Needle insertion due to overpressure

Abstract

To provide a mechanism for insertion or detention of a needle and / or cannula of a medicine delivery device, and a method.SOLUTION: An insertion mechanism 100 for a drug delivery device includes a proximal end 112, a distal end 114, a first opening 120 disposed near the proximal end, and a second opening 124 disposed in the distal end. A needle or cannula assembly 130 is disposed within a housing 110 and has a base 132 with a proximal surface 134 and a distal surface 136 and a needle or cannula 140 coupled to the distal surface. A retraction member 142 is disposed within the housing to maintain the needle or cannula assembly in a retracted position before movement to an extended position, the retraction member in contact with the base. Upon supplying pressure through the first opening until an amount of pressure P1 applies an application force to the proximal surface of the base that surpasses a resistive force of the retraction member, the needle assembly is moved from the retracted position to the extended position.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 468,190, filed March 7, 2017, which is incorporated by reference in its entirety.

[0002] FIELD OF THE DISCLOSURE The present disclosure relates generally to drug delivery devices, and more particularly to mechanisms and methods for inserting or placing needles and / or cannulas in drug delivery devices. [Background technology]

[0003] Some drug delivery devices, such as wearable injectors, may be temporarily attached to a patient to deliver a drug over an extended period of time through a needle or any other means. The drug delivery device may be attached to tissue in the patient's abdomen, thigh, arm, or any other part of the patient's body.

[0004] In some cases, the drug delivery device may be worn by the patient for minutes or hours during drug injection. For example, highly viscous drugs, such as biologics, may require long injection times due to the force required to push them out of the drug delivery device. Furthermore, some drug delivery devices are configured to be fitted to the patient in a clinic and deliver the drug to the patient once the patient has returned home. For these and other reasons, a rigid injection member may be left inside the patient for a substantial period of time, which may cause discomfort and anxiety to the patient.

[0005] Additionally, some existing drug delivery devices use external features for needle safety, which require the patient to remove the drug delivery device while the rigid needle is still in the body. Depending on the angle, depth, and stiffness of the needle, this can cause patient discomfort and subsequent anxiety at the sight of the needle.

[0006] As a result, insertion mechanisms have been positioned within the drug delivery device to effectuate needle insertion and / or retraction movements, however such insertion mechanisms may increase the overall size, complexity, and / or cost of the drug delivery device. Summary of the Invention [Means for solving the problem]

[0007] According to a first aspect, the wearable drug delivery device includes a main housing having a container, a fluid pathway connector coupled to the container, and a pressure supply. The drug delivery device further includes an insertion mechanism disposed within the main housing and operatively coupled to the pressure supply, the fluid pathway connector defining a fluid flow path between the container and the insertion mechanism. The insertion mechanism includes a housing having a proximal end, a distal end, a first opening disposed near the proximal end, and a second opening disposed at the distal end, the first opening being coupled to the pressure supply. A needle or cannula assembly is disposed within the housing and is movable between a retracted position and an extended position. The needle or cannula assembly includes a base having a proximal face and a distal face, and a needle or cannula coupled to the distal face of the base. The base divides the housing into a proximal chamber and a distal chamber. A retraction member is disposed within the housing to hold the needle or cannula assembly in the retracted position until moved to the extended position. The retraction member contacts the base and exerts a resistive force. The pressure supply supplies pressure through the first opening to the proximal chamber until the amount of pressure P1 in the proximal chamber overcomes the resistive force of the retraction member and exerts an actuation force on the proximal face of the base such that the needle assembly moves from the retracted position to the extended position. The needle is positioned out of the opening at the distal end of the housing in the extended position for needle deployment.

[0008] According to a second aspect, an insertion mechanism for a drug delivery device includes a housing having a proximal end, a distal end, a first opening disposed near the proximal end of the housing adapted to be operatively coupled to a pressure supply device, and a second opening disposed at the distal end of the housing. A needle or cannula assembly is disposed within the housing and is movable between a retracted position and an extended position. The needle or cannula assembly includes a base having a proximal face and a distal face, and a needle or cannula attached to the base. A retraction member contacts the base and applies a resistive force to hold the needle or cannula assembly in the retracted position until it is moved to the extended position. Pressure is applied from the first opening until an amount of pressure P1 applies an actuation force to the proximal face of the base that overcomes the resistive force of the retraction member to move the needle or cannula assembly from the retracted position to the extended position, with the needle extending from the second opening at the distal end of the housing in the extended position.

[0009] According to yet another aspect, a method of deploying a needle of an insertion mechanism from a drug delivery device is disclosed. The method includes holding a retracted position of a needle or cannula assembly deployed in a housing of the insertion mechanism by a retraction member. The method also includes providing pressure to a first opening of the housing of the insertion mechanism until an amount of pressure P1 in the housing applies an actuation force to a base of the needle or cannula assembly that exceeds a resistance force applied to the base by one or more of the retraction members or pressures P2 in a distal chamber of the housing. The method also includes moving the needle assembly from the retracted position to an extended position when the actuation force exceeds the resistance force. The method still further includes disposing a needle of the needle or cannula assembly into a second opening at a distal end of the housing of the insertion mechanism when the needle assembly moves to the extended position for deploying the needle.

[0010] According to any one or more of the first and second aspects and methods above, the insertion mechanism and method for a drug delivery device may include any one or more of the following features or method steps:

[0011] In one form, the retraction member may include a biasing mechanism, the biasing mechanism including a spring having a first end attached to the base and a second end attached to the distal end of the housing, the spring retracting the needle to the retracted position after pressure P1 in the proximal chamber is released. Additionally, the insertion mechanism may further include a first connector extending upwardly from the proximal surface of the base, and a flexible fluid path member having a first end operatively coupled to the connector extending upwardly from the proximal surface of the base and a second end operatively coupled to a second connector extending downwardly from the proximal end of the housing. The flexible fluid path member is movable with the needle assembly. Additionally, the flexible fluid path member may be in an extended position when the needle assembly is in the extended position and in a compressed position when the needle assembly is in the retracted position.

[0012] In another embodiment, the insertion mechanism may further include a step disposed about the housing sidewall near the distal end of the housing. The step may include a sealing mechanism, which may include an O-ring. Additionally, a distal surface of the base may contact the O-ring to cushion the needle or cannula assembly as it moves from the retracted position to the extended position. Additionally, the housing may include a sidewall having a threaded inner surface, and the base may further include one or more of a surface or pair of sides that contact the inner surface of the sidewall. The sides of the base may each have a threaded surface that corresponds to the threaded inner surface of the housing sidewall. Additionally, the threaded inner surface of the housing sidewall and the threaded surface of the side of the base may include one of a coarse thread or a fine thread, with the coarse thread allowing the needle to rotate at least 2-3 times during insertion, and with the fine thread allowing the needle to rotate at least 8-10 times during insertion.

[0013] In another embodiment, the base may include a surface or a pair of side walls that are minimally spaced from the side wall of the housing, thereby minimizing flow-around when pressure is applied to the proximal chamber. The retraction member may also include a friction element that contacts the side wall of the base. The friction element may include one or more of at least one sealing mechanism or O-ring. Additionally, when negative pressure is applied from the first opening or positive pressure is applied to a third opening in the side wall of the housing, located near the distal end of the housing, the pressure P2 in the distal chamber exceeds the pressure P1 in the proximal chamber, thereby causing the needle or cannula assembly to return upward to the retracted position after the needle is deployed.

[0014] In yet another embodiment, the needle or cannula assembly may be secured back into the retracted position by one or more of: (1) at least one spring-loaded directional latch; or (2) at least one groove disposed on the side wall of the housing. The at least one groove for receiving the at least one sealing mechanism may be disposed on the side wall of the base to prevent the needle assembly from being moved back into the extended position. Additionally, the at least one spring-loaded directional latch may include a first spring-loaded directional latch disposed on one region of the side wall of the housing and a second spring-loaded latch disposed on another region of the side wall of the housing. Each latch may have an angled side that contacts a corresponding angled side of the base on each side of the base to secure the base of the needle or cannula assembly and prevent it from being re-deployed. Additionally, the at least one groove may include a first groove disposed on one region of the side wall of the housing and a second groove disposed on another region of the side wall of the housing. Each groove may be adapted to receive a corresponding friction element disposed on a side wall of the base to secure the base of the needle or cannula assembly and prevent redeployment.

[0015] Additionally, in other configurations, the needle or cannula assembly may move from the retracted position to the extended position when pressure P1 in the proximal chamber exceeds pressure P2 in the distal chamber.

[0016] In one form of the method, maintaining the needle or cannula assembly in a retracted position may include one of the steps of: (1) applying a resistive force to a distal face of the base of the needle assembly via a biasing mechanism; or (2) disposing a friction element on at least one region of a sidewall of the base to apply a resistive force toward the proximal end of the housing via the friction element.

[0017] In another aspect of the method, the method may further include one of applying a negative pressure through the first opening or applying a positive pressure to the housing at a third opening disposed near the distal end of the housing until the pressure P2 in the distal chamber of the housing exceeds the pressure P1 in the proximal chamber and the needle or cannula assembly moves from the extended position back to the retracted position. Additionally, the method may further include locking the needle assembly in the retracted position after moving from the extended position to prevent the needle of the needle assembly from being redeployed. In some examples, locking the needle assembly in the retracted position may include one of (1) providing at least one spring-loaded directional latch on a side wall of the housing, the spring-loaded directional latch contacting at least one side of the base when moved into the at least one spring-loaded directional latch, or (2) inserting at least one sealing mechanism disposed on at least one side of the base into a corresponding groove disposed on the side wall of the housing. Additionally, the method may further include increasing the size of the proximal chamber as the needle or cannula assembly moves from the retracted position to the extended position and reducing the ejection force present during needle deployment.

