EA046555B1 - MACHINE FOR CONNECTING PISTON ROD WITH SYRINGE ASSEMBLY - Google Patents

Abstract

A machine for connecting a piston rod to a syringe assembly may comprise a rotary part comprising a tray having a mounting portion, the dimensions of which are suitable for accommodating the syringe assembly, and an open portion, which is located above the mounting portion and the dimensions of which are suitable for accommodating the piston rod. A drive device may be operatively connected to the rotary part and configured to move the tray from a first position to a second position for connecting the piston rod to the syringe assembly. The rotary part may be selected from separate and interchangeable first and second rotary parts, wherein the first rotary part comprises a tray configured to accommodate a syringe assembly of a first size, and the second rotary part comprises a tray, the dimensions of which are suitable for accommodating a syringe assembly of a second size, which differs from the first size.

Description

Cross reference to related application

The priority is claimed to U.S. Provisional Patent Application No. 62/477521, filed March 28, 2017, the entire contents of which are incorporated herein by reference.

Field of technology to which the invention relates

The present invention relates generally to medical syringes and, more particularly, to machines for connecting a plunger rod to a syringe assembly in the form of a medical syringe.

Prerequisites for creating the invention

A conventional medical syringe includes a syringe assembly containing a liquid, such as a drug or pharmaceutical product, and a plunger rod connected to the syringe assembly. The plunger rod may be connected to a plunger located in the barrel of the syringe assembly after the syringe has been filled with liquid. The piston may include internal threads sized to connect to external threads at the distal end of the piston rod. When the distal end of the plunger rod is threaded onto the plunger, the plunger rod is connected to the syringe assembly. The force applied to the plunger rod can then drive the plunger through the barrel of the syringe to dispense the liquid contained in the syringe. The plunger rod includes a proximal end of the rod having a flange that can be pressed by the operator's thumb while grasping the syringe barrel between two fingers. Syringe assemblies are sized to hold different amounts of liquid, and the plunger rods can also be sized to fit their counterpart in the syringe assembly. When connecting the piston rod to the piston, care should be taken not to apply excessive pressure, which could cause premature release of fluid and/or compromise the seal integrity of the airtight prefilled syringe container. In a prefilled syringe, the fill level of liquid contained within the syringe barrel may vary within a batch of prefilled syringes, and thus the position of the plunger within the syringe barrel may also vary within a batch. Therefore, existing systems that connect plunger rods to prefilled syringes must be designed to accommodate fluctuations in fill level to prevent premature release of fluid.

A conventional machine used to connect plunger rods and syringe assemblies is fully automatic and is designed to perform a series of process steps including loading the plunger rods and syringe assemblies into the machine, applying the machine, connecting the plunger rod to the piston, and unloading the finished product from the machine. Fully automated technology is especially suitable for preparing large batches consisting of 2,000 or more connected plunger rods and syringe assemblies. To adjust a fully automated machine to assemble plunger rods and syringe assemblies of a different size, referred to herein as a changeover process, the machine must be partially disassembled, adjusted and/or reassembled before operation. This changeover process often requires a skilled operator to handle the many components involved in disassembling, adjusting and tooling, and reassembling the machine, which can be a very time-consuming procedure. Moreover, the known machine has a large footprint and is generally not moveable once the machine is installed in a process laboratory. Using such a machine for large batches may not be practical when assembling small batches and simply assembling syringe assemblies of different sizes.

Brief description of the invention

In accordance with the invention, a machine for connecting a piston rod to a syringe assembly may comprise a rotating portion having a movable tray containing a mounting portion sized to accommodate the syringe assembly and an open portion located above the mounting portion sized to accommodate the rod. piston The machine may include a drive device operably coupled to the rotatable portion and configured to step the tray from a first position to a second position only once upon activation to connect the plunger rod to the syringe assembly. The pressure plate may be positioned adjacent the pivot portion such that the tray moves under the pressure plate when the tray is moved from a first position to a second position, the pressure plate being configured to apply a downward force to a piston rod located in the open portion of the tray when the tray moves from the first position to the second position. The drive device may include a servo drive and a function switch for operatively controlling the servo drive, wherein the servo drive is coupled to the rotary portion for incrementally moving the tray by the rotary portion.

In a preferred form, the machine may include a selectable pressure plate located above the tray such that the tray moves under the selectable pressure plate when the tray is moved from a first position to a second position. The selectable pressure plate may be configured to apply a downward force to a piston rod located in an open portion of the tray while moving the tray from a first position to a second position.

- 1 046555

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

In a preferred form, the machine may comprise a quick-change fixture and a table, wherein the selectable rotatable portion may be releasably coupled to the table via the quick-change fixture.

In a preferred form of the machine, the first rotary portion may include a first base and the second rotatable portion may include a second base, wherein the drive device may include a servo drive operatively coupled to the first and second bases.

In a preferred form, the machine may include a selectable friction element located adjacent to the selectable rotary portion. The selectable friction member may be configured to contact the barrel of the syringe assembly carried by the tray when the tray is moved from a first position to a second position. The friction member may be configured to apply a turning force to the syringe barrel to rotate the syringe assembly relative to the plunger rod as the tray moves from a first position to a second position.

In a preferred form of the machine, the first rotary portion may include a first guide plate coupled to the first pivot portion and carrying a first friction element, and the second rotary portion may include a second guide plate coupled to the second pivot portion and carrying a second friction element, whereby the selectable friction element carried by a selectable guide plate connected to a selectable rotating part.

In a preferred form, the machine may comprise a selectable constant tension spring operably coupled to a selectable pressure plate. A selectable pressure plate defining the inlet portion may be configured to accommodate the proximal end of the piston rod when moving the tray from a first position to a second position. The selectable constant tension spring may provide a downward force to the piston rod applied by the selectable pressure plate as the tray moves between the first position and the second position.

In a preferred form, the machine may include a servo motor and a function switch for operatively controlling the servo motor, the servo motor being coupled to the rotary portion for moving the tray by the rotary portion.

In a preferred form of the machine, the inlet end may include an inclined surface located above the outlet end relative to the rotating part.

In a preferred form, the machine may include at least one guide bar, wherein the pressure plate is movably connected to the at least one guide bar in a direction parallel to the longitudinal axis of the rotating part.

In a preferred form, the machine may include a threaded rod for adjustably positioning the pressure plate relative to the turntable, whereby the pressure plate can be adjusted in a direction parallel to the longitudinal axis of the turntable to accommodate the piston rods at different heights.

In a preferred form, the machine may include a friction element located adjacent to the turning portion and under the pressure plate. The friction member may be configured to contact a syringe barrel assembly that is carried by the tray when the tray is moved from a first position to a second position. The friction element may be configured to apply a turning force to the syringe barrel to rotate the syringe assembly relative to the plunger rod.

In a preferred form of machine, the friction element may be fixedly mounted relative to the tray.

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

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

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

In a preferred form of machine, the drive device may be configured to step the tray between a first position and a second position in response to an actuating action.

In a preferred form of machine, the drive device can step the tray only once during the actuation action.

- 2 046555

In a preferred form of machine, the drive device may step the tray two or more times upon actuation.

In a preferred form of machine, the drive device may include a lever that allows the user to manually step the tray from a first position to a second position.

In a preferred form of the machine, the lever may be movably attached to the base of the rotating portion, and the lever may be configured to effect an actuating action when the lever is moved from a non-operating position to an activated position.

In a preferred form of machine, the drive device may include a motor-driven bracket located adjacent to the lever, which bracket may be configured to move the lever between a non-operating position and an activated position.

In a preferred form of machine, the drive device may include a movable arm for moving the arm.

In a preferred form, the machine may include a pressure plate positioned adjacent the pivot portion such that the tray moves under the pressure plate when the tray is moved from a first position to a second position, the pressure plate being configured to apply a downward force to a piston rod located at the open portion of the tray when the tray is moved from the first position to the second position.

In a preferred form, the machine may include a two-handed, momentary function switch for performing an actuating action.

In a preferred form of machine, the drive device may comprise a lever operatively coupled to the rotatable portion, the lever being configured to be manually operated to effect an actuating action.

In a preferred form of machine, the drive device may include a lever that allows the user to manually step the tray from a first position to a second position.

In a preferred form of machine, the tray mounting portion may include a first roller and a second roller separated by a gap. The first and second rollers of the mounting portion may be configured to contact the syringe barrel assembly and hold the syringe barrel in the gap when carried by the tray, the first and second rollers allowing the syringe assembly to rotate as the tray is stepped from a first position to a second position.

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

In a preferred form of machine, the servo may be programmed to respond to an actuating action by moving the rotary portion, the actuating action including operating a function switch.

In a preferred form of machine, the servo may be programmed to step the tray more than once in response to an actuation action.

In a preferred form of machine, the servo may be configured to be operatively coupled to another rotary part.

In a preferred form of machine, the tray may have a tray axis that is aligned with the longitudinal axes of the syringe assembly and the plunger rod, where the syringe assembly and the plunger rod are located in the tray and the tray axis is located at an angle greater than zero degrees relative to the vertical.

In a preferred form of the machine, the rotary portion may comprise a rotating carousel with a pivot axis that is parallel to the axis of the tray, whereby the pivot axis of the rotary portion is located at an angle greater than zero degrees relative to the vertical.

In a preferred form of the machine, the base may include a bottom surface located at a first angle relative to the horizontal, with the longitudinal axis of the tray offset from the vertical by a first angle.

In a preferred form, the machine may include a movable base for the piston rod connected to the rotating part. The plunger rod base may be located above the tray and may include an opening sized to accommodate the flanged proximal end of the plunger rod, the opening being axially aligned with the open portion of the tray. The piston rod base may be configured to move with the tray from a first position to a second position.

In a preferred form, the machine may comprise a retaining cap having an outwardly projecting tongue positioned to project into an opening of the piston rod base, the retaining cap being removably attached to the piston rod base. The holding cover can be fixed relative to the rotating part and located

- 3 046555 in the hole when the tray is in the first position.

In a preferred form, the machine may comprise a selectable movable base for the piston rod coupled to a selectable rotating portion.

In a preferred form of machine, the piston rod base may be selected from separate and interchangeable first and second piston rod bases, the first piston rod base comprising an opening sized to accommodate the flanged end of a first size piston rod, and the second rod base The piston is sized to accommodate the flanged end of a second size piston rod that is different from the first size.

In a preferred form of the machine, the rotating portion may be positioned to rotate relative to the pressure plate.

In a preferred form of the machine, the rotary part may include a plurality of trays carried by the rotary part.

In a preferred form, the machine may include an outlet chute located adjacent to the rotating portion in a second chute position. The outlet chute may be configured to receive the plunger rod and syringe assembly from the tray after connecting the plunger rod to the syringe assembly.

In a preferred form, the first rotary portion may include a first outlet chute coupled to the first rotary portion, and the second rotary portion may include a second outlet chute coupled to the second rotary portion, whereby the selectable outlet chute is coupled to the selectable rotary portion.

