INJECTOR AND DEVICE FOR USE WITH AN INJECTOR HAVING AN INJECTION NEEDLE

专利摘要:
injector and devices. an injector such as a needle-type autoinjector having a flexible flange disposed at an injection end of the injector to stretch or compress the skin of the injection site. the flexible flange can be detachably attached to the injector or integrated into the injector during manufacturing. in addition, an injector having a palm button disposed on an injector activation end for activating an injector injection cycle. the palm button can be detachably attached to the injector or integrated into the injector during manufacturing. still further, a holding device for one-handed operation of an injector, the holding device having a sleeve and at least one palm rest coupled to the sleeve, the sleeve and hand rest providing ergonomic holding and operation of the injector. still additionally, an autoinjector needle shield having an enlarged, rounded flap for contacting the skin at the injection site.
公开号:BR112015008687B1
申请号:R112015008687-0
申请日:2013-10-18
公开日:2021-08-24
发明作者:Valerie M. Fenster；Stephanie Toy；Mark Ka Lai Lee；Denise Meyer
申请人:Amgen Inc；
IPC主号:

专利说明:

FIELD
[001] The present invention relates to self-injector devices. More particularly, the present invention relates to an autoinjector device having an ability to stretch and compress skin, an ergonomic autoinjector holding device, and other ergonomic improvements to autoinjectors. FUNDAMENTALS
[002] Self-injecting (AI) devices are held against the body, while an injection needle pierces the skin to administer a drug. While compressing the AI, the user applies a downward motion against the skin that activates the AI. The user then presses a button to make the needle inject and stop to move the drug down into the skin.
[003] During needle insertion and piston movement, the surface area / interface between the user's skin and the physical area of the AI touching the skin (and encompassing the needle) must remain in place to prevent AI slippage and/or needle or movement on the surface of the skin. This must be to allow full drug dose delivery, to prevent drug leakage on the skin surface, and most importantly, to prevent user injury from a bent or broken needle during the injection process. Also, for user comfort, it is advisable that the area of skin at the injection site, and directly under the AI, be kept taut to facilitate the injection procedure.
[004] Today's AI procedures advise users to stretch or compress the skin at the injection site with one hand and to maintain this stretch or compression when positioning the AI over the same area. With the AI in place, the user applies a downward force over the location area to activate or unlock the device. While keeping the skin taut or compressed with one hand and the AI gripped in position with the other, the user must then use the thumb of the hand holding the AI to press a button located on top of the AI, thus activating downward movement of the needle and plunger to inject the drug. After the injection is complete, the needle can be retracted from the skin and the user removes the device.
[005] During the act of positioning and activating the AI into place, users have been observed to: 1) lose concentration, letting go of stretched or compressed skin, and trying to maneuver the AI into place; 2) release stretched or compressed skin in order to squeeze the AI with two hands due to your lack of physical hand strength or dexterity; and 3) withdraw the device too soon before the injection is complete. Furthermore, the use of AIs can be a significant challenge for the elderly or users with compromised finger function and, consequently, treatment may be impaired.
[006] Therefore, there are several considerations for the front wall at the injection end of the AI. One such consideration is the ability of AIs to stretch the skin. The user is not expected to stretch the skin during injection with the AI, therefore it would be very beneficial to have a feature on the AI that will provide this function. Another consideration is to provide the AI with a feature that improves the stability of the AI so that it remains approximately perpendicular to the body during injection, thus allowing the user to operate the AI with one hand. Yet another consideration is that some commercial AIs require the application of an axial force to a trigger release mechanism on the front wall of the AI where it contacts the user's skin. Some body types have less surface tension and resistance to the required activation force thus causing the AI to press against the skin and deflect a significant amount into the body. Some patients do not apply the required activation force, thus not allowing the AI to arm and be ready to inject. Some commercial AIs have an activation button and shield trigger that must be pressed to arm and initiate delivery. Other commercial AIs only require a shield trigger to be pressed to arm and initiate delivery.
[007] Thus, methods are needed that solve the issues of positioning, activation and ergonomic design of conventional AIs. SUMMARY
[008] An injector comprising a housing having an injection tip, an injection needle wrapped within the housing, the injection needle penetrating the skin at a selected injection site and delivering a drug when an injection cycle of the injector is activated , and a flexible extension disposed at the injection end of the housing to stretch or compress the skin of the injection site.
[009] In some injector modes, the flexible extension can
[0010] In being integral with the housing.some modalities of the injector, the flexible extension can be detachably fixed to the housing.
[0011] Some embodiments of the injector may further comprise a locking arrangement to releasably secure the flexible extension to the housing, the locking arrangement including interlocking first and second members, the flexible extension including one of the first and second elements and the housing including the other of the first and second members.
[0012] In some injector modalities, the flexible extension can be selected from a kit of flexible extensions, in which one of the flexible extensions of the kit can be constructed to stretch the skin of the injection site and in which the other of the kit's flexible extensions can be constructed to compress the skin of the injection site.
[0013] In some injector embodiments, the flexible extension is non-removably attached to the injector housing.
[0014] Some embodiments of the injector may further comprise an adapter for attaching to an injector housing, wherein the flexible extension can be detachably attached to the adapter.
[0015] Some embodiments of the injector may further comprise a locking arrangement for detachably attaching the flexible extension to the adapter, the locking arrangement including interlocking first and second members, the flexible extension including one of the first and second members, and the adapter including the another from the first and second members.
[0016] In some injector embodiments, the flexible extension is constructed as a flange.
[0017] In some embodiments of the injector, the flexible extension is made of a polyurethane-silicon or polyurethane copolymer material.
[0018] Some embodiments of the injector may further comprise a needle shield to cover the injection needle after removing the injection needle from the skin of the injection site.
[0019] In some injector modalities, the flexible extension may be integral with the needle.
[0020] In some injector embodiments, the flexible extension can be detachably attached to the needle.
[0021] In some injector embodiments, the needle shield may be colored to indicate completion of the injection cycle.
[0022] Some embodiments of the injector may further comprise a soft shield attached to the needle shield, the shield to prevent the needle shield from contacting the skin at the injection site.
[0023] In some embodiments of the injector, the flexible extension may have one or more ring-shaped protrusions or ribs formed in or on a working surface of the extension.
[0024] In some embodiments of the injector, the flexible extension may have a plurality of protrusions formed in or on a working surface of the extension.
[0025] In some injector embodiments, the flexible extension may have a textured or tacky work surface.
[0026] Some embodiments of the injector may further comprise a palm button device for at least activating the injection cycle of the injector.
[0027] In some embodiments of the injector, the palm button device may have a mushroom-shaped palm button.
[0028] In some embodiments of the injector, the palm button device may have a cable-shaped palm button.
[0029] In some embodiments of the injector, the palm button device may comprise a palm button having at least one notch for placement of a user's thumb.
[0030] In some injector embodiments, the palm button may have a polyurethane gel elastomer coating.
[0031] In some modes of the injector, the palm button device may be integral with the injector.
[0032] In some embodiments of the injector, the palm button device may be detachably attached to the injector housing.
[0033] In some injector embodiments, the palm button device may be non-removably attached to the injector housing.
[0034] In some embodiments of the injector, the palm button device may comprise a palm button and a mounting arrangement for operatively coupling the palm button to the injector.
[0035] In some embodiments of the injector, the mounting arrangement may comprise a base extending from the palm button and an adapter for attaching to an injector housing, wherein the base is movably coupled to the adapter.
[0036] Some embodiments of the injector may further comprise a restraint device to assist a user in operating the injector, the restraint device comprising a sleeve for ergonomically holding and operating the injector with one hand and at least one hand rest extending outwardly from the sleeve to keep the user's hand in the sleeve when holding and operating the injector.
[0037] In some injector embodiments, the retainer sleeve may have a layer of polyurethane gel elastomer that defines a handshake.
[0038] In some embodiments of the injector, the sleeve may have a top wall operative as a stop to properly position the sleeve on the injector so that a user can operate the injector with one hand.
[0039] In some injector embodiments, the top wall may include an opening to allow an injector activation button to extend through the top wall.
[0040] In some embodiments of the injector, the at least one palm rest can pivotally engage to the sleeve.
[0041] In some embodiments of the injector, the at least one palm rest may include a projection that engages a side wall of the housing if the at least one palm rest is in a clamping position, thereby releasably securing the device. retention for the injector.
[0042] In some embodiments of the injector, the retaining device may further comprise a detent arrangement for retaining the at least one palm rest in the clamping position.
[0043] In some injector modalities, the at least one palm rest can be bypassed to receive the hypothenar muscular area of the user's hand.
[0044] In some embodiments of the injector, the retaining device may be integral with the injector.
[0045] In some injector embodiments, the retaining device may be detachably attached to the injector housing.
[0046] In some embodiments of the injector, the retaining device may include a locking arrangement for non-removably attaching the retaining device to the housing of the injector.
[0047] In some injector embodiments, the holding device may allow a user to arm and initiate the injector injection cycle.
[0048] In some injector modalities, the holding device may allow a user to initiate the injector injection cycle.
[0049] In some injector embodiments, the sleeve may be able to move slidingly in the injector housing to initiate the injector injection cycle.
[0050] Furthermore, an injector comprising a housing having an activation end and an injection end disposed opposite and in line with the activation end, and further comprising the previously described palm button device disposed at the activation end of the housing , in which the palm button device activates an injector injection cycle.
[0051] Furthermore, an injector comprising a housing and the retention device described above, to assist a user in the operation of the injector.
[0052] Further, a skin manipulation device for use with an injector having an injection needle, the device comprising a flexible extension for stretching or compressing the skin at the selected injection site.
[0053] In some embodiments of the skin handling device, the flexible extension may have one or more ring-shaped protrusions or ribs formed in or on a work surface thereof.
[0054] In some embodiments of the skin handling device, the flexible extension may have a plurality of protrusions formed in or on a work surface thereof.
[0055] In some embodiments of the skin handling device, the flexible extension may have a textured or tacky work surface.
[0056] In some skin manipulation device embodiments, the flexible extension may be integral with the injector.
[0057] In some embodiments of the skin handling device, the flexible extension can be detachably attached to the injector.
[0058] In some embodiments of the skin handling device, the flexible extension may further comprise an adapter to be attached to an injector housing, the flexible extension being detachably attachable to the adaptor.