[0018] The present disclosure will be better understood from the following description read in conjunction with the accompanying drawings. Some of the drawings may have been simplified by omitting selected elements for the purpose of more clearly showing other elements. The omission of such elements in some drawings does not necessarily indicate the presence or absence of a particular element in any of the illustrative embodiments, unless expressly stated in the corresponding legend. Additionally, none of the drawings are necessarily drawn to scale. [Brief description of the drawings]

[0019] [Figure 1] 1 is a schematic diagram of one embodiment of a drug delivery device having an insertion mechanism in accordance with the teachings of the present disclosure. [Diagram 2] 2 is a cross-sectional view of an insertion mechanism according to one embodiment of the present disclosure taken along line AA of FIG. 1, the insertion mechanism being in a retracted position. [Diagram 3] FIG. 3 is a cross-sectional view of a portion of the insertion mechanism of FIG. 2, the insertion mechanism having a base and a housing according to another embodiment of the present disclosure. [Figure 4] 3 is another cross-sectional view of a portion of the insertion mechanism of FIG. 2, the insertion mechanism having another base and another housing according to another embodiment of the disclosure. [Diagram 5] 2 is a cross-sectional view of another insertion mechanism according to another embodiment of the present disclosure taken along line AA of FIG. 1, the insertion mechanism being in a retracted position. [Figure 6] 2 is a cross-sectional view of another insertion mechanism according to another alternative embodiment of the present disclosure taken along line AA of FIG. 1, the insertion mechanism being in a retracted position. [Figure 7] FIG. 13 is a cross-sectional view of another insertion mechanism according to yet another aspect of the present disclosure, the insertion mechanism being in a retracted position. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] A wearable drug delivery device having a novel insertion mechanism is disclosed. The insertion mechanism is disposed within a main housing of the drug delivery device and includes a housing having a proximal end, a distal end, a sidewall, a first opening disposed near the proximal end, and a second opening disposed near the distal end of the housing. Generally, the first opening receives pressure from a pressure supply device to deploy a needle through the second opening in the housing.

[0021] More specifically, the insertion mechanism further includes a needle or cannula assembly disposed within the housing and movable between a retracted position and an extended position. The needle or cannula assembly includes a base having a proximal face and a distal face, and a needle coupled to the distal face, the base dividing the housing into a proximal chamber and a distal chamber. A retraction member holds the needle in the retracted position until it is moved to the extended position to deploy the needle. Pressure is applied into the proximal chamber through a first opening in the housing until an amount of pressure P1 in the proximal chamber applies an actuation force to the proximal face of the base that overcomes the resistance of the retraction member to move the needle or cannula assembly from the retracted position to the extended position. In the extended position, the needle is deployed through a second opening in the housing to deploy the needle. To withdraw the needle and move the needle or cannula assembly from the extended position back to the retracted position, a negative pressure is either provided to the proximal chamber or a positive pressure is applied to the distal chamber, for example, until pressure P2 in the distal chamber is greater than pressure P1 in the proximal chamber, at which point the needle assembly is retracted and again locked in the retracted position to prevent reuse.

[0022] More specifically, referring now to FIG. 1, a wearable drug delivery device 10 having an insertion mechanism 12 according to the present disclosure is shown. In at least one example, the drug delivery device 10 may be configured as a wearable drug delivery device, such as a wearable injector, that may be configured to be attached to a patient's tissue 11 (e.g., the patient's skin) to administer a drug therapy. The drug delivery device 10 may automatically deliver a fixed or patient / operator configurable amount of drug subcutaneous injection over a controlled or selected time period. The drug delivery device 10 may be used for self-administration by the patient or to administer an injection by a caregiver or formally trained medical personnel.

[0023] The drug delivery device 10 may include a container 14, a drive mechanism 24, and a controller 26 coupled to the insertion mechanism 12 by a fluid pathway connector 22, each of which may be disposed within a main housing 30 of the drug delivery device 10. An actuator 28 (e.g., a push button) may be disposed external to the main housing 30 and configured to initiate operation of the drug delivery device 10 by actuating the insertion mechanism 12, the drive mechanism 24, and / or the controller 26 via mechanical and / or electrical means (shown in dashed lines in FIG. 1 ). The fluid pathway connector 22 defines a sterile fluid flow path 38 between the container 14 and the insertion mechanism 12. The fluid pathway connector 22 may include a container access mechanism 29 configured to pierce a septum 32 associated with the container 14 with a needle 31 of the container 14 to establish fluid communication between the container 14 and the sterile fluid flow path 38 in response to actuation of the drug delivery device 10, e.g., via the actuator 28. The main housing 30 may include a bottom wall 36 that is releasably attached (e.g., adhered with an adhesive) to the patient's skin 11, and a top wall 40 that includes one or more indicator lights 42 and / or a window (not shown) for viewing the container 14. An opening 44 may be formed in the bottom wall 36, and optionally a septum 48 may extend across the opening 44 such that the interior of the main housing 30 remains sealed prior to use. The exterior of the insertion mechanism 12 may be defined by an insertion mechanism housing that is separate from the main housing 30, as will be further described below with respect to each exemplary insertion mechanism.

[0024] Generally, upon actuation of the drug delivery device 10, the insertion mechanism 12 may insert the needle or cannula 34 and / or trocar 66 of the needle or cannula assembly through the opening 44 and / or septum 48 into the patient's body. Simultaneously, or subsequently, the drug delivery device 10 may enable, make, or open the connections necessary to establish fluid communication between the container 14 and the fluid pathway connector 22. The drive mechanism 24 may then push the drug 46 stored in the container 14 through the sterile fluid flow path of the fluid pathway connector 22 and into the cannula 34 for subcutaneous delivery to the patient.

[0025] 2-4 show an insertion mechanism 100 corresponding to one example of the insertion mechanism 12 shown in FIG. 1. The insertion mechanism 100 may be incorporated into a drug delivery device such as the drug delivery device 10 shown in FIG. 1. The insertion mechanism 100 includes a housing 110 having a proximal end 112, a distal end 114 disposed opposite the proximal end 112, a sidewall 116 disposed between the proximal and distal ends 112, 114, a first opening 120 disposed near the proximal end 112, and a second opening 124 disposed at the distal end 114. The first opening 120 is adapted to be coupled to a pressure supply 126. The pressure supply 126 may provide a pressurized fluid or gas and may include any pressure source, such as an air pressure source and any other pressure providing source, as will be appreciated by those skilled in the art. In addition, a pressure supply 126 may be disposed within the main housing 30 of the drug delivery device 10 of FIG. 1 and directly or indirectly coupled to the first opening 120 of the insertion mechanism 100 .

[0026] As further shown in FIG 2, the needle or cannula assembly 130 is disposed within the housing 110 of the insertion system 100 and is movable between a retracted position, shown in FIG 2, and an extended position. The extended position is shown in phantom in FIG 2 and will be further described below. The needle or cannula assembly 130 includes a base 132 having a proximal face 134 and a distal face 136. The proximal face 134 is disposed closer to the proximal end 112 of the housing 110. Similarly, the distal face 136 is disposed closer to the distal end 114 of the housing 110. Additionally, a hub 138 extends downwardly from the base 132 and the distal face 136, and in this example, the needle or cannula 140 is attached to the base 132 via the hub 138. More specifically, in one example, needle or cannula 140 is attached to hub 138 and extends downwardly therefrom and is adapted to, in the extended position, enter and exit second opening 124 disposed at distal end 114 of housing 110. Although not shown in this example, needle or cannula 140 may alternatively be attached directly to base 132 and still be within the scope of the present disclosure. Base 132 and hub 138 may be circular or cylindrical. Alternatively, base 132 and hub 138 may be a variety of other shapes and configurations and still be within the scope of the present disclosure.

[0027] 2, a base 132 of the needle or cannula assembly 130 divides the housing 110 into a proximal chamber 118 and a distal chamber 119. In one example, the proximal chamber 118 has a pressure P1 and the distal chamber 119 has a pressure P2. Each of the pressures P1 and P2 in each of the proximal and distal chambers 118, 119 may be different, which determines whether the needle or cannula assembly 130 is in a retracted or extended position, as will be further described below.

[0028] 2, the base 132 may include one or more of a side or pair of sides 133 that are minimally spaced from the side wall 116 of the housing 110, which, together with, for example, the thickness of the base 132, minimizes flow-around when pressure is applied to the proximal chamber 118. In this other manner, a small gap between the side wall 116 of the housing 110 and the side 133 of the base 132 minimizes flow-around when the proximal chamber 118 is pressurized.

[0029] A retraction member 142 is also disposed within the housing 110. The retraction member 142 contacts the base 132 and exerts a resistive force that holds the needle or cannula assembly 130 in the retracted position until the needle or cannula assembly 130 is moved to the extended position, as described further below. More specifically, in this example, the retraction member 142 exerts a resistive force, such as a biasing force, on the distal surface 136 of the base and includes a first end 143 attached to the distal surface 136 of the base 132 and a second end 144 in contact with the distal end 114 of the housing 110. The retraction member 142 extends downwardly from the distal surface 136 of the base 132 around the needle 140 to the distal end 114 of the housing 110. More specifically, in one example, the retraction member 142 is a biasing mechanism, such as a compression spring, and is biased in the retracted position shown in FIG. 2. For example, when pressure P1 in proximal chamber 118 is released, a biasing mechanism, such as a spring, retracts needle or cannula 140 back to the retracted position.

[0030] In another example, retraction member 142 may alternatively be a tension spring having a first end attached to proximal face 134 of base 132 and a second end attached to proximal end 112 of housing 110. Having a tension spring as retraction member 142 would accomplish the same purpose as having a compression spring as retraction member 142 described above. For example, a tension spring would also bias needle or cannula assembly 130 in the retracted position of FIG. 2 and thus retract needle or cannula 140 back to the retracted position when pressure P1 is released from proximal chamber 118.

[0031] In another example, the insertion mechanism 100 further includes a first connector 145 extending upward from the proximal face 134 of the base 132 and a second connector 152 extending downward from the proximal end 112 of the housing 110 into the proximal chamber 118. The flexible fluid path member 146 includes a first end 148 operatively coupled to the first connector 145 and a second end 150 operatively connected to the second connector 152. So configured, the flexible fluid path member 146 expands and contracts with the needle or cannula assembly 130. In other words, the flexible fluid path member 146 also moves from a retracted position to an extended position as the needle assembly 130 moves from a retracted position to an extended position. In other words, the flexible fluid path member 146 moves with the needle assembly from a retracted position, where the flexible fluid path member 146 is in a compressed position, to an extended position, where the flexible fluid path member 146 is in an extended position.

[0032] In other examples, the flexible fluid path member 146 may alternatively and / or additionally be used as a retraction member. More specifically, the flexible fluid path member 146 may act as a biasing mechanism to bias the needle or cannula assembly 130 in the retracted position of FIG. 2. So configured, when pressure P1 increases in the proximal chamber 118, the flexible fluid path member 146 extends or expands to the extended position. Similarly, when pressure P1 decreases, the flexible fluid path member 146 moves again to the retracted position of FIG. 2 to retract the needle 140 after deployment. In this example, the flexible fluid path member 146 includes a conduit having an appropriately elastic material to accomplish this function.

[0033] In another example, the insertion system 100 may include a third connector 153 extending upwardly out of the housing 110 from the proximal end 112 of the housing 110. The external fluid path member 155 includes a first end 157 operatively coupled to the third connector 153 and a second end 159 operatively coupled to the fluid path connector (FIG. 1). So configured, in one example, a drug may be pushed through the fluid path connector 22, through the flexible fluid path member 146, through the needle or cannula 140, and to the patient. Although the external fluid path member 155 is shown as a bent L-shaped member, the external fluid path member 155 may alternatively include a variety of other forms and shapes and still be within the scope of the present disclosure. For example, the external fluid path member 155 may be any other connecting member that operatively couples the flexible fluid path member 146 to the fluid path connector 22 (FIG. 1).

