Platform assembly process for drug delivery device

Abstract

To provide a method for assembling a platform drug delivery device.SOLUTION: A method includes providing a set of base components, and identifying, based on at least one desired characteristic of a platform drug delivery device 100, a rear sub-assembly for the drug delivery device from a group of rear sub-assemblies. The identified rear sub-assembly is selected, and a front sub-assembly is identified based on the at least one desired characteristic from a group of front sub-assemblies. The identified front-assembly is selected, and the drug delivery device is assembled using the set of base components, the rear sub-assembly, and the front sub-assembly.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS Priority is claimed to U.S. Provisional Patent Application No. 62 / 745,739, filed October 15, 2018, which is incorporated herein by reference in its entirety.

[0002] The present disclosure relates generally to drug delivery devices, and more particularly to platform-based manufacturing techniques for drug delivery devices. [Background technology]

[0003] Drug delivery devices such as autoinjectors and on-body injectors offer several advantages in the delivery of medications and / or therapies, including, for example, ease of use when compared to traditional delivery methods using traditional syringes.

[0004] Autoinjectors can be used to deliver a number of different drugs with varying viscosities and / or desired amounts. As a result, assembly of these devices can be complicated due to the need to precisely identify the appropriate components that can effectively deliver the drug to the user. As an example, drugs with higher viscosities may require a stronger drive assembly with more robust components to properly deliver the drug within the correct time frame. Similarly, larger doses of drug may also require a more robust drive assembly. Summary of the Invention [Means for solving the problem]

[0005] According to a first aspect, a method for assembling a platform-based drug delivery device includes providing a set of base components and identifying a rear subassembly of the drug delivery device from a group of rear subassemblies based on at least one desired characteristic of the platform-based drug delivery device. The identified rear subassembly is selected, and a front subassembly is identified from a group of front subassemblies based on the at least one desired characteristic. The identified front assembly is selected, and the drug delivery device is assembled using the set of base components, the rear subassembly, and the front subassembly. The method may optionally include applying a skin to the device, where the skin may be selected based on at least one attribute from an intended user group.

[0006] In some embodiments, the at least one desired characteristic is at least one of drug viscosity or drug amount. In some embodiments, each of the rear subassemblies in the group of rear subassemblies may include a different drive mechanism. Furthermore, each of the front subassemblies may include a different syringe assembly, which may be made from one of glass or polymeric materials. In some examples, the set of base components is geometrically identical between configurations of the drug delivery device.

[0007] According to another aspect, a method for assembling a platform-based drug delivery device includes providing a set of base components for the device, identifying a first subassembly for the device from a first group of selectable subassemblies, and selecting the identified first subassembly. A second subassembly is identified from the second group of selectable subassemblies, and the second subassembly is selected. A third subassembly is also identified from the third group of selectable subassemblies, and the third subassembly is selected. The drug delivery device is assembled using the set of base components, the first subassembly, the second subassembly, and the third subassembly.

[0008] According to a third aspect, a platform-based drug delivery device is prepared by a process including providing a set of base components of the device, identifying a first subassembly of the device from a first group of selectable subassemblies, and selecting the identified first subassembly. A second subassembly is identified from the second group of selectable subassemblies, and the second subassembly is selected. A third subassembly is also identified from the third group of selectable subassemblies, and the third subassembly is selected. The drug delivery device is assembled using the set of base components, the first subassembly, the second subassembly, and the third subassembly.

[0009] According to a fourth aspect, a platform system for a drug delivery device includes a set of base components of the drug delivery device, a first group of selectable subassemblies of the drug delivery device, a second group of selectable subassemblies of the drug delivery device, and a third group of selectable subassemblies of the drug delivery device. The drug delivery device is assembled by identifying and selecting a first subassembly from the first group of selectable subassemblies, a second subassembly from the second group of selectable subassemblies, and a third subassembly from the third group of selectable subassemblies using at least one desired characteristic of the drug delivery device. The set of base components are coupled to the first group of selectable subassemblies, the second group of selectable subassemblies, and the third group of selectable subassemblies.

[0010] The above needs are met, at least in part, through the provision of a platform-based assembly process for a delivery device as described in the following detailed description, particularly when studied in conjunction with the drawings. [Brief description of the drawings]

[0011] [Figure 1] 1 illustrates an exemplary approach to assembly of a platform-based drug delivery device, according to various embodiments. [Diagram 2]1 illustrates an exemplary approach to supply chain and assembly of a platform-based drug delivery device, according to various embodiments. [Diagram 3] 1 illustrates a first exemplary approach for applying a skin to a drug delivery device, according to various embodiments. [Figure 4] 13 illustrates a second approach for applying a skin to a drug delivery device, according to various embodiments. [Diagram 5] 1 illustrates exemplary pre-filled syringes having different material properties for use in a platform-based drug delivery device, according to various embodiments. [Figure 6] 6 shows an expanded view of the exemplary pre-filled syringe of FIG. 5, according to various embodiments. [Figure 7] 7 illustrates the exemplary pre-filled syringe of FIGS. 5 and 6 mounted within a drug delivery device, according to various embodiments. [Figure 8a] 1 illustrates a first exemplary pre-filled syringe having a first exemplary support structure according to different embodiments. [Figure 8b] 1 illustrates a first exemplary pre-filled syringe having a first exemplary support structure according to different embodiments. [Figure 9a] 1 illustrates a second exemplary pre-filled syringe having a second exemplary support structure according to a different embodiment. [Figure 9b] 1 illustrates a second exemplary pre-filled syringe having a second exemplary support structure according to a different embodiment. [Figure 10a] 13 shows a third exemplary pre-filled syringe having a third exemplary support structure according to a different embodiment. [Figure 10b] 13 shows a third exemplary pre-filled syringe having a third exemplary support structure according to a different embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Those skilled in the art will appreciate that the elements in the figures are depicted for simplicity and clarity and are not necessarily drawn to scale. For example, the dimensions and / or relative positions of some of the elements in the figures may be exaggerated relative to other elements to improve understanding of various embodiments of the present invention. Also, common, but well-understood elements that are useful or necessary in commercially feasible embodiments are often not shown in order to lessen the clutter of the drawings of these various embodiments. Furthermore, it will be appreciated that certain acts and / or steps may be described or shown in a particular occurring order, although those skilled in the art will appreciate that such specificity with respect to the order is not actually required. It will also be understood that the terms and expressions used herein have the ordinary technical meaning that one skilled in the art would ascribe to such terms and expressions, as described above, unless a different specific meaning is explained herein.