[0059] Some embodiments of the skin manipulation device may further comprise a locking arrangement for detachably attaching the flexible extension to the adaptor, the locking arrangement 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.
[0060] Furthermore, a holding device to assist a user in the operation of an injector. The holding device may comprise a sleeve for ergonomically holding and operating the injector with one hand, and at least one palm rest extending outwardly from the sleeve to keep the user's hand in the sleeve while holding and operating the injector.
[0061] In some embodiments of the support device, the sleeve may have a layer of polyurethane gel elastomer that defines a handshake.
[0062] In some embodiments of the support device, the sleeve may have a top wall operative as a stop to properly position the sleeve on the injector so that a user can operate the injector with one hand.
[0063] In some embodiments of the support device, the top wall may include an opening for an injector activation button.
[0064] In some embodiments of the holding device, at least one palm rest can be hingedly coupled to the sleeve.
[0065] In some embodiments of the holding device, the at least one palm rest may include a projection for engaging a side wall of the housing, if the at least one palm rest is in a clamping position, thus allowing removable attachment of the retention device for the injector.
[0066] Some embodiments of the retaining device may further comprise a detent arrangement for retaining the at least one palm rest in the clamping position.
[0067] In some embodiments of the holding device, the at least one palm rest may be contoured to receive the hypothenar muscular area of the user's hand.
[0068] Some embodiments of the retaining device may further comprise a locking arrangement for non-removably attaching the retaining device to the injector housing.
[0069] Some modes of the holding device may allow a user to initiate the injector injection cycle.
[0070] In some embodiments of the retaining device, the sleeve may be able to be slidably moved in the injector housing to initiate the injector injection cycle.
[0071] Furthermore, a palm button device for at least activating one injection cycle of an injector. The palm button device may comprise a palm button and a mounting arrangement for operatively coupling the palm button to the injector.
[0072] In some embodiments of the palm button device, the mounting arrangement may comprise a base extending from the palm button and an adapter for attaching to an injector housing, wherein the base is movably coupled to the adapter .
[0073] In some embodiments of the palm button device, the palm button may have a mushroom shape.
[0074] In some embodiments of the palm button device, the palm button may have a handle shape.
[0075] In some embodiments of the palm button device, the palm button may have at least one notch for placing a user's thumb.
[0076] In some embodiments of the palm button device, the palm button may have a polyurethane gel elastomer coating.
[0077] In some embodiments of the palm button device, the adapter may non-removably attach to the injector housing.
[0078] Some modalities of the injectors described above may further comprise a container or syringe containing a therapeutic product. BRIEF DESCRIPTION OF THE DRAWINGS
[0079] Figure 1A is a sectional elevation view of an embodiment of a flexible skin handling flange detachably attached to or integrated with an autoinjector, prior to activation of an autoinjector injection cycle.
[0080] Figure 1B is a sectional elevation view of the flexible skin manipulation flange and autoinjector of Figure 1A, illustrating a user pressing the autoinjector down on the skin at the injection site during an autoinjector injection cycle.
[0081] Figure 2A is an end view of a flexible skin handling flange embodiment illustrating a flange surface facing the autoinjector.
[0082] Figure 2B is a sectional view through line 2B-2B of the flexible skin handling flange illustrated in Figure 2A.
[0083] Figure 3A is an end view of another embodiment of a flexible skin handling flange illustrating a flange surface facing the autoinjector.
[0084] Figure 3B is a sectional view through line 3B-3B of the flexible skin handling flange illustrated in Figure 3A.
[0085] Figure 4A is an end view of an autoinjector illustrating a surface of the autoinjector housing that has been adapted to engage a removable variant of a flexible skin handling flange.
[0086] Figure 4B is a sectional view of the flexible skin handling flange illustrated in Figures 2A and 2B detachably attached to the surface of the autoinjector housing illustrated in Figure 4A.
[0087] Figure 4C is a sectional view of the flexible skin handling flange illustrated in Figures 3A and 3B detachably attached to the surface of the autoinjector housing illustrated in Figure 4A.
[0088] Figures 4D-4F are section views of another embodiment of a docking arrangement that can detachably attach the SMF to the AI.
[0089] Figure 5A is a sectional view illustrating another embodiment of a flexible skin handling flange attached to a surface of an autoinjector housing having a layer or film of adhesive.
[0090] Figure 5B is a sectional view illustrating another embodiment of a flexible skin handling flange attached to the surface of an autoinjector housing having an adhesive layer or film.
[0091] Figure 6A is a sectional view illustrating another embodiment of a flexible skin handling flange attached to an edge surface of an autoinjector needle shield having a layer or film of adhesive.
[0092] Figure 6B is a sectional view illustrating another embodiment of a flexible skin handling flange attached to an edge surface of an autoinjector needle shield having a layer or film of adhesive.
[0093] Figure 7A is an elevation view illustrating the operation of a flexible skin handling flange having one or more ring-shaped protrusions or ribs provided on the working surface of the flange, which aid in spreading or stretching the S skin at the injection site. Figure 7A illustrates the radial flattening and expansion of the flange when the autoinjector is pressed down by a user during the activation of an injection cycle, thereby spreading or stretching the skin S at the injection site.
[0094] Figure 7B is an elevation view illustrating the operation of a flexible skin handling flange having a circle of protrusions or spaced protrusions provided on the working surface of the flange, which aids in spreading or stretching the skin S on the injection site. Figure 7B illustrates the flattening and radial expansion of the flange when the autoinjector is pressed down by a user during the activation of an injection cycle, thereby spreading or stretching the skin S at the injection site.
[0095] Figure 7C is an elevation view illustrating the operation of a flexible skin handling flange having a sticky or sticky texture provided on the working surface of the flange, which aids in spreading or stretching the skin S at the location of injection. Figure 7C illustrates the flattening and radial expansion of the flange when the autoinjector is pressed down by a user during the activation of an injection cycle, thereby spreading or stretching the skin S at the injection site.
[0096] Figure 8A is an elevation view illustrating an embodiment of a palm button device (shown in partial section) for an autoinjector.
[0097] Figure 8B is an enlarged sectional view illustrating one embodiment of a detent arrangement for coupling a base and an adapter to the palm button device of Figure 8A.
[0098] Figure 8C is an elevation view illustrating the palm button of Figure 8A attached to one embodiment of an autoinjector.
[0099] Figure 9A is an elevation view illustrating another embodiment of the palm button device (shown in partial section).
[00100] Figure 9B is a top plan view of the palm button of the device palm button of Figure 9A.
[00101] Figures 10A and 10B are elevation views of one embodiment of a hand holding device for one-handed operation of an autoinjector. Figure 10A illustrates the hand holding device with its hand rests arranged in an up position for packaging and Figure 10B illustrates the hand holding device affixed to an autoinjector embodiment having its hand rests in a down position .
[00102] Figures 10C and 10D are n enlarged sectional views of a palm rest mode. Figure 10C illustrates the palm rest in an up position and Figure 10D illustrates the palm rest in a down position engaging the autoinjector housing.
[00103] Figure 10E is a sectional view through line 10E-10E of Figure 10C.
[00104] Figure 10F is a sectional view through line 10F-10F of Figure 10D.
[00105] Figure 10G is an elevation view of another embodiment of a hand holding device attached to an embodiment of an autoinjector.
[00106] Figures 11A and 11B are elevation views of another embodiment of a hand holding device for one-handed operation of an autoinjector. Figure 11A illustrates the hand holding device and Figure 11B illustrates the hand holding device attached to an embodiment of an autoinjector.
[00107] Figure 12A is an elevation view illustrating an embodiment of an ergonomic needle shield for an autoinjector.
[00108] Figure 12B is a bottom plan view of an embodiment of an autoinjector illustrating the ergonomic needle shield and a skin handling flange that has been adapted for use with the needle shield.
[00109] Figure 12C is a sectional view through line 12C-12C of Figure 12A. DETAILED DESCRIPTION
[00110] Figures 1A and 1B illustrate an embodiment of a flexible skin manipulation flange-shaped extension (skin manipulation flange) 130 detachably attached to or integrated with an autoinjector (AI) 100 or other body injector. The Skin Handling Flange (SMF) 130 increases the surface area of the AI 100 at an injection end thereof and therefore provides the AI 100 with a stable platform that discourages skidding / device movement on the skin surface when the user feel the AI 100 completely pressed into 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, thus helping the user to keep the AI 100 at an angle. 90 degrees to the skin (injection angle preferred). The SMF 130 also facilitates device placement and simplifies the injection procedure by eliminating the step of stretching or compressing the skin for injection site preparation, thus allowing the user to freely use one or two hands to manipulate and stabilize the AI 100, keeps the skin held taut under the AI 100 for user comfort, allows the user, in some modalities, to view the injection needle through the SMF material, thus ensuring visual feedback that the injection needle is in place and/or after completion of the injection, the injection needle is retracted. The SMF 130 does not uncomfortably adhere to the skin using glue or adhesive coating and can be constructed, shaped, and adapted to accommodate any autoinjector or in-body injectors positioned on the skin.