[0034] The insertion system 100 further includes a step 156 disposed on and / or about the sidewall 116 of the housing 110 near the distal end 114 of the housing 110. The step 156 includes a sealing mechanism 160, such as an O-ring or any other sealing mechanism known to one of ordinary skill in the art capable of performing the same function. The distal surface 136 of the base 132 contacts the sealing mechanism 160 to cushion the distal surface 136 of the base 132 against the shoulder 160 when the needle or cannula assembly 130 moves to its extended position. Additionally, the sealing mechanism 160, e.g., an O-ring, prevents leakage, retains pressure, and provides cushioning, e.g., when the needle or cannula 140 is inserted into the skin of a patient.

[0035] In operation, the needle assembly 130 is biased to the retracted position by the resistance of the retraction member 142 to prevent the needle 140 or the needle assembly 130 from moving during shipping, storage, or other handling. To deploy the needle 140, for example, the pressure supply 126 supplies pressure through the first opening 120 to the proximal chamber 118. The needle or cannula assembly 130 is held stationary via the retraction member 142 while the pressure in the proximal chamber 118 increases. When the pressure P1 in the proximal chamber applies an actuation force to the proximal face 134 that exceeds the resistance of the retraction member 142, the needle or cannula assembly 130 begins to move from the retracted position to the extended position. In another example, the needle or cannula assembly 130 moves from the retracted position to the extended position when the pressure P1 in the proximal chamber 118 exceeds the pressure P2 in the distal chamber 119. In the extended position, the distal face 136 of the base 132 contacts a sealing feature 160 disposed on a shoulder 158 near the distal end 114 of the housing 110, and the needle 140 extends through the second opening 124 and into the patient's skin with sufficient force. As the needle assembly 130, and thus the base 132, moves toward the distal end 114 of the housing 110, the proximal chamber 118 becomes larger, thereby reducing the ejection force of the needle 140. In other words, because an initial increase in pressure P1 occurs in the proximal chamber P1 while the needle assembly 130 is in the retracted position, the increased volume of the proximal chamber P1 necessarily reduces the ejection force.

[0036] Therefore, as will be appreciated by those skilled in the art, the insertion force and speed of the needle 140 can be controlled within the insertion system 100 by adjusting the pressure supplied to the proximal chamber 118, the flow rate of the pressure supplied, and the area of ​​the base 132 of the needle or cannula assembly 130. Additionally, slight over-penetration resulting from rebound at the sealing feature 160 located on the step 158 when contacting the distal surface 136 of the base 132 may reduce the incidence of tissue occlusion of the needle or cannula 140 during needle placement. Additionally, only a light force is required to return the needle or cannula 140 into the housing 110 of the insertion system 100, thereby reducing the need for a retraction member 142, such as a spring. When the pressure supplied is reduced, the needle 140 will return to the retracted position again.

[0037] 3 and 4, the insertion mechanism of FIG. 2 may alternatively include a threaded sidewall 116. More specifically, the housing 110 of the insertion mechanism 100 may include a sidewall 116 having a threaded inner surface 166. In a similar manner, instead of being minimally spaced from the sidewall 116, the base 132 of the needle or cannula assembly 130 may alternatively include a side surface 168 that contacts the threaded inner surface 166 of the sidewall 116 of the housing 110. More specifically, each side surface 168 of the base 132 may also be threaded, e.g., having a threaded surface that precisely corresponds to the threaded inner surface 166 of the sidewall 116. In one example, as shown in FIG. 3, the threaded inner surface 166 of the sidewall 116 and the threaded side surface 168 of the base 132 include fine threads. In this example, the fine threads allow the needle or cannula 140 to rotate at least 8-10 times during deployment, for example. As will be appreciated by one of ordinary skill in the art, the needle or cannula 140 may alternatively rotate more than 8-10 times during deployment and still be within the scope of the present disclosure. In another example, as shown in FIG. 4, the threaded inner surface 166 of the sidewall(s) 116 and the threaded side surface 168 of the base 132 include coarse threads. This larger pitch thread allows the needle 140 to rotate fewer times during deployment. In one example, the coarse thread allows the needle or cannula 140 to rotate 2-3 times during deployment.

[0038] So configured, this threaded interface between the side wall 116 of the housing 110 and the side surface 168 of the base 132 allows for controlled rotation of the needle or cannula 140 during entry of the needle or cannula 140. Additionally, as shown in Figure 4, the corresponding threaded portions may fit loosely together, such as with a small space between the threaded side wall 166 of the housing 110 and the threaded side surface 168 of the base 132, thereby reducing friction and providing smoother rotation during needle placement. Additionally, in both the examples of Figures 3 and 4, rotation during needle placement helps to reduce axial runout of the needle or cannula 140, thereby allowing for more comfortable and effective needle placement.

[0039] 5, another exemplary insertion mechanism 200 according to the present disclosure is shown. More specifically, as described further below, the retraction member of the insertion mechanism 200 includes at least one friction element 280 rather than a spring 142 as shown in FIG. 2, for example. The at least one friction element 280 applies a resistive force to hold the needle or cannula assembly 130 in a retracted position, as described further below, and is in contact with the side wall 133 of the base 132. More generally, the insertion mechanism 200 is the same as the insertion mechanism 100 shown in FIG. 2 and described above, but differs in additional and / or alternative structural features included in FIG. 5 and described below. For the sake of brevity, parts of the insertion mechanism 200 that are the same as the insertion mechanism 100 are labeled with the same reference numerals and will be described only with respect to the insertion mechanism 100.

[0040] More specifically, the at least one frictional element 280 of the insertion mechanism 200 includes a pair of sealing features 282 disposed on the sidewall 133 of the base 132. The at least one frictional element 280, such as the sealing features 282, exerts a resistive force toward the proximal end 112 of the housing 110. In this example, each sealing feature 282 is disposed at approximately the midpoint of the sidewall of the base 133. Alternatively, the sealing features 282 may be disposed on any other portion of the sidewall 133 of the base 132 and still fall within the scope of the present disclosure. In one example, the sealing features 282 are O-rings. Any other similar types of seals may alternatively be used and still fall within the scope of the present disclosure. Similar to the retraction member 142 of the insertion mechanism 100, at least one frictional element 280, such as a sealing mechanism 282, prevents movement of the needle or cannula 140 of the needle assembly 130 during one or more of shipping, storage, or any other handling of the insertion mechanism 200.

[0041] In operation, pressure is applied to the first opening 120 of the housing 110 of the insertion mechanism 200 to deploy the needle or cannula 140 of the needle or cannula assembly 130. More specifically, when the pressure P1 in the proximal chamber 118 applies an actuation force to the proximal surface 134 of the base 132 that exceeds the resistance of the at least one frictional member 280, the needle or cannula assembly 130 moves from the retracted position to the extended position. In another example, when the actuation force of pressure P1 on the proximal surface 134 of the base exceeds the resistance of pressure P2 in the distal chamber 119, the actuation force of pressure P1 overcomes the force of at least one frictional element 280, e.g., sealing mechanism 282, to move the needle or cannula assembly 130 from the retracted position to the extended position, achieving needle deployment.

[0042] In this example, the housing 110 of the insertion system 200 further includes a third opening 284. The third opening 284 is located near the distal end 114 of the housing 110, for example in the side wall 116, and opens into the distal chamber 119. Alternatively, the third opening 284 may be located in any other portion of the housing 110 such that the third opening 282 opens into or communicates with the distal chamber 119 of the housing 110. After the needle or cannula assembly 130 is moved to the extended position, and in some cases after the pressure P1 in the proximal chamber 118 is vented, pressure is supplied to the third opening 284 and the distal chamber 119. When the pressure P2 in the distal chamber 119 exceeds the pressure P1 in the proximal chamber 118, the needle 140 is retracted back into the housing 110 through the opening 124, and the needle assembly 130 is returned to the retracted position. In this example, a small pressure is provided as tactile feedback after needle 140 is withdrawn, and pressure is subsequently applied or supplied to distal chamber 119 via third opening 284 .

[0043] Alternatively, negative pressure may be applied to the proximal chamber 118 through the first opening 120 to reduce the pressure P1 in the proximal chamber 118. When the pressure P1 in the proximal chamber 118 becomes lower than the pressure P2 in the distal chamber 119, the needle 140 moves from the extended position back to the retracted position. In the alternative, whether positive pressure is applied through the third opening 284 or negative pressure is applied through the first opening 120, once the needle 140 is deployed and pressure P2 exceeds pressure P1, the needle 140 and needle assembly 130 move from the extended position back to the retracted position.

[0044] When the needle or cannula assembly 130 is returned to the retracted position, the insertion mechanism 200 locks the needle or cannula assembly 130 in the retracted position, for example, to prevent the needle 140 from being reused. More specifically, as shown in FIG. 5, the insertion mechanism 200 further includes at least one latch 286 for locking or holding the needle or cannula assembly 140 in the retracted position again. In one example, the at least one latch 286 includes a pair of spring-loaded directional latches 288. The first spring-loaded directional latch 288 is disposed in one region of the housing sidewall 116 and the second spring-loaded directional latch 288 is disposed in another region of the housing sidewall 116, the first and second spring-loaded latches being disposed at the same height and position on corresponding regions of the housing sidewall 116. Additionally, each of the first and second spring-loaded latches includes a spring 289 and an inclined surface 290 facing the inside of the housing 110. Each spring 289 is disposed about each latch 288 and biases each latch 288 in a direction toward the base 134 of the needle or cannula assembly 130. In this example, the base 134 further includes a sloped corner or surface 292 on each side 133. The sloped surface 292 on each side wall 133 of the base 132 contacts a corresponding sloped surface 290 of the latch 288 after the needle or cannula assembly 130 moves to the retracted position. The biasing force of each spring loaded latch 288 toward the base 134 secures the base 134, and thus the needle or cannula assembly 140, in the retracted position preventing repositioning.

[0045] 6, another exemplary insertion mechanism 300 according to the present disclosure is shown. More specifically, similar to the insertion mechanism 200 of FIG. 5, the retraction member of the insertion mechanism 300 includes at least one friction element 280 in contact with the base 132, rather than a spring 142 as shown in FIG. 2, for example. The at least one friction element 280 exerts a resistive force to hold the needle or cannula assembly 130 in the retracted position, as will be further described below. In addition, the insertion mechanism 300 also includes a different method than either of the insertion mechanisms 100 and 200 for locking the needle or cannula assembly 130 back into the retracted position to prevent reuse. More generally, the insertion mechanism 300 is the same as the insertion mechanism 100 shown in FIGS. 2 and 5, respectively, and described above, but differs in additional and / or alternative structural features included in FIG. 6 and described below. For simplicity, parts of the insertion mechanism 300 that are the same as those of the insertion mechanism 100 are given the same reference numbers and will be described only with reference to the insertion mechanism 100.

