HK1208831B - Improved autoinjector - Google Patents

Description

Improved autoinjector

Technical Field

The present disclosure relates to an autoinjector device and, more particularly, to an autoinjector device with skin stretching and pinching capabilities, an ergonomic autoinjector grip, and other ergonomic improvements for autoinjectors.

Background Art

While the injection needle is piercing the skin, the autoinjector (AI) device is held against the body to administer the drug product. While holding the autoinjector, the user applies a downward motion against the skin to trigger the autoinjector. The user then presses a button to cause the needle to inject and a stopper to push the drug down into the skin.

During needle insertion and plunger movement, the contact surface/surface area between the user's skin and the physical area of the autoinjector touching the skin (and surrounding the needle) must remain in place to prevent the autoinjector and/or needle from slipping or moving on the skin surface. This must be achieved to ensure the delivery of the full dose of medication, to avoid leakage of medication on the skin surface, and most importantly, to avoid injury to the user due to a bent or broken needle during the injection process. In addition, for user comfort, it is recommended that the skin area at the injection site and the skin area directly below the autoinjector be kept taut to facilitate the injection procedure.

The current injection procedure for autoinjectors requires the user to stretch or pinch the skin at the injection site with one hand and maintain this stretch or pinch while placing the autoinjector on the same area. With the autoinjector in place, the user applies a downward force to the area of the injection site to trigger or unlock the injection device. While keeping the skin stretched or pinched with one hand and holding the autoinjector in place with the other hand, the user must then grip the autoinjector with their thumb to press a button on the top of the autoinjector, thereby triggering the needle and plunger to move downward to inject the drug. After completing the injection, the user must retract the needle from the skin and remove the injection device.

During the process of placing the autoinjector on the injection site and triggering the autoinjector, users have observed the following problems: 1) becoming distracted, releasing the skin from stretching or pinching, and attempting to maneuver the autoinjector into position; 2) releasing the skin from stretching or pinching in order to grasp the autoinjector with both hands due to a lack of physical hand strength or dexterity; and 3) prematurely removing the injection device before completing the injection. Furthermore, for elderly users or users with impaired finger function, using the autoinjector can be very difficult, which can hinder treatment.

Therefore, there are several considerations regarding the front wall of an autoinjector's injection tip. One such consideration is the autoinjector's ability to stretch the skin. Users don't necessarily think about stretching their skin when injecting with an autoinjector, so it's highly advantageous to have a structure on the autoinjector that provides this functionality. Another consideration is providing an autoinjector with a structure that improves its stability, allowing it to remain substantially perpendicular to the body during injection, thereby allowing the user to operate the autoinjector with one hand. Another consideration is that some commercial autoinjectors require a trigger release mechanism that applies an axial force to the front wall of the autoinjector, where it contacts the user's skin. Certain body types have lower surface tension and resistance than the required trigger force, causing the autoinjector to press against the skin and deflect significantly toward the body. Some patients fail to apply the required trigger force, and therefore are unable to set the autoinjector and prepare it for injection. Some commercial autoinjectors have a guard trigger and a trigger button that must be pressed to set and initiate delivery. Other commercial autoinjectors only require pressing the guard trigger to set and initiate delivery.

Therefore, there is a need for a method that addresses the placement, triggering, and ergonomic design issues of conventional autoinjectors.

Summary of the Invention

A syringe comprises: a housing having an injection end; an injection needle encapsulated in the housing, which, when the injection operation of the syringe is triggered, pierces the skin at a selected injection site and dispenses a drug product; and a flexible extension member arranged at the injection end of the housing for stretching or pinching the skin at the injection site.

In some embodiments of the syringe, the flexible extension may be integral with the housing.

In some embodiments of the syringe, the flexible extension is removably attachable to the housing.

Some embodiments of the syringe may also include a locking device for removably attaching the flexible extension to the housing, the locking device including interlocking first and second members, the flexible extension including one of the first and second members and the housing including the other of the first and second members.

In some embodiments of the syringe, the flexible extension can be selected from a set of flexible extensions, wherein one flexible extension in the set of flexible extensions can be configured to stretch the skin at the injection site and another flexible extension in the set can be configured to pinch the skin at the injection site.

In some embodiments of the syringe, the flexible extension is non-removably attached to the housing of the syringe.

Some embodiments of the syringe may further comprise an adapter for attaching to the housing of the syringe, wherein the flexible extension is removably attachable to the adapter.

Some embodiments of the syringe may also include a locking device for removably attaching the flexible extension to the adapter, the locking device including interlocking first and second members, the flexible extension including one of the first and second members and the adapter including the other of the first and second members.

In some embodiments of the syringe, the flexible extension is configured as a flange.

In some embodiments of the syringe, the flexible extension is made of polyurethane or a silicone-polyurethane copolymer material.

Some embodiments of the injector may also include a needle guard for covering the needle as it is withdrawn from the skin at the injection site.

In some embodiments of the syringe, the flexible extension may be integrated with the needle guard.

In some embodiments of the syringe, the flexible extension is removably attachable to the needle guard.

In some embodiments of the injector, the needle guard may be colored to indicate completion of the injection procedure.

Some embodiments of the syringe may further comprise a soft guard attached to the needle guard, the guard being used to prevent the needle guard from contacting the skin at the injection site.

In some embodiments of the syringe, the flexible extension may have one or more annular protrusions or ridges formed in or on a working surface of the flexible extension.

In some embodiments of the syringe, the flexible extension may have a plurality of nubs formed in or on a working surface of the extension.

In some embodiments of the syringe, the flexible extension may have a non-slip or textured working surface.

Some embodiments of the injector may further include a palm button arrangement for at least triggering an injection operation of the injector.

In some embodiments of the injector, the palm button arrangement may have a mushroom-shaped palm button.

In some embodiments of the injector, the palm button arrangement may have a handle-shaped palm button.

In some embodiments of the injector, the palm button arrangement may comprise a palm button having at least one recess for receiving a thumb of a user.

In some embodiments of the syringe, the palm button may have a polyurethane gel elastomer coating.

In some embodiments of the injector, the palm button device may be integrated into the injector.

In some embodiments of the syringe, the palm button is removably attachable to the housing of the syringe.

In some embodiments of the injector, the palm button device is non-removably attachable to the housing of the injector.

In some embodiments of the injector, the palm button arrangement may include a palm button and a mounting arrangement for operatively coupling the palm button to the injector.

In some embodiments of the syringe, the mounting device may include a base extending from the palm button and an adapter for attaching to a housing of the syringe, wherein the base is movably coupled to the adapter.

Some embodiments of the syringe may further include a holding device for assisting a user in operating the syringe, the holding device comprising: a sleeve for ergonomically holding and operating the syringe with one hand; and at least one hand rest extending from the sleeve for keeping the user's hand on the sleeve when holding and operating the syringe.

In some embodiments of the syringe, the sleeve of the gripping device may have a polyurethane gel elastomer layer defining a hand grip.

In some embodiments of the syringe, the sleeve may have a top wall operable as a stop to accurately position the sleeve on the syringe to enable a user to operate the syringe with one hand.

In some embodiments of the syringe, the top wall may include an opening for allowing a firing button of the syringe to extend through the top wall.

In some embodiments of the syringe, the at least one hand rest may be pivotally coupled to the sleeve.

In some embodiments of the syringe, the at least one hand rest may include a protrusion that engages a side wall of the housing when the at least one hand rest is in the clamped position, thereby removably attaching the gripping device to the syringe.

In some embodiments of the syringe, the gripping means may further comprise detent means for maintaining the at least one hand rest in the clamped position.

In some embodiments of the injector, at least one hand rest may be contoured to receive the hypothenar region of a user's hand.

In some embodiments of the syringe, the gripping device may be integrated with the syringe.

In some embodiments of the syringe, the gripping device is removably attachable to the housing of the syringe.

In some embodiments of the syringe, the gripping means may comprise locking means for irremovably attaching the gripping means to the housing of the syringe.

In some embodiments of the syringe, the gripping device may allow a user to set and initiate an injection procedure of the syringe.

In some embodiments of the syringe, the gripping device may allow a user to initiate an injection procedure of the syringe.

In some embodiments of the syringe, the sleeve is slidably movable on the housing of the syringe to initiate an injection procedure of the syringe.

In addition, a syringe includes a housing having a trigger end and an injection end arranged opposite to and colinear with the trigger end, and the syringe also includes the palm button device described previously, which is arranged at the trigger end of the housing, wherein the palm button device triggers the injection operation process of the syringe.

Furthermore, the syringe comprises the housing and the gripping means as previously described for assisting the user in handling the syringe.

Also, a skin manipulation device for use with a syringe having an injection needle includes a flexible extension for stretching or pinching the skin at a selected injection site.

In some embodiments of the skin manipulation device, the flexible extension may have one or more annular protrusions or ridges formed in or on a working surface of the flexible extension.

In some embodiments of the skin manipulation device, the flexible extension may have a plurality of nodules formed in or on a working surface of the flexible extension.

In some embodiments of the skin manipulation device, the flexible extension may have a non-slip or textured working surface.

In some embodiments of the skin manipulation device, the flexible extension may be integrated with the syringe.

In some embodiments of the skin manipulation device, the flexible extension is removably attachable to the syringe.

In some embodiments of the skin manipulation device, the flexible extension may further comprise an adapter that attaches to the housing of the syringe, the flexible extension being removably attachable to the adapter.

Some embodiments of the skin manipulation device may also include a locking device for removably attaching the flexible extension to the adapter, wherein the locking device includes interlocking first and second members, the flexible extension includes one of the first and second members and the adapter includes the other of the first and second members.

Furthermore, a gripping device for assisting a user in operating a syringe may include: a sleeve for ergonomically holding and operating the syringe with one hand; and at least one hand rest extending from the sleeve for holding the user's hand on the sleeve when holding and operating the syringe.

In some embodiments of the gripping device, the sleeve may have a polyurethane gel elastomer layer defining a hand grip.

In some embodiments of the gripping device, the sleeve may have a top wall operable as a stop to accurately position the sleeve on the syringe to enable a user to operate the syringe with one hand.

In some embodiments of the gripping device, the top wall may include an opening for allowing a trigger button of a syringe to extend through the top wall.

In some embodiments of the holding device, the at least one hand rest may be pivotally coupled to the sleeve.

In some embodiments of the gripping device, the at least one hand rest may comprise a protrusion for engaging a side wall of the housing with the at least one hand rest in the clamped position, thereby allowing the gripping device to be removably attached to the syringe.

Some embodiments of the holding device may further comprise a detent arrangement for retaining the at least one hand rest in the clamped position.

In some embodiments of the holding device, at least one hand rest may be contoured to receive the hypothenar region of a user's hand.

Some embodiments of the gripping device may further comprise locking means for irremovably attaching the gripping device to the housing of the syringe.

Some embodiments of the gripping device may allow a user to initiate an injection procedure of the syringe.