[00111] The AI 100 may conventionally comprise a medicine container carrier 102, a container or syringe 104 pre-filled with a fluid-based medicine, a drive unit 106, a drive and activation control unit 108, a housing 110 for enclosing one or more of the medication container carrier 102, the container 104, the drive unit 106, and the drive and activation control unit 108. The AI 100 may also comprise a needle shield or shield 112 disposed. inside (as shown) or external to housing 110. Container or syringe 104 may include an injection needle 116 and a stop 118 for dispensing medication. Container carrier 102 may be configured to receive and retain container 104 in defined relationship to housing 110 and be axially movable with respect to housing 110, for needle penetration purposes, between a rear position and a front position, movement between these positions is used for needle penetration. Housing 110 100 of the AI may have a first or rear end wall 120 and an opposing second or front end wall 122, which define actuating and injection ends of the AI 100, respectively. injection needle opening 124 which allows injection needle 116 of the container or syringe 104 to extend therethrough during operation of the AI 100, as illustrated in Figure 1B. Drive unit 106 may include a self-penetrating mechanism for moving carrier 102 or container 104 relative to housing 110 or carrier 102, respectively to insert injection needle 116 into the skin S. Drive unit 106 may further include a self-injection mechanism for moving or dipping the stop 118 through the container or syringe 104 to dispense the medication, and a needle shield deployment mechanism for deploying the needle shield 112 around the injection needle 116 after completion of the injection. . If the AI 100 is not provided with the optional needle shield 112, the self-penetration mechanism can also be configured to automatically withdraw the injection needle 116 back into the housing 110. The various drive unit mechanisms can utilize stored energy in any known form including, without limitation, electrical, mechanical (e.g., elastic member such as springs), gas pressure, gas release, and any combination thereof. The stored energy can be transmitted by corresponding conventional transmission mechanisms, eg electromechanical, such as electric motors or solenoids, hydraulics, pneumatics, mechanical springs, gears, rods, and so on. Drive activation and control unit can be provided to activate and sequence the drive mechanisms of drive unit 106 and can comprise any well-known type of releasable locking arrangements, electronic controllers, their combinations, and so on. The actuation and activation control unit 108 can be both armed and injection initiated by a button or switch 114 extending through the rear end wall 120 of the housing 110 at the activation end of the AI 100. In other embodiments, the needle shield 112 may extend slightly beyond the front end wall 122 of the AI housing 110 and be adapted to function as a trigger for arming the trigger and trigger control unit 108 when the needle shield 112 is pressed by contact with the skin. In these other embodiments, depression of the enable button 114 would cause the trigger and enable control unit 108 to initiate delivery.
[00112] The SMF 130 extends the surface area of the injection tip (front wall 122) of the AI 100, which contacts the skin S of the injection site during initial activation and/or unblocking. As the user presses down to cock the AI 100, the SMF 130 gently stretches the taut skin S, and out of the way of the center of the injection site and injection needle 116 of the AI 100.
[00113] As collectively illustrated in Figures 2A, 2B, 3A, and 3B, the SMF 130, 230 may comprise a flexible, annular body 132, 232 having a first end surface 134, 234, a second opposite end surface 136 , 236, a cylindrical side surface 138, 238 extending between the first end surface 134, 234 and the second end surface 136, 236, and an aperture 140, 240 extending through a generally central portion of the body 132, 232. embodiments of the SMF 130, 132 may optionally include protrusions 142, 242 disposed on the first surface 134, 234 thereof, the purpose of which will be explained later. In some embodiments, the SMF 130, 230 can be made from a flexible material, such as clear polyurethane or silicone-polyurethane copolymer, which allows the user to see injection needle 116 through the SMF 130, 230 during an injection. . In other embodiments, the SMF 130, 230 can be made from a translucent or opaque polyurethane material, a nitrile rubber copolymer material, or any other suitable material capable of flexing. As shown in the embodiment illustrated in Figures 2A and 2B, the side surface 138 of the SMF 130 can be constructed to flare outwardly from the first surface 134 to the second surface 136 to allow the SMF 130 to be easily compressed and flattened, as illustrated in Figure 1B, by pressing the AI 100 down onto the skin S at the injection site, thus maximizing the radial expansion of the SMF 130, in particular the second surface 136 thereof. As shown in Figures 1A and IB, opening 140 of SMF 132 aligns axially with injection needle opening 124 formed in front end wall 122 of AI housing 110 to allow injection needle 116 of container or syringe 104 extend through it during operation of the AI 100.
[00114] In certain embodiments, the SMF can be a separate accessory that the user can detachably attach to AI at injection time. In such modalities, the SMF can be selected from a kit of differently configured SMFs. The kit may be provided with the AI or be available separately for use with the AI. For example, but not limiting, one or more of the SMFs can be configured to spread or stretch stretched skin at the injection site while one or more of the other SMFs can be configured to compress the skin at the injection site. Thus, the user can select the desired one of the SMFs in the kit depending on whether the user wants a skin spreading or skin compression effect. In some modalities, the SMF can be configured to either spread/stretch the skin or compress the skin at the injection site, depending on whether the user is pressing down on the AI or lifting it up.
[00115] Any suitable coupling arrangement can detachably attach the SMF to the AI 100. Figures 4A-4C illustrate one embodiment of a torsion locking arrangement that can be used to detachably attach the SMF 130, 230 illustrated in Figures 2A-2B and Figures 3A-3B, to the AI 100. The torsion locking arrangement may comprise two or more arcuate slots 126 formed in the front end wall 122 of the AI 100 in, for example, a circularly spaced arrangement. The twist locking arrangement may further comprise a corresponding number of protrusions 142, 242 formed on the first surface 134, 234 of the SMF 130, 230 in, for example, a circularly spaced arrangement. Protrusions 142, 242 of SMF 130, 230 are configured to slideably move within arcuate slots 126 formed in front end wall 122 of AI 100. Although not shown, the two or more arcuate slots may be formed in the first end surface of the SMF and the corresponding number of protrusions can be formed on the front end wall of the AI. The protrusions 142, 242 may have a pin head configuration or any other suitable configuration capable of being removably retained in the arcuate slots. One end 128 of each of the arcuate slots 126 can be enlarged to allow insertion and removal of the pinhead protrusions of 142, 242. To secure the SMF 130, 230 to the injection end of the AI 100, the user can insert the protrusions 142, 242 at the flared ends 128 of the arcuate slots 126 and twist the SMF 130, 230 in a first direction relative to the AI 100 to lock the SMF 130, 230 into the AI 100. The SMF 130, 230 can 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 SMP 130, 230 from the AI 100.
[00116] Figures 4D-4F illustrate another embodiment of a coupling arrangement that can detachably attach the SMF 130, 230 to the AI 100. The coupling arrangement comprises an adapter collar 260, which slides over the injection end of the AI 110 housing and allows a snap-in locking 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 AI 110 housing. Metal sleeve may comprise two or more spaced apart barb-like fasteners 274 formed on an interior surface 272 of metal sleeve 270. Metal sleeve 270 may be installed on adapter collar 260 on an interior surface 266 thereof adjacent to a first open end 262 of collar 260. Metal sleeve 270 is sized to friction fit against interior surface 266 of adapter collar 260 so that it will not pull off collar 260 to d. and snap an SMF 130, 230 from collar 260 or snap an SMF 130, 230 to collar 260. When adapter collar 260 is pressed onto the injection end of the AI housing 110, the barb clamping elements 274 of the sleeve metal 270 can dig and pinch the AI housing 110 thus preventing removal of the adapter collar 260 from the AI, particularly when disengaging an SMF 130, 230 from the collar 260. A first member 268 of a snap-in locking arrangement may be formed on the inner surface 266 of the adapter collar 260 adjacent a second open end 264 thereof, and a second member 276 of the interlocking arrangement may be formed on the side surface 138, 238 of the SMF 130, 230 adjacent the first end surface. 134, 234 of the same. One of the first and second members 268, 276 of the mortise locking arrangement may comprise a continuous or segmented bead (e.g., first member 268 illustrated in Figures 4D-4F) and the other of the first and second members 268, 276 may comprise a continuous or segmented groove (eg, second member 276 illustrated in Figures 4D-4F) adapted to removably receive the bead in a snap fit shape. The snap-on locking arrangement allows users with hand strength / dexterity issues to easily position and withdraw a desired SMF 130, 230.
[00117] According to other embodiments, the SMF 130, 230 can be integrated into or permanently connected to the AI 100 during fabrication. In some such embodiments, permanent integration or 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 AI housing 110 with a layer or film 150 250 µg of adhesive as illustrated in Figures 5A and 5B. In other embodiments, permanent attachment or 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 shield 112 with a layer or film 152, 252 of adhesive, as illustrated in Figures 6A and 6B.
[00118] Referring now to Figures 7A-7C, the second end surface 134, 234 of the SMF 130, 230 may be provided with features, which aid in spreading or stretching the skin S at the stretched injection site under the SMF 130, 230, when the SMF 130, 230 is pressed down to radially expand the SMF 130, 230. For example, in some embodiments, the second surface 134 of the SMP 130 (Figures 2A and 2B) may be provided with one or more protrusions or ring-shaped ribs 244, as illustrated in Figure 7A, or with a circle of bulges or spaced protrusions 148, as illustrated in Figure 7B, which are selectively positioned to grip, stretch, and stabilize the skin S under the SMF 130, when the SMF 130 compresses, flattens, and expands radially in response to the AI 100 being pressed down into the skin S at the injection site. When the AI 100 is lifted out of the S-head, the SMF 130 returns to its original uncompressed and peeled-off shape, thereby releasing the S-head.
[00119] If skin compression S is desired, the ring-shaped protrusions or ribs of the SMF 130 illustrated in Figure 7A can also be used to lift skin S to the SMF 130 to simulate skin compression by slightly lifting it on the AI 100 after compressing and flattening the SMF 130.
[00120] In some embodiments, the second end surface 236 of the SMF 230 (Figures 3A and 3B) may be provided with a tacky or tacky texture, as illustrated in Figure 7C, that retains, stretches and stabilizes the skin under the SMF, when the SMF compresses, flattens, and expands radially in response to the AI 100 being pressed down into the skin at the injection site. When the AI 100 is lifted out of the skin, the SMF returns to its original shape and releases the skin. If skin S compression is desired, the sticky or tacky texture provided on the second end surface 236 of the SMF 230 can also be used to lift skin S to simulate skin compression by lifting slightly over the AI 100 then compressing and flattening the SMF 230.
[00121] Figure 8A illustrates an embodiment of a palm button device 330 to easily arm and initiate needle injection of an AI. Palm button device 330 generally comprises a palm button 331 and a mounting arrangement 340 for affixing palm button device 330 to an AI. The 330 palm button device provides better AI stability and easy activation with palm operation than finger operation, and allows one-handed operation of the AI. In addition, the 330 palm button device makes it easier to train a user to manipulate and use the AI.
[00122] Referring now to Figures 8A-8C, the palm button 331 of device 330 may have a flat bottom surface 332 and a curved top surface 334. The curved top surface 334 can be sized to accommodate the interior surface or the user's palm so that the 331 palm button naturally conforms to most hand profiles. In some embodiments, the 331 palm button can be 6.0 cm long, 4.5 cm wide and 3.5 cm high. In other embodiments, the palm button 331 may have other dimensions. The curved top surface 334 provides an ergonomic actuation surface for the palm button 331 so the user can arm and initiate the needle injection cycle of an AI with a palm push motion. In some embodiments, the curved top surface 334 of palm button 331 may be mushroom shaped or hemispherical in shape to maximize compression and easy pressure of palm button 331.