[0046] More specifically, similar to the insertion mechanism 200 of FIG. 5, the at least one friction element 280 of the insertion mechanism 300 includes a pair of sealing mechanisms 282 disposed on the sidewall 133 of the base 132. The at least one friction element 280, e.g., the sealing mechanisms 282, exert a force toward the proximal end 112 of the housing 110. Again, in this example, each sealing mechanism 282 is disposed at approximately the midpoint of the sidewall of the base 133. Alternatively, the sealing mechanisms 282 may be disposed on any other portion of the sidewall 133 of the base 132 and still fall within the scope of the present disclosure. In one example, the sealing mechanisms 282 are O-rings. Any other similar types of seals may alternatively be used and still fall within the scope of the present disclosure. Similar to the retraction member 142 of the insertion mechanism 100, at least one frictional element 280, such as a sealing mechanism 282, prevents movement of the needle or cannula 140 of the needle assembly 130 during one or more of shipping, storage, or any other handling of the insertion mechanism 200.

[0047] In addition to the sealing feature 282, the insertion mechanism 300 may further include at least one groove 392 to help hold the needle or cannula assembly 130 in the retracted position until the needle is inserted. In one example, the at least one groove 392 includes a pair of grooves 394. A first groove 394 is disposed in one area of ​​the housing sidewall 116 and a second groove 394 is disposed in another area of ​​the housing sidewall 116, the first and second grooves 394 being disposed at the same height and position in corresponding areas of the sidewall 116 of the housing 110. Additionally, each of the first and second grooves 394 is shown as semicircular so that each groove 394 can readily and easily receive a corresponding circular sealing feature 282 disposed on each side 133 of the base 132 when the needle assembly 130 is again returned to the retracted position. Alternatively, each groove 392 may take the form of a variety of other shapes and still be within the scope of the present disclosure. More specifically, in another example, the shape of each groove 394 essentially matches the shape of each sealing feature 282 of the base 132, such that each groove 392 can easily receive a corresponding sealing feature 282, e.g., a friction element, on each side 133 of the base 132 to secure the base 32 of the needle or cannula assembly 130 in a retracted position and prevent reuse. In operation, pressure is applied to the first opening 120 of the housing 110 of the insertion mechanism 200 to deploy the needle or cannula 140 of the needle or cannula assembly 130. More specifically, when the amount of pressure P1 in the proximal chamber 118 applies an actuation force to the proximal surface 134 of the base 132 that exceeds the resistance of the at least one friction element 280, the needle or cannula assembly 130 moves from the retracted position to the extended position. In another example, when the amount of pressure P1 in the proximal chamber 118 applies an actuation force to the base 132 that exceeds the resistance force applied to the base 132 by the pressure P2 in the distal chamber 119, the needle or cannula assembly 130 moves from the retracted position to the extended position, deploying the needle.

[0048] In this example, the at least one groove 392 increases the force threshold above which the needle assembly 130 moves. The force threshold is much greater than, for example, frictional resistance alone. More specifically, in one example, the force threshold is at least five times greater than the frictional resistance. Said another way, in this example, the combined resistance of the at least one friction element 280 and the at least one groove 392 is much greater than the resistance of the at least one friction element 280 alone (FIG. 5) without the groove 392. As will be appreciated by those skilled in the art, the force threshold of the friction element 280 and groove 392 can be less than or greater than five times the frictional resistance and still be within the scope of the present disclosure, so long as the force threshold is greater than the frictional resistance.

[0049] This configuration with at least one groove 392 allows for more pressure to be applied, ensuring rapid insertion or placement of the needle 140. With less resistance, the needle assembly 130 may begin to move slowly. A needle 140 speed of 1 m / s is desired during needle placement or insertion. The particularly high initial resistance in this example allows for a fast initial acceleration without the pressure in the proximal chamber 118 continuing to rise or increase after the needle 140 begins to move.

[0050] Pressure P1 may be vented or a negative pressure may be applied to proximal chamber 118 through first opening 120 to reduce pressure P1 in proximal chamber 118. When pressure P1 in proximal chamber 118 is lower than pressure P2 in distal chamber 119, needle 140 may move from the extended position back to the retracted position. In the alternative, when pressure P2 exceeds pressure P1 after needle 140 is deployed, needle 140 and assembly 130 move from the extended position back to the retracted position.

[0051] After the needle or cannula assembly 130 is again returned to the retracted position, the insertion mechanism 300 also locks the needle or cannula assembly 130 in the retracted position, e.g., to prevent re-use of the needle 140. More specifically, as further shown in FIG. 6, the at least one groove 392 receives at least one friction element 282, such as a sealing mechanism, disposed on the sidewall 133 of the base 132 to prevent the needle 140 from being actuated back to the extended position. In the alternative, the at least one groove 392 includes first and second grooves 394, each of which receives a corresponding friction element 282, e.g., one or more of a sealing mechanism, an O-ring, or a C-clip, disposed on the sidewall 133 of the base 132 to lock the base 132 of the needle or cannula assembly 140 in the retracted position, to prevent re-deployment of the needle 130. In one example, high friction between each groove 394 and friction element 282 stops movement of needle assembly 130 after returning to the retracted position, locking needle assembly 130 in the retracted position.

[0052] Referring now to FIG. 7, another exemplary insertion mechanism 400 according to the present disclosure is shown. More specifically, similar to the insertion mechanism 300 of FIG. 6, the retraction member of the insertion mechanism 400 includes at least one friction element 280 in contact with the base 132, rather than a spring 142 as shown in FIG. 2, for example. The at least one friction element 280 exerts a resistive force to hold the needle or cannula assembly 130 in a retracted position, as will be further described below. In addition, the insertion mechanism 400 also includes a modified base 132 and a proximal chamber 118 with a volume smaller than the volume of the proximal chamber 118 of the insertion mechanisms 100, 200, and 300 shown in FIGS. 2, 5, and 6, respectively, as will be further described below. More generally, the insertion mechanism 400 is the same as the insertion mechanisms 100 and 300 shown in FIGS. 2 and 6, respectively, but differs in additional and / or alternative structural features included in FIG. 7 and described below. For simplicity, parts of the insertion mechanism 400 that are the same as those of the insertion mechanism 100 are given the same reference numbers and will only be described with respect to the insertion mechanisms 100 and 300.

[0053] More specifically, the insertion mechanism of FIG. 7 further includes a guide member 496 extending downwardly from the proximal end 112 of the housing 110. One side of the guide member 496 contacts the sidewall 116 of the housing and the opposite side of the guide member 496 is spaced from another area of ​​the sidewall 116 to allow pressure applied through, for example, the first opening 120 to enter the proximal chamber 118. The guide member 496 includes a central bore 497 and is cylindrical in one example. Those skilled in the art will appreciate that the guide member 496 may alternatively take on a variety of other shapes and still fall within the scope of the present disclosure. In other examples, the guide member 496 may include a pair of guide members 496, including a two-part configuration in which the guide member 496 is not comprised of a single piece. In this example, each guide member 496 of the pair of guide members 496 may be, for example, one or more of a circular, cylindrical, semicircular, semicylindrical, or rectangular shape, or any other shape or combination of shapes, and still be within the scope of the present disclosure.

[0054] In addition, the base 132 further includes a guide shaft 498 extending from the center of the proximal face 134 of the base 132 toward the proximal end 112 of the housing 110. The guide shaft 498 extends into a central bore 497 of the guide member 496. In this manner, the central bore 497 of the guide member 496 serves to guide the shaft 498 of the base 132 as the needle assembly 130 moves between the retracted and extended positions. In this alternative manner, the central bore 497 is the guide bore 497 of the guide member 496, which receives and guides the shaft 498 during deployment and retraction of the needle 140. As further shown in FIG. 7, when the guide shaft 498 is disposed within the central bore 497, there is a small radial gap 499 on either side of the guide shaft 498. As further shown, the diameter of the guide shaft 498 is less than the diameter D of the base 132 of the needle assembly 130.

[0055] So configured, the volume of the proximal chamber 118 is smaller than, for example, the proximal chamber 118 of the insertion mechanism 300 of Fig. 6, yet the stability of the needle assembly 130 is not compromised when moving from and between the retracted and extended positions. Additionally, by including the guide shaft 498 in the base 132, the effective length of the base 132 is extended from L to a length of L2 as in the other insertion mechanisms 100, 200, 300, as shown in Fig. 7. This greater length increases the stability of the base 132 while allowing the diameter D of the base to remain constant, e.g., to maintain a desired insertion force given the available pressure.

[0056] In one example, decreasing the diameter D of the base 132 reduces the insertion force relative to the available pressure. Additionally, decreasing the length L of the base 132 reduces the stability and predictability of the movement of the base 132 and, therefore, the needle assembly 130, for example, when the guide shaft 498 is not included. Thus, by including the guide shaft 498 extending from the base 132 toward the proximal end 112 of the housing 110, the combined effective length of the base 132 and the guide shaft 498 is increased to L2, while the diameter D of the base 132 remains constant, preserving the stability of the movement of the base 132 and, therefore, the needle assembly 130.

[0057] In view of the above, a person skilled in the art will recognize the following exemplary method for inserting the needle or cannula 140 of the needle or cannula assembly 130 of any of the insertion mechanisms 100, 200, 300, 400 for the drug delivery device 10 (FIG. 1) into a patient's skin.

[0058] More specifically, the method includes the step of holding the retracted position of the needle or cannula assembly 130 disposed within the housing 110 of the insertion mechanisms 100, 200, 300, 400 by a retraction member. The method also includes supplying pressure to the first opening 120 of the housing 110 of the insertion mechanisms 100, 200, 300, 400 until an operating force at which the amount of pressure P1 in the proximal chamber 118 of the housing 110 exceeds the resistance force applied to the base 132 by one or more of the retraction members or the pressure P2 in the distal chamber 119 is applied to the base 132 of the needle or cannula assembly 130. In addition, the method includes moving the needle assembly 130 from the retracted position to the extended position when the operating force exceeds the resistance force, and disposing the needle 140 of the needle or cannula assembly 130 through the second opening 124 at the distal end 114 of the housing 110 of the insertion mechanisms 100, 200, 300, 400 when the needle assembly 130 has moved to the extended position for placing the needle 140.