In some embodiments of the gripping device, the sleeve is slidably movable on the housing of the syringe to initiate an injection procedure of the syringe.

Furthermore, a palm button device is provided for at least triggering an injection operation of a syringe. The palm button device may include a palm button and a mounting device for operatively coupling the palm button to the syringe.

In some embodiments of the palm button device, the mounting device may include a base extending from the palm button and an adapter for attaching to a housing of the syringe, wherein the base is movably coupled to the adapter.

In some embodiments of the palm button device, the palm button may have a mushroom shape.

In some embodiments of the palm button device, the palm button may have a handle shape.

In some embodiments of the palm button device, the palm button may have at least one recess for receiving a user's thumb.

In some embodiments of the palm button device, the palm button may have a polyurethane gel elastomer coating.

In some embodiments of the palm button device, the adapter is non-removably attachable to the housing of the syringe.

Some embodiments of the above-described syringes may further include a container or barrel containing a therapeutic product.

BRIEF DESCRIPTION OF THE DRAWINGS

1A is a cross-sectional elevational view of an embodiment of a flexible skin manipulation flange removably attached to or integral with the auto-injector prior to triggering an injection procedure of the auto-injector.

1B is a cross-sectional elevational view of the flexible skin manipulation flange and autoinjector of FIG. 1A , illustrating a user pressing the autoinjector down onto the skin at an injection site during an injection procedure of the autoinjector.

2A is an end view of an embodiment of a flexible skin manipulation flange illustrating the surface of the flange facing the autoinjector.

2B is a cross-sectional view of the flexible skin-manipulating flange shown in FIG. 2A , taken along line 2B- 2B.

3A is an end view of another embodiment of a flexible skin manipulation flange illustrating the surface of the flange facing the autoinjector.

3B is a cross-sectional view of the flexible skin-manipulating flange illustrated in FIG. 3A , taken along line 3B- 3B.

4A is an end view of an autoinjector illustrating the surface of the autoinjector housing that has been modified to accommodate a removable variation of the flexible skin manipulation flange.

4B is a cross-sectional view of the flexible skin manipulation flange shown in FIGS. 2A and 2B removably attached to a surface of the autoinjector housing illustrated in FIG. 4A .

4C is a cross-sectional view of the flexible skin manipulation flange illustrated in FIGS. 3A and 3B removably attached to a surface of the autoinjector housing illustrated in FIG. 4A .

4D-4F are cross-sectional views of another embodiment of a coupling device capable of removably attaching a skin manipulation flange (SMF) to an autoinjector.

5A is a cross-sectional view illustrating another embodiment of a flexible skin manipulation flange attached to an autoinjector housing surface having an adhesive layer or film.

5B is a cross-sectional view illustrating yet another embodiment of a flexible skin-manipulating flange attached to an autoinjector housing surface having an adhesive layer or film.

6A is a cross-sectional view illustrating yet another embodiment of a flexible skin-manipulating flange attached to an edge surface of a needle guard of an autoinjector with an adhesive layer or an adhesive film.

6B is a cross-sectional view illustrating yet another embodiment of a flexible skin-manipulating flange attached to an edge surface of a needle guard of an autoinjector with an adhesive layer or an adhesive film.

FIG7A is a front view illustrating the operation of a flexible skin manipulation flange having one or more annular protrusions or ridges disposed on a working surface of the flange that assist in stretching or stretching the skin S at the injection site. FIG7A illustrates the flattening and radial expansion of the flange when the autoinjector is depressed by the user during a triggered injection procedure, thereby stretching or stretching the skin S at the injection site.

FIG7B is a front view illustrating the operation of a flexible skin manipulation flange having a ring of spaced-apart protrusions and nubs disposed on a working surface of the flange that assist in stretching or stretching the skin S at the injection site. FIG7B illustrates the flattening and radial expansion of the flange upon depression of the autoinjector by the user during a triggered injection operation, thereby stretching or stretching the skin S at the injection site.

FIG7C is a front view illustrating the operation of a flexible skin manipulation flange having a sticky or non-slip texture provided on a working surface of the flange that helps to stretch or stretch the skin S at the injection site. FIG7C illustrates the flattening and radial expansion of the flange when the autoinjector is pressed downward by the user during a triggered injection operation, thereby stretching or stretching the skin S at the injection site.

8A is a front view illustrating an embodiment of a palm button device (shown in partial section) for an autoinjector.

8B is an enlarged cross-sectional view illustrating an embodiment of a detent arrangement for coupling the base and adapter of the palm button arrangement of FIG. 8A .

8C is a front view illustrating the palm button of FIG. 8A secured to an autoinjector embodiment.

9A is a front view illustrating another embodiment of a palm button device (shown in partial section).

9B is a top plan view of the palm button of the palm button device of FIG. 9A .

Figures 10A and 10B are front views of an embodiment of a hand grip for one-handed operation of an autoinjector. Figure 10A illustrates the hand grip with the hand rest positioned in an upper position for packaging, and Figure 10B illustrates the hand grip secured to an embodiment of the autoinjector with the hand rest in a lower position.

Figures 1OC and 1OD are enlarged cross-sectional views of embodiments of a hand rest. Figure 1OC illustrates the hand rest in an up position, and Figure 1OD illustrates the hand rest in a down position engaged with the autoinjector housing.

FIG10E is a cross-sectional view taken along line 10E-10E in FIG10C.

FIG10F is a cross-sectional view taken along line 10F-10F in FIG10D .

10G is a front view of another embodiment of a hand grip secured to an autoinjector embodiment.

Figures 11A and 11B are front views of yet another embodiment of a hand grip for one-handed operation of an autoinjector. Figure 11A illustrates the hand grip and Figure 11B illustrates the hand grip secured to an embodiment of an autoinjector.

12A is a front view illustrating an embodiment of an ergonomic needle guard for an autoinjector.

12B is a bottom plan view of an embodiment of an autoinjector illustrating an ergonomic needle guard and a skin manipulation flange that has been modified for use with the needle guard.

FIG12C is a cross-sectional view taken along line 12C-12C in FIG12A.

DETAILED DESCRIPTION

1A and 1B illustrate an embodiment of a flexible skin manipulation flange extension (SMF) 130 that is removably attached to or integrated with an auto-injector (AI) 100 or other body injector. The SMF 130 increases the surface area of the AI 100 at its injection end and thereby provides a stable platform for the AI 100 that prevents the device from slipping/moving on the skin surface as the user feels the AI 100 being fully depressed onto the skin. The stable platform provided by the SMF 130 also prevents the user from tilting the AI 100 to the right, left, forward, or backward or moving the AI 100 in a circular motion, thereby helping the user to maintain the AI 100 at 90 degrees (the preferred injection angle) relative to the skin. The SMF 130 also facilitates placement of the device and simplifies the injection procedure by eliminating the skin stretching or pinching step required to prepare the injection site, thereby allowing the user to freely use one or both hands to manipulate and stabilize the AI 100, keeping the skin beneath the AI 100 taut for user comfort, and allowing the user to, in some embodiments, view the injection needle through the SMF material, thereby ensuring visual feedback that the injection needle is in place and/or retracting the injection needle after the injection is completed. The SMF 130 does not use glue or adhesive backing to adhere uncomfortably to the skin and can be constructed, shaped, and adjusted to fit any autoinjector or body injector placed on the skin.

The AI 100 may generally include a drug product container carrier 102, a container or syringe 104 pre-filled with a fluid-based drug product, a drive unit 106, a trigger and drive control unit 108, and a housing 110 for enclosing one or more drug product container carriers 102, the container 104, the drive unit 106, and the trigger and drive control unit 108. The AI 100 may also include a needle guard or shield 112 disposed within the housing 110 (as shown) or external to the housing 110. The container or syringe 104 may include a needle 116 and a stop 118 for dispensing the drug product. The container carrier 102 may be configured to receive the container 104 in a defined relationship and retain the container 104 to the housing 110, and the container carrier 102 may be axially movable relative to the housing 110 between a rearward position and a forward position for needle puncture, with movement between these positions being used for needle puncture. The housing 110 of the AI 100 can have a first or rear end wall 120 and an opposing second or front end wall 122, which define the trigger end and injection end of the AI 100, respectively. The front end wall 122 can have a needle opening 124 to allow the needle 116 of the container or syringe 104 to extend through the needle opening 124 during operation of the AI 100, as shown in FIG1B . The drive unit 106 can include an automatic piercing mechanism for moving the carrier 102 or container 104 relative to the housing 110 or carrier 102, respectively, to insert the needle 116 into the skin S. The drive unit 106 can also include an automatic injection mechanism for moving or advancing the stopper 118 through the container or syringe 104 to dispense the drug product, and a needle guard deployment mechanism for deploying the needle guard 112 around the needle 116 after the injection is completed. If the AI 100 is not provided with the optional needle guard 112, the automatic piercing mechanism may also be configured to automatically retract the needle 116 into the housing 110. The various drive unit mechanisms may utilize any known form of stored energy, including but not limited to electrical, mechanical (e.g., resilient members such as springs), gas pressure, gas release, and any combination thereof. The stored energy may be transferred by corresponding conventional transfer mechanisms, such as electromechanical (e.g., electric motors or solenoids), hydraulic, pneumatic, mechanical springs, gears, rods, etc. The drive control and trigger unit may be used to trigger and set the timing of the drive mechanism of the drive unit 106, and may include any known type of releasable locking device, electronic controller, combinations thereof, etc. The trigger and drive control unit 108 may be set and the injection initiated by a button or switch 114 extending through the rear end wall 120 of the housing 110 at the trigger end of the AI 100. In other embodiments, the needle guard 112 may extend slightly beyond the front end wall 122 of the autoinjector housing 110 and be adapted to act as a trigger so that when the needle guard 112 is depressed by contact with the skin, the trigger and drive control unit 108 is set. In these other embodiments, depressing the trigger button 114 will cause the trigger and drive control unit 108 to initiate delivery.

The SMF 130 expands the surface area of the injection end (front wall 122) of the AI 100 that contacts the skin S at the injection site during initial activation and/or unlocking. When the user presses down to set the AI 100, the SMF 130 gradually tightens the skin S and avoids the center of the injection site and the injection needle 116 of the AI 100.

2A , 2B, 3A, and 3B , the SMF 130, 230 may include a flexible, annular body 132, 232 having a first end surface 134, 234, an opposing second end surface 136, 236, a cylindrical side surface 138, 238 extending between the first and second end surfaces 134, 234, 136, 236, and a bore 140, 240 extending through a generally central portion of the body 132, 232. Certain embodiments of the SMF 130, 132 may optionally include a protrusion 142, 242 disposed on the first surface 134, 234 thereof, the purpose of which will be explained below. In some embodiments, the SMF 130, 230 can be made of a flexible material, such as transparent polyurethane or a silicone-polyurethane copolymer, which allows the user to observe the injection needle 116 passing through the SMF 130, 230 during injection. In other embodiments, the SMF 130, 230 can be made of a translucent or opaque polyurethane material, a nitrile rubber copolymer material, or any other suitable material that can be bent. As shown in the embodiment illustrated in Figures 2A and 2B, the side surface 138 of the SMF 130 can be configured to flare outward from the first surface 134 to the second surface 136 so as to allow the SMF 130 to be easily compressed and flattened by pressing the AI 100 downward against the skin S at the injection site, thereby maximizing the radial expansion of the SMF 130, especially its second surface 136 (as shown in Figure 1B). 1A and 1B , the aperture 140 of the SMF 130 is axially aligned with the needle opening 124 formed in the front end wall 122 of the autoinjector housing 110 to allow the needle 116 of the container or syringe 104 to extend therethrough during operation of the AI 100 .

