Patent Description:
A new class of medicines is gaining much attention. This class of medicines employs functional cells for disease treatment. These medicines, either autologous or allogenic in nature, present certain challenges for therapy manufacturers or providers, however.

From a historical standpoint, cell-based therapies most commonly have been delivered from flexible plastic containers, or bags. With most cell-based therapeutics requiring cryopreservation at liquid nitrogen temperatures to preserve cell function during shipping or patient preparations regimens, bags present several challenges. The bags can be fragile when frozen, and are susceptible to breakage and/or contamination. In addition, fluids held up in the bag can prevent incomplete dosing.

In the alternative, vials have been considered. Vials are generally easy to handle and can be compatible with cryopreservation. The filling of vials is considered an "open" manipulation, however, and carries increased risk of drug product contamination, especially for small lot drugs that would require hand-filling. Thus, vials are not a complete answer.

Prefilled syringes are another option, in the form of a delivery vessel that is ready-to-use. However, the designs of conventional syringes do not allow them to maintain closure during cryopreservation. Conventional syringes are for example described in <CIT>, <CIT> or <CIT>.

It would be desirable to provide a container that overcame, at least in part, the disadvantages of conventional containers for use with cell-based medicines.

In an aspect, a syringe includes a barrel, a plunger, and a vented closure. The barrel has a bore, and an end with an opening in communication with the bore and a barrel flange disposed outwardly of the opening. The plunger is disposed in the bore, and is movable along the bore. The vented closure is attached to the barrel at the end, and includes a stopper, a cap and a filter. The stopper is disposed over and/or in the opening in communication with the bore. The cap includes a body disposed over the stopper, and a fastener engaged with the barrel flange. The filter is disposed between the stopper and the cap, or in at least one of the stopper and the cap. The stopper comprises a first end comprising a plug disposed within the bore and a second end comprising a stopper flange depending from the second end of the stopper outside the bore, and the cap secures the stopper flange between the body of the cap and the barrel flange.

A more detailed description of the systems and methods in accordance with the present disclosure is set forth below. It should be understood that the description below of specific devices and methods is intended to be exemplary, and not exhaustive of all possible variations or applications. Thus, the scope of the disclosure is not intended to be limiting, and should be understood to encompass variations or embodiments that would occur to persons of ordinary skill.

Furthermore, while certain relative spatial terms, such as left, right, upper, lower, inner and outer, have been used relative to the embodiments as illustrated in the drawings, these terms have been used for ease of explanation relative to those particular illustrations. The terms are not intended to require a particular orientation of the syringe and closure in use. Other relative spatial terms might be substituted for those used in the text if the embodiments were illustrated in a different orientation on the page, as will be recognized by the reader.

Starting with reference to <FIG>, a syringe <NUM> includes a barrel <NUM>, a plunger <NUM>, and a vented closure <NUM>. The syringe <NUM> according to these embodiments may be used to contain, for example, a cell-based medicine, and may be adapted to store that medicine at a variety of temperatures. Moreover, the syringe <NUM> may provide a container that is a ready-to-use delivery vessel, pre-filled syringes <NUM> being used alone or as a component of an autoinjector or autoinfuser. In addition, the syringe <NUM> described herein may be used with pneumatic driving system, or drivers, to reduce the risks of contamination during filling.

The barrel <NUM> of the syringe <NUM> has a bore <NUM>. The barrel <NUM> also has a first end <NUM> with an opening <NUM> in communication with the bore <NUM>, and a barrel flange <NUM> disposed outwardly of the opening <NUM>. The plunger <NUM> is disposed in the bore <NUM>, and is movable along the bore <NUM>, for example between the first end <NUM> and a second end <NUM>.

The vented closure <NUM> is attached to the barrel <NUM> at the first end <NUM> (via a snap-fit, for example), and includes a stopper <NUM>, a cap <NUM> and a filter <NUM>. The stopper <NUM> is disposed over and/or in the opening <NUM> in communication with the bore <NUM>. The cap <NUM> includes a body <NUM> disposed over the stopper <NUM>, and a fastener <NUM> engaged with the barrel flange <NUM>. The filter <NUM> is disposed between the stopper <NUM> and the cap <NUM>, or in at least one of the stopper <NUM> and the cap <NUM>. While the cap <NUM> appears spaced from the stopper <NUM> by the width of the filter <NUM>, this is an exaggeration for purposes of illustration of each of the parts - in actuality the cap <NUM> may abut the stopper <NUM> as well as the filter <NUM>.