[0059] In one example, as described above, the step of holding the retracted position of the needle or cannula assembly 130 includes applying a resistance force to the distal surface 136 of the base 132 of the needle assembly 130 via a biasing mechanism 142. In another example, the step of holding the retracted position of the needle or cannula assembly 130 includes disposing a friction element 282 on the side wall 133 of the base 132 and applying a resistance force toward the proximal end 112 of the housing 110 via the friction element 282.

[0060] In yet another example, the method may also include either supplying a negative pressure from the first opening 120 or supplying a positive pressure from a third opening 284 (FIG. 6) disposed near the distal end 114 of the housing 110 of the housing until the pressure P2 in the distal chamber 119 of the housing 110 exceeds the pressure P1 in the proximal chamber 118. Thereby, this time, the needle or cannula assembly 130 moves from the extended position to the retracted position.

[0061] The method may further include locking the needle assembly 130 in the retracted position after it has been moved from the extended position to prevent repositioning of the needle 140 of the needle assembly 130. In one example, locking the needle assembly 140 in the retracted position includes providing at least one spring-loaded directional latch 288 on the sidewall 116 of the housing 110 that contacts either side 133 of the base 132 that has been moved into the at least one spring-loaded directional latch 288. In another example, locking the needle assembly 130 in the retracted position to prevent repositioning includes inserting at least one sealing mechanism 282 disposed on each side 133 of the base 132 into a corresponding groove 392 disposed on the sidewall 116 of the housing 110. In either case, the method may also include increasing the size of the proximal chamber 118 as the needle or cannula assembly 130 moves from the retracted position to the extended position and reducing the ejection force present at the time of needle deployment.

[0062] Those skilled in the art will appreciate many of the advantages of the aforementioned insertion mechanisms 100, 200, and 300 and methods of the present disclosure. For example, in each of the insertion mechanisms 100, 200, and 300, the insertion force and speed of the needle or cannula 140 of the needle or cannula assembly 130 can be controlled, for example, by adjusting the pressure provided by the pressure supply 126 or any other pressure source, the flow rate, and / or the proximal face 134 of the base 132, which is subjected to pressure P1, for example, in the added proximal chamber 118. Additionally, the inclusion of an O-ring or similar sealing mechanism in the distal chamber 119 just prior to the distal end 114 of the housing 110 allows the distal face 136 of the base 132 to "bounce" slightly upon contact with the O-ring 160 when moved to the extended position. This slight "bounce" may result in a slight over-penetration of the needle 140 during initial insertion, thereby reducing the incidence of tissue blockage of the needle or cannula 140.

[0063] Additionally, a preferred insertion speed may require increasing the pressure P1 in the proximal chamber 118 prior to the release of the needle or cannula assembly 130, thereby reducing friction just prior to entering the patient's skin. As a result, sufficient force is present for insertion, making insertion quicker and less painful. The insertion mechanism 100, 200, 300, 400 may also increase patient comfort and reduce the possibility of patient anxiety. For example, with conventional methods and mechanisms, the patient may need to insert a rigid needle themselves while pressing a button on the device. This type of insertion mechanism may cause patient anxiety and fear due to the patient pressing a button to control the insertion of the trocar. Additionally, known methods and mechanisms include a rigid needle combined with an external safety guard that may remain on the patient's skin when the patient removes the wearable device. In contrast, the disclosed wearable drug delivery device has a smaller injection site and can be configured to retract the cannula 140 before the patient removes the wearable device. Additionally, the automatic deployment and retraction of the needle 140 ensures that the needle 140 remains hidden at all times, improving comfort for the patient when removing the wearable drug delivery device. Furthermore, retraction of the needle 140 can also help the patient know that an injection is complete, or in the event of an error, it is acceptable to remove the wearable drug delivery device after the needle 140 has been retracted. However, the scope of the disclosure is not limited to these and any other advantages and benefits described herein, and other benefits and advantages may result from the disclosed embodiments and modifications thereto according to the principles of the present disclosure.

[0064] The above description describes various systems and methods for use with a drug delivery device. It should be clear that the system, drug delivery device, or method can further include the use of the drugs described below, but it should be noted that the following list should not be considered exhaustive or limiting. The drug is contained in a reservoir. In some examples, the reservoir is a primary container that is filled or pre-filled for treatment with the drug. The primary container can be a cartridge or a pre-filled syringe.

[0065] For example, the drug delivery device, or more specifically the reservoir of the device, may be loaded with a colony stimulating factor, such as granulocyte colony stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neupogen® (filagrastim) and Neulasta® (pegfigrastim). In various other embodiments, the drug delivery device may be used with a variety of pharmaceutical products, such as erythropoietin stimulating agents (ESAs), which may be in liquid or lyophilized form.An ESA is any molecule that stimulates erythropoiesis, such as Epogen® (epothienone alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxypolyethylene glycol epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (registered trademark), and others. Trademark) (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin zeta, epoetin sirolimus In addition to epoetin delta, each of the molecules or variants or analogs thereof disclosed in the following patents or patent applications, each of which is incorporated by reference in its entirety: U.S. Pat. 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; Nos. 5,955,422, 5,986,047, 6,583,272, 7,084,245, and 7,271,689, and PCT application publication numbers WO 91 / 05867, WO 95 / 05465, WO 96 / 40772, WO 00 / 24893, WO 01 / 81405, and WO 2007 / 136752.

[0066] The ESA can be an erythropoietin stimulating protein. As used herein, "erythropoietin stimulating protein" refers to any protein that directly or indirectly activates the erythropoietin receptor, for example, by binding to the receptor and causing dimerization. Erythropoietin stimulating proteins include erythropoietin and variants, analogs, or derivatives thereof that bind to and activate the erythropoietin receptor, antibodies that bind to and agonize the erythropoietin receptor, or peptides that bind to and activate the erythropoietin receptor. Erythropoietin stimulating proteins include, but are not limited to, epoetin alpha, epoetin beta, epoetin delta, epoetin omega, epoetin iota, epoetin zeta, and analogs thereof, pegylated erythropoietin, carbamylated erythropoietin, pseudopeptides (including EMP1 / mematide), and pseudoantibodies. Exemplary erythropoietin stimulating proteins include erythropoietin, darbepoietin, erythropoietin agonist variants, and peptides or antibodies that bind to and activate the erythropoietin receptor (and include the compounds reported in U.S. Patent Application Publication Nos. 2003 / 0215444 and 2006 / 0040858, each of which is incorporated herein by reference in its entirety), as well as erythropoietin molecules or variants or analogs thereof disclosed in the following patents or patent applications, each of which is incorporated herein by reference in its entirety: U.S. Patent Nos. 4,703,008; 5,441,868; 5,547,933; and 5,547,933. Specification No. 5,618,698, Specification No. 5,621,080, Specification No. 5,756,349, Specification No. 5,767,078, Specification No. 5, Specification No. 773,569, Specification No. 5,955,422, Specification No. 5,830,851, Specification No. 5,856,298, Specification No. 5,986,047 Specification, Specification No. 6,030,086, Specification No. 6,310,078, Specification No. 6,391,633, Specification No. 6,583,272, Specification No. 6,58 Specification No. 6,398, Specification No. 6,900,292, Specification No. 6,750,369, Specification No. 7,030,226, Specification No. 7,084,245,and 7,217,689, and U.S. Patent Application Publication Nos. 2002 / 0155998, 2003 / 0077753, 2003 / 0082749, 2003 / 0143202, 2004 / 0009902, 2004 / 0071694, 2004 / 0091961, 2004 / 0143857, 2004 / 0157293, 2004 / 0175379, 2004 / 0175824, 2004 / 02 Specification No. 29318, Specification No. 2004 / 0248815, Specification No. 2004 / 0266690, Specification No. 2005 / 001991 Specification No. 4, Specification No. 2005 / 0026834, Specification No. 2005 / 0096461, Specification No. 2005 / 0107297 , Specification No. 2005 / 0107591, Specification No. 2005 / 0124045, Specification No. 2005 / 0124564, No. 20 Specification No. 05 / 0137329, Specification No. 2005 / 0142642, Specification No. 2005 / 0143292, Specification No. 2005 / 01 Nos. 53879, 2005 / 0158822, 2005 / 0158832, 2005 / 0170457, 2005 / 0181359, 2005 / 0181482, 2005 / 0192211, 2005 / 0202538, 2005 / 0227289, 2005 / 0244409, 2006 / 0088906, and 2006 / 0111279, and PCT publication number WO 91 / 05867. Brochure, Brochure No. 95 / 05465, Brochure No. 99 / 66054, Brochure No. 00 / 24893, Brochure No. 01 / 81405, Brochure No. 00 / 61637, Brochure No. 01 / 36489, Brochure No. 02 / 014356, Brochure No. 02 / 19963, Brochure No. 02 / 20034, Brochure No. 02 / 49673, Brochure No. 02 / 085940, Brochure No. 03 / 029291, Brochure No. 2003 / 055526,Brochure No. 2003 / 084477, Brochure No. 2003 / 094858, Brochure No. 2004 / 002417, Brochure No. 2004 / 002424, Brochure No. 2004 / 009627, Brochure No. 2004 / 024761, Brochure No. 2004 / 033651, Brochure No. 2004 / 035603 , pamphlet No. 2004 / 043382, pamphlet No. 2004 / 101600, pamphlet No. 2004 / 101606, pamphlet No. 2004 / 101611, pamphlet No. 2004 / 106373, pamphlet No. 2004 / 018667, pamphlet No. 2005 / 001025, pamphlet No. 2005 / 001 Brochure No. 136, Brochure No. 2005 / 021579, Brochure No. 2005 / 025606, Brochure No. 2005 / 032460, Brochure No. 2005 / 051327, Brochure No. 2005 / 063808, Brochure No. 2005 / 063809, Brochure No. 2005 / 070451, Brochure No. 2005 / 081687, Brochure No. 2005 / 084711, Brochure No. 2005 / 103076, Brochure No. 2005 / 100403, Brochure No. 2005 / 092369, Brochure No. 2006 / 50959, Brochure No. 2006 / 02646 and Brochure No. 2006 / 29094. ,

[0067] Examples of other pharmaceutical products for use in the device may include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab), and Prolia™ (denosumab), other biological agents such as Enbrel® (etanercept, TNF-receptor / Fc fusion protein, TNF blocker), Neulasta® (pegfigrastim, pegylated filgratim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CS, hu-MetG-CSF), and Nplate® (romiplostim), small molecule drugs such as Sensipa® (cinacalcet). The device may also be a therapeutic antibody, polypeptide, protein, or other chemical such as iron, for example ferumoxytol, iron dextran, iron glyconate, and iron sucrose. The pharmaceutical product may be either liquid or reconstituted from a lyophilized state.

