EA042893B1 - METHOD FOR PLATFORM ASSEMBLY FOR DRUG DELIVERY DEVICE - Google Patents

Description

Cross-reference to related application

Priority is claimed for U.S. Provisional Application No. 62/745,739, filed Oct. 15, 2018, the entire contents of which are incorporated herein by reference.

The technical field to which the invention belongs

The present invention relates generally to drug delivery devices, and more particularly to platform approaches to the manufacture of drug delivery devices.

Background of the invention

Drug delivery devices such as auto-injectors and wearable injectors offer some advantages in terms of drug delivery and/or therapeutic agents. One advantage may be considered ease of use compared to traditional delivery methods using, for example, conventional syringes.

Autoinjectors can be used to deliver a wide variety of drugs with different viscosities and/or target volumes. As a result, assembly of these devices can be difficult due to the need to correctly identify suitable components that can effectively deliver drug to the user. As an example, drugs with higher viscosities may require stronger drive assemblies with stronger components for adequate drug delivery within a reasonable time frame. Likewise, large doses of drugs may also require stronger drive assemblies.

Short description

According to a first aspect, an approach for assembling a platform drug delivery device includes providing a set of basic components and identifying, based on at least one target characteristic of the platform drug delivery device, a rear assembly for a drug delivery device from a group of rear assembly units. A certain rear subassembly is selected, and a front subassembly is determined, based on at least one target characteristic, from a group of front subassemblies. A specific subassembly is selected and the drug delivery device is assembled using a set of base components, a back subassembly, and a front subassembly. This approach may optionally include applying an outer coating to the device, which may be selected based on at least one attribute of the intended user group.

In some aspects, at least one target property is at least one of drug viscosity or drug volume. In some aspects, each of the rear subassemblies in a group of rear subassemblies may comprise a different drive mechanism. In addition, each of the front assemblies may include a syringe assembly, which may be constructed from one of glass or a polymeric material. In some examples, the set of base components is geometrically identical in drug delivery device configurations.

In accordance with another aspect, an approach to assembling a drug delivery platform device includes providing a set of base components for the device, determining a first assembly for the device from a first group of selectable assemblies, and selecting the determined first assembly. The second assembly unit is determined from the second group of selectable assembly units, and the second assembly unit is selected. The third assembly unit is also determined from the third group of selectable assembly units, and the third assembly unit is selected. The drug delivery device is assembled using a set of base components, a first assembly, a second assembly, and a third assembly.

According to a third aspect, a drug delivery platform device is manufactured by a method comprising the steps of providing a set of base components for the device, determining a first assembly for the device from a first group of selectable assemblies, and selecting the determined first assembly. The second assembly unit is determined from the second group of selectable assembly units, and the second assembly unit is selected. The third assembly unit is also determined from the third group of selectable assembly units, and the third assembly unit is selected. The drug delivery device is assembled using a set of base components, a first assembly, a second assembly, and a third assembly.

According to a fourth aspect, a platform system for a drug delivery device comprises a set of basic components for a drug delivery device, a first group of selectable assembly units for the drug delivery device, a second group of selectable assembly units for the drug delivery device, and a third group of selectable assembly units for the drug delivery device. drug delivery devices. The drug delivery device is assembled using at least one target drug delivery device characteristic to identify and select the first assembly.

- 1 042893 units from the first group of selectable assembly units, the second assembly unit from the second group of selectable assembly units, and the third assembly unit from the third group of selectable assembly units.

The base component set is attached to the first selectable assembly group, the second selectable assembly group, and the third selectable assembly group.

Brief description of graphic materials

The foregoing needs are at least partially met by providing a delivery device platform assembly method described in the following detailed description, considered in particular in conjunction with the drawings in which:

in fig. 1 depicts an exemplary approach to assembling a platform drug delivery device in accordance with various embodiments;

in fig. 2 depicts an exemplary approach to product movement and drug delivery platform assembly in accordance with various embodiments;

in fig. 3 depicts an exemplary first approach for topcoating a drug delivery device in accordance with various embodiments;

in fig. 4 depicts a second approach for topcoating a drug delivery device in accordance with various embodiments;

in fig. 5 depicts exemplary pre-filled syringes having various material properties for use with a platform drug delivery device in accordance with various embodiments;

in fig. 6 is an enlarged view of exemplary pre-filled syringes of FIG. 5 according to various embodiments;

in fig. 7 depicts exemplary pre-filled syringes of FIG. 5 and 6 installed in a drug delivery device according to various embodiments;

in fig. 8a and 8b depict a first example of a pre-filled syringe having a first illustrative support structure in accordance with various embodiments;

in fig. 9a and 9b depict a second example of a pre-filled syringe having a second illustrative support structure in accordance with various embodiments; and in FIG. 10a and 10b depict a third example of a pre-filled syringe having a third illustrative support structure in accordance with various embodiments.