The vented closure <NUM> permits a pneumatic driver to be attached to the syringe <NUM> to move the plunger <NUM> along the bore <NUM>. Because only filtered gas (e.g., air) enters and exits the bore <NUM> to move the plunger <NUM>, the possible contamination risks that might be related to the use of a mechanical driver (including plunger handle and linear actuator) entering the bore through an open end can be eliminated. Further, the stopper <NUM> provides a further seal useful under cryopreservation conditions, thereby reducing the role that the plunger <NUM> has to play under such conditions in sealing the bore <NUM>. Further, where the closure <NUM> is removeable, the syringe <NUM> represents an easily configurable, ready-to-use delivery vessel.

Having discussed the syringe <NUM> in general terms, the details of the syringe <NUM> are discussed, as well as some of its uses.

As mentioned above with reference to <FIG>, the barrel <NUM> has a first end <NUM>, the first end <NUM> including the opening <NUM> and the barrel flange <NUM>, and a second end <NUM> located at the opposite end of the barrel <NUM>. According to the illustrated embodiment, the barrel <NUM> may have a tip <NUM> at the second end <NUM>, the tip <NUM> being in fluid communication with the bore <NUM>. The tip <NUM> may be configured to connect to a needle, for example as a luer lock or a luer slip tip. Alternatively, the tip <NUM> may include a septum that will be pierced by a canula that is attached to or is part of a delivery system, such as may be found in an autoinjector or autoinfuser device. The tip <NUM> may be closed with a cap or cover (not shown) in storage, or when not in use.

According to certain embodiments, the tip <NUM> may be connected to tubing, and define a processing set that may be used with other equipment. In fact, more than one syringe <NUM> may be attached to such tubing to define the processing set. When the syringe <NUM> is pre-connected to tubing in such a processing set, the syringe can be terminally sterilized, further reducing the chances of contamination when processed cells or other material is transferred into and out of the syringe <NUM>.

At the first end <NUM>, the barrel flange <NUM> may depend outwardly from the barrel <NUM>, but may not depend radially outwardly from the barrel <NUM> to the same distance in all directions. See, e.g., <FIG>. That is, the barrel flange <NUM> may not form an annular shelf depending from the barrel in a cantilevered fashion, but instead may be in the form of two opposite cantilevered structures that depend from the barrel <NUM> from opposite sides (e.g., left and right) of the barrel <NUM>. These structures may be used during delivery of the medicine from the syringe <NUM>, by placing the index and middle fingers against the flange <NUM> while depressing on a plunger handle that is attached to the plunger <NUM>. In other variants, the barrel flange <NUM> may be too narrow to be used in this fashion, with index and middle fingers disposed against the flange <NUM>.

According to still other embodiments, the barrel flange <NUM> may not be formed as a single structure with the barrel <NUM> (i.e., an integral or unitary structure). One such alternate embodiment is illustrated in <FIG>. As illustrated in <FIG>, the barrel <NUM> may have a slight taper between the first end <NUM> and the second end <NUM>, and an annular structure, referred to herein as a collar <NUM>, may be positioned on the barrel <NUM> to define the barrel flange <NUM>. In particular, the collar <NUM> has an opening <NUM> that connects to a passage <NUM> formed therethrough, and the barrel <NUM> is disposed into the opening <NUM> and through the passage <NUM> as the collar <NUM> is moved along the barrel <NUM> from the second end <NUM> to the first end <NUM>. The collar <NUM> may be held in place at the first end of the barrel <NUM> by the taper of the barrel <NUM> and a friction-fit of the collar <NUM> and the barrel <NUM>. According to other embodiments, the barrel <NUM> may not have a taper, and the collar <NUM> may be held in place by friction-fit alone. According to still other embodiments, the collar <NUM> may be joined to the barrel <NUM> using conventional joining methods.

In addition, while the illustrated embodiments may disclose a single barrel flange <NUM>, according to other embodiments, more than one flange may be disposed along the barrel <NUM>. For example, there may be a first barrel flange formed integrally with the barrel <NUM>, and a second barrel flange that is formed or defined by a collar, like the collar <NUM>, that is disposed along the barrel <NUM>. The closure <NUM> may cooperate with one or more of these barrel flanges <NUM>.

The barrel <NUM>, including the flange <NUM>, may be formed of any of a number of different plastics. For example, the barrel <NUM> and the flange <NUM> may be made from a cyclic olefin polymer or copolymer. It is believed that such a polymer may provide suitable performance over a range of temperatures, including those that the syringe <NUM> may experience during cryopreservation. In addition, where the flange <NUM> is not formed integrally with the barrel <NUM>, the two structures may be made of different plastics.

