Plunger rod / syringe assembly system and method

Abstract

To provide a mechanism coupling a plunger rod to a syringe assembly.SOLUTION: A machine for coupling a plunger rod to a syringe assembly may include a carriage including a cradle having a seat portion sized to receive the syringe assembly and an aperture portion disposed above the seat portion and sized to receive the 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 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 includes a cradle sized to receive a syringe assembly of a second size that is different from the first size.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 477,521, filed Mar. 28, 2017, the entire contents of which are incorporated herein by reference.

[0002] This disclosure generally relates to medical syringes, and more particularly, to mechanisms and methods for coupling a plunger rod to a syringe assembly of a medical syringe.

Background Art

[0003] A typical medical syringe includes a syringe assembly containing a fluid such as a drug or formulation, and a plunger rod coupled to the syringe assembly. The plunger rod can be coupled to a plunger disposed within a barrel of the syringe assembly after the syringe is filled with fluid. The plunger can include an internal thread sized to engage a male thread at a distal end of the plunger rod. When the distal end of the plunger rod is screwed into and secured to the plunger, the plunger rod is coupled to the syringe assembly. Thereafter, a force applied to the plunger rod can advance the plunger in the barrel to dispense the fluid contained within the syringe. The plunger rod includes a proximal rod end having a flange, and an operator can press on the flange with a thumb while sandwiching the barrel between two fingers. The syringe assemblies are sized to hold different amounts of fluid, and the plunger rods can also be sized to fit their mating parts of those syringe assemblies. Care should be taken to avoid applying an excessive pressure that can prematurely discharge the fluid and / or compromise the integrity of the container closure of a sealed prefilled i.e., preloaded syringe when coupling the plunger rod to the plunger. In a prefilled syringe, the fill level of the fluid contained within the barrel can vary within a batch of prefilled syringes, and thus the position of the plunger within the barrel can also vary within the batch. As such, existing systems for coupling a plunger rod to a prefilled syringe need to be adaptable to accommodate variations in fill level to prevent premature discharge of the fluid.

[0004] A typical machine used to couple a plunger rod and a syringe assembly is fully automated and designed to perform several process steps, including loading the plunger rod and syringe assembly into the machine, operating the machine, coupling the plunger rod to the plunger, and unloading the finished product from the machine. The fully automated technique is particularly useful for preparing batches of over 2,000 coupled plunger rods and syringe assemblies. In this specification, to adjust a fully automatic machine for assembling plunger rods and syringe assemblies of different sizes, which is referred to herein as the "switching process", the machine needs to be partially disassembled, adjusted, and / or reassembled prior to operation. This switching process often requires a skilled operator to manage many components involved in the disassembly, adjustment, and tooling of the machine, and reassembly, which can be a very time-consuming procedure. Further, known machines are large in footprint and generally are stationary once established in a processing laboratory. Using such large batch machines may not be practical for small batch assembly and easy assembly of different sized syringe assemblies. Summary of the Invention Means for Solving the Problems

[0005] According to a first exemplary aspect, a machine for coupling a plunger rod to a syringe assembly may have a selected carriage that includes a cradle sized to receive the syringe assembly, the cradle having a sheet portion sized to receive the syringe assembly and an aperture portion disposed above the sheet portion and sized to receive the 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 compatible first and second carriages, the first carriage including 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 different from the first size.

[0006] According to a second exemplary aspect, a method of using a machine to couple a plunger rod to a syringe assembly may include disconnecting a second carriage from an actuating device and, after disconnecting the second carriage from the actuating device, coupling a first carriage to the actuating device, the first carriage including a first movable cradle adapted to receive a syringe assembly of a first size. Next, the method may include positioning a first syringe assembly in the first movable cradle of the first carriage, the first syringe assembly including a distal end, a proximal end, a barrel, and a plunger disposed within the barrel. Thereafter, the method may include positioning a first plunger rod in 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 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 to cause the first plunger rod to be coupled to the first syringe assembly.

[0007] According to a third exemplary aspect, a machine for coupling a plunger rod to a syringe assembly can include a carriage having a movable cradle that includes a sheet portion sized to receive the syringe assembly and an aperture portion disposed above the sheet portion and sized to receive the plunger rod. An actuating device can be operably 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 can further include an elongate 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 to apply a downward force to the proximal end of the plunger rod as the plunger rod moves from the inlet to the outlet. A constant-tension spring can be coupled to the pressure plate, the constant-tension spring providing a downward force to the pressure plate such that when the cradle moves between the first position and the second position, the downward force is transmitted to the plunger rod through the pressure plate.

[0008] According to a fourth exemplary aspect, a machine for coupling a plunger rod to a syringe assembly can include a carriage having a movable cradle that includes a sheet portion sized to receive the syringe assembly and an aperture portion disposed above the sheet portion and sized to receive the plunger rod. The machine can include an actuating device operably 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. Since a pressure plate can be positioned adjacent to the carriage, the cradle is configured to move directly beneath the pressure plate when the cradle moves from the first position to the second position, and the pressure plate is 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 can include a lever operably coupled to the carriage and adapted to be operated to index the cradle from the first position to the second position.

[0009] According to a fifth exemplary aspect, a machine for coupling a plunger rod to a syringe assembly can include a carriage having a movable cradle that includes a sheet portion sized to receive the syringe assembly and an aperture portion sized to receive the plunger rod disposed above the sheet portion. An actuating device can be operably coupled to the carriage and adapted to index the cradle only once from a first position to a second position to couple the plunger rod to the syringe assembly upon occurrence of an activation event.

[0010] According to a sixth exemplary aspect, a method of using a machine to couple a plunger rod to a syringe assembly can include positioning the syringe assembly on the movable cradle of the carriage, the syringe assembly including a distal end portion and a proximal end portion, a barrel, and a plunger disposed within the barrel at the proximal end portion of the syringe assembly. The method can then include positioning the plunger rod on the cradle, where the plunger rod can include a distal rod end portion and a proximal rod end portion, and the distal rod end portion of the plunger rod is disposed above the proximal end portion of the syringe assembly and axially aligned with the plunger. The method can include activating an actuating device operably connected to the carriage. Further, the method can include indexing the cradle only once from a first position to a second position in response to activation of the actuating device, where a force can 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 the plunger of the syringe assembly.

[0011] According to 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 sheet portion sized to receive the syringe assembly and an aperture portion sized to receive the plunger rod disposed above the sheet portion. An actuating device may be operably 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 a pressure plate, where the friction element may be adapted to engage the barrel of the syringe assembly carried by the cradle while the cradle moves from the first position to the second position, thereby applying a rotational force to the syringe assembly and spinning the syringe assembly relative to the plunger rod when the cradle moves from the first position to the second position.

[0012] According to an eighth exemplary aspect, a method of using a machine to couple a plunger rod to a syringe assembly may include positioning the syringe assembly on the movable cradle of the carriage, the syringe assembly including a distal end, a proximal end, a barrel, and a plunger disposed within the barrel at the proximal end of the syringe assembly. The method may include positioning the plunger rod on the cradle, the plunger rod including a distal rod end and a proximal rod end, and the distal rod end of the plunger rod being disposed above the proximal end of the syringe assembly and axially aligned with the plunger. The method may then include activating an actuating device operably 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 as the cradle moves between the first and second positions, thereby causing a first threaded portion of the distal rod end of the plunger rod to be threadedly coupled to a second threaded portion of the plunger of the syringe assembly.

[0013] According to 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 sheet portion sized to receive the syringe assembly and an aperture portion disposed above the sheet portion and sized to receive the plunger rod. The machine may include actuation means operatively coupled to the carriage and adapted to index the cradle only once from a first position to a second position upon the occurrence of an activation event to couple the plunger rod to the syringe assembly. A pressure plate may be positioned adjacent to the carriage such that the cradle moves directly beneath the pressure plate as the cradle moves from the first position to the second position, and the pressure plate is adapted to apply a downward force to the plunger rod disposed in the aperture portion of the cradle as the cradle moves from the first position to the second position. The actuation means may include a servo motor and an actuation switch for operatively controlling the servo motor, and the servo motor is coupled to the carriage to index the cradle via the carriage.

[0014] According to 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 sheet portion sized to receive the syringe assembly and an aperture portion disposed above the sheet portion and sized to receive the plunger rod. Actuation means 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 such that the cradle moves directly beneath the pressure plate as the cradle moves from the first position to the second position, and the pressure plate is 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 the longitudinal axes of the syringe assembly and the plunger rod when the syringe assembly and the plunger rod are disposed within the cradle, and the cradle axis is disposed at an angle greater than zero degrees relative to the vertical direction.

[0015] According to the 11th exemplary aspect, a machine for coupling a plunger rod to a syringe assembly has a carriage having a movable cradle including a sheet portion sized to receive the syringe assembly and an aperture portion disposed above the sheet portion and sized to receive the plunger rod, an operating device operably 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, wherein the cradle moves directly beneath the pressure plate when the cradle moves from the first position to the second position, and the pressure plate may include a 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 aspects (a) - (e). In aspect (a), a constant tension spring may be operably coupled to the pressure plate, and the pressure plate may define an inlet portion adapted to receive the proximal end of the plunger rod when the cradle moves from the first position to the second position. The constant tension spring may provide a downward force applied to the plunger rod via the pressure plate when the cradle moves between the first and second positions. 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 the barrel of the syringe assembly carried by the cradle while the cradle moves from the first position to the second position. The friction element may be adapted to apply a rotational force to the barrel and 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 operating device may be operably connected to the carriage and adapted to shuttle the cradle between the first and second positions in response to a triggering event. In aspect (d), the cradle may include a cradle axis that is coaxial with the longitudinal axis of the syringe assembly and the plunger rod when the syringe assembly and the plunger rod are disposed within the cradle. The cradle axis may be disposed at an angle greater than zero degrees relative to the vertical direction. 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 sheet portion sized to receive a syringe assembly of a first size, and the second carriage may include a cradle having a sheet portion sized to receive a syringe assembly of a second size.

[0016] According to a twelfth exemplary aspect, a method of using a machine to couple a plunger rod to a syringe assembly may include positioning the syringe assembly on a movable cradle of the carriage, the syringe assembly including a distal end, a proximal end, a barrel, and a plunger disposed within the barrel at the proximal end of the syringe assembly. Next, the method may include positioning the plunger rod on the cradle, where the plunger rod may include a distal rod end and a proximal rod end, and where the distal rod end of the plunger rod is disposed above the proximal end of the syringe assembly and axially aligned with the plunger. The method may include activating an actuating device operably connected to the carriage. Further, the method may include indexing the cradle two or more times from a first position to a second position in response to activation of the actuating device, where when the cradle indexes from the first position to the second position, a force is applied to either or both of the syringe assembly and the plunger rod to couple the plunger rod to the plunger of the syringe assembly.

[0017] Furthermore, according to any one or more of the first through twelfth aspects and methods described above, a machine for coupling a plunger rod to a syringe assembly and a method of using the machine may include any one or more of the following configurations or method steps.

[0018] In a preferred form, the machine may include a selected pressure plate positioned above the cradle, such that the cradle moves beneath the selected pressure plate as the cradle moves from a first position to a second position. The selected pressure plate may be adapted to apply a downward force to a plunger rod disposed in an aperture portion of the cradle as the cradle moves from the first position to the second position.

[0019] 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.

[0020] In a preferred form, the machine may include a quick-change fastener and a table, such that the selected carriage may be removably coupled to the table by the quick-change fastener.

[0021] 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 operating equipment may include a servo motor adapted to be operably connected to the first and second bases.

[0022] 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 a syringe assembly carried by the cradle while 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 as the cradle moves from the first position to the second position.

[0023] In a preferred form of the machine, the first carriage may include a first guide plate coupled to the first carriage and supporting a first friction element, and the second carriage may include a second guide plate coupled to the second carriage and supporting a second friction element, so that the selected friction element is supported by the selected guide plate coupled to the selected carriage.

[0024] In a preferred form, the machine may include a selected constant tension spring operably coupled to a selected pressure plate. The selected pressure plate defining an inlet portion may be adapted to receive the proximal end of the plunger rod as the cradle moves from the first position to the second position. The selected constant tension spring may provide a downward force applied by the selected pressure plate to the plunger rod as the cradle moves between the first and second positions.

[0025] In a preferred form, the machine may include a servo motor and an operating switch for operably controlling the servo motor, the servo motor being coupled to the carriage to move the cradle via the carriage.

[0026] In a preferred form of the machine, the inlet may include an inclined surface positioned above the outlet with respect to the carriage.

[0027] In a preferred form, the machine may include at least one guide post, and the pressure plate is slidably coupled to at least one guide post in a direction parallel to the longitudinal axis of the carriage.

[0028] In a preferred form, the machine may include a threaded rod for adjustably mounting the pressure plate with respect to the carriage, so that the pressure plate is adjustable in a direction parallel to the longitudinal axis of the carriage to accommodate plunger rods of different heights.

[0029] In a preferred form, the machine may include a friction element adjacent to the carriage and disposed below the pressure plate. The friction element may be adapted to engage the syringe barrel of the syringe assembly carried by the carriage as the carriage 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.

[0030] In a preferred form of the machine, the friction element may be fixedly secured immovably relative to the carriage.

[0031] In a preferred form, the machine may include a guide plate, and the friction element may be fixed to the guide plate.

[0032] In a preferred form of the machine, the friction element may be an elongated cord.

[0033] In a preferred form of the machine, the friction element may be an elastomeric material.

[0034] In a preferred form of the machine, the actuating device may be adapted to shuttle the carriage between the first and second positions in response to an activation event.

[0035] In a preferred form of the machine, the actuating device may shuttle the carriage only once upon occurrence of the activation event.

[0036] In a preferred form of the machine, the actuating device may shuttle the carriage two or more times upon occurrence of the activation event.

[0037] In a preferred form of the machine, the actuating device may include a lever for the user to manually shuttle the carriage from the first position to the second position.

[0038] In a preferred form of the machine, the lever may be movably attached to the base of the carriage, and the lever may be arranged to effect the activation event as the lever moves from the rest position to the activation position.

[0039] In a preferred form of the machine, the actuating device may include a motor-operated bracket disposed adjacent to the lever, and the bracket may be adapted to move the lever between a rest position and a starting position.

[0040] In a preferred form of the machine, the actuating device may include a slidable bracket arranged to move the lever.

[0041] In a preferred form, the machine may include a pressure plate positioned adjacent to the carriage, such that when the cradle moves from a first position to a second position, the cradle moves directly beneath the pressure plate, and the pressure plate is adapted to apply a downward force to a plunger rod disposed in an aperture portion of the cradle when the cradle moves from the first position to the second position.

[0042] In a preferred form, the machine may include a two-hand anti-tie down operation switch arranged to perform a starting event.

[0043] In a preferred form of the machine, the actuating device may include a lever operably coupled to the carriage, and the lever is arranged to manually operate the performance of a starting event.

[0044] In a preferred form of the machine, the actuating device may include a lever for the user to manually index the cradle from a first position to a second position.

[0045] 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 engage a syringe barrel of a syringe assembly and be adapted to hold the syringe barrel within the gap when carried by the cradle, and the first and second rollers allow the syringe assembly to spin when the cradle indexes from the first position to the second position.

[0046] In a preferred form of the machine, each of the first and second rollers may include a rotation axis, the first roller is rotatable about the rotation axis of the first roller, and the second roller is rotatable about the rotation axis of the second roller.

[0047] In a preferred form of the machine, the servo motor may be programmed to move the carriage in response to a startup event, the startup event including triggering an operation switch.

[0048] In a preferred form of the machine, the servo motor may be programmed to divide and feed the cradle two or more times in response to a startup event.

[0049] In a preferred form of the machine, the servo motor may be adapted to be operably coupled to different carriages.

[0050] In a preferred form of the machine, the cradle may include a cradle axis that is coaxial with the longitudinal axes of the syringe assembly and the plunger rod when the syringe assembly and the plunger rod are disposed within the cradle, and the cradle axis is disposed at an angle greater than zero degrees with respect to the vertical direction.

[0051] In a preferred form of the machine, the carriage may include a rotational carousel having a rotation axis parallel to the cradle axis, and the rotation axis of the carriage is disposed at an angle greater than zero degrees with respect to the vertical direction.

[0052] In a preferred form of the machine, the base may include a bottom surface disposed at a first angle with respect to the horizontal, and the longitudinal axis of the cradle is offset from the vertical by the first angle.

[0053] 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 the flanged proximal end of the plunger rod, the orifice being aligned coaxially with the aperture portion of the cradle. The plunger rod base may be movable with the cradle from a first position to a second position.

[0054] In a preferred form, the machine may include a retaining cap having an outwardly extending tab disposed to extend into the orifice of the plunger rod base, the retaining cap being removably attached to the plunger rod base. The retaining cap may be fixed relative to the carriage and may be disposed within the orifice when the cradle is in the first position.

[0055] In a preferred form, the machine may include a selected movable plunger rod base coupled to a selected carriage.

[0056] In a preferred form of the machine, the plunger rod base may be selected from separate and compatible 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 being sized to receive a flanged plunger rod end of a second size different from the first size.

[0057] In a preferred form of the machine, the carriage may be rotatably disposed relative to the pressure plate.

[0058] In a preferred form of the machine, the carriage may include a plurality of cradles supported by the carriage.

[0059] In a preferred form, the machine may include an outlet chute adjacent to the carriage and disposed at a second position of the cradle. The outlet chute may be adapted to receive the plunger rod and the syringe assembly from the cradle after the plunger rod is coupled to the syringe assembly.

