Patent Description:
For some drug dispensing devices, a healthcare provider is required to transfer a therapeutic product from a prefilled syringe to a cartridge or device reservoir that is configured for the drug dispensing device. Typically, a prefilled syringe is filled with a predetermined amount of the therapeutic product along with a predetermined amount of air. To transfer the therapeutic product to the cartridge or device reservoir, a healthcare provider can orient the prefilled syringe so that the air is adjacent to the needle and depress a plunger of the prefilled syringe to dispense the air. This air dispensing operation may inadvertently dispense some of the therapeutic product, which can waste an expensive product and may cause the amount of therapeutic product in the prefilled syringe to fall below a prescribed amount for the patient. On the other hand, if the air is not fully dispensed from the prefilled syringe, some air may be transferred to the cartridge or device reservoir. Air within a fluid flow path of the drug dispensing device can negatively impact the operation of the device, such as by causing uncontrolled forward or backward flow due to barometric pressure changes. <CIT>, <CIT>, <CIT>, <CIT>, <CIT> and <CIT> disclose various arrangements of syringes.

In accordance with a first exemplary aspect, a syringe is disclosed that includes a barrel that has an interior, a dispensing opening at a distal end, and an open proximal end having an end surface. A stopper is disposed within the interior of the barrel. The syringe further includes a plunger rod that has a first end operably coupled to the stopper and a second end that extends through the open proximal end of the barrel. The plunger rod is configured to be engaged by a user to drive the stopper through the barrel to thereby dispense contents within the barrel through the dispensing opening during a dispensing operation. The plunger rod further includes an outwardly projecting stop that is adjacent the second end. The barrel is configured to contain a fluid therapeutic product. Headspace between the dispensing opening and the stopper and the stop of the plunger rod is configured to engage the end surface of the open proximal end of the barrel to stop movement of the plunger rod during the dispensing operation so that the headspace is left within the barrel.

In accordance with a second exemplary aspect, a syringe is disclosed that includes a barrel that has an interior, a dispensing opening at a distal end, and an open proximal end having an end surface. A stopper is disposed within the interior of the barrel. The syringe further includes a plunger rod that has a first end operably coupled to the stopper and a second end that extends through the open proximal end of the barrel. The plunger rod is configured to be engaged by a user to drive the stopper through the barrel to thereby dispense contents within the barrel through the dispensing opening during a dispensing operation. The plunger rod further includes an outwardly projecting stop that is adjacent the second end. In a first configuration with the stop of the plunger rod spaced from the end surface of the proximal end of the barrel a first distance, the barrel is configured to contain a fluid therapeutic product and headspace between the dispensing opening and the stopper. In a second configuration with the stop of the plunger rod abutting the end surface of the proximal end of the barrel and the stopper shifted the first distance within the interior of the barrel, the barrel contains the headspace.

In further accordance with the foregoing first and/or second aspects, a syringe may further include any one or more of the following preferred forms.

In accordance with one preferred form, the stop can have at least one radial dimension greater than a corresponding radius of an opening of the open proximal end of the barrel.

In accordance with one preferred form, the stop can include a portion having a diameter greater than a corresponding diameter of an opening of the open proximal end of the barrel such that the stop is configured to abut the end surface on opposing radial edge portions.

In accordance with one preferred form, the barrel can include a flange that extends around the open proximal end The flange is configured to be gripped by a user during the dispensing operation and provide the end surface for engagement with the stop of the plunger rod.

In accordance with one preferred form, the syringe can further include a needle that is fluidly coupled to the interior of the barrel at the dispensing opening.

In accordance with one preferred form, the plunger rod can further include a thumb rest portion at the second end In accordance with a further preferred form, the thumb rest portion can be spaced from the stop.

In accordance with one preferred form, the syringe can further include the fluid therapeutic product disposed within the barrel.

