM>. If required, the method may include decoupling the second carriage from the table <NUM> by unlocking a plurality of quick-release or quick-change fasteners <NUM> to remove a second base plate from the table <NUM>. Additionally, decoupling the second carriage from the actuating device <NUM> includes decoupling a spline shaft <NUM> of the servomotor <NUM> from a receiving member of the second carriage. Further, the method includes coupling the first carriage <NUM> and <NUM> to the actuating device <NUM> and <NUM> after decoupling the second carriage from the actuating device <NUM> and <NUM>. Coupling the first carriage <NUM> and <NUM> to the actuating device <NUM> and <NUM> may include coupling the spline shaft <NUM> of the servomotor <NUM> to the receiving member <NUM> of the first carriage <NUM> and <NUM>. The first carriage <NUM> and <NUM> includes a first movable cradle <NUM> and <NUM> adapted to receive a syringe assembly <NUM> of a first size. Additionally, the method may include fastening the first carriage <NUM> and <NUM> to the table <NUM> and/or base plate <NUM> by quick-change fasteners <NUM>. The method further includes positioning a first syringe assembly <NUM> and a first plunger rod <NUM> onto the first movable cradle <NUM> and <NUM> of the first carriage <NUM> and <NUM>. After both the first plunger rod <NUM> and the first syringe assembly <NUM> are positioned onto the cradle <NUM> and <NUM>, the method includes activating the actuating device <NUM> and <NUM> coupled to the first carriage <NUM> and <NUM> to move the first cradle <NUM> and <NUM> from the first position P1 to the second position P2, thereby applying a force to the first plunger rod <NUM> causing the first plunger rod <NUM> to become coupled to the first syringe assembly <NUM>. As recited above, the method includes applying a downward force to the proximal end <NUM> of the first plunger rod <NUM> and/or a rotational force to the syringe barrel <NUM> of the first syringe assembly when the first cradle <NUM> and <NUM> moves from the first position P1 to the second position P2. The method steps may be repeated to changeover the machine <NUM> and <NUM> to accommodate different sizes of syringe assemblies <NUM>.

Prior to operating the plunger rod assembly system <NUM>, <NUM>, and <NUM>, the actuating device <NUM> and <NUM> may be programmed to index the cradle <NUM> and <NUM> via the carriage <NUM> and <NUM> only once upon an activation event. Indexing the cradle <NUM> and <NUM> from the first position P1 to the second position P2 includes rotating the carriage <NUM> and <NUM> about the rotational axis A to couple the plunger rod <NUM> and the syringe assembly <NUM>. Rotating the carriage <NUM> and <NUM> may include rotating the carriage <NUM> and <NUM> less than <NUM> degrees to move the cradle <NUM> and <NUM> from the first position P1 to the second position P2. When operating the first example machine <NUM>, activating the actuating device <NUM> includes manually moving the lever <NUM> to rotate the carriage <NUM> and index the cradle <NUM> from the first position P1 to the second position P2. When operating the machine <NUM> with the adaptive actuating system <NUM> of <FIG> and <FIG>, activating the actuating device <NUM> includes triggering the operation switch <NUM> coupled to the servomotor <NUM> to slide the rigid member <NUM> and bracket <NUM> into engagement with the lever <NUM>. When operating the third example system <NUM>, activating the actuating device <NUM> includes triggering the operation switch <NUM> coupled to the servomotor <NUM> connected to the carriage <NUM>.

In other embodiments, the machine <NUM> and <NUM> may be adapted to couple a plunger rod and a plunger of a syringe assembly according to the mating relationship of the plunger rod and the plunger. For example, the illustrated machines <NUM> and <NUM> are designed to couple the threaded distal end <NUM> the plunger rod <NUM> to the threaded surface of the plunger <NUM> by applying both a downward force to the plunger rod <NUM> and a rotational force to the syringe barrel <NUM>. In another example, the plunger rod assembly system <NUM> and <NUM> may be adapted to couple a plunger rod <NUM> to a plunger <NUM> having a snap-fit mating relationship. In this example, each machine <NUM> and <NUM> may be configured to apply a downward force to the plunger rod <NUM> to sufficiently couple the plunger rod <NUM> and the plunger <NUM> without spinning the syringe assembly <NUM> relative to the cradle <NUM> and <NUM>. The friction element <NUM> and <NUM> may be removed from the guide plate <NUM> and <NUM> so that the syringe assembly <NUM> does not rotate relative to the cradle <NUM> and <NUM> and the plunger rod <NUM>.