[0060] In a preferred form, the first carriage may include a first outlet chute coupled to the first carriage, and the second carriage may include a second outlet chute coupled to the second carriage, so that the selected outlet chute is coupled to the selected carriage.

[0061] In a preferred form of the machine, the outlet chute may include an inclined surface, and the inclined surface includes a slot sized to receive the plunger rod and the syringe assembly after the cradle has moved to the second position.

[0062] 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.

[0063] 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 activation of the actuating device.

[0064] In a preferred form, the method may include fastening the first carriage to the table by a quick-change fastener, the table being connected to the actuating device.

[0065] In a preferred form of the method, disconnecting the second carriage from the actuating device may include disconnecting a quick-change fastener that secures the second carriage to the table.

[0066] In a preferred form of the method, disconnecting the second carriage from the actuating device may include disconnecting the servo motor of the actuating device from the receiving member of the second carriage.

[0067] In a preferred form of the method, coupling the first carriage to the actuating device may include coupling a servo motor of the actuating device to a receiving member of the first carriage.

[0068] In a preferred form, the method may include positioning a second syringe assembly on a second cradle of the second carriage before disconnecting the second carriage from the actuating device, the second cradle being adapted to receive a second syringe assembly of a second size, the second syringe assembly including a distal end, a proximal end, a syringe barrel, and a plunger disposed within the syringe barrel, and the second cradle of the second carriage being sized to receive a second syringe barrel of the second size. Further, a preferred form of the method may include positioning a second plunger rod on the second cradle of the second carriage, the second plunger rod including a distal rod end and a proximal rod end, and the distal rod end being disposed above the proximal end of the second syringe assembly and axially aligned with the plunger. In a preferred form, the method may include activating an 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 such that the second plunger rod is coupled to the second syringe assembly.

[0069] In a preferred form of the method, indexing the cradle may include rotating the carriage about the axis of rotation of the carriage.

[0070] In a preferred form of the method, rotating the carriage may include rotating the carriage beyond zero degrees to index the cradle from a first position to a second position.

[0071] In a preferred form of the method, activating the actuating device may include moving a lever, where the lever causes the carriage to index the cradle from a first position to a second position.

[0072] In a preferred form of the method, activating the operating device may include triggering an operating switch coupled to the servo motor, where the servo motor is arranged to slide a bracket to move a lever.

[0073] In a preferred form of the method, activating the operating device may include triggering an operating switch coupled to the servo motor, where the servo motor is operably coupled to the carriage.

[0074] In a preferred form, the method may include applying a downward force to the proximal rod end of the plunger rod as the cradle moves from the first position towards the second position.

[0075] 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 directly below a pressure plate positioned adjacent to the carriage as the cradle moves from the first position to the second position.

[0076] In a preferred form, the method may include applying a rotational force to the syringe barrel of the syringe assembly while the cradle moves from the first position to the second position.

[0077] In a preferred form of the method, applying a rotational force may include engaging the syringe assembly with a friction element arranged adjacent to the carriage as the cradle moves from the first position to the second position. The syringe assembly may be rotatable about the longitudinal axis of the cradle.

[0078] In a preferred form, the method may include rotating the carriage about the axis of rotation of the carriage in a first direction to feed the cradle from the first position to the second position.

[0079] In a preferred form of the method, rotating the syringe assembly may include rotating the syringe assembly in a direction opposite to the first direction of the carriage, and the axis of rotation of the carriage is parallel to the longitudinal axis of the cradle.

[0080] This disclosure is considered to be more fully understood from the following description when taken in conjunction with the accompanying drawings. Some of the drawings may be simplified by omitting selected elements to more clearly show other elements. Such omissions of elements in some of the drawings do not necessarily indicate the presence or absence of specific elements in any of the exemplary embodiments, except as may be clearly depicted in the corresponding description. Also, the drawings are not necessarily to scale.

Brief Description of the Drawings

[0081]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15

Best Mode for Carrying Out the Invention

[0082] This specification illustrates and describes a plunger rod assembly system for coupling a plunger rod to a prefilled syringe assembly. FIGS. 1-4 show a first example of a plunger rod assembly machine 10 shown at various stages of coupling a plunger rod 14 to a prefilled syringe assembly 18. FIGS. 5-10 show various components of the machine 10 in more detail, and FIGS. 11 and 12 show an adaptability system for converting the non-automatic machine 10 of FIGS. 1-4 into a second example of a semi-automatic plunger rod assembly system. A third example of a plunger rod assembly system is shown in FIGS. 13-15, and may incorporate any or all of the various components of the previous figures to couple the plunger rod 14 to the syringe assembly 18. The term "syringe assembly" 18 refers to a prefilled syringe or an empty syringe.

[0083] Figure 1 shows a first example of a plunger rod assembly system 10 for coupling a plunger rod 14 to a syringe assembly 18. The plunger rod assembly system 10 is a machine having a carriage 22 with a movable cradle 26 and an actuating device 30 operatively coupled to the carriage 22 and adapted to move the cradle 26 from a first position to a second position. The cradle 26 includes a seat portion 34 sized to receive the syringe assembly 18 and an aperture portion 38 disposed above the seat portion 34 and sized to receive the plunger rod 14. In the description of the illustrated example, the carriage 22 is a carousel turntable, and a plurality of cradles 26 are supported by the carriage 22 and disposed around the outer periphery of the turntable 22. For ease of reference, a single cradle 26 will be described for the case where the carriage 22 rotates the cradle 26 between a first position and a second position. As used herein, a "loaded cradle" 26 refers to a cradle 26 in which the plunger rod 14 and the syringe assembly 18 are positioned therein. The machine 10 provides a plurality of cradles 26 in various positions, and the "first position" P1 (shown in FIG. 1) refers to a position where the plunger rod 14 and the syringe assembly 18 are positioned in the cradle 26 but not yet coupled to each other. The "second position" P2 (shown in FIG. 3) refers to any position of the loaded cradle 26 where the plunger rod 14 has been coupled to the syringe assembly 18. As used herein, an "assembled plunger rod syringe assembly" 46 refers to the final product in which the plunger rod 14 is coupled to the syringe assembly 18. The plunger rod 14 and the syringe assembly 18 may be loosely attached, removably fixed, or suitably fitted to the cradle 26.

[0084] Describe the function and operation of the machine 10 when the cradle 26 is in three consecutive positions: a first position P1, a position between the first position P1 and a second position P2, and the second position P2. The machine 10 is configured to couple the plunger rod 14 with the prefilled syringe assembly 18 by moving the cradle 26 from the first position P1 shown in FIG. 1, through the intermediate position shown in FIG. 2, and finally to the second position P2 shown in FIG. 3 where the plunger rod 14 is coupled to the syringe assembly 18. The actuating device 30 disposed within the base 48 of the machine 10 drives the rotation of the carriage 22 and the loaded cradle 26 about the axis A of rotation of the carriage 22. Due to the rotation of the carriage 22, the loaded cradle 26 passes through a guide assembly 50 attached to the base 48. The guide assembly 50 includes a pre-force plunger unit 54 which is configured to apply a constant downward force to the plunger rod 14 when the plunger rod 14 engages the pressure plate 58. At the same time, a friction element 60 (FIG. 9) of the guide assembly 50 engages the syringe assembly 18 to apply a rotational force (e.g., torque) to spin the syringe assembly 18 relative to the plunger rod 14 as the loaded cradle 26 passes under the pressure plate 58. The combined force of the downward force applied by the pressure plate 58 and the rotational force applied by the friction element 60 effectively couples the plunger rod 14 to the syringe assembly 18 by the time the loaded cradle 26 reaches the second position P2. In FIG. 3, the coupled plunger rod syringe assembly 46 is in the second position P2 adjacent to an exit chute 62 that receives the coupled plunger rod syringe assembly 46. The cradle 26 is configured to release the coupled plunger rod syringe assembly 46 when the carriage 22 rotates again, and as shown in FIG. 4, the cradle 26 is configured to place the coupled plunger rod syringe assembly 46 into the exit chute 62. The carriage 22 described herein may be controlled or operated by a rotary actuator, although other embodiments may include a linear actuator.For example, carriage 22 can be replaced with a linear assembly line such as a conveyor belt, where the cradle 26 is linearly fed. Carriage 22 can include one or more movable cradles 26 coupled to a linear drive mechanism that moves the cradle 26 linearly. In this example, the guide assembly 50 can be positioned relative to a linear conveyor belt or other linear conveyance method that interacts with the movable cradle 26 to couple the plunger rod 14 to the syringe assembly 18.

[0085] As shown in FIGS. 1, 3, and 4, when the base 48 of the machine 10 is placed on a plane, the machine 10 is oriented at an angle. As shown in FIG. 3, the axis of rotation A of the carriage 22 is disposed at an angle α with respect to the vertical direction V, and the bottom surface 66 of the base 48 is disposed at an angle β with respect to the horizontal direction H. The axis of rotation and / or the longitudinal axis A of the carriage 22 is also parallel to the axis B of the cradle, which is coaxial with the longitudinal axis C of the plunger rod 14 and the syringe assembly 18 when the plunger rod 14 and the syringe assembly 18 are disposed within the cradle 26. The axis B of the cradle and the axis of rotation A are disposed at an angle α greater than zero degrees with respect to the vertical direction V. In one variation, the angle α can be from 1 degree to 10 degrees, from 5 degrees to 10 degrees, from 5 degrees to 15 degrees, from 5 degrees to 20 degrees, from 5 degrees to 30 degrees, or any other suitable angle.

[0086] As described above, the term "receptacle" 26 refers to a structure that receives the plunger rod 14 and the syringe assembly 18. Each receptacle 26 includes a seat portion 34 defined by a pair of rollers 68, an orifice 70 of the plunger rod positioning base 72, and an aperture portion 38 defined by the plunger rod gripping disk 74. The rollers 68, the plunger rod positioning base 72, and the plunger rod gripping disk 74 are attached to the carriage 22 and are rotatable about the axis of rotation A when the carriage 22 is actuated by the actuating device 30. The positioning base 72 includes a plurality of equally spaced orifices 70, and the plunger rod gripping disk 74 includes a plurality of equally spaced apertures 38. Since the positioning base 72 and the gripping disk 74 are spaced apart and positioned relative to the rollers 68, each receptacle 26 is defined by one orifice 70, one aperture 38, and one seat portion 34, which are coaxial and arranged to receive the plunger rod 14 aligned with the syringe assembly 18. Each roller 68 is rotatable about a pin 76 disposed through the central axis D of the roller 68, and each pin 76 is fixed to the bottom 24 of the carriage 22. Each roller 68 is spaced apart from an adjacent roller 68 by a predetermined distance defining a gap G, so that the syringe barrel 78 can fit between and engage two adjacent rollers 68 and rest in the seat portion 34. The first and second adjacent rollers 68 of the seat portion 34 are adapted to engage the syringe barrel 78 of the syringe assembly 18 and hold the syringe barrel 78 in the gap G when carried by the receptacle 26.

[0087] When the roller 68 holds the syringe barrel 78 of the syringe assembly 18 loosely when the syringe assembly 18 is attached to or otherwise positioned on the machine 10 at the first position P1, and releases the syringe barrel 78 when the cradle 26 moves towards the outlet chute 62. In a disclosed variant, the angled orientation of the carriage 22 allows the cradle 26 to hold the syringe barrel 78 while the cradle 26 moves from the first position P1 towards the second position P2. Further, the angled orientation of the machine 10 allows the cradle 26 to release the coupled plunger rod syringe assembly 46 into the outlet chute 62 after the cradle 26 has passed through the second position P2. When the carriage 22 rotates again, the coupled plunger rod syringe assembly 46 is received in the slot 64 of the outlet chute 62, and the coupled plunger rod syringe assembly 46 can slide along the ramp 63, where the coupled plunger rod syringe assembly 46 remains until removed. Since the slot 64 is sized to receive a syringe assembly 18 of a particular size, the coupled plunger rod and syringe assembly 46 easily slides along the ramp 63 and is stored in the outlet chute 62. The ramp 63 can be sized and angled to hold a batch of the coupled plunger rod syringe assemblies 46.

[0088] The dimensions of the receptacle 26 are based on the conditions of the syringe assembly 18 and the plunger rod 14. In particular, the seat portion 34 is sized to receive a particular type / size of syringe assembly 18, and the aperture portion 38 and the orifice 70 of the receptacle 26 are also sized to receive a particular type / shape of plunger rod 14. In the illustrated example, the machine 10 is specifically designed to couple a plunger rod 14 and a syringe assembly 18 of a particular size. In other embodiments, the machine 10 can be adjusted to accommodate plunger rods 14 and syringe assemblies 18 of different sizes. The machine 10 can be designed to accommodate one syringe assembly size, for example, a 2.25 mL glass syringe assembly 18. As such, the spacing between two adjacent rollers 68 is arranged such that a syringe assembly 18 having a 2.25 mL syringe barrel 78 can be loosely attached to the receptacle 26. Each aperture 38 of the plunger rod gripping disk 74 is designed to accommodate a particular shaped plunger rod body 82 used with the 2.25 mL syringe assembly 18. In the case of a plunger rod 14 having an X-shaped cross-section, the aperture portion 38 includes a plurality of ridges to receive the plunger rod body 82 and limit the rotational movement, angular movement, and lateral movement of the plunger rod 14 with respect to the axis C when the loaded receptacle 26 moves from the first position P1 to the second position P2. On the other hand, as will be described in more detail below, the rollers 68 are freely rotatable about the axis D and allow the syringe barrel 78 to rotate about the axis B of the receptacle 26 when the friction element 60 contacts the syringe barrel 78. The rollers 68, the plunger rod gripping disk 74, and the plunger rod positioning base 72 can be positioned to accommodate a plunger rod body 82 of a particular height.

[0089] Machine 10 is configured to accommodate various different fill levels of a syringe assembly 18 of a particular size by compatibility plunger rod positioning bases 72 and 86. Figures 5 - 8 show that the plunger rod positioning base 72 is selected from separate and compatible first and second plunger rod positioning bases 72 and 86. The first plunger rod positioning base 72 includes an orifice 70 sized to receive a proximal end 90 of a particular size of the plunger rod 14, and the second plunger rod positioning base 86 includes an orifice 104 sized to receive a proximal end 90 of a different size of the plunger rod 14. The first plunger rod positioning base 72 and corresponding plunger rod retaining cap 84 shown in Figures 5 and 7 can be exchanged with the different positioning base 86 and associated retaining cap 84 shown in Figures 6 and 8. The first and second plunger rod positioning bases 72 and 86 can have different heights to accommodate different plunger rod heights and can have different orifice 70 and 104 sizes to accommodate two sizes of the plunger rod proximal end 90. In the illustrated embodiment, the orifice 70 of the first positioning base 72 has a smaller radius than the orifice 104 of the second positioning base 86. Although not shown, machine 10 can be configured to operate with any number of different plunger rod positioning bases and machine 10 is not limited to the two embodiments described and illustrated herein.

[0090] Referring to FIGS. 5 and 6, the first plunger rod positioning base 72 and the retaining cap 84 are removably attached to the machine 10. The first plunger rod positioning base 72 is coupled to the carriage 22 and is disposed above the plunger rod gripping disk 74, so that the orifices 70 provided around the outer periphery of the positioning base 72 are coaxial with the aperture 38 of the gripping disk 74. Each orifice 70 is sized to receive the flanged proximal end 90 of the plunger rod 14 and provides sufficient clearance for the flanged proximal rod end 90 to pass through the orifice 70 and drop when the cradle 26 moves from the first position P1 to the second position P2. The retaining cap 84 is disposed on the positioning base 72 and includes an outwardly extending tab 94 that is disposed to extend into the orifice 70 when the positioning base 72 and the retaining cap 84 are attached to the machine 10. Both the retaining cap 84 and the plunger rod positioning base 72 are removably attached to the machine 10 by screw components 98. The positioning base 72 is movably coupled to the carriage 22 (such that the positioning base 72 rotates with the carriage 22), but the retaining cap 84 and the screw components 98 are fixed to the machine 10 and do not rotate about the axis A with the carriage 22. The retaining cap 84 provides a retaining function for the plunger rod 14 when the plunger rod 14 is first positioned in the cradle 26. As shown in FIGS. 1 and 2, the flanged proximal end 90 of the plunger rod 14 is received by the orifice 70 of the positioning base 72 and rests on a portion 96 of the tab 94 that extends into the orifice 70. The portion 96 of the tab 94 disposed within the orifice 70 holds the plunger rod 14 in a floating state above the syringe assembly 18 positioned in the seat portion 34. When the loaded cradle 26 moves from the first position P1, the positioning base 72 rotates relative to the extending tab 94 and the orifice 70 of the cradle 26 moves away from the portion 96, releasing the plunger rod 14 therefrom.The flanged proximal end 90 of the plunger rod 14 drops below the orifice 70 of the positioning base 72, and the distal end 156 of the plunger rod 14 contacts the plunger 158 disposed in the syringe barrel 78, as shown in FIG. 2.