[0013] Generally, according to these various embodiments, a drug delivery device may include a housing, a syringe assembly that contains the drug to be injected into the user, and an actuation assembly that includes a drive mechanism (e.g., a torque spring) to inject the drug into the user. The drive mechanism rotates to administer the drug and may require a variety of forces to efficiently and completely deliver the drug to the user. An exemplary drug delivery device is described in U.S. Patent Application No. 62 / 719,367, filed September 17, 2018, the entire contents of which are incorporated herein by reference. The approaches described herein cover a wide range of drug fluid volumes and viscosities, allowing for further customization for user populations. Furthermore, the approaches described herein allow for some components to be reused across drug products, thereby allowing for cost savings from investing in higher cavity count tools. As a result, the drug delivery device may be more likely to be ready for the necessary clinical trials as soon as the process of determining the appropriate drug dose (e.g., appropriate amount and concentration) has been performed.

[0014] 1, the assembly approach of the platform drug delivery device 100 allows for any number of base configurations as the device supports various subassemblies that can be used to address different technical requirements (e.g., dosage time versus volume and / or drug viscosity combinations). Additionally, any number of "fits" can be used to accommodate different user groups, markets, etc., to create a better user experience and / or market differentiation.

[0015] In different configurations, any number of components may be reused, but the number of selection areas to obtain a desired output device may vary. At the first or top level 102, an example platform layout is illustrated that provides information related to a basic device layout. The example top level 102 shows a "long pen" device, but any number of desired devices may be shown at the top level 102.

[0016] At the next level, a set of base or common components 104 are provided that are geometrically identical among all possible configurations of the top level device. These components may include, but are not limited to, a housing, a shield member, a spring housing, a syringe holder, a plunger rod, a plunger rod guide, a cap, a nut, a shield spring, an end of dose click device, a trigger ring, a shield lock, an upper housing, a damper member, a spring guide, and / or a damper grease. Other base components 104 may also be provided.

[0017] The remaining components and / or subassemblies may be identified and selected based on at least one desired characteristic of the drug delivery device. For example, these components may be identified using a desired drug having a specified viscosity and / or viscosity range, a specified amount, etc. The first subassembly 106 may include components specific to a pre-filled syringe ("PFS") shape. These components may include a syringe barrel, a portion of a needle assembly, etc. In the illustrated platform 100, the first subassembly 106 includes only two options that differ only in the PFS used to optimize both the PFS and their supporting components, but it is understood that the first subassembly may include any number of separate assemblies having any number of separate components.

[0018] The second subassembly 108 may include a spring component. This level illustrates how many different drive mechanisms are used within the platform to support various drug fluid volumes and / or viscosities within the dosage time requirements. In this example, the drive mechanisms shown only differ in height, not length, thickness, or other treatments. Importantly, the base components (e.g., plunger rod guide, housing, and spring guide) are designed to allow for dimensional variation of the drive mechanisms. Although the subassembly 108 shown includes only two options, it is understood that the second subassembly may include any number of separate assemblies having any number of components.

[0019] The third subassembly 110 may include a volume adaptor. This level illustrates how the platform configuration may be adapted to function optimally with different drug fluid volumes. For example, some drug delivery devices may include a damper that is used to partially reduce the shock seen when the PFS is low filled. Thus, some components (e.g., plunger rod) may take longer to descend to the plunger in the PFS. A volume adaptor may be used to occlude some of this space, thereby reducing the overall injection time in low volume configurations. It will be appreciated that the third subassembly may also include any number of separate assemblies with any number of components.

[0020] As configured, the platform assemblies described herein may be used with drugs having a viscosity of about 1 cP to about 30 cP and a deliverable volume of about 0.2 ml to about 3.5 ml, however, in other examples drugs having increased or decreased viscosities and varying amounts of drugs may be used.

[0021] Platform device 100 may also include a skin level 112 to adapt the device to different user demographics and / or markets. For example, as illustrated in Figures 3 and 4, skin 112 is provided on the exterior of device 100 in the form of a shell having two portions 112a, 112b. As illustrated in Figure 3, shell 112 includes two longitudinally aligned sides or halves, and in Figure 4, shell 112 includes upper and lower portions that join together near the midpoint of device 100. Other examples are possible.

[0022] In some approaches, the skin 112 may also be selected based on desired attributes. For example, the skin 112 may be selected based on attributes of the intended user population, such as whether the medication will be administered by medical personnel, whether the device is intended for individuals with certain limiting conditions (e.g., rheumatoid arthritis, migraines, etc.) that may require ergonomic affordances such as a larger or smaller grip, etc.

[0023] In the platform assembly process, it is particularly important to manufacture different configurations as efficiently as possible. One approach to achieving this efficiency is by allowing the creation of variants to occur late in the assembly process, such as by providing different rear subassemblies ("RSAs") and front subassemblies ("FSAs"). In these examples, the RSAs provided differ only in the particular drive mechanism (e.g., clock spring) implemented. These subassemblies are typically stored unwound to minimize the risk of creep or degradation during storage due to the high forces contained within the modules, and so that the wound springs allow for varying load amounts depending on the drug used. As previously mentioned, the particular springs used depend on the desired drug amount and / or the viscosity of the desired drug. In one example, different spring sizes are used to accommodate injection times of about 4 seconds to about 10 seconds for a particular drug amount / viscosity relationship.

[0024] In the examples provided, the FSA can accommodate any number (e.g., two or more) of PFS designs made from any number of different materials (e.g., polymeric materials such as glass, cyclic olefin copolymers or cyclic olefin polymers, etc.). This variation advantageously accommodates different drug products that may not be compatible with certain components (e.g., silicone oil, which may be a requirement for glass syringes). Similarly, low viscosity products may experience flow challenges across the components of a polymeric PFS device. Thus, accommodating these requirements increases the likelihood of suitability for a multitude of drug products. In some examples, customizing the syringe holder components to be a universal device with interfaces for multiple types of PFS devices (e.g., syringes made from glass or plastic materials) allows for the use of a single subassembly design that differs only in the specific PFS. In these examples, minimal modifications to the FSA may be required to accommodate different PFS designs. For example, the needle shield to cover the interface may be modified as needed.

[0025] Now, referring to FIG. 2, an exemplary approach for supply chain and assembly of platform-based drug delivery devices is provided. In some of these examples, the turns of the drive mechanism may be adjusted during final assembly. This may involve an adjustable feedback mechanism that uses the number of turns of the turns to identify how many or how many turns must be made to complete dosing. Such a feature may be useful in end-of-dosing indicator applications. Although not specifically detailed herein, it is understood that any number of skins may be applied to the device during the final assembly stage, along with a device label.

[0026] At the first level 202, the components required to assemble the device are sourced and stocked by downstream suppliers. At the second level 204, subassemblies are prepared and stocked as different SKUs. As shown in box 204, two RSAs 204a with different drive mechanisms are assembled and a single FSA 204b is assembled. The overall stock subassembly may include any additional common components such as RSAs, FSAs and dampers.