The design of the plunger <NUM> and the materials used in its manufacture may vary. In fact, because of the closure <NUM>, and in particular the stopper <NUM> being present to seal, at least in part, the bore <NUM>, the design of the plunger <NUM> and the material selection may be even more varied because it is not necessary to design the plunger <NUM> to provide a complete seal even under cryopreservation conditions. This permits the plunger <NUM> to be designed to optimize for (or at least emphasize) other issues, such as deliverability, instead of having to trade off performance relative to storage capability over a wide range of temperatures.

Returning then to the closure <NUM> and <FIG>, the embodiment of the stopper <NUM> illustrated not only covers the opening <NUM>, it is also disposed within the bore <NUM> of the barrel <NUM>. That is, the stopper <NUM> includes a first end <NUM> in the form of a plug <NUM> that is disposed within the bore <NUM>, and a second end <NUM> that has a stopper flange <NUM> that depends therefrom outside the bore <NUM> and over the opening <NUM>. The plug <NUM> may have a cross-section that is substantially similar to the cross-section of the bore <NUM>; for example, where the bore <NUM> is cylindrical, the plug <NUM> may be cylindrical. Similarly, the stopper flange <NUM> may have a shape that is complementary to the shape of the barrel flange <NUM>; for example the stopper flange <NUM> may include cantilevered structures (or wings) that depend from opposite sides (e.g., left and right) from the stopper <NUM>. According to other embodiments, the stopper <NUM> may be disposed only over the opening <NUM>, or may be disposed only within the bore <NUM>.

The stopper <NUM> may be maintained in place in part because of the presence of the plug <NUM> in the bore <NUM>. In fact, an outer surface of the plug <NUM> facing an inner surface of the bore <NUM> may have structures (such as ribs) that cooperate with the inner surface of the bore <NUM> to prevent material from passing between the outer surface of the plug <NUM> and the inner surface of the bore <NUM> and to improve the securement of the plug <NUM> in the bore <NUM>. The stopper <NUM> is also maintained in place as a consequence of the cooperation of the cap <NUM> with the stopper <NUM>, an in particular the cap <NUM> with the stopper flange <NUM>.

As illustrated, the body <NUM> of the cap <NUM> overlies the stopper flange <NUM>. According to certain embodiments, the body <NUM> may be shaped to be complementary to the shape of the stopper flange <NUM>, so that the body <NUM> is coextensive with the periphery of the stopper flange <NUM>. According to other embodiments, the body of the cap <NUM> may overlie only those regions of the stopper flange <NUM> that also overlie the barrel flange <NUM>. For example, the body of the cap <NUM> may include a relatively large opening, such that the regions of the body <NUM> of the cap <NUM> that overlie the flange <NUM> are connected with a web of material, but the cap <NUM> is still considered to secure the stopper flange <NUM> between the body <NUM> of the cap <NUM> and the barrel flange <NUM>,.

The cap <NUM> also includes the fastener <NUM>, and the fastener <NUM> may take a variety of shapes as is reflected in the alternative embodiments discussed later. Many embodiments of the fastener <NUM> are configured to cooperate or engage, directly or indirectly, with a surface of the barrel flange <NUM> to secure the stopper <NUM> to the barrel <NUM>. That is, the fastener <NUM> may have a feature (e.g., a barb) that it is disposed directly against the surface of the barrel flange <NUM> to secure the stopper <NUM> to the barrel <NUM>. Alternatively, the fastener <NUM> may include an intermediate structure (e.g., a collar, similar to the collar <NUM> introduced above) that is disposed directly against the surface of the barrel flange <NUM>, and then the fastener <NUM> may include a feature (e.g., a barb) that is disposed directly against a surface of the intermediate structure (e.g., collar) to secure the stopper <NUM> to the barrel <NUM>.

According to the illustrated embodiment of <FIG>, and with particular reference to <FIG>, the fastener <NUM> includes a skirt <NUM> that depends from the body <NUM>, at least those regions that overlie the barrel flange <NUM>, the skirt <NUM> having one or more barbs <NUM> depending therefrom. The barb(s) <NUM> cooperated with the barrel flange <NUM> to secure the stopper in place, and may also cause the cap <NUM> to compress the stopper <NUM> to create a hermetic static seal in the bore <NUM>, which hermetic seal may be compatible with room temperature, refrigeration, and cryogenic storage.