[0091] FIG. 7 shows a first side 100a of a retaining cap 84 associated with a first plunger rod positioning base 72, and FIG. 8 shows a second side 100b of the retaining cap 84 associated with a second plunger rod positioning base 86. In each illustrated embodiment, the extending tabs 94 of the retaining cap 84 include edges 101a and 101b having an asymmetric profile, which can be shaped according to the profile of the flanged ends 90 of different plunger rods 14. Each side 100a and 100b of the retaining cap 84 includes specific marks or indicia 102a and 102b associated with corresponding marks 103a and 103b on the plunger rod positioning bases 72 and 86. The gripping disk 74 also includes marks 105a and 105b that align exactly with the marks 102a and 102b to ensure proper alignment of the orifices 70 and 104 and the aperture 38 when assembling the cradle 26. As shown in FIG. 5, the marks 102a, 103a, and 105a can provide a visual indication that the plunger cap 84 is properly aligned with both the first plunger rod positioning base 72 and the gripping disk 74. To replace the first plunger rod positioning base 72 with the second plunger rod positioning base 86, a threaded component 98 including a manual knurled knob is removed from the machine 10, and the retaining cap 84 and the first positioning base 72 are removed. The second positioning base 86 is placed on the carriage 22 so that the mark 103b aligns with the corresponding mark 105b on the gripping disk 74. The second side 100b faces outward as viewed from the carriage 22, and then the retaining cap 84 is flipped so that it is placed on top of the second positioning base 86, causing the mark 102b on the retaining cap 84 to align with the mark 103b on the second positioning base 86 and the mark 105b on the gripping disk 74. When properly assembled, the extending tab 94 is disposed within the orifice 104 of the cradle 26 at the first position P1. In the illustrated embodiment, the machine 10 includes a plunger rod retaining cap 84 and plunger rod positioning bases 72 and 86 for suspending the plunger rod 14 above the syringe assembly 18 when loaded onto the cradle 26 at the first position P1.In different embodiments, the plunger rod 14 and the syringe assembly 18 can be loaded together such that the plunger rod 14 is not held by the retaining cap 84 and the positioning bases 72 and 86, and instead, when the cradle 26 is in the first position P1, the distal end portion 156 can be applied by the plunger 158. In this case, since the positioning bases 72 and 86 and the retaining cap 84 can optionally be attached to the machine 10, the cradle 26 is not defined by the orifices 70 and 104 of the positioning bases 72 and 86.

[0092] The guide assembly 50 of FIGS. 9 and 10 includes a preforce plunger unit 54 of the machine 10 attached to the feed guide assembly 110. The feed guide assembly 110 includes a plurality of struts 114 that connect the strut retaining guide 116, the upper feed guide 118, the guide plate 120, the bottom feed guide 122, and the support base 126. Generally, the strut retaining guide 116, the upper feed guide 118, the guide plate 120, and the bottom feed guide 122 are contoured to partially surround and conform to the outer periphery of the carriage 22. The support base 126 can be attached to the base 48 of the machine 10, and the struts 114 support the remaining elements of the feed guide assembly 110 and the preforce plunger unit 54. The upper and bottom feed guides 118 and 120 each include cut-off ends 119 and 121 to receive and guide the loaded cradle 26 and prevent jamming while the carriage 22 rotates. The syringe guide 130 attached to the upper feed guide 118 assists the feed guides 118 and 120 by providing a barrier to the proximal end portion 132 of the syringe assembly 18 when the loaded cradle 26 moves through the guide assembly 50 to the second position P2. As shown in FIG. 2, the syringe guide 130 is an L-shaped bracket sized to receive and guide the proximal end portion 132 of the syringe assembly 18.

[0093] FIG. 9 shows a friction element 60 fixed to the inner edge surface 134 of the guide plate 120, adjacent to the carriage 22, and disposed below the pressure plate 58. The friction element 60 is adapted to engage the syringe barrel 78 of the syringe assembly 18 attached to the cradle 26 when the cradle 26 moves from the first position P1 to the second position P2. Therefore, the friction element 60 applies a rotational force to the syringe barrel 78 to spin the syringe assembly 18 relative to the plunger rod 14. In the illustrated example, since the friction element 60 is an elongated cord extending along the inner edge surface 134 of the guide plate 120, the friction element 60 remains in contact with the syringe barrel 78 as the syringe assembly 18 moves along at least a portion of its path from the first position P1 to the second position P2. When the cradle 26 moves from the first position P1 to the second position P2, the syringe assembly 18 passes through the guide assembly 50 and engages the friction element 60 projecting from the inner edge surface 134 of the guide plate 120. The friction element 60 contacts the syringe barrel 78 and rotates the syringe barrel 78 and the syringe assembly 18 about the longitudinal axis B of the cradle 26. Configured in this way, when the cradle 26 carries the syringe assembly 18 in the first direction, the friction element 60 engages the syringe barrel 78 and applies a rotational force to the syringe barrel 78 to rotate the syringe barrel 78 between the rollers 68 of the cradle 26 in a direction opposite to the first rotational direction of the carriage 22. During that time, the plunger rod 14 disposed in the aperture portion 38 of the cradle 26 does not rotate relative to the cradle 26 or the syringe assembly 18, and instead receives a downward force from the preforce - plunger unit 54.

[0094] In a preferred example, the pressure plate 58 of the preforce plunger unit 54 applies a constant force (e.g., about 2 N in some variations) to the plunger rod 14, and the friction element 60 rotates the syringe barrel 78 up to four times to couple the plunger rod 14 and the syringe assembly 18. The length of the friction element 60 can be determined based on the fitting relationship between the plunger 158 of the syringe assembly 18 and the plunger rod 14. For example, the plunger 158 can complete three rotations relative to the plunger rod 14 before the threaded distal end 156 of the plunger rod 14 is properly coupled to the plunger 158. If the friction element 60 rotates the syringe assembly 18 more than necessary, the excessive rotational force applied to the syringe assembly 18 can have an adverse effect on the plunger 158, the syringe barrel 78, or some other component of the syringe assembly 18. Therefore, the length of the friction element 60 is based on the minimum number of rotations required for the syringe assembly 18 to rotate about axis B to sufficiently couple the plunger 158 to the plunger rod 14 during a single dose delivery and without breaking. The friction element 60 can be an elastomeric material, such as a silicon-based rubber, a rubbery substance, latex, or some other suitable material that induces the syringe assembly 18 to spin relative to the cradle 26 when contacting the friction element 60. In another embodiment, the friction element 60 can be disposed on the roller 68 instead of the inner edge surface 134 of the guide plate 120. In this example, as the cradle 26 moves through the guide assembly 50, a portion of the guide plate 120 can contact the friction element 60 disposed on the roller 68 to position the guide plate 120 so as to spin the syringe assembly 18 on the roller 68.

[0095] In FIGS. 9 and 10, the preforce plunger unit 54 includes a base plate 136 attached to the strut retaining guide 116, a pressure plate 58, a constant tension spring 138 coupled to the pressure plate 58, and first and second guide posts 142. The elongated pressure plate 58 is positioned adjacent to the carriage 22 such that the cradle 26 moves directly beneath the pressure plate 58 as the cradle 26 moves from the first position P1 to the second position P2. In other words, the carriage 22 is rotatably disposed relative to the pressure plate 58. The pressure plate 58 is adapted to apply a downward force to the plunger rod 14 disposed in the aperture portion 38 of the cradle 26. In particular, the pressure plate 58 defines an inlet 144 (see FIG. 2) and an outlet 148, where the inlet 144 is sized to receive the proximal end portion 90 of the plunger rod 14 and to apply a downward force to the proximal rod end portion 90 of the plunger rod 14 as the plunger rod 14 moves from the inlet 144 to the outlet 148. The constant tension spring 138 is coupled to the pressure plate 58 and provides a downward force to the plunger rod 14 through the pressure plate 58 as the cradle 26 moves between the first position P1 and the second position P2. The pressure plate 58 is elongated with an inclined surface 145 at the inlet 144 to receive the proximal rod end portion 90 without colliding with the body 82 of the plunger rod 14.

[0096] The pressure plate 58 is slidably coupled to the first and second guide posts 142 such that the pressure plate 58 can move along the posts 142 in a direction parallel to the axis of rotation A. The guide posts 142 are disposed through the first and second apertures of the pressure plate 58 and adjustably mount the pressure plate 58 to the carriage 22 such that the pressure plate 58 can be adjusted to accommodate plunger rods 14 and plungers 158 disposed at different heights. The tension spring 138 is disposed through the third aperture of the pressure plate 58 and secured to the upper surface 150 of the pressure plate 58 such that a constant force, e.g., 2 N, is always applied to the plunger rod 14. That is, when the plunger rod 14 moves from the first position P1 to the second position P2, the proximal rod end 90 of the plunger rod 14 applies an upward force to the pressure plate 58, thereby being able to slightly lift the pressure plate 58. However, the tension spring 138 ensures that a sufficient non-zero force is always applied to the plunger rod 14 so as to favorably affect the coupling of the plunger rod 14 to the plunger 158. A threaded rod 152 is disposed through the bore of the base plate 136 and engages the bottom surface 154 of the pressure plate 58 and is adapted to adjust the height of the pressure plate 58 along the guide posts 142.

[0097] The pressure plate 58 can be adjusted to accommodate different fill levels of the syringe assembly 18 that correlate with different positions of the plunger 158 within the syringe barrel 78. For example, it may be desirable to fill the syringe assembly 18 up to above the syringe assembly volume marked by the fill line and position the plunger 158 at a position higher than the fill line at the distal end 133 of the syringe assembly 18. In another example, it may be desirable to fill the syringe assembly 18 down to below the fill line of the syringe assembly volume and thereby position the plunger 158 at a position lower than the fill line. To accommodate different fill levels or plunger rod heights, the position of the pressure plate 58 relative to the cradle 26 can be adjusted by rotating the screw rod 152 in the clockwise or counterclockwise direction to raise or lower the pressure plate 58, respectively. A gauge 153 can be attached to the guide assembly 50 and remains stationary relative to the pressure plate 58 as the pressure plate 58 moves. The gauge 153 can be used to measure the distance by which the pressure plate 58 needs to be adjusted to accommodate a standard fill level. For example, a syringe assembly 18 having a volume capacity of 1 mL can be filled to a fill level below or above the 1 mL fill line. The fill level determined by the rulings measured in the syringe barrel 78 can indicate how much the position of the pressure plate 58 needs to be adjusted outside of the standard fill level. The machine 10 and system disclosed herein can be configured to operate with any number of different syringe assemblies 18 and are not limited to the 1 mL and 2.25 mL sizes described herein.

[0098] According to the present disclosure, the machine 10 is configured to shuttle the cradle 26 to couple the plunger rod 14 to the syringe assembly 18. In one shuttle rotation, the distal end 156 of the plunger rod 14 can be threadedly coupled to the female thread of the plunger 158 disposed at the proximal end 132 of the syringe assembly 18. For example, the loaded cradle 26 moves the plunger rod 14 to engage the pressure plate 58, while the friction element 60 engages the barrel 78 to spin the syringe assembly 18. The combined force of the downward force applied to the plunger rod 14 by the pressure plate 58 and the rotational force applied to the syringe assembly 18 induced by the friction element 60 enables the threaded distal end 156 of the plunger rod 14 to be coupled to the threaded surface of the plunger 158. In some variations, the machine may not include the pressure plate 58 at all, and in such variations, the coupling of the plunger rod 14 to the plunger 158 can occur simply by the friction element 60 applying a rotational force to the barrel 78. In yet other variations, the machine 10 may not include the friction element 60 at all, and in those variations, the coupling of the plunger rod 14 to the plunger 158 can occur simply by applying a downward force to the plunger rod 14 together with the pressure plate 58. In the latter configuration, the plunger rod 14 need not be screwed into the plunger 158 and can simply be frictionally fitted.

[0099] The machine 10 is arranged or programmed to shuttle the cradle 26 such that, in one movement of the carriage 22, the loaded cradle 26 moves between a first position P1 and a second position P2. Since the actuating device 30 operably connected to the carriage 22 is adapted to shuttle the cradle 26, the plunger rod 14 and the syringe assembly 18 are coupled in less than 3 seconds. Each shuttle of the cradle 26 may include a rotation of the carriage 22 about the axis of rotation A, such as 120 degrees, which is about one third of a full 360-degree rotation. For example, the cradle 26 at the first position P1 may reach the second position P2 by rotating approximately 120 degrees about the axis A of the carriage 22 relative to the first position P1. Depending on the position of the guide assembly 50 and the size of the carriage 22, the carriage 22 may be configured to shuttle the cradle 26 with a rotation of less than 120 degrees about the axis A. In this way, the machine 10 limits examples of user error or repeated start-up and stop of a continuously moving machine. The machine 10 is configured to couple one plunger rod 14 to one syringe assembly 18 at a time.

[0100] The actuating device 30 may be arranged or programmed to shuttle the cradle 26 only once via the carriage 22 upon the occurrence of a start event. The start event may be, for example, manually operating the lever 160 of the actuating device 30 or triggering a switch. Pulling the lever 160 once, for example, activates a servo motor or other mechanical drive system of the actuating device 30 to shuttle the cradle 26 between the first position P1 and the second position P2. The actuating device 30 may be further programmed such that the carriage 22 does not rotate until the lever 160 is pulled again or until some other start event occurs. In other embodiments, the machine 10 may be actuated using another suitable mechanism other than the lever 160.

[0101] The lever 160 of the non-automatic machine 10 shown in FIGS. 1-6 is operably coupled to the carriage 22 and is adapted to index the cradle 26 between a first position P1 and a second position P2. The lever 160 is movably mounted to the base 48 and is disposed within the slot 164. When the lever 160 is pulled from its rest position to the leftmost end of the slot 164, the carriage 22 rotates until the lever 160 returns to its initial rest position within the slot 164. The lever 160 may be coupled to a mechanical operating device or an electric drive mechanism housed within the base 48, which converts the movement of the lever 160 into a rotational movement of the carriage 22. In another embodiment, the actuating device 30 may be arranged or programmed to index the cradle 26 more than twice upon the occurrence of an activation event. For example, the slot 164 of the lever 160 may be marked to indicate where the lever 160 is to be pulled to index the cradle 26 a certain number of times. For example, when the lever 160 is pulled to a first activation position, the cradle 26 indexes once; and when the lever 160 is pulled to another second activation position along the slot 164, the cradle 26 indexes twice.

[0102] Figures 11 and 12 show an adaptable system 170 for converting the non-automatic machine 10 of FIGS. 1-6 into a semi-automatic plunger rod assembly system 170. FIG. 11 shows the adaptable system 170, and FIG. 12 shows the machine 10 of FIGS. 1-6 deployed on the operating platform 172 of the adaptable system 170. The operating platform 172 receives the base 48 of the machine 10 and secures it to the table 178. A rigid member 182 is movably attached to the table 178 and extends vertically through a semi-circular bracket 186 from the table 178. The rigid member 182 carries a semi-circular bracket 186 that is adapted to smoothly glide on the surface of the table 178 when the rigid member 182 is actuated to move the lever 160. As shown in FIG. 12, the rigid member 182 is positioned adjacent to the lever 160 of the machine 10 when the lever 160 is in the rest or non-activated position. The semi-circular bracket 186 is shaped to conform to the outer peripheral contour of the base 48. A servo motor 190 attached to the table 178 is operably connected to the rigid member 182 via wiring disposed directly below the table 178. First and second two-handed anti-tie-down operation switches 194 are fixed to both sides of the table 178 and positioned such that an operator can simultaneously trigger the operation switches 194. The operation switches 194 are coupled to the servo motor 190 and are configured to trigger the servo motor 190 only when the switches 194 are simultaneously pressed. During operation, the servo motor 194 engages the rigid member 182 with the lever 160 of the machine 10 and operates to move the lever 160 within the slot 164. The rigid member 182 moves in an arcuate path to engage the lever 160 until the lever 160 reaches the leftmost end of the slot 164. The servo motor 190 can be programmed to move the rigid member 182 only once when both operation switches 194 are triggered to eject the cradle 26. In another embodiment, the servo motor 194 can be programmed to eject more than once, if desired. In this case, a control panel coupled to the activation switch 194 and the servo motor 190 can be configured to eject the cradle 26 more than once when the switch on the control panel is activated.

[0103] The adaptability system 170 of FIGS. 11 and 12 shows a plunger rod assembly system that can convert the non-automatic plunger rod assembly system 10 into a semi-automatic system using the existing machine 10 of FIGS. 1-6. In FIGS. 13-15 below, a semi-automatic plunger rod assembly system 310 is described according to another embodiment of the present disclosure. The plunger rod assembly system 310 is similar to the above-described machine 10, except that the system 310 is semi-automatic and includes different operating equipment 330. Elements of the system 310 in FIGS. 13-15 that are similar to the elements of the machine 10 are denoted by the same reference numerals incremented by 300. Many descriptions of these elements are omitted or excluded for the sake of brevity.

[0104] The plunger rod assembly system 310 of FIGS. 13-15 includes a machine 312 and an outlet chute 362 fixed to a removable base plate 472. The base plate 472 is removably attached to the table 478 by a plurality of quick-change fasteners 480. The operating equipment 330 is operably coupled to a carriage 322 and shuttles a cradle 326 that is carried by the carriage 322 from a first position P1 to a second position P2 to couple a plunger rod 14 to a syringe assembly 18. The plunger rod 14 and the syringe assembly 18 are not shown together with the plunger rod assembly system 310, but can be positioned or attached to the machine 312 in the same or similar manner as described and illustrated in previous drawings. The operating equipment 330 includes a servo motor 490 and first and second operation switches 494 that operably control the servo motor 490. The servo motor 490 shown in FIGS. 14 and 15 is attached to the table 478 and positioned below the machine 312, so the servo motor 490 can be directly connected to the carriage 322.