[0027] Next, the desired characteristics of the device are identified. For example, a particular drug with a particular required dosage may be desired. As illustrated in box 206, during the final assembly, labeling and packaging stage in step 206a, the first subassembly 106 is assembled by inserting the desired PFS into the FSA. The PFS may be filled at any point during the assembly process using any number of techniques. In some examples, the PFS may be filled at a different location (e.g., another facility with a clean environment) and then shipped to the final assembly site. Further, in step 206b, the desired second subassembly is assembled and the drive mechanism is inserted into the RSA. If the device incorporates a third subassembly in the form of a volume adapter, this is attached in step 206c. Next, in step 206d, the FSA is coupled to the RSA. Finally, the device is labeled and packaged in step 206e.

[0028] Typically, PFSs come in standard configurations with container volumes and sizes that comply with international standards. Thus, PFSs are generally dimensionally identical across suppliers. By using the platform approach described herein, PFS designs can be optimized for improved robustness of the interface with the device. Typically, PFSs are supported by a flange when mounted in an autoinjector. The combined tolerance build-up of the PFS and autoinjector often leads to large variations in needle extension and plunger position relative to the autoinjector components, especially since glass PFSs can have large tolerances on the length of the syringe barrel. Supporting the PFS by a shoulder can reduce this variation.

[0029] FIG. 5 shows two exemplary PFS assemblies 106 for use in the platform device 100. The PFS 106a is made from a glass material, and the PFS 106b is made from a polymeric material such as COP. The heights of the two plunger stoppers in the PFS 106a, 106b are optimized to allow the same plunger retraction position at the end of dose, advantageously helping to support a potential end-of-dose feedback function of the device. Specifically, in some applications, end-of-dose feedback may be provided in various forms by a mechanical trigger to inform the user that dose delivery is complete. This trigger must occur while components are still moving to enable the trigger, but as close to the actual end of dose as possible (i.e., when the plunger rod and stopper are at their lowest position within the PFS). The plunger rod (or other components directly coupled to the plunger rod) may be used to implement the feedback function, but importantly, the feedback trigger mechanism must be adjusted between platform variations if the plunger rod travel ends in different positions based on different container and / or stopper dimensions. However, since the platform design described herein includes an FSA and a PFS that avoid different end-of-dose terminal positions of the plunger, no additional application-specific components are required to implement end-of-dose feedback for use with selectable components.

[0030] Additionally, these designs are optimized while considering the minimum distance requirements between sealing ribs and the ratio of plunger diameter to height to enable orientation during feeding into the vibratory bowl. Additionally, the outer diameter of PFS 106a and the outer diameter of PFS 106b are identical or nearly identical to avoid the need for device-specific parts in each PFS. The dimensions of the PFS can be divided into two groups: interface dimensions and non-interface dimensions. Exemplary interface dimensions include the overall length and diameter of PFS 106a, 106b. As previously mentioned, the exemplary PFS 106a, 106b have the same overall length (e.g., length from needle tip to PFS support and / or flange back to PFS support) and diameter. Exemplary non-interface dimensions include similar flange height and diameter as well as inner diameter.

[0031] 5, 6 and 8a-10b, in some examples, the PFS 106b is made by injection molding. This provides more freedom in terms of design of features when compared to the glass PFS 106a. The design of the PFS 106b advantageously includes a support feature 120 located on the shoulder 118 of the syringe barrel. The support 120 provides a less ambiguous interface to the device that is easily controllable. For example, with reference to FIGS. 8a-10b, three exemplary PFS 106a made from a polymeric material are provided. As shown in FIGS. 8a and 8b, the PFS 106a includes a support feature 120 in the form of a number of ribs extending radially from the shoulder surface 118. As shown in Figures 9a and 9b, the PFS 106a includes a support feature 120 in the form of a surface or protrusion extending outwardly from the shoulder surface 118, and as shown in Figures 10a and 10b, the PFS 106a includes a support feature 120 in the form of a ring protruding from the shoulder surface 118. Other examples are possible.

[0032] Additionally, the interface between the exterior surface of the PFS and the inner diameter of the device may be advantageously engineered. The interface may be in the form of a complete cylindrical contact throughout the barrel length (as illustrated in FIG. 7), ribs on or along the length of the barrel (not shown), rings around the barrel (not shown), and / or small protrusions or dots (not shown) located on the surface of the device or barrel. Configured in this manner, a syringe carrier component may be provided that includes a dual support surface that is compatible with both glass and plastic PFS devices.

[0033] Advantageously, the described platform approach eliminates the need for multiple final device stock keeping units ("SKUs") for each drug product used in the autoinjector. Otherwise, an identical number of subassemblies would be required, each of which would require a minimum stocking level based on expected product demand, in order to properly manage the supply chain and inventory. However, with the present platform approach, a single front subassembly is utilized to meet all of the requirements for a variety of drug products, with an additional rear subassembly also being used to accommodate all of these products. This flexibility in applying the same subassemblies for different drug products results in a more agile supply chain and further reduces the total amount of inventory maintained without increasing the risk of backlog.

[0034] In the above description, various assemblies, devices and methods are described for use with drug delivery devices. It should be clear that the assemblies, drug delivery devices or methods can further include the use of drugs as described below, but it should be noted that the following list should not be considered exhaustive or limiting. The drug is placed in a reservoir. In some cases, the reservoir is a primary container that is filled or pre-filled with a drug for treatment. The primary container can be a cartridge or a pre-filled syringe.

[0035] For example, the drug delivery device, or more specifically the reservoir of the device, may be loaded with colony stimulating factors, such as granulocyte colony stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neupogen® (filgrastim) and Neulasta® (pegfilgrastim). In various other embodiments, the drug delivery device may be used with various pharmaceutical agents, such as erythropoietin stimulating agents (ESAs), which may be in liquid or lyophilized form.ESAs include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxy polyethylene glycol epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo®, and others. any molecule that stimulates erythropoiesis, such as Epoetin Alpha, Epoetin Beta, Epoetin Zeta, Epoetin Theta, and Epoetin Delta, as well as ... Zeta, Epoetin Zeta, Epoetin The following patents or patent applications, each of which is incorporated herein by reference in its entirety: U.S. Pat. No. 4,703,008; U.S. Pat. No. 5,441,868; U.S. Pat. No. 5,547,933; U.S. Pat. No. 5,618,698; U.S. Pat. No. 5,621,080; U.S. Pat. No. 5,756,349; U.S. Pat. No. 5,767,078; U.S. Pat. No. 5,773,569; U.S. Pat. No. 5,955,422; U.S. Pat. No. 5,986,047 Nos. 6,583,272, 7,084,245 and 7,271,689, and PCT Publication Nos. WO 91 / 05867, WO 95 / 05465, WO 96 / 40772, WO 00 / 24893, WO 01 / 81405 and WO 2007 / 136752, or variants or analogs thereof.