According to the illustrated embodiment, the cap <NUM> includes a skirt <NUM> that depends downwardly from the body <NUM>. It will be recognized that directional references are adopted herein for the convenience of the reader, such that downward does not place an absolute limitation on the nature of the skirt <NUM>. Instead, it is meant to convey that the skirt <NUM> depends from the cap <NUM> in a direction toward the barrel flange <NUM> , considering that the cap <NUM> previously been described as disposed over the stopper flange <NUM>, which in turn overlies the barrel flange <NUM>.

The skirt <NUM> is not continuous about the perimeter of the body <NUM> of the cap <NUM>, although it could be according to certain embodiments. Instead the skirt <NUM> includes two sections, each of which borders the sections of the body <NUM> the overlie the barrel flange <NUM>. This skirt <NUM> could, in other embodiments, be divided even further, so as to define a plurality of skirt sections, or fingers. In the same fashion that the barb <NUM> is defined along the perimeter of the skirt sections <NUM> illustrated, each of these fingers could have a barb disposed at a downward end thereof, each barb cooperating with the barrel flange <NUM>. Such an arrangement may provide for a more flexible skirt <NUM> overall, making separation of the closure <NUM> from the barrel <NUM> easier.

As mentioned above, the barb <NUM> engages the barrel flange <NUM> to secure the closer <NUM> to the barrel <NUM>. It will be recognized that the barb <NUM> may have a head <NUM> with an inner surface <NUM>, and the barrel flange <NUM> may have an outer surface <NUM>. In considerable of the spatial directions being used elsewhere for ease of explanation, the surface <NUM> may be referred to as facing upward, while the surface <NUM> may be referred to as facing downward. The surfaces <NUM>, <NUM> abut each other with the stopper <NUM> and cap <NUM> arranged on the barrel <NUM> as illustrated.

According to embodiments such as the illustrated embodiment, the engagement of the surfaces <NUM>, <NUM> is the primary attachment mechanism between the barrel <NUM> and the snap-fit closure <NUM>, such that with sufficient force applied to the closure <NUM>, the closure <NUM> may be separated from the barrel <NUM>. The closure <NUM> may be referred to as removable even if the force applied causes permanent deformation, or even failure, of the cap <NUM> (and in particular the skirt <NUM>). In fact, according to certain embodiments, the skirt <NUM> and/or barbs <NUM> may be separated from the cap <NUM> to permit the closure <NUM> to be removed from the barrel <NUM>. According to such an embodiments, a rupturable boundary (e.g., a line of weakness in the material) may be formed between the skirt <NUM> and/or barbs <NUM> and the remainder of the cap <NUM>, thereby permitting the skirt and/or barbs <NUM> to be separated from the remainder of the cap <NUM> with peeling or tearing of the material along the rupturable boundary. The skirt <NUM> and/or barbs <NUM> also may be removable after separation. On the other hand, the closure <NUM> may be referred to as reversibly removeable if the force required may cause the cap <NUM> to separate causes the cap <NUM>, and in particular the skirt <NUM>, to deflect or flex, but is not sufficient to cause permanent deformation or failure.

The closure <NUM> may be removeable so that, after filling, a mechanical control mechanism can cooperate with the plunger <NUM> directly. That is, the closure <NUM> is designed to permit gas (e.g., air) to move the plunger <NUM> along the bore <NUM>. However, while a pneumatic system may be used during filling to move the plunger <NUM>, a large number of delivery systems use mechanical control mechanisms instead of gaseous ones. For example as illustrated in <FIG>, the closure <NUM> may be removed so that a first end <NUM> of a plunger handle <NUM> may be disposed through the opening <NUM> and into the bore <NUM>. The plunger <NUM> may have an attachment mechanism <NUM> formed therein or on a surface thereof that cooperates with the plunger handle <NUM>, for example the first end <NUM>. According to an embodiment, the first end <NUM> may have a thread formed thereon, and the plunger <NUM> may have a threaded bore formed therein, the first end <NUM> capable of being attached to the plunger <NUM> by screwing the first end <NUM> into the threaded bore <NUM> of the plunger <NUM>.

As mentioned generally above, the closure <NUM> is vented, which venting permits the syringe <NUM> to be used with a pneumatic driver during filing, and perhaps also with a gaseous driver as part of a delivery system. To this end, the stopper <NUM> and the body <NUM> of the cap <NUM> each have at least one through-lumen <NUM>, <NUM> according to the illustrated embodiment. See <FIG> and <FIG>. As is also illustrated, the through-lumens <NUM>, <NUM> of the stopper <NUM> and cap <NUM> are aligned along a common longitudinal axis <NUM>, which axis <NUM> happens to be central axis of the syringe <NUM> as well. The filter <NUM> is disposed between the body <NUM> of the cap <NUM> and the stopper <NUM> along the axis <NUM>, and thus between the through lumen <NUM> of the stopper <NUM> and the through-lumen <NUM> of the cap <NUM>. The filter <NUM> may be made of filter media that can filter particle as small as <NUM> microns.