[0105] To switch to syringe assemblies 18 of different sizes, carriage 322 can be selected from separate and compatible first and second carriages. System 310 is configured such that an operator can easily remove the selected carriage 322 and / or machine 312 from servo motor 490 removably coupled or attached to table 478, and replace the selected carriage 322 with a first carriage capable of receiving syringe assemblies 18 of different sizes. The first carriage 322 includes a cradle 326 having a seat portion 334 sized to receive a syringe assembly 18 of a first size, such as a 1 mL syringe, and the second carriage includes a cradle having a seat portion sized to receive a syringe assembly of a second size, such as a 2.25 mL syringe. Servo motor 490 of actuating device 330 is adapted to couple to the base portion 328 of the first carriage 322 and the base portion of the second carriage. For example, servo motor 490 may include a spline shaft 332 or other suitable device that extends into a receiving member 336 disposed within base portion 328 of carriage 322. Receiving members 336 of both the first carriage 322 and the second carriage are adapted to couple with spline shaft 332 of servo motor 490 when base 348 of machine 312 is attached to table 478. Machine 312 and outlet chute 362 may be compatible with a second machine and a second outlet chute. Each machine 312 may include a mounted guide assembly 350 and a preforce plunger unit 354 adapted to interact with carriage 322 as already described in connection with machine 10 of FIGS. 1-6.

[0106] For example, the selected carriage 322 can be selected by an operator based on the size of the syringe assembly 18 to be assembled. Each selected carriage 322 can correspond to a selected pressure plate 358, a selected friction element 360, and a selected guide plate 420. The first carriage 322 includes a first pressure plate 358 coupled to the carriage 322, and the second carriage includes a second pressure plate coupled to the second carriage. The first carriage 26 includes a first guide plate 420 coupled to the first carriage 322 and supporting the first friction element 360, and the second carriage includes a second guide plate coupled to the second carriage and supporting the second friction element. Accordingly, the selected pressure plate 358 is coupled to the selected carriage 322, and the selected friction element 360 is supported by the selected guide plate 420 coupled to the selected carriage 322.

[0107] According to a preferred method of using plunger rod assembly systems 10 and 310, the method may include positioning syringe assembly 18 on cradles 26 and 326 of carriages 22 and 322, where cradles 26 and 326 of carriages 22 and 322 are sized to receive a syringe assembly 18 of a particular size. Syringe assembly 18 includes a distal end 133, a proximal end 132, a barrel 78, and a plunger 158 disposed within barrel 78. Plunger rod 14 is positioned on cradles 26 and 326 of carriages 22 and 322, where plunger rod 14 includes a distal rod end 156 and a proximal rod end 90, where distal rod end 156 is disposed above proximal end 132 of syringe assembly 18 and is axially aligned with plunger 158. After both plunger rod 14 and first syringe assembly 18 are positioned on cradles 26 and 326, the method includes activating actuators 30 and 330 coupled to carriages 22 and 322 to move cradles 26 and 326 from position P1 to a second position P2, thereby applying a force to plunger rod 14 to couple plunger rod 14 to syringe assembly 18.

[0108] The activation of the actuating machines 30 and 330 includes rotating the carriages 22 and 322 such that the cradles 26 and 326 are fed from the first position P1 to the second position P2, where the syringe assemblies 18 and the plunger rods 14 are positioned on the cradles 26 and 326 in the first position P1, and the plunger rod 14 is coupled to the syringe assembly 18 in the second position P2. Further, the method includes rotating the carriages 22 and 322 about the axis A. When the cradles 26 and 326 are between the first position P1 and the second position P2, the method includes applying a downward force to the proximal rod end 90 of the plunger rod 14 as the cradles 26 and 326 move from the first position P1 towards the second position P2. Applying a downward force to the proximal end 90 of the plunger rod 14 includes moving the plunger rod 14 directly below the pressure plates 58 and 358 positioned adjacent to the carriages 22 and 322 as the cradles 26 and 326 move from the first position P1 to the second position P2. Further, the method includes applying a rotational force to the barrel 78 of the syringe assembly 18 while the cradles 26 and 326 move from the first position P1 to the second position P2. Applying a rotational force includes engaging the syringe assembly 18 with the friction elements 60 and 360 arranged adjacent to the carriages 22 and 322 as the cradles 26 and 326 move from the first position P1 to the second position P2. Rotating the syringe assembly 18 when the carriages 22 and 322 rotate in the first direction includes engaging the barrel 78 with the friction elements 60 and 360 and rotating the syringe assembly 18 in a direction opposite to the first direction of rotation of the carriages 22 and 322.

[0109] In order to switch the machines 10 and 312 in the second and third plunger rod assembly systems 170 and 310 of FIGS. 11 - 15, the method further includes disconnecting the carriage, e.g., the second carriage, from the actuating devices 30 and 330. If necessary, the method may include disconnecting the second carriage from the table 478 by unlocking a plurality of quick - release or quick - change fasteners 480 to remove the second base plate from the table 478. Further, disconnecting the second carriage from the actuating device 330 includes disconnecting the splined shaft 332 of the servo - motor 490 from the receiving member of the second carriage. Further, after disconnecting the second carriage from the actuating devices 30 and 330, the method includes coupling the first carriages 22 and 322 to the actuating devices 30 and 330. Coupling the first carriages 22 and 322 to the actuating devices 30 and 330 may include coupling the splined shaft 332 of the servo - motor 490 to the receiving members 336 of the first carriages 22 and 322. The first carriages 22 and 322 include first movable cradles 26 and 326 adapted to receive the syringe assembly 18 of the first size. Further, the method may include fastening the first carriages 22 and 322 to the table 478 and / or the base plate 472 by the quick - change fasteners 480. The method further includes positioning the first syringe assembly 18 and the first plunger rod 14 on the first movable cradles 26 and 326 of the first carriages 22 and 322. After both the first plunger rod 14 and the first syringe assembly 18 are positioned on the cradles 26 and 326, the method includes activating the actuating devices 30 and 330 coupled to the first carriages 22 and 322 to move the first cradles 26 and 326 from the first position P1 to the second position P2, thereby applying a force to the first plunger rod 14 to couple the first plunger rod 14 to the first syringe assembly 18. As described above, the method includes applying a downward force to the proximal end 90 of the first plunger rod 14 and / or a rotational force to the barrel 78 of the first syringe assembly when the first cradles 26 and 326 move from the first position P1 to the second position P2.The method steps can be repeated until the machines 10 and 312 are switched to accommodate syringe assemblies 18 of different sizes.

[0110] Before the operation of the plunger rod assembly systems 10, 170, and 310, the actuating devices 30 and 330 can be programmed to index the cradles 26 and 326 only once via the carriages 22 and 322 upon the occurrence of a start event. The indexing of the cradles 26 and 326 from the first position P1 to the second position P2 includes rotating the carriages 22 and 322 about the axis of rotation A to couple the plunger rod 14 with the syringe assembly 18. The rotation of the carriages 22 and 322 can include rotating the carriages 22 and 322 by less than 120 degrees to move the cradles 26 and 326 from the first position P1 to the second position P2. When operating the machine 10 of the first example, the actuation of the actuating device 30 includes manually moving the lever 160 to rotate the carriage 22 and index the cradle 26 from the first position P1 to the second position P2. When operating the machine 10 equipped with the adaptable actuation system 170 of FIGS. 11 and 12, the actuation of the actuating device 30 includes triggering an actuation switch 194 coupled to the servo motor 190 to slide the rigid member 182 and the bracket 186 to engage the lever 160. When operating the system 310 of the third example, the actuation of the actuating device 330 includes triggering an actuation switch 494 coupled to a servo motor 490 connected to the carriage 322.

[0111] In other embodiments, machines 10 and 312 are adapted to couple a plunger rod to a plunger of a syringe assembly in accordance with a mating relationship between the plunger rod and the plunger. For example, the illustrated machines 10 and 312 are designed to couple the threaded distal end portion 156 of the plunger rod 14 to the threaded surface of the plunger 158 by applying both a downward force to the plunger rod 14 and a rotational force to the syringe barrel 78. In another example, plunger rod assembly systems 10 and 310 are adapted to couple the plunger rod 14 to a plunger 158 having a snap-fit engagement relationship. In this example, each of the machines 10 and 312 can be configured to apply a downward force to the plunger rod 14 to sufficiently couple the plunger rod 14 and the plunger 158 without spinning the syringe assembly 18 relative to the cradles 26 and 326. Since the friction elements 60 and 360 are removed from the guide plates 120 and 420, the syringe assembly 18 does not rotate relative to the cradles 26 and 326 and the plunger rod 14.

[0112] The plunger rod assembly system disclosed herein provides significant advantages over current methods of automatic plunger rod assembly systems. Non-automatic and semi-automatic systems have a significantly reduced footprint compared to existing automatic machines configured to assemble large batches. The disclosed systems are an economical and efficient alternative to existing automatic machines. Generally, due to the low demand for plunger rods and syringe assemblies, the large capital investment required to purchase, operate, and maintain expensive and complex automatic machines designed to prepare large batches cannot be justified. However, the disclosed systems 10 and 310 are particularly useful for assembling small batches of plunger rod syringe assemblies where access to fully automatic machines is restricted or prohibitively expensive. Further, the disclosed systems are configured to shuttle such that the plunger rod and syringe assemblies are positioned and coupled to the carriage before another plunger rod and syringe assembly is attached to or positioned on the carriage. The shuttle feature improves safety and reduces operator error because the system is preconfigured to assemble the plunger rod syringe assembly without the operator having to know each step of the operation sequence or interface with the machine between assembly steps. Further, the two-handed anti-tie-down motion switch ensures that machines 10 and 312 cannot operate unless the operator triggers the switch with both hands. In other words, accidental operation or switch-on of the machine is significantly reduced, if not completely prevented. The disclosed systems 10 and 310 are very simple to load, operate, and unload and do not require complex training, specialized education, or technical expertise to use. These features of the disclosed systems can both facilitate accessibility and responsiveness to plunger rod syringe assembly technology.

[0113] The semi - automatic system significantly simplifies the assembly operation of components for assembling syringe assemblies of different sizes, materials, and fill levels, and the process for adjusting and / or replacing them. For example, the switching process for adapting existing machinery to assemble syringe assembly sizes of two or more sizes is generally labor - intensive and requires disassembly, retooling, and reassembly before the operation of the machinery. In contrast, some components of the disclosed plunger rod assembly system can be easily exchanged or adjusted within minutes without any additional tooling required to switch to assembling syringe assemblies of different sizes. These features reduce the time and cost of skilled labor and enhance simplicity and efficiency.

[0114] Drug information The above description has been explaining various systems and methods for use with the plunger rod - syringe assembly system. It is apparent that the system, machine, or method may further include the use of the drugs listed below, noting that the following list is considered neither comprehensive nor limiting. The drugs are placed in the reservoir of the barrel of the syringe assembly. In some cases, the reservoir is the main container, either filled or pre - filled, for treating with the drug. The main container can be a pre - filled syringe.

[0115] For example, a syringe or syringe assembly can be filled with a colony stimulating factor such as granulocyte colony stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neupogen® (filgrastim) and Neulasta® (pegfilgrastim). In various other embodiments, the drug delivery device can be used with various pharmaceuticals, such as an erythropoiesis stimulating agent (ESA) that can be in liquid or lyophilized form.ESA is any molecule that stimulates erythropoiesis, such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin zeta, epoetin theta, and epoetin delta, and molecules or variants or analogs thereof as disclosed in the following patents or patent applications, each of which is hereby incorporated by reference in its entirety: U.S. Patent Nos. 4,703,008; 5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078; 5,773,569; 5,955,422; 5,986,047; 6,583,272; 7,084,245; and 7,271,689; and International Publication Pamphlets Nos. 91 / 05867; 95 / 05465; 96 / 40772; 00 / 24893; 01 / 81405; and 2007 / 136752.

[0116] 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 the receptor and causing dimerization. Erythropoiesis-stimulating proteins include erythropoietin and its variants, analogs, or derivatives that bind to and activate the erythropoietin receptor; antibodies that bind to and activate the erythropoietin receptor; or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis-stimulating proteins include, but are not limited to, epoetin alpha, epoetin beta, epoetin delta, epoetin omega, epoetin iota, epoetin zeta, and their analogs, 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 to and activate the erythropoietin receptor (including the compounds reported in U.S. Patent Application Publication Nos. 2003 / 0215444 and 2006 / 0040858, the entire disclosures of each of which are incorporated herein by reference), and erythropoietin molecules or their variants or analogs as disclosed in the following patents or patent applications, the entire disclosures of each of which are incorporated herein by reference: U.S. Patent Nos. 4,703,008; 5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078; 5,773,569; 5,955,422; 5,830,851; 5,856,298; 5,986,047; 6,030,086; 6,310,078; 6,391,633; 6,583,272; 6,586,398; 6,900,292; 6,750,369; 7,030,226; 7,084,245;and U.S. Patent No. 7,217,689; U.S. Patent Application Publication No. 2002 / 0155998; No. 2003 / 0077753; No. 2003 / 0082749; No. 2003 / 0143202; No. 2004 / 0009902; No. 2004 / 0071694; No. 2004 / 0091961; No. 2004 / 0143857; No. 2004 / 0157293; No. 2004 / 0175379; No. 2004 / 0175824; No. 2004 / 0229318; No. 2004 / 0248815; No. 2004 / 0266690; No. 2005 / 0019914; No. 2005 / 0026834; No. 2005 / 0096461; No. 2005 / 0107297; No. 2005 / 0107591; No. 2005 / 0124045; No. 2005 / 0124564; No. 2005 / 0137329; No. 2005 / 0142642; No. 2005 / 0143292; No. 2005 / 0153879; No. 2005 / 0158822; No. 2005 / 0158832; No. 2005 / 0170457; No. 2005 / 0181359; No. 2005 / 0181482; No. 2005 / 0192211; No. 2005 / 0202538; No. 2005 / 0227289; No. 2005 / 0244409; No. 2006 / 0088906; and No. 2006 / 0111279; and International Publication Pamphlets No. 91 / 05867; No. 95 / 05465; No. 99 / 66054; No. 00 / 24893; No. 01 / 81405; No. 00 / 61637; No. 01 / 36489; No. 02 / 014356; No. 02 / 19963; No. 02 / 20034; No. 02 / 49673; No. 02 / 085940; No. 03 / 029291; No. 2003 / 055526; No. 2003 / 084477;Same as Pamphlet No. 2003 / 094858; same as Pamphlet No. 2004 / 002417; same as Pamphlet No. 2004 / 002424; same as Pamphlet No. 2004 / 009627; same as Pamphlet No. 2004 / 024761; same as Pamphlet No. 2004 / 033651; same as Pamphlet No. 2004 / 035603; same as Pamphlet No. 2004 / 043382; same as Pamphlet No. 2004 / 101600; same as Pamphlet No. 2004 / 101606; same as Pamphlet No. 2004 / 101611; same as Pamphlet No. 2004 / 106373; same as Pamphlet No. 2004 / 018667; same as Pamphlet No. 2005 / 001025; same as Pamphlet No. 2005 / 001136; same as Pamphlet No. 2005 / 021579; same as Pamphlet No. 2005 / 025606; same as Pamphlet No. 2005 / 032460; same as Pamphlet No. 2005 / 051327; same as Pamphlet No. 2005 / 063808; same as Pamphlet No. 2005 / 063809; same as Pamphlet No. 2005 / 070451; same as Pamphlet No. 2005 / 081687; same as Pamphlet No. 2005 / 084711; same as Pamphlet No. 2005 / 103076; same as Pamphlet No. 2005 / 100403; same as Pamphlet No. 2005 / 092369; same as Pamphlet No. 2006 / 50959; same as Pamphlet No. 2006 / 02646; and same as Pamphlet No. 2006 / 29094.;

[0117] Examples of other pharmaceuticals for use with the device can include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva® (denosumab), and Prolia® (denosamab); other biological agents such as Enbrel® (etanercept, a TNF-receptor / Fc fusion protein, a TNF blocker), Neulasta® (pegfilgrastim, pegylated filgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-MetG-CSF), and Nplate® (romiplostim); and small molecule drugs such as Sensipar® (cinacalcet). The device can also be used with other chemicals such as therapeutic antibodies, polypeptides, proteins, or iron, such as ferumoxitol, iron dextran, ferric glyconate, and iron sucrose. The pharmaceuticals can be in liquid form or reconstituted from a lyophilized form.

[0118] Among the proteins of certain descriptions are the specific proteins described below, including fusions, fragments, analogs, variants, or derivatives.

[0119] OPGL-specific antibodies, peptibodies, and related proteins (also referred to as RANKL-specific antibodies, peptibodies, etc.), including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies, including, but not limited to, the antibodies described in WO 03 / 002713 pamphlet (which is hereby incorporated by reference in its entirety with respect to OPGL-specific antibodies and antibody-related proteins), particularly those having the sequences described therein, particularly, but not limited to, those shown therein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, including OPGL-specific antibodies having either the light chain of SEQ ID NO: 2 as described in FIG. 2 and / or the heavy chain of SEQ ID NO: 4 as described in FIG. 4, each of which is hereby incorporated by reference in its entirety and specifically into this specification as disclosed in the above-mentioned publication.