[0036] The ESA may be an erythropoiesis stimulating protein. As used herein, "erythropoiesis stimulating protein" refers to any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to the receptor and causing receptor dimerization. Erythropoiesis stimulating proteins include erythropoietin and its variants, analogs or derivatives that bind to and activate the erythropoietin receptor, antibodies that bind to and activate the erythropoietin receptor, or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis 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, mimetic peptides (including EMP1 / hematide), and mimetic antibodies. Exemplary erythropoiesis stimulating proteins include erythropoietin, darbepoietin, erythropoietin agonist variants, and peptides or antibodies that bind to and activate the erythropoietin receptor (as well as the compounds reported in U.S. Patent Application Publication Nos. 2003 / 0215444 and 2006 / 0040858, the entire disclosures of each of which are incorporated herein by reference), as well as the following patents or patent applications, the entire disclosures of which are incorporated herein by reference: U.S. Patent No. 4,703,008; U.S. Patent No. 5,441,868; U.S. Patent No. 5,547,93 ... 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WO 91 / 05867, WO 95 / 05465, WO 99 / 66054, WO 00 / 24893, WO 01 / 81405, WO 00 / 61637, WO 01 / 36489, WO 02 / 014356, and WO 02 / 19963. , WO 02 / 20034, WO 02 / 49673, WO 02 / 085940, WO 03 / 029291, WO 2003 / 055526, WO 2003 / 084477, WO 2003 / 094858, WO 2004 / 002417, WO 2004 / 002424, WO 2004 / 009627, WO 2004 / 024 No. 761, International Publication No. 2004 / 033651, International Publication No. 2004 / 035603, International Publication No. 2004 / 043382, International Publication No. 2004 / 101600, International Publication No. 2004 / 101606, International Publication No. 2004 / 101611, International Publication No. 2004 / 106373, International Publication No. 2004 / 018667, International Publication No. 2005 / 001025, International Publication No. 2005 / 001136 brochure, International Publication No. 2005 / 021579 pamphlet, International Publication No. 2005 / 025606 pamphlet, International Publication No. 2005 / 032460 pamphlet, International Publication No. 2005 / 051327 pamphlet, International Publication No. 2005 / 063808 pamphlet, International Publication No. 2005 / 063809 pamphlet, International Publication No. 2005 / 070451 pamphlet, International Publication No. 2005 / 081687 pamphlet, International Publication No. 2005 / 084711 pamphlet, International Publication No. 2005 / 103076 pamphlet,The erythropoietin molecules disclosed in WO 2005 / 100403, WO 2005 / 092369, WO 2006 / 50959, WO 2006 / 02646 and WO 2006 / 29094, or variants or analogs thereof, are included.

[0037] Examples of other pharmaceuticals for use with the device may include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab) and Prolia™ (denosumab); other biologics such as Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Neulasta® (pegfilgrastim, PEGylated filgastriam, PEGylated G-CSF, PEGylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-MetG-CSF) and Nplate® (romiplostim); small molecule drugs such as Sensipar® (cinacalcet). The device may be used with other chemicals such as therapeutic antibodies, polypeptides, proteins or iron, e.g., ferumoxytol, iron dextran, ferric gluconate and ferric oxide. The pharmaceutical agent may be in liquid form or may be reconstituted from a lyophilized form.

[0038] Among specific exemplary proteins are the specific proteins discussed below, including fusions, fragments, analogs, variants or derivatives thereof.

[0039] As disclosed in PCT Publication WO 03 / 002713, each of which is individually and specifically incorporated herein by reference in its entirety in its entirety, includes OPGL-specific antibodies having either a light chain of SEQ ID NO:2 as set forth in Figure 2 of said publication and / or a heavy chain of SEQ ID NO:4 as set forth in Figure 4 of said publication, with regard to OPGL-specific antibodies and antibody related proteins, particularly those having the sequences set forth in said publications, specifically those set forth above: 9H7, 18B2, 2D8, 2E11, 16E1 and 22B3, but not limited to, the antibodies described in said publications, which are incorporated herein in their entirety, OPGL-specific antibodies (also referred to as RANKL-specific antibodies, peptibodies, etc.), peptibodies and related proteins, etc., including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies.

[0040] TN8-19-1 to TN8-19-40, TN8-19 con1 and TN8-19 con2 are individually and specifically incorporated herein by reference in their entirety as disclosed in U.S. Patent Application Publication No. 2004 / 0181033 and PCT Publication No. WO 2004 / 058988. peptibodies of the mTN8-19 family, including those of SEQ ID NOs: 305-351, including con2; myostatin binding proteins, peptibodies and related proteins, including myostatin-specific peptibodies, which are particularly relevant in part to myostatin-specific peptibodies and which are described in the above publications, which are incorporated by reference in their entirety herein, including, but not limited to, the mL2 family of SEQ ID NOs: 357-383, the mL15 family of SEQ ID NOs: 384-409, the mL17 family of SEQ ID NOs: 410-438, the mL20 family of SEQ ID NOs: 439-446, the mL21 family of SEQ ID NOs: 447-452, the mL24 family of SEQ ID NOs: 453-454, and the peptibodies of SEQ ID NOs: 615-631.

[0041] L1H1, L1H2, L1H3, L1H4, L1H5, L1H6, L1H7, L1H8, L1H9, L1H10, L1H11, L2H1, L2H2, L2H3, L2H4, L2H5, L2H6, L2H7, L2H8, L2H9, L2H10, L1H11, L2H1, L2H2, L2H3, L2H4, L2H5, L2H6, L2H7, L2H8, L2H9, L2H11, L2H12, L2H13, L2H14, L2H15, L2H16, L2H17, L2H18, L2H19, L2H20, L2H21, L2H22, L2H23, L2H24, L2H25, L2H26, L2H27, L2H28, L2H29, L2H30, L2H31, L2H32, L2H33, L2H34, L2H35, L2H36, L2H37, L2H38, L2H39, L2H40, L2H41, L2H42, L2H43, L2H44, L2H45, L2H46, L2H47, L2H48, L2H49 ...0, L2H41, L2H42, L2H43, L2H44, L2H45, L2H4 2H10, L2H11, L2H12, L2H13, L2H14, L3H1, L4H1, L5H1, L6H1, and IL-4 receptor-specific antibodies, particularly those antibodies as described in the above publications, including, but not limited to, those described in the above publications, particularly those that are in part related to those set forth in the above publications and are incorporated herein by reference in their entirety, IL-4 receptor-specific antibodies, peptibodies and related proteins, particularly those that inhibit activities mediated by the binding of IL-4 and / or IL-13 to the receptor.