Those skilled in the art will appreciate that elements in the figures are depicted for simplicity and clarity and are not necessarily shown to scale.

For example, the dimensions and/or relative positions of some elements in the figures may be exaggerated relative to other elements in order to facilitate understanding of various embodiments of the present invention. Also common but well-known elements desired or required for a commercially viable embodiment are often not depicted to help create a less cluttered appearance of these various embodiments. It should also be understood that certain actions and/or steps may be described or depicted in a particular order of occurrence, while those skilled in the art will recognize that such sequence specificity is not actually necessary. It is also to be understood that the terms and expressions used herein have their usual technical meaning, as defined above, with respect to such terms and expressions by those skilled in the art, except where specific other specific meanings are used hereinafter.

Detailed description

In general, according to these various embodiments, the drug delivery device may include a housing, a syringe assembly containing a drug to be injected to a user, and a drive assembly containing a drive mechanism (e.g., a torsion spring). ) to provide an injection of the medicinal product to the user. As the drive mechanism rotates to effect drug administration, different forces may be required to effectively and completely deliver the drug to the user. An exemplary drug delivery device is described in US Patent Application No. 62/719,367, filed September 17, 2018, the contents of which are incorporated herein by reference in its entirety. The approaches described herein cover a wide range of volumes and viscosities of drug liquids, and allow for further tailoring to user groups. In addition, the approaches described herein allow for the reuse of a number of components in relation to drug products, thereby making it possible to invest in tools with a large number of molds for manufacturing in order to reduce cost. As a result, drug delivery devices may be more likely to be ready

- 2 042893 for required clinical trials shortly after the process of setting the required dosage of the drug (eg, the required volume and concentration).

With reference to FIG. 1, the assembly approach for platform drug delivery device 100 implies any number of basic configurations as devices supporting different assemblies that can be applied to meet different specifications (e.g., dosing times for volume combinations and/or drug densities). ). In addition, any number of adaptations may be used to serve different user groups, markets, and the like. for the purpose of producing a better user experience and/or market differentiation.

Any number of components may be reused in different configurations, but they may differ in the choice of the number of regions to provide the target output device. The first, or top, level 102 depicts an exemplary platform diagram that provides information regarding the underlying device layout. Although the exemplary top level 102 depicts a stick-shaped device, any number of target devices may be depicted in the top level 102.

At the next level, a set of basic or common components 104 is provided that are geometrically identical in all possible top-level device configurations. These components may include, but are not limited to, housing, guard, spring housing, syringe holder, plunger rod, plunger rod guide, cap, nut, safety spring, dose end click device, ring trigger device, security lock , upper housing, damper element, spring guide and/or damping grease. Other base components 104 may also be provided.

The remaining components and/or subassemblies may be defined and selected based on at least one target characteristic of the drug delivery device. For example, a target drug having a specific viscosity and/or a range of viscosity values, a specific volume, and the like can be used to determine these components. The first assembly 106 may contain specific components in the form of a pre-filled syringe (PFS). These components may include a syringe barrel, a needle assembly, and the like. In the depicted platform 100, the first assembly 106 includes only two options, differing only in PFS, used to optimize both the PFS and their supporting components, but it should be understood that the first assembly may include any number of different assemblies having any number of individual components. inside yourself.

The second assembly 108 may contain spring components. This level depicts how many different drive mechanisms are used in the platform to support different drug liquid volumes and/or other viscosities within time requirements. In this example, the drive mechanisms shown differ only in height, not in length, thickness, or other processing options. It is important to note that the basic components (such as the piston rod guide, housing, and spring guide) have been designed to allow for variation in the dimensions of the actuator mechanism. Although the depicted subassembly 108 contains only two options, it should be understood that the second subassembly may include any number of different subassemblies having any number of individual components within them.

The third assembly 110 may contain adapters for different volumes. This level depicts how platform configurations can be adapted to work optimally with different drug liquid volumes. For example, some drug delivery devices may contain dampers used in part to reduce the initial shock wave at smaller PFS fill volumes. Accordingly, some components (such as the piston rod) may take longer to move down to the piston in the PFS. A volume adapter can be used to take up some of this space and thereby reduce the overall injection time for low volume configurations. It should be understood that the third assembly may also include any number of different assemblies having any number of individual components within them.