[0120] Myostatin-binding proteins, peptibodies, and related proteins, including myostatin-specific peptibodies, particularly those described in US Patent Application Publication No. 2004 / 0181033 and WO 2004 / 058988 pamphlet, each of which is hereby incorporated by reference in its entirety, particularly in part with respect to myostatin-specific peptibodies, including, but not limited to, peptibodies of the mTN8-19 family having SEQ ID NOs: 305 to 351 including TN8-19-1 to TN8-19-40, TN8-19 con1, and TN8-19 con2; peptibodies of the mL2 family having SEQ ID NOs: 357 to 383; the mL15 family having SEQ ID NOs: 384 to 409; the mL17 family having SEQ ID NOs: 410 to 438; the mL20 family having SEQ ID NOs: 439 to 446; the mL21 family having SEQ ID NOs: 447 to 452; the mL24 family having SEQ ID NOs: 453 to 454; and those having SEQ ID NOs: 615 to 631, each of which is hereby incorporated by reference in its entirety and specifically into this specification as disclosed in the above-mentioned publication.

[0121] Particularly, IL-4 receptor specific antibodies, peptibodies, and related proteins, such as those that block activities mediated by the binding of IL-4 and / or IL-13 to receptors, including those described in International Publication No. WO 2005 / 047331 pamphlet or in the specification of PCT application PCT / US2004 / 37242 and US Patent Application Publication No. US 2005 / 112694, the entireties of which are hereby incorporated by reference into the present specification, particularly in part in relation to IL-4 receptor specific antibodies, and in particular, such antibodies are described therein, and in particular, and without limitation, here are: 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 as expressly stated, and the entireties of each of them are hereby incorporated by reference into the present specification individually and specifically as disclosed in the above-mentioned publications.

[0122] Interleukin 1-receptor 1 ("IL1-R1") specific antibodies, peptibodies, and related proteins, including but not limited to those described in US Patent Application Publication No. US 2004 / 097712 (the entireties of which are hereby incorporated by reference into the present specification, particularly in part in relation to IL1-R1 specific binding proteins, particularly monoclonal antibodies), and in particular, and without limitation: those expressly stated as 15CA, 26F5, 27F2, 24E12, and 10H7 are included, and the entireties of each of them are hereby incorporated by reference into the present specification individually and specifically as disclosed in the above-mentioned publications.

[0123] Ang2-specific antibodies, peptibodies, and related proteins, including but not limited to those described in WO 03 / 057134 and US 2003 / 0229023, the entireties of which are hereby incorporated by reference in their entirety, in particular in part, in relation to Ang2-specific antibodies and peptibodies, in particular those of the sequences described herein, and including but not limited to: L1(N); L1(N)WT; L1(N)1K WT; 2xL1(N); 2xL1(N)WT; Con4(N), Con4(N)1K WT, 2xCon4(N)1K; L1C; L1C 1K; 2xL1C; Con4C; Con4C 1K; 2xCon4C 1K; Con4-L1(N); Con4-L1C; TN-12-9(N); C17(N); TN8-8(N); TN8-14(N); Con 1(N), and also anti-Ang2 antibodies and formulations such as those described in WO 2003 / 030833 (the entirety of which is hereby incorporated by reference in relation hereto), in particular 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; AblF; AblK, AblP; and AblP, in their various permutations as described herein, each of which is hereby incorporated by reference in its entirety, individually and specifically, as disclosed in the above-mentioned publications.

[0124] NGF-specific antibodies, peptibodies, and related proteins, including, but not limited to, those described in U.S. Patent Application Publication No. 2005 / 0074821 and U.S. Patent No. 6,919,426, the entireties of which are hereby incorporated by reference in their entirety, particularly in relation to NGF-specific antibodies and related proteins, including, but not limited to, the NGF-specific antibodies designated herein as 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11, the entireties of each of which are hereby incorporated by reference in their entirety and specifically as disclosed in the above publications.

[0125] CD22-specific antibodies, peptibodies, and related proteins, such as those described in U.S. Patent No. 5,789,554, the entirety of which is hereby incorporated by reference in relation to CD22-specific antibodies and related proteins, including, but not limited to, human CD22-specific antibodies, such as humanized and fully human antibodies, including, but not limited to, humanized and fully human monoclonal antibodies, including, but not limited to, human CD22-specific IgG antibodies, such as a dimer of a human-mouse monoclonal hLL2 gamma chain disulfide bound to a human-mouse monoclonal hLL2 kappa chain, including, but not limited to, human CD22-specific fully humanized antibodies in epratuzumab, CAS Registry Number 501423-23-0, etc.

[0126] IGF-1 receptor-specific antibodies, peptibodies, and related proteins such as those described in International Publication No. WO 2006 / 069202, the entireties of which are hereby incorporated by reference into the present specification with respect to IGF-1 receptor-specific antibodies and related proteins, and which are not limited thereto, but where 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 are represented as IGF-1 specific antibodies, and IGF-1R-binding fragments and derivatives thereof, the entireties of each of which are hereby incorporated by reference into the present specification individually and specifically as disclosed in the above-mentioned publication.

[0127] Also included 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 below.

[0128] (i) U.S. Patent Application Publication Nos. 2006 / 0040358 (published Feb. 23, 2006), 2005 / 0008642 (published Jan. 13, 2005), 2004 / 0228859 (published Nov. 18, 2004), which are not limited thereto, but include, for example, antibody 1A (DSMZ deposit number DSM ACC2586), antibody 8 (DSMZ deposit number DSM ACC2589), antibody 23 (DSMZ deposit number DSM ACC2588) and antibody 18 as described herein.

[0129] (ii) International Publication No. WO 2006 / 138729 pamphlet (published on December 28, 2006), International Publication No. WO 2005 / 016970 pamphlet (published on February 24, 2005), and Lu et al. (2004), J. Biol. Chem. 279:2856 - 2865, including, but not limited to, antibodies 2F8, A12, and IMC - A12 as described herein.

[0130] (iii) International Publication No. WO 2007 / 012614 pamphlet (published on February 1, 2007), WO 2007 / 000328 pamphlet (published on January 4, 2007), WO 2006 / 013472 pamphlet (published on February 9, 2006), WO 2005 / 058967 pamphlet (published on June 30, 2005), and WO 2003 / 059951 pamphlet (published on July 24, 2003).

[0131] (iv) U.S. Patent Application Publication No. 2005 / 0084906 (published on April 21, 2005), including, but not limited to, antibodies 7C10, chimeric antibody C7C10, antibody h7C10, antibody 7H2M, chimeric antibody *7C10, antibody GM607, humanized antibody 7C10 version 1, humanized antibody 7C10 version 2, humanized antibody 7C10 version 3, and antibody 7H2HM as described herein.

[0132] (v) U.S. Patent Application Publication No. 2005 / 0249728 specification (published on November 10, 2005), 2005 / 0186203 specification (published on August 25, 2005), 2004 / 0265307 specification (published on December 30, 2004), 2003 / 0235582 (published on December 25, 2003), and Maloney et al. (2003), Cancer Res. 63:5073 - 5083, including, but not limited to, antibodies EM164, resurfaced EM164, humanized EM164, huEM164v1.0, huEM164v1.1, huEM164v1.2, and huEM164v1.3 as described herein.

[0133] (vi) U.S. Patent No. 7,037,498 (issued May 2, 2006), U.S. Patent Application Publication No. 2005 / 0244408 (published Nov. 30, 2005), and U.S. Patent Application Publication No. 2004 / 0086503 (published May 6, 2004), and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073, including, for example, antibody CP-751,871, and ATCC accession numbers PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, and antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3 produced by hybridomas having the same, respectively, as described herein.

[0134] (vii) U.S. Patent Application Publication No. 2005 / 0136063 (published Jun. 23, 2005) and U.S. Patent Application Publication No. 2004 / 0018191 (published Jan. 29, 2004), including, for example, antibody 19D12, and an antibody comprising a heavy chain encoded by a polynucleotide in plasmid 15H12 / 19D12 HCA(γ4) deposited with the ATCC under accession number PTA-5214 and a light chain encoded by a polynucleotide in plasmid 15H12 / 19D12 LCF(κ) deposited with the ATCC under accession number PTA-5220, as described herein.

[0135] (viii) U.S. Patent Application Publication No. 2004 / 0202655 (published on October 14, 2004), including, but not limited to, antibodies PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2, PINT-12A3, PINT-12A4, and PINT-12A5 as described herein; each and all of them are incorporated herein by reference with respect to the above-mentioned antibodies, peptibodies, and related proteins, particularly those targeting the IGF-1 receptor.

[0136] B-7 related protein 1 specific antibodies, peptibodies, related proteins, etc. (「B7RP-1」 is also referred to in the literature as B7H2, ICOSL, B7h, and CD275), in particular B7RP-1 specific fully human monoclonal IgG2 antibodies, in particular fully human IgG2 monoclonal antibodies that bind to epitopes in the first immunoglobulin-like domain of B7RP-1, in particular those that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, in activated T cells, and in particular those disclosed in U.S. Patent Application Publication No. 2008 / 0166352 and International Publication No. 07 / 011941 pamphlet in all of the above respects, the entireties of which are incorporated herein by reference with respect to such antibodies and related proteins, and are not limited thereto, but hereinafter: antibodies represented as 16H (having light chain variable and heavy chain variable sequences, SEQ ID NO: 1 and SEQ ID NO: 7 respectively); 5D (having light chain variable and heavy chain variable sequences, SEQ ID NO: 2 and SEQ ID NO: 9 respectively); 2H (having light chain variable and heavy chain variable sequences, SEQ ID NO: 3 and SEQ ID NO: 10 respectively); 43H (having light chain variable and heavy chain variable sequences, SEQ ID NO: 6 and SEQ ID NO: 14 respectively); 41H (having light chain variable and heavy chain variable sequences, SEQ ID NO: 5 and SEQ ID NO: 13 respectively); and 15H (having light chain variable and heavy chain variable sequences, SEQ ID NO: 4 and SEQ ID NO: 12 respectively), the entireties of each of which are incorporated herein by reference individually and specifically as disclosed in the above publications.

[0137] IL-15 specific antibodies, peptibodies, and related proteins, etc., in particular humanized monoclonal antibodies, in particular those disclosed in U.S. Patent Application Publication No. 2003 / 0138421; No. 2003 / 023586; and No. 2004 / 0071702; and U.S. Patent No. 7,153,507, etc., the entireties of each of which are incorporated herein by reference with respect to IL-15 specific antibodies and related proteins, including, for example, but not limited to, peptibodies including HuMax IL-15 antibodies and related proteins, such as 146B7.

[0138] IFN-gamma specific antibodies, peptibodies, and related proteins, especially human IFN-gamma specific antibodies, especially fully human anti-IFN-gamma antibodies, such as those described in U.S. Patent Application Publication No. 2005 / 0004353, which are hereby incorporated by reference in their entirety with respect to IFN-gamma specific antibodies, especially, for example, the antibodies designated herein as 1118; 1118*; 1119; 1121; and 1121*. The entire sequences of the heavy and light chains of each of these antibodies, as well as the sequences of their heavy and light chain variable regions and complementarity determining regions, are hereby incorporated by reference individually and specifically into this specification as disclosed in the above-mentioned publication and Thakur et al. (1999), Mol. Immunol. 36:1107-1115. Further, the descriptions of the properties of these antibodies provided in the above-mentioned publication are also hereby incorporated by reference in their entirety into this specification. Specific antibodies include those having the heavy chain of SEQ ID NO: 17 and the light chain of SEQ ID NO: 18; those having the heavy chain variable region of SEQ ID NO: 6 and the light chain variable region of SEQ ID NO: 8; those having the heavy chain of SEQ ID NO: 19 and the light chain of SEQ ID NO: 20; those having the heavy chain variable region of SEQ ID NO: 10 and the light chain variable region of SEQ ID NO: 12; those having the heavy chain of SEQ ID NO: 32 and the light chain of SEQ ID NO: 20; those having the heavy chain variable region of SEQ ID NO: 30 and the light chain variable region of SEQ ID NO: 12; those having the heavy chain sequence of SEQ ID NO: 21 and the light chain sequence of SEQ ID NO: 22; those having the heavy chain variable region of SEQ ID NO: 14 and the light chain variable region of SEQ ID NO: 16; those having the heavy chain of SEQ ID NO: 21 and the light chain of SEQ ID NO: 33; and those having the heavy chain variable region of SEQ ID NO: 14 and the light chain variable region of SEQ ID NO: 31. A specific antibody considered is antibody 1119 as disclosed in the above-mentioned U.S. publication and having the complete heavy chain of SEQ ID NO: 17 as disclosed therein and the complete light chain of SEQ ID NO: 18 as disclosed therein.

[0139] TALL-1 specific antibodies, peptibodies, and related proteins, and other TALL specific binding proteins such as those described in U.S. Patent Application Publication Nos. 2003 / 0195156 and 2006 / 0135431, the entireties of each of which are incorporated herein by reference with respect to the TALL-1 binding proteins, particularly the molecules of Tables 4 and 5B, and the entireties of each of which are incorporated herein by reference individually and specifically as disclosed in the above-mentioned publications.

[0140] Parathyroid hormone (''PTH'') specific antibodies, peptibodies, and related proteins such as those described in U.S. Patent No. 6,756,480, the entirety of which is incorporated herein by reference with respect to the proteins that bind to PTH, particularly in part.

[0141] Thrombopoietin receptor (''TPO-R'') specific antibodies, peptibodies, and related proteins such as those described in U.S. Patent No. 6,835,809, the entirety of which is incorporated herein by reference with respect to the proteins that bind to TPO-R, particularly in part.

[0142] Hepatocyte growth factor (''HGF'') specific antibodies, peptibodies, and related proteins, including those that target the HGF / SF:cMet axis (HGF / SF:c-Met), such as the fully human monoclonal antibody that neutralizes hepatocyte growth factor / scatter factor (HGF / SF) described in U.S. Patent Application Publication No. 2005 / 0118643 and International Publication No. 2005 / 017107 pamphlet, huL2G7 described in U.S. Patent No. 7,220,410, and OA-5d5 described in U.S. Patent Nos. 5,686,292, 6,468,529, and International Publication No. 96 / 38557 pamphlet, the entireties of each of which are incorporated herein by reference with respect to the proteins that bind to HGF, particularly in part.

[0143] TRAIL-R2 specific antibodies, peptibodies, related proteins, etc., such as those described in U.S. Patent No. 7,521,048, are hereby incorporated by reference into the present specification in their entirety, particularly in part, with respect to proteins that bind to TRAIL-R2.

[0144] Activin A specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Application Publication No. 2009 / 0234106, are hereby incorporated by reference into the present specification in their entirety, particularly in part, with respect to proteins that bind to Activin A.

[0145] TGF-beta specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent No. 6,803,453 and U.S. Patent Application Publication No. 2007 / 0110747, are hereby incorporated by reference into the present specification in their entirety, particularly in part, with respect to proteins that bind to TGF-beta.

[0146] Amyloid beta protein specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in International Publication No. 2006 / 081171 pamphlet, are hereby incorporated by reference into the present specification in their entirety, particularly in part, with respect to proteins that bind to amyloid beta protein. One possible antibody is an antibody having a heavy chain variable region containing SEQ ID NO: 8 and a light chain variable region having SEQ ID NO: 6, as disclosed in the above-mentioned publication.

[0147] c-Kit specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Application Publication No. 2007 / 0253951, are hereby incorporated by reference into the present specification in their entirety, particularly in part, with respect to proteins that bind to c-Kit and / or other stem cell factor receptors.

[0148] OX40L-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Application Publication No. 2006 / 0002929, the entire content of which is hereby incorporated by reference herein, particularly in part, with respect to proteins that bind to OX40L and / or other ligands of the OX40 receptor.