In addition to capturing the filter <NUM> between the stopper <NUM> and the cap <NUM>, the filter <NUM> may be joined to either the stopper <NUM> or the cap <NUM>. For example, the filter <NUM> may be irreversibly joined to either the stopper <NUM> or the cap <NUM> through the use of adhesives, or common plastic joining techniques. These techniques may include spin welding, hot plate welding, radio-frequency (RF) welding, and laser welding, for example, and may be selected based on the materials used for the stopper <NUM> or cap <NUM> and the filter <NUM>.

According to other embodiments, the filter <NUM> may be embedded in the stopper <NUM> or the cap <NUM>. According to such an embodiment, the filter <NUM> may be in one of the through-lumens <NUM>, <NUM>, for example, but still at the junction between the through-lumens <NUM>, <NUM>. According to still other embodiments, the filter <NUM> may be disposed not between the through-lumens <NUM>, <NUM>, but at an inner end of the through-lumen <NUM> or an outer end of the through lumen <NUM>. Further alternative arrangements are also possible.

The closure <NUM> may be used with a pneumatic driver, as mentioned above. The closure <NUM> may be connected to the pneumatic driver, such as the driver <NUM> illustrated in <FIG>. It will be recognized that the pneumatic driver <NUM> may be in the form of a pneumatic pump, for example, and may be capable of coupling pressure, vacuum or vent to the syringe <NUM>. As an alternative, the pneumatic driver may include a combination of valves and pressurized reservoirs.

It will be recognized that while an embodiment of the syringe <NUM> with closure <NUM> has been illustrated in <FIG>, other embodiments are possible, as illustrated in <FIG>, <FIG>, <FIG>. The same numbering scheme has been used for the features of the syringe <NUM>, with the caveat that the above discussion as to variants of the syringe <NUM> (e.g., with reference to <FIG>) applies with equal force to these additional embodiments. A numbering scheme where structures of the closure of <FIG>, <FIG>, <FIG> similar to those of the closure <NUM> have been numbered in a similar, but not identical, fashion has been adopted for readability.

<FIG> illustrate a vented closure <NUM> that is attached to the barrel <NUM> of the syringe <NUM> at the first end <NUM>. The vented closure <NUM> includes a stopper <NUM>, a cap <NUM>, and a filter <NUM>. As in the embodiment of <FIG>, the stopper <NUM> is disposed over and in the opening <NUM> in communication with the bore <NUM>. The cap <NUM> includes a body <NUM> disposed over the stopper <NUM>, and a fastener <NUM> engaged with the barrel flange <NUM>. The filter <NUM> is illustrated as disposed between the stopper <NUM> and the cap <NUM>.

The embodiment of the cap <NUM> of <FIG> differs from that of the embodiment of the cap <NUM> of <FIG> in that the fastener <NUM> does not directly engage the barrel flange <NUM>. Instead, the cap <NUM> engages an intermediate structure that is disposed between the cap <NUM> and the barrel flange <NUM>, with surfaces of the cap <NUM> and the intermediate structure abutting (i.e. in direct contact) and surfaces of the intermediate structure and the barrel flange <NUM> abutting.

The cap <NUM> includes a skirt <NUM> having a plurality of spaced barbs <NUM>, each of the barbs <NUM> being supported separately about the periphery of the cap <NUM>. Each of the barbs <NUM> has a head <NUM> with an inner surface <NUM>, which has a function similar to the surface <NUM> of the barb <NUM> of the cap <NUM>. The closure <NUM> also includes the afore-mentioned intermediate structure, or collar, <NUM>, which cooperates with the cap <NUM>, and in particular the barbs <NUM>, to secure the cap <NUM> to the barrel <NUM> of the syringe <NUM>.

The collar <NUM> has a passage <NUM>, through which the barrel <NUM> of the syringe <NUM> is received when the collar <NUM> is disposed on the barrel <NUM>. Similar to the collar <NUM>, the barrel <NUM> may be disposed in the passage <NUM> as the collar <NUM> is moved from the second end <NUM> to the first end <NUM>. The movement of the collar <NUM> may be halted at the first end <NUM> by the barrel flange <NUM>, when a surface of the collar <NUM> abuts the barrel flange <NUM>. According to the illustrated embodiment, the collar <NUM> may have a recess <NUM> formed in an upper surface thereof to receive the barrel flange when an upper surface of the collar <NUM> abuts the barrel flange <NUM>.