By configuration, the platform assembly described herein can be used with drugs with viscosities from about 1 centipoise to about 30 centipoise, and delivery volumes from about 0.2 ml to about 3.5 ml. However, in other examples, drugs with increased or decreased viscosity values, as well as different volumes, can be used.

The platform device 100 may also include an overcoating layer 112 to allow the device to be adapted to different user populations and/or markets. For example, as shown in FIG. 3 and 4, the outer covers 112 are provided in the form of a shell having two parts 112a, 112b on the outside of the device 100. As shown in FIG. 3, the shell 112 has two sides or halves aligned in the longitudinal direction, and in FIG. 4, shell 112 includes a top and bottom that are joined together near the center of device 100. Possible

- 3 042893 other examples.

In some approaches, the outer coatings 112 may also be selected based on the target attribute. For example, outer cover 112 may be selected based on an attribute of the intended user group, such as, for example, whether the drug is administered by a healthcare professional, whether the device is intended for individuals with certain physical limiting conditions (e.g., rheumatoid arthritis, migraine, etc.). etc.), which may require the provision of ergonomic features such as larger or smaller gripping parts, etc.

In the platform assembly method, it is especially important to make different configurations as efficiently as possible. One approach to achieving this efficiency is to push the creation of variants to a late stage in the assembly process, for example by providing rear assembly units (RSA) and front assembly units (FSA). In these examples, the RSAs provided differ only in the implementation of the specific actuator mechanism (eg clock spring). These assemblies are kept unwinded to minimize the risk of accidental displacement or disassembly during storage due to the high internal forces applied to the module and to allow different loads to be applied to the wound spring depending on the drug being used. As mentioned above, the use of a particular spring depends on the target volume of the drug and/or the viscosity of the target drug. In one example, varying the size of the spring is used to adjust the injection time to a range of about four seconds to about 10 seconds for a particular volume/viscosity ratio of the drug.

In the example provided, the FSA can accommodate any number (eg, two or more) of PFS structures constructed from any number of different materials (eg, glass, polymeric material such as a cyclic olefin copolymer or cyclic olefin polymer, etc.). This variety advantageously accommodates various drug products that may be incompatible with certain components (eg, silicone oil, which may be required for glass syringes). Likewise, low viscosity products can lead to flow problems for PFS polymer device components. Accordingly, meeting these requirements provides a high likelihood of suitability for a large number of drug products. In some instances, by modifying the syringe retainer component to be a general purpose device having an interface for several types of PFS devices (e.g., syringes made of glass or plastic materials) allows a single assembly design to exist that differs only in specific applications. pfs. In these examples, minimal changes to the FSA may be needed to cover the various PFS constructs. For example, the needle guard for closing the interface can be modified according to need.

Consider now FIG. 2, which provides an illustrative approach to the supply chain and assembly of a platform drug delivery device. In some of these examples, the cocking of the drive mechanism may be adjusted during final assembly. As a result, adjustable feedback mechanisms can be employed in which the number of windings is used to determine how much or how many turns are left before the end of a dose. Such a detail may be useful in applications with a dosing completion indicator. It should be understood that although not described in detail herein, any number of outer coatings may be applied to the device during the final assembly steps, in conjunction with the marking of the device.

At the first level 202, components required to assemble devices are supplied and stored by component suppliers. At the second level, 204 assembly units are prepared and stored in different SKUs. As shown in box 204, two RSA 204a having different drive mechanisms are assembled and one FSA 204b is assembled. Assemblies stored as a whole can include RSA, FSA, and any additional common components such as dampers.

Next, target characteristics for the device are determined. For example, the target may be a specific required dose volume of a particular drug. As shown in box 206, during the final assembly, labeling, and packaging step of step 206a, the first assembly 106 is assembled by inserting the target PFS into the FSA. The PFS can be filled at any time during the build process with any number of passes. In some examples, the PFS may be filled at different locations (eg, separate sterile manufacturing facilities) and may then be transported to the final assembly site. Thereafter, in step 206b, the target second assembly is assembled and the drive mechanism is inserted into the RSA. If the device contains a third assembly in the form of an adapter for different volumes, it is attached at step 206c. Next, the FSA is attached to the RSA in step 206d. Finally, the device is labeled and packaged in step 206e.