[0149] Other exemplary proteins include Activase® (alteplase, tPA); Aranesp® (darbepoetin alfa); Epogen® (epoetin alfa, or erythropoietin); GLP-1, Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonal antibody); Betaseron® (interferon beta); Campath® (alemtuzumab, anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokine receptor mAb); Enbrel® (etanercept, TNF-receptor / Fc fusion protein, TNF blocker); Eprex® (epoetin alfa); Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1); Genotropin® (somatropin, human growth hormone); Herceptin® (trastuzumab, anti-HER2 / neu (erbB2) receptor mAb); Humatrope® (somatropin, human growth hormone); Humira® (adalimumab); insulin in solution; Infergen® (interferon alfa-con-1); Natrecor® (nesiritide; recombinant human B-type natriuretic peptide (hBNP); Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide® (epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin);Raptiva (registered trademark) (efalizumab); Cimzia (registered trademark) (certolizumab pegol, CDP870); Soliris (trademark) (eculizumab); pexelizumab (anti-C5 complement); Numax (registered trademark) (MEDI-524); Lucentis (registered trademark) (ranibizumab); Panorex (registered trademark) (17-1A, edrecolomab); Trabio (registered trademark) (lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4); Osidem (registered trademark) (IDM-1); OvaRex (registered trademark) (B43.13); Nuvion (registered trademark) (visilizumab); cantuzumab mertansine (huC242-DM1); NeoRecormon (registered trademark) (epoetin beta); Neumega (registered trademark) (oprelvekin, human interleukin 11); Neulasta (registered trademark) (pegfilgrastim, pegylated G-CSF, pegylated hu-Met-G-CSF); Neupogen (registered trademark) (filgrastim, G-CSF, hu-MetG-CSF); Orthoclone OKT3 (registered trademark) (muromonab-CD3, anti-CD3 monoclonal antibody); Procrit (registered trademark) (epoetin alpha); Remicade (registered trademark) (infliximab, anti-TNFα monoclonal antibody); Reopro (registered trademark) (abciximab, anti-GP lIb / Ilia receptor monoclonal antibody); Actemra (registered trademark) (anti-IL6 receptor mAb); Avastin (registered trademark) (bevacizumab); HuMax-CD4 (zanolimumab); Rituxan (registered trademark) (rituximab, anti-CD20 mAb); Tarceva (registered trademark) (erlotinib); Roferon-A (registered trademark) - (interferon alpha-2a); Simulect (registered trademark) (basiliximab); Prexige (registered trademark) (lumiracoxib); Synagis (registered trademark) (palivizumab);146B7-CHO (see US Patent No. 7,153,507 for anti-IL15 antibody); Tysabri® (natalizumab, anti-α integrin mAb); Valortim® (MDX-1303, anti-Bacillus anthracis protective antigen mAb); ABthrax™; Vectibix® (panitumumab); Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-1 trap (Fc portion of human IgG1 and extracellular domains of both IL-1 receptor components (type I receptor and receptor accessory protein)); VEGF trap (Ig domain of VEGFR1 fused to IgG1 Fc); Zenapax® (daclizumab); Zenapax® (daclizumab, anti-IL-2Rα mAb); Zevalin® (ibritumomab tiuxetan); Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonal antibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist); CNTO148 (golimumab, anti-TNFα mAb); HGS-ETR1 (mapatumumab; human anti-TRAIL receptor-1 mAb); HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab); M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-Clostridium difficile Toxin A and Toxin B C mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22 dsFv-PE38 complex (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333 (anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-Cripto mAb;Anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-3019); anti-CTLA4 mAb; anti-Eotaxin-1 mAb (CAT-213); anti-FGF8 mAb; anti-Ganglioside GD2 mAb; anti-Ganglioside GM2 mAb; anti-GDF-8 human mAb (MYO-029); anti-GM-CSF Receptor mAb (CAM-3001); anti-HepC mAb (HuMax HepC); anti-IFNα mAb (MEDI-545, MDX-1103); anti-IGF1R mAb; anti-IGF-1R mAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12 / IL23 mAb (CNTO1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5 Receptor mAb; anti-Integrin Receptor mAb (MDX-018, CNTO95); anti-IP10 Ulcerative Colitis mAb (MDX-1100); anti-LLY Antibody; BMS-66513; anti-Mannose Receptor / hCGβ mAb (MDX-1307); anti-Mesothelin dsFv-PE38 Conjugate (CAT-5001); anti-PD1 mAb (MDX-1106 (ONO-4538)); anti-PDGFRα Antibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL Receptor-2 human mAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR / Flt-1 mAb; anti-ZP3 mAb (HuMax-ZP3); NVS Antibody #1; and NVS Antibody #2.;

[0150] Similarly, sclerostin antibodies, such as, but not limited to, romosozumab, brodalumab, or BPS 804 (Novartis) may also be included. Further, therapeutic agents such as rilotumumab, voxelotor, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA may be included. Further, the device may include monoclonal antibodies (IgG) that bind to human proprotein convertase subtilisin / kexin type 9 (PCSK9), such as those described in U.S. Patent No. 8,030,547, U.S. Patent Application Publication No. 2013 / 0064825, International Publication Nos. 2008 / 057457, 2008 / 057458, 2008 / 057459, 2008 / 063382, 2008 / 133647, 2009 / 100297, 2009 / 100318, 2011 / 037791, 2011 / 053759, 2011 / 053783, 2008 / 125623, 2011 / 072263, 2009 / 055783, 2012 / 0544438, 2010 / 029513, 2011 / 111007, 2010 / 077854, 2012 / 088313, 2012 / 101251, 2012 / 101252, 2012 / 101253, 2012 / 109530, and 2001 / 031007.

[0151] Similarly, for the treatment of melanoma or other cancers, talimogene laherparepvec or another oncolytic HSV may be included. Examples of oncolytic HSVs include, but are not limited to, talimogene laherparepvec (U.S. Patent Nos. 7,223,593 and 7,537,924); OncoVEXGALV / CD (U.S. Patent No. 7,981,669); OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143); G207, 1716; NV1020; NV12023; NV1034 and NV1042 (Vargehes et al. (2002), Cancer Gene Ther., 9(12):967-978).

[0152] Similarly, TIMP is included. TIMP is an endogenous tissue inhibitor of metalloproteinases (TIMPs) and is important in many natural processes. TIMP-3 is expressed by various cells and / or is present in the extracellular matrix; it can play a role in inhibiting all major cartilage-degrading metalloproteinases and 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-3 and the nucleic acid sequence of the DNA encoding TIMP-3 are disclosed in U.S. Patent No. 6,562,596, issued May 13, 2003, the disclosure of which is incorporated herein by reference. Descriptions of TIMP mutations can be found in U.S. Patent Application Publication No. 2014 / 0274874 and International Publication No. 2014 / 152012 pamphlet.

[0153] Similarly, human calcitonin gene-related peptide (CGRP) receptors, and bispecific antibody molecules that target CGRP receptors and antagonist antibodies against other headache targets are included. Further information regarding these molecules can be found in International Publication No. 2010 / 075238 pamphlet.

[0154] Furthermore, bispecific T cell engager antibody (BiTe), such as blinatumomab, can be used in the device. Alternatively, an APJ macromolecular agonist, such as apelin or an analog thereof, can be included in the device. Information regarding such molecules can be found in WO 2014 / 099984 pamphlet.

[0155] In some embodiments, the agent comprises a therapeutically effective amount of anti-thymic stromal lymphopoietin (TSLP) or a TSLP receptor antibody. Examples of anti-TSLP antibodies that can be used in such embodiments include, but are not limited to, those described in U.S. Pat. No. 7,982,016, U.S. Pat. No. 8,232,372, and U.S. Patent Application Publication No. 2009 / 0186022. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in U.S. Pat. No. 8,101,182. In a particularly preferred embodiment, the agent comprises a therapeutically effective amount of an anti-TSLP antibody designated as A5 in U.S. Pat. No. 7,982,016.

[0156] The plunger rod assembly system, machine, method, and elements thereof have been described with respect to exemplary embodiments, but are not limited thereto. The detailed description is to be regarded as illustrative only and does not describe all possible embodiments of the invention. This is because it is not practical, if not impossible, to describe all possible embodiments. Using either current technology or technology developed after the filing date of this patent, numerous alternative embodiments can be implemented, and these are within the scope of the claims that define the invention.

[0157] It should be understood that the legal scope of the present invention is defined by the language of the claims set forth at the end of this patent. The appended claims should be broadly construed to include other variations and embodiments thereof that may be made by those skilled in the art without departing from the scope of equivalents of those systems, machines, methods, and elements.

Claims

1. 1. A machine for coupling a plunger rod to a syringe assembly, the machine comprising: a selected carriage including a cradle having a seat portion sized to receive the syringe assembly and an aperture portion disposed above the seat portion and sized to receive a plunger rod; an actuator 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; and The selected carriage is selected from separate and interchangeable first and second carriages, the first carriage including 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 different from the first size.

2. 2. The machine of claim 1, further comprising a selected pressure plate positioned above said cradle such that said cradle moves directly beneath said selected pressure plate as said cradle moves from said first position to said second position, said selected pressure plate adapted to apply a downward force to said plunger rod disposed in said aperture portion of said cradle as said cradle moves from said first position to said second position.

3. 3. The machine of claim 2, further comprising a selected constant tension spring operably coupled to the selected pressure plate, the selected pressure plate defining an entrance portion adapted to receive a proximal end of the plunger rod as the cradle moves from the first position to the second position, the selected constant tension spring providing the downward force applied via the selected pressure plate to the plunger rod as the cradle moves between the first position and the second position.

4. 4. The machine of claim 1, wherein the first carriage includes a first pressure plate coupled to the first carriage and the second carriage includes a second pressure plate coupled to the second carriage, such that the selected pressure plate is coupled to the selected carriage.

5. The machine of any one of claims 1 to 4, further comprising a quick change fastener and a table, the selected carriage being removably coupled to the table by the quick change fastener.

6. 6. The machine of claim 1, wherein the first carriage includes a first base and the second carriage includes a second base, and the actuation device includes a servo motor adapted to be operatively connected to the first and second bases.

7. 7. The machine of claim 1, further comprising a selected friction element disposed adjacent to the selected carriage, the selected friction element adapted to engage a barrel of the syringe assembly carried by the cradle during movement of the cradle from the first position to the second position, the friction element adapted to apply a rotational force to the barrel to spin the syringe assembly relative to the plunger rod as the cradle moves from the first position to the second position.

8. 8. The machine of claim 7, wherein the first carriage includes a first guide plate coupled to the first carriage and supporting a first friction element, and the second carriage includes a second guide plate coupled to the second carriage and supporting a second friction element, such that the selected friction element is supported by a selected guide plate coupled to the selected carriage.

9. further, a selected movable plunger rod base coupled to the selected carriage, the selected plunger rod base being positioned above the pedestal and including an orifice sized to receive a flanged proximal end of the plunger rod, the orifice being coaxially aligned with the aperture portion of the pedestal, the plunger rod base being movable together with the pedestal from the first position to the second position; a selected retaining cap having an outwardly extending tab disposed to extend into the orifice of the selected plunger rod base, the selected retaining cap being removably attached to the selected plunger rod base; and A machine according to any preceding claim, wherein the selected retaining cap is fixed relative to the selected carriage and disposed within the orifice when the pedestal is in the first position.

10. 10. The machine of claim 9, wherein the selected plunger rod base is selected from distinct and interchangeable first and second plunger rod bases, the first plunger rod base including an orifice adapted to accept a plunger rod of a first size and the second plunger rod base including an orifice sized to accept a plunger rod of a second size different from the first size.

11. 11. The machine of claim 1, wherein the cradle includes a cradle axis that is coaxial with a longitudinal axis of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed within the cradle, the cradle axis being disposed at an angle greater than zero degrees relative to the vertical.

12. 12. The machine of claim 11, wherein the selected carriage includes a carousel-style turntable with an axis of rotation that is parallel to the cradle axis such that the axis of rotation of the selected carriage is disposed at an angle greater than zero degrees relative to vertical.

13. A machine according to any preceding claim, wherein the actuation device is adapted to index the cradle between the first and second positions in response to an actuation event.

14. The machine of claim 13 , wherein the actuator indexes the cradle only once upon the occurrence of the activation event.

15. A machine according to any one of claims 1 to 14, wherein the actuation device includes a servo motor and an operating switch for operably controlling the servo motor, the servo motor being coupled to the selected carriage to move the cradle via the selected carriage.

16. A machine according to any preceding claim, wherein the actuation device comprises a lever for a user to manually index the cradle from the first position to the second position.

17. 17. The machine of claim 16, wherein the actuation device includes a slidable bracket arranged to move the lever.

18. A machine as claimed in any one of claims 2 to 17, wherein the selected carriage is rotationally arranged relative to the selective pressure plate.

19. 19. The machine of any one of claims 1 to 18, wherein the seat portion of the cradle includes a first roller and a second roller separated by a gap, the first and second rollers of the seat portion adapted to engage the barrel of the syringe assembly and retain the barrel within the gap when carried by the cradle, and the first and second rollers enable the syringe assembly to spin as the cradle indexes from the first position to the second position.

20. A machine according to any preceding claim, wherein the selected carriage includes a plurality of cradles supported by the selected carriage.

21. further comprising a selected exit chute disposed adjacent the selected carriage at the second position of the cradle, the selected exit chute adapted to receive the plunger rod and syringe assembly from the cradle after the plunger rod is coupled to the syringe assembly; 21. The machine of any one of claims 1 to 20, wherein the first carriage includes a first exit chute coupled to the first carriage, and the second carriage includes a second exit chute coupled to the second carriage, such that the selected exit chute is coupled to the selected carriage.

22. 22. The machine of claim 21, wherein the selected exit chute includes a ramp, the ramp including a slot sized to receive the plunger rod and syringe assembly after the cradle moves to the second position.

23. 1. A method of using a machine to couple a plunger rod to a syringe assembly, the method comprising: Decoupling the second carriage from the actuator; coupling a first carriage to the actuation device after decoupling the second carriage from the actuation device, the first carriage including a first movable cradle adapted to receive a syringe assembly of a first size; positioning a first syringe assembly on the first movable 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; positioning a first plunger rod in the first cradle of the first carriage, the first plunger rod including a distal rod end and a proximal rod end, the distal rod end being disposed above the proximal end of the first syringe assembly and in axial alignment with the plunger; and activating the actuator coupled to the first carriage to move the first cradle from a first position to a second position, thereby exerting a force on the first plunger rod such that the first plunger rod is coupled with the first syringe assembly. A method comprising:

24. 24. The method of claim 23, further comprising applying a downward force to the proximal rod end of the first plunger rod as the first cradle moves from the first position toward the second position.

25. 25. The method of claim 23 or 24, further comprising fastening the first carriage to a table by a quick change fastener, the table being connected to the actuation device.

26. 26. The method of claim 25, wherein decoupling the second carriage from the actuation device includes decoupling the quick change fasteners that secure the second carriage to the table.

27. A method according to any one of claims 23 to 26, wherein decoupling the second carriage from the actuation device comprises decoupling a servo motor of the actuation device from a receiving member of the second carriage.

28. The method of any one of claims 23 to 27, wherein coupling the first carriage to the actuation device comprises coupling a servo motor of the actuation device to a receiving member of the first carriage.

29. further comprising positioning a second syringe assembly in a second cradle of the second carriage prior to decoupling the second carriage from the actuation device, the second cradle adapted to receive the second syringe assembly of a second size, the second syringe assembly including distal and proximal ends, a syringe barrel, and a plunger disposed within the syringe barrel, the second cradle of the second carriage sized to receive the second syringe barrel of the second size; positioning a second plunger rod in the second cradle of the second carriage, the second plunger rod including a distal rod end and a proximal rod end, the distal rod end being disposed above the proximal end of the second syringe assembly and in axial alignment with the plunger; and activating the actuator coupled to the second carriage to move the second cradle from a first position to a second position, thereby exerting a force on the second plunger rod such that the second plunger rod is coupled to the second syringe assembly. The method according to any one of claims 23 to 28, comprising:

30. 1. A machine for coupling a plunger rod to a syringe assembly, the machine comprising: 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 actuation device operably 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; an elongated pressure plate positioned adjacent the carriage and defining an inlet and an outlet, the inlet sized to receive a proximal end of the plunger rod and apply a downward force to the proximal end of the plunger rod as the plunger rod moves from the inlet to the outlet; and a constant tension spring coupled to the pressure plate, the constant tension spring providing a downward force to the pressure plate such that the downward force is transmitted through the pressure plate to the plunger rod as the pedestal moves between the first position and the second position; Including, machinery.

31. 31. The machine of claim 30, wherein the inlet includes an inclined surface positioned above the outlet relative to the carriage.

32. 32. The machine of claim 30 or 31, further comprising at least one guide post, the pressure plate being slidably coupled to the at least one guide post in a direction parallel to a longitudinal axis of the carriage.

33. 33. The machine of claim 32, further comprising a threaded rod for adjustably mounting said pressure plate to said carriage such that said pressure plate is adjustable in a direction parallel to said longitudinal axis of said carriage to accommodate plunger rods of different heights.

34. 34. The machine of claim 30, further comprising a friction element disposed adjacent to the carriage and below the pressure plate, the friction element adapted to engage a barrel of the syringe assembly carried by the cradle during movement of the cradle from the first position to the second position, the friction element adapted to apply a rotational force to the barrel to spin the syringe assembly relative to the plunger rod.

35. 35. The machine of claim 34, further comprising a guide plate and said friction element secured to said guide plate, said friction element being an elongated cord of elastomeric material.

36. 36. A machine according to any one of claims 30 to 35, wherein the actuation device is operatively connected to the carriage and adapted to index the cradle between the first and second positions in response to an actuation event.

37. 37. The machine of claim 36, wherein the actuator indexes the cradle only once upon the occurrence of the activation event.

38. further, a movable plunger rod base coupled to the carriage, the plunger rod base being disposed above the pedestal and including an orifice sized to receive a flanged proximal end of the plunger rod, the orifice being coaxially aligned with the aperture portion of the pedestal, the plunger rod base being movable together with the pedestal from the first position to the second position; A retaining cap removably attached to the plunger rod base, the retaining cap having an outwardly extending tab disposed to extend into the orifice of the plunger rod base. and A machine according to any one of claims 30 to 37, wherein the retaining cap is fixed relative to the carriage and is located within the orifice when the pedestal is in the first position.

39. 39. The machine of claim 38, wherein the plunger rod base is selected from separate and interchangeable first and second plunger rod bases, the first plunger rod base including an orifice sized to accept a flanged plunger rod end of a first size, and the second plunger rod base sized to accept a flanged plunger rod end of a second size different from the first size.

40. 40. A machine as claimed in any one of claims 30 to 39, wherein the cradle includes a cradle axis that is coaxial with a longitudinal axis of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed within the cradle, the cradle axis being disposed at an angle greater than zero degrees with respect to the vertical.

41. 41. The machine of claim 40, wherein the carriage includes a carousel-style turntable with an axis of rotation that is parallel to the cradle axis such that the axis of rotation of the carriage is disposed at an angle greater than zero degrees with respect to vertical.

42. A machine as claimed in any one of claims 30 to 41, wherein the carriage is arranged in rotation relative to the pressure plate.

43. A machine as claimed in any one of claims 30 to 42, wherein the actuation device includes a servo motor and an operating switch for operably controlling the servo motor, the servo motor being coupled to the carriage to move the cradle via the carriage.

44. A machine according to any one of claims 30 to 43, wherein the actuation device includes a lever for a user to manually index the cradle from the first position to the second position.