In some embodiments, the skin manipulation flange can be a separate accessory that the user can removably attach to the auto-injector during injection. In such embodiments, the SMF can be selected from a kit of different SMFs. The kit can be provided with the auto-injector or can be provided separately for use with the auto-injector. For example, but not by way of limitation, one or more SMFs can be configured to stretch or pull the skin at the injection site, while other one or more SMFs can be configured to pinch the skin at the injection site. Thus, the user can select the desired SMF in the kit based on whether the user wishes to obtain the effect of pinching the skin or stretching the skin. In some embodiments, the SMF can be configured to stretch/stretch the skin at the injection site or pinch the skin at the injection site depending on whether the user presses the auto-injector downward or lifts the auto-injector upward.

Any suitable coupling device can removably attach the SMF to the AI 100. Figures 4A-4C illustrate an embodiment of a twist-lock device that can be used to removably attach the SMFs 130, 230 shown in Figures 2A-2B and 3A-3B to the AI 100. The twist-lock device can include two or more arcuate slots 126 formed, for example, in a circularly spaced arrangement, in the front end wall 122 of the AI 100. The twist-lock device can also include a corresponding number of protrusions 142, 242 formed, for example, in a circularly spaced arrangement, on the first surface 134, 234 of the SMFs 130, 230. The protrusions 142, 242 of the SMFs 130, 230 are configured to be slidably movable within the arcuate slots 126 formed in the front end wall 122 of the AI 100. Although not shown, two or more arcuate grooves can be formed in the first end surface of the skin manipulation flange, and a corresponding number of protrusions can be formed on the front end wall of the automatic injector. The protrusions 142, 242 can have a pin-shaped configuration or any other suitable configuration that can be removably retained in the arcuate grooves. One end 128 of each arcuate groove 126 can be enlarged to allow insertion and retraction of the pin-shaped protrusions 142, 242. To attach the SMF 130, 230 to the injection end of the AI 100, the user can insert the protrusions 142, 242 into the enlarged end 128 of the arcuate groove 126 and twist the SMF 130, 230 relative to the first direction of the AI 100 to lock the SMF 130, 230 to the AI 100. The SMF 130 , 230 may be removed from the AI 100 by twisting the SMF 130 , 230 relative to the AI 100 in a second direction and then separating the SMF 130 , 230 from the AI 100 .

4D-4F illustrate another embodiment of a coupling device that removably attaches an SMF 130, 230 to an AI 100. The coupling device includes an adapter collar 260 that slides onto the injection end of the autoinjector housing 110 and allows for snap-lock attachment of interchangeable SMFs 130, 230 to the AI 100. The adapter collar 260 may include a metal sleeve 270 for securing the adapter collar 260 to the autoinjector housing 110. The metal sleeve may include two or more spaced apart barbed gripping elements 274 formed on an inner surface 272 of the metal sleeve 270. The metal sleeve 270 may be mounted into the adapter collar 260 on an inner surface 266 thereof adjacent a first open end 262 of the collar 260. The metal sleeve 270 is shaped to frictionally fit with the inner surface 266 of the adapter collar 260 so that it cannot be pulled out of the collar 260 when the clasp securing the SMF 130, 230 is unfastened from the collar 260 or the SMF 130, 230 is snapped onto the collar 260. When the adapter collar 260 is pressed into the injection end of the autoinjector case 110, the barbed gripping elements 274 of the metal sleeve 270 can penetrate into the autoinjector case 110 and grip the autoinjector case 110, thereby preventing the adapter collar 260 from being removed from the autoinjector, especially when the SMF 130, 230 is unfastened from the collar 260. The first member 268 of the snap-lock mechanism can be formed on the inner surface 266 of the adapter collar 260 adjacent to the second open end 264 thereof, while the second member 276 of the snap-lock mechanism can be formed on the side surface 138, 238 of the SMF 130, 230 adjacent to the first end surface 134, 234 thereof. One of the first and second members 268, 276 of the snap-lock fastening mechanism can include a continuous or segmented bead (e.g., the first member 268 illustrated in Figures 4D to 4F), and the other of the first and second members 268, 276 can include a continuous or segmented groove (e.g., the second member illustrated in Figures 4D to 4F) adapted to removably receive the bead in a snap-fit manner. The snap-lock mechanism allows users with hand strength/dexterity issues to easily attach and remove the desired SMF 130, 230.

In other embodiments, the SMF 130, 230 may be integrally bonded to the AI 100 during manufacture or permanently attached to the AI 100. In some of these embodiments, bonding or permanent attachment of the SMF 130, 230 may be facilitated by bonding the first end surface 134, 234 of the SMF 130, 230 to the front end wall 122 of the autoinjector housing 110 using an adhesive layer or film 150, 250, as shown in Figures 5A and 5B. In other embodiments, bonding or permanent attachment may be facilitated by bonding the first end surface 134, 234 of the SMF 130, 230 to the bottom edge surface 113 of the needle guard 112 using an adhesive layer or film 152, 252, as shown in Figures 6A and 6B.

7A-7C , the second end surface 134, 234 of the SMF 130, 230 may be provided with structures that help stretch or pull taut the skin S at the injection site beneath the SMF 130, 230 when the SMF 130, 230 is pressed downward to radially expand the SMF 130, 230. For example, in some embodiments, the second surface 134 of the SMP 130 (FIGS. 2A and 2B) can be provided with one or more annular protrusions or ridges 144 as shown in FIG. 7A or a ring of spaced-apart protrusions or nodules 148 as shown in FIG. 7B, which are selectively positioned to hold, stretch, and stabilize the skin S beneath the SMF 130 as the SMF 130 compresses the protrusions or ridges 144 or the ring of spaced-apart protrusions or nodules to flatten and radially expand in response to pressing the AI 100 downwardly into the skin S at the injection site. When the AI 100 is removed from the skin S, the SMF 130 returns to its original uncompressed and unflattened shape, thereby releasing the skin S.

If a skin lift S is desired, the annular protrusions or ridges of the SMF 130 shown in FIG. 7A can also be used to lift the skin S into the SMF 130 so as to mimic a skin lift by slightly elevating the AI 100 after the SMF 130 has been compressed and flattened.

In some embodiments, the second end surface 236 of the SMF 230 (FIGS. 3A and 3B) can be provided with a tacky or non-slip texture 244, as shown in FIG7C, which holds, stretches, and stabilizes the skin beneath the skin manipulation flange as the SMF compresses, flattens, and radially expands in response to pressing the AI 100 downwardly into the skin at the injection site. When the AI 100 is removed from the skin, the SMF returns to its original shape and releases the skin. If a skin pinch S is desired, the tacky or non-slip texture 244 provided on the second end surface 236 of the SMF 230 can also be used to elevate the skin S, simulating a skin pinch by slightly lifting the AI 100 after the SMF 230 has been compressed and flattened.

FIG8A illustrates an embodiment of a palm button device 330 for conveniently setting up an autoinjector and activating a needle injection within the autoinjector. The palm button device 330 generally includes a palm button 331 and a mounting device 340 for securing the palm button device 330 to the autoinjector. Palm button device 330, when operated with the palm of the hand, makes the autoinjector more stable and easier to trigger than with a finger, and allows for single-handed operation of the autoinjector. Furthermore, the palm button device 330 makes it easier to train a user to manipulate and use the autoinjector.

Referring now to Figures 8A-8C, the palm button 331 of the device 330 can have a flat bottom surface 332 and a curved top surface 334. The curved top surface 334 can be shaped to accommodate the inner surface of the user's hand or palm, allowing the palm button 331 to naturally conform to most of the hand's contours. In some embodiments, the palm button 331 has a length of 6.0 cm, a width of 4.5 cm, and a height of 3.5 cm. In other embodiments, the palm button 331 can have other dimensions. The curved top surface 334 provides an ergonomic trigger surface for the palm button 331, allowing the user to set and initiate the needle injection process of the autoinjector using a pushing motion with the palm of the hand. In some embodiments, the curved top surface 334 of the palm button 331 can have a mushroom or hemispherical shape to maximize grip and ease of pressing the palm button 331.

Mounting device 340 may include a base 342 extending from a generally central portion of bottom surface 332 of palm button 331, and an adapter 350 movably or retractably disposed within base 342. Mounting device 340 mechanically and operatively couples palm button device 330 to AI 300 ( FIG. 8C ). More specifically, base 342 of mounting device 340 operatively couples palm button 330 of device 330 to trigger button 314 of AI 300 and mechanically couples palm button 330 to adapter 350. Adapter 350, in turn, is configured to be pressed onto trigger end 320 of autoinjector housing 310 to mechanically couple palm button device 330 to AI 300. Base 342 of mounting device 340 may include a top wall 344 and a cylindrical sidewall 346 depending from the periphery of top wall 344. A biasing element 348, such as a coil spring, can extend downwardly from a top wall 344 of the base 342. The adapter 350 of the mounting device 340 can include a top wall 352 and a cylindrical side wall 354 depending from the periphery of the top wall 352. The top wall 352 can include an opening 356 to allow the trigger button 314 of the AI 300 to extend therethrough. The adapter 350 can also include a metal sleeve 360 including two or more spaced-apart, barbed gripping elements 364 extending from an inner surface 362 of the metal sleeve 360. The metal sleeve 360 can be disposed on an inner surface 358 of the adapter side wall 354 in a friction fit so that the metal sleeve 360 cannot be pulled out of the adapter 350 during operation of the AI 300. When the adapter 350 is slidably placed onto the trigger end of the autoinjector housing 310, the barbed gripping elements 364 of the metal sleeve 360 can penetrate into the autoinjector housing 310 and grip the autoinjector housing 310, thereby preventing the palm button device 330 from being removed from the AI 300. When the user presses the palm button 331 downward to set and initiate an injection procedure of the autoinjector 330, the biasing element 348 presses the trigger button 314 of the AI 300 downward and is compressed between the top wall 344 of the base 342 and the trigger button of the AI 300. When the user releases the palm button 331, the compressed biasing element 348 causes the palm button 331 to return to an undepressed position and allows the trigger button 314 of the autoinjector 330 to return to an undepressed position.