Usually PFS have standard configurations, the volumes and dimensions of which are regulated by international standards. Accordingly, PFS are generally the same in terms of dimensions y times

- 4 042893 suppliers. By applying the platform approaches described in this document, PFS designs can be optimized for greater interface strength in the device. Typically the PFS is supported by a flange when installed in an autoinjector. Because particularly glass PFSs can have large tolerances in syringe barrel length, overlapping tolerances for PFS and autoinjector combination often results in great variability in needle extension and plunger position relative to autoinjector components. Supporting the PFS on the shoulder can reduce this variability.

In FIG. 5 depicts two exemplary PFS assemblies 106 for use with platform device 100. PFS 106a is constructed from a glass material and PFS 106b is constructed from a polymeric material such as COP. In the PFS 106a, 106b, the height of the two piston stroke stops is optimized to ensure that the piston returns to the same back position at the end of a dose, which advantageously aids in supporting potential end-of-dose feedback functions in the device. In particular, in some applications, the mechanical trigger device may provide end-of-dose feedback in various forms to signal to the user that the dose delivery has been completed. This trigger device must fire while the components are still moving to actuate the trigger device, but should fire as close to the actual end of the dose as possible (ie when the piston rod and limiter bottom out in the PFS). The piston rod (or other component directly connected to the piston rod) can be used to implement the feedback functionality, although it is important that when the piston rod stroke is interrupted in a different position, based on other tank and/or limiter dimensions, the feedback trigger mechanism could be configured for different platform options. However, the platform design now described includes FSAs and PFSs that do not have different end-of-dose piston positions, so no additional application-specific components are needed to implement end-of-dose feedback for use with selectable components.

In addition, these designs are optimized to meet the minimum spacing between sealing ribs and piston diameter to height ratio to allow orientation during feeding in vibratory cup feeders. In addition, the outside diameters of the PFS 106a, 106b are identical or nearly identical to eliminate the need for device-specific parts for each PFS. PFS sizes can be divided into two groups: interface-related and non-interface sizes. Exemplary interface dimensions include the overall length and diameter of the PFS 106a, 106b. As mentioned, exemplary PFS 106a, 106b have the same overall length (eg, length from needle tip to PFS pedestal and/or flange to PFS pedestal) and diameters. Illustrative non-interface dimensions include similar flange heights and diameters as well as inside diameters.

With reference to FIG. 5, fig. 6 and FIG. 8a-10b, in some examples, the PFS 106b is constructed using injection molding approaches that provide additional freedom in terms of part design compared to glass PFS 106a. The design of the PFS 106b mainly includes a support piece 120 placed on the shoulder 118 of the syringe barrel. Support 120 provides a less uncertain device interface that is easy to control. For example, with reference to FIG. 8a-10b provide three examples of PFS 106a made from a polymeric material. As shown in FIG. 8a and 8b, the PFS 106a includes a support member 120 in the form of a plurality of ribs extending radially from the shoulder surface 118. As shown in FIG. 9a and fig. 9b, the PFS 106a includes a support piece 120 in the form of a surface or protrusion extending outwardly from the shoulder surface 118 and, as shown in FIG. 10a and fig. 10b, PFS 106a includes an annular support 120 protruding from shoulder surface 118. Other examples are possible.

In addition, an interface between the outer surface of the PFS and the inner diameter of the device can be advantageously designed. The interface may be in the form of full cylindrical contact along the entire length of the cylinder (as depicted in Fig. 7), ribs located on or along the length of the cylinder (not shown), rings around the circumference of the cylinder (not shown) and/or small protrusions or points located on the surface of the device or cylinder (not shown). With this configuration, a syringe carrier component can be provided that contains dual support surfaces compatible with both plastic and glass PFS devices.

Advantageously, the described platform approach eliminates the need for multiple SKUs for each autoinjector drug product. Proper supply chain and inventory management would otherwise require an identical number of assembly units, each requiring a minimum level of inventory based on expected demand for the product. However, the present platform approach uses a single front subassembly to meet the requirements of all the various drug products, and a combination of additional rear subassemblies will also fit all of these products. This flexibility in applying the same assembly units to different drug products allows for a more flexible supply chain, which in turn reduces the overall amount of inventory held without increasing the risk of lead times being delayed.

The description above describes various assemblies, methods, and devices for use with a drug delivery device. It should be understood that assemblies, drug delivery devices, or methods may additionally provide for the use of the medicinal product listed below, with the proviso that the following list is not to be construed as either inclusive or limiting. The drug will be stored in a reservoir. In some cases, the reservoir is the main container that is filled or pre-filled for drug treatment. The main container may be a cartridge or a pre-filled syringe.