In accordance with one preferred form, the syringe the stop and plunger rod can be separate components and the syringe can further include a securing mechanism that is configured to couple the stop and the plunger rod together. In accordance with a further preferred form, the syringe can be provided in combination with a storage container, where the storage container is configured to engage the securing mechanism so that the stop and plunger rod are in an uncoupled configuration when the syringe is disposed within the storage container.

In accordance with a third exemplary aspect, a method of filling a syringe with a fluid therapeutic product is disclosed that includes filling a barrel of the syringe with a dose of fluid therapeutic product, disposing a stopper within the barrel to contain the dose within the syringe along with a headspace, and providing a plunger rod having an outward projecting stop and a length. The plunger being configured so that, with the plunger rod coupled to the stopper, the stop is spaced from an end of the barrel a distance corresponding to depth of the headspace in the barrel.

In accordance with a fourth exemplary aspect, a method of dispensing a predetermined amount of fluid therapeutic product from a syringe is disclosed that includes engaging a thumb rest of a plunger rod of the syringe, where the plunger rod extends into a barrel of the syringe to couple to a stopper disposed within the barrel. The method further includes pushing the thumb rest of the plunger rod toward the barrel of the syringe to thereby drive the stopper through the barrel which dispenses the fluid therapeutic product through a needle of the syringe fluidly coupled to the barrel and abutting a stop of the plunger rod with an end surface of the barrel, thereby stopping movement of the stopper and preventing any headspace within the barrel from being expelled.

In accordance with one preferred form, the method can further include agitating the barrel with the barrel in a generally vertical orientation to with the thumb rest above the barrel to ensure that all of the headspace is above the fluid therapeutic product prior to pushing the thumb rest of the plunger rod toward the barrel.

In accordance with one preferred form, engaging the thumb rest can include engaging an end portion of the plunger rod spaced from the stop.

In accordance with one preferred form, the method can further include removing the syringe from a storage container to cause a securing mechanism to couple the plunger rod and stop together.

The above needs are at least partially met through provision of the embodiments described in the following detailed description, particularly when studied in conjunction with the drawings, wherein:.

For example, the dimensions and/or relative positioning of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in a commercially feasible embodiment are often not depicted in order to facilitate a less obstructed view of these various embodiments. It will further be appreciated that certain actions and/or steps may be described or depicted in a particular order of occurrence while those skilled in the art will understand that such specificity with respect to sequence is not actually required. It will also be understood that the terms and expressions used herein have the ordinary technical meaning as is accorded to such terms and expressions by persons skilled in the technical field as set forth above except where different specific meanings have otherwise been set forth herein.

A syringe is provided with a plunger assembly that is adapted to have a dispensing stroke sized to dispense a fluid therapeutic product from the syringe without dispensing any air or headspace. More specifically, the syringe includes a plunger rod having a stop feature that stops a dispensing stroke of the plunger rod at a distance corresponding to a level of air or headspace within the syringe.

Referring now to the drawings, <FIG> shows a syringe <NUM> extending along a longitudinal axis X. The syringe <NUM> is illustrated in a pre-filled state having a dose or other predetermined amount of a fluid therapeutic product <NUM> contained within a barrel or reservoir <NUM>. The barrel <NUM> has tubular configuration oriented along the longitudinal axis X with an annular sidewall <NUM> extending between a dispensing opening <NUM> at a distal end <NUM> and an open proximal end <NUM>. The proximal end <NUM> includes a radially projecting flange <NUM> that provides an upwardly facing end surface <NUM>. if desired, the barrel <NUM> can include measurement markings <NUM> distributed along a length L thereof to provide a visual indication of the amount of product <NUM>. The barrel <NUM> can be made of any suitable material, such as glass or a polymer.