[0068] Among certain exemplary proteins are the following specific proteins, including fusions, fragments, analogs, variants, or derivatives thereof: OPGL-specific antibodies and antibody-related proteins, including, but not limited to, fully humanized and human OPGL-specific antibodies, particularly OPGL-specific antibodies, including fully humanized monoclonal antibodies, peptibodies, and related proteins, and others (also referred to as RANKL-specific antibodies, peptibodies, and others), including those antibodies described in PCT Publication No. WO 03 / 002713, which are incorporated herein by reference in their entireties, particularly those having the sequences set forth therein, 9H7, 18B2, 2D8, 2E11, 16E1, and 22B3, including OPGL-specific antibodies having either the light chain of SEQ ID NO:2 as shown in Figure 2 therein and / or the heavy chain of SEQ ID NO:4 as shown in Figure 4 therein, each of which is individually and expressly disclosed in the above publications, which are incorporated herein by reference in their entireties.

[0069] myostatin-specific peptibodies, particularly those described in U.S. Patent Application Publication No. 2004 / 0181033 and PCT Patent Publication No. WO 2004 / 058988, each of which is incorporated by reference in its entirety, particularly in the portions relating to myostatin-specific peptibodies, including the mTN8-19 family, including those in SEQ ID NOs: 305-351, e.g., TN8-19-1 to TN8-19-40, TN8-19 con1 and TN8-19 These include, but are not limited to, con2, peptibodies of the mL2 family of SEQ ID NOs: 357 to 383, the mL15 family of SEQ ID NOs: 384 to 409, the mL17 family of SEQ ID NOs: 410 to 438, the mL20 family of SEQ ID NOs: 439 to 446, the mL21 family of SEQ ID NOs: 447 to 452, the mL24 family of SEQ ID NOs: 453 to 454, and those of SEQ ID NOs: 615 to 631.

[0070] IL-4 receptor specific antibodies, peptibodies and related proteins and others, particularly those that inhibit activities mediated by the binding of IL-4 and / or IL-13 to the receptor, as described in PCT Publication No. WO 2005 / 047331 or PCT Application No. PCT / US2004 / 37242 and US Patent Publication No. 2005 / 112694, which are incorporated herein by reference in their entireties, particularly in the portions relating to IL-4 receptor specific antibodies, and in particular the antibodies described therein, particularly including, but not limited to, 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 and those designated therein, each of which is individually and specifically incorporated by reference in its entirety as if disclosed in the above publications.

[0071] Interleukin 1-receptor ("IL1-R1") specific antibodies, peptibodies, and related proteins and others, including those described in U.S. Patent Application Publication No. 2004 / 097712, which is incorporated herein by reference in its entirety, particularly in the portion relating to IL1-R1 specific binding proteins, particularly monoclonal antibodies, including, but not limited to, 15CA, 26F5, 27F2, 24E12, and 10H7 and those designated therein, each of which is incorporated herein by reference in its entirety as individually and specifically disclosed in the above publication.

[0072] Ang2 specific antibodies, peptibodies, and related proteins and the like, as described in PCT Publication No. WO 03 / 057134 and U.S. Patent Publication No. 2003 / 0229023, each of which is incorporated by reference in its entirety, particularly in the portions relating to Ang2 specific antibodies and peptibodies and the like, and in particular the sequences described therein, L1(N), L1(N)WT, L1(N)1K WT, 2xL1(N), 2xL1(N)WT, Con(N), Con4(N)1K WT, 2xCon4(N)1K, L1C, L1C 1K, 2xL1C, Con4C, Con4C 1K, 2xCon4C Anti-Ang2 antibodies and formulations such as those described in PCT Publication No. WO 2003 / 030833, including, but not limited to, Con4-L1(N), Con4-L1C, TN-12-9(N), C17(N), TN8-8(N), TN8-14(N), Con 1(N), and the various substituted sequences thereof described therein, each of which is individually and specifically disclosed in the above publications, and the various substituted sequences thereof described therein, each of which is individually and specifically disclosed in the above publications, and the various substituted sequences thereof described therein, each of which is individually and specifically disclosed in the above publications, and the various substituted sequences thereof described therein, , Ab531, Ab533, Ab535, Ab536, Ab537, Ab540, Ab543, Ab544, Ab545, Ab546, A551, Ab553, Ab555, Ab558, Ab559, Ab565, AbF1AbFD, AbFE, AbFJ, AbFK, AbG1D4, AbGC1E8, AbH1C12, AbIA1, AbIF, AbIK, AbIP, and AbIP.

[0073] NGF-specific antibodies, peptibodies, and related proteins and others, including but not limited to those described in U.S. Patent Application Publication No. 2005 / 0074821 and U.S. Patent No. 6,919,426, which are incorporated by reference in their entireties in this regard with respect to NGF-specific antibodies and related proteins, and specifically including but not limited to 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11 and the NGF-specific antibodies designated therein, each of which is incorporated by reference in its entirety as individually and specifically disclosed in the above publications.

[0074] CD22-specific antibodies, peptibodies, and related proteins and others, such as those described in U.S. Pat. No. 5,789,554, the entirety of which is incorporated herein by reference, particularly human CD22-specific antibodies, such as, but not limited to, humanized and fully human antibodies, including, but not limited to, humanized and fully human monoclonal antibodies, particularly human CD22-specific IgG antibodies, such as dimers of human-mouse monoclonal hLL2 gamma chain disulfide crosslinked to human-mouse monoclonal hLL2 kappa chain, such as, but not limited to, epratuzumab, a human CD22-specific fully humanized antibody having CAS Registry Number 501423-23-0.

[0075] IGF-1 receptor specific antibodies, peptibodies, and related proteins, and others, such as those described in PCT Publication No. WO 06 / 069202, which is incorporated herein by reference in its entirety with respect to IGF-1 receptor specific antibodies and related proteins, each of which is individually and specifically disclosed in said publication, L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11, L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, which are incorporated herein by reference in their entireties. , L20H20, L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L 30H30, L31H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40 These include, but are not limited to, IGF-1 specific antibodies designated H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52 and IGF-1R binding fragments and derivatives thereof.

[0076] Also among the non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the invention are each and every one of the following:

[0077] (i) U.S. Patent Application Publication Nos. 2006 / 0040358 (published February 23, 2006), 2005 / 0008642 (published January 13, 2005), and 2004 / 0228859 (published November 18, 2004), including, but not limited to, 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 described therein.

[0078] (ii) PCT Application Publication Nos. WO 06 / 138729 (published December 28, 2006) and WO 05 / 016970 (published February 24, 2005), and Lu et al. (2004), J. Biol. Chem. 279:2856-2865, including, but not limited to, the antibodies 2F8, A12, and IMC-A12 described therein.

[0079] (iii) PCT application publication numbers WO 07 / 012614 (published February 1, 2007), WO 07 / 000328 (published January 4, 2007), WO 06 / 013472 (published February 9, 2006), WO 05 / 058967 (published June 30, 2005), and WO 03 / 059951 (published July 24, 2003).

[0080] (iv) U.S. Patent Application Publication No. 2005 / 0084906 (published April 21, 2005), including antibody 7C10, chimeric antibody C7C10, antibody h7C10, antibody 7H2M, and chimeric antibodies described therein. * Humanized antibody 7C10, antibody GM 607, humanized antibody 7C10 version 1, humanized antibody 7C10 version 2, humanized antibody 7C10 version 3, and antibody 7H2HM.

[0081] (v) U.S. Patent Application Publication Nos. 2005 / 0249728 (published November 10, 2005), 2005 / 0186203 (published August 25, 2005), 2004 / 0265307 (published December 30, 2004), and 2003 / 0235582 (published December 25, 2003), and Maloney et al. (2003), Cancer Res. 63:5073-5083, including, but not limited to, antibody EM164, resurfaced antibody EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2, and huEM164 v1.3 as described therein.

[0082] (vi) U.S. Pat. No. 7,037,498, issued May 2, 2006; U.S. Patent Application Publication Nos. 2005 / 0244408, published November 30, 2005, and 2004 / 0086503, published May 6, 2004; and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073, such as antibody CP-751,871, including antibodies produced by hybridomas having ATCC Accession Nos. PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, and each of antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3.

[0083] (vii) U.S. Patent Application Publication Nos. 2005 / 0136063 (published June 23, 2005) and 2004 / 0018191 (published January 29, 2004), including, but not limited to, antibody 19D12 and antibodies therein comprising a heavy chain encoded by plasmid 15H12 / 19D12 HCA(γ4), deposited with the ATCC under no. PTA-5214, and a light chain encoded by the polynucleotide of plasmid 15H12 / 19D12 LCF(K), deposited with the ATCC under no. PTA-5220.

[0084] (viii) U.S. Patent Application Publication No. 2004 / 0202655 (published October 14, 2004), including, but not limited to, the antibodies PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2, PINT-12A3, PINT-12A4, and PINT-12A5 described therein, each and every of which is incorporated by reference in its entirety, particularly with respect to the above antibodies, peptibodies, and related proteins that target the IGF-1 receptor, and others.

[0085] B7-related protein 1-specific antibodies, peptibodies, related proteins and the like ("B7RP-1", or also referred to in the literature as B7H2, ICOSL, B7h, and CD275), particularly B7RP-specific fully human monoclonal IgG2 antibodies, particularly fully human IgG2 monoclonal antibodies that bind to an epitope within the first immunoglobulin-like domain of B7RP-1, particularly those that inhibit the interaction of B7RP-1 with its natural receptor ICOS on activated T cells, particularly those disclosed in U.S. Patent Application Publication No. 2008 / 0166352 and PCT Application Publication No. WO 07 / 011941, which are hereby incorporated by reference in their entireties with respect to such antibodies and related proteins, in all of the above respects, and in which each is individually and expressly described above. As disclosed in the above publications, these include, but are not limited to, the antibodies designated as 16H (of which the light chain variable region and heavy chain variable region sequences are SEQ ID NO:1 and SEQ ID NO:7, respectively), 5D (of which the light chain variable region and heavy chain variable region sequences are SEQ ID NO:2 and SEQ ID NO:9, respectively), 2H (of which the light chain variable region and heavy chain variable region sequences are SEQ ID NO:3 and SEQ ID NO:10, respectively), 43H (of which the light chain variable region and heavy chain variable region sequences are SEQ ID NO:6 and SEQ ID NO:14, respectively), 41H (of which the light chain variable region and heavy chain variable region sequences are SEQ ID NO:5 and SEQ ID NO:13, respectively), and 15H (of which the light chain variable region and heavy chain variable region sequences are SEQ ID NO:4 and SEQ ID NO:12, respectively), which are incorporated herein by reference in their entireties.