The plunger rod assembly systems disclosed herein provide considerable benefits over current methods of automated plunger rod assembly systems. The non-automated and the semi-automated systems have a greatly reduced footprint compared to existing automated machines configured to assemble large batches. The disclosed system is an economical and efficient alternative over the existing automated machine. Typically, a small demand for plunger rod and syringe assemblies cannot justify the large capital investment for purchasing, operating, and maintaining expensive and complex automated machines designed to prepare large batches. However, the disclosed systems <NUM> and <NUM> are especially useful for assembling small batches of plunger rod syringe assemblies where access to fully automated machines is limited or unaffordable. Additionally, the disclosed systems are configured to index so that a plunger rod and syringe assembly are positioned onto the carriage and coupled before another plunger rod and syringe assembly are attached to, or positioned onto, the carriage. The indexing feature improves safety and reduces operator error because the systems are preconfigured to assemble plunger rod syringe assemblies without requiring the operator to know each step of the operating sequence or to interfere with the machinery between assembly steps. Additionally, the two hand anti-tie down operation switches ensure that the machine <NUM> and <NUM> cannot operate unless both hands of an operator trigger the switches. In other words, accidental operation or switching-on the machine would be greatly reduced if not completely prevented. The disclosed systems <NUM> and <NUM> are very simple to load, operate, and unload and do not require complex training, specialized education, or technical expertise to use the machinery. Both of these features of the disclosed systems may promote affordability and access to plunger rod syringe assembly technology.

The semi-automated systems greatly simply the operation of the assembly and process for adjusting and/or interchanging the components to assemble syringe assemblies of different sizes, materials, and fill levels. For example, the changeover process to adapt existing machines to assemble more than one size syringe assembly size is generally labor-intensive and requires disassembly, retooling, and re-assembly before operating the machine. In contrast, certain components of the disclosed plunger rod assembly systems can easily be replaced or adjusted within minutes and without requiring any additional tooling to changeover to assemble a syringe assembly of a different size. These features reduce costs of time and skilled labor and increase convenience and efficiency.

The above description describes various systems and methods for use with a plunger rod and syringe assembly system. It should be clear that the system, machine or methods can further comprise use of a medicament listed below with the caveat that the following list should neither be considered to be all inclusive nor limiting. The medicament will be contained in a reservoir of the syringe barrel of the syringe assembly. In some instances, the reservoir is a primary container that is either filled or pre-filled for treatment with the medicament. The primary container can be a pre-filled syringe.

For example, the syringe or syringe assembly may be filled with colony stimulating factors, such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neupogen® (filgrastim) and Neulasta® (pegfilgrastim). In various other embodiments, the drug delivery device may be used with various pharmaceutical products, such as an erythropoiesis stimulating agent (ESA), which may be in a liquid or a lyophilized form. An ESA is any molecule that stimulates erythropoiesis, such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta), Hematide®, MRK-<NUM>, INS-<NUM>, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin zeta, epoetin theta, and epoetin delta, as well as the molecules or variants or analogs thereof as disclosed in the following patents or patent applications.

<CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>; and <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>.

An ESA can be an erythropoiesis stimulating protein. As used herein, "erythropoiesis stimulating protein" means any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to and causing dimerization of the receptor. Erythropoiesis stimulating proteins include erythropoietin and variants, analogs, or derivatives thereof that bind to and activate erythropoietin receptor; antibodies that bind to erythropoietin receptor and activate the receptor; or peptides that bind to and activate erythropoietin receptor. Erythropoiesis stimulating proteins include, but are not limited to, epoetin alfa, epoetin beta, epoetin delta, epoetin omega, epoetin iota, epoetin zeta, and analogs thereof, pegylated erythropoietin, carbamylated erythropoietin, mimetic peptides (including EMP1/hematide), and mimetic antibodies. Exemplary erythropoiesis stimulating proteins include erythropoietin, darbepoetin, erythropoietin agonist variants, and peptides or antibodies that bind and activate erythropoietin receptor (and include compounds reported in <CIT> and <CIT>) as well as erythropoietin molecules or variants or analogs thereof as disclosed in the following patents or patent applications. <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>;<CIT>; <CIT>; <CIT>;<CIT>;<CIT>; <CIT>; <CIT>; <CIT>;<CIT>; <CIT>; <CIT>;<CIT>; <CIT>; <CIT>;<CIT>;<CIT>; <CIT>; <CIT>;<CIT>;<CIT>; <CIT>; <CIT>;<CIT>; <CIT>; <CIT>; <CIT>; and <CIT>; and <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; <CIT>; and <CIT>.