At the distal end <NUM> of the barrel <NUM>, the syringe <NUM> includes a needle <NUM> and a needle hub <NUM> coupled to the barrel <NUM>, such that the needle <NUM> is fluidly coupled with an interior <NUM> of the barrel <NUM>. The syringe <NUM> further includes a stopper (plungerstopper) <NUM> and a plunger rod <NUM> engaging the stopper <NUM> and projecting outwardly through the open proximal end <NUM> of the barrel <NUM> along the longitudinal axis X. The plunger rod <NUM> includes an elongate body <NUM> that is coaxial with the barrel <NUM>. The body <NUM> engages the stopper <NUM> at a distal end <NUM> and includes a thumb rest <NUM> at an opposite, proximal end <NUM>. The plunger rod <NUM> can engage the stopper <NUM> by any suitable method, such as embedded therein, having mating components, abutting an end surface, and so forth. As shown, the thumb rest <NUM> can include a flange <NUM> that extends outwardly from the body <NUM> generally perpendicular to the longitudinal axis X providing a user with a flat or contoured upwardly facing engagement surface <NUM>. So configured, a user can grip the flange <NUM> of the proximal end <NUM> of the barrel <NUM> with two fingers and the engagement surface <NUM> with a thumb to press down and drive the stopper <NUM> through the barrel <NUM> in a dispensing operation.

As shown, the barrel <NUM> also contains an air bubble or headspace <NUM> along with the product <NUM>. Traditionally, a healthcare provider handles the syringe <NUM> so that the needle <NUM> is oriented upwardly and depresses the plunger rod <NUM> to drive the stopper <NUM> through the barrel <NUM> to dispense the air <NUM> through the needle <NUM> or eyes the level of product <NUM> during dispensing to avoid expelling air. The plunger rod <NUM> of the syringe <NUM> described herein avoids this operation by including a stop <NUM> that extends outwardly from the plunger rod body <NUM> generally perpendicular to the longitudinal axis X thereof. The stop <NUM> is sized to engage the end surface <NUM> of the barrel proximal end <NUM> during a dispensing operation. Specifically, the stop <NUM> has at least one radial dimension greater than a corresponding radius of the opening of the barrel proximal end <NUM>. In one form, the stop <NUM> includes a portion having a diameter greater than a corresponding diameter of the opening of the barrel proximal end <NUM> such that the stop <NUM> abuts the end surface <NUM> on opposing radial edge portions <NUM>. In some examples, the stop <NUM> can have an oval or track-shaped configuration where at least the larger diameter is greater than the corresponding diameter of the opening of the barrel proximal end <NUM>. In another example, the stop <NUM> can have a circular configuration where the diameter is greater than the corresponding diameter of the opening of the barrel proximal end <NUM>.

So configured, the stop <NUM> prevents further displacement of the plunger rod <NUM> and, thus, the stopper <NUM>, through the barrel <NUM> so that the dispensing operation dispenses a predetermined volume. Although the plunger rod <NUM> of the illustrated form includes the stop <NUM> spaced from the thumb rest <NUM>, it should be understood that a plunger rod can be configured so that the stop also provides the thumb rest.

Stated another way, by configuring the plunger rod <NUM> to have a predetermined length between the distal end <NUM> and the stop <NUM> that corresponds to a desired portion of the barrel <NUM>, the syringe <NUM> can be preconfigured to dispense a specific volume of fluid. Advantageously, this can be utilized to avoid the problems associated with headspace within conventional prefilled syringes by limiting a dispensing operation to a volume that prevents the air <NUM> from being expelled.

The predetermined length of the plunger rod <NUM> between the distal end <NUM> and the stop <NUM>, combined with a length of the stopper <NUM>, corresponds to a portion L1 of a length L of the barrel <NUM>. This length L1 is shown in <FIG> with the plunger rod <NUM> fully inserted into the barrel <NUM> and the stop <NUM> abutting the end surface <NUM>. Accordingly, during preparation of the syringe <NUM>, the barrel <NUM> can be filled to a desired amount or dosage of the product <NUM> and the stopper <NUM> can be positioned within the barrel <NUM> so that the headspace <NUM> has a length, and corresponding volume, generally equal to a remaining portion L2 of the length L of the barrel <NUM>.