In a preferred form of machine, the outlet chute may include an inclined portion, the inclined portion comprising a slot sized to accommodate the plunger rod and syringe assembly once the tray has been moved to a second position.

Brief description of graphic materials

It is believed that the present invention will become more apparent from the following description taken in conjunction with the accompanying drawings. Some of the graphics may be simplified by eliminating selectable elements to show other elements more clearly. Such exclusions of elements in certain graphics do not necessarily imply the presence or absence of specific elements in any of the exemplary embodiments, unless expressly stated in the relevant description. In addition, none of the figures in the graphic materials are depicted to scale.

In fig. 1 is a front perspective view of a first exemplary plunger rod installation machine with a plunger rod and syringe assembly disposed thereon, in accordance with the principles of the present invention.

In fig. 2 is a partial front perspective view of the first exemplary piston rod installation machine of FIG. 1 with plunger rod and syringe assembly in intermediate configuration.

In fig. 3 is a rear perspective view of the first exemplary piston rod installation machine of FIG. 1 with plunger rod and syringe assembly in connected configuration.

In fig. 4 is a front perspective view of the first exemplary piston rod installation machine of FIG. 1 with a first plunger rod and syringe assembly in a disconnected configuration and a second plunger rod and syringe assembly in a connected configuration.

In fig. 5 is a top perspective view of the first exemplary piston rod installation machine of FIG. 1, which shows a first exemplary piston rod positioning base, a first exemplary piston rod holding cap, and a fastening.

In fig. 6 is a top perspective view of the first exemplary piston rod installation machine of FIG. 1 with a second exemplary positioning base for the piston rod and a second retaining cap for the piston rod without fastening.

In fig. 7 is a top view of the first exemplary piston rod retaining cap of FIG. 5.

In fig. 8 is a top view of a second exemplary piston rod retaining cap according to FIG. 6.

In fig. 9 is a perspective view of the guide assembly of the first exemplary piston rod installation machine of FIG. 1, wherein the guide assembly includes a pressure block for preliminary application of force.

In fig. 10 is a perspective view of the pressure block for pre-applying force of the guide assembly according to FIG. 9.

In fig. 11 is a top perspective view of an adaptive drive system designed to

- 4 046555 use with the first exemplary piston rod installation machine according to FIG. 1.

In fig. 12 is a perspective view of a second exemplary piston rod installation system comprising the machine of FIG. 1 connected to the adaptive drive system according to FIG. eleven.

In fig. 13 is a perspective view of a third exemplary system for installing a piston rod in accordance with the principles of the present invention.

In fig. 14 is a side view of the third exemplary piston rod mounting system of FIG. 13.

In fig. 15 is a front view of the third exemplary piston rod mounting system of FIG. 13.

Detailed description of graphic materials

A plunger rod installation system for connecting the plunger rod to a prefilled syringe assembly is illustrated and described herein. In fig. 1-4 show a first exemplary plunger rod installation machine 10 depicted in various stages of connecting the plunger rod 14 and the prefilled syringe assembly 18. FIG. 5-10 show various components of the machine 10 in more detail, and FIG. 11 and 12 show an adaptive system for converting a manual machine 10 according to FIG. 1-4 into a second exemplary piston rod installation system, which is semi-automated. A third exemplary system for installing a piston rod is shown in FIG. 13-15 and may include any or all of the various components of the previous illustrated embodiments for connecting the plunger rod 14 to the syringe assembly 18. The term syringe assembly 18 may refer to a prefilled syringe or an empty syringe.

In fig. 1 shows a first example of a plunger rod installation system 10 for connecting the plunger rod 14 to a syringe assembly 18. The plunger rod installation system 10 is a machine having a rotary portion 22 with a movable tray 26 and a drive device 30 operatively coupled to the rotary portion 22 and configured to move the tray 26 from a first position to a second position. Tray 26 includes a mounting portion 34 that is sized to accommodate the syringe assembly 18 and an open portion 38 that is located above the mounting portion 34 and that is sized to accommodate the plunger rod 14 . The illustrated example shows that the rotating portion 22 is a rotating carousel with a plurality of trays 26 carried by the rotating portion 22 and located around the perimeter of the carousel 22. For ease of notation, one tray 26 will be described as follows: the rotating portion 22 rotates the tray 26 between a first position and second position. As used herein, the expression loaded tray 26 refers to the tray 26 on which the plunger rod 14 and syringe assembly 18 are located. Although the machine 10 is provided with a plurality of trays 26 in various positions, the first position P1 (shown in FIG. 1) refers to the position in which the plunger rod 14 and syringe assembly 18 are located on the tray 26, but are not yet connected to each other. The second position P2 (shown in FIG. 3) refers to any position of the loaded tray 26 after the plunger rod 14 is coupled to the syringe assembly 18. As used herein, the expression syringe assembly 46 with attached rod refers to the end product in which the plunger rod 14 connected to the syringe assembly 18. The plunger rod 14 and the syringe assembly 18 may be loosely attached to, removably attached to, or suitably mounted to the tray 26.

The function and operation of the machine 10 will be described when the tray 26 is in three successive positions: a first position P1, a position between the first position P1 and the second position P2, and a second position P2. The machine 10 is configured to connect the plunger rod 14 and the prefilled syringe assembly 18 by moving the tray 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, in which the piston rod 14 is connected to the syringe assembly 18. The drive device 30, located inside the base 48 of the machine 10, rotates the rotary part 22 and the loaded tray 26 about the axis A of rotation of the rotary part 22. When rotating the rotary part 22, the loaded tray 26 passes through a guide assembly 50 attached to the base 48. The guide assembly 50 includes a pre-force pressure block 54 that is configured to apply a constant downward force to the piston rod 14 when the piston rod 14 contacts the pressure plate 58. At the same time , the friction element 60 (FIG. 9) of the guide assembly 50 contacts and applies a turning force (e.g., torque) to the syringe assembly 18 to rotate the syringe assembly 18 relative to the plunger rod 14 as the loaded tray 26 passes under the pressure plate 58 The combination of the downward force applied by the pressure plate 58 and the turning force applied by the friction element 60 effectively connects the plunger rod 14 to the syringe assembly 18 by the time the loaded tray 26 reaches the second position P2. In fig. 3, the syringe assembly 46 with the attached rod is in the second position P2, next to the outlet chute 62, in which

- 5 046555 a syringe assembly 46 with an attached rod is placed. The tray 26 is configured to discharge the syringe assembly 46 with its attached rod when the rotary portion 22 is rotated again, and the tray 26 is configured to place the syringe assembly 46 with its attached rod into the discharge chute 62, as shown in FIG. 4. The rotary portion 22 described herein may be controlled or controlled by a rotary actuator, but in other embodiments a linear actuator may be provided. For example, the rotary portion 22 may be replaced by a linear assembly line, such as a conveyor belt, in which the tray 26 steps along a linear path. The rotating portion 22 may include one or more movable trays 26, which are connected to a linear drive mechanism that moves the trays 26 along a linear path. In this example, the guide assembly 50 may be positioned relative to a linear conveyor belt or other linear conveying means to cooperate with the movable trays 26 to connect the plunger rod 14 to the syringe assembly 18.

As shown in FIG. 1, 3 and 4, the machine 10 is oriented at an angle with the base 4 8 of the machine 10 resting on a flat surface. As shown in FIG. 3, the axis A of rotation of the rotating part 22 is located at an angle a relative to the vertical V, and the lower surface 66 of the base 48 is located at an angle p relative to the horizontal H. The axis of rotation and/or longitudinal axis A of the rotating part 22 is also parallel to the axis B of the tray, which is located on one line with the longitudinal axes C of the piston rod 14 and the syringe assembly 18, when the piston rod 14 and the syringe assembly 18 are located in the tray 26. The axis B of the tray and the axis A of rotation are located at an angle a, which is greater than zero degrees relative to the vertical V. B In one embodiment, angle a may 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.

As mentioned previously, the term tray 26 refers to the structure that houses the plunger rod 14 and the syringe assembly 18. Each tray 26 includes a mounting portion 34 defined by a pair of rollers 68, an opening 70 of the plunger rod positioning base 72, and an open portion 38. formed by a disk 74 for gripping the piston rod. Rollers 68, a piston rod positioning base 72, and a piston rod gripping disc 74 are attached to the rotating portion 22 and are rotatable about a pivot axis A when the rotating portion 22 is driven by the driving device 30. The positioning base 72 includes a plurality of evenly spaced holes. 70, and the piston rod gripping disc 74 includes a plurality of evenly spaced openings 38. The positioning base 72 and the gripping disc 74 are spaced apart from each other and positioned relative to the rollers 68 such that each tray 26 is defined by one opening 70, one opening 38, and one mounting portion 34 that are coaxial and designed to accommodate a plunger rod 14 aligned with the syringe assembly 18. Each roller 68 is rotatable about a pin 76 extending along the central axis D of the roller 68, with each pin 7 6 attached to lower portion 24 of the rotating part 22. Each roller 68 is located at a predetermined distance from the adjacent roller 68 to form a gap G, whereby the syringe barrel 78 can fit into the mounting portion 34 between two adjacent rollers 68 and be in contact with them. The first and second adjacent rollers 68 of the mounting portion 34 are configured to contact the barrel 78 of the syringe assembly 18 and hold the syringe barrel 78 in the gap G when transferred by the tray 26.

The rollers 68 are positioned to freely hold the barrel 78 of the syringe assembly 18 when the syringe assembly 18 is attached to, or otherwise located on, the machine 10 in the first position P1, and to release the barrel 78 of the syringe when the tray 26 is moved to the outlet channel 62. In the disclosed embodiments, the inclined orientation of the rotating portion 22 allows the tray 26 to support the syringe barrel 78 as the tray 26 moves from a first position P1 to a second position P2. Additionally, the inclined orientation of the machine 10 allows the tray 26 to release the syringe assembly 46 with its attached rod into the discharge chute 62 after the tray 26 has passed the second position P2. When the rotary portion 22 is rotated again, the syringe assembly 46 with its attached rod enters the slot 64 of the discharge chute 62 and the syringe assembly 46 with its attached rod can move down the inclined portion 63, where the syringe assembly 46 with its attached rod remains until removed. The slot 64 is sized to accommodate a particular size syringe assembly 18 so that the syringe assembly 46 and its attached plunger rod can be easily moved down the ramp 63 for storage in the outlet chute 62. The ramp 63 may be sized and tilt to hold the batch of syringes assembly 46 with the attached plunger rod.