Examples of other pharmaceutical products for use with the device may include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab) and Prolia™ (denosamab); other biological agents such as Enbrel® (etanercept, TNF-receptor /Fc fusion protein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim , G-CSF, hu-MetG-CSF), and Nplate® (romiplostim); small molecule drugs such as Sensipar® (cinacalcet). The device may also be used with a therapeutic antibody, a polypeptide, a protein or other chemical, such as an iron, for example, ferumoxytol, iron dextrans, ferric glyconate, and iron sucrose. The pharmaceutical product may be in liquid form, or reconstituted from lyophilized form.

Among particular illustrative proteins are the specific proteins set forth below, including fusions, fragments, analogs, variants or derivatives thereof:.

OPGL specific antibodies, peptibodies, and related proteins, and the like (also referred to as RANKL specific antibodies, peptibodies and the like), including fully humanized and human OPGL specific antibodies, particularly fully humanized monoclonal antibodies, including but not limited to the antibodies described in <CIT> as to OPGL specific antibodies and antibody related proteins, particularly those having the sequences set forth therein, particularly, but not limited to, those denoted therein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, including the OPGL specific antibodies having either the light chain of SEQ ID NO:<NUM> as set forth therein in <FIG> and/or the heavy chain of SEQ ID NO:<NUM>, as set forth therein in <FIG>.

Myostatin binding proteins, peptibodies, and related proteins, and the like, including myostatin specific peptibodies, particularly those described in <CIT> and PCT Publication No. WO particularly in parts pertinent to myostatin specific peptibodies, including but not limited to peptibodies of the mTN8-<NUM> family, including those of SEQ ID NOS:<NUM>-<NUM>, including TN8-<NUM>-<NUM> through TN8-<NUM>-<NUM>, TN8-<NUM> con1 and TN8-<NUM> con2; peptibodies of the mL2 family of SEQ ID NOS:<NUM>-<NUM>; the mL15 family of SEQ ID NOS:<NUM>-<NUM>; the mL17 family of SEQ ID NOS:<NUM>-<NUM>; the mL20 family of SEQ ID NOS:<NUM>-<NUM>; the mL21 family of SEQ ID NOS:<NUM>-<NUM>; the mL24 family of SEQ ID NOS:<NUM>-<NUM>; and those of SEQ ID NOS:<NUM>-<NUM>.

IL-<NUM> receptor specific antibodies, peptibodies, and related proteins, and the like, particularly those that inhibit activities mediated by binding of IL-<NUM> and/or IL-<NUM> to the receptor, including those described in <CIT> or PCT Application No. <CIT> and in <CIT>, particularly in parts pertinent to IL-<NUM> receptor specific antibodies, particularly such antibodies as are described therein, particularly, and without limitation, those designated therein: L1H1; L1H2; L1H3; L1H4; L1H5; L1H6; L1H7; L1H8; L1H9; L1H10; L1H11; L2H1; L2H2; L2H3; L2H4; L2H5; L2H6; L2H7; L2H8; L2H9; L2H10; L2H11; L2H12; L2H13; L2H14; L3H1; L4H1; L5H1; L6H1.

Interleukin <NUM>-receptor <NUM> ("IL1-R1") specific antibodies, peptibodies, and related proteins, and the like, including but not limited to those described in <CIT>, in parts pertinent to IL1-R1 specific binding proteins, monoclonal antibodies in particular, especially, without limitation, those designated therein: 15CA, 26F5, 27F2, 24E12, and 10H7.

Ang2 specific antibodies, peptibodies, and related proteins, and the like, including but not limited to those described in <CIT> and <CIT> particularly in parts pertinent to Ang2 specific antibodies and peptibodies and the like, especially those of sequences described therein and including but not limited to: L1(N); L1(N) WT; L1(N) <NUM> WT; 2xL1(N); 2xL1(N) WT; Con4 (N), Con4 (N) <NUM> WT, 2xCon4 (N) <NUM>; L1C; L1C <NUM>; 2xL1C; Con4C; Con4C <NUM>; 2xCon4C <NUM>; Con4-L1 (N); Con4-L1C; TN-<NUM>-<NUM> (N); C17 (N); TN8-<NUM>(N); TN8-<NUM> (N); Con <NUM> (N), also including anti-Ang <NUM> antibodies and formulations such as those described in <CIT> as to the same, particularly Ab526 Ab528; Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12; AblA1; AbIF; AbIK, AbIP; and AbIP, in their various permutations as described therein, as disclosed in the foregoing publication;.