[0042] As disclosed in U.S. Patent Application Publication No. 2004 / 097712, each of which is individually and specifically incorporated herein by reference in its entirety in its entirety, including, but not limited to, those set forth in the above publications: 15CA, 26F5, 27F2, 24E12 and 10H7, including, in part, IL1-R1 specific binding proteins, particularly interleukin 1-receptor 1 ("IL1-R1") specific antibodies, peptibodies and related proteins, including, but not limited to, those described in the above publications, each of which is individually and specifically incorporated herein by reference in its entirety in connection with monoclonal antibodies.

[0043] The following publications are individually and specifically incorporated by reference in their entirety as disclosed therein, in particular those sequences described in the following publications: L1(N), L1(N)WT, L1(N)1K WT, 2xL1(N), 2xL1(N)WT, Con4(N), Con4(N)1K WT, 2xCon4(N)1K, L1C, L1C 1K, 2xL1C, Con4C, Con4C 1K, 2xCon4C and Ang2 specific antibodies and peptibodies, including, but not limited to, those described in PCT Publication No. WO 03 / 057134 and U.S. Patent Application Publication No. 2003 / 0229023, each of which is incorporated by reference in its entirety in part with particular reference to Ang2 antibodies and formulations, including, but not limited to, Ab526, Ab528, Ab531, Ab541, Ab542, Ab543, Ab544, Ab545, Ab546, Ab547, Ab548, Ab549 ... Ang2 specific antibodies, peptibodies and related proteins, including anti-Ang2 antibodies and formulations such as those described in PCT Publication WO 2003 / 030833, which is incorporated by reference in its entirety with respect to Ab533, Ab535, Ab536, Ab537, Ab540, Ab543, Ab544, Ab545, Ab546, A551, Ab553, Ab555, Ab558, Ab559, Ab565, AbF1AbFD, AbFE, AbFJ, AbFK, AbG1D4, AbGC1E8, AbH1C12, AblA1, AblF, AblK, AblP and AblP.

[0044] As disclosed in U.S. Patent Application Publication No. 2005 / 0074821 and U.S. Patent No. 6,919,426, each of which is individually and specifically incorporated herein by reference in its entirety, specifically including, but not limited to, NGF-specific antibodies, peptibodies and related proteins, including, but not limited to, the NGF-specific antibodies 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11 set forth in the above publications, and NGF-specific antibodies and related proteins thereof, including, but not limited to, the NGF-specific antibodies 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11 set forth in the above publications, and NGF-specific antibodies, peptibodies and related proteins, including, but not limited to, those described in the above publications, each of which is individually and specifically incorporated herein by reference in its entirety, specifically including, but not limited to, the NGF-specific antibodies 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11 set forth in the above publications, and

[0045] For example, humanized and fully human antibodies, including but not limited to, humanized and fully human monoclonal antibodies, including but not limited to, human CD22-specific IgG antibodies, such as, but not limited to, a dimer of human-mouse monoclonal hLL2 gamma chain disulfide linked to a human-mouse monoclonal hLL2 kappa chain, including, but not limited to, humanized and fully human antibodies, including but not limited to, human CD22-specific IgG antibodies, specifically, human CD22-specific antibodies, CD22-specific antibodies, peptibodies and related proteins, such as those described in U.S. Pat. No. 5,789,554, the entirety of which is incorporated herein by reference with respect to CD22-specific antibodies and related proteins.

[0046] The IGF-1 specific antibodies L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11, L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L30H30, L31H30, L32H30, L33H30, L34H30, L35H30, L36H30, L37H30, L38H30, L39 ... H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52 and IGF-1 R-binding fragments and derivatives thereof, such as those described in the above publications, which are incorporated by reference in their entireties herein with respect to IGF-1 receptor specific antibodies and related proteins.

[0047] Also among the non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the invention are each of those described below. (i) antibodies described in U.S. Patent Application Publication No. 2006 / 0040358 (published February 23, 2006), U.S. Patent Application Publication No. 2005 / 0008642 (published January 13, 2005), and U.S. Patent Application Publication No. 2004 / 0228859 (published November 18, 2004), including, but not limited to, antibody 1A (DSMZ Accession No. DSM ACC 2586), antibody 8 (DSMZ Accession No. DSM ACC 2589), antibody 23 (DSMZ Accession No. DSM ACC 2588), and antibody 18; (ii) antibodies including, but not limited to, 2F8, A12 and IMC-A12, described in PCT Publication No. WO 06 / 138729 (published December 28, 2006) and PCT Publication No. WO 05 / 016970 (published February 24, 2005) and Lu et al. (2004), J. Biol. Chem. 279:2856-2865; (iii) PCT Publication No. 07 / 012614 (published on February 1, 2007), PCT Publication No. 07 / 000328 (published on January 4, 2007), PCT Publication No. 06 / 013472 (published on February 9, 2006), PCT Publication No. 05 / 058967 (published on June 30, 2005) and PCT Publication No. 03 / 059951 (published on July 24, 2003); (iv) antibodies described in U.S. Patent Application Publication No. 2005 / 0084906 (published April 21, 2005), including, but not limited to, antibody 7C10, chimeric antibody C7C10, antibody h7C10, antibody 7H2M, chimeric antibody *7C10, antibody GM607, humanized antibody 7C10 version 1, humanized antibody 7C10 version 2, humanized antibody 7C10 version 3, and antibody 7H2HM; (v) antibodies including, but not limited to, EM164, resurfaced EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2 and huEM164 v1.3, as described in U.S. Patent Application Publication No. 2005 / 0249728 (published November 10, 2005), U.S. Patent Application Publication No. 2005 / 0186203 (published August 25, 2005), U.S. Patent Application Publication No. 2004 / 0265307 (published December 30, 2004) and U.S. Patent Application Publication No. 2003 / 0235582 (published December 25, 2003), and Maloney et al. (2003) Cancer Res. 63:5073-5083; (vi) U.S. Pat. No. 7,037,498, issued May 2, 2006; U.S. Patent Application Publication No. 2005 / 0244408, published November 30, 2005; and U.S. Patent Application Publication No. 2004 / 0086503, published May 6, 2004; and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073, including, but not limited to, each of the antibodies produced by hybridomas having ATCC Accession Nos. PTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, and antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3, e.g., antibody CP-751,871, (vii) including, but not limited to, antibody 19D12, as described in U.S. Patent Application Publication No. 2005 / 0136063 (published June 23, 2005) and U.S. Patent Application Publication No. 2004 / 0018191 (published January 29, 2004), and an antibody comprising a heavy chain encoded by the polynucleotides of plasmid 15H12 / 19D12 HCA(γ4), deposited with the ATCC under accession number PTA-5214, and a light chain encoded by the polynucleotides of plasmid 15H12 / 19D12 LCF(κ), deposited with the ATCC under accession number PTA-5220; (viii) With respect to the foregoing antibodies, peptibodies and related proteins specifically targeting the IGF-1 receptor, 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, each of which is incorporated by reference in its entirety herein.