The collar <NUM> also has a rim <NUM> disposed radially outward from the passage <NUM>, and from the recess <NUM>. The rim <NUM> has a plurality of apertures <NUM> disposed about the periphery of the rim <NUM>. As illustrated, there are six apertures <NUM>, although according to other embodiments there may be a greater number or a lesser number of apertures <NUM>. The apertures <NUM> are spaced from each other in a pattern that is a mirror image about at least one axis, although again that need not be the case according to all embodiments.

The apertures <NUM> are formed through the collar <NUM>, such that the barbs <NUM> are received through the apertures <NUM>, and abut an outer surface <NUM> of the collar <NUM> to secure the cap <NUM> to the barrel flange <NUM>. In particular, the surface of the recess <NUM> abuts the barrel flange <NUM>, while the opposing surfaces <NUM>, <NUM> of the barb <NUM> and the collar <NUM> also abut. In this fashion, the closure <NUM> is secured indirectly to the barrel flange <NUM>.

In use, the collar <NUM> may be positioned on the barrel <NUM> first, with the collar <NUM> being advanced from the second end <NUM> to the first end <NUM>, until the barrel flange <NUM> abuts the collar <NUM> and is received within the recess <NUM>. At this point, the filter <NUM> may be disposed between the stopper <NUM> and the cap <NUM>, and the cap <NUM> pressed downward towards the collar <NUM>. The barbs <NUM> may deflect outwardly as the barbs <NUM> are moved through the apertures <NUM>, until the head <NUM> of the barb <NUM> passes beyond the outer surface <NUM> of the collar <NUM>. At this point, the barbs <NUM> move inwardly and the surfaces <NUM>, <NUM> abut to hold the cap <NUM> to the collar <NUM>, with the barrel flange <NUM>, stopper <NUM> and filter <NUM> sandwiched between the cap <NUM> and the collar <NUM>.

<FIG> illustrated a vented closure <NUM> that is attached to the barrel <NUM> of the syringe <NUM> as the first end <NUM>. The vented closure <NUM> includes a stopper <NUM>, a cap <NUM>, and a filter <NUM>. As in the embodiment of <FIG>, the stopper <NUM> is disposed over and in the opening <NUM> in communication with the bore <NUM>. The cap <NUM> includes a body <NUM> disposed over the stopper <NUM>, and a fastener <NUM> engaged with the barrel flange <NUM>. The filter <NUM> is illustrated as disposed between the stopper <NUM> and the cap <NUM>.

The embodiment of <FIG> is similar to that of the embodiment of <FIG> in that the skirt <NUM> has a plurality of spaced barbs <NUM>, each of the barbs <NUM> being supported separately about the periphery of the cap <NUM>. Each of the barbs <NUM> has a head <NUM> with an inner surface <NUM>, which has a function similar to the barbs in the embodiments discussed above. In the illustrated embodiment, the surface <NUM> abuts a surface <NUM> of the barrel flange <NUM>; in a further embodiment, a collar may be used as in the embodiment of <FIG>, and the surface <NUM> may abut a surface of the collar, which is itself in contact with the barrel flange <NUM>.

A significant difference with the preceding embodiments is that the fastener <NUM> (and in particular the barbs <NUM>) are connected to the body <NUM> of the cap <NUM> by a hinge <NUM>. As illustrated, the hinge <NUM> is a living hinge, made of the material that forms the body <NUM> of the cap <NUM> and the skirt <NUM>. According to other embodiments, the hinge <NUM> may be a separate structure as to at least one of the body <NUM> and the skirt <NUM>, and joined to the body <NUM> and/or the skirt <NUM>. The hinge <NUM> permits the fastener <NUM> to be spaced at a distance from the syringe <NUM> during the attachment of the closure <NUM> to the syringe <NUM>.

In use, the filter <NUM> is disposed on the stopper <NUM>, or according to certain embodiments the filter <NUM> is joined to the stopper <NUM>, The cap <NUM> is then disposed over the stopper <NUM> and filter <NUM>, as seen in <FIG>. The fasteners <NUM> may then be brought from a first position or state illustrated in <FIG> to a second position or state illustrated in <FIG>. As illustrated, in the first position, the barbs <NUM> are spaced radially outward of the body <NUM> of the cap <NUM>, thereby limiting interference between the barbs <NUM> and the barrel flange <NUM> (or collar, in those embodiments where included) as the cap <NUM> is fitted onto the syringe. In the second position, the barbs <NUM> are brought into the second position where the surfaces <NUM>, <NUM> abut to secure the cap <NUM> (and the closure <NUM>) to the syringe <NUM>.