[00123] The mounting arrangement 340 may comprise a base 342 extending from a generally central portion of the bottom surface 332 of the palm button 331 and an adapter 350 movably or telescopically disposed within the base 342. The mounting arrangement 340 mechanically and functionally couples the palm button device 330 to an AI 300 (Figure 8C). More specifically, base 342 of mounting arrangement 340 operatively couples palm button 330 of device 330 to activation button 314 of AI 300 and mechanically couples palm button 330 to adapter 350. Adapter 350, in turn, is constructed to be pressed against the actuating end 320 of the AI housing 310 to mechanically couple the palm button device 330 to the AI 300. The base 342 of the mounting arrangement 340 may comprise a top wall 344 and a cylindrical sidewall 346 depending from the periphery of the top wall 344. A biasing element 348, such as a coil spring, may extend downwardly from the top wall 344 of the base 342. mount 340 may comprise a top wall 352 and a cylindrical side wall 354 depending from the periphery of the top wall 352. The top wall 352 may include an opening 356 to enable the activation button 314 of the AI 300 extends through it. Adapter 350 may further include a metal sleeve 360 comprising two or more spaced apart barb-like fasteners 36 projecting from an inner surface 362 of metal sleeve 360. Metal sleeve 360 may be disposed on an inner surface 358 of the wall side of adapter 354 in a friction fit mode so that the metal sleeve 360 will not pull out of the adapter 350 when operating the AI 300. When the adapter 350 is slidably positioned on the activation end of the AI 310 housing , the barb-like clamping elements 364 of the metal sleeve 360 can dig and squeeze the AI 310 housing, thus preventing the removal of the palm button device 330 from the AI 300. When the user presses the palm button 331 downwards to arm and initiate the injection cycle of the AI 330, the push element 348 presses the activation button 314 of the AI 300 down and becomes compressed between the top wall 344 of the base 342 and the AI 300 enable button. When the user releases the palm button 331, the compressed pressure element 348 returns the palm button 331 to the non-pressed position and allows the AI 330 enable button 314 to return to the position. not pressed.
[00124] As best illustrated in Figure 8B, a detent arrangement 370 may be provided to prevent the base 342 from being removed from the adapter 350 when the palm button 331 is in an unpressed state, and to enable the base 342 move down relative to adapter 350 when palm button 331 is pressed. A first member 372 of the detent arrangement may be formed on an interior surface 347 of the base 342 and a second member 374 of the detent arrangement may be formed on an exterior surface 355 of the adapter 350. One of the first and second members 372, 374 of the detent arrangement may comprise a continuous or segmented, wedge-shaped, face-down projection (e.g., the first member 372 illustrated in Figures 8A-8C) and the other of the first and second members 372, 374 may comprise a projection. continuous or segmented, facing down, wedge-shaped (e.g., second member 374 illustrated in Figures 8A-8C), which is adapted to receive wedge-shaped projection 372.
[00125] The palm button device 330 may be made of a plastic material or any other suitable material including metals, hard rubber, and fiberglass. A soft, grippy coating 336 can be disposed on top surface 334 of palm button 331 to provide palm button 331 with a softer feel and grip. Coating 336 can be a polyurethane gel elastomer layer or silicone-polyurethane copolymer layer.
[00126] In some embodiments, the palm button 331 of the palm button device 330 can be integrated into the AI during manufacturing, rather than being adapted for installation in existing AIs. For example, in some embodiments, palm button 330 can be adapted to replace the conventional AI activation button, as illustrated in Figure 8D.
[00127] Figures 9A and 9B illustrate another embodiment of the palm button device 430 where like elements are identified by the same reference numerals. The palm button device 430 is similar to the palm button device 330 illustrated in Figures 8A-8C, except for the palm button structure 431, having an elongated shape formed by top and bottom walls 432 and 434, respectively. which are connected by side walls 438, and end walls 440. Therefore, palm button 431 and mounting arrangement 340 define a T-shaped cable structure. Polyurethane gel elastomer layer 436 can be arranged over the top wall 432 of the 431 palm button to provide the 431 palm button with a softer feel and grip. In some embodiments, palm button 431 may be 10.0 cm long, 4.0 cm wide, and 2.0 cm high, although other embodiments of palm button 431 may have other dimensions. In some embodiments, the palm button 431 may have recessed side areas 442 (best illustrated in Figure 9B) to receive the user's thumb so that the user can more easily grasp or hold the palm button 431. In addition, the button Palm 431 can be configured for both left and right hand use.
[00128] Figures 10A and 10B illustrate an embodiment of a 530 hand holding device (HH) for use with an AI 500. The 530 HH device provides an ergonomic shape for better ease of use due to the various physical limitations of a user's disease state. The HH device 530 may comprise a sleeve 532 which functions as a handgrip, and one or more hand rests 540 pivotally connected to the sleeve 532 (two opposing hand rests 540 are illustrated in Figures 10A and 10B).
[00129] Sleeve 532 may comprise a top wall 534 and a cylindrical side wall 536 that depends from the periphery of top wall 534. Wall 534 may include an opening 538 to allow activation button 514 of the AI 500 to extend through it. Top wall 534 of sleeve 532 can operate as a stop to correctly position sleeve 532 on AI 500 during installation thereof. Once installed, the sleeve 532 of the HH 530 device forces the user to squeeze the AI 500 into place so that the user can use the same hand to comfortably hold, stabilize, and press the AI 500's activation button 514.
[00130] Referring now to Figures 10C-10F, the hand rests 540 of the HH 530 device can be constructed as arm-like members. The palm rest arms 540 may be pivotally connected to the sleeve 532 by pivot pin structures. As best illustrated in Figures 10E and 10F, each pivot pin structure may include a slot 552 formed in sleeve 532, a pair of axially aligned pivot pins 554, and a pair of axially aligned pivot pin receiving openings 556. slots 552 may be formed just above open end 533 of sleeve 532. Pivot pins 554 may extend from side edges 553 of slots 552 and pivot pin receiving openings 556 may be formed on side surfaces542 of the rest arms 540, beside the 544 attachment ends of the palm rest arms 540. The pivot pin structure allows the handrest arm 540 to be pivoted between an up position (Figure 10A) and a down position (Figure 10B). In the down position, the palm rest arms 540 extend from and are generally perpendicular to the sleeve 532 and therefore operated to hold the user's hand on the AI 500 in the proper position by preventing the user's hand from sliding down the sleeve. 532 and for the AI 500. The palm rest arms 540 can be contoured to receive the hypothenar muscle area of the user's hand next to the little finger ("digiti minimi"). The palm rest arms 540 can also function as clamps in the down position to secure the HH 500 device to the AI 500. As best illustrated in Figures 10E and 10F, the hand rest arms 540 in such embodiments each may include a projection 546 on the attachment end 544 thereof (Figure 10C and 10D), which engages the housing 510 of the AI 500 when the palm rest arm 540 is in the down position, thus allowing the arm 540 to secure and secure the device. HH 500 for the AI 500. In addition, each of the palm rest arms 540 can be provided with a retaining arrangement to hold the palm rest arms 540 in the down (grip) position. The detent arrangement may comprise a projection 560 extending from each side surface 542 of the palm rest arm 540 and a recess 562 formed in the surface of each side edge 553 of the slot 552. When the hand rest arm 540 is in position upwardly, as illustrated in Figure 10E, the projections 560 of the detent arrangement slidingly engage the side edge surfaces 553 of the slot 552. When the palm rest arm 540 is pivoted down to the clamping position, as illustrated in the Figure 10F, projections 560 slide along side edge surfaces 553 of slot 552 and enter recesses 562, thereby locking palm rest arm 540 in the down and clamping position. The detent arrangement can be unlocked by applying an upward force to the palm rest arm 540, which is sufficient to withdraw the projections 560 from the recesses 562, thus allowing the arm 540 to be rotated back to the up position. .
[00131] According to other embodiments, an adhesive or a metallic sleeve comprising spaced apart barb-like clamping members similar to the metallic sleeve described above with respect to the palm button device may be provided on the inner surface of the sleeve 532 to secure the device from HH 530 to the AI 500. The adhesive or metal sleeve can be used in addition to the handrest arms 540 with the previously described attachment structures or alone with the handrest arms 540 that do not have the attachment structures.
[00132] When the palm rest arms 540 are in the up position, as illustrated in Figure 10A, the HH device 530 can be easily packaged. Once removed from the packaging, the HH 530 device can be installed into the AI 500. During installation, the HH 530 device can be slidably positioned over the end of the AI 500 until the activation button 514 extends through the opening 538 in the wall of top 534 of sleeve 532 and top wall 534 engage the end wall of the AI 500 that surrounds the activation button 514, thereby correctly positioning the sleeve of the HH device on the AI. The palm rest arms 540 can then be pivoted down from the up position to the down position where the hand rest arms 540 can engage the AI 500 to secure the HH device 530 to the AI 500 and avoid the downward sliding of the user's hand as described above.
[00133] As illustrated in Figure 10G, some embodiments of the HH 530 device may have a sleeve 572 with a 574 contoured handgrip that enhances the ergonomic holding function of the HH 530 device. with sleeve 572 or applied to sleeve as a separate layer or false cuff. Separate layer or faux cuff types of 574 handgrips can be made of a soft polyurethane gel elastomer material, or any other material suitable for finger or hand grips.
[00134] Figures 11A and 11B illustrate another embodiment of a hand holding device (HH) 630 for use with an AI 600. The HH device 630 may comprise an open end sleeve 632 and a hand rest arrangement Fixed hand rest 640 disposed over one of the open ends of sleeve 632. Fixed hand rest arrangement 640 may be a unitary member that includes a top wall 642 and two L-shaped hand rests 644 that hang from the periphery of the wall. top 642. The lower portion 645 of each palm rest extends outward from the sleeve and can be contoured to receive the hypothenar muscle area of the user's hand alongside the little finger (digiti minimi). The top wall 642 may include an opening 646 to allow the activation button 614 of the AI 600 to extend therethrough. As in the prior embodiment, top wall 642 can function as a stop to correctly position sleeve 632 on AI 600 during installation thereof. Once installed, the sleeve 632 of the HH 630 device forces the user to squeeze the AI 600 into place so that the user can use the same hand to comfortably hold, stabilize, and press the AI 600's activation button 614. hand rest arms hold the user's hand on the AI 600 in the correct position by preventing the user's hand from sliding down the sleeve 632 and onto the AI 600. The inner surface of sleeve 632 of the HH 630 device can be supplied with a metal sleeve having spaced apart barb-like fasteners similar to the metal sleeve described above with respect to the palm button device, for affixing the HH 630 device to the housing 610 of the AI 600. An adhesive can also be used alone or with the metal sleeve or other mechanical means, for affixing the HH 630 device to the housing 610 of the AI 600.