CD22 specific antibodies, peptibodies, and related proteins, and the like, such as those described in <CIT>, as to CD22 specific antibodies and related proteins particularly human CD22 specific antibodies, such as but not limited to humanized and fully human antibodies, including but not limited to humanized and fully human monoclonal antibodies, particularly including but not limited to human CD22 specific IgG antibodies, such as, for instance, a dimer of a human-mouse monoclonal hLL2 gamma-chain disulfide linked to a human-mouse monoclonal hLL2 kappa-chain, including, but limited to, for example, the human CD22 specific fully humanized antibody in Epratuzumab, <NPL>;.

IGF-<NUM> receptor specific antibodies, peptibodies, and related proteins, and the like, such as those described in <CIT>, as to IGF-<NUM> receptor specific antibodies and related proteins, including but not limited to the IGF-<NUM> specific antibodies therein designated L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11, L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L30H30, L31H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1R-binding fragments and derivatives thereof.

Also among non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the present invention are each and all of those described in:.

Also included can be a sclerostin antibody, such as but not limited to romosozumab, blosozumab, or BPS <NUM> (Novartis). Further included can be therapeutics such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA. Additionally, included in the device can be a monoclonal antibody (IgG) that binds human Proprotein Convertase Subtilisin/Kexin Type <NUM> (PCSK9), e.g. <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, and <CIT>.

Also included can be talimogene laherparepvec or another oncolytic HSV for the treatment of melanoma or other cancers. Examples of oncolytic HSV include, but are not limited to talimogene laherparepvec (<CIT> and <CIT>); OncoVEXGALV/CD (<CIT>); OrienX010 (<NPL>); G207, <NUM>; NV1020; NV12023; NV1034 and NV1042 (<NPL>).

Also included are TIMPs. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) and are important in many natural processes. TIMP-<NUM> is expressed by various cells or and is present in the extracellular matrix; it inhibits all the major cartilage-degrading metalloproteases, and may play a role in role in many degradative diseases of connective tissue, including rheumatoid arthritis and osteoarthritis, as well as in cancer and cardiovascular conditions. The amino acid sequence of TIMP-<NUM>, and the nucleic acid sequence of a DNA that encodes TIMP-<NUM>, are disclosed in <CIT>.

Description of TIMP mutations can be found in <CIT> and <CIT>.

Also included are antagonistic antibodies for human calcitonin gene-related peptide (CGRP) receptor and bispecific antibody molecule that target the CGRP receptor and other headache targets. Further information concerning these molecules can be found in <CIT>.

Additionally, a bispecific T cell engager antibody (BiTe), e.g. Blinotumomab can be used in the device. Alternatively, included can be an APJ large molecule agonist e.g., apelin or analogues thereof in the device. Information relating to such molecules can be found in <CIT>.

In certain embodiments, the medicament comprises a therapeutically effective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptor antibody. Examples of anti-TSLP antibodies that may be used in such embodiments include, but are not limited to, those described in <CIT>, and <CIT>, and <CIT>. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in <CIT>. In particularly preferred embodiments, the medicament comprises a therapeutically effective amount of the anti-TSLP antibody designated as A5 within <CIT>.

Although the plunger rod assembly systems, machine, methods, and elements thereof, have been described in terms of exemplary embodiments, they are not limited thereto. The detailed description is to be construed as exemplary only and does not describe every possible embodiment of the invention because describing every possible embodiment would be impractical, if not impossible. Numerous alternative embodiments could be implemented, using either current technology or technology developed after the filing date of this patent that would still fall within the scope of the claims defining the invention.

Claim 1:
A machine (<NUM>) for coupling a plunger roc (<NUM>) to a syringe assembly (<NUM>), the machine comprising:
a carriage (<NUM>, <NUM>) having a movable cradle (<NUM>, <NUM>) including a seat portion (<NUM>, <NUM>) sized to receive a syringe assembly and an aperture portion (<NUM>) disposed above the seat portion sized to receive a plunger rod;
an actuating device (<NUM>,<NUM>) operatively coupled to the carriage, characterised in that said actuating device is further adapted to move the cradle from a first position to a second position to couple the plunger rod to the syringe assembly;
an elongated pressure plate (<NUM>) positioned adjacent to the carriage and defining an inlet (<NUM>) and an outlet (<NUM>), the inlet being sized to receive a proximal end of the plunger rod and apply a downward force on the proximal end of the plunger rod as the plunger rod moves from the inlet to the outlet; and
a constant tension spring (<NUM>) coupled to the pressure plate, the constant tension spring providing a downward force to the pressure plate such that the downward force is transferred to the plunger rod via the pressure plate as the cradle moves between the first position and the second position.