<FIG> illustrate a vented closure <NUM> that is attached to the barrel <NUM> of the syringe <NUM> at the first end <NUM>. The vented closure <NUM> includes a stopper <NUM>, a cap <NUM>, and a filter <NUM>. As in the previous embodiments, the stopper <NUM> is disposed over and in the opening <NUM> in communication with the bore <NUM>. The cap <NUM> includes a body <NUM> disposed over the stopper <NUM>. Unlike the previous embodiments, the cap <NUM> has a fastener <NUM> that is a separate structure from the body <NUM> of the cap <NUM>.

The fastener <NUM> is in the form of a C-shaped clamp <NUM>, as viewed in the cross-section of <FIG>. It may be suggested that the clamp <NUM> performs the function of the skirt and the barb in the previous embodiments. The clamp <NUM> includes an upper section <NUM>, a lower section <NUM>, and a bridging section <NUM> that connects the upper section <NUM> to the lower section <NUM>.

As installed in <FIG>, an inner surface <NUM> of the upper section <NUM> abuts an outer surface <NUM> of the body <NUM> of the cap <NUM>. Similarly, an inner surface <NUM> of the lower section <NUM> abuts an outer surface <NUM> of the barrel flange <NUM>. As a consequence, the body <NUM> of the cap <NUM>, the filter <NUM>, the stopper flange <NUM> and the barrel flange <NUM> are sandwiched between the opposed inner surfaces <NUM>, <NUM> of the clamp <NUM> to secure the closure <NUM> to the syringe <NUM>, and each of the components in place.

According to the illustrated embodiment, the clamp <NUM> has two mating halves <NUM>, <NUM> (which may be referred to as a left half <NUM> and a right half <NUM> according to the orientation of the clamp <NUM> in <FIG>) which connect to each other to hold the clamp <NUM> in place on the syringe <NUM>. To this end, one or more connectors may be disposed on the left half <NUM> or the right half <NUM> of the clamp <NUM>, or mating portions of the connectors may be disposed on the left half <NUM> or the right half <NUM>. The connectors hold the halves <NUM>, <NUM> of the clamp <NUM> together to ensure that the closure <NUM> remains secured to the syringe <NUM>.

As illustrated in <FIG>, the upper section <NUM> has two connectors <NUM>, <NUM> disposed on opposite sides of the clamp <NUM> (which may also be opposite sides of the syringe <NUM>). The lower section <NUM> may also have connectors (not shown) disposed on opposite sides of the clamp <NUM>. While one arrangement has been illustrated, this not the only possible configuration for the connectors.

As best seen in <FIG>, each connector (e.g., the connector <NUM>) may include a barb <NUM> and a recess <NUM>. As illustrated, the barb <NUM> may be part of (joined to or integral with) the right half <NUM>, while the recess <NUM> may be formed in the left half <NUM>. This is an example of an embodiment of the connector where mating portions of the connectors may be disposed either on the left half <NUM> or the right half <NUM>. The barb <NUM> may be received in the recess <NUM> such that complementary structures of the barb <NUM> and receive <NUM> mate, preventing the barb <NUM> from being removed or separated from the recess <NUM> without a particular amount of force being applied. This amount of force may be selected according to the normal operating conditions for the closure, and whether the fastener <NUM> is intended to be reversibly or irreversibly removable.

The connectors may be configured such that one half (e.g., the right half <NUM>) has only the barbs <NUM>, and the other half (e.g., the left half <NUM>) has only the recesses configured to receive the barbs <NUM>. Alternatively, the connectors of the upper section <NUM> may have barbs <NUM> on the right half <NUM> and recesses on the left half <NUM>, while the lower section <NUM> has barbs on the left half <NUM> and recesses <NUM> on the right half <NUM>. As a further alternative the connector <NUM> may have a barb <NUM> on the right half <NUM> and a recess <NUM> on the left half <NUM>, while the connector <NUM> has a barb <NUM> on the left half <NUM> and a recess <NUM> on the right half <NUM>. According to such an embodiment, the connectors on the lower section <NUM> may be the same as their counterparts on the upper section <NUM>, or may be reversed.