[0086] IL-15 specific antibodies, peptibodies, and related proteins and others, such as those disclosed in U.S. Patent Application Publication Nos. 2003 / 0138421, 2003 / 023586, 2004 / 0071702, and U.S. Patent No. 7,153,507, each of which is incorporated by reference in its entirety with respect to IL-15 specific antibodies and related proteins, including human monoclonal antibodies, particularly peptibodies, including, but not limited to, HuMax IL-15 antibodies and related proteins, such as 146B7.

[0087] IFN-gamma specific antibodies, peptibodies, and related proteins, and others, particularly human IFN-gamma specific antibodies, particularly fully human anti-IFN-gamma antibodies, such as those described in U.S. Patent Application Publication No. 2005 / 0004353, which is hereby incorporated by reference in its entirety with respect to IFN-gamma specific antibodies, particularly, for example, those designated as 1118, 1118 * , 1119, 1121, and 1121 * and the antibodies so designated. In addition to the entire sequences of the heavy and light chains of each of these antibodies, the sequences of their heavy and light chain variable regions and complementarity-determining regions are each individually and expressly incorporated by reference in their entirety into the present application as disclosed in the above-mentioned publication and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115. In addition, the descriptions of the properties of these antibodies provided in the above-mentioned publication are also incorporated by reference in their entirety into the present application. Specific antibodies include 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-mentioned U.S. patent application publication. Antibody 1119 having the complete heavy chain of SEQ ID NO: 17 and the complete light chain of SEQ ID NO: 18 as disclosed in the above-mentioned U.S. patent application publication and as disclosed therein.

[0088] TALL-1 specific antibodies, peptibodies, and related proteins and others, and TALL specific binding proteins, such as those described in U.S. Patent Application Publication Nos. 2003 / 0195156 and 2006 / 0135431, each of which is incorporated by reference in its entirety for TALL-1 binding proteins, particularly the molecules in Tables 4 and 5B, each of which is incorporated by reference in its entirety as if fully disclosed in the above publications.

[0089] Parathyroid hormone ("PTH")-specific antibodies, peptibodies, and related proteins and others, such as those described in U.S. Pat. No. 6,756,480, which is incorporated by reference in its entirety, specifically with respect to proteins that bind PTH.

[0090] Thrombopoietin receptor ("TPO-R")-specific antibodies, peptibodies, and related proteins, and others, such as those described in U.S. Pat. No. 6,835,809, the entirety of which is incorporated herein by reference, specifically with respect to proteins that bind to TPO-R.

[0091] Hepatocyte growth factor ("HGF") specific antibodies, peptibodies, and related proteins and others that target the HGF / SF:cMet axis (HGF / SF:c-Met), including, for example, the fully human monoclonal antibody that neutralizes hepatocyte growth factor / scatter factor (HGF / SF), described in U.S. Patent Application Publication No. 2005 / 0118643 and PCT Application Publication No. WO 2005 / 017107, each of which is incorporated by reference in its entirety, particularly in the portions relating to proteins that bind HGF, huL2G7, described in U.S. Patent No. 7,220,410, and OA-5d5, described in U.S. Patent Nos. 5,686,292 and 6,468,529, and PCT Application Publication No. WO 96 / 38557.

[0092] TRAIL-R2 specific antibodies, peptibodies, related proteins and others, such as those described in U.S. Pat. No. 7,521,048, which is incorporated by reference in its entirety, particularly in the portion relating to proteins that bind TRAIL-R2.

[0093] Activin A-specific antibodies, peptibodies, related proteins, and the like, including, but not limited to, those described in U.S. Patent Application Publication No. 2009 / 0234106, the entirety of which is incorporated herein by reference in its entirety in the section concerning proteins that bind activin A.

[0094] TGF-beta specific antibodies, peptibodies, related proteins, and others, including but not limited to those described in U.S. Pat. No. 6,803,453 and U.S. Patent Application Publication No. 2007 / 0110747, which are incorporated by reference in their entireties in their portions relating to proteins that bind TGF-beta.

[0095] Amyloid beta protein specific antibodies, peptibodies, related proteins, and the like, including but not limited to those described in PCT Publication No. WO 2006 / 081171, which is incorporated herein by reference in its entirety, particularly in the portion relating to proteins that bind to amyloid beta protein. One contemplated antibody 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 above publication.

[0096] c-Kit specific antibodies, peptibodies, related proteins, and the like, including but not limited to those described in U.S. Patent Application Publication No. 2007 / 0253951, which is incorporated herein by reference in its entirety, particularly in the portion relating to proteins that bind c-Kit and / or other stem cell factor receptors.

[0097] OX40L-specific antibodies, peptibodies, related proteins, and the like, including but not limited to those described in U.S. Patent Application Publication No. 2006 / 0002929, which is incorporated by reference in its entirety, particularly in the portion relating to proteins that bind OX40L and / or other ligands of the OX40 receptor.

[0098] Activase® (alteplase, tPA), Aranesp® (darbepoetin), Epogen® (epoetin alfa, or erythropoietin), GLP-1, Avonex® (interferon beta 1a), Bexxar® (tositumomab, an anti-CD22 monoclonal antibody), Betaseron® (interferon-beta), Campath® (alemtuzumab, an anti-CD52 monoclonal antibody), Dynepo® (epoetin delta), Velcade® (bortezomib), MLN0002 (anti-alpha4beta7 mAb), MLN1202 (anti-CCR2 chemokine receptor mAb), Enbrel (etanercept, TNF-receptor / Fc fusion protein, TNF blocker), Eprex® (epoetin alfa), Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1), Genotropin® (somatropin, human growth hormone), Herceptin® (trastuzumab, anti-HER2 / neu(erbB2) receptor mAb), Hu Matrope® (somatropin, human growth hormone), Humira® (adalimumab), insulin solution, Infergen® (interferon alfacon-1), Natrecor® (nesiritide, recombinant human B-type natriuretic peptide (hBNP), Kineret® (anakinra), Leukine® (sargamostim, rhuGM-CSF), LymphoCide® (epratuzumab, anti-CD22 mAb), Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb), Metalyse® (tenecteplase, t-PA analog), Mircera® (methoxypolyethylene glycol epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP870), Soliris™ (eculizumab), pexelizumab (anti-C5 complement), Numax® (MEDI-524), Lucentis® (ranibizumab), Panorex® (17-1A, edrecolomab), Trabio® (lerdelimumab), TheraCim hR3 (nimotuzumab), Omnitarg (pertuzumab, 2C4), Osidem® (IDM-1), OvaRex® (B43.13), Nuvion® (vigilizumab), cantuzumab mertansine (huC242-DM1), NeoRecormon® (epoetin beta), Neumega® (oprelvekin, human interleukin-11), Neulasta® (pegylated filgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filagrastim, G-CSF, hu-MetG-CSF), Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody), Procrit® (epoetin alfa), Remicade® (infliximab, anti-TNFα monoclonal antibody), Reopro® (abciximab, anti-GP llb / llia 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-IL 15 antibody, see U.S. Pat. No. 7,153,507), Tysabri® (natalizumab, anti-α4 integrinmAb), Valortim® (MDX-1303, anti-B, anthrax protective antigen mAb), ABthrax™, Vectibix® (panitumumab), Xolair® (omalizumab), ETI211 (anti-MRSA mAb), IL-1 Trap (the Fc portion of human IgG1 and the extracellular domains of both IL-1 receptor components (type I receptor and receptor accessory protein)), VEGF Trap (the Ig domain of VEGFR1 fused to IgG1 Fc), Zenapax® (daclizumab), Zenapax® (daclizumab, anti-IL-2Rα mAb), Zevalin® (ibritumomab tiuxetan), Zetia® (ezetimibe), Orencia® (atacicept, TACI-Ig), anti-CD80 monoclonal antibody (galiximab), anti-CD23 mAb (lumiliximab), BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist), CNTO 148 (golimumab, anti-TNFα mAb), HGS-ETR1 (mapatumumab, human anti-TRAIL receptor-1 mAb), HuMax-CD20 (ocrelizumab, anti-CD20 human mAb), HuMax-EGFR (zalutumumab), M200 (volociximab, anti-α5β1 integrin mAb), MDX-010 (ipilimumab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1), anti-BR3 mAb, anti-C, difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388), anti-CD22 dsFv-PE38 conjugate (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-Cripto mAb, anti-CTGF idiopathic pulmonary fibrosis phase I fibrogen (FG-3019), anti-CTLA4 mAb, anti-eotaxin 1 mAb (CAT-213), anti-FGF8 mAb, anti-ganglioside GD2 mAb, anti-ganglioside GM2 mAbmAb, anti-GDF-8 human mAb (MYO-029), anti-GM-CSF receptor mAb (CAM-3001), anti-HepC mAb (HuMax HepC), anti-IFNα mAb (MEDI-545, MDX-1103), anti-IGF1R mAb, anti-IGF-1R mAb (HuMax-Inflam), anti-IL12 mAb (ABT-874), anti-IL 12 / IL23 mAb (CNTO 1275), anti-IL 13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-integrin receptor mAb (MDX-018, CNTO 95), anti-IP10 ulcerative colitis mAb (MDX-1100), anti-LLY antibody, BMS-66513, anti-mannose receptor / hCGβ mAb (MDX-1307), anti-mesothelin dsFv-PE38 conjugate (CAT-5001), anti-PD1 mAb (MDX-1106 (ONO-4538)), anti-PDGFRα antibody (IMC-3G3), anti-TGFβ mAb (GC-1008), anti-TRAIL receptor 2 human mAb (HGS-ETR2), anti-TWEAK mAb, anti-VEGFR / Flt-1 mAb, anti-ZP3 mAb (HuMax-ZP3), NVS antibody #1, and NVS antibody #2.

[0099] Sclerostin antibodies may also be included, such as, but not limited to, romosozumab, biosozumab, or BPS 804 (Novartis). Additionally, therapeutic agents such as rilotumumab, bixaloma, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, bizupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX, or XGEVA may be included. Additionally, the device may include a human Proprotein Convertase Subtilisin / Kexin Type I inhibitor. The present invention can include monoclonal antibodies (IgG) that bind to PCSK9 (prostate cancer cell type 9), and are described, for example, in U.S. Pat. No. 8,030,547, U.S. Patent Application Publication No. 2013 / 0064825, WO 2008 / 057457, WO 2008 / 057458, WO 2008 / 057459, WO 2008 / 063382, WO 2008 / 133647, WO 2009 / 100297, WO 2009 / 100318, WO 2011 / 037791, WO 2011 / 053759, WO 2011 / 053 These are Brochure No. 783, Brochure No. 2008 / 125623, Brochure No. 2011 / 072263, Brochure No. 2009 / 055783, Brochure No. 2012 / 0544438, Brochure No. 2010 / 029513, Brochure No. 2011 / 111007, Brochure No. 2010 / 077854, Brochure No. 2012 / 088313, Brochure No. 2012 / 101251, Brochure No. 2012 / 101252, Brochure No. 2012 / 101253, Brochure No. 2012 / 109530 and Brochure No. 2001 / 031007.