[00135] The HH device can be supplied as an accessory item to the AI or integrated into the AI. In some embodiments, the HH device can function as an extension to the AI housing once attached or attached to the AI, thus functioning as an ergonomic retention feature as described above. The HH device can be used on several types of AIs, including AIs that only have a single activation feature (eg a needle shield) and AIs that have two activation features (eg a needle shield and a button. activation). In some embodiments, the activation button can be located on the side of the AI instead of the top or back wall of the AI.
[00136] In other embodiments, the HH device can be constructed and adapted as an active component of the AI, such that once affixed, attached, or positioned on the AI, it can operate to activate the AI activation button on response to the application of a downward force on the HH device that causes the HH device sleeve to move axially relative to the AI housing and press the AIs activation button. Such modalities will allow the user to use the ergonomic design benefit of the AIs to provide additional leverage for pressing the activation button (for AIs having two activation features (eg a needle shield and an activation button).
[00137] In still other embodiments, the HH device can be permanently attached to the AI during fabrication. In such embodiments, the HH device can be constructed and adapted as a single or multiple use component.
[00138] Figures 12A-12C illustrate an embodiment of a needle shield 712 for use in an AI 700. The needle shield 712 may be cylindrical in shape and includes a first edge surface 713 and an opposing second edge surface 715. to the first edge surface 713. The needle shield 712 can be constructed so that the second edge surface 715 contacts the skin at the injection site during operation of the AI. As illustrated in Figures 12A and 12C, the second edge surface of the needle shield can be configured as an enlarged rounded flap that contacts the wearer's skin more comfortably. The 715 rounded flared flap has a larger surface area than the sharp edges of conventional needle shields, thus making skin contact more comfortable during the injection process. As illustrated in Figure 12B, the above-described SMFs 130, 230 can be modified for use with AIs using the needle shield of the present disclosure, by increasing the diameter of the needle aperture 140, 240 extending through the SMF 130, 230, to accommodate the 715 rounded flared flap of the needle shield.
[00139] In some embodiments, the 700 needle shield may be colored to indicate to the user that the injection is complete. More specifically, when the injection cycle has been completed and the colored needle shield 712 is subsequently implanted to cover the exposed injection needle, the colored implanted needle shield 700 indicates to the user that the injection is complete.
The syringe or other primary AI container can be prefilled with a pharmaceutical, such as an erythropoiesis stimulating agent (ESA), which can be a liquid or in a lyophilized form. An ESA may be an erythropoiesis-stimulating protein. As used herein, "erythropoiesis-stimulating protein" means any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to and causing dimerization of the receptor. Erythropoiesis-stimulating proteins comprise erythropoietin and variants, analogs, or derivatives thereof that bind to and activate the erythropoietin receptor; antibodies that bind to the erythropoietin receptor and activate the receptor; or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis-stimulating proteins comprise, but are not limited to, epoetin alfa, epoetin beta, epoetin delta, epoetin omega, epoetin iota, epoetin zeta, and their analogues, pegylated erythropoietin, carbamylated erythropoietin, EMP1 peptides and antibodies (comprising EMP1) mimetics. Exemplary erythropoiesis-stimulating proteins comprise erythropoietin, darbepoetin, erythropoietin agonist variants, and peptides or antibodies that bind to and activate the erythropoietin receptor.
[00141] The term erythropoiesis-stimulating protein comprises without limitation Epogen® (epoetin alpha), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxy polyethylene glycol - epoetin beta), Hematide ™ (peginesatide), MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo™ (epoetin zeta), Binocrit® (epoetin alpha), epoetin alfa Hexal, Abseamed ™ (epoetin alpha), Ratioepo ™ ( epoetin theta), Eporatio™ (epoetin theta), Biopoin™ (epoetin theta), epoetin alfa, epoetin beta, epoetin zeta, epoetin theta, and epoetin delta.
The term erythropoiesis-stimulating protein further comprises the molecules or variants or analogs as described in the following patents or patent applications, which are each incorporated herein by reference in their entirety: US Patent Nos. 4,703,008.; 5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078; 5,773,569; 5,830,851; 5,856,298; 5,955,422; 5,986,047; 6,030,086; 6,310,078; 6391,633; 6,583,272; 6,586,398; 6,900,292; 6,750,369; 7,030,226; 7,084,245; and 7,271,689; US Publication Nos. 2002/0155998; 2003/0077753; 2003/0082749; 2003/0143202; 2003/0215444; 2004/0009902; 2004/0071694; 2004/0091961; 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 Publication Nos. WO 91/05867; WO 95/05465; WO 96/40772; WO 99/66054; WO 00/24893; WO 01/81405; WO 00/61637; WO 01/36489; WO 02/014356; WO 02/19963; WO 02/20034; WO 02/49673; WO 02/085940; WO 03/029291; WO 2003/055526; WO 2003/084477; WO 2003/094858; WO 2004/002417; WO 2004/002424; WO 2004/009627; WO 2004/024761; WO 2004/033651; WO2004/035603; WO 2004/043382; WO 2004/101600; WO 2004/101606; WO 2004/101611; WO 2004/106373; WO 2004/018667; WO2005/001025; WO 2005/001136; WO 2005/021579; WO 2005/025606; WO 2005/032460; WO 2005/051327; WO 2005/063808; WO2005/063809; WO 2005/070451; WO 2005/081687; WO 2005/084711; WO 2005/103076; WO 2005/100403; WO 2005/092369; WO2006/50959; WO 2006/02646; WO 2006/29094; and WO 2007/136752.
Alternatively, the syringe or other primary AI container can also be pre-filled with other products. Examples of other pharmaceuticals that may be used may include, but are not limited to, therapeutic agents, such as a biological (eg, Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNF blocker), anti-antibodies. -TNF such as adalimumab, infliximab, certolizumab pegol, and golimumab; anti-IL-12 antibodies such as ustekinumab, other Fc fusions such as CTL4A:Fc also known as abacept; Neulasta® (Filgastrim pegylated, G-CSF pegylated, pegylated hu-met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-met-G-CSF), Nplate® (romiplostim), Vectibix® (panitumumab), Sensipar® (cinacalcet) and Xgeva® and Prolia® (each denosamab, AMG 162); as well as other small molecule drugs, therapeutic antibodies, some polypeptides, proteins or other chemicals such as iron (eg ferumoxytol, iron dextrans, ferric gluconate, sucrose and iron). The therapeutic agent can be in liquid form, or reconstituted from a in a lyophilized form.
[00144] Among the specific illustrative proteins that can be used in the syringe or other primary AI container are antibodies, peptibodies, pegylated proteins, polypeptides and related proteins (comprising fusions, fragments, analogs, variants or their derivatives), e.g., proteins that specifically bind to: OPGL; IL-4 receptor; interleukin 1-receptor 1 ("IL1-R1"); angiopoietin-2 (Ang2); NGF; CD22; IGF-1; Related protein 1 B-7 (B7RP1); IL-15; IL-17 A receptor: IFN gamma; TALL-1; parathyroid hormone ("PTH"); thrombopoietin receptor ("TPO-R"); hepatocyte growth factor ("HGF"); TRAIL-R2; Activin A; TGF-beta; amyloid-beta; c-Kit; α4β7: and IL-23 or one of its subunits; and other therapeutic proteins.
The syringe or other primary AI container may also be pre-filled with OPGL-specific antibodies, peptibodies, and related proteins, and the like (also referred to as RANKL-specific antibodies, peptibodies, and the like), comprising OPGL-specific antibodies. fully humanized and human, particularly fully humanized monoclonal antibodies, comprising, but not limited to the antibodies described in Publication No. WO 03/002713, which is incorporated herein in its entirety as for OPGL specific antibodies and antibody-related proteins, particularly those which have the sequences attached thereto, particularly, but not limited to, those indicated herein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, comprising the OPGL specific antibodies with either the light chain of SEQ ID NO:2 herein as defined in Figure 2 within it and/or the heavy chain of SEQ ID NO:4 within it as defined in Figure 4 herein, each is individually and specifically incorporated herein by reference in its entirety as disclosed in the foregoing publication.
The syringe or other primary AI container may also be prefilled with the myostatin binding proteins, peptibodies, and related proteins, and the like, comprising myostatin-specific peptibodies, particularly those described in US Publication No. 2004/ 0181033 and Publication No. WO 2004/058988, which are incorporated herein by reference in their entirety, in particular parts pertinent to myostatin-specific peptibodies, comprising, but not limited to, mTN8-19 family peptibodies, comprising those of SEQ ID NOS : 305-351, comprising TN8-19-1 to TN8-19-40, TN8-19 con1 and TN8-19 con2; peptibodies from the ML2 family of SEQ ID NOS: 357-383 herein; the 111L15 family of SEQ ID NOS: 384-409; the ML17 family of SEQ ID NOS: 410-438 herein; the ML20 family of SEQ ID NOS: 439-446 herein; the ML21 family of SEQ ID NOS: 447-452 herein; the ml24 family of SEQ ID NOS: 453-454 herein; and SEQ ID NOS: 615-631 herein, each being individually and specifically incorporated herein by reference in its entirety as disclosed in the foregoing publication.
The syringe or other primary AI container may also be pre-filled with IL-4 receptor specific antibodies, peptibodies, and related proteins, and the like, particularly those that inhibit the activities mediated by binding of IL-4 and / or IL-13 for the receptor, comprising those described in Publication No. WO 2005/047331 or PCT Application No. PCT / US2004 / 03742 and in US Publication No. 2005/112694, which are incorporated herein by reference in their entirety, particularly in the parts pertinent to IL-4 receptor specific antibodies, especially antibodies as described herein, in particular, and without limitation, those designated herein: 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 specifically incorporated herein by reference in its entirety as disclosed in the foregoing publication.