It will also be recognized that while we have referred to the fastener <NUM> (and specifically the clamp <NUM>) has having right and left halves <NUM>, <NUM>, this has been done for ease of explanation. The clamp <NUM> may have two relatively equal parts that are joined together to form the clamp <NUM>, but it is not required that each part be exactly or approximately <NUM>% of the overall structure. Further, while the clamp <NUM> has been illustrated as disposed about the entire periphery of the barrel flange <NUM> and stopper flange <NUM>, this need not be the case with every instance of this embodiment of the closure <NUM>.

In use, the filter <NUM> may be disposed over the stopper <NUM>, and then the body <NUM> is disposed over the filter <NUM> and the stopper <NUM>. A downward force may be applied to the body <NUM> to the filter <NUM> and stopper <NUM> as the halves <NUM> and <NUM> are advanced toward the syringe <NUM> from opposite sides of the syringe <NUM>. The inner surface <NUM> of the upper section <NUM> of the clamp faces, and may even abut, the outer surface <NUM> of the body <NUM>, and the inner surface <NUM> faces, and may even abut, the outer surface <NUM> of the barrel flange <NUM>. The halves <NUM>, <NUM> are advanced toward each other until the barbs <NUM> are advanced so far in the direction of the recess <NUM> that the barbs <NUM> and recess <NUM> mate, connecting the two halves <NUM>, <NUM> of the clamp <NUM> together. In this position or state, the body <NUM>, filter <NUM> and stopper <NUM>, and barrel flange <NUM> are disposed between the opposing surfaces <NUM>, <NUM> of the clamp <NUM>.

It may also be possible to have a further embodiment, similar to that of <FIG>, where the body <NUM> of the cap <NUM> is integrated into the upper section <NUM> of the clamp <NUM>. For example, where the filter <NUM> is joined to or embedded in the stopper <NUM>, the body <NUM> may be integrated into the supper section <NUM>. In such a case, the opening in the center of the upper section <NUM> may be smaller than is illustrated in <FIG>, as it is not necessary to apply force on the separate element of the cap <NUM> when advancing the halves <NUM>, <NUM> toward each other.

The syringe with syringe closure according to the disclosed embodiments provides certain advantages relative to conventional syringes for use with pneumatic pumps. As mentioned above, the closure permits use of a pneumatic driver during filling, which limits or eliminates a potential source of contaminants as the air may be filtered easily. Further, the closure permits the syringe to be stored over a wide range of temperatures, while reducing the design burden on the plunger (particularly the plunger stopper) to provide the seal required during cryostorage. A syringe with incorporating such a closure can provide a ready-to-use delivery vessel, and one that is amenable to direct integration into instrumentation. The rigid nature of the container also may permit robotic instrumentation to facilitate connection for highly-scaled operations.

Claim 1:
A syringe (<NUM>) comprising:
a barrel (<NUM>) with a bore (<NUM>), the barrel having an end (<NUM>) with an opening (<NUM>) in communication with the bore and a barrel flange (<NUM>) disposed outwardly of the opening (<NUM>);
a plunger (<NUM>) disposed in the bore (<NUM>), the plunger (<NUM>) movable along the bore (<NUM>); and
a vented closure (<NUM>, <NUM>, <NUM>, <NUM>) attached to the barrel (<NUM>) at the end (<NUM>), the vented closure (<NUM>, <NUM>, <NUM>) comprising a stopper (<NUM>), a cap (<NUM>, <NUM>, <NUM>, <NUM>) and a filter (<NUM>, <NUM>, <NUM>, <NUM>),
the stopper (<NUM>) disposed over the opening (<NUM>) and at least partially within the bore (<NUM>),
the cap (<NUM>, <NUM>, <NUM>, <NUM>) having a body (<NUM>, <NUM>, <NUM>, <NUM>) disposed over the stopper (<NUM>), and a fastener (<NUM>, <NUM>, <NUM>, <NUM>) engaged with the barrel flange (<NUM>),
the filter (<NUM>, <NUM>, <NUM>, <NUM>) disposed between the stopper (<NUM>) and the cap (<NUM>, <NUM>, <NUM>, <NUM>), or in at least one of the stopper (<NUM>) and the cap (<NUM>, <NUM>, <NUM>, <NUM>),
characterized in that the stopper (<NUM>) comprises a first end (<NUM>) comprising a plug (<NUM>) disposed within the bore (<NUM>) and a second end (<NUM>) comprising a stopper flange (<NUM>) depending from the second end (<NUM>) of the stopper (<NUM>) outside the bore (<NUM>), and the cap (<NUM>, <NUM>, <NUM>, <NUM>) secures the stopper flange (<NUM>) between the body (<NUM>) of the cap (<NUM>, <NUM>, <NUM>, <NUM>) and the barrel flange (<NUM>).