[0048] B-7 related protein 1 specific antibodies, peptibodies, related proteins and the like ("B7RP-1," also referred to in the literature as B7H2, ICOSL, B7h and CD275), particularly B7RP specific fully human monoclonal IgG2 antibodies, particularly fully human IgG2 monoclonal antibodies that bind to an epitope in the first immunoglobulin-like domain of B7RP-1, particularly those that inhibit the interaction of B7RP-1 with ICOS, the natural receptor for B7RP-1, particularly on activated T cells, particularly as disclosed in the following publications, each of which is individually and specifically incorporated by reference in its entirety herein: 16H (within which are light and heavy chain variable region sequences, SEQ ID NO:1 and SEQ ID NO:7, respectively), 5D (within which are light and heavy chain variable region sequences, SEQ ID NO:2 and SEQ ID NO:3, respectively), and / or and SEQ ID NO:9), 2H (having therein light chain variable region sequences and heavy chain variable region sequences, SEQ ID NO:3 and SEQ ID NO:10, respectively), 43H (having therein light chain variable region sequences and heavy chain variable region sequences, SEQ ID NO:6 and SEQ ID NO:14, respectively), 41H (having therein light chain variable region sequences and heavy chain variable region sequences, SEQ ID NO:5 and SEQ ID NO:13, respectively), and 15H (having therein light chain variable region sequences and heavy chain variable region sequences, SEQ ID NO:4 and SEQ ID NO:12, respectively) and those disclosed in U.S. Patent Publication No. 2008 / 0166352 and PCT Publication No. WO 07 / 011941, which are incorporated by reference in their entireties with respect to such antibodies and related proteins, including, but not limited to, the antibodies set forth in the following publications:

[0049] For example, those disclosed in U.S. Patent Application Publication Nos. 2003 / 0138421, 2003 / 023586 and 2004 / 0071702, and U.S. Patent No. 7,153,507, each of which is incorporated herein by reference in its entirety, for IL-15 specific antibodies and related proteins, including, inter alia, peptibodies, including, but not limited to, HuMax IL-15 antibodies and related proteins, such as 146B7, in particular antibodies, particularly IL-15 specific antibodies, such as humanized monoclonal antibodies, peptibodies and related proteins.

[0050] IFNγ-specific antibodies, peptibodies and related proteins, etc., particularly human IFNγ-specific antibodies, particularly fully human anti-IFNγ antibodies, such as, for example, IFNγ-specific antibodies, particularly those described in the following patent publications, U.S. Patent Application Publication No. 2005 / 0004353, which is incorporated herein by reference in its entirety for the antibodies designated 1118, 1118*, 1119, 1121 and 1121*. The entire sequences of the heavy and light chains of each of these antibodies, and the sequences of their heavy and light chain variable regions and complementarity determining regions, are individually and specifically incorporated herein by reference in their entirety as disclosed in the aforementioned publications and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115, respectively. In addition, the descriptions of the properties of these antibodies provided in the above publications are also incorporated herein by reference in their entirety. Specific antibodies include those having a heavy chain of SEQ ID NO:17 and a light chain of SEQ ID NO:18, those having a heavy chain variable region of SEQ ID NO:6 and a light chain variable region of SEQ ID NO:8, those having a heavy chain of SEQ ID NO:19 and a light chain of SEQ ID NO:20, those having a heavy chain variable region of SEQ ID NO:10 and a light chain variable region of SEQ ID NO:12, those having a heavy chain of SEQ ID NO:32 and a light chain of SEQ ID NO:20, those having a heavy chain variable region of SEQ ID NO:30 and a light chain variable region of SEQ ID NO:12, those having a heavy chain sequence of SEQ ID NO:21 and a light chain sequence of SEQ ID NO:22, those having a heavy chain variable region of SEQ ID NO:14 and a light chain variable region of SEQ ID NO:16, those having a heavy chain of SEQ ID NO:21 and a light chain of SEQ ID NO:33, and those having a heavy chain variable region of SEQ ID NO:14 and a light chain variable region of SEQ ID NO:31, as disclosed in the aforementioned publications. A specific antibody contemplated is antibody 1119, disclosed in the aforementioned U.S. Patent Application Publication, having a complete heavy chain of SEQ ID NO: 17, disclosed in the aforementioned U.S. Patent Application Publication, and a complete light chain of SEQ ID NO: 18, disclosed in the aforementioned U.S. Patent Application Publication.

[0051] As disclosed in the following publications, each of which is individually and specifically incorporated herein by reference in its entirety, and with respect to TALL-1 binding proteins, particularly the molecules in Tables 4 and 5B, TALL-1 specific antibodies, peptibodies and related proteins such as those described in U.S. Patent Application Publication No. 2003 / 0195156 and U.S. Patent Application Publication No. 2006 / 0135431, each of which is incorporated herein by reference in its entirety, as well as other TALL specific binding proteins.

[0052] Parathyroid hormone ("PTH")-specific antibodies, peptibodies and related proteins, such as those described in U.S. Pat. No. 6,756,480, the entirety of which is incorporated herein by reference, with particular reference in part to proteins that bind PTH.

[0053] Thrombopoietin receptor ("TPO-R")-specific antibodies, peptibodies and related proteins, such as those described in U.S. Pat. No. 6,835,809, the entirety of which is incorporated herein by reference, with particular reference in part to proteins that bind to TPO-R.

[0054] With particular reference in part to proteins that bind HGF, hepatocyte growth factor ("HGF")-specific antibodies, peptibodies and related proteins, including those that target the HGF / SF:Met axis (HGF / SF:c-Met), such as fully human monoclonal antibodies that neutralize hepatocyte growth factor / scatter (HGF / SF), as described in U.S. Patent Application Publication No. 2005 / 0118643 and PCT Publication No. WO 2005 / 017107, huL2G7, as described in U.S. Patent No. 7,220,410, and OA-5d5, as described in U.S. Patent Nos. 5,686,292 and 6,468,529, and PCT Publication No. WO 96 / 38557, each of which is incorporated by reference in its entirety herein.