8B , a detent arrangement 370 can be provided to prevent the base 342 from being removed from the adapter 350 when the palm button 331 is in an undepressed state, while allowing the base 342 to move downward relative to the adapter 350 when the palm button 331 is depressed. A first member 372 of the detent arrangement can be formed on the inner surface 347 of the base 342, while a second member 374 of the detent arrangement can be formed on the outer surface 355 of the adapter 350. One of the first and second members 372, 374 of the detent arrangement can include a continuous or segmented downwardly facing wedge-shaped protrusion (e.g., the first member 372 illustrated in FIGS. 8A to 8C ), and the other of the first and second members 372, 374 can include a continuous or segmented downwardly facing wedge-shaped recess (the second member 374 illustrated in FIGS. 8A to 8C ) adapted to receive the wedge-shaped protrusion 372.

Palm button assembly 330 may be formed from a plastic material or any other suitable material, including metal, hard rubber, and fiberglass. A soft, non-slip coating 336 may be deposited on top surface 334 of palm button 331 to provide a softer feel and grip to palm button 331. Coating 336 may be a polyurethane gel elastomer layer or a silicone-polyurethane copolymer layer.

In some embodiments, palm button 331 of palm button device 330 can be integrated with the auto-injector during manufacturing rather than being adapted to be installed on an existing auto-injector. For example, in some embodiments, palm button 330 can be adapted to replace the conventional trigger button of the auto-injector, as shown in FIG8D .

Figures 9A and 9B illustrate another embodiment of a palm button assembly 430, where like reference numerals represent like elements. Palm button assembly 430 is similar to palm button assembly 330 illustrated in Figures 8A to 8C, except that palm button 431 has an elongated shape formed by top and bottom walls 432 and 434, respectively, and end wall 440, with sidewall 438 connecting top and bottom walls 432 and 434. Thus, palm button 431 and mounting assembly 340 define a T-shaped handle structure. A polyurethane gel elastomer layer 436 may be deposited on top wall 432 of palm button 431 to provide a softer feel and grip. In some embodiments, palm button 431 may have a length of 10.0 cm, a width of 4.0 cm, and a height of 2.0 cm, although palm button 431 may have other dimensions. In some embodiments, palm button 431 can have a serrated side region 442 (best shown in FIG. 9B ) for receiving a user's thumb, making it easier for the user to grip or grasp palm button 431. Additionally, palm button 431 can be configured for left-handed or right-handed use.

10A and 10B illustrate an embodiment of a hand-held (HH) device 530 for use with the AI 500. The HH device 530 provides an ergonomic shape for improved usability taking into account the varying physical limitations of a user's medical condition. The HH device 530 may include a sleeve 532 that serves as a hand grip and one or more hand rests 540 pivotally coupled to the sleeve 532 (two opposing hand rests 540 are illustrated in FIG10A and FIG10B ).

The sleeve 532 can include a top wall 534 and a cylindrical side wall 536 depending from the periphery of the top wall 534. The wall 534 can include a hole 538 for allowing the trigger button 514 of the AI 500 to extend therethrough. The top wall 534 of the sleeve 532 can act as a stop to properly position the sleeve 532 on the AI 500 during installation thereof. Once installed, the sleeve 532 of the HH device 530 forces the user to grasp the correct portion of the AI 500, allowing the user to comfortably hold, stabilize, and press the trigger button 514 of the AI 500 using the same hand.

Referring now to Figures 10C to 10F , the hand rest 540 of the HH device 530 can be configured as an arm-like member. The hand rest arm 540 can be pivotally attached to the sleeve 532 via a pivot pin structure. As shown in Figures 10E and 10F , each pivot pin structure can include a slot 552 formed in the sleeve 532, a pair of axially aligned pivot pins 554, and a pair of axially aligned pivot pin receiving holes 556. The slot 552 can be formed directly above the open end 533 of the sleeve 532. The pivot pin 554 can extend from a side edge 553 of the slot 552, and the pivot pin receiving hole 556 can be formed on a side surface 542 of the hand rest arm 540 adjacent to the attachment end 544 of the hand rest arm 540. The pivot pin structure allows the hand rest arm 540 to pivot between an upper position (Figure 10A) and a lower position (Figure 10B). In the down position, the hand rest arms 540 extend from and are generally perpendicular to the sleeve 532, and thus operate to hold the user's hand in place on the AI 500 by preventing the user's hand from sliding down the sleeve 532 and onto the AI 500. The hand rest arms 540 can be contoured to receive the hypothenar muscles of the user's hand adjacent to the pinky fingers. The hand rest arms 540 can also serve as clamps in the down position to secure the HH device 530 to the AI 500. As shown in Figures 10C and 10D, the hand rest arms 540 in this embodiment can each include a protrusion 546 at their attachment end 544 that engages the housing 510 of the AI 500 when the hand rest arms 540 are in the down position, thereby enabling the arms 540 to clamp and secure the HH device 530 to the AI 500. In addition, each of the hand rest arms 540 may be provided with a detent mechanism for maintaining the hand rest arm 540 in the lower (clamped) position. The detent mechanism may include a protrusion 560 extending from each side surface 542 of the hand rest arm 540 and a recess 562 formed in each side edge surface 553 of the slot 552. When the hand rest arm 540 is in the upper position, as shown in FIG10E , the protrusion 560 of the detent mechanism slidably engages the side edge surface 553 of the slot 552. When the hand rest arm 540 is pivoted downward to the clamped position, as shown in FIG10F , the protrusion 560 slides along the side edge surface 553 of the slot 552 and enters the recess 562, thereby locking the hand rest arm 540 in the lower and clamped position. The detent arrangement can be released by applying an upward force on the hand rest arm 540 sufficient to retract the protrusion 560 from the recess 562, thereby allowing the arm 540 to pivot back to the upper position.

In other embodiments, an adhesive or metal sleeve can be provided on the inner surface of the sleeve 532 to secure the HH device 530 to the AI 500, similar to the metal sleeve described above with respect to the palm button device, including spaced apart barbed gripping elements. The adhesive or metal sleeve can also be used with the hand rest arm 540 having the aforementioned clamping structure or with the hand rest 540 without a clamping structure.

When the hand rest arm 540 is in the upper position, as shown in FIG10A , the HH device 530 can be easily packaged. Once the HH device 530 is removed from its packaging, it can be installed on the autoinjector 500. During installation, the HH device 530 can be slidably placed on the end of the AI 500 until the trigger button 514 extends through the hole 538 in the top wall 534 of the sleeve 532 and the top wall 534 engages the end wall of the AI 500 surrounding the trigger button 514, thereby accurately positioning the sleeve of the HH device on the autoinjector. The hand rest arm 540 can then be pivoted from the upper position to the lower position, in which the hand rest arm 540 can engage the AI 500 to secure the HH device 530 to the AI 500 and prevent the user's hand from sliding downward as previously described.

10G , some embodiments of the HH device 530 can have a sleeve 572 with a contoured hand grip 574 that enhances the ergonomic gripping characteristics of the HH device 530. The hand grip 574 can be integral with the sleeve 572 or applied to the sleeve as a separate layer or sleeve. The separate layer or sleeve-type hand grip 574 can be made of a soft polyurethane gel elastic material or any other material suitable for finger or hand gripping.

Figures 11A and 11B illustrate another embodiment of a hand-hold (HH) device 630 for use with the AI 600. The HH device 630 may include an open-ended sleeve 632 and a fixed hand rest device 640 disposed on one of the open ends of the sleeve 632. The fixed hand rest device 640 may be a unitary member comprising a top wall 642 and two L-shaped hand rests 644 depending from the periphery of the top wall 642. The bottom portion 645 of each hand rest extends from the sleeve and may be contoured to receive the digiti minimi muscle near the pinky finger of the user's hand. The top wall 642 may include an aperture 646 for allowing the trigger button 614 of the AI 600 to extend therethrough. As in the previous embodiment, the top wall 642 may serve as a stop to properly position the sleeve 632 on the AI 600 during installation. Once installed, the sleeve 632 of the HH device 630 forces the user to grasp the correct portion of the AI 600, enabling the user to comfortably hold, stabilize, and depress the trigger button 614 of the AI 600 with the same hand. The hand rest arm holds the user's hand in place on the AI 600 by preventing the user's hand from sliding down the sleeve 632 and onto the AI 600. The inner surface of the sleeve 632 of the HH device 630 can be provided with a metal sleeve having spaced-apart, barbed gripping elements, similar to the metal sleeve described above with respect to the palm button device, to secure the HH device 630 to the housing 610 of the AI 600. An adhesive can be used alone or in combination with the metal sleeve or other mechanical means to secure the HH device 630 to the housing 610 of the AI 600.

The HH device can be provided as an accessory for the auto-injector or integrated with the auto-injector. In some embodiments, the HH device can serve as an extension to the housing of the auto-injector after being fixed or attached to the auto-injector, thereby serving as an ergonomic grip structure, as described above. The HH device can be used on a variety of types of auto-injectors, including auto-injectors with only one trigger structure (e.g., a needle guard) and auto-injectors with two trigger structures (e.g., a needle guard and a trigger button). In some embodiments, instead of being located on the top and back walls of the auto-injector, the trigger button can be located on the side of the auto-injector.

In other embodiments, the HH device can be constructed and adapted to serve as a triggering component of an autoinjector such that, once secured, attached, or placed on the autoinjector, it is operable to trigger the autoinjector's trigger button in response to a downward force being applied to the HH device, which forces the HH device's sleeve to move axially relative to the autoinjector's housing and depress the autoinjector's trigger button. Such an embodiment would allow the user to utilize the autoinjector's ergonomic design to provide additional leverage for depressing the trigger button (for autoinjectors having two triggering structures (e.g., a needle guard and a trigger button)).

In other embodiments, the HH device may be permanently attached to the autoinjector during manufacture. In this embodiment, the HH device may be constructed and adapted to be a single-use or multiple-use component.

Figures 12A-12C illustrate an embodiment of a needle guard 712 for use in the AI 700. The needle guard 712 can have a cylindrical shape and include a first edge surface 713 and a second edge surface 715, the second edge surface 715 being opposite the first edge surface 713. The needle guard 712 can be configured so that the second edge surface 715 contacts the skin at the injection site during operation of the autoinjector. As shown in Figures 12A and 12C, the second edge surface of the needle guard can be configured with an enlarged, rounded edge that provides a more comfortable contact with the user's skin. The enlarged, rounded edge 715 has a larger surface area than the sharp edge of a conventional needle guard, thereby providing a more comfortable contact with the user's skin during the injection process. As shown in FIG. 12B , the previously described SMF 130 , 230 can be modified for use with an autoinjector utilizing the needle guard of the present disclosure by increasing the diameter of the needle hole 140 , 240 extending through the SMF 130 , 230 to accommodate the enlarged rounded edge 715 of the needle guard.

In some embodiments, the needle guard 700 may be colored to indicate to the user that the injection is complete. More specifically, when the injection procedure is complete and the colored needle guard 712 is subsequently deployed to cover the exposed needle, the deployed colored needle guard 700 indicates to the user that the injection is complete.