Of course, as represented in the figures, the fluid of the product <NUM> may interact with the barrel <NUM> to have a meniscus rather than a flat top surface. In order to ensure that none of the air <NUM> is dispensed, the length L2 can have a value equal to or greater than a length of the therapeutic product <NUM> at its raised periphery adjacent to the barrel <NUM>.

After the syringe <NUM> has been filled with the product <NUM>, the syringe <NUM> can be packaged for transportation and storage. A storage configuration can include a removable needle guard or cap <NUM> and/or a removable collar <NUM> disposed between the barrel end surface <NUM> and the stop <NUM> to prevent undesired depression of the plunger rod <NUM>.

When a user would like to dispense the product <NUM>, the user can orient the syringe in a generally vertical orientation, e.g., within <NUM> degrees of vertical and preferably within <NUM> degrees of vertical, with the thumb rest <NUM> disposed above the barrel <NUM> and the needle <NUM> pointed downward. This orientation allows the product <NUM> to be positioned adjacent to the dispensing opening <NUM> with the headspace <NUM> positioned above the product <NUM>. The user can then agitate the barrel <NUM>, such as by tapping, or can pause a predetermine interval, such as about <NUM> seconds to about <NUM> minute, to ensure that all of the headspace <NUM> is above the product <NUM> before dispensing. Thereafter, the user can depress the plunger rod <NUM> to drive the stopper <NUM> through the barrel <NUM>. Advantageously, as described above, the plunger rod <NUM> moves until the stop <NUM> abuts the end surface <NUM> of the barrel <NUM>, stopping movement of the stopper <NUM> within the barrel <NUM>. As shown in <FIG>, the plunger rod <NUM> and barrel <NUM> are adapted so that this position of the plunger rod <NUM> and stopper <NUM> leaves the headspace <NUM> within the barrel <NUM> while dispensing the predetermined amount of the product <NUM>.

Another embodiment of a syringe <NUM> is shown in <FIG>. This embodiment includes many features similar to the above embodiment shown in <FIG> and, thus, similar reference characters will be utilized for similar features. For example, the syringe <NUM> includes a barrel or reservoir <NUM> having a fluid therapeutic product <NUM> and headspace <NUM> therein, a needle <NUM>, a needle hub <NUM>, a stopper <NUM>, a plunger rod <NUM>, and so forth.

In this embodiment, the plunger rod <NUM> is coupled or otherwise secured to the stopper <NUM> and is separate from a plunger rod stop <NUM>. Accordingly, absent a coupling, the plunger rod <NUM> can move freely with respect to the stop <NUM>. For example, the stop <NUM> can include a central opening <NUM> extending therethrough that has a diameter or other dimension larger than the plunger rod <NUM>.

As is understood, altitude changes can affect the headspace <NUM> in a prefilled syringe <NUM>. For example, altitude changes can cause the stopper <NUM> to move and increase the volume of headspace <NUM>. As a result, subsequent use of the delivery device can include injecting some air from the headspace into the patient subcutaneously. By providing a freely movable stop <NUM>, the stop <NUM> can be positioned on the plunger rod <NUM> at a position corresponding to a length of the fluid therapeutic product <NUM> after any movement by the stopper <NUM> and plunger rod <NUM> during transport or storage.

By one approach, the syringe <NUM> can be stored in a tray or other storage container <NUM> having recesses <NUM>, <NUM> that hold the barrel <NUM> and the stop <NUM>, respectively, at static positions relative to one another. The recesses <NUM>, <NUM> can be sized to frictionally engage the barrel <NUM> and stop <NUM> so that movement thereof is restricted. This ensures that the stop <NUM> is spaced from the barrel flange <NUM> a distance corresponding to the length of the product <NUM> regardless of any movement of the stopper <NUM> and plunger rod <NUM>. The tray <NUM> can further include a recess <NUM> for the thumb rest <NUM> that provides clearance for any movement by the stopper <NUM> imparted on the plunger rod <NUM>.