For example, the drug delivery device, or more specifically the reservoir of the device, can be filled with colony stimulating factors such as granulocyte colony stimulating factor (G-CSF). Such G-CSF-based agents include, without limitation, Neupogen® (filgrastim) and Neulasta® (pegfilgrastim). In various other embodiments, the drug delivery device may be used with various pharmaceuticals, such as an erythropoiesis stimulating agent (ESA), which may be in liquid or lyophilized form. ESA is any molecule that stimulates erythropoiesis such as Epogen® (epoetin-alpha), Aranesp® (darbepoetin-alpha), Dynepo® (epoetin-delta), Mircera® (methoxypolyethylene glycol-epoetin-beta), Hematide®, MRK -2578, INS-22, Retacrit® (epoetinzeta), Neorecormon® (epoetin-beta), Silapo® (epoetin-zeta), Binocrit® (epoetin-alpha), Hexal epoetin-alpha, Abseamed® (epoetin-alpha), Ratioepo® (epoetin-theta), Eporatio® (epoetin-theta), Biopoin® (epoetin-theta), epoetin-alpha, epoetin-beta, epoetin-zeta, epoetin-theta and epoetin-delta, and molecules or variants thereof or equivalents disclosed in the following patents or patent applications, all of which are incorporated herein by reference in their entirety: US Pat. No. 4,703,008; 5441868; 5547933; 5618698; 5621080; 5756349; 5767078; 5773569; 5955422; 5986047; 6583272; 7084245 and 7271689; and PCT Publication No. WO 91/05867; W095/05465; WO 96/40772; W000/24893; WO 01/81405 and WO 2007/136752.

ESA may be an erythropoiesis-stimulating protein. In the context of this document, the expression erythropoiesis-stimulating protein means any protein that directly or indirectly causes the activation of the erythropoietin receptor, for example, by binding to the receptor and causing its dimerization. Proteins that stimulate erythropoiesis include erythropoietin and its variants, analogs or derivatives, which bind to and activate the erythropoietin receptor; antibodies that bind to the erythropoietin receptor and activate the receptor; or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis-stimulating proteins include, but are not limited to, epoetin-alpha, epoetin-beta, epoetin-delta, epoetin-omega, epoetin-iota, epoetin-zeta and their analogues, pegylated erythropoietin, carbamylated erythropoietin, peptidomimetic agents (including EMP1/hematide) and antibody mimetics. Exemplary erythropoietic-stimulatory proteins include erythropoietin, darbepoetin, erythropoietin agonist variants, and peptides or antibodies that bind and activate the erythropoietin receptor (and include compounds set forth in U.S. Patent Application Publication Nos. 2003/0215444 and 2006/0040858, each disclosed incorporated herein by reference in its entirety), as well as erythropoietin molecules, or variants or analogues thereof, disclosed in the following patents or patent applications, all of which are incorporated herein by reference in their entirety: US Pat. Nos. 4,703,008; 5441868; 5547933; 5618698; 5621080; 5756349; 5767078; 5773569; 5955422; 5830851; 5856298; 5986047; 6030086; 6310078; 6391633; 6583272; 6586398; 6900292; 6750369; 7030226; 7084245 and 7217689; U.S. Patent Application Publication No. 2002/0155998; 2003/0077753; 2003/0082749; 2003/0143202; 2004/0009902; 2004/0071694; 2004/0091961; 2004/0143857; 2004/0157293; 2004/0175379; 2004/0175824;

2004/0229318; 2004/0248815; 2004/0266690; 2005/0019914; 2005/0026834; 2005/0096461; 2005/0107297;

2005/0107591; 2005/0124045; 2005/0124564; 2005/0137329; 2005/0142642; 2005/0143292; 2005/0153879;

2005/0158822; 2005/0158832; 2005/0170457; 2005/0181359; 2005/0181482; 2005/0192211; 2005/0202538;

2005/0227289; 2005/0244409; 2006/0088906 and 2006/0111279; and PCT Publication No. WO 91/05867; W095/05465; W099/66054; W000/24893; WO 01/81405; W000/61637; WO 01/36489; WO 02/014356; WO02/19963; WO02/20034; WO 02/49673; WO 02/085940; WO 03/029291; W02003/055526; W02003/084477; WO2003/094858; WO2004/002417; WO2004/002424; WO2004/009627; WO2004/024761; WO2004/033651; WO2004/035603; WO2004/043382; WO2004/101600; WO2004/101606; WO2004/101611; WO2004/106373; W02004/018667; WO2005/001025; WO2005/001136; W02005/021579; WO2005/025606; WO2005/032460; W02005/051327; WO2005/063808; WO2005/063809; WO2005/070451; WO2005/081687; WO2005/084711; WO2005/103076; WO 2005/100403; WO2005/092369;

- 6 042893

WO 2006/50959; WO 2006/02646 and WO 2006/29094.