The syringe barrel or other primary container of the automatic syringe can be pre-filled with a drug product, such as an erythropoiesis-stimulating agent (ESA), which can be a liquid or lyophilized product. The ESA can be an erythropoiesis-stimulating protein. As used herein, "erythropoiesis-stimulating protein" refers to any protein that directly or indirectly activates an erythropoietic receptor, for example, by binding to the receptor and promoting receptor dimerization. Erythropoiesis-stimulating proteins include: erythropoietin and its variants, analogs, or derivatives, which bind to and activate the erythropoietin receptor; antibodies, which bind to the erythropoietin receptor and activate the receptor; or peptides, which bind to and activate the erythropoietin receptor. Erythropoiesis-stimulating proteins include, but are not limited to, recombinant artificial erythropoietin, erythropoietin-β, erythropoietin-δ, erythropoietin-i, erythropoietin-ζ and its analogs, pegylated erythropoietin, carbamoyl erythropoietin, mimetic peptides (including EMP1/Hematide), and mimetic antibodies. Exemplary erythrocyte stimulating proteins include erythropoietin, darbepoetin alfa, agonist variants of erythropoietin, and polypeptides or antibodies that bind to and activate the erythropoietin receptor.

The term erythropoiesis-stimulating protein includes, but is not limited to, (epoetin alfa (erythropoietin-α), (darbepoetin alfa (erythropoietin)), (epoetin delta (erythropoietin-δ)), (methoxy polyethylene glycol-epoetin beta (methoxy polyethylene glycol erythropoietin-β)), Hematide ^™ (peginesatide (polyethylene glycol peptide)), MRK-2578, INS-22, (epoetin zeta (erythropoietin-ζ)), (epoetinbeta (erythropoietin-β)), Silapo ^™ (epoetin zeta (erythropoietin-ζ)), (epoetin alfa (erythropoietin-α)), epoetin alfa Hexal, Abseamed ^™ (epoetin alfa (erythropoietin-α)), Ratioepo ^™ (epoetin theta (erythropoietin-θ)), Eporatio ^™ (epoetin Therapeutic indications include epoetin theta (erythropoietin-θ), Biopoin ^™ (epoetin theta (erythropoietin-θ), epoetin alfa (erythropoietin-α), epoetin beta (erythropoietin-β), epoetin zeta (erythropoietin-ζ), epoetin theta (erythropoietin-θ), and epoetin delta (erythropoietin-δ).

The term erythropoiesis stimulating protein also includes molecules or variants or analogs as disclosed in the following patents or patent applications, the entire contents of which are hereby incorporated by reference into the present invention: U.S. Patent Nos. 4,703,008; 5,441,868; 5,547,993; 5,618,698; 5,621,080; 5,756,349; 5,767,078; 5,773,569; 5,830,851; 5,856,298; 5,955,422; 5,986,047; 6,030,0 86; 6,631,078; 6,391,633; 6,583,272; 6,586,398; 6,900,292; 6,750,369; 7,030,226; 7,084,245; and 7,271,689; U.S. Gazette Nos. 2002/0155998; 2003/0077753; 2003/0082749; 2003/0143202; 2003/0215444; 2004/0009902; 2004/0071694; 2004/00919 61;2004/0143857;2004/0157293;2004/0175379;2004/0175824;2004/0229318;2004/0248815;2004/0266690;2005/0019914;2005/0026834;2005/0096461;2005/0107297;2005/0107591;2005/0124045;2005/0124564;2005/0137329;2005 /0142642; 2005/0143292; 2005/0153879; 2005/0158822; 2005/0158832; 2005/0170457; 2005/0181359; 2005/0181482; 2005/0192211; 2005/0202538; 2005/0227289; 2005/0244409; 2006/0040858; 2006/0088906 and 2006/0111279; and PCT Gazette Nos. WO WO 91/05867; WO 95/05465; WO 96/40772; WO 99/66054; WO 00/24893; WO 01/81405; WO 00/61637; WO 01/36489; WO02/014356; WO 02/19963; WO 02/20034; WO 02/49673; WO02/085940; WO 03/029291; WO 2003/055526; WO 2003/084477; WO 2003/094858; WO 2004/002417; WO 2004/002424;WO2004/009627;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; WO2005/103076; WO 2005/100403; WO2005/092369; WO 2006/50959; WO 2006/02646; WO 2006/29094 and WO 2007/136752.

Alternatively, the autoinjector syringe or other primary container may also be prefilled with other products. Examples of other drug products that may be used include, but are not limited to, therapeutic agents such as biologics (e.g., etanercept, tumor necrosis factor receptor/Fc fusion proteins, TNF blockers); anti-TNF antibodies (e.g., adalimumab, such as inximab, tocilizumab, and golimumab); anti-IL-12 antibodies (e.g., ustekinumab); other Fc fusions of CTL4A:Fc, such as abatacept; (pegylated filgastim, pegylated G-CSF, pegylated hu-met-G-CSF); (filgrastim, granulocyte colony-stimulating factor (G-CSF), hu-met-G-CSF); (romiplosim (romiplosim)); (panitumumab (panitumumab)); (cinacalcet (cinacalcet)) and (each denosumab, AMG162); and other small molecule drugs, therapeutic antibodies, peptides, proteins or other chemicals, such as iron (e.g., nano-iron oxide, iron dextran, iron gluconate and iron sucrose). The therapeutic agent can be in liquid form or reduced from a lyophilized form.

Among the proteins specifically exemplified, proteins that can be used in the syringe barrel or other primary container of an autoinjector are antibodies, peptibodies, pegylated proteins, polypeptides and related proteins (including protein fusions, protein fragments, protein analogs, variants or derivatives thereof), such as proteins that specifically bind to: osteoprotegerin ligand (OPGL); IL-4 receptor; interleukin-1-receptor 1 ("IL1-R1"); angiopoietin-2 (Ang2); nerve growth factor; CD22; interferon-1; B-7 related protein 1 (B7RP1); IL-15; IL-17 receptor A: type gamma interferon; TALL-1; parathyroid hormone ("PTH"); thrombopoietin receptor ("TPO-R"); hepatocyte growth factor ("HGF"); TRAIL-R2; activin A; transforming growth factor-β; amyloid-β; hepatocyte factor; α4β7; and IL-23 or one of its subclasses; and other therapeutic proteins.

The syringe barrel or other primary container of the automatic syringe can also be pre-filled with specific antibodies, peptibodies and related proteins of osteoprotegerin ligand (OPGL) (also known as osteoclast activation cell differentiation factor specific antibodies, peptibodies, etc.), such as those described in PCT Publication No. WO 03/002713, which are incorporated herein by reference in their entirety with respect to OPGL-specific antibodies and antibodies to proteins, especially antibodies having the sequences set forth herein, such sequences being particularly but not limited to the sequences set forth herein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, including OPGL-specific antibodies having a light chain of SEQ ID NO: 2 as set forth in FIG. 2 and/or SEQ ID NO: 3 as set forth in FIG. 4. The heavy chain of NO: 4, each of which is individually and expressly incorporated herein in its entirety as disclosed in the aforementioned publications.

The syringe barrel or other primary container of the autoinjector can also be prefilled with myostatin binding proteins, peptides, and related proteins, including myostatin-specific peptides, particularly those described in U.S. Publication No. 2004/0181033 and PCT Publication No. WO 2004/058988, the entire contents of which are incorporated herein by reference with respect to myostatin-specific peptides, including but not limited to the mTN8-19 family of peptides, including those of SEQ ID NOS: 305-351, including TN8-19-1 to TN8-19-40, TN8-19con1, and TN8-19con2; the mL2 family of peptides of SEQ ID NOS: 357-383; the mL15 family of SEQ ID NOS: 384-409; The mL17 family of SEQ ID NOS: 410-438; the mL20 family of SEQ ID NOS: 439-446; the mL21 family of SEQ ID NOS: 447-452; the mL24 family of SEQ ID NOS: 453-454; and those of SEQ ID NOS: 615-631, each of which is individually and expressly incorporated into the present invention in its entirety as disclosed in the aforementioned publications.

The syringe barrel or other primary container of the autoinjector can also be prefilled with IL-4 receptor specific antibodies, peptides and related proteins, etc., particularly those IL-4 receptor specific antibodies, peptides and related proteins that inhibit the mediated activity of IL-4 and/or IL-13 by binding to the receptor, including those described in PCT Publication No. WO2005/047331 or PCT Application No. PCT/US2004/03742 and U.S. Publication No. 2005/112694, portions of which are incorporated herein by reference in their entirety with respect to IL-4 receptor specific antibodies, particularly those antibodies as described herein. Incorporated into the present invention, the antibodies are particularly but not limited to those represented herein 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, each of which is individually and expressly incorporated into the present invention in its entirety as disclosed in the aforementioned publications.

A syringe barrel or other primary container for an automatic injector can be prefilled with IL1-R1 specific antibodies, peptides and related proteins, etc., including but not limited to those described in U.S. Publication No. 2004/097712A1, the entire disclosure of which is incorporated herein by reference with respect to IL1-R1 specific binding proteins and monoclonal antibodies, particularly but not limited to those antibodies represented herein as: 15CA, 26F5, 27F2, 24E12 and 10H7, each of which is individually and expressly incorporated herein in its entirety as disclosed in the aforementioned publication.

The syringe barrel or primary container of the automatic injector can be prefilled with Ang2-specific antibodies, peptides, and related proteins, etc., including but not limited to those described in PCT Publication No. WO03/057134 and U.S. Publication No. 2003/0229023, the contents of which are incorporated herein by reference in their entirety with respect to Ang2-specific antibodies and peptides, etc., and particularly those sequences described therein and including but not limited to: L1(N); L1(N)WT; L1(N)1K WT; 2xL1(N)WT; Con4(N), Con4(N)1KWT; 2xCon4(N)1K; L1C; L1C 1K; 2x L1C; Con4C; Con4C 1K; 2x Con4C 1K; Con4-L1(N); Con4-L1C; TN-12-9(N); C17(N); TN8-8(N); TN8-14(N); Con1(N), which also includes the anti-Ang2 antibodies and formulations described, for example, in PCT Publication No. WO2003/030833 (the entire contents of which are incorporated herein by reference with respect to such anti-Ang2 antibodies and formulations), in particular, various arrangements of Ab526; Ab528; Ab531; Ab533; A b535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; Ab551; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12; Ab1A1; Ab1F; Ab1K; Ab1P; and Ab1P, each of which is individually and expressly incorporated herein in its entirety as disclosed in the aforementioned publications.

The syringe barrel or main container of the automatic syringe can also be pre-filled with NGF (nerve growth factor) specific antibodies, peptides and related proteins, etc., and the NGF (nerve growth factor) specific antibodies, peptides and related proteins, etc. specifically include but are not limited to those described in U.S. Gazette No. 2005/0074821 and U.S. Patent No. 6,919,426, all of which are incorporated herein by reference in their entirety with respect to NGF-specific antibodies and related proteins, including but not limited to the NGF-specific antibodies represented herein as 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11, each of which is individually and explicitly incorporated herein in its entirety as disclosed in the aforementioned gazettes.