The syringe <NUM> can further include a securing mechanism <NUM> mounted on or incorporated into the plunger rod <NUM> and/or stop <NUM> that is engaged by the tray <NUM> when the syringe <NUM> is stored therein. The securing mechanism <NUM> includes a member or portion that is biased to engage the other of the plunger rod <NUM> or stop <NUM> to thereby hold the plunger rod <NUM> and stop <NUM> together so that the syringe <NUM> can dispense the product <NUM> as described with respect to the above embodiment. The securing mechanism <NUM> can include any desired biasing mechanism, such as a spring, pressurized gas, and so forth. The tray <NUM> engages the securing mechanism <NUM> so that the plunger rod <NUM> and stop <NUM> are held in an uncoupled state during storage, thereby allowing the plunger rod <NUM> to float and move in response to head space fluctuations that might occur as a result of altitude changes during transportation for example. When the syringe <NUM> is removed from the tray <NUM>, however, the securing mechanism <NUM> automatically biases the member or portion to engage a corresponding member, portion, recess, etc. on the other of the plunger rod <NUM> or stop <NUM> so that the plunger rod <NUM> and stop <NUM> are secured together in a fixed relationship. Such a configuration can advantageously ensure that headspace fluctuations do not detrimentally effect the delivery of the drug.

In one example, the syringe <NUM>, <NUM> described herein can provide a desired accuracy of fluid therapeutic product injection of +/- <NUM> microliters. In a <NUM> syringe, the movement of the plunger can be controlled to +/- <NUM> to achieve this desired accuracy.

The disclosure provided herein can be utilized with any desired dosage and syringe size, while ensuring a delivery amount for accurate dosages. This is particularly suitable for pre-filled syringes for patient self-injection. The components of the syringe <NUM>, such as the barrel <NUM> and plunger rod <NUM>, can be made of any suitable material, such as plastic or glass.

The above description describes various syringes, devices, assemblies, components, subsystems and methods for use related to drug delivery. The syringes, devices, assemblies, components, subsystems, methods or drug delivery devices can further comprise or be used with a therapeutic product (aka, a drug) including but not limited to those drugs identified below as well as their generic and biosimilar counterparts. The term therapeutic product or drug, as used herein, can be used interchangeably with other similar terms and can be used to refer to any type of medicament or therapeutic material including traditional and non-traditional pharmaceuticals, nutraceuticals, supplements, biologics, biologically active agents and compositions, large molecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules and generics. Non-therapeutic injectable materials are also encompassed. The drug may be in liquid form, a lyophilized form, or in a reconstituted from lyophilized form. The following example list of drugs should not be considered as all-inclusive or limiting.

The drug will be contained in a reservoir. In some instances, the reservoir is a primary container that is either filled or pre-filled for treatment with the drug. The primary container can be a vial, a cartridge or a pre-filled syringe.

In some embodiments, the reservoir of the drug delivery device may be filled with or the device can be used with colony stimulating factors, such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF agents include but are not limited to Neulasta® (pegfilgrastim, pegylated filgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-MetG-CSF).

In other embodiments, the drug delivery device may contain or be used with an erythropoiesis stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoiesis. In some embodiments, an ESA is an erythropoiesis stimulating protein. As used herein, "erythropoiesis stimulating protein" means any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to and causing dimerization of the receptor. Erythropoiesis stimulating proteins include erythropoietin and variants, analogs, or derivatives thereof that bind to and activate erythropoietin receptor; antibodies that bind to erythropoietin receptor and activate the receptor; or peptides that bind to and activate erythropoietin receptor. Erythropoiesis stimulating proteins include, but are not limited to, Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta), Hematide®, MRK-<NUM>, INS-<NUM>, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta, and epoetin delta, pegylated erythropoietin, carbamylated erythropoietin, as well as the molecules or variants or analogs thereof.