The syringe or other primary AI container may also be pre-filled with IL1-R1 specific antibodies, peptibodies, and related proteins, and the like, comprising, but not limited to, those described in US Publication No. 2004/097712A1, which is incorporated herein by reference in its entirety in parts pertinent to IL1-R1 specific binding proteins, monoclonal antibodies, in particular, in particular, without limitation, those designated herein: 15CA, 26F5, 27F2, 24E12 and 10H7, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the aforementioned US publication.
The syringe or other primary AI container may also be pre-filled with Ang2 specific antibodies, peptibodies, and related proteins, and the like, comprising, but not limited to, those described in PCT Publication No. WO 03/057134 and Publication US 2003/0229023, each of which is incorporated herein by reference in its entirety, particularly in parts pertinent to Ang2 specific antibodies and peptibodies and the like, especially those of sequences described herein and comprising, but not limited to: L1 (N ); L1(N)WT; L1 (N) 1K WT; 2xL1 (N); 2xL1(N)WT; Con4 (N), Con4 (N) 1K WT, 2xCon4 (N) 1K; L1C; L1C 1K; 2xL1C; Con4C; Con4C 1K; 2xCon4C1K; Con4-L1(N); Con4-LLC; TN-12-9 (N); C17 (N); TN8-8 (N); TN8-14 (N); Con 1 (N), further comprising anti-Ang 2 antibodies and formulations such as those described in Publication No. WO 2003/030833, which is incorporated herein by reference in its entirety as thereto, particularly Ab526; Ab528; Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543;Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12; Ab1A1; Ab1F; Ab1K, Ab1P; and Ab1P, in its various permutations as described therein, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the foregoing publication.
The syringe or other primary AI container may also be pre-filled with NGF-specific antibodies, peptibodies, and related proteins, and comprising, as, in particular, but not limited to those described in US Publication No. 2005/0074821 and US Patent No. 6,919,426, which are incorporated herein by reference in their entirety, particularly as NGF-specific antibodies and related proteins in this regard, particularly comprising, but not limited to, NGF-specific antibodies designated therein. 4D4, 4G6, 6H9, 7h2, 14D10 and 14d11, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the preceding publication.
The syringe or other primary AI container may also be pre-filled with CD22-specific antibodies, peptibodies, and related proteins, and the like, such as those described in US Patent No. 5,789,554, which is incorporated herein by reference in its entirety as CD22-specific antibodies and related proteins, particularly human CD22-specific antibodies, such as, but not limited to, fully human and humanized antibodies, comprising, but not limited to, humanized and fully human monoclonal antibodies, in particular comprising, but not limited to human CD22 specific IgG antibodies, such as, for example, a dimer of a human-mouse monoclonal hLL2 gamma chain disulfide associated with a mouse-human monoclonal hLL2 kappa chain comprising, but limited to, for example, the fully humanized antibody specific for human CD22 on Epratuzumab, CAS registry number 501423-23-0.
The syringe or other primary AI container may also be pre-filled with IGF-1 receptor specific antibodies, peptibodies, and related proteins, and the like, such as those described in Publication No. WO 06/069202, which is incorporated herein by reference in its entirety as to IGF-1 receptor specific antibodies and related proteins, comprising, but not limited to, IGF-1 specific antibodies designated herein L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7 , L8H8, L9H9, L10H10, L11S11, L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21, L22H22, L23H23, L24H24, L27H30, L26H31H , L33H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L41H41, L51H51 IR thereof, each of which is individually and specifically incorporated herein by reference. in its entirety entirely as disclosed in the previous International Publication.
[00153] Also among non-limiting examples of anti-IGF-IR antibodies for use in the methods and compositions of the present invention are, each and every one described in: (i) US Publication No. 2006/0040358 (published 23rd February 2006), 2005/0008642 (posted January 13, 2005), 2004/0228859 (posted November 18, 2004), comprising, but not limited to, for example, antibody 1A (DSMZ Deposit No. DSM ACC 2586), antibody 8 (DSMZ Deposit No. DSM ACC 2589), antibody 23 (DSMZ Deposit No. DSM ACC 2588) and antibody 18 as described herein; (ii) Publication No. WO 06/138729 (Published December 28, 2006) and WO 05/016970 (published February 24, 2005), and Lu et al., 2004, J. Biol. Chem. 279:2856-65, comprising, but not limited to, 2F8, A12, and IMC-A12 antibodies as described herein; (iii) Publication No. WO 07/012614 (Published Feb 1, 2007), WO 07/000328 (Published Jan 4, 2007), WO 06/013472 (Published Feb 9, 2006), WO 05 /058967 (published June 30, 2005), and WO 03/059951 (published July 24, 2003); (iv) US Publication No. 2005/0084906 (published April 21, 2005), comprising, but not limited to, 7C10 antibody, C7C10 chimeric antibody, h7C10 antibody, 7H2M antibody, *7C10 chimeric antibody, GM 607 antibody, humanized antibody 7C10 version 1, 7C10 version 2 humanized antibody, 7C10 version 3 humanized antibody, and 7H2HM antibody, as described herein; (V) US Publication Nos. 2005/0249728 (posted November 10, 2005), 2005/0186203 (posted August 25, 2005), 2004/0265307 (posted December 30, 2004), and 2003/0235582 (posted December 25, 2003) and Maloney et al, 2003, Cancer Res. 63:5073-83, comprising, but not limited to, EM164 antibody, EM164 with new surface, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2 and huEM164 v1 .3 as described here; (Vi) US Patent No. 7,037,498 (issued May 2, 2006), US Publication Nos. 2005/0244408 (posted November 30, 2005) and 2004/0086503 (posted May 6, 2004), and Cohen, et al, 2005, Clinical Cancer Res. 11: 2063-73, eg CP-antibody 751, 871, comprising, but not limited to, each of the antibodies produced by the hybridomas having ATCC accession numbers PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, and antibodies 2.12. 1, 2.13.2,2.14.3, 3.1.1, 4.9.2 and 4.17.3, as described herein; (vii) US Publication Nos. 2005/0136063 (posted June 23, 2005) and 2004/0018191 (posted January 29, 2004), comprising, but not limited to, the 19D12 antibody and an antibody comprising a heavy chain encoded by a polynucleotide in plasmid 15H12 / 19D12 HCA (Y4), deposited with the ATCC under number PTA-5214, and a light chain encoded by a polynucleotide in plasmid 15H12 / 19D12LCF (K), deposited with the ATCC under number PTA-5220, as described herein; and (viii) US Publication No. 2004/0202655 (published October 14, 2004), comprising but not limited to PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT antibodies -8A1, PINT-9A2, PINT-11Al, PINT-11A2, A3 PINT-11, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2, PINT-12A3, PINT- 12A4, and PINT-12A5, as described herein; each and every of which are incorporated herein by reference in their entirety, particularly as to the aforementioned antibodies, peptibodies, and related proteins and targeting IGF-1 receptors such as these.
The syringe or other primary AI container may also be pre-filled with B-7 related protein 1 specific antibodies, peptibodies, related proteins and the like ("B7RP-1", it is 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 antibody that binds to an epitope in the immunoglobulin-like first domain of B7RP-1, especially those that inhibit the interaction of B7RP -1 with its natural receptor, ICOS, on activated T cells in particular, especially in all of the above relationships, those disclosed in US Publication No. 2008/0166352 and Publication No. WO 07/011941, which are incorporated herein by reference. in its entirety as to such antibodies and related proteins, comprising, but not limited to antibodies designated herein as follows: 16H (having light chain variable sequences and heavy chain of SEQ ID NO: 2 and SEQ ID NO: 7, respectively, here); 5D (having light chain variable and heavy chain variable sequences of SEQ ID NO: 2 and SEQ ID NO: 9, respectively, here); 2H (having light chain variable and heavy chain variable sequences of SEQ ID NO: 3 and SEQ ID NO. 10 respectively herein); 43h (having light chain variable and heavy chain variable sequences of SEQ ID NO: 6 and SEQ ID NO: 14, respectively, here); 41H (having light chain variable sequences and heavy chain variable sequences SEQ ID NO: 5 and SEQ ID NO: 13, respectively, here); and 15H (having light chain variable and heavy chain variable sequences of SEQ ID NO: 4 and SEQ ID NO: 12, respectively, herein), each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the previous US Publication.
The syringe or other primary AI container may also be pre-filled with IL-15, specific antibodies, peptibodies, and related proteins, and the like, such as, in particular, humanized monoclonal antibodies, particularly antibodies such as those described. in US Publication Nos. 2003/0138421.; 2003/023586; e2004/0071702; and US Patent No. 7,153,507, each of which is incorporated herein by reference in their entirety as to IL-15 specific antibodies and related proteins, comprising peptibodies, in particular comprising, for example, but not limited to, IL-15 antibodies. HuMax IL-15 and related proteins such as, for example, 146B7.
The syringe or other primary AI container may also be prefilled with pharmaceutical compositions comprising antagonist human monoclonal antibodies against human IL-17 receptor A. The characterization, cloning or preparation of IL-1 Receptor A is described in USPN 6,072,033, issued June 6, 2000, which is incorporated herein by reference in its entirety. The amino acid sequence of human IL-17RA is shown in SEQ ID NO: 10 of USPN 6,072,033 (GenBank accession number NM 014339). Such antibodies may comprise those disclosed in WO 2008/054603 which is incorporated by reference in its entirety or the antibodies claimed in USPN 7,767,206, issued August 3, 2010, and in US Serial No. 11/906,094 , which are incorporated herein by reference in their entirety.