The syringe barrel or primary container of the automatic injector can also be pre-filled with CD22-specific antibodies, peptides and related proteins, such as those described in U.S. Patent No. 5,789,554, the entire contents of which are incorporated herein by reference with respect to CD22-specific antibodies and related proteins, and the CD22-specific antibodies and related proteins are particularly human CD22-specific antibodies, such as but not limited to human and fully human antibodies, including but not limited to human and fully human monoclonal antibodies, and particularly including but not limited to human CD22-specific IgG antibodies, such as humanized mouse monoclonal hLL2 gamma chain sulfide linked to a humanized mouse monoclonal hLL2 kappa chain, including but not limited to, for example, epratuzumab, a human CD22-specific fully human antibody with CAS (Chemical Substance) Registry No. 501423-23-0.

The syringe barrel or other primary container of the automatic syringe can also be pre-filled with IGF-1 receptor specific antibodies, peptides and related proteins, such as those described in PCT Gazette No. WO 17H17, L18H18, L19H19, L20H20, L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H30, L31H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H50, L51H51, L52H52, L53H53, L54H54, L55H55 The IGF-1 specific antibodies and IGF-IR-binding fragments of 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 variants thereof, each of which is individually and specifically incorporated herein by reference in its entirety.

Also, in non-limiting examples of anti-IGF-IR antibodies, the anti-IGF-IR antibodies used in the methods and compositions of the present invention are each and all of those antibodies described in: (i) U.S. Publication Nos. 2006/0040358 (published February 23, 2006), 2005/0008642 (published January 13, 2005), 2004/0228859 (published November 18, 2004), including but not limited to Antibody 1A (DSMZ Accession No. DSM ACC 2586), Antibody 8 (DSMZ Accession No. DSM ACC 2589), Antibody 23 (DSMZ Accession No. DSM ACC 2588), and Antibody 18 as described therein; (ii) PCT Publication No. WO 06/138729 (published on December 28, 2006) and WO 05/016970 (published on February 24, 2005) and Lu et al., 2004, Journal of Biol. Chem., 279:2826-65 (38), which include but are not limited to antibodies 2F8, A12 and IMC-A12 as described in; (iii) PCT Publication Nos. WO 07/012614 (published on February 1, 2007), WO 07/000328 (published on January 4, 2007), WO 06/013472 (published on February 9, 2006), WO 05/058967 (published on June 30, 2005) and WO 03/059951 (published on July 24, 2003); (iv) U.S. Publication No. 2005/0084906 (published on April 21, 2005), which includes, but is not limited to, antibody 7C10, chimeric antibody C7C10, antibody h7C10, antibody 7H2M, chimeric antibody *7C10, antibody GM607, human antibody 7C10 variant 1, human antibody 7C10 variant 2, human antibody 7C10 as described herein. Variant 2 and antibody 7H2HM; (v) U.S. Publication 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., 63:5073-83, including but not limited to the antibodies EM164, resurfaced EM164, humanized EM164, hu EM164 v1.0, hu EM164 v1.1, hu EM164 v1.2, and hu EM164 v1.3 as described herein; (vi) U.S. Patent No. 7,037,498 (issued May 2, 2006), U.S. Publication Nos. 2005/0244408 (published November 30, 2005), and 2004/0086503 (published May 6, 2004), and Cohen et al., 2005, Clinical Cancer Res., 11:2063-73, e.g., antibody CP-751,871, including but not limited to antibodies produced by hybridomas having ATCC accession numbers PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793 as described herein, and each of antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3; (vii) U.S. Publication Nos. 2005/0136063 (published June 23, 2005) and 2004/0018191 (published January 29, 2004), including but not limited to antibody 19D12 and antibodies comprising the hybridomas 15H12/19D12 as described herein. and (viii) U.S. Publication No. 2004/0202655 (published October 14, 2004), which includes, but is not limited to, antibodies PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT-7A7, PINT-7A8, PINT-7A9, PINT-7A10, PINT-7A11, PINT-7A12, PINT-7A13, PINT-7A14, PINT-7A15, PINT-7A16, PINT-7A17, PINT-7A18, PINT-7A19, PINT-7A20, PINT-7A21, PINT-7A22, PINT-7A23, PINT-7A24, PINT-7A25, PINT-7A26, PINT-7A27, PINT-7A28, PINT-7A29, PINT-7A30, PINT-7A31, PINT-7A32, PINT-7A33, PINT-7A34, PINT-7A35, PINT-7A36, PINT-7A37, PINT-7A38, PINT-7A39, PINT-7A40, PINT-7A41, PINT-7A42, PINT-7A43, PINT-7A44, PINT-7A45, PINT-7A46, PINT-7A47, PINT-7A48, PINT-7A49, PINT-7A51, PINT-7A52, PINT-7A53, PINT-7A54, PINT-7A55, PINT-7A56, PINT-7A57, PINT-7A58, PINT-7A59, PINT-7A61, PINT-7 PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2, PINT-12A3, PINT-12A4 and PINT-12A5; the entire contents of the above-mentioned cited publications and patents, especially those concerning the above-mentioned antibodies, peptides and related proteins targeting IGF-1 receptor, are hereby incorporated into the present invention by reference.

The syringe barrel or other primary container of the autoinjector may also be made of antibodies, peptides, related proteins, etc. specific for B-7 related protein 1 ("B7RP-1", also referred to in the literature as B7H2, ICOSL, B7h, and CD275), particularly B7RP-specific fully human monoclonal IgG2 antibodies, particularly fully human IgG2 monoclonal antibodies that bind to antigens within the 1 immunoglobulin-like domain of B7RP-1, particularly those that prevent B7RP-1 from reacting with its natural receptor, ICOS on activated T cells, particularly those disclosed in U.S. Publication No. 2008/0166352 and PCT Publication No. WO 07/011941, the entire disclosures of which with respect to such antibodies and related proteins are hereby incorporated by reference into the present invention, including but not limited to the antibodies designated herein as follows: 16H (having therein a light chain variable sequence of SEQ ID NO: 1 and a heavy chain variable sequence of SEQ ID NO: 7, respectively); 5D (having therein a light chain variable sequence of SEQ ID NO: 2 and a heavy chain variable sequence of SEQ ID NO: 3, respectively); NO:9); 2H (having a light chain variable sequence of SEQ ID NO:3 and a heavy chain variable sequence of SEQ ID NO:10, respectively); 43H (having a light chain variable sequence of SEQ ID NO:6 and a heavy chain variable sequence of SEQ ID NO:14, respectively); 41H (having a light chain variable sequence of SEQ ID NO:5 and a heavy chain variable sequence of SEQ ID NO:13, respectively); and 15H (having a light chain variable sequence of SEQ ID NO:4 and a heavy chain variable sequence of SEQ ID NO:12, respectively), each of which is individually and expressly incorporated into the present invention in its entirety as disclosed in the aforementioned U.S. publications.

IL-15 specific antibodies, peptides and related proteins, etc. (e.g., particularly human monoclonal capsids, especially those described in U.S. Publication Nos. 2003/0138421; 2003/023586; and 2004/0071702; and U.S. Patent No. 7,153,507, the entire contents of which are incorporated herein by reference with respect to IL-15 specific antibodies and related proteins, including peptides, including, in particular, but not limited to, the HuMax IL-5 antibody and related proteins, such as, for example, 146B7) can also be used.

The syringe barrel or primary container of the autoinjector can also be prefilled with a drug combination comprising an anti-human monoclonal antibody directed against the human IL-17 receptor. The characterization, cloning, and preparation of IL-17 receptor A are described in USPN 6,072,003, issued June 6, 2000, the entire contents of which are hereby incorporated by reference herein. The amino acid sequence of human IL-17RA is set forth in SEQ ID NO: 10 of USPN 6,072,033 (GenBank No. NM_014339). Such antibodies may include those disclosed in WO 2008/054603, the entire contents of which are hereby incorporated by reference herein, or those claimed in USPN 7,767,206, issued August 3, 2010; and those claimed in U.S. Serial No. 11/906,094, the entire contents of which are hereby incorporated by reference herein.

The syringe barrel or other container of the automatic injector can also be prefilled with IFN gamma-specific antibodies, peptides and related proteins, such as those described in U.S. Publication No. 2005/000453, the entire disclosure of which is incorporated herein by reference with respect to IFN gamma-specific antibodies, particularly antibodies designated herein as 1118; 1118*; 1119; 1121 and 1121*. The entire sequences of the heavy and light chains of each of these antibodies, as well as the sequences of their heavy and light chain variable regions and complementarity determining regions, are each incorporated herein by reference as disclosed in the aforementioned U.S. Publication No. 2005/000453 and in Thakur et al., Mol. Immunol, 36: 1107-1115 (1999). Additionally, the entire contents of the description of the properties of the antibodies provided in the aforementioned US publications are also incorporated herein by reference. As disclosed in the aforementioned U.S. Gazette, specific antibodies include: a specific antibody having a heavy chain of SEQ ID NO: 17 and a light chain of SEQ ID NO: 18; a specific antibody having a heavy chain variable region of SEQ ID NO: 6 and a light chain variable region of SEQ ID NO: 8; a specific antibody having a heavy chain variable region of SEQ ID NO: 19 and a light chain variable region of SEQ ID NO: 20; a specific antibody having a heavy chain variable region of SEQ ID NO: 10 and a light chain variable region of SEQ ID NO: 12; a specific antibody having a heavy chain variable region of SEQ ID NO: 32 and a light chain variable region of SEQ ID NO: 20; a specific antibody having a heavy chain variable region of SEQ ID NO: 30 and a light chain variable region of SEQ ID NO: 12; a specific antibody having a heavy chain variable region of SEQ ID NO: 21 and a light chain variable region of SEQ ID NO: 22; a specific antibody having a heavy chain variable region of SEQ ID NO: 14 and a light chain variable region of SEQ ID NO: 16; a specific antibody having a heavy chain variable region of SEQ ID NO: 15 and a light chain variable region of SEQ ID NO: 17; a specific antibody having a heavy chain variable region of SEQ ID NO: 16 and a light chain variable region of SEQ ID NO: 18; a specific antibody having a heavy chain variable region of SEQ ID NO: 17 and a light chain variable region of SEQ ID NO: 19; a specific antibody having a heavy chain variable region of SEQ ID NO: 10 and a light chain variable region of SEQ ID NO: 12 A specific antibody having a heavy chain variable region of SEQ ID NO: 21 and a light chain variable region of SEQ ID NO: 33; and a specific antibody having a heavy chain variable region of SEQ ID NO: 14 and a light chain variable region of SEQ ID NO: 31. The complementary specific antibody is antibody 1119 as disclosed in the aforementioned U.S. publication and having the complete heavy chain of SEQ ID NO: 17 as disclosed herein and the complete light chain of SEQ ID NO: 18 as disclosed herein.