Among particular illustrative proteins are the specific proteins set forth below, including fusions, fragments, analogs, variants or derivatives thereof: OPGL specific antibodies, peptibodies, related proteins, and the like (also referred to as RANKL specific antibodies, peptibodies and the like), including fully humanized and human OPGL specific antibodies, particularly fully humanized monoclonal antibodies; Myostatin binding proteins, peptibodies, related proteins, and the like, including myostatin specific peptibodies; IL-<NUM> receptor specific antibodies, peptibodies, related proteins, and the like, particularly those that inhibit activities mediated by binding of IL-<NUM> and/or IL-<NUM> to the receptor; Interleukin <NUM>-receptor <NUM> ("IL1-R1") specific antibodies, peptibodies, related proteins, and the like; Ang2 specific antibodies, peptibodies, related proteins, and the like; NGF specific antibodies, peptibodies, related proteins, and the like; CD22 specific antibodies, peptibodies, related proteins, and the like, particularly human CD22 specific antibodies, such as but not limited to humanized and fully human antibodies, including but not limited to humanized and fully human monoclonal antibodies, particularly including but not limited to human CD22 specific IgG antibodies, such as, a dimer of a human-mouse monoclonal hLL2 gamma-chain disulfide linked to a human-mouse monoclonal hLL2 kappa-chain, for example, the human CD22 specific fully humanized antibody in Epratuzumab, CAS registry number <NUM>-<NUM>-<NUM>; IGF-<NUM> receptor specific antibodies, peptibodies, and related proteins, and the like including but not limited to anti-IGF-1R antibodies; B-<NUM> related protein <NUM> specific antibodies, peptibodies, related proteins and the like ("B7RP-<NUM>" and also referring to B7H2, ICOSL, B7h, and CD275), including but not limited to B7RP-specific fully human monoclonal IgG2 antibodies, including but not limited to fully human IgG2 monoclonal antibody that binds an epitope in the first immunoglobulin-like domain of B7RP-<NUM>, including but not limited to those that inhibit the interaction of B7RP-<NUM> with its natural receptor, ICOS, on activated T cells; IL-<NUM> specific antibodies, peptibodies, related proteins, and the like, such as, in particular, humanized monoclonal antibodies, including but not limited to HuMax IL-<NUM> antibodies and related proteins, such as, for instance, 146B7; IFN gamma specific antibodies, peptibodies, related proteins and the like, including but not limited to human IFN gamma specific antibodies, and including but not limited to fully human anti-IFN gamma antibodies; TALL-<NUM> specific antibodies, peptibodies, related proteins, and the like, and other TALL specific binding proteins; Parathyroid hormone ("PTH") specific antibodies, peptibodies, related proteins, and the like; Thrombopoietin receptor ("TPO-R") specific antibodies, peptibodies, related proteins, and the like;Hepatocyte growth factor ("HGF") specific antibodies, peptibodies, related proteins, and the like, including those that target the HGF/SF:cMet axis (HGF/SF:c-Met), such as fully human monoclonal antibodies that neutralize hepatocyte growth factor/scatter (HGF/SF); TRAIL-R2 specific antibodies, peptibodies, related proteins and the like; Activin A specific antibodies, peptibodies, proteins, and the like; TGF-beta specific antibodies, peptibodies, related proteins, and the like; Amyloid-beta protein specific antibodies, peptibodies, related proteins, and the like; c-Kit specific antibodies, peptibodies, related proteins, and the like, including but not limited to proteins that bind c-Kit and/or other stem cell factor receptors; OX40L specific antibodies, peptibodies, related proteins, and the like, including but not limited to proteins that bind OX40L and/or other ligands of the OX40 receptor; Activase® (alteplase, tPA); Aranesp® (darbepoetin alfa); Epogen® (epoetin alfa, or erythropoietin); GLP-<NUM>, Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonal antibody); Betaseron® (interferon-beta); Campath® (alemtuzumab, anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (anti- α4β7 mAb); MLN1202 (anti-CCR2 chemokine receptor mAb); Enbrel® (etanercept, TNF-receptor /Fc fusion protein, TNF blocker); Eprex® (epoetin alfa); Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-<NUM>); Genotropin® (somatropin, Human Growth Hormone); Herceptin® (trastuzumab, anti-HER2/neu (erbB2) receptor mAb); Humatrope® (somatropin, Human Growth Hormone); Humira® (adalimumab); Vectibix® (panitumumab), Xgeva® (denosumab), Prolia® (denosumab), Enbrel® (etanercept, TNF-receptor /Fc fusion protein, TNF blocker), Nplate® (romiplostim), rilotumumab, ganitumab, conatumumab, brodalumab, insulin in solution; Infergen® (interferon alfacon-<NUM>); Natrecor® (nesiritide; recombinant human B-type natriuretic peptide (hBNP); Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide® (epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxy polyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin); Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP <NUM>); Soliris™ (eculizumab); pexelizumab (anti-C5 complement); Numax® (MEDI-<NUM>); Lucentis® (ranibizumab); Panorex® (<NUM>-1A, edrecolomab); Trabio® (lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4); Osidem® (IDM-<NUM>); OvaRex® (B43. <NUM>); Nuvion® (visilizumab); cantuzumab mertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega® (oprelvekin, human interleukin-<NUM>); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody); Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNFα monoclonal antibody); Reopro® (abciximab, anti-GP Ilb/llia receptor monoclonal antibody); Actemra® (anti-IL6 Receptor mAb); Avastin® (bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20 mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2a); Simulect® (basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO (anti-IL15 antibody, see <CIT>); Tysabri® (natalizumab, anti-α4integrin mAb); Valortim® (MDX-<NUM>, anti-B. anthracis protective antigen mAb); ABthrax™; Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-<NUM> trap (the Fc portion of human IgG1 and the extracellular domains of both IL-<NUM> receptor components (the Type I receptor and receptor accessory protein)); VEGF trap (Ig domains of VEGFR1 fused to IgG1 Fc); Zenapax® (daclizumab); Zenapax® (daclizumab, anti-IL-2Rα mAb); Zevalin® (ibritumomab tiuxetan); Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonal antibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist); CNTO <NUM> (golimumab, anti-TNFα mAb); HGS-ETR1 (mapatumumab; human anti-TRAIL Receptor-<NUM> mAb); HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab); M200 (volociximab, anti-α5β1 integrin mAb); MDX-<NUM> (ipilimumab, anti-CTLA-<NUM> mAb and VEGFR-<NUM> (IMC-18F1); anti-BR3 mAb; anti-C. difficile Toxin A and Toxin B C mAbs MDX-<NUM> (CDA-<NUM>) and MDX-<NUM>); anti-CD22 dsFv-PE38 conjugates (CAT-<NUM> and CAT-<NUM>); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (Nl-<NUM>); adecatumumab; anti-CD30 mAb (MDX-<NUM>); MDX-<NUM> (anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-Cripto mAb; anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-<NUM>); anti-CTLA4 mAb; anti-eotaxin1 mAb (CAT-<NUM>); anti-FGF8 mAb; anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; anti-GDF-<NUM> human mAb (MYO-<NUM>); anti-GM-CSF Receptor mAb (CAM-<NUM>); anti-HepC mAb (HuMax HepC); anti-IFNα mAb (MEDI-<NUM>, MDX-<NUM>); anti-IGF1R mAb; anti-IGF-1R mAb (HuMax-Inflam); anti-IL12 mAb (ABT-<NUM>); anti-IL12/IL23 mAb (CNTO <NUM>); anti-IL13 mAb (CAT-<NUM>); anti-IL2Ra mAb (HuMax-TAC); anti-IL5 Receptor mAb; anti-integrin receptors mAb (MDX-<NUM>, CNTO <NUM>); anti-IP10 Ulcerative Colitis mAb (MDX-<NUM>); BMS-<NUM>; anti-Mannose Receptor/hCGβ mAb (MDX-<NUM>); anti-mesothelin dsFv-PE38 conjugate (CAT-<NUM>); anti-PD1mAb (MDX-<NUM> (ONO-<NUM>)); anti-PDGFRa antibody (IMC-3G3); anti-TGFβ mAb (GC-<NUM>); anti-TRAIL Receptor-<NUM> human mAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR/Flt-<NUM> mAb; and anti-ZP3 mAb (HuMax-ZP3).