45. 45. A machine as claimed in claim 44, wherein the actuation device includes a slidable bracket arranged to move the lever.

46. 46. ​​The machine of any one of claims 30 to 45, wherein the seat portion of the cradle includes first and second rollers separated by a gap, the first and second rollers of the seat portion adapted to engage the barrel of the syringe assembly and hold the barrel within the gap when carried by the cradle, and the first and second rollers enable the syringe assembly to spin as the cradle indexes from the first position to the second position.

47. A machine according to any one of claims 30 to 46, wherein the carriage includes a plurality of cradles supported by the carriage.

48. 48. The machine of any one of claims 30 to 47, further comprising an exit chute positioned adjacent to the carriage at the second position of the cradle, the exit chute adapted to receive the plunger rod and syringe assembly from the cradle after the plunger rod is coupled to the syringe assembly.

49. 49. The machine of claim 48, wherein the exit chute includes a ramp, the ramp including a slot sized to receive the plunger rod and syringe assembly after the cradle moves to the second position.

50. 50. The machine of any one of claims 30 to 49, wherein the carriage is selected from separate and interchangeable first and second carriages, the first carriage including a cradle with a seat portion sized to receive a syringe assembly of a first size, and the second carriage including a cradle with a seat portion sized to receive a syringe assembly of a second size.

51. 1. A machine for coupling a plunger rod to a syringe assembly, the machine comprising: 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 actuation device operably 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 positioned adjacent to the carriage such that the pedestal moves beneath the pressure plate as the pedestal 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 pedestal as the pedestal moves from the first position to the second position. and The actuation device includes a lever operatively coupled to the carriage and adapted to be manipulated to index the cradle from the first position to the second position.

52. 52. The machine of claim 51, wherein the actuator is configured to index the cradle only once upon the occurrence of an activation event.

53. 53. A machine as claimed in claim 52, wherein the lever is movably mounted to a base of the carriage and the lever is arranged to effect the actuation event when the lever moves from a rest position to an actuation position.

54. A machine as claimed in any one of claims 51 to 53, wherein the actuation device includes a motor-operated bracket disposed adjacent the lever, the bracket adapted to move the lever between the rest position and the activation position.

55. further, a movable plunger rod base coupled to the carriage, the plunger rod base being disposed above the pedestal and including an orifice sized to receive a flanged proximal end of the plunger rod, the orifice being coaxially aligned with the aperture portion of the pedestal, the plunger rod base being movable together with the pedestal from the first position to the second position; A retaining cap removably attached to the plunger rod base, the retaining cap having an outwardly extending tab disposed to extend into the orifice of the plunger rod base. and A machine as claimed in any one of claims 51 to 54, wherein the retaining cap is fixed relative to the carriage and located within the orifice when the pedestal is in the first position.

56. 56. The machine of claim 55, wherein the plunger rod base is selected from separate and interchangeable first and second plunger rod bases, the first plunger rod base including an orifice sized to accept a flanged plunger rod end of a first size, and the second plunger rod base sized to accept a flanged plunger rod end of a second size different from the first size.

57. 57. A machine as claimed in any one of claims 51 to 56, wherein the cradle includes a cradle axis that is coaxial with a longitudinal axis of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed within the cradle, the cradle axis being disposed at an angle greater than zero degrees with respect to the vertical.

58. 58. The machine of claim 57, wherein the carriage includes a carousel-style turntable with an axis of rotation that is parallel to the cradle axis such that the axis of rotation of the carriage is disposed at an angle greater than zero degrees with respect to vertical.

59. A machine as claimed in any one of claims 51 to 58, wherein the carriage is arranged in rotation relative to the pressure plate.

60. A machine as claimed in any one of claims 51 to 59, wherein the actuation device includes a servo motor and an operating switch for operably controlling the servo motor, the servo motor being coupled to the carriage to move the cradle via the carriage.

61. 61. The machine of any one of claims 51 to 60, wherein the seat portion of the cradle includes first and second rollers separated by a gap, the first and second rollers of the seat portion adapted to engage the barrel of the syringe assembly and hold the barrel within the gap when carried by the cradle, and the first and second rollers enable the syringe assembly to spin as the cradle indexes from the first position to the second position.

62. A machine according to any one of claims 51 to 61, wherein the carriage includes a plurality of cradles supported by the carriage.

63. 63. The machine of any one of claims 51 to 62, further comprising an exit chute positioned adjacent to the carriage at the second position of the cradle, the exit chute adapted to receive the plunger rod and syringe assembly from the cradle after the plunger rod is coupled to the syringe assembly.

64. 64. The machine of claim 63, wherein the exit chute includes a ramp, the ramp including a slot sized to receive the plunger rod and syringe assembly after the cradle moves to the second position.

65. 65. The machine of any one of claims 51 to 64, wherein the carriage is selected from separate and interchangeable first and second carriages, the first carriage including a cradle with a seat portion sized to receive a syringe assembly of a first size, and the second carriage including a cradle with a seat portion sized to receive a syringe assembly of a second size.

66. 66. The machine of any one of claims 51 to 65, further comprising a friction element disposed adjacent to the carriage and below the pressure plate, the friction element adapted to engage a barrel of the syringe assembly carried by the cradle during movement of the cradle from the first position to the second position, the friction element adapted to apply a rotational force to the barrel to spin the syringe assembly relative to the plunger rod.

67. 67. The machine of claim 66, further comprising a guide plate and said friction element secured to said guide plate, said friction element being an elongated cord of elastomeric material.

68. 68. The machine of any one of claims 51 to 67, further comprising a constant tension spring coupled to the pressure plate, the constant tension spring providing a downward force to the pressure plate as the cradle moves between the first position and the second position, the downward force being transmitted through the pressure plate to the plunger rod.

69. 1. A machine for coupling a plunger rod to a syringe assembly, the machine comprising: 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; and an actuation device operably coupled to the carriage and adapted to index the cradle only once, upon the occurrence of an activation event, from a first position to a second position to couple the plunger rod to the syringe assembly. Including, machinery.

70. 70. The machine of claim 69, further comprising a pressure plate positioned adjacent to the carriage such that the cradle moves directly beneath the pressure plate as 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 as the cradle moves from the first position to the second position.

71. 71. A machine as claimed in claim 69 or 70, wherein the actuation device includes a servo motor and an operating switch for operably controlling the servo motor, the servo motor coupled to the carriage to move the pedestal via the carriage.

72. 72. The machine of claim 71, further comprising a two-handed anti-tie-down operating switch, said operating switch being positioned to effect said activation event.

73. A machine as claimed in any one of claims 69 to 72, wherein the actuation device includes a lever operably coupled to the carriage, the lever being arranged to be manipulated to effect the activation event.

74. 74. A machine as claimed in claim 73, wherein the lever is movably mounted to a base of the carriage and the lever is arranged to effect the actuation event when the lever moves from a rest position to an actuation position.

75. 75. A machine as claimed in claim 73 or 74, wherein the actuation device includes a motor-operated bracket disposed adjacent the lever, the bracket adapted to move the lever between the rest position and the activation position.

76. further, a movable plunger rod base coupled to the carriage, the plunger rod base being disposed above the pedestal and including an orifice sized to receive a flanged proximal end of the plunger rod, the orifice being coaxially aligned with the aperture portion of the pedestal, the plunger rod base being movable together with the pedestal from the first position to the second position; A retaining cap removably attached to the plunger rod base, the retaining cap having an outwardly extending tab disposed to extend into the orifice of the plunger rod base. and A machine as claimed in any one of claims 69 to 75, wherein the retaining cap is fixed relative to the carriage and located within the orifice when the pedestal is in the first position.

77. 77. The machine of claim 76, wherein the plunger rod base is selected from separate and interchangeable first and second plunger rod bases, the first plunger rod base including an orifice sized to accept a flanged plunger rod end of a first size, and the second plunger rod base sized to accept a flanged plunger rod end of a second size different from the first size.

78. 78. A machine as claimed in any one of claims 69 to 77, wherein the cradle includes a cradle axis that is coaxial with a longitudinal axis of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed within the cradle, the cradle axis being disposed at an angle greater than zero degrees with respect to the vertical.

79. 79. The machine of claim 78, wherein the carriage includes a carousel-style turntable with an axis of rotation that is parallel to the cradle axis such that the axis of rotation of the carriage is disposed at an angle greater than zero degrees with respect to vertical.

80. A machine as claimed in any one of claims 69 to 79, wherein the carriage is rotationally arranged relative to the pressure plate.

81. 81. The machine of any one of claims 69 to 80, wherein the seat portion of the cradle includes first and second rollers separated by a gap, the first and second rollers of the seat portion adapted to engage the barrel of the syringe assembly and hold the barrel within the gap when carried by the cradle, and the first and second rollers enable the syringe assembly to spin as the cradle indexes from the first position to the second position.

82. A machine according to any one of claims 69 to 81, wherein the carriage includes a plurality of cradles supported by the carriage.

83. 83. The machine of any one of claims 69 to 82, further comprising an exit chute positioned adjacent to the carriage at the second position of the cradle, the exit chute adapted to receive the plunger rod and syringe assembly from the cradle after the plunger rod is coupled to the syringe assembly.

84. 84. The machine of claim 83, wherein the exit chute includes a ramp, the ramp including a slot sized to receive the plunger rod and syringe assembly after the cradle moves to the second position.

85. 85. The machine of any one of claims 69 to 84, wherein the carriage is selected from separate and interchangeable first and second carriages, the first carriage including a cradle with a seat portion sized to receive a syringe assembly of a first size, and the second carriage including a cradle with a seat portion sized to receive a syringe assembly of a second size.

86. 86. The machine of any one of claims 69 to 85, further comprising a friction element disposed adjacent to the carriage and below the pressure plate, the friction element adapted to engage a barrel of the syringe assembly carried by the cradle during movement of the cradle from the first position to the second position, the friction element adapted to apply a rotational force to the barrel to spin the syringe assembly relative to the plunger rod.

87. 87. The machine of claim 86, further comprising a guide plate and said friction element secured to said guide plate, said friction element being an elongated cord of elastomeric material.

88. 88. The machine of any one of claims 69 to 87, further comprising a constant tension spring coupled to the pressure plate, the constant tension spring providing a downward force to the pressure plate as the cradle moves between the first position and the second position, the downward force being transmitted through the pressure plate to the plunger rod.

89. 1. A method of using a machine to couple a plunger rod to a syringe assembly, the method comprising: positioning a syringe assembly on a movable cradle of a carriage, the syringe assembly including 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; positioning a plunger rod in the cradle, the plunger rod including a distal rod end and a proximal rod end, the distal rod end of the plunger rod being disposed above the proximal end of the syringe assembly and in axial alignment with the plunger; activating an actuator operably connected to the carriage; and indexing the cradle from the first position to the second position only once in response to activation of the actuator, wherein as the cradle indexes from the first position to the second position, a force is applied to either or both of the syringe assembly and the plunger rod to couple the plunger rod to the plunger of the syringe assembly. A method comprising:

90. 90. The method of claim 89, wherein indexing the cradle comprises rotating the carriage about an axis of rotation of the carriage.

91. 91. The method of claim 90, wherein rotating the carriage comprises rotating the carriage greater than zero degrees to index the cradle from the first position to the second position.

92. 92. The method of any one of claims 89 to 91, wherein actuating the actuation device comprises moving a lever, the lever causing the carriage to index the cradle from the first position to the second position.

93. 93. The method of claim 92, wherein activating the actuator includes triggering an operating switch coupled to a servo motor, the servo motor being positioned to slide a bracket to move the lever.

94. 94. The method of any one of claims 89 to 93, wherein activating the actuation device comprises triggering an operating switch coupled to a servo motor, the servo motor being operably coupled to the carriage.

95. 95. The method of any one of claims 89 to 94, further comprising applying a downward force to the proximal rod end of the plunger rod as the cradle moves from the first position toward the second position.

96. 96. The method of claim 95, wherein applying a downward force to the proximal rod end of the plunger rod includes moving the plunger rod beneath a pressure plate positioned adjacent to the carriage as the cradle moves from the first position to the second position.

97. 97. The method of any one of claims 89 to 96, further comprising applying a rotational force to the barrel of the syringe assembly while the cradle moves from the first position to the second position.

98. 98. The method of claim 97, wherein applying the rotational force comprises engaging the syringe assembly with a friction element disposed adjacent the carriage as the cradle moves from the first position to the second position.

99. 1. A machine for coupling a plunger rod to a syringe assembly, the machine comprising: 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 actuation device operably 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 friction element disposed adjacent to the carriage, the friction element adapted to engage a barrel of the syringe assembly carried by the cradle during movement of the cradle from the first position to the second position, thereby applying a rotational force to the syringe assembly and spinning the syringe assembly relative to the plunger rod as the cradle moves from the first position to the second position; Including, machinery.

100. 100. The machine of claim 99, wherein the friction element is fixedly secured to the cradle.

101. 101. The machine of claim 99 or 100, further comprising a pressure plate positioned adjacent to the carriage such that the cradle moves directly beneath the pressure plate as 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 as the cradle moves from the first position to the second position.

102. 102. The machine of any one of claims 99 to 101, wherein the seat portion of the cradle includes a first roller and a second roller separated by a gap, the first and second rollers of the seat portion adapted to engage the barrel of the syringe assembly and hold the barrel within the gap when carried by the cradle, and the first and second rollers enable the syringe assembly to spin as the cradle indexes from the first position to the second position.

103. 103. The machine of claim 102, wherein each of the first and second rollers includes an axis of rotation, the first roller being rotatable about the axis of rotation of the first roller, and the second roller being rotatable about the axis of rotation of the second roller.

104. A machine according to any one of claims 99 to 103, further comprising a guide plate and the friction element fixed to the guide plate.

105. A machine as claimed in any one of claims 99 to 104, wherein the friction element is an elongated cord.

106. 106. The machine of claim 105, wherein the elongated cord is an elastomeric material.

107. A machine as claimed in any one of claims 99 to 106, wherein the actuation device is operatively connected to the carriage and adapted to index the cradle between the first position and the second position in response to an actuation event.

108. 108. The machine of claim 107, wherein the actuator indexes the cradle only once upon the occurrence of the activation event.

109. 109. A machine as claimed in claim 107 or 108, wherein the actuation device includes a servo motor and an operating switch for operably controlling the servo motor, the servo motor being coupled to the carriage to move the cradle via the carriage.

110. A machine as claimed in any one of claims 107 to 109, wherein the actuation device includes a lever operably coupled to the carriage, the lever being arranged to be manipulated to effect the activation event.

111. 111. The machine of claim 110, wherein the actuation device includes a slidable bracket arranged to move the lever.

112. further, a movable plunger rod base coupled to the carriage, the plunger rod base being disposed above the pedestal and including an orifice sized to receive a flanged proximal end of the plunger rod, the orifice being coaxially aligned with the aperture portion of the pedestal, the plunger rod base being movable together with the pedestal from the first position to the second position; A retaining cap removably attached to the plunger rod base, the retaining cap having an outwardly extending tab disposed to extend into the orifice of the plunger rod base. and A machine as claimed in any one of claims 99 to 111, wherein the retaining cap is fixed relative to the carriage and located within the orifice when the pedestal is in the first position.

113. 113. The machine of claim 112, wherein the plunger rod base is selected from separate and interchangeable first and second plunger rod bases, the first plunger rod base including an orifice sized to accept a flanged plunger rod end of a first size, and the second plunger rod base is sized to accept a flanged plunger rod end of a second size different from the first size.

114. A machine as described in any one of claims 99 to 113, wherein the cradle includes a cradle axis that is coaxial with a longitudinal axis of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed within the cradle, the cradle axis being disposed at an angle greater than zero degrees with respect to the vertical.

115. 115. The machine of claim 114, wherein the carriage includes a carousel-style turntable with an axis of rotation that is parallel to the cradle axis such that the axis of rotation of the carriage is disposed at an angle greater than zero degrees relative to vertical.

116. A machine as claimed in any one of claims 99 to 115, wherein the carriage is arranged in rotation relative to the pressure plate.

117. A machine according to any one of claims 99 to 116, wherein the carriage includes a plurality of cradles supported by the carriage.

118. A machine as described in any one of claims 99 to 117, further comprising an exit chute positioned adjacent to the carriage at the second position of the cradle, the exit chute adapted to receive the plunger rod and syringe assembly from the cradle after the plunger rod is coupled to the syringe assembly.

119. 119. The machine of claim 118, wherein the exit chute includes a sloped surface, the sloped surface including a slot sized to receive the plunger rod and syringe assembly after the cradle moves to the second position.

120. 120. A machine according to any one of claims 99 to 119, wherein the carriage is selected from separate and interchangeable first and second carriages, the first carriage including a cradle with a seat portion sized to receive a syringe assembly of a first size, and the second carriage including a cradle with a seat portion sized to receive a syringe assembly of a second size.

121. 121. The machine of any one of claims 101 to 120, further comprising a constant tension spring coupled to the pressure plate, the constant tension spring providing a downward force to the pressure plate as the cradle moves between the first position and the second position, the downward force being transmitted through the pressure plate to the plunger rod.

122. 1. A method of using a machine to couple a plunger rod to a syringe assembly, the method comprising: positioning a syringe assembly on a movable cradle of a carriage, the syringe assembly including 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; positioning a plunger rod in the cradle, the plunger rod including a distal rod end and a proximal rod end, the distal rod end of the plunger rod being disposed above the proximal end of the syringe assembly and in axial alignment with the plunger; activating an actuator 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 as the cradle moves between the first position and the second position, whereby a first threaded portion of the distal rod end of the plunger rod is threadably coupled to a second threaded portion of the plunger of the syringe assembly. A method comprising:

123. 123. The method of claim 122, further comprising applying a downward force to the proximal rod end of the plunger rod as the cradle moves from the first position toward the second position.