The syringe barrel or other primary container of the automatic injector can also be prefilled with TALL-1 specific antibodies, peptides and related proteins, etc., as described, for example, in U.S. Publication Nos. 2003/0195156 and 2006/013543, and other TALL-specific binding proteins, the entire contents of which are incorporated by reference herein with respect to TALL-1 binding proteins, particularly the molecules of Tables 4 and 5B, which are all incorporated by reference herein in their entirety as disclosed in the aforementioned U.S. Publications.

The barrel of an autoinjector or other primary container may also be prefilled with PTH-specific antibodies, peptides, and related proteins, such as those described in U.S. Pat. No. 6,756,480, the disclosure of which, in particular, proteins that bind to PTH, is incorporated herein by reference in its entirety.

The syringe barrel or other primary container of an autoinjector can also be prefilled with TPO-R specific antibodies, peptides, and related proteins, such as those described in U.S. Patent No. 6,835,809, which is incorporated herein by reference in its entirety, particularly with respect to proteins that bind to TPO-R.

The syringe barrel or other primary container of the autoinjector can also be prefilled with HGF-specific antibodies, peptides, and related proteins, including those that target the HGF/SF:cMet axis (HGF/SF:c-Met), such as the fully human monoclonal antibodies neutralizing hepatocyte growth factor/discrete factor (HGF/SF) described in U.S. Publication No. 2005/0118643 and PCT Publication No. 2005/017107, huL2G7 described in U.S. Patent No. 7,220,410, and OA-5d5 described in U.S. Patent Nos. 5,686,292 and 6,468,529 and PCT Publication No. WO 96/38557, the contents of which are hereby incorporated by reference in their entirety, particularly with respect to proteins that bind HGF.

The syringe barrel or other primary container of an automatic injector can also be pre-filled with TRAIL-R2-specific antibodies, peptides, related proteins, etc., such as those described in U.S. Patent No. 7,521,048, which is incorporated herein by reference in its entirety with respect to proteins that bind to TRAIL-R2.

The syringe or other primary container can also be pre-filled with Activin A-specific antibodies, peptides, related proteins, etc., including but not limited to those described in U.S. Publication No. 2009/0234106, which is incorporated herein by reference in its entirety with respect to portions thereof that particularly relate to proteins that bind to Activin A.

The syringe barrel or other primary container of an automatic injector may also be prefilled with TGF-β (transforming growth factor β) antibodies, peptides, related proteins, etc., including but not limited to those described in U.S. Patent No. 6,803,453 and U.S. Publication No. 2007/0110747, the contents of which are incorporated herein by reference in their entirety, particularly with respect to proteins that bind TGF-β.

The barrel or other primary container of an autoinjector can also be prefilled with amyloid-beta-specific antibodies, peptides, related proteins, and the like, including, but not limited to, those described in PCT Publication No. WO 2006/081171, the disclosure of which is incorporated herein by reference in its entirety, particularly with respect to proteins that bind to amyloid-beta. One contemplated antibody is an antibody having a heavy chain variable region comprising SEQ ID NO: 8 and a light chain variable region comprising SEQ ID NO: 6, as described in PCT Publication No. WO 2006/081171.

The syringe barrel or other primary container of the automatic injector can also be pre-filled with c-Kit-specific antibodies, peptides, related proteins, etc., including but not limited to those described in Publication No. 2007/0253951, which is incorporated herein by reference in its entirety with particular regard to proteins that bind to c-Kit and/or other stem cell factor receptors.

The syringe barrel or other primary container of the autoinjector may also be prefilled with OX40L-specific antibodies, peptides, related proteins, etc., including but not limited to those described in U.S. Application No. 11/068,289, the disclosure of which is incorporated herein by reference in its entirety, particularly with respect to proteins that bind OX40L and/or other ligands of the OXO40 receptor.

The syringe barrel or other primary container of the autoinjector may also be prefilled with other exemplary proteins including, but not limited to, (Alteplase, tPA); (Darbepoetin α), (Erythropoietin α or Erythropoietin); (Interferon β-1a); (Tositumomab, anti-CD22 monoclonal antibody); (Interferon-β); (Alemtuzumab, anti-CD52 monoclonal antibody); (Erythropoietin δ); (bortezomib); MLN0002 (anti-α4β7 monoclonal antibody); MLN1202 (anti-CC R2 chemokine receptor monoclonal antibody); (etanercept, TNF-receptor/Fc fusion protein, TNF blocker); (erythropoietin alfa); (Cetuximab, anti-EGFR/HER1/c-ErbB-1); (Somatropin, human growth hormone); (Trastuzumab, anti-HER2/neu(erbB2) receptor monoclonal antibody); (Somatropin, human growth hormone); (Adalimumab); Insulin solution; (Interferon Alfacon-1 (interferon injection); (nesiritide; recombinant human brain natriuretic peptide (hBNP)); (Anakinra); (Sargamostim; rhuGM-CSF); Lympho (Epratuzumab; anti-CD22 monoclonal antibody); Lymphostat (Belimumab; anti-BlyS monoclonal antibody); (Tenecteplase; t-PA analog); (methoxypolyethylene glycol-epoetin beta); (Gemtuzumab ozogamicin); (efalizumab); (certolizumab pegol; CDP 870); Soliris ^™ (Eculizumab); Pexelizumab (anti-C5 complement); MEDI-524 (Ranibizumb); 17-1A (Edrecolomab); (lerdelimumab); TheraCim hR3 (Nimotuzumab); Omnitarg (Pertuzumab, 2C4); (IDM-1); (B43.13); (visilizumab); Cantuzumab mertansine (huC242-DM1); (erythropoietin beta); (Oprelvekin, human interleukin-11); (Pegylated filgastim, pegylated G-CSF, pegylated hu-Met-G-CSF); (Filgrastim, G-CSF, hu-MetG-CSF); Orthoclone (Muromonab-CD3, anti-CD3 monoclonal antibody); (Erythropoietin alfa); (Infliximab, anti-TNFα monoclonal antibody); (Abciximab, anti-GP11b/Ilia receptor monoclonal antibody); (Anti-IL6 receptor monoclonal antibody); (Bevacizumab); HuMax-CD4 (zanolimumab); (Rituximab, anti-CD20 monoclonal antibody); (Erlotinib); Roferon-(Interferon alfa-2a (interferon alpha-2a); (Basiliximab); (lumiracoxib); (Palivizumab); 146B7-CHO (anti-IL15 antibody, see U.S. Patent No. 7,153,507); (Natalizumab, anti-α4 integrin monoclonal antibody); (MDX-1303, anti-B. anthracis protective antigen mAb); ABthrax ^™ ; (Panitumumab); (Omalizumab); ETI211 (anti-MRSA mAb); IL-1 Trap (the Fc portion of human immunoglobulin and the extracellular domains of the two IL-1 receptor components (type I receptor and receptor accessory protein)), VEGF Trap (Immunoglobulin domain of vascular endothelial growth factor receptor 1 fused to IgG1 Fc), Daclizumab (Daclizumab anti-IL-2Rα mAb), Ibritumomab tiuxetan (Ibritumomab tiuxetan), Zetia (ezetimibe), Atacicept (TACI-Ig), Anti-CD80 monoclonal antibody (mAb) (galiximab), Anti-CD23 mAb (lumiliximab), BR2-Fc (huBR3/huFc fusion protein, soluble BAFF antagonist); CNTO148 (Golimumab, anti-TNFα mAb); HGS-ETR1 (Mapatumumab, human anti-TRAIL receptor-1 mAb); HuMax-CD20 (Ocrelizumab, anti-CD20 human monoclonal antibody); HuMax-EGF R (zalutumumab); M200 (Volociximab, anti-α5β1 integrin monoclonal antibody); MDX-010 (ipilimumab, anti-CTLA-4 monoclonal antibody and VEGFR-1 (IMC-18F1)); anti-BR3 monoclonal antibody; anti-C difficile A and difficile BC monoclonal antibodies MDX-066 (CDA-1) and MDX-1388); anti-CD22 dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 monoclonal antibody (HuMax-TAC); anti-CD3 monoclonal antibody (NI-0401); adecatumumab; anti-CD30 monoclonal antibody (MDX-060); MDX-1333 (anti-IFNAR); anti-CD38 monoclonal antibody (HuMax CD38); anti-CD40L monoclonal antibody; anti-Cripto monoclonal antibody; anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-3019); anti-CTLA4 monoclonal antibody; anti-eotaxin 1 monoclonal antibody (CAT-213); anti-FGF8 monoclonal antibody; anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb (anti-ganglioside GM2 monoclonal antibody); anti-GDF-8 human monoclonal antibody (MYO-029); anti-GM-CSF-receptor monoclonal antibody (CAM-3001); anti-HepC monoclonal antibody (HuMax HepC); anti-IFNα monoclonal antibody (MEDI-545, MDX-1103); anti-IGF1R monoclonal antibody; anti-IGF-1R monoclonal antibody (HuMax-Inflam); anti-IL12 monoclonal antibody (ABT-874); anti-IL12/IL23 monoclonal antibody (CNTO1275); anti-IL13 monoclonal antibody (CAT-354); anti-IL2Ra monoclonal antibody (HuMax-TAC); anti-IL5 receptor monoclonal antibody; anti-integrin receptor monoclonal antibody (MDX-018, CNTO 95); anti-IP10 ulcerative colitis monoclonal antibody (MDX-1100); anti-LLY antibody; BMS-66513; anti-mannose receptor/hCGβ monoclonal antibody (MDX-1307); anti-mesothelindsFv-PE38 conjugate (CAT-5001); anti-PD1 monoclonal antibody (MDX-1106 (ONO-4538)); anti-PDGFRα antibody (IMC-3G3); anti-TGFβ monoclonal antibody (GC-1008); anti-TRAIL receptor-2 human monoclonal antibody (HGS-ETR2); anti-TWEAK monoclonal antibody; anti-VEGFR/Flt-1 monoclonal antibody; anti-ZP3 monoclonal antibody (HuMax-ZP3); NVS Antibody #1; and NVS Antibody #2; sclerostin antibodies, such as, but not limited to, romosozumab, blosozumab, or BPS 804 (Novartis). It can also include therapeutic agents such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX, or XGEVA. Additionally, a monoclonal antibody (IgG) that binds to human Proprotein Convertase Subtilisin/Kexin can be included in the autoinjector. Type 9 (PCSK9), e.g., U.S. Pat. No. 8,030,547, U.S. Pat. No. 13/469,032, WO2008/057457, WO2008/057458, WO2008/057459, WO2008/063382, WO2008/133647, WO2009/100297, WO2009/100318, WO2011/037791, WO2011/053759, WO2011/053783, W WO2008/125623, WO2011/072263, WO2009/055783, WO2012/0544438, WO2010/029513, WO2011/111007, WO2010/077854, WO2012/088313, WO2012/101251, WO2012/101252, WO2012/101253, WO2012/109530 and WO2001/031007.