The dimensions of tray 26 are based on the requirements of the syringe assembly 18 and plunger rod 14. Specifically, the mounting portion 34 is sized to accommodate a particular type/size of syringe assembly 18, and the open portion 38 and opening 70 of the tray 26 are also sized to accommodate a particular type/shape of plunger rod 14. In the illustrated example, machine 10 is specifically designed to connect a plunger rod 14 and a syringe assembly 18 of a particular size. In other embodiments, the machine 10 may be configured to accommodate plunger rods 14 and syringe assemblies 18 of different sizes. Machine 10 may be designed to

- 6 046555 placement of a syringe assembly of one size, for example a glass syringe assembly 18 with a volume of 2.25 ml. Thus, the distance between two adjacent rollers 68 is such that the syringe assembly 18 having a 2.25 ml syringe barrel 78 can be loosely attached to the tray 26. Each opening 38 of the plunger rod gripping disc 74 is designed to accommodate a rod body 82 specific size plunger used with syringe assembly 18 2.25 ml. For a piston rod 14 with an X-shaped cross-section, the open portion 38 may include a plurality of projections designed to receive the piston rod body 82 and limit the rotational, angular, and lateral movement of the piston rod 14 relative to the C-axis as the loaded tray 26 moves from the first position P1 to the second position P2. The rollers 68, on the other hand, are freely rotatable about an axis D and allow the syringe barrel 78 to rotate about the axis B of the tray 26 when the friction element 60 contacts the syringe barrel 78, which will be described in more detail below. The rollers 68, the piston rod grip disc 74, and the piston rod positioning base 72 may be positioned to accommodate the piston rod body 82 of a specific height.

The machine 10 can be adjusted to a variety of different fill levels for a particular size syringe assembly 18 through interchangeable plunger rod positioning bases 72 and 86. As shown in FIG. 5-8, the piston rod positioning base 72 is selected from the separate and interchangeable first and second piston rod positioning bases 72 and 86. The first piston rod positioning base 72 includes an opening 70 sized to accommodate the proximal end 90 of a particular size of piston rod 14, and the second piston rod positioning base 86 includes an opening 104 sized to accommodate the proximal end 90 of a different size of piston rod 14. . The first piston rod positioning base 72 and the corresponding piston rod holding cap 84 shown in FIG. 5 and 7 may be mutually replaced by another positioning base 86 and associated holding cap 84 shown in FIG. 6 and 8. The first and second piston rod positioning bases 72 and 86 may differ in height to accommodate piston rods of different heights, and they may have differently sized holes 70 and 104 to receive two sizes of piston rod proximal ends 90. In the illustrated embodiment, the holes 70 of the first positioning base 72 have a smaller radius than the holes 104 of the second positioning base 86. Although not shown, the machine 10 may be configured to operate with any number of different positioning bases for the piston rod, and the machine 10 does not is limited to the two embodiments described and depicted herein.

Let's return to fig. 5 and 6, which show that the first piston rod positioning base 72 and the retaining cap 84 are removably attached to the machine 10. The first piston rod positioning base 72 is connected to the rotating portion 22 and is located above the disk 74 for gripping the piston rod therewith. such that the openings 70 located around the perimeter of the positioning base 72 are on the same axis as the openings 38 of the gripping disk 74. Each opening 70 is sized to accommodate the flanged proximal end 90 of the piston rod 14 and provides sufficient space to allow the flanged proximal end 90 of the piston rod to fall through the opening 70 when tray 26 is moved from the first position P1 to the second position P2. The retaining cap 84 is located on top of the positioning base 72 and includes an outwardly projecting tongue 94 positioned to protrude into the opening 70 when the positioning base 72 and the retaining cap 84 are attached to the machine 10. Both the retaining cap 84 and the positioning base 72 for the piston rod releasably attached to the machine 10 via a threaded attachment 98. While the positioning base 72 is movably coupled to the rotating portion 22 (such that the positioning base 72 rotates with the rotating portion 22), the retaining cover 84 and the threaded attachment 98 are stationary attached to the machine 10 and does not rotate with the rotating portion 22 about axis A. The holding cap 84 provides the function of holding the piston rod 14 when the piston rod 14 is first placed on the tray 26. As shown in FIG. 1 and 2, the flanged proximal end 90 of the piston rod 14 fits into the bore 70 of the positioning base 72 and abuts a portion 96 of the tongue 94 that projects into the bore 70. The portion 96 of the tongue 94 located in the bore 70 holds the piston rod 14 suspended. above the syringe assembly 18 located on the mounting portion 34. As the loaded tray 26 moves from the first position P1, the positioning base 72 rotates relative to the protruding tongue 94 and the opening 70 of the tray 26 moves away from the portion 96 to release the piston rod 14 from it. The flanged proximal end 90 of the piston rod 14 falls down through the opening 70 of the positioning base 72, and the distal end 156 of the piston rod 14 contacts the piston 158 located in the syringe barrel 78, as shown in FIG. 2.

In fig. 7 shows a first side 100a of the retaining cap 84 that is associated with the first piston rod positioning base 72, and FIG. 8 shows a second side 100b of the retaining cap 84 that is associated with the second positioning base 86 for the piston rod. In each illustrated embodiment, the protruding tab 94 of the retaining cover 84

- 7 046555 contains an edge 101a and 101b with an asymmetrical contour, the shape of which can correspond to embodiments of the flanged ends 90 of different piston rods 14. Each side 100a and 100b of the retaining cap 84 includes specific markings or marks 102a and 102b associated with corresponding marks 103a and 103b on the piston rod positioning base 72 and 86. The grip disk 74 also includes marks 105a and 105b that are aligned with marks 102a and 102b to ensure alignment of the holes 70 and 104 and the openings 38 when the trays 26 are assembled. As shown in FIG. 5, marks 102a, 103a, and 105a may provide a visual indication that the piston cover 84 is properly aligned with both the first piston rod positioning base 72 and the grip disk 74. To replace the first piston rod positioning base 72 with a second piston rod positioning base 86, a threaded fastener 98 that includes a manually operated knurled knob is removed from the machine 10, and the retaining cover 84 and the first positioning base 72 are also removed. The second positioning base 86 is positioned on the rotary portion 22 so as to align the marks 103b with the corresponding marks 105b on the grip disk 74. The holding cap 84 is inverted so that the second side 100b faces away from the rotating portion 22 and then placed on top of the second positioning base 86 so that the marks 102b of the holding cap 84 are aligned with the marks 103b of the second positioning base 86 and the disc marks 105b 74 to capture. Once properly assembled, the protruding tongue 94 is placed inside the hole 104 of the tray 26 at the first position P1. In the illustrated embodiments, 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 it is loaded into the tray 26 in a first position P1. In another embodiment, the plunger rod 14 and syringe assembly 18 may be loaded together such that the plunger rod 14 is not held by the retaining cap 84 and positioning base 72 and 86, and the distal end 156 may instead rest against the plunger 158 when the tray 26 is in the first position P1. In this case, the positioning base 72 and 86 and the holding cover 84 may optionally be attached to the machine 10 such that the tray 26 is not limited by the opening 70 and 104 of the positioning base 72 and 86.

The guide unit 50 in FIG. 9 and 10 includes a pressure block 54 for pre-applying force of the machine 10 attached to a feed guide assembly 110. The feed guide assembly 110 includes a plurality of support rods 114 that connect a rod holding guide 116, an upper feed guide 118, a guide plate 120, a lower feed guide 122 and support base 126. In general, the rod holding guide 116, the upper feed guide 118, the guide plate 120 and the lower feed guide 122 are contoured to partially surround and correspond to the outer perimeter of the rotary portion 22. A support base 126 is attached to the base 48 of the machine 10, and support rods 114 support the remaining elements of the feed guide assembly 110 and the pressure block 54 to pre-apply force. The upper and lower feed rails 118 and 120 include cut ends 119 and 121, respectively, to accommodate and guide the loaded tray 26 and prevent jamming when the turntable 22 is rotated. A syringe barrel guide 130 attached to the top feed rail 118 assists the feed rails 118 and 120 by providing a barrier from the proximal end 132 of the syringe assembly 18 as the loaded tray 26 moves through the guide assembly 50 to the second position P2. As shown in FIG. 2, the syringe barrel guide 130 is an L-shaped bracket sized to accommodate and guide the proximal end 132 of the syringe assembly 18.

In fig. 9 shows a friction element 60 attached to the inner edge surface 134 of the guide plate 120 and located adjacent to the rotating portion 22 and under the pressure plate 58. The friction element 60 is configured to contact the barrel 78 of the syringe assembly 18, which is attached to the tray 26, when moving tray 26 from the first position P1 to the second position P2. The friction element 60 thus applies a turning force to the syringe barrel 78 to rotate the syringe assembly 18 relative to the plunger rod 14. In the illustrated example, the friction element 60 is an elongated cord that extends along the inner edge surface 134 of the guide plate 120 such that the friction element 60 remains in contact with the syringe barrel 78 as the syringe assembly 18 moves along at least part of its path. from the first position P1 to the second position P2. As tray 26 moves from a first position P1 to a second position P2, the syringe assembly 18 passes through the guide assembly 50 and comes into contact with a friction element 60 protruding from the inner edge surface 134 of the guide plate 120. The friction element 60 contacts the syringe barrel 78 and drives to rotate the syringe barrel 78 and the syringe assembly 18 about the longitudinal axis B of the tray 26. According to this configuration, when the tray 26 carries the syringe assembly 18 in the first direction, the friction element 60 comes into contact with the syringe barrel 78 and applies a turning force to the syringe barrel 78 syringe, which leads to rotation of the syringe cylinder 7 8 between the rollers 68 of the tray 26 in on

- 8 046555 direction opposite to the first direction of rotation of the rotary part 22. At this time, the piston rod 14 located in the open part 38 of the tray 26 does not rotate relative to the tray 26 or the syringe assembly 18, but instead receives a downward force from pressure block 54 for preliminary application of force.

In the preferred example, the pre-force pressure plate 58 of the pressure block 54 applies a constant force (e.g., approximately 2 N in some embodiments) to the plunger rod 14 and the friction element 60 causes the syringe barrel 78 to rotate no more than four times to engage the plunger rod 14 and syringe assembly 18. The length of the friction element 60 can be determined based on the mating relationship between the piston 158 of the syringe assembly 18 and the piston rod 14. For example, the plunger 158 may rotate three times relative to the plunger rod 14 before the threaded distal end 156 of the plunger rod 14 is properly engaged with the plunger 158. If the friction element 60 causes the syringe assembly 18 to rotate more than necessary, excessive turning force applied to the syringe assembly 18 may adversely affect the syringe plunger 158, syringe barrel 78, or some other component of the syringe assembly 18. Thus, the length of the friction element 60 is based on the minimum number of revolutions that the syringe assembly 18 must make about axis B so that the piston 158 is connected to the piston rod 14 sufficiently during one step movement and without damage. The friction element 60 may be made of an elastic material, such as silicone rubber, unfilled rubber, latex, or other suitable material that would cause the syringe assembly 18 to rotate relative to the tray 26 upon contact with the friction element 60. In another embodiment, the friction element 60 may be located on the rollers 68 rather than on the inner outer surface 134 of the guide plate 120. In this example, the guide plate 120 may be positioned such that a portion of the guide plate 120 contacts a friction element 60 located on the rollers 68, causing the rollers 68 to scroll the syringe assembly 18 while moving the tray 26 passing through the guide assembly 50.