In some embodiments, the drug delivery device may contain or be used with a sclerostin antibody, such as but not limited to romosozumab, blosozumab, or BPS <NUM> (Novartis) and in other embodiments, a monoclonal antibody (IgG) that binds human Proprotein Convertase Subtilisin/Kexin Type <NUM> (PCSK9). Such PCSK9 specific antibodies include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab). In other embodiments, the drug delivery device may contain or be used with rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant or panitumumab. In some embodiments, the reservoir of the drug delivery device may be filled with or the device can be used with IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers including but are not limited to OncoVEXGALV/CD; OrienX010; G207, <NUM>; NV1020; NV12023; NV1034; and NV1042. In some embodiments, the drug delivery device may contain or be used with endogenous tissue inhibitors of metalloproteinases (TIMPs) such as but not limited to TIMP-<NUM>. Antagonistic antibodies for human calcitonin gene-related peptide (CGRP) receptor such as but not limited to erenumab and bispecific antibody molecules that target the CGRP receptor and other headache targets may also be delivered with a drug delivery device of the present disclosure. Additionally, bispecific T cell engager (BiTE®) antibodies such as but not limited to BLINCYTO® (blinatumomab) can be used in or with the drug delivery device of the present disclosure. In some embodiments, the drug delivery device may contain or be used with an APJ large molecule agonist such as but not limited to apelin or analogues thereof. In some embodiments, a therapeutically effective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptor antibody is used in or with the drug delivery device of the present disclosure.