The syringe or other primary AI container may also be pre-filled with IFN gamma specific antibodies, peptibodies, and related proteins and the like, especially human IFN gamma specific antibodies, particularly fully human anti-IFN gamma antibodies, such as as, for example, those described in US Publication No. 2005/0004353, which is incorporated herein by reference in its entirety as to IFN gamma specific antibodies, in particular, for example, the antibodies designated herein 1118; 1118*; 1119; 1121; and 1121*. The complete heavy and light chain sequences of each of these antibodies, as well as their heavy and light chain variable region sequences and complementarity determining regions are each individually and specifically incorporated herein by reference in their entirety as disclosed in Previous US publication and in Thakur et al., Mol. Immunol. 36: 1107-1115 (1999). Furthermore, the description of the properties of these antibodies given in the above US publication is also incorporated herein by reference in its entirety. Specific antibodies comprise those having the heavy chain of SEQ ID NO: 17 and the light chain of SEQ ID NO: 18; those having the heavy chain variable region of SEQ ID NO: 6 and the light chain variable region of SEQ ID NO: 8; those having the heavy chain of SEQ ID NO:19 and the light chain of SEQ ID NO:20; those having the heavy chain variable region of SEQ ID NO: 10 and the light chain variable region of SEQ ID NO: 12; those having the heavy chain of SEQ ID NO: 32 and the light chain of SEQ ID NO. 20; those having the heavy chain variable region of SEQ ID NO:30 and the light chain variable region of SEQ ID NO:12; those having the heavy chain sequence of SEQ ID NO:21 and the light chain sequence of SEQ ID NO:22; those having the heavy chain variable region of SEQ ID NO: 14 and the light chain variable region of SEQ ID NO: 16; those having the heavy chain of SEQ ID NO:21 and the light chain of SEQ ID NO:33; and those having the heavy chain variable region of SEQ ID NO: 14 and the light chain variable region of SEQ ID NO: 31, as disclosed in the above US Publication. A specific antibody contemplated is antibody 1119 as described in the preceding US publication and having a complete heavy chain of SEQ ID NO: 17 as described herein and having a complete light chain of SEQ ID NO: 18 as disclosed herein.
The syringe or other primary AI container may also be pre-filled with TALL-1 specific antibodies, peptibodies, and related proteins, and the like, and other TALL specific binding proteins, such as those described in US Publication US. 2003/0195156 and 2006/0135431, each of which are incorporated herein by reference in their entirety as to TALL-1 binding proteins, in particular the molecules of Tables 4 and 5B herein, each individually and specifically incorporated herein by reference in the its entirety as described in preceding US Publications.
The syringe or other primary AI container may also be pre-filled with PTH-specific antibodies, peptibodies, and related proteins, and the like, such as those described in US Patent No. 6,756,480, which is incorporated herein by reference in its entirety, particularly in parts pertinent to PTH-binding proteins.
The syringe or other primary AI container may also be pre-filled with TPO-R specific antibodies, peptibodies, and related proteins, and the like, such as those described in US Patent No. 6,835,809, which is herein. incorporated by reference in its entirety, particularly in parts pertinent to proteins that bind TPO-R.
The syringe or other primary AI recipient may also be pre-filled with HGF-specific antibodies, peptibodies, and related proteins, and the like, comprising those that target the HGF / SF.cMet axis (HGF / SF: c- Met), such as the fully human monoclonal antibodies that neutralize hepatocyte growth factor/scatter (HGF/SF) described in US Publication No. 2005/0118643 and Publication No. WO 2005/017107, huL2G7 described in US Patent No. 7,220 .410 and OA-5D5 described in US Patent 5,686,292 and 6,468,529 and in Publication No. WO 96/38557, each of which is incorporated herein by reference in its entirety, particularly in the relevant portions for proteins that bind to HGF.
The syringe or other primary AI container may also be pre-filled with TRAIL-R2 specific antibodies, peptibodies, related proteins, and the like, such as those described in US Patent No. 7,521,048, which is incorporated herein by reference in its entirety, particularly in parts pertinent to proteins that bind TRAIL-R2.
The syringe or other primary AI container may also be pre-filled with Activin A-specific antibodies, peptibodies, related proteins, and the like, comprising, but not limited to, those described in US Publication No. 2009/0234106, which is incorporated herein by reference in its entirety, particularly in parts pertinent to proteins that bind Activin A.
The syringe or other primary AI container may also be pre-filled with TGF-beta specific antibodies, peptibodies, related proteins, and the like, comprising, but not limited to, those described in US Patent No. 6,803,453 and US Publication No. 2007/0110747, each of which is incorporated herein by reference in their entirety, particularly in parts pertinent to proteins that bind TGF-beta.
The syringe or other primary AI container may also be pre-filled with beta-amyloid protein-specific antibodies, peptibodies, related proteins, and the like, comprising, but not limited to, those described in PCT Publication No. WO 2006 /081171, which is incorporated herein by reference in its entirety, particularly in parts pertinent to proteins that bind beta-amyloid proteins. An antibody contemplated is an antibody having a heavy chain variable region comprising SEQ ID NO: 8 and a light chain variable region having SEQ ID NO: 6, as disclosed in the International Publication.
The syringe or other primary AI container may also be prefilled with c-Kit specific antibodies, peptibodies, related proteins, and the like, comprising, but not limited to, those described in Publication No. 2007/0253951, which is incorporated herein by reference in its entirety, particularly in parts pertinent to proteins that bind to c-kit and/or other stem cell factor receptors.
The syringe or other primary AI container may also be prefilled with OX40L-specific antibodies, peptibodies, related proteins, and the like, comprising, but not limited to, those described in US Application No. 11/068289, which is herein incorporated by reference in its entirety, particularly in parts pertinent to proteins that bind to OX40L and/or other OXO40 receptor ligands.
The syringe or other primary AI container may also be pre-filled with other exemplary proteins comprising but not limited to Activase®t (alteplase, tPA); Aranesp® (darbepoetin alfa), Epogen® (epoetin alfa, or erythropoietin); Avonex® (interferon beta-1a); Bexxar® (Tositumomab, anti-CD22 monoclonal antibody); Betaseron® (interferon-beta); Campath® (alemtuzumab, anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (anti a4B7 mAb); MLN1202 (anti-chemokine receptor CCR2 mAb); Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker); Eprex® (epoetin alpha); Erbitux® (cetuximab anti-EGFR / HER1 / c-ErbB-1); Genotropin® (somatropin, human growth hormone); Herceptin (trastuzumab, anti-HER2/neu (erbB2) receptor mAb); Humatrope® (Somatropin, human growth hormone); Humira® (adalimumab); insulin in solution; Infergen® (interferon alfacon-1); Natrecor® (nesiritide; recombinant human type B natriuretic peptide (hBNP); Kineret® (Anakinra), Leukine® (Sargamostim, rhuGM-CSF); LymphoCide® (Epratuzumab, anti-CD22 mAb); LymphoStat B® (Belimumab, anti- BlyS mAb); Metalyse® (Tenecteplase, t-PA analogue); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (used GO); Raptiva® (Efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris ™ (used GO); Eculizumab); Pexelizumab (anti-C5 complement); MEDI-524 (Numax®); Lucentis (Rambizumab); 17-1A (edrecolomab, Panorex®); Trabio® (lerdelimumab); TheraCIM hr3 (Nimotuzumab); Omnitarg (pertuzumab, 2C4); Osidem® (iDM-1); OvaRex® (B43.13); Nuvion® (visilizumab); Cantuzumab mertansine (huC242-DML); NeoRecormon® (Epoetin beta); Neumega® (oprelvecin, Human interleukin-11) ; Neulasta® (pegylated filgrastim, pegylated G-CSF, pegylated hu-Met-G-CSF); Neupogen® (Filgrastim, G-CSF, hu-MetG-CSF); Orthoclone OKT3® (muromonab-CD3, anti monoclonal antibody -CD3), Procrit® (Epoetin alpha); Rem icade® (infliximab, anti-TNFα monoclonal antibody), ReoPro® (abciximab, anti-GP 11b/Ilia receptor monoclonal antibody), Actemra® (anti-IL6 Receptor mAb), Avastin (bevacizumab), HuMax-CD4 ( Zanolimumab), Rituxan (rituximab, anti CD20 mAb); Tarceva® (erlotinib); Roferon-A®- (interferon alpha-2a); Simulect® (Basiliximab); Prexige® (lumiracoxib); Synagis® (Palivizumab); 146B7-CHO (anti-IL15 antibody, see US Patent No. 7,153,507), Tysabri® (natalizumab, anti-α4integrin mAb); Valortim® (MDX-1303, anti-B. Anthracis mAb protection antigen); ABthrax™; Vectibix® (panitumumab); Xolair® (Omalizumab), ETI211 (anti-MRSA mAb), IL-1 Trap (the Fc portion of human IgGl and the extracellular domains of both IL-1 receptor components (the type I receptor and the accessory protein) of receptor)), VEGF Trap (VEGFR1 Ig domains fused to IgG1 Fc), Zenapax® (daclizumab); Zenapax® (daclizumab, anti-IL-2RA mAb), Zevalin® (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); CNTO 148 (Golimumab, anti-TNF-mAb); HGS-ETR1 (mapatumumab; human anti-TRAIL receptor-1 mAb); HuMax-CD20 (ocrelizumab, human anti-CD20 mAb); HuMax-EGFR(zalutumumab); M200 (Volociximab, anti-α5βi integrin mAb); MDX-010 (ipilimumab, anti-CTLA-4 mAb and VEGFR-1 (iMC-18F1); anti-BR3 mAb; anti-C. difficult toxin A and toxin BC mAbs MDX -066 (CDA-1) and MDX-1388); anti-CD22 dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333 (anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-Crypto mAb; Anti-CTGF Phase I Idiopathic Pulmonary FibroGeni FibroGeni (FG-3019); anti-CTLA4 mAb; anti-eotaxinl mAb (CAT-213); anti-FGF8 mAb; anti-GD2 ganglioside mAb; anti-ganglioside GM2 mAb; anti-human GDF-8 mAb (MYO-029); Anti-GM-CSF receptor mAb (CAM-3001); anti-HepC mAb (HuMax HepC); anti-IFN mAb (MEDI-545, MDX-1103); anti-IGFIRmAb; anti-IGF-IR mAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12 / IL23 mAb (CNTO 1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL-5 receptor mAb; anti-integrin mAb receptors (MDX-018, CNTO 95); Ulcerative Colitis anti-IP10 mAb (MDX-1100); anti-LLY antibody; BMS-66513; anti-mannose receptor / hCGβ mAb (MDX-1307); dsFv-PE38 anti-mesothelin conjugate (CAT-5001); anti-PD1mAb (MDX-1106 (ONO-4538)); anti-PDGFRα antibody (iMC-3G3); anti-TGFB mAb (GC-1008); human receptor-2 anti-TRAIL mAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR / Flt-1 mAb; anti-ZP3 mAb (HuMax-ZP3); NVS #1 antibody; and NVS Antibody #2; a sclerostin antibody, such as, but not limited to, romosozumab, blosozumab, or BPS804 (Novartis). Also included may be therapeutics such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA. Furthermore, included in the AI may be a monoclonal antibody (igG) which binds Human Proprotein Convertase Subtilisin / Kexin Type 9 (PCSK9), e.g., US 8030547, US 13/469,032, WO2008/057457, WO2008/057458, WO2008/057459, WO2008/063382, WO2008/133647, WO2009/100297, WO2009/100318, WO2011/037791, WO2011/053759, WO2011/053783, 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 syringe or other primary AI container may also be pre-filled with antibodies comprising, but not limited to, those that recognize any one or a combination of proteins comprising, but not limited to, the aforementioned proteins and/ or the following antigens: CD2, CD3, CD4, CD8, CD11a, 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, receptor of IL-6, IL-13 receptor, IL-18 receptor subunits, FGL2, PDGF-β and their analogs (see US Patent Nos. 5,272,064 and 5,149,792.), VEGF, TGF, TGF-β2, TGF-β1, EGF receptor (see US Patent No. 6235883) VEGF receptor, hepatocyte growth factor, osteoprotegerin ligand, interferon gamma, B lymphocyte stimulator (BlyS, also known as BAFF, THANK, TALL-1, and zTNF4; see Do and Chen-Kiang (2002), Cytokine Growth Factor Rev. 13 (1): 19-25), complement C5, IgE, tumor antigen CA125, tumor antigen MUC1, PEM antigen, LCG (which is a gene product that is expressed in association with lung cancer), HER-2, a tumor-associated glycoprotein of TAG-72, the SK-1 antigen, tumor-associated epitopes that are present at high levels in the sera of patients with colon and/or pancreatic cancer, cancer-associated epitopes or proteins expressed in breast, colon, squamous cell, prostate , pancreas, lung, and/or kidney cancer cells and/or in melanoma, glioma, or neuroblastoma cells, the necrotic nucleus of a tumor, alpha 4 beta 7 integrin, VLA-4 integrin, B2 integrins, receptors TRAIL 1, 2, 3 and 4, RANK, RANK ligand, TNF-α, VAP-1 adhesion molecule, epithelial cell adhesion molecule (EpCAM), intercellular adhesion molecule-3 (iCAM-3), leukointegrin adhesin , platelet glycoprotein gp IIb / IIIa, cardiac myosin heavy chain, parathyroid hormone, rNAPc2 (which is an inhibitor of and Factor VIIa-tissue), MHC I, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), tumor necrosis factor (TNF), CTLA-4 (which is an antigen associated with cytotoxic T lymphocytes), Fc-receptor yI, HLA-DR 10 beta, HLA-DR antigen, L-selectin, respiratory syncytial virus, human immunodeficiency virus (HIV), hepatitis B virus (HBV), Streptococcus mutans, eStaphlycoccus aureus.