[0055] TRAIL-R2 specific antibodies, peptibodies, related proteins, etc., such as those described in U.S. Pat. No. 7,521,048, which is incorporated by reference in its entirety, with particular reference in part to proteins that bind TRAIL-R2.

[0056] 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, particularly in part, with reference to proteins that bind activin A.

[0057] Particularly relevant to proteins that bind TGF-β are TGF-β specific antibodies, peptibodies, related proteins, and the like, including, but not limited to, those described in U.S. Pat. No. 6,803,453 and U.S. Patent Application Publication No. 2007 / 0110747, each of which is incorporated by reference in its entirety herein.

[0058] Amyloid β protein specific antibodies, peptibodies, related proteins, etc., including but not limited to those described in PCT Publication WO 2006 / 081171, which is incorporated herein by reference in its entirety, particularly in relation to proteins that bind to amyloid β protein. One possible 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.

[0059] 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 by reference in its entirety, with particular reference in part to proteins that bind c-Kit and / or other stem cell factor receptors.

[0060] 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, the entirety of which is incorporated herein by reference, with particular reference in part to proteins that bind OX40L and / or other ligands of the OX40 receptor.

[0061] Activase® (alteplase, tPA), Aranesp® (darbepoetin alfa), 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), Humatopeptide® (Humatopeptide, anti-HER2 / neu(erbB2) receptor mAb), rope® (somatropin, human growth hormone), Humira® (adalimumab), insulin in 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-BlySmAb), Metalyse® (tenecteplase, t-PA analog), Mircera® (methoxypolyethylene glycol-epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP870), Soliris™ (eculizumab), pexelizumab (anti-complement C5), 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® (filgrastim, 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 lIb / Ilia receptor monoclonal antibody), Actemra® (anti-IL6 receptor mAb), Avastin® (bevacizumab), HuMax-CD4 (zanolimumab), Rituxan® (rituximab, anti-CD20mAb), Tarceva® (erlotinib), Roferon-A® (interferon alpha-2a), Simulect® (basiliximab), Prexige® (lumiracoxib), Synagis® (palivizumab), 146B7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507), Tysabri® (natalizumab, anti-alpha4 integrin mAb), Valortim® (MDX-1303, anti-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), CNTO148 (golimumab, anti-TNFα mAb), HGS-ETR1 (mapatuzumab, 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-CD30mAb (MDX-060), MDX-1333 (anti-IFNAR), anti-CD38 mAb (HuMax CD38), anti-CD40L mAb, anti-Cripto mAb, anti-CTGF Idiopathic Pulmonary Fibrosis Phase 1 Fibrinogen (FG-3019), anti-CTLA4 mAb, anti-Eotaxin 1 mAb (CAT-213), anti-FGF8 mAb, anti-Ganglioside GD2 mAb, anti-Ganglioside GM2 mAb, 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-IL12 / IL23 mAb (CNTO1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 Receptor mAb, anti-Integrin Receptor mAb (MDX-018, CNTO95), 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), other exemplary proteins including NVS Antibody No. 1 and NVS Antibody No. 2.

[0062] Sclerostin antibodies, such as, but not limited to, romosozumab, brosozumab, or BPS804 (Novartis), may also be included. Further therapeutic agents may be included, such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX, or XGEVA. Additionally, a monoclonal antibody (IgG) that binds to human proprotein convertase subtilisin / kexin type 9 (PCSK9) may be included in the device.Such PCSK9-specific antibodies include those described in the following patents or patent applications, each of which is incorporated by reference in its entirety for all purposes: 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 International Publication No. 2008 / 133647, International Publication No. 2009 / 100297, International Publication No. 2009 / 100318, International Publication No. 2011 / 037791, International Publication No. 2011 / 053759, International Publication No. 2011 / 053783, International Publication No. 2008 / 125623, International Publication No. 2 International Publication No. 011 / 072263, International Publication No. 2009 / 055783, International Publication No. 2012 / 0544438, International Publication No. 2010 / 029513, International Publication No. 2011 / 111007, International Publication No. 2010 / 077854, International Publication No. 2012 / 088313, International Publication No. 2012 / 101251, International These include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab) and molecules, variants, analogs or derivatives thereof as disclosed in Publication No. WO 2012 / 101252, WO 2012 / 101253, WO 2012 / 109530, and WO 2001 / 031007.

[0063] Also included may be talimogene laherparepvec or another oncolytic HSV for the treatment of melanoma or other cancers. Examples of oncolytic HSV include, but are not limited to, talimogene laherparepvec (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, NV1020, NV12023, NV1034 and NV1042 (Vargehes et al. (2002), Cancer Gene Ther., 9(12):967-978).

[0064] Also included are TIMPs. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) and are important in many natural processes. TIMP-3 is expressed by various cells and / or present in the extracellular matrix, inhibits all major cartilage-degrading metalloproteinases, and may play a role in many degradative diseases of connective tissue, including rheumatoid arthritis and osteoarthritis, as well as in 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. Descriptions of TIMP mutations can be found in U.S. Patent Application Publication No. 2014 / 0274874 and PCT Publication No. WO 2014 / 152012.

[0065] Also included are antagonistic antibodies of the human calcitonin gene-related peptide (CGRP) receptor and bispecific antibody molecules targeting the CGRP receptor and other headache targets. More information regarding these molecules can be found in PCT Publication WO 2010 / 075238.

[0066] Additionally, bispecific T cell engaging (BiTE®) antibody constructs, such as BLINCYTO® (blinatumomab), can be used in the device. Alternatively, an APJ macromolecule agonist, such as apelin or an analog thereof, can be included in the device. Information regarding such molecules can be found in PCT Publication WO 2014 / 099984.

[0067] In some embodiments, the medicament comprises a therapeutically effective amount of anti-thymic stromal lymphopoietin (TSLP) or a TSLP receptor antibody. Examples of 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.

[0068] Although the drug delivery device, method and their components have been described in terms of exemplary embodiments, the drug delivery device, method and their components are not limited thereto. The detailed description is to be construed as an example only and does not describe all possible embodiments of the invention, since describing every possible embodiment would be impractical, if not impossible. Many alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, and such embodiments would still fall within the scope of the claims that define the invention. For example, components described herein with reference to a particular type of drug delivery device, such as an on-body injector drug delivery device, or other types of drug delivery devices, can also be utilized in other types of drug delivery devices, such as an autoinjector drug delivery device.

[0069] Those skilled in the art will understand that various modifications, alterations and combinations may be made to the above-described embodiments without departing from the scope of the present invention, and such modifications, alterations and combinations are to be construed as being within the scope of the concept of the present invention.