Although the drug delivery devices, assemblies, components, subsystems and methods have been described in terms of exemplary embodiments, they are not limited thereto. The detailed description is to be construed as exemplary only and does not describe every possible embodiment of the present disclosure. Numerous alternative embodiments could be implemented, using either current technology or technology developed after the filing date of this patent that would still fall within the scope of the claims defining the invention(s) disclosed herein.

Claim 1:
A syringe comprising:
a barrel (<NUM>, <NUM>) having an interior (<NUM>), a dispensing opening (<NUM>) at a distal end (<NUM>), and an open proximal end (<NUM>) having an end surface (<NUM>);
a stopper (<NUM>, <NUM>) disposed within the interior of the barrel;
a plunger rod (<NUM>, <NUM>) having a first end (<NUM>) operably coupled to the stopper and a second end (<NUM>) extending through the open proximal end of the barrel, the plunger rod configured to be engaged by a user to drive the stopper through the barrel to thereby dispense contents within the barrel through the dispensing opening during a dispensing operation; and
an outwardly projecting stop (<NUM>, <NUM>) coupled to the plunger rod adjacent the second end, and extending generally perpendicular to the longitudinal axis of the plunger rod;
characterized in that the barrel contains a fluid therapeutic product (<NUM>, <NUM>) and headspace (<NUM>, <NUM>) between the dispensing opening and the stopper, and the stop is configured to stop a dispensing stroke of the plunger rod at a distance corresponding to a level of the headspace within the syringe by engaging the end surface of the open proximal end of the barrel to stop movement of the plunger rod during the dispensing operation so that the headspace is left within the barrel.