In fig. 9 and 10, the pre-force pressure block 54 includes a support plate 136 attached to a rod retaining guide 116, a pressure plate 58, a constant tension spring 138 coupled to the pressure plate 58, and first and second guide rods 142. The elongated pressure plate 58 is positioned adjacent to the rotating portion 22 such that the tray 26 moves under the pressure plate 58 as the tray 26 moves from the first position P1 to the second position P2. In other words, the rotating portion 22 is rotatably positioned relative to the pressure plate 58. The pressure plate 58 is configured to apply a downward force to the piston rod 14 located in the open portion 38 of the tray 26. Specifically, the pressure plate 58 defines the inlet end 144 (shown). 2) and an outlet end 148, wherein the inlet end 144 is sized to accommodate the proximal end 90 of the piston rod 14 and apply a downward force to the proximal end 90 of the piston rod 14 as the piston rod 14 moves from the inlet end 144 to the outlet end. end 148. A constant tension spring 138 is connected to the pressure plate 58 and imparts a downward force to the piston rod 14 via the pressure plate 58 as the tray 26 moves between the first position P1 and the second position P2. The pressure plate 58 is elongated and includes an inclined surface 145 at the upstream end 144 to accommodate the proximal end 90 of the rod without colliding with the body 82 of the piston rod 14.

The pressure plate 58 is movably connected to the first and second guide rods 142, whereby the pressure plate 58 can be moved along the rods 142 in a direction parallel to the rotation axis A. Guide rods 142 extend through the first and second openings of the pressure plate 58 and adjustably attach the pressure plate 58 relative to the rotating portion 22, whereby the pressure plate 58 can be adjusted to accommodate the piston rods 14 and pistons 158 at different heights. The tension spring 138 extends through the third opening of the pressure plate 58 and is attached to the upper surface 150 of the pressure plate 58, whereby a constant force, such as 2 N, is always applied to the piston rod 14. That is, as the piston rod 14 moves from the first position P1 to the second position P2, the proximal end 90 of the piston rod 14 applies an upward force to the pressure plate 58, which may slightly lift the pressure plate 58. But the tension spring 138 ensures that sufficient, non-zero force is applied to the piston rod 14 to positively affect the connection of the piston rod 14 with a piston 158. A threaded rod 152 extends through a passage in the support plate 136 and is configured to contact the bottom surface 154 of the pressure plate 58 to adjust the height of the pressure plate 58 along the guide rods 142.

The pressure plate 58 can be adjusted to accommodate different fill levels of the syringe assembly 18, which correspond to different positions of the piston 158 in the syringe barrel 78. For example, it may be desirable to fill the syringe assembly 18 above the capacity of the syringe assembly marked by the fill line to ensure that the plunger 158 is positioned at a position that is above the fill line at the distal end 133 of the syringe assembly 18. In another example, it may be

- 9 046555 It is advisable to fill the syringe assembly 18 below the fill line indicating the capacity of the syringe assembly to ensure that the plunger 158 is placed in a position that is below the fill line. To accommodate a different fill level or a different piston rod height, the position of the pressure plate 58 relative to the tray 26 can be adjusted by rotating the threaded rod 152 in a clockwise direction or a counterclockwise direction to raise or lower the pressure plate 58 accordingly. Ruler 153 may be attached to guide assembly 50 and remain stationary relative to pressure plate 58 as pressure plate 58 moves. Ruler 153 may be used to measure the distance that pressure plate 58 must be adjusted to accommodate standard fill levels. For example, syringe assembly 18 having a volume capacity of 1 ml may be filled to a fill level below or above the 1 ml fill line. The fill level, determined by the meter marks on the syringe barrel 78, may indicate how much the position of the pressure plate 58 may need to be adjusted beyond standard fill levels. The machine 10 and systems described herein may be configured to handle any number of different syringe assemblies 18, and are not limited to the 1 ml and 2.25 ml sizes described herein.

According to the present invention, the machine 10 is configured to step the tray 26 to connect the plunger rod 14 to the syringe assembly 18. In one step rotation, the distal end 156 of the plunger rod 14 can be threaded with the internal threads of the piston 158 located at the proximal end 132 of the syringe. assembly 18. For example, a loaded tray 26 moves a plunger rod 14 to contact a pressure plate 58, causing a friction member 60 to contact a syringe barrel 78 to rotate the syringe assembly 18. The combination of downward force applied to the push rod 14 plate 58, and the turning force applied to the syringe assembly 18 by the friction element 60 allows the threaded distal end 156 of the piston rod 14 to engage the threaded surface of the piston 158. In some embodiments, the machine may not include a pressure plate 58 at all, and in such embodiments The connection between the piston rod 14 and the piston 158 may be accomplished solely by means of a friction element 60 imparting a turning force to the syringe barrel 78. In still other embodiments, the machine 10 may not include a friction element 60 at all, and in these embodiments, the connection of the piston rod 14 to the piston 158 may be accomplished solely by applying a downward force to the piston rod 14 via a pressure plate 58. In the latter configuration, the piston rod 14 does not can certainly be screwed into piston 158, but, rather, is simply installed using a friction fit.

The machine 10 is designed or programmed to step the tray 26 such that the loaded tray 26 moves between the first position P1 and the second position P2 in one movement of the rotary part 22. The drive device 30, which is operatively connected to the rotary part 22, is configured to be stepped. tray 26 such that the plunger rod 14 and syringe assembly 18 are connected in less than three seconds. Each incremental movement of the tray 26 may include rotating the rotating portion 22 approximately one-third of a full 360 degree rotation, such as 120 degrees about the rotation axis A. For example, the tray 26 at the first position P1 may be rotated about the axis A of the rotating portion 22 approximately 120 degrees relative to the first position P1 to achieve the second position P2. Depending on the position of the guide assembly 50 and the size of the rotating portion 22, the rotating portion 22 may be configured to step the tray 26 with a rotation of less than 120 degrees about axis A. Thus, the machine 10 limits user error or repetitive starting and stopping of a continuously running machine. The machine 10 is configured to connect one plunger rod 14 to one syringe assembly 18 at a time.

The drive device 30 may be configured or programmed to step the tray 26 via the rotary portion 22 only once per activation action. The activation action may be, for example, manually operating the lever 160 of the drive device 30 or operating a switch. A single press of lever 160, for example, activates a servo or other mechanically driven system of drive device 30 to step the tray 26 between a first position P1 and a second position P2. The drive device 30 may be further programmed so that the rotary portion 22 does not rotate until the lever 160 is pressed again or some other activating action occurs. In other embodiments, machine 10 may be activated by another suitable mechanism other than lever 160.

Lever 160 of the manual machine 10 shown in FIG. 1-6, is operatively connected to the rotary part 22 and is configured to move the tray 26 stepwise between the first position P1 and the second position P2. The lever 160 is movably attached to the base 48 and located within the slot 164. When the lever 160 is moved from the non-operating position to the leftmost end of the slot 164, the rotary portion 22 is rotated until the lever 160 returns to its original non-operating position in the slot 164 The lever 160 may be connected to a mechanical device or an electrical drive mechanism located in the base 48, which is converted.

- 10 046555 drives the movement of the lever 160 into the pivoting movement of the rotary portion 22. In another embodiment, the drive device 30 may be configured or programmed to step the tray 26 more than once during an actuating action. For example, the slot 164 of the lever 160 may be provided with marks to indicate to which positions the lever 160 can be moved to step the tray 26 a certain number of times. For example, when the lever 160 is moved to the first activated position, the tray 26 moves one step at a time; and when the lever 160 is moved to an additional, second activated position along the slot 164, the tray 26 makes two incremental movements.

In fig. 11 and 12 depict an adaptive system 170 for converting the manual machine 10 shown in FIG. 1-6, into the semi-automated system 170 for installing the piston rod. In fig. 11 shows the adaptive system 170, and FIG. 12 shows the machine 10 according to FIG. 1-6, fixedly mounted on the actuating platform 172 of the adaptive system 170. The actuating platform 172 provides placement and attachment of the base 48 of the machine 10 to the table 178. The rigid element 182 is movably attached to the table 178 and extends vertically from the table 178 through the semicircular bracket 186. The rigid element 182 moves the semi-circular bracket 186, which is configured to move smoothly across the surface of the table 178 when the rigid element 182 is activated to move the lever 160. As shown in FIG. 12, the rigid member 182 is located adjacent to the lever 160 of the machine 10 when the lever 160 is in a resting or non-activated position. The semicircular bracket 186 is shaped to fit the perimeter of the base 48, which has a complex shape. A servo 190 attached to the table 178 is operatively coupled to the rigid member 182 via a wire located under the table 178. The first and second function switches 194, momentarily pressed by both hands, are attached to opposite sides of the table 178 and are located to enable the operator to operate function switches 194 simultaneously. Function switches 194 are coupled to servo 190 and are configured to operate servo 190 only when switches 194 are depressed simultaneously. In operation, servo 194 activates rigid member 182 to contact arm 160 of machine 10 and move arm 160 within slot 164. Rigid member 182 moves along an arcuate path to contact lever 160 until lever 160 reaches the leftmost end of slot 164. Servo 190 may be programmed to move rigid member 182 only once when both function switches 194 are engaged to step tray 26. In another embodiment implementation, servo 194 can be programmed to step more than once if desired. In this case, the control panel coupled to the activation switches 194 and the servo motor 190 may also be configured to step the tray 26 more than once when the control panel switch is activated.

The adaptive system 170 shown in FIG. 11 and 12 is a piston rod installation system configured to convert a manual piston rod installation system 10 into a semi-automated system using the existing machine 10 shown in FIG. 1-6. In the following figs. 13-15 show a semi-automated system 310 for installing a piston rod in accordance with another embodiment of the present invention. The piston rod installation system 310 is similar to the machine 10 described above, except that the system 310 is semi-automated and includes a different drive device 330. Elements of the system 310 in FIG. 13-15, which are similar to the elements of machine 10, are designated by the same numeric reference numerals, but increased by 300. The description of many of these elements is abbreviated or even omitted for the sake of brevity.

The piston rod mounting system 310 shown in FIG. 13-15, includes a machine 312 and a discharge chute 362 attached to a removable support plate 472. The support plate 472 is removably attached to the table 478 by means of a plurality of quick-change fasteners 480. The drive device 330 is operatively connected to the rotary part 322 and is configured to be stepwise movable. tray 326, carried by a rotating portion 322, from a first position P1 to a second position P2 for connecting the plunger rod 14 to the syringe assembly 18. The plunger rod 14 and syringe assembly 18 are not shown with the plunger rod mounting system 310, but may be located or attached to the machine 312 in the same or similar manner as described and depicted in the previous figures. The drive device 330 includes a servo drive 490 and first and second function switches 494 for operatively controlling the servo drive 490. The servo drive 490 shown in FIG. 14 and 15 is attached to the table 478 and located underneath the machine 312 such that the servo 490 can be directly coupled to the rotary portion 322.