Claims

1. A method for assembling a platform-type drug delivery device, To provide a set of base components for the drug delivery device, Identifying a rear subassembly of a drug delivery device from a group of rear subassemblies based on at least one desired characteristic, including at least one of drug viscosity or drug volume, wherein each rear subassembly in the group of rear subassemblies includes a different drive mechanism in the form of a torque spring selected from a plurality of torque springs, and each of the plurality of torque springs has a variable characteristic. Selecting the aforementioned specified rear subassembly, Based on the desired characteristics, the front subassembly of the drug delivery device is identified from the group of front subassemblies, Selecting the identified front subassembly, A method comprising assembling the drug delivery device using the set of base components, the selected rear subassembly, and the selected front subassembly.

2. The method according to claim 1, wherein each front sub-assembly includes a different syringe assembly.

3. The method according to claim 2, wherein the syringe assembly is made from one of glass or polymer materials.

4. The method according to any one of claims 1 to 3, wherein the set of base components is geometrically identical among the configurations of the drug delivery device.

5. The method according to any one of claims 1 to 4, further comprising applying a skin to the drug delivery device.

6. The method according to claim 5, wherein the skin is selected based on at least one attribute from a group of intended users.

7. A method for assembling a platform-type drug delivery device, To provide a set of base components for the drug delivery device, Identifying a first subassembly of the drug delivery device from a first group of selectable subassemblies based on at least one desired characteristic, including at least one of drug viscosity or drug volume, Selecting the identified first subassembly, Identifying a second subassembly of the drug delivery device from a second group of selectable subassemblies based on the desired characteristics, wherein each subassembly in the second group of selectable subassemblies includes a different drive mechanism in the form of a torque spring selected from a plurality of torque springs, and each of the plurality of torque springs has a variable characteristic. Selecting the identified second subassembly, Based on the desired characteristics, a third subassembly of the drug delivery device is identified from a third group of selectable subassemblies. Selecting the identified third subassembly, A method comprising assembling the drug delivery device using the set of base components, the selected first subassembly, the selected second subassembly, and the selected third subassembly.

8. The method according to claim 7, wherein the first group of selectable subassemblies comprises a plurality of prefilled syringe assemblies.

9. The method according to claim 7 or 8, wherein the third group of selectable subassemblies includes a plurality of volume adapters.

10. The method according to any one of claims 7 to 9, further comprising applying a skin to the drug delivery device.

11. The method according to claim 10, wherein the skin is selected based on at least one attribute from a group of intended users.

12. The method according to any one of claims 7 to 11, wherein the set of base components is geometrically identical among the configurations of the drug delivery device.

13. A platform-type drug delivery device manufactured by the method described in any one of claims 1 to 6.

14. A platform system for assembling a platform-type drug delivery device, The set of base components of the drug delivery device, A first group of selectable subassemblies of the drug delivery device, A second group of selectable subassemblies of the drug delivery device, wherein each subassembly from the second group of selectable subassemblies includes a different drive mechanism in the form of a torque spring selected from a plurality of torque springs, and each of the plurality of torque springs has a variable characteristic, A third group of selectable subassemblies of the drug delivery device, The drug delivery device is Identifying and selecting a first subassembly from the first group of selectable subassemblies, a second subassembly from the second group of selectable subassemblies, and a third subassembly from the third group of selectable subassemblies using at least one desired characteristic, including at least one of drug viscosity or drug volume, A platform system assembled by combining the set of base components with the selected first subassembly, the selected second subassembly, and the selected third subassembly.

15. The platform system according to claim 14, wherein the first group of selectable subassemblies comprises a plurality of prefilled syringe assemblies.

16. The platform system according to claim 14 or 15, wherein the third group of selectable subassemblies includes a plurality of volume adapters.

17. A method for assembling a platform-type drug delivery device, To provide a set of base components for the drug delivery device, wherein the set of base components includes a plunger rod, and the set of base components is geometrically identical among the configurations of the drug delivery device. Identifying a rear subassembly of a drug delivery device from a group of rear subassemblies based on at least one of drug viscosity or drug volume, wherein each rear subassembly in the group comprises a different drive mechanism in the form of a torque spring selected from a plurality of torque springs, each of the plurality of torque springs having variable properties, and the set of base components is configured to accept the variable properties of each of the plurality of torque springs. Selecting the aforementioned specified rear subassembly, Identifying the front subassembly of the drug delivery device from the group of front subassemblies based on at least one of the drug viscosity or the drug quantity, Selecting the identified front subassembly, A method comprising assembling the drug delivery device using the set of base components, the selected rear subassembly, and the selected front subassembly.

18. The method according to claim 17, wherein the set of base components includes at least one of a housing, a shield member, a spring housing, a syringe holder, a plunger rod, a plunger rod guide, a cap, a nut, a shield spring, a drug dispensing termination device, a trigger ring, a shield lock, an upper housing, a damper member, or a spring guide.

19. A method for assembling a platform-type drug delivery device, To provide a set of base components for the drug delivery device, wherein the set of base components includes a plunger rod, and the set of base components is geometrically identical among the configurations of the drug delivery device. Identifying a first subassembly of the drug delivery device from a first group of selectable subassemblies based on at least one of drug viscosity or drug volume, Selecting the identified first subassembly, Identifying a second subassembly of the drug delivery device from a second group of selectable subassemblies based on at least one of the drug viscosity or the drug quantity, wherein each subassembly from the second group of selectable subassemblies includes a different drive mechanism in the form of a torque spring selected from a plurality of torque springs, each of the plurality of torque springs having variable properties, and the set of base components is configured to accept the variable properties of each of the plurality of torque springs. Selecting the identified second subassembly, Identifying a third subassembly of the drug delivery device from a third group of selectable subassemblies based on at least one of the drug viscosity or the drug quantity, Selecting the identified third subassembly, A method comprising assembling the drug delivery device using the set of base components, the selected first subassembly, the selected second subassembly, and the selected third subassembly.

20. A platform system for assembling a drug delivery device, A set of base components of the drug delivery device, wherein the set of base components includes a plunger rod and is geometrically identical among the configurations of the drug delivery device, A first group of selectable subassemblies of the drug delivery device, A second group of selectable subassemblies of the drug delivery device, wherein each subassembly from the second group of selectable subassemblies includes a different drive mechanism in the form of a torque spring selected from a plurality of torque springs, each of the plurality of torque springs having variable properties, and the set of base components is configured to accept the variable properties of each of the plurality of torque springs, A third group of selectable subassemblies of the drug delivery device, The drug delivery device is Identifying and selecting a first subassembly from the first group of selectable subassemblies, a second subassembly from the second group of selectable subassemblies, and a third subassembly from the third group of selectable subassemblies using at least one of drug viscosity or drug quantity, The set of base components is assembled by combining the selected first subassembly, the selected second subassembly, and the selected third subassembly. Platform system.

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