The barrel or primary container of the autoinjector may also be prefilled with antibodies that recognize any one or combination of proteins including, but not limited to, those listed above and/or the following antigens: CD2, CD3, CD4, CD8, C11a, CD14, CD18, CD20, CD22, CD23, CD25, CD33, CD40, CD44, CD52, CD80 (B7.1), CD86 (B7.2), CD147, IL-1α, IL-1β, IL-2, IL-3, IL-7, IL-4, IL-5, IL-8, IL-10, IL-2 receptor, IL-4 receptor, IL-6 receptor, IL-13 receptor, IL-18 receptor subgroup, FGL2, PDGF-β and its analogs (see U.S. Pat. Nos. 5,272,064 and 5,149,792), VEGF, TGF, TGF-β2, TGF-β1, EGF receptor (see U.S. Pat. No. 6,235,883), VEGF receptor, hepatocyte growth factor, osteoprotegerin ligand, interferon gamma, B lymphocyte stimulating factor (Blys, also known as BAFF, THANK, TALL-1 and zTNF4; see Do and Chen-Kiang (2002), Cytokine Growth Factor Receptor (see U.S. Pat. No. 6,235,883), TNF-α, ... Factor Rev.13(1):19-25), C5 complement, IgE, tumor antigen CA125, tumor antigen MUC1, PEM antigen, LCG (which is a gene product associated with lung cancer), HER-2, tumor-associated carbohydrate antigen TAG-72, SK-1 antigen, tumor-associated antigen (which is present at high levels in the serum of patients with colon cancer and/or pancreatic cancer), breast cancer cells, colon cancer cells, squamous cells, prostate cancer cells, lung cancer cells and/or kidney cancer cells and/or melanoma, glioma, neuroblastoma cells, cancer-associated antigens or proteins in the necrotic center of tumors, integrin α4β7, integrin VLA-4, B2 integrin, TRAIL receptors 1, 2, 3 and 4, RANK, RANK ligand, TNF-α, adhesion molecule VAP-1, epithelial cell adhesion molecule (EpCAM), cell adhesion molecule-3 (ICAM-3), leukointegrin adhesion, platelet membrane glycoprotein gpIIb/IIIa, cardiac myosin heavy chain, parathyroid hormone, rNAPc2 (which is an inhibitor of factor-VIIa-tissue factor), MHC I, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), tumor necrosis factor (TNF), CTLA-4 (which is a cytotoxic T lymphocyte-associated antigen), Fc-γ-1 receptor, HLA-DR 10β, HLA-DR antigen, L-selectin, respiratory syncytial virus, human immunodeficiency virus (HIV), hepatitis B virus (HBV), Streptococcus mutans and Staphylococcus aureus.

Additional examples of known antibodies that may be contained in the syringe or other primary container of an autoinjector include, but are not limited to, adalimumab, bevacizumab, infliximab, abciximab, alemtuzumab, bapineuzumab, basiliximab, belimumab, briakinumab, canakinumab, certolizumab pegol, cetuximab, conatumumab, denosumab, eculizumab, gemtuzumab tuzumab, golimumab, ibritumomab, and tiuxetan), labetuzumab, mapatumumab, matuzumab, mepolizumab, motavizumab, muromonab-CD3, natalizumab, nimotuzumab, ofatumumab, omalizumab, oregovomab, palivizumab ivizumab), panitumumab, pemtumomab, pertuzumab, ranibizumab, rituximab, rovelizumab, tocilzumab, tositumomab, trastuzumab, ustekinumab, zalutumumab, and zanolimumab.

Although the skin manipulation flange, palm button, HH device, needle guard, and auto-injector device have been described with respect to the illustrated embodiments, they are not limited thereto. Moreover, the appended claims should be broadly construed to include other variations and embodiments of the skin manipulation flange, palm button, HH device, needle guard, and auto-injector device that may be implemented by those skilled in the art without departing from the scope of equivalents of the skin manipulation flange, palm button, HH device, needle guard, and auto-injector device, and components thereof.

Claims (49)

1. A syringe, comprising: A housing having an injection end; An injection needle, encapsulated within the housing, which, when the injection process of the syringe is triggered, pierces the skin at a selected injection site and dispenses the drug product. A flexible extension, disposed at the injection end of the housing, for stretching or pinching the skin at the injection site; and An adapter, separate from and for attachment to the housing, a flexible extension removably attached to the adapter, the adapter having a hollow interior configured to receive an injection end of the housing and an end of the flexible extension, the adapter including at least two inwardly projecting barbs configured to penetrate into and grip the outer surface of the housing to prevent removal of the adapter from the housing. 2. The syringe of claim 1, wherein the flexible extension is selected from a set of flexible extensions, wherein one flexible extension in the set of flexible extensions is configured to stretch the skin at the injection site, and wherein another flexible extension in the set is configured to pinch the skin at the injection site. 3. The syringe of claim 1, further comprising a locking device for removably attaching the flexible extension to the adapter, the locking device comprising an interlocking first member and a second member, the flexible extension comprising one of the first member and the second member, and the adapter comprising the other of the first member and the second member. 4. The syringe of claim 1, further comprising a needle protector for covering the needle when withdrawing it from the skin at the injection site. 5. The syringe according to claim 4, wherein the flexible extension is integrally formed with the injection needle guard. 6. The syringe of claim 4, wherein the flexible extension is removably attached to the needle guard. 7. The syringe of claim 6, wherein the flexible extension is selected from a set of flexible extensions, wherein one flexible extension in the set of flexible extensions is configured to stretch the skin at the injection site, and wherein another flexible extension in the set is configured to pinch the skin at the injection site. 8. The syringe of claim 4, wherein the flexible extension is non-removably attached to the needle guard. 9. The syringe of claim 4, wherein the bottom portion of the needle guard extends from the injection end of the housing, and wherein the needle guard is capable of positioning the syringe when the user presses the injection end of the housing down against the skin at the injection site. 10. The syringe of claim 4, wherein the needle guard is colored to indicate the completion of the injection operation. 11. The syringe of claim 4, wherein the needle guard has a rounded edge for contacting the skin at the injection site. 12. The syringe of claim 1, wherein the flexible extension has one or more annular protrusions or ridges formed in or on the working surface of the flexible extension. 13. The syringe according to claim 1, wherein the flexible extension has a plurality of nodules formed in or on the working surface of the flexible extension. 14. The syringe of claim 1, wherein the flexible extension has a non-slip or textured working surface. 15. The syringe of claim 1, wherein the flexible extension is configured as a flange. 16. The syringe according to claim 1, wherein the flexible extension is made of polyurethane or silicone-polyurethane copolymer material. 17. The syringe according to claim 1, further comprising a palm button device for at least triggering the injection operation of the syringe. 18. The syringe of claim 17, wherein the palm button device has a mushroom-shaped palm button. 19. The syringe according to claim 17, wherein the palm button device has a handle-shaped palm button. 20. The syringe of claim 17, wherein the palm button device comprises a palm button having at least one recess for placing a user's thumb. 21. The syringe of claim 17, wherein the palm button device comprises a palm button having a polyurethane gel elastomer coating. 22. The syringe according to claim 17, wherein the palm button device is integrated with the syringe. 23. The syringe of claim 17, wherein the palm button device is removably attached to the housing of the syringe. 24. The syringe of claim 17, wherein the palm button device is non-removably attached to the housing of the syringe. 25. The syringe of claim 17, wherein the palm button device comprises a palm button and a mounting device for operatively connecting the palm button to the syringe. 26. The syringe of claim 25, wherein the mounting device comprises: a base extending from the palm button; and an adapter for attaching to the housing of the syringe, the base being movably coupled to the adapter. 27. The syringe according to claim 17, wherein the operation of the palm button device sets the syringe. 28. The syringe of claim 1, further comprising a gripping device for assisting a user in operating the syringe, the gripping device comprising: A sleeve, the sleeve being designed for ergonomic one-handed grip and operation of the syringe; and At least one hand rest extends from the sleeve for holding the user's hand on the sleeve when holding and operating the syringe. 29. The syringe of claim 28, wherein the sleeve of the gripping device has a polyurethane gel elastomer layer defining a hand grip portion. 30. The syringe of claim 28, wherein the sleeve has a top wall that acts as a stop for accurately positioning the sleeve on the syringe so that the user can operate the syringe with one hand. 31. The syringe of claim 30, wherein the top wall includes an opening for allowing a trigger button of the syringe to extend through the top wall. 32. The syringe of claim 28, wherein the at least one hand rest is pivotally connected to the sleeve. 33. The syringe of claim 32, wherein the at least one hand rest includes a protrusion that engages a sidewall of the housing when the at least one hand rest is in a clamping position, thereby removably attaching the gripping device to the syringe. 34. The syringe of claim 33 further includes a pawl device for holding the at least one hand rest in the clamping position. 35. The syringe of claim 28, wherein the contour of the at least one hand rest is shaped to receive the hypothenar eminence region of the user's hand. 36. The syringe of claim 28, wherein the gripping device is integrally formed with the syringe. 37. The syringe of claim 28, wherein the gripping device is removably attached to the housing of the syringe. 38. The syringe of claim 28, wherein the gripping device includes a locking device for non-removably attaching the gripping device to the housing of the syringe. 39. The syringe of claim 28, wherein the gripping device allows a user to set and initiate the injection operation process of the syringe. 40. The syringe of claim 28, wherein the gripping device allows a user to initiate the injection process of the syringe. 41. The syringe of claim 40, wherein the sleeve is slidably movable on the housing of the syringe to initiate the injection operation of the syringe. 42. The syringe of claim 1, further comprising a container or syringe disposed in the housing, the container or syringe containing a therapeutic product. 43. A device for use with a syringe having an injection needle, the device including a flexible extension for attaching to an injection end of the syringe, the flexible extension for stretching or pinching skin at a selected injection site, the device further including an adapter separate from and for attaching to the housing of the syringe, the flexible extension being removably attached to the adapter, the adapter having a hollow interior configured to receive the injection end of the syringe and an end of the flexible extension, the adapter including at least two inwardly projecting barbs configured to penetrate into and grip the outer surface of the injection end of the syringe to prevent removal of the adapter from the syringe. 44. The apparatus of claim 43, wherein the flexible extension has one or more annular protrusions or ridges formed in or on the working surface of the flexible extension. 45. The apparatus of claim 43, wherein the flexible extension has a plurality of nodules formed in or on the working surface of the flexible extension. 46. The apparatus of claim 43, wherein the flexible extension has a non-slip or textured working surface. 47. The device of claim 43, wherein the flexible extension is configured to be removably attached to the syringe. 48. The apparatus of claim 43, further comprising a locking device for removably attaching the flexible extension to the adapter, the locking device comprising an interlocking first member and a second member, the flexible extension comprising one of the first member and the second member, and the adapter comprising the other of the first member and the second member. 49. The device according to any one of claims 43 to 48, wherein the flexible extension is configured as a flange.