124. 124. The method of claim 123, wherein applying a downward force comprises moving the plunger rod between the first position and the second position beneath a pressure plate positioned adjacent to the carriage, the pressure plate adapted to apply the downward force to the plunger rod.

125. The method of any one of claims 122 to 124, wherein rotating the syringe assembly relative to the plunger rod includes engaging the barrel of the syringe assembly carried by the cradle with a friction element fixed adjacent to the carriage, and the syringe assembly is rotatable about a longitudinal axis of the cradle.

126. 126. The method of claim 125, further comprising 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.

127. 127. The method of claim 126, wherein rotating the syringe assembly includes rotating the syringe assembly in a direction opposite to the first direction of the carriage, the axis of rotation of the carriage being parallel to the longitudinal axis of the pedestal.

128. 1. A machine for coupling a plunger rod to a syringe assembly, the machine comprising: 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 actuation device operably coupled to the carriage and adapted to, upon the occurrence of an activation event, index the cradle only once from a first position to a second position to couple the plunger rod to the syringe assembly; a pressure plate positioned adjacent to the carriage such that the pedestal moves beneath the pressure plate as the pedestal 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 pedestal as the pedestal moves from the first position to the second position; and The machine, wherein the actuation device includes a servo motor and an operating switch for operably controlling the servo motor, the servo motor coupled to the carriage to index the pedestal through the carriage.

129. 129. The machine of claim 128, wherein the servo motor is programmed to move the carriage in response to an actuation event, the actuation event including triggering the motion switch.

130. 130. The machine of claim 129, wherein the actuation device includes a lever operably coupled to the carriage, the lever being arranged to be manipulated to effect an actuation event.

131. 131. The machine of claim 130, wherein the actuation device includes a slidable bracket arranged to move the lever, the slidable bracket operably coupled to the servo motor.

132. A machine as claimed in any one of claims 129 to 131, wherein the actuator indexes the cradle only once on the occurrence of the triggering event.

133. 133. A machine as claimed in any one of claims 128 to 132, wherein the operating switch comprises a two-handed anti-tie-down operating switch.

134. A machine according to any one of claims 128 to 133, wherein the servo motors are adapted to be operatively coupled to different carriages.

135. further, a movable plunger rod base coupled to the carriage, the plunger rod base being disposed above the pedestal and including an orifice sized to receive a flanged proximal end of the plunger rod, the orifice being coaxially aligned with the aperture portion of the pedestal, the plunger rod base being movable together with the pedestal from the first position to the second position; A retaining cap removably attached to the plunger rod base, the retaining cap having an outwardly extending tab disposed to extend into the orifice of the plunger rod base. Including, A machine as claimed in any one of claims 128 to 134, wherein the retaining cap is fixed relative to the carriage and located within the orifice when the pedestal is in the first position.

136. 136. The machine of claim 135, wherein the plunger rod base is selected from separate and interchangeable first and second plunger rod bases, the first plunger rod base including an orifice sized to accept a flanged plunger rod end of a first size, and the second plunger rod base sized to accept a flanged plunger rod end of a second size different from the first size.

137. A machine as described in any one of claims 128 to 136, wherein the cradle includes a cradle axis that is coaxial with a longitudinal axis of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed within the cradle, the cradle axis being disposed at an angle greater than zero degrees with respect to the vertical.

138. A machine as claimed in any one of claims 128 to 137, wherein the carriage includes a carousel-style turntable with an axis of rotation that is parallel to the cradle axis, such that the axis of rotation of the carriage is disposed at an angle greater than zero degrees relative to the vertical.

139. A machine as claimed in any one of claims 128 to 138, wherein the carriage is arranged in rotation relative to the pressure plate.

140. 140. A machine as claimed in any one of claims 128 to 139, wherein the seat portion of the cradle includes a first roller and a second roller separated by a gap, the first and second rollers of the seat portion adapted to engage the barrel of the syringe assembly and hold the barrel within the gap when carried by the cradle, and the first and second rollers enable the syringe assembly to spin as the cradle indexes from the first position to the second position.

141. A machine as claimed in any one of claims 128 to 140, wherein the carriage includes a plurality of cradles supported by the carriage.

142. A machine as described in any one of claims 128 to 141, further comprising an exit chute positioned adjacent to the carriage at the second position of the cradle, the exit chute adapted to receive the plunger rod and syringe assembly from the cradle after the plunger rod is coupled to the syringe assembly.

143. 143. The machine of claim 142, wherein the exit chute includes a ramp including a slot sized to receive the plunger rod and syringe assembly after the cradle moves to the second position.

144. 144. A machine as claimed in any one of claims 128 to 143, wherein the carriage is selected from separate and interchangeable first and second carriages, the first carriage including a cradle having a seat portion sized to receive a syringe assembly of a first size, and the second carriage including a cradle having a seat portion sized to receive a syringe assembly of a second size.

145. 145. The machine of any one of claims 128 to 144, further comprising a friction element disposed adjacent to the carriage and below the pressure plate, the friction element adapted to engage a barrel of the syringe assembly carried by the cradle during movement of the cradle from the first position to the second position, the friction element adapted to apply a rotational force to the barrel to spin the syringe assembly relative to the plunger rod.

146. 146. The machine of claim 145, further comprising a guide plate and the friction element secured to the guide plate, the friction element being an elongated cord of elastomeric material.

147. 147. The machine of any one of claims 128 to 146, further comprising a constant tension spring coupled to the pressure plate, the constant tension spring providing a downward force to the pressure plate as the cradle moves between the first position and the second position, the downward force being transmitted through the pressure plate to the plunger rod.

148. 1. A machine for coupling a plunger rod to a syringe assembly, the machine comprising: base; a carriage attached to 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 actuator coupled to the carriage and adapted to index the cradle from a first position to a second position; a pressure plate supported by the base and positioned adjacent the carriage such that the pedestal moves beneath the pressure plate as the pedestal 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 pedestal. and The cradle includes a cradle axis that is coaxial with a longitudinal axis of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed within the cradle, the cradle axis being oriented at an angle greater than zero degrees with respect to vertical.

149. 149. The machine of claim 148, wherein the carriage includes a carousel-style turntable with an axis of rotation that is parallel to the cradle axis such that the axis of rotation of the carriage is positioned at an angle greater than zero degrees relative to vertical.

150. 150. A machine as described in claim 148 or 149, wherein the base includes a bottom surface disposed at a first angle relative to the horizontal, and the longitudinal axis of the cradle is offset from the vertical by the first angle.

151. A machine as described in any one of claims 148 to 150, wherein the actuator is operably connected to the carriage and adapted to index the cradle between the first position and the second position in response to an actuation event.

152. 152. The machine of claim 151, wherein the actuator indexes the cradle only once upon the occurrence of the activation event.

153. A machine as claimed in any one of claims 148 to 152, wherein the actuation device includes a servo motor and an operating switch for operably controlling the servo motor, the servo motor coupled to the carriage to index the cradle through the carriage.

154. 154. The machine of claim 153, wherein the servo motor is programmed to move the carriage in response to the actuation event, the actuation event including triggering the motion switch.

155. A machine as claimed in any one of claims 151 to 154, wherein the actuation device includes a lever operably coupled to the carriage, the lever being arranged to be manipulated to effect the activation event.

156. 156. The machine of claim 155, wherein the actuation device includes a slidable bracket arranged to move the lever, the slidable bracket operably coupled to the servo motor.

157. A machine as described in any one of claims 148 to 156, wherein the carriage is selected from separate and compatible first and second carriages, the first carriage including a cradle having a seat portion sized to accept a syringe assembly of a first size, and the second carriage including a cradle having a seat portion sized to accept a syringe assembly of a second size.

158. The machine of any one of claims 148 to 157, further comprising a friction element disposed adjacent to the carriage and below the pressure plate, the friction element adapted to engage a barrel of the syringe assembly carried by the cradle during movement of the cradle from the first position to the second position, the friction element adapted to apply a rotational force to the barrel to spin the syringe assembly relative to the plunger rod.

159. 159. The machine of claim 158, further comprising a guide plate and the friction element secured to the guide plate, the friction element being an elongated cord of elastomeric material.

160. 160. The machine of any one of claims 148 to 159, further comprising a constant tension spring coupled to the pressure plate, the constant tension spring providing a downward force to the pressure plate as the cradle moves between the first position and the second position, the downward force being transmitted through the pressure plate to the plunger rod.

161. A machine according to any one of claims 153 to 160, wherein the servo motors are adapted to be operatively coupled to different carriages.

162. further, a movable plunger rod base coupled to the carriage, the plunger rod base being disposed above the pedestal and including an orifice sized to receive a flanged proximal end of the plunger rod, the orifice being coaxially aligned with the aperture portion of the pedestal, the plunger rod base being movable together with the pedestal from the first position to the second position; A retaining cap removably attached to the plunger rod base, the retaining cap having an outwardly extending tab disposed to extend into the orifice of the plunger rod base. and A machine as claimed in any one of claims 148 to 161, wherein the retaining cap is fixed relative to the carriage and disposed within the orifice when the pedestal is in the first position.

163. 163. The machine of claim 162, wherein the plunger rod base is selected from separate and interchangeable first and second plunger rod bases, the first plunger rod base including an orifice sized to accept a flanged plunger rod end of a first size, and the second plunger rod base is sized to accept a flanged plunger rod end of a second size different from the first size.

164. A machine as claimed in any one of claims 148 to 163, wherein the carriage is arranged in rotation relative to the pressure plate.

165. 165. A machine as described in any one of claims 148 to 164, wherein the seat portion of the cradle includes a first roller and a second roller separated by a gap, the first and second rollers of the seat portion adapted to engage the syringe barrel of the syringe assembly and hold the syringe barrel within the gap when carried by the cradle, and the first and second rollers enable the syringe assembly to spin as the cradle indexes from the first position to the second position.

166. A machine as claimed in any one of claims 148 to 165, wherein the carriage includes a plurality of cradles supported by the carriage.

167. A machine as described in any one of claims 148 to 166, further comprising an exit chute positioned adjacent to the carriage at the second position of the cradle, the exit chute adapted to receive the plunger rod and syringe assembly from the cradle after the plunger rod is coupled to the syringe assembly.

168. 168. The machine of claim 167, wherein the exit chute includes a slope including a slot sized to receive the plunger rod and syringe assembly after the cradle moves to the second position.

169. 1. A machine for coupling a plunger rod to a syringe assembly, the machine comprising: 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 actuation device operably 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 positioned adjacent to the carriage such that the pedestal moves beneath the pressure plate as the pedestal 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 pedestal as the pedestal moves from the first position to the second position; and At least one of the following (a) to (e): (a) a constant tension spring operatively coupled to the pressure plate, the pressure plate defining an entrance portion adapted to receive a proximal end of the plunger rod as the cradle moves from the first position to the second position, the constant tension spring providing the downward force applied via the pressure plate to the plunger rod as the cradle moves between the first position and the second position; (b) a friction element disposed adjacent the carriage and below the pressure plate, the friction element adapted to engage a barrel of the syringe assembly carried by the cradle during movement of the cradle from the first position to the second position, the friction element adapted to apply a rotational force to the barrel to spin the syringe assembly relative to the plunger rod as the cradle moves from the first position to the second position; (c) the actuation device is operatively connected to the carriage and is adapted to index the cradle between the first position and the second position in response to an actuation event; (d) the cradle includes a cradle axis that is coaxial with a longitudinal axis of the syringe assembly and plunger rod when the syringe assembly and plunger rod are disposed within the cradle, the cradle axis being disposed at an angle greater than zero degrees with respect to vertical; and (e) the carriage is selected from separate and interchangeable first and second carriages, the first carriage including a pedestal with a seat portion sized to receive a syringe assembly of a first size, and the second carriage including a pedestal with a seat portion sized to receive a syringe assembly of a second size. Including, machinery.

170. 170. The machine of claim 169, further comprising a guide plate and the friction element secured to the guide plate, the friction element being an elongated cord of elastomeric material.

171. further, a movable plunger rod base coupled to the carriage, the plunger rod base being disposed above the pedestal and including an orifice sized to receive a flanged proximal end of the plunger rod, the orifice being coaxially aligned with the aperture portion of the pedestal, the plunger rod base being movable together with the pedestal from the first position to the second position; A retaining cap removably attached to the plunger rod base, the retaining cap having an outwardly extending tab disposed to extend into the orifice of the plunger rod base. Including, 171. A machine as claimed in claim 169 or 170, wherein the retaining cap is fixed relative to the carriage and disposed within the orifice when the pedestal is in the first position.

172. 172. The machine of claim 171, wherein the plunger rod base is selected from separate and interchangeable first and second plunger rod bases, the first plunger rod base including an orifice sized to accept a flanged plunger rod end of a first size, and the second plunger rod base is sized to accept a flanged plunger rod end of a second size different from the first size.

173. A machine as claimed in any one of claims 169 to 172, wherein the carriage includes a carousel-style turntable with an axis of rotation that is parallel to the cradle axis, such that the axis of rotation of the carriage is disposed at an angle greater than zero degrees relative to the vertical.

174. A machine as claimed in any one of claims 169 to 173, wherein the actuator indexes the cradle only once upon the occurrence of the activation event.

175. A machine as claimed in any one of claims 169 to 174, wherein the actuation device includes a servo motor and an operating switch for operably controlling the servo motor, the servo motor being coupled to the carriage to move the cradle via the carriage.

176. A machine according to any one of claims 169 to 175, wherein the actuation device includes a lever for a user to manually index the cradle from the first position to the second position.

177. 177. The machine of claim 176, wherein the actuation device includes a slidable bracket arranged to move the lever.

178. A machine as claimed in any one of claims 169 to 177, wherein the carriage is rotationally arranged relative to the pressure plate.

179. 179. A machine as described in any one of claims 169 to 178, wherein the seat portion of the cradle includes a first roller and a second roller separated by a gap, the first and second rollers of the seat portion adapted to engage the syringe barrel of the syringe assembly and hold the syringe barrel within the gap when carried by the cradle, and the first and second rollers enable the syringe assembly to spin as the cradle indexes from the first position to the second position.

180. A machine according to any one of claims 169 to 179, wherein the carriage includes a plurality of cradles supported by the carriage.

181. A machine as described in any one of claims 169 to 180, further comprising an exit chute positioned adjacent to the carriage at the second position of the cradle, the exit chute adapted to receive the plunger rod and syringe assembly from the cradle after the plunger rod is coupled to the syringe assembly.

182. 182. The machine of claim 181, wherein the exit chute includes a slope including a slot sized to receive the plunger rod and syringe assembly after the cradle moves to the second position.

183. 170. The machine of any one of claims 13, 36, 107, 151 or 169, wherein the actuator indexes the cradle two or more times upon the occurrence of the activation event.

184. 52. The machine of claim 51, wherein the actuator is configured to index the cradle two or more times upon the occurrence of an activation event.

185. 129. The machine of claim 128, wherein the servo motor is programmed to index the cradle two or more times in response to an actuation event.

186. 30. The method of any one of claims 23 to 29, further comprising indexing the cradle from the first position to the second position two or more times in response to activation of the actuation device.

187. 1. A method of using a machine to couple a plunger rod to a syringe assembly, the method comprising: positioning a syringe assembly on a movable cradle of a carriage, the syringe assembly including 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; positioning a plunger rod in the cradle, the plunger rod including a distal rod end and a proximal rod end, the distal rod end of the plunger rod being disposed above the proximal end of the syringe assembly and in axial alignment with the plunger; activating an actuator operably connected to the carriage; and indexing the cradle from the first position to the second position two or more times in response to activation of the actuator, wherein as the cradle indexes from the first position to the second position, a force is applied to one or both of the syringe assembly and the plunger rod to couple the plunger rod to a plunger of the syringe assembly. A method comprising:

188. 188. The method of claim 187, wherein indexing the cradle includes rotating the carriage about an axis of rotation of the carriage.

189. 189. The method of claim 188, wherein rotating the carriage includes rotating the carriage through an angle greater than zero degrees to index the cradle from the first position to the second position.

190. 190. The method of any one of claims 187 to 189, wherein actuating the actuation device includes moving a lever, the lever causing the carriage to index the cradle from the first position to the second position two or more times.

191. 191. The method of claim 190, wherein activating the actuator includes triggering an operating switch coupled to a servo motor, the servo motor being arranged to slide a bracket to move the lever.

192. A method according to any one of claims 187 to 191, wherein activating the actuation device comprises triggering an operating switch coupled to a servo motor, the servo motor being operably coupled to the carriage.

193. 193. The method of any one of claims 187 to 192, further comprising applying a downward force to the proximal rod end of the plunger rod as the cradle moves from the first position toward the second position.

194. 194. The method of claim 193, wherein applying a downward force to the proximal rod end of the plunger rod includes moving the plunger rod beneath a pressure plate positioned adjacent to the carriage as the cradle moves from the first position to the second position.

195. 195. The method of any one of claims 187 to 194, further comprising applying a rotational force to the barrel of the syringe assembly while the cradle moves from the first position to the second position.

196. 200. The method of claim 195, wherein applying the rotational force includes engaging the syringe assembly with a friction element disposed adjacent the carriage as the cradle moves from the first position to the second position.

Images