For conversion to a different size syringe assembly 18, the rotary portion 322 may be selected from separate and interchangeable first and second rotary portions. System 310 is configured to allow an operator to easily detach selectable rotary portion 322 and/or machine 312 from servo 490 that is coupled or removably attached to table 478 and replace selectable rotary portion 322 with a first rotary portion suitable for placement.

- 11 046555 syringe assembly 18 of a different size. The first pivot portion 322 includes a tray 326 having a mounting portion 334 sized to accommodate a first size syringe assembly 18, such as a 1 mL syringe, and the second pivot portion includes a tray having a mounting portion sized to accommodate a syringe assembly 18. assembly of a second size, such as a 2.25 ml syringe. The servo 490 of the drive device 330 is configured to be coupled to a base portion 328 of the first rotary portion 322 and a base portion of the second rotary portion. For example, the servo 490 may include a spline shaft 332 or other suitable device extending into a receiving member 336 located in a base portion 328 of the rotary portion 322. The receiving member 336 of both the first rotating portion 322 and the second rotating portion is configured to be coupled to the spline shaft. 332 of the servos 490 when the base 348 of the machine 312 is attached to the table 478. The machine 312 and the outlet chute 362 may be mutually replaced by a second machine and a second outlet chute. Each machine 312 may include an attached guide assembly 350 and a pre-force pressure block 354 operative to engage the rotary portion 322 as described above with respect to the machine 10 of FIG. 1-6.

For example, the selectable rotary portion 322 may be selected by the operator based on the size of the syringe assembly 18 to be assembled. Each selectable rotary portion 322 may correspond to a selectable pressure plate 358, a selectable friction member 360, and a selectable guide plate 420. The first rotary portion 322 includes a first pressure plate 358 coupled to the rotary portion 322, and the second rotary portion includes a second pressure plate coupled to the second turning part. The first pivot portion 26 includes a first guide plate 420 coupled to the first pivot portion 322 and carrying a first friction member 360, and the second pivot portion includes a second guide plate coupled to the second pivot portion and carrying a second friction member. Accordingly, selectable pressure plate 358 is coupled to selectable pivot portion 322, and selectable friction member 360 is carried by selectable guide plate 420 coupled to selectable pivot portion 322.

A preferred application of the plunger rod mounting system 10 and 310 may include positioning the syringe assembly 18 on a tray 26 and 326 of the pivot 22 and 322, the tray 26 and 326 of the pivot 22 and 322 being sized to accommodate the syringe. assembled 18 specific size. The syringe assembly 18 includes a distal end 133 and a proximal end 132, a syringe barrel 78, and a piston 158 located within the syringe barrel 78. The piston rod 14 is located on the tray 26 and 326 of the rotary part 22 and 322, and the piston rod 14 includes a distal end 156 of the rod and a proximal end 90 of the rod, and the distal end 156 of the rod is located above the proximal end 132 of the syringe assembly 18 and is axially aligned with the piston 158. After placing the plunger rod 14 and the first syringe assembly 18 on the tray 26 and 326, this application involves activating an actuator 30 and 330 coupled to the rotary portion 22 and 322 to move the tray 26 and 326 from position P1 to a second position P2 with the application of force to the piston rod 14, which leads to the connection of the piston rod 14 with the syringe assembly 18.

Activation of the drive device 30 and 330 involves rotating the rotary portion 22 and 322 such that the tray 26 and 326 steps from a first position P1 to a second position P2, with the syringe assembly 18 and plunger rod 14 located on the tray 26 and 326 in the first position P1, and the piston rod 14 is connected to the syringe assembly 18 in the second position P2. In addition, this application includes rotating the rotating portion 22 and 322 about axis A. When the tray 26 and 326 is located between the first and second positions P1 and P2, this application includes applying a downward force to the proximal end 90 of the piston rod 14 while moving the tray 26 and 326 from the first position P1 to the second position P2. Applying a downward force to the proximal end 90 of the piston rod 14 involves moving the piston rod 14 under the pressure plate 58 and 358 located adjacent to the pivot portion 22 and 322 while moving the tray 26 and 326 from a first position P1 to a second position P2. Additionally, this application includes applying a turning force to the barrel 78 of the syringe assembly 18 while moving the tray 26 and 326 from a first position P1 to a second position P2. Applying a turning force involves bringing the syringe assembly 18 into contact with a friction member 60 and 360 adjacent the rotating portion 22 and 322 while moving the tray 26 and 326 from a first position P1 to a second position P2. When rotating the rotating portion 22 and 322 in a first direction, rotating the syringe assembly 18 involves bringing the syringe barrel 78 into contact with the friction member 60 and 360 and rotating the syringe assembly 18 in a direction opposite to the first direction of rotation of the rotating portion 22 and 322.

To reconfigure the machine 10 and 312 into the second and third piston rod installation systems 170 and 310 shown in FIG. 11-15, this application further includes disconnecting the rotary portion, such as a second rotating portion, from the drive device 30 and 330. If desired, this application may include detaching the second rotating portion from the table 478 by disengaging a plurality of quick release or quick release fasteners 480 for removing the second support plate from the table 478. Additionally, detaching the second rotating part from the

- 12 046555 of the water device 330 includes disconnecting the spline shaft 332 of the servo 490 from the receiving element of the second rotary part. In addition, this application includes connecting the first rotary part 22 and 322 to the drive device 30 and 330 after disconnecting the second rotary part from the drive device 30 and 330. The connection of the first rotary part 22 and 322 to the drive device 30 and 330 may include connecting a spline shaft 332 servos 490 with a receiving element 336 of the first rotary part 22 and 322. The first rotary part 22 and 322 includes a first movable tray 26 and 326 configured to accommodate a first size syringe assembly 18. Additionally, the method may include attaching the first rotary portion 22 and 322 to the table 478 and/or support plate 472 via quick-change fasteners 480. This application further includes positioning the first syringe assembly 18 and the first plunger rod 14 on the first movable tray 26 and 326 of the first rotary parts 22 and 322. After placing the first plunger rod 14 and the first syringe assembly 18 on the tray 26 and 326, this application involves activating the actuator 30 and 330 coupled to the first rotating part 22 and 322 to move the first tray 26 and 326 from the first position P1 to the second position P2 by applying a force to the first plunger rod 14, resulting in the connection of the first plunger rod 14 with the first syringe assembly 18. As mentioned above, this application involves applying a downward force to the proximal end 90 of the first rod 14 of the piston and/or turning force to the syringe barrel 78 of the first syringe assembly as the first tray 26 and 326 moves from the first position P1 to the second position P2. The steps of this application can be repeated to reconfigure machine 10 and 312 to accommodate other sizes of syringe assemblies 18.

Before using the system 10, 170 and 310 to install the piston rod, the actuator 30 and 330 may be programmed to step the tray 26 and 326 via the rotary portion 22 and 322 only once per activation action. Stepping the tray 26 and 326 from the first position P1 to the second position P2 involves rotating the rotary portion 22 and 322 about a rotation axis A to connect the plunger rod 14 and the syringe assembly 18. Rotating the rotating portion 22 and 322 may include rotating the rotating portion 22 and 322 less than 120 degrees to move the tray 26 and 326 from the first position P1 to the second position P2. When using the first exemplary machine 10, activation of the drive device 30 involves manually moving the lever 160 to rotate the rotary portion 22 and step the tray 26 from a first position P1 to a second position P2. When using the machine 10 with the adaptive drive system 170 shown in FIG. 11 and 12, activation of the drive device 30 involves operating a function switch 194 coupled to the servo actuator 190 to move the rigid member 182 and bracket 186 into contact with the lever 160. When using the third exemplary system 310, activation of the drive device 330 includes activation a function switch 494 connected to a servo 490, which is connected to a rotary portion 322.

In other embodiments, the machine 10 and 312 may be configured to connect a plunger rod and a syringe plunger assembly according to a mating relationship between the plunger rod and the plunger. For example, the illustrated machines 10 and 312 are designed to connect the threaded distal end 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 turning force to the syringe barrel 78. In another example, the piston rod installation system 10 and 310 may be configured to connect the piston rod 14 to the piston 158 in a snap-fit manner. In this example, each machine 10 and 312 may be configured to apply a downward force to the plunger rod 14 to sufficiently engage the plunger rod 14 and the plunger 158 without rotating the syringe assembly 18 relative to the tray 26 and 326. Friction element 60 and 360 can be removed from the guide plate 120 and 420, as a result of which the syringe assembly 18 does not rotate relative to the tray 26 and 326 and the piston rod 14.

The piston rod installation systems described herein provide significant advantages over existing automated piston rod installation systems. Manual and semi-automated systems have a significantly reduced footprint compared to existing automated machines designed for large batch assembly. The disclosed system is a cost effective and efficient alternative to an existing automated machine. Typically, the small demand for plunger rods and syringe assemblies cannot meet the large capital investment of purchasing, operating and maintaining expensive and complex automated machines designed to prepare large batches. However, the disclosed systems 10 and 310 are particularly suitable for assembling small quantities of plunger rod and syringe assemblies in cases where access to fully automated machines is limited or inconvenient. Additionally, the disclosed systems are configured to provide incremental movement such that the plunger rod and syringe assembly are located on the rotating portion and connected before other plunger rod and syringe assemblies are attached to or positioned on the rotating portion. The stepping function ensures safety and reduces the likelihood of operator error because the system

- 13 046555 threads are preset to assemble piston rod and syringe assemblies without the operator having to know each step of the work sequence or interfere with the equipment workflow between assembly steps. Additionally, two-handed momentary function switches ensure that the machine 10 and 312 cannot be used unless both hands of the operator operate the switches. In other words, the likelihood of accidental use or activation of the machine will be greatly reduced, if not completely eliminated. The disclosed systems 10 and 310 are very easy to load, use and unload and do not require extensive training, special education or technical knowledge to use the equipment. Both of these features of the disclosed systems can contribute to the cost-effectiveness and availability of plunger rod and syringe assembly technology.

Semi-automated systems greatly simplify the use of the assembly and the process of adjusting and/or replacing components to assemble syringe assemblies of different sizes, materials and fill levels. For example, the conversion process to adapt existing machines to assemble more than one size syringe assembly is typically labor intensive and requires disassembly, retooling, and reassembly before using the machine. In contrast, certain components of the disclosed plunger rod installation systems can be easily replaced or adjusted in a few minutes and without the need for additional retooling hardware to assemble a different size syringe assembly. These features reduce time and labor costs for qualified personnel, and increase convenience and efficiency.