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™ (denosamab); other biologics such as Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgrastim, 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 can also be used with a therapeutic antibody, polypeptide, protein, or other chemical such as iron, such as ferumoxytol, iron complexed dextrans, ferrous gluconate, and sucrose-iron complex. The pharmaceutical preparation may be in liquid form or reconstituted from a lyophilized form.

Specific illustrative proteins include the specific proteins set forth below, including their fusions, fragments, analogs, variants, or derivatives:

OPGL-specific antibodies, peptibodies and related proteins, and the like. (also referred to as RANKL-specific antibodies, peptibodies, and the like), including fully humanized and human OPGL-specific antibodies, in particular fully humanized monoclonal antibodies, including, but not limited to, the antibodies described in PCT Publication No. WO 03 /002713, which is incorporated herein in its entirety with respect to OPGL-specific antibodies and antibody-related proteins, in particular those having the sequences set forth therein, in particular, without limitation, those designated therein as: 9H7; 18B2; 2D8; 2E11; 16E1 and 22B3, including OPGL-specific antibodies having either the light chain sequence identification number 2 set forth therein in FIG. 2 and/or the heavy chain with sequence identification number 4 set forth therein in FIG. 4, all of which are individually and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

myostatin binding proteins, peptibodies and related proteins, and the like, including myostatin-specific peptibodies, such as those described in U.S. Patent Application Publication No. 2004/0181033 and PCT Publication No. WO 2004/058988, which are incorporated herein. document by reference in its entirety, in particular in parts relating to myostatin-specific peptibodies, including, without limitation, peptitiles from the mTN8-19 family, including those under sequence identification numbers: 305-351, including from TN8-19-1 to TN8-19-40, TN8-19 con1 and TN8-19 con2; mL2 family peptiform under sequence identification numbers: 357-383; mL15 families under sequence identification numbers: 384-409; mL17 families under sequence identification numbers: 410-438; mL20 families under sequence identification numbers: 439-446; mL21 families under sequence identification numbers: 447-452; the mL24 families under sequence identification numbers: 453-454 and those under sequence identification numbers: 615-631, all of which are individually and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

IL-4 receptor-specific antibodies, peptibodies and related proteins, and the like, in particular those that inhibit activities mediated by IL-4 and/or IL-13 binding to the receptor, including those described in PCT- Publication No. WO 2005/047331 or PCT Application No. PCT/US2004/37242 and US Patent Application Publication No. 2005/112694, which are incorporated herein by reference in their entirety, in particular in parts relating to specific IL-4 receptor antibodies, in particular those antibodies as described therein, in particular and without limitation those designated therein as: L1H1; L1H2; L1H3; L1H4; L1H5; L1H6; L1H7; L1H8; L1H9; L1H10; L1H11; L2H1; L2H2; L2H3; L2H4; L2H5; L2H6; L2H7; L2H8; L2H9; L2H10; L2H11; L2H12; L2H13; L2H14; L3H1; L4H1; L5H1; L6H1, all of which are individually and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

interleukin-1 receptor-1 (IL1-R1) specific antibodies, peptibodies and related proteins, and the like, including, without limitation, those described in US Patent Application Publication No. 2004/097712, which is incorporated herein by reference in its entirety in parts relating to binding proteins specific for IL1-R1, monoclonal antibodies, in particular in the first place, without limitation those designated herein as: 15CA, 26F5, 27F2, 24E12 and 10H7, all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the aforementioned publication;

Ang2-specific antibodies, peptibodies, and related proteins, and the like, including, without limitation, those described in PCT Publication No. WO 03/057134 and US Patent Application Publication No. 2003/0229023, each of which is incorporated herein. document by reference in its entirety, in particular in parts relating to Ang2-specific antibodies and peptides, etc., in the first place, those having the sequences described therein, including without restrictions: 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 1K; Con4-L1 (N); Con4-L1C; TN-12-9(N); C17(N); TN8-8(N); TN