Additional examples of known antibodies that may be contained in the syringe or other primary AI container may include, but are not limited to adalimumab, bevacizumab, infliximab, abciximab, alemtuzumab, bapineuzumab, basiliximab, belimumab, briakinumab, canakinumab, certolizumab pegol , cetuximab, conatumumab, denosumab, eculizumab, gemtuzumab ozogamycin, golimumab, ibritumomab tiuxetan, labetuzumab, mapatumumab, matuzumab, mepolizumab, motavizumab, muromonab-CD3, natalizumab, nimotumab, ore, ore , rituximab, rovelizumab, tocilizumab, tositumomab, trastuzumab, ustekinumab, zalutumumab and zanolimumab.
[00171] Although the SMF, palm button, HH device, needle shield, and AI have been described in terms of illustrative embodiments, they are not limited to these. Rather, the appended claims are to be interpreted broadly to include other variants and modalities of the SMF, the palm button, the HH device, the needle shield, and the AI device, which can be made by those skilled in the art. art without departing from the scope and range of equivalents of the SMF, the palm button, the HH device, the needle shield, and the AI device and its elements.

权利要求:
Claims (29)
[0001]
1. Injector (100), characterized in that it comprises: a housing (110) having an injection end; an injection needle (116) enclosed within the housing (110), the injection needle (116) penetrating the skin at a selected injection site and delivering a drug when an injection cycle of the injector (100) is activated; a flexible extension (130, 230) disposed at the injection end of the housing (110) to stretch or compress the skin at the site injection; and an adapter (260) separate from the flexible extension (130, 230) and for attaching to the injection end of the housing (110), the flexible extension (130, 230) being detachably attached to and received within an interior of the adapter (260) .
[0002]
2. Injector (100) according to claim 1, characterized in that the flexible extension (130, 230) is integral with the housing (110).
[0003]
3. Injector (100) according to claim 1, characterized in that the flexible extension (130, 230) is detachably fixed to the housing (110).
[0004]
4. Injector (100) according to claim 3, characterized in that it further comprises a locking device for detachably attaching the flexible extension (130, 230) to the housing (110), the locking arrangement including interlocking first and second members (274, 276), the flexible extension including one of the first and second members and the housing (110) including the other of the first and second members.
[0005]
5. Injector (100) according to claim 3, characterized in that the flexible extension (130, 230) is selected from a kit of flexible extensions, in which one of the flexible extensions of the kit is constructed so stretching the skin of the injection site and wherein another of the kit's flexible extensions is constructed to compress the skin of the injection site.
[0006]
6. Injector (100) according to claim 1, characterized in that the flexible extension (130, 230) is non-removably attached to the housing (110) of the injector (100).
[0007]
7. Injector (100) according to claim 1, characterized in that it further comprises a locking arrangement for releasably securing the flexible extension (130, 230) to the adapter (260), the locking arrangement including interlocking first and second members (274, 276), the flexible extension (130, 230) including one of the first and second members and the adapter (260) including the other of the first and second members.
[0008]
8. Injector (100) according to claim 1, characterized in that it additionally comprises a needle shield (112) to cover the injection needle (116) after withdrawing the injection needle (116) from the injection site skin.
[0009]
9. Injector (100) according to claim 8, characterized in that the flexible extension (130, 230) is integral with the needle shield (112).
[0010]
10. Injector (100) according to claim 8, characterized in that the flexible extension is detachably attached to the needle shield (112).
[0011]
11. Injector (100) according to claim 10, characterized in that the flexible extension is selected from a kit of flexible extensions (130, 230), in which one of the flexible extensions of the kit is constructed so stretching the skin of the injection site and wherein another of the kit's flexible extensions is constructed to compress the skin of the injection site.
[0012]
12. Injector (100) according to claim 8, characterized in that the flexible extension (130, 230) is non-removably attached to the needle shield (112).
[0013]
13. Injector (100) according to claim 8, characterized in that a lower portion of the needle shield (112) extends outwardly from the injection end of the housing (110) and wherein the needle shield (112) is capable of cocking the injector (100) if a user presses the injection end of the housing (110) down against the skin at the injection site.
[0014]
14. Injector (100), according to claim 8, characterized in that the needle shield (112) is colored to indicate the completion of the injection cycle.
[0015]
15. Injector (100) according to claim 8, characterized in that the needle shield (112) has a rounded edge to contact the skin at the injection site.
[0016]
16. Injector (100) according to claim 1, characterized in that the flexible extension (130, 230) has one or more ring-shaped protrusions or ribs formed in or on a working surface of the extension (130 , 230).
[0017]
17. Injector (100) according to claim 1, characterized in that the flexible extension (130, 230) has a plurality of protrusions formed in or on a work surface of the extension.
[0018]
18. Injector (100) according to claim 1, characterized in that the flexible extension (130, 230) has a textured or adherent work surface (136).
[0019]
19. Injector (100) according to claim 1, characterized in that the flexible extension (130, 230) is constructed as a flange.
[0020]
20. Injector (100) according to claim 1, characterized in that the flexible extension (130, 230) is made of a polyurethane-silicon or polyurethane copolymer material.
[0021]
21. Injector (100) according to claim 1, characterized in that it additionally comprises a palm button device (331, 431) to at least activate the injection cycle of the injector (100).
[0022]
22. Injector (100) according to claim 1, characterized in that it further comprises a holding device to assist a user in the operation of the injector (100), the holding device comprising: a sleeve for ergonomically holding and operating the gun with one hand; and at least one palm rest extending outward from the sleeve to keep the user's hand in the sleeve when holding and operating the injector (100).
[0023]
23. Injector (100) according to claim 1, characterized in that it additionally comprises a container or syringe (104) disposed in the housing (110), the container or syringe (104) containing a therapeutic product.
[0024]
24. Device for use with an injector (100) having an injection needle (116), the device characterized in that it comprises: a flexible extension (130, 230) for stretching or compressing the skin at a selected injection site, and an adapter (260) separate from the flexible extension (130, 230) and for attaching to an injection end of the injector (100), the flexible extension (130, 230) being detachably attached to and received within an interior of the adapter (260 ).
[0025]
25. Device (330, 430) according to claim 24, characterized in that the flexible extension (130, 230) has one or more ring-shaped protrusions or ribs (276) formed in or on a surface of work of the same.
[0026]
26. Device according to claim 24, characterized in that the flexible extension (130, 230) has a plurality of protrusions formed in or on a work surface thereof.
[0027]
27. Device according to claim 24, characterized in that the flexible extension (130, 230) has a textured or adherent work surface.
[0028]
28. The device of claim 24, characterized in that the flexible extension (130, 230) is configured to be detachably attached to the injector (100).
[0029]
29. The device of claim 28, further comprising a locking arrangement for releasably securing the flexible extension (130, 230) to the adapter (260), the locking arrangement including interlocking first and second members ( 274, 276), the flexible extension (130, 230) including one of the first and second members and the adapter (260) including the other of the first and second members.

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法律状态:
2018-11-21| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2019-11-12| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2021-01-05| B07A| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]|

---

2021-06-15| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

---

2021-08-24| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 18/10/2013, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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US201261716425P| true| 2012-10-19|2012-10-19|

---

US61/716,425|2012-10-19|

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PCT/US2013/065798|WO2014063123A1|2012-10-19|2013-10-18|Improved autoinjector|

---