Information about the medicine

The above description discloses various machines designed to utilize a plunger rod and syringe assembly system. It should be understood that these machines may additionally provide for the use of a drug listed below, with the caveat that the following list should not be considered either inclusive or limiting. The drug is contained in the reservoir of the syringe barrel assembly. In some cases, the reservoir is a main container that is filled or pre-filled for treatment with a drug. The main container may be a pre-filled syringe.

For example, the syringe or syringe assembly can be filled with colony-stimulating factors such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF-based 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), which may be in liquid or lyophilized form. ESA is any molecule that stimulates erythropoiesis, such as Epogen® (epoetin alpha), Aranesp® (darbepoetinal alpha), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol epoetin beta), Hematide®, MRK-2578 , INS-22, Retacrit® (epoetin-zeta), Neorecormon® (epoetin-beta), Silapo® (epoetin-zeta), Binocrit® (epoetin-alpha), Epoetin-alpha Hexal, Abseamed® (epoetin-alpha), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin zeta, epoetin theta and epoetin delta, as well as molecules or variants or analogs thereof , disclosed in the following patents or patent applications, all of which are incorporated herein by reference in their entirety: US Patent Nos. 4,703,008; 5441868; 5547933; 5618698; 5621080; 5756349; 5767078; 5773569; 5955422; 5986047; 6583272; 7084245 and 7271689; and PCT Publication No. WO 91/05867; WO 95/05465; WO 96/40772; WO 00/24893; WO 01/81405 and WO 2007/136752.

ESA may be an erythropoiesis-stimulating protein. As used herein, the expression 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 its dimerization. Erythropoiesis-stimulating proteins include erythropoietin and its variants, analogs or derivatives, which bind to and activate the erythropoietin receptor; antibodies that bind to the erythropoietin receptor and activate the receptor; or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis-stimulating proteins include, but are not limited to, epoetin alfa, epoetin beta, epoetin delta, epoetin omega, epoetin iota, epoetin zeta and analogs thereof, pegylated erythropoietin, carbamylated erythropoietin, peptidomimetics (including EMP1/hematide) and mimetic antibodies. Exemplary erythropoiesis-stimulating proteins include erythropoietin, darbepoietin, erythropoietin agonist variants, and peptides or antibodies that bind and activate the erythropoietin receptor (and include the compounds set forth in U.S. Patent Application Publications Nos. 2003/0215444 and 2006/0040858, disclosures of each which are incorporated herein by reference in their entirety), as well as the erythropoietin molecules or variants or analogs thereof disclosed in the following patents or patent applications, all of which are incorporated herein by reference in their entirety: U.S. Patent Nos. 4703008; 5441868; 5547933; 5618698; 5621080; 5756349; 5767078; 5773569; 5955422; 5830851; 5856298;

- 14 046555

5986047; 6030086; 6310078; 6391633; 6583272; 6586398; 6900292; 6750369; 7030226; 7084245 and 7217689; publication of US patent applications No. 2002/0155998; 2003/0077753; 2003/0082749; 2003/0143202; 2004/0009902; 2004/0071694; 2004/0091961; 2004/0143857; 2004/0157293; 2004/0175379; 2004/0175824; 2004/0229318; 2004/0248815; 2004/02 66690; 2005/0019914; 2005/002 6834; 2005/0096461; 2005/0107297; 2005/0107591; 2005/0124045; 2005/0124564; 2005/0137329; 2005/0142 642; 2005/0143292; 2005/0153879; 2005/0158822; 2005/0158832; 2005/0170457; 2005/0181359; 2005/0181482; 2005/0192211; 2005/0202538; 2005/0227289; 2005/0244409; 2006/0088906 and 2006/0111279; and PCT Publication No. WO 91/05867; WO 95/05465; WO 99/66054; WO 00/24893; WO 01/81405; WO 00/61637; WO 01/36489; WO 02/014356; WO 02/19963; WO 02/20034; WO 02/49673; WO 02/085940; WO 03/029291; WO 2003/055526; WO 2003/084477; WO 2003/094858; WO 2004/002417; WO 2004/002424; WO 2004/009627; WO 2004/024761; WO 2004/033651; WO 2004/035603; WO 2004/043382; WO 2004/101600; WO 2004/101606; WO 2004/101611; WO 2004/106373; WO 2004/018667; WO 2005/001025; WO 2005/001136; WO 2005/021579; WO 2005/025606; WO 2005/032460; WO 2005/051327; WO 2005/063808; WO 2005/063809; WO 2005/070451; WO 2005/081687; WO 2005/084711; WO 2005/103076; WO 2005/100403; WO 2005/092369; WO 2006/50959; WO 2006/02646 and WO 2006/29094.

Examples of other pharmaceuticals for use with the device may include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab) and Prolia™ (denosamab); other biologics such as Enbrel® (etanercept, ΤΝΈ^^πτορ/Γο fusion protein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgrastim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® ( filgrastim, G-CSF, hu-MetG-CSF) and Nplate® (romiplostim); small molecule drugs such as Sensipar® (cinacalcet). The device can also be used with a therapeutic antibody, polypeptide, protein or other chemical such as iron, eg ferumoxytol, iron complexed dextrans, ferrous gluconate and sucrose iron complex. The pharmaceutical preparation may be in liquid form or reconstituted from a lyophilized form.

Specific exemplary proteins include the specific proteins set forth below, including fusions, fragments, analogs, variants or derivatives thereof:

OPGL-specific antibodies, peptibodies and related proteins, etc. (also referred to as RANKL-specific antibodies, peptibodies, etc.), including fully humanized and human OPGL-specific antibodies, in particular fully humanized monoclonal antibodies antibodies, including without limitation the antibodies described in PCT Publication No. WO 03/002713, which is incorporated herein in its entirety with respect to OPGL-specific antibodies and antibody-related proteins, in particular those having the sequences set forth therein, in particular, without limitation, those designated therein as: 9N7; 18B2; 2D8; 2E11; 16E1 and 22B3, including OPGL-specific antibodies having either the light chain of SEQ ID NO:2 set forth therein in FIG. 2, and/or the heavy chain of SEQ ID NO:4 set forth therein in FIG. 4, all of which are separately and specifically incorporated herein by reference in their entirety, fully as disclosed in the above publication;

myostatin-binding proteins, peptibodies and related proteins, etc., including myostatin-specific peptibodies, particularly those described in US Patent Application Publication No. 2004/0181033 and PCT Publication No. WO 2004/058988, which are incorporated herein document by reference in its entirety, in particular in the parts relating to myostatin-specific peptibodies, including without limitation peptibodies from the mTN8-19 family, including those of SEQ ID NO:305-351, including from TN8-19-1 to TN8-19-40, TN8-19 con1 and TN8-19 con2; peptibodies of the mL2 family under SEQ ID NO: 357-383;

mL15 family under SEQ ID NO: 384-409; mL17 family under SEQ ID NO: 410-438; mL20 family under SEQ ID NO: 439-446; mL21 family under SEQ ID NO: 447-452; the mL24 family of SEQ ID NOs: 453-454 and those of SEQ ID NOs: 615-631, all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

IL-4 receptor-specific antibodies, peptibodies and related proteins, etc., in particular those that inhibit activities mediated by the binding of IL-4 and/or IL-13 to the receptor, including those described in PCT- Publication No. WO 2005/047331 or PCT Application No. PCT/US2004/37242 and US Patent Application Publication No. 2005/112694, which are incorporated herein by reference in their entirety, particularly in those portions specific to IL-4 receptor antibodies, in particular those antibodies described therein, in particular and without limitation those designated therein as: 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, all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above

- 15 046555 publications;

interleukin-1 receptor-1 (IL1-R1)-specific antibodies, peptibodies and related proteins, etc., including, without limitation, those described in US Patent Application Publication No. 2004/097712, which is incorporated herein by reference in their entirety in the portions relating to IL1-R1-specific binding proteins, monoclonal antibodies, in particular, and without limitation, those designated herein as: 15CA, 26F5, 27F2, 24E12 and 10H7, all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the aforementioned publication;

Ang2-specific antibodies, peptibodies and related proteins, etc., including without limitation those described in PCT Publication No. WO 03/057134 and US Patent Application Publication No. 2003/0229023, each of which is incorporated herein document by reference in its entirety, in particular in the parts relating to Ang2-specific antibodies and peptibodies, etc., primarily those having the sequences described therein, including without limitation: 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; TN12-9 (N); C17 (N); TN8-8(N); TN8-14(N); Con 1 (N), and also including antibodies to Ang 2 and compositions based thereon, such as those described in PCT publication No. WO 2003/030833, which is incorporated herein by reference in its entirety with respect to the same, in particular AB526; Ab528; Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545; AB546; A551; Ab553; Ab555; Ab558; Ab559; Ab565; AbFlAbFD; Abfe; AbFJ; AbFK; AbGlD4; AbGC1E8; AbH1d2; AblA1; AblF; AblK, AblP and AblP with their various permutations as described therein, all of which are separately and specifically incorporated herein by reference in their entirety, fully as disclosed in the above publication;

NGF-specific antibodies, peptibodies and related proteins, etc., including, without limitation, those described in US Patent Application Publication No. 2005/0074821 and US Patent No. 6,919,426, which are incorporated herein by references in their entirety to NGF-specific antibodies and related proteins in this context, including, in particular, without limitation, the NGF-specific antibodies designated therein as 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11, all of which are separately and specifically incorporated herein by reference in their entirety, fully as disclosed in the foregoing publication;

CD22-specific antibodies, peptibodies and related proteins, etc., such as those described in US Pat. No. 5,789,554, which is incorporated herein by reference in its entirety with respect to CD22-specific antibodies and related proteins, in particular, human CD22-specific antibodies, such as, but not limited to, humanized and fully human antibodies, including, without limitation, humanized and fully human monoclonal antibodies, in particular, including, without limitation, human CD22-specific IgG antibodies, such as, for example, a dimer of the gamma chain of the humanized murine monoclonal antibody hLL2 linked via a disulfide bond to the kappa chain of the humanized murine monoclonal antibody hLL2, including without limitation, for example, the human CD22-specific fully humanized antibody epratuzumab having CAS registration number 50142 3- 2 3-0;

IGF-1 receptor-specific antibodies, peptibodies and related proteins, etc., such as those described in PCT Publication No. WO 06/069202, which is incorporated herein by reference in its entirety with respect to IGF-1 receptor-specific -1 antibodies and related proteins, including, without limitation, IGF-1 specific antibodies, referred to herein as L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11,

L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21, L22H22,

L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L30H30, L31H31, L32H32, L33H33,

L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44,

L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1R binding fragments and derivatives thereof, all of which are separately and specifically incorporated herein by reference in their entirety, fully as disclosed in the above publication .