[0100] It may also include oncolytic immunotherapeutics or other oncolytic HSVs for the treatment of malignant melanoma and other cancers. Examples of oncolytic HSVs include, but are not limited to, oncolytic immunotherapeutics (U.S. Pat. Nos. 7,223,593 and 7,537,924), OncoVEXGALV / CD (U.S. Pat. No. 7,981,669), OrienX010 (Lei et al. (2013), World J. Gastroenterol, 19:5138-5143), G207, 1716, NV 1020, NV12023, NV1034, and NV1042 (Vargehes et al. (2002), Cancer Gene Ther., 9(12):967-978).

[0101] Also included are TIMPs. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) that are important in many natural processes. TIMP-3 is made by a variety of cells and is present in the extracellular matrix, inhibiting all major cartilage-degenerating metalloproteinases and may play a role in many degenerative diseases of connective tissue, including rheumatoid arthritis and osteoarthritis, as well as cancer and cardiovascular conditions. The amino acid sequence of TIMP-3 and the nucleic acid sequence of DNA encoding TIMP-3 are disclosed in U.S. Patent No. 6,562,596, issued May 13, 2003, the disclosure of which is incorporated herein by reference. TIMP mutation descriptions can be found in U.S. Patent Application Publication No. 2014 / 0274874 and PCT Application Publication No. WO 2014 / 152012.

[0102] Also included are antagonistic antibodies for the human calcitonin gene-related peptide (CGRP) receptor and bispecific antibody molecules that target the CGRP receptor and other headache targets. More information regarding these molecules can be found in PCT Application No. WO 2010 / 075238.

[0103] Additionally, the device can use bispecific T cell-engaging (BiTE®) antibodies, such as BLINCYTO® (blinatumomab). Alternatively, an APJ macromolecular agonist, such as apelin or an analog thereof, can be included in the device. Information regarding such molecules can be found in PCT Application Publication No. WO 2014 / 099984.

[0104] In certain embodiments, the medicament comprises a therapeutically effective amount of an anti-thymic stromal lymphocyte growth factor (TSLP) or TSLP receptor antibody. Anti-TSLP antibodies that may be used in such embodiments include, but are not limited to, those described in U.S. Patent Nos. 7,982,016 and 8,232,372, and U.S. Patent Publication No. 2009 / 0186022. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in U.S. Patent No. 8,101,182. In a particularly preferred embodiment, the medicament comprises a therapeutically effective amount of the anti-TSLP antibody designated A5 in U.S. Patent No. 7,982,016.

[0105] The drug infusion device, system, method, and elements thereof are described with respect to exemplary embodiments, but are not limited thereto. The detailed description is to be construed as an example only, and does not describe every possible embodiment of the invention, since describing every single possible embodiment would be impractical, if not impossible. Numerous alternative embodiments can be implemented using current technology, or technology developed after the filing date of this patent, and are included within the scope of the claims that define the invention.

[0106] It should be understood that the legal scope of the present invention is defined by the language of the claims set forth at the end of this patent, and that the scope of the appended claims should be interpreted broadly to include devices, systems, methods, and other modifications and embodiments thereof that may be made by those skilled in the art without departing from the scope of equivalents of the elements thereof.

Claims

1. a main housing having a reservoir, a fluid path connector coupled to the reservoir, and a pressure supply; an insertion mechanism disposed within the main housing and operatively connected to the pressure source, the fluid pathway connector defining a fluid flow path between the container and the insertion mechanism; a housing having a proximal end, a distal end, a sidewall disposed between the distal end and the proximal end, a first opening disposed near the proximal end, and a second opening disposed at the distal end, the first opening being coupled to the pressure supply; a needle or cannula assembly disposed within the housing and movable between a retracted position and an extended position, the needle or cannula assembly including a base having a proximal surface and a distal surface, the needle or cannula assembly being disposed between an inner surface of a sidewall of the housing and coupled to the distal surface of the base, the base dividing the housing into a proximal chamber and a distal chamber; a retraction member disposed within the housing to hold the needle or cannula assembly in the retracted position until the needle or cannula assembly is moved to the extended position, the retraction member contacting and exerting a resistive force on the base; an insertion mechanism including: A wearable medication delivery device comprising: the pressure supply device supplies pressure to the proximal chamber through the first opening until an amount of pressure P1 in the proximal chamber applies an actuation force to the proximal face of the base of the needle or cannula assembly such that the amount of pressure P1 in the proximal chamber overcomes the resistance of the retraction member to move the needle or cannula assembly from the retracted position to the extended position, and the needle or cannula assembly is disposed in the extended position for deploying the needle or cannula assembly through a second opening in the distal end of the housing; the needle or cannula assembly is secured back in the retracted position by one or more of: (1) at least one spring-loaded directional latch disposed on a sidewall of the housing when the needle or cannula assembly is disposed between the inner surfaces of the sidewalls; or (2) at least one groove disposed on the sidewall of the housing, the at least one groove for receiving at least one sealing mechanism disposed on the sidewall of the base. Wearable drug delivery devices.

2. 2. The wearable medication delivery device of claim 1, wherein the retraction member includes a biasing mechanism comprising one or more of a spring having a first end attached to the base and a second end attached to the distal end of the housing, or a flexible fluid path member having a first end attached to the base and a second end attached to the proximal end of the housing, the biasing mechanism retracting the needle or cannula assembly to the retracted position after pressure P1 in the proximal chamber is released.

3. 3. The wearable medication delivery device of claim 2, wherein the insertion mechanism further includes a first connector extending upward from the proximal surface of the base, and a flexible fluid path member having a first end operatively connected to the first connector extending upward from the proximal surface of the base and a second end operatively connected to a second connector extending downward from the proximal end of the housing, the flexible fluid path member being movable with the needle or cannula assembly.

4. 3. The wearable medication delivery device of claim 2, further comprising a step disposed on the side wall near the distal end of the housing, the step having a sealing mechanism, the sealing mechanism being an O-ring, and the distal surface of the base contacts the O-ring to provide shock absorbing support when the needle or cannula assembly is moved from the retracted position to the extended position.

5. The wearable medication delivery device of claim 2, wherein the housing includes a sidewall having a threaded inner surface, and the base further includes a side surface that contacts the threaded inner surface of the sidewall, the side surface of the base having a threaded surface that corresponds to the threaded inner surface of the sidewall of the housing.

6. The wearable medication delivery device of claim 1 , wherein the retraction member comprises at least one friction element, the at least one friction element contacting the side wall of the base and comprising one or more of at least one sealing mechanism or O-ring.

7. 7. The wearable drug delivery device of claim 6, wherein when negative pressure is applied from the first opening or positive pressure is applied to a third opening in the side wall of the housing, located near the distal end of the housing, the pressure P2 in the distal chamber exceeds the pressure P1 in the proximal chamber, thereby causing the needle or cannula assembly to return to the retracted position again after the needle or cannula assembly is deployed.

8. The wearable medication delivery device of claim 6, wherein the at least one groove for receiving the at least one sealing mechanism of the needle or cannula assembly is disposed in the side wall of the base to prevent the needle or cannula assembly from being moved back to the extended position.

9. 9. The wearable medication delivery device of claim 8, wherein the at least one spring-loaded directional latch includes a first spring-loaded directional latch disposed in one region of the side wall of the housing and a second spring-loaded latch disposed in another region of the side wall of the housing, each of the first spring-loaded directional latch and the second spring-loaded latch having an inclined side that contacts a corresponding inclined side of the base on each side of the base to lock the base of the needle or cannula assembly and prevent re-deployment.

10. 9. The wearable medication delivery device of claim 8, wherein the at least one groove includes a first groove disposed in one region of the side wall of the housing and a second groove disposed in another region of the side wall of the housing, each of the first groove and second groove adapted to receive a corresponding friction element to secure the base of the needle or cannula assembly and prevent re-deployment.

11. The wearable medication delivery device of claim 6, wherein the housing further includes a guide member extending downwardly from the proximal chamber of the housing and having a central hole, and the base further includes a shaft extending from the center of the proximal face of the base into the central hole, the central hole guiding the shaft of the base as the needle or cannula assembly moves between the retracted and extended positions to reduce the volume of the proximal chamber.

12. a housing having a proximal end, a distal end, a sidewall disposed between the distal end and the proximal end, a first opening disposed within the housing near the proximal end, the first opening adapted to be operatively coupled to a pressure source, and a second opening disposed at the distal end of the housing; a needle or cannula assembly disposed within the housing and movable between a retracted position and an extended position, the needle or cannula including a base having a proximal surface and a distal surface, the needle or cannula being disposed between an inner surface of a sidewall of the housing and attached to the base; a retraction member contacting the base and applying a resistive force to hold the needle or cannula assembly in the retracted position until moved to the extended position; a flexible fluid path member having a first end operatively coupled to a connector extending from the proximal face of the base and a second end operatively coupled to a connector extending from the proximal end of the housing; An insertion mechanism for a medication delivery device, comprising: Pressure is supplied through the first opening until an amount of pressure P1 applies an actuation force to the proximal surface of the base of the needle or cannula assembly that overcomes the resistance of the retraction member and moves the needle or cannula assembly from the retracted position to the extended position, the needle or cannula assembly extending from the second opening at the distal end of the housing in the extended position.

13. 13. The insertion mechanism of claim 12, wherein the base divides the housing into a proximal chamber and a distal chamber such that when pressure P1 in the proximal chamber exceeds pressure P2 in the distal chamber, the needle or cannula assembly moves from the retracted position to the extended position.

14. 13. The insertion mechanism of claim 12, further comprising a pair of sealing mechanisms disposed on the housing side walls near the distal end of the housing, whereby the distal face of the base contacts the sealing mechanisms when the needle or cannula assembly is in the extended position.

15. 13. The insertion mechanism of claim 12, wherein the housing includes a sidewall having a threaded inner surface, the base further includes a side surface in contact with the threaded inner surface of the sidewall, the side surface of the base having a threaded surface that corresponds to the threaded inner surface of the sidewall of the housing, the threaded inner surface of the sidewall of the housing and the threaded surface of the side surface of the base are one of coarse threads or fine threads, the coarse threads allow the needle or cannula to rotate at least 2-3 times during insertion and the fine threads allow the needle or cannula to rotate at least 8-10 times during insertion.

16. The insertion mechanism of claim 12 , wherein the flexible fluid path member is movable between a retracted position and an extended position corresponding to the retracted position and the extended position of the needle or cannula assembly.

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