Also, non-limiting examples of anti-IGF-1R antibodies for use in the compositions of the present invention include each and every one of those described in:

(i) US Patent Application No. 2006/0040358 (published February 23, 2006), 2005/0008642 (published January 13, 2005), 2004/0228859 (published November 18, 2004), including without limitation , for example, Antibody 1A (DSMZ Deposit No. DSM ACC 2586), Antibody 8 (DSMZ Deposit No. DSM ACC 2589), Antibody 23 (DSMZ Deposit No. DSM ACC 2 588) and Antibody 18 described therein;

(ii) PCT Publication No. WO 06/138729 (published December 28, 2006) and WO 05/016970 (published

- 16 046555 gleeful February 24, 2005), and Lu et al. (2004), J. Biol. Chem. 279:2856-2865, including without limitation the antibodies 2F8, A12 and IMC-A12 described therein;

(iii) PCT Publication No. WO 07/012614 (published February 1, 2007), WO 07/000328 (published January 4, 2007), WO 06/013472 (published February 9, 2006), WO 05/058967 (published June 30, 2005) and WO 03/059951 (published July 24, 2003);

(iv) US Patent Application No. 2005/0084906 (published April 21, 2005), including, without limitation, 7C10 antibody, C7C10 chimeric antibody, h7d0 antibody, 7H2M antibody, *7C10 chimeric antibody, GM 607 antibody, humanized antibody 7C10 version 1, humanized antibody 7C10 version 2, humanized antibody 7C10 version 3 and antibody 7H2HM described therein;

(v) US Patent Application Publications Nos. 2005/0249728 (published November 10, 2005), 2005/0186203 (published August 25, 2005), 2004/0265307 (published December 30, 2004), and 2003/0235582 (published December 25, 2003) and Maloney et al. (2003), Cancer Res. 63:5073-5083, including without limitation the EM164 antibody, surface engineered EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2 and huEM164 v1.3 described therein;

(vi) US Patent No. 7,037,498 (issued May 2, 2006), US Patent Application Publications Nos. 2005/0244408 (published November 30, 2005) and 2004/0086503 (published May 6, 2004), and Cohen, et. al. (2005), Clinical Cancer Res. 11:2063-2073, for example antibody CP-751871, including without limitation each of the antibodies produced by hybridomas having ATCC accession numbers PTA2792, 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 described therein;

(vii) U.S. Patent Application Publications Nos. 2005/0136063 (published June 23, 2005) and 2004/0018191 (published January 29, 2004), including, without limitation, the 19D12 antibody and the polynucleotide-encoded heavy chain antibody in plasmid 15H12/19D12 HCA (γ4), deposited in ATCC under number PTA-5214, and the light chain encoded by the polynucleotide in plasmid 15H12/19D12 LCF (k), deposited in ATCC under number PTA-5220, described therein; and (viii) publication of US Patent Application No. 2004/0202655 (published October 14, 2004), including, without limitation, 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, PINT12A1, PINT-12A2, PINT-12A3, PINT-12A4 and PINT- 12A5 described therein; each and every one of which is incorporated herein by reference in its entirety, particularly with respect to the aforementioned antibodies, peptibodies and related proteins, etc., that target IGF-1 receptors;

B7-related protein-1 specific antibodies, peptibodies, related proteins, etc. (B7RP-1 is also called B7H2, ICOSL, B7h and CD275 in the literature), in particular B7RP-specific fully human IgG2 monoclonal antibodies, in particular, a fully human IgG2 monoclonal antibody that binds an epitope in the first immunoglobulin-like domain of B7RP-1, especially those that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, on activated T cells, in particular, primarily , all of the foregoing refer to those disclosed in US Patent Application Publication No. 2008/0166352 and PCT Publication No. WO 07/011941, which are incorporated herein by reference in their entirety with respect to such antibodies and related proteins, including without limitation, antibodies designated therein as follows: 16H (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO: 1 and SEQ ID NO:, respectively, described therein); 5D (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO: 2 and SEQ ID NO: 9, respectively, described therein); 2H (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO: 3 and SEQ ID NO: 10, respectively, described therein); 43H (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO: 6 and SEQ ID NO: 14, respectively, described therein); 41H (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO: 5 and SEQ ID NO: 13, respectively, described therein) and 15H (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO: 4 and SEQ ID NO: 12, respectively, described therein), all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

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

- 17 046555 IFN-gamma-specific antibodies, peptibodies and related proteins, etc., in particular human IFN-gamma-specific antibodies, in particular fully human anti-IFN-gamma antibodies, such as e.g. , described in US Patent Application Publication No. 2005/0004353, which is incorporated herein by reference in its entirety with respect to IFN-gamma-specific antibodies, particularly, for example, the antibodies designated therein as 1118; 1118*; 1119; 1121 and 1121*. The complete sequences of the heavy and light chains of each of these antibodies, as well as the sequences of the variable regions and complementarity determining regions of their heavy and light chains are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication and in Thakur et al . (1999), Mol. Immunol. 36:1107–1115. In addition, the description of the properties of these antibodies presented in the above publication is also incorporated herein by reference in its entirety. Specific antibodies include those having a heavy chain of SEQ ID NO: 17 and a light chain of SEQ ID NO: 18; antibodies having a heavy chain variable region of SEQ ID NO: 6 and a light chain variable region of SEQ ID NO: 8; antibodies having a heavy chain of SEQ ID NO: 19 and a light chain of SEQ ID NO: 20; antibodies having a heavy chain variable region of SEQ ID NO: 10 and a light chain variable region of SEQ ID NO: 12; antibodies having a heavy chain of SEQ ID NO: 32 and a light chain of SEQ ID NO: 20; antibodies having a heavy chain variable region of SEQ ID NO: 30 and a light chain variable region of SEQ ID NO: 12; antibodies having the heavy chain sequence of SEQ ID NO: 21 and the light chain sequence of SEQ ID NO: 22; antibodies having a heavy chain variable region of SEQ ID NO: 14 and a light chain variable region of SEQ ID NO: 16; antibodies having a heavy chain of SEQ ID NO: 21 and a light chain of SEQ ID NO: 33; and antibodies having a heavy chain variable region of SEQ ID NO: 14 and a light chain variable region of SEQ ID NO: 31 disclosed in the above publication. The specific antibody contemplated is Antibody 1119 disclosed in the above US patent application publication and having the entire heavy chain sequence of SEQ ID NO: 17 disclosed therein and having the entire light chain sequence of SEQ ID NO: 18 disclosed therein;

TALL-1-specific antibodies, peptibodies and related proteins, etc. and other TALL-specific binding proteins such as those described in US Patent Application Publications Nos. 2003/0195156 and 2006/0135431, each of which is included herein by reference in their entirety with respect to the TALL-1 binding proteins, in particular the molecules of Tables 4 and 5B, all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publications;

parathyroid hormone (PTH)-specific antibodies, peptibodies and related proteins, etc., such as those described in US Pat. No. 6,756,480, which is incorporated herein by reference in its entirety, particularly in its protein portions , which bind PTH;

thrombopoietin receptor (TPO-R)-specific antibodies, peptibodies and related proteins, etc., such as those described in U.S. Patent No. 6,835,809, which is incorporated herein by reference in its entirety, particularly in the portions relating to proteins that bind TPO-R;

hepatocyte growth factor (HGF)-specific antibodies, peptibodies and related proteins, etc., including those that target the HGF/SF:c-Met signaling pathway axis (HGF/SF:c-Met), such as completely human monoclonal antibodies that neutralize hepatocyte growth factor/scatter factor (HGF/SF), described in US Patent Application Publication No. 2005/0118643 and PCT Publication No. WO 2005/017107, huL2G7, described in US Patent No. 7220410, and OA ^5. described in US Patent Nos. 5,686,292 and 6,468,529 and PCT Publication No. WO 96/38557, all of which are incorporated herein by reference in their entirety, particularly in the portions relating to proteins that bind HGF;

TRAIL-R2 specific antibodies, peptibodies, related proteins, etc., such as those described in US Pat. No. 7,521,048, which is incorporated herein by reference in its entirety, particularly in the portions relating to proteins that bind TRAIL-R2;

Activin A-specific antibodies, peptibodies, related proteins, etc., including, without limitation, those described in US Patent Application Publication No. 2009/0234106, which is incorporated herein by reference in its entirety, in particular , in parts related to proteins that bind activin A;

TGF-beta specific antibodies, peptibodies, related proteins, and the like, including, without limitation, those described in U.S. Patent No. 6,803,453 and U.S. Patent Application Publication No. 2007/0110747, all of which are incorporated herein by references in their entirety, in particular in parts relating to proteins that bind TGF-beta;

amyloid beta protein specific antibodies, peptibodies, related proteins, etc., including without limitation those described in PCT Publication No. WO 2006/081171, which

- 18 046555 is incorporated herein by reference in its entirety, particularly in the portions relating to proteins that bind amyloid beta proteins. One contemplated antibody is an antibody having a heavy chain variable region having SEQ ID NO: 8 and a light chain variable region having SEQ ID NO: 6 disclosed in the above publication;

c-Kit specific antibodies, peptibodies, related proteins, etc., including without limitation those described in US Patent Application Publication No. 2007/0253951, which is incorporated herein by reference in its entirety, in in particular, in parts relating to proteins that bind c-Kit and/or other stem cell factor receptors;

OX40L-specific antibodies, peptibodies, related proteins, etc., including, without limitation, those described in US Patent Application Publication No. 2006/0002929, which is incorporated herein by reference in its entirety, in particular, in parts relating to proteins that bind OX40L and/or other OX40 receptor ligands; and other exemplary proteins, including Activase® (alteplase, tPA); Aranesp® (darbepoetin alfa); Epogen® (epoetin alfa or erythropoietin); GLP-1, Avonex® (interferon beta-1a); Bexxar® (tositumomab, an anti-CD22 monoclonal antibody); Betaseron® (interferon beta); Campath® (alemtuzumab, an anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (mAb to α4β7); MLN1202 (mAb to chemokine receptor CCR2); Enbrel® (etanercept, ΤΝΕ^^πτορ/Ρο fusion protein, TNF blocker); Ergekh® (epoetin-alpha); Erbitux® (cetuximab, anti-EGFR/HER1/c-ErbB-1 antibody); Genotropin® (somatropin, human growth hormone); Herceptin® (trastuzumab, mAb to the HER2/neu receptor (erbB2)); Humatrope® (somatropin, human growth hormone); Humira® (adalimumab); insulin in solution; Infergen® (interferon alfacon-1); Natrecor® (nesiritide; recombinant human B natriuretic peptide (hBNP); Kineret® (anakinra); Leukine® (sargramostim, rhuGM-CSF); LymphoCide® (epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat-B, belimumab, mAb to BlyS); Metalyse® (tenecteplase, t-PA analog); Mylotarg® (gemtuzumab ozogamicin); Cimzia® (certolizumab pegol, CDP 870); ™ (eculizumab); pexelizumab (anti-complement component C5); Lucentis® (ranibizumab); Trabio® (lerdelimumab); ; Omnitarg (pertuzumab, 2C4); OvaRex® (B43.13); cantuzumab mertansine (huC242-DM1); , human interleukin-11); Neulasta® (PEGylated filgrastim, PEGylated G-CSF, PEGylated hu-Met-G-CSF); CD3, anti-CD3 monoclonal antibody); Procrit® (epoetin alfa); Remicade® (infliximab, a monoclonal antibody to TNFa); Reopro® (abciximab, monoclonal antibody to the GP lIb/Ilia receptor);

Actemra® (IL6 receptor mAb); Avastin® (bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20 mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alpha-2a); Simulect® (basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO (anti-IL15 antibody, see US Patent No. 7153507); Tysabri® (natalizumab, mAb to integrin a4); Valortim® (MDX-1303, mAb to the protective antigen of B. anthracis); ABthrax™; Vectibix® (panitumumab); Xolair® (omalizumab); ETI211 (mAb to MRSA); IL-1 decoy (the Fc portion of human IgG1 and the extracellular domains of both components of the IL1 receptor (type I receptor and receptor accessory protein)); VEGF decoy (VEGFR1 Ig domains fused to IgG1 Fc); Zenapax® (daclizumab); Zenapax® (daclizumab, mAb to IL-2Ra); Zevalin® (ibritutomab tiuxetan); Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); monoclonal antibody to CD80 (galiximab); mAb to CD23 (lumiliximab); BR2-Fc (huBR3/huFc fusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, mAb to TNFa); HGS-ETR1 (mapatumumab; mAb to human TRAIL receptor 1); HuMax-CD20 (ocrelizumab, mAb to human CD20); HuMax-EGFR (zalutumumab); M200 (volociximab, mAb to integrin α5β 1); MDX-010 (ipilimumab, mAb to CTLA-4 and VEGFR-1 (IMC-18F1); mAb to BR3; mAb to toxin A and toxin B of C. difficile C, MDX-066 (CDA-1) and MDX-1388) ; dsFv conjugates to CD22PE38 (CAT-3888 and CAT-8015); mAb to CD25 (HuMax-TAC); mAb to CD3 (NI-0401); adecatumumab; mAb to CD30 (MDX-060); MDX-1333 (anti-IFNAR antibody); mAb to CD38 (HuMax CD38); mAb to CD40L; mAb to Cripto; an anti-CTGF antibody for idiopathic pulmonary fibrosis in a phase I study (FG-3019) from Fibrogen; mAb to CTLA4; mAb to eotaxin-1 (CAT-213); mAb to FGF8; mAb to ganglgioside GD2; mAb to ganglgioside GM2; mAb to human GDF-8 (MYO-029); mAb to the GM-CSF receptor (CAM3001); mAb to NerS (HuMax NerS); mAb to IFNa (MEDI-545, MDX-1103); mAb to IGF1R; mAb to IGF-1R (NiMax-Inflam); mAb to IL12 (AVT-874); mAb to IL12/IL23 (CNTO 1275); mAb to IL13 (CAT-354); mAb to IL2Ra (HuMax-TAS); IL5 receptor mAb; mAb to integrin receptors (MDX-018, CNTO 95); IP10 mAb for ulcerative colitis (MDX-1100); anti-LLY antibody; BMS-66513; mAb to mannose/Hcge receptor (MDX-1307); dsFv conjugate to mesothelin-PE38 (CAT-5001); mAb to PD1 (MDX-1106 (ONO-4538)); anti-PDGFRa antibody (IMC-3G3); mAb to TGFe (GC-1008); mAb to human TRAIL receptor-2 (HGS-ETR2); mAb to TWEAK; mAb to VEGFR/Flt-1; mAb to ZP3 (HuMax-ZP3); NVS antibody #1 and NVS antibody #2.

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Claims (15)

An anti-sclerostin antibody such as, but not limited to, romosozumab, blosozumab, or BPS 804 (Novartis) may also be included. In addition, therapeutic agents such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA may be included. Additionally, a monoclonal antibody (IgG) that binds human proprotein convertase subtilisin-kexin type 9 (PCSK9), such as that described in US Patent No. 8,030,547, US Patent Application Publication No. 2013/0064825, WO 2008/057457, may be included in the device. WO 2008/057458, WO 2008/057459, WO 2008/063382, WO 2008/133647, WO 2009/100297, WO 2009/100318, WO 2011/037791, WO 2011/053759, WO 2011/053783, WO 2008/125623, WO 2011/072263, WO 2009/055783, WO 2012/0544438, WO 2010/029513, WO 2011/111007, WO 2010/077854, WO 2012/088313, WO 2012/101251, 2012/101252, WO 2012/101253, WO 2012/109530 and WO 2001/031007. Talimogene laherparepvec or another oncolytic HSV may also be included to treat melanoma or other types of cancer. Examples of oncolytic HSV include, but are not limited to, talimogene laherparepvec (US Patent Nos. 7,223,593 and 7,537,924); OncoVEXGALV/CD (US Patent No. 7981669); OrienXO10 (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). TIMPs are also included. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) and play important roles in many natural processes. TIMP-3 is expressed by various cells and/or is present in the extracellular matrix; it inhibits all major cartilage-degrading metalloproteases and may be involved in the development of many destructive connective tissue diseases, including rheumatoid arthritis and osteoarthritis, as well as cancer and cardiovascular conditions. The amino acid sequence of TIMP-3 and the nucleic acid sequence of the DNA molecule that encodes TIMP-3 are disclosed in US Pat. No. 6,562,596, issued May 13, 2003, the disclosure of which is incorporated herein by reference. Descriptions of mutations in TIMP can be found in US Patent Application Publication No. 2014/0274874 and PCT Publication No. WO 2014/152012. Also included are antibodies that antagonize the human calcitonin-related peptide (CGRP) receptor and a bispecific antibody molecule that targets the CGRP receptor and other targets associated with headache development. Additional information regarding these molecules can be found in PCT Application No. WO 2010/075238. In addition, the device can use a bispecific T cell recruiter antibody (BiTe), such as blinatumomab. Alternatively, a high molecular weight APJ agonist, such as apelin or analogues thereof, may be included in the device. Information related to such molecules can be found in PCT Publication No. WO 2014/099984. In certain embodiments, the medicinal product contains a therapeutically effective amount of an antibody to thymic stromal lymphopoietin (TSLP) or TSLP receptor. Examples of anti-TSLP antibodies that can be used in such embodiments include, but are not limited to, those described in US Patent Nos. 7,982,016 and 8,232,372 and US Patent Application Publication No. 2009/0186022. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in US Pat. No. 8,101,182. In particularly preferred embodiments, the drug formulation contains a therapeutically effective amount of an anti-TSLP antibody, designated A5 in US Pat. No. 7,982,016. Although machines for connecting a plunger rod to a syringe assembly through exemplary embodiments have been described, they are not limited to them. The detailed description is to be interpreted as being given by way of example only and does not set forth every possible embodiment of the present invention since it would be impractical, if not impossible, to set forth every possible embodiment. Numerous alternative embodiments may be implemented using modern technology or technology developed after the filing date of this patent, which nevertheless fall within the scope of the present invention. It should be understood that the scope of protection of the present invention is determined by the language of the claims set forth below at the end of this patent. The appended claims should be interpreted broadly to include other variations and embodiments thereof as may be made by those skilled in the art without departing from the scope and scope of machine equivalents and components thereof. CLAIM 1. A machine for connecting a piston rod with a syringe assembly, containing: a rotating portion having a movable tray containing a mounting portion sized to accommodate the syringe assembly and an open portion located above the mounting portion sized to accommodate the piston rod; - 20 046555 a drive device operatively connected to the rotating part and configured to step the tray from a first position to a second position once upon activation to connect the piston rod to the syringe assembly; and a pressure plate located adjacent the rotating portion such that the tray moves under the pressure plate when the tray is moved from the first position to the second position, wherein the pressure plate is configured to apply a downward force to a piston rod located in the open portion of the tray when the tray moves from the first position to the second position, wherein the driving device includes a servo drive and a function switch for operatively controlling the servo drive, wherein the servo drive is connected to the rotary part for moving the tray stepwise by the rotary part. 2. The machine of claim 1, wherein the servo is programmed to respond to an actuating action to move the rotary portion, the actuating action including operating a function switch. 3. The machine of claim 2, wherein the driving device comprises a lever operatively coupled to the rotatable portion, the lever being configured to be operated to effect an actuating action. 4. The machine of claim 3, wherein the drive device comprises a movable arm for moving the lever, the movable arm being operatively coupled to the servo drive. 5. The machine according to any one of claims 2 to 4, in which the drive device provides stepwise movement of the tray only once during the activating action. 6. The machine according to any one of claims 1 to 5, wherein the function switch includes a momentary function switch pressed simultaneously by both hands. 7. The machine according to any one of claims 1 to 6, in which the servo drive is configured to be functionally connected to another rotary part. 8. The machine according to any one of claims 1 to 7, which further comprises a movable piston rod base connected to the rotatable portion, the piston rod base located above the tray and comprising an opening sized to accommodate a flanged proximal end of the piston rod, wherein the hole is axially aligned with the open portion of the tray, and the base for the piston rod is movable with the tray from a first position to a second position; and a holding cap having an outwardly projecting tongue positioned to project into an opening of the piston rod base, wherein the holding cap is removably attached to the piston rod base, and wherein the holding cap is secured relative to the rotatable portion and positioned in the opening when the tray is in the first position. 9. The machine of claim 8, wherein the piston rod base is selected from separate and interchangeable first and second piston rod bases, wherein the first piston rod base includes an opening sized to receive a flanged end of the first size piston rod, and the second piston rod base is sized to accommodate the flanged end of a second size piston rod that is different from the first size. 10. The machine according to any one of claims 1 to 9, in which the tray has a tray axis that is in line with the longitudinal axes of the syringe assembly and the piston rod, when the syringe assembly and the piston rod are located in the tray, and the axis of the tray is located under at an angle greater than zero degrees relative to the vertical. 11. The machine according to any one of claims 1 to 10, in which the turning part contains a turning carousel with a turning axis that is parallel to the axis of the tray, so that the turning axis of the turning part is located at an angle greater than zero degrees relative to the vertical. 12. The machine according to any one of claims 1 to 11, in which the rotating part is rotatable relative to the pressure plate. 13. The machine according to any one of claims 1 to 12, in which the installation part of the tray includes a first roller and a second roller separated by a gap, and the first and second rollers of the installation part are configured to contact the syringe barrel assembly and hold the syringe barrel in the gap when transferred by a tray, while the first and second rollers ensure scrolling of the syringe assembly as the tray moves stepwise from the first position to the second position. 14. The machine according to any one of claims 1 to 13, in which the rotary part contains a plurality of trays carried by the rotary part. 15. The machine according to any one of claims 1 to 14, which further comprises an outlet chute located adjacent to the rotating part in the second position of the tray, wherein the outlet chute is configured to accommodate the piston rod and syringe assembly from the tray after connecting the piston rod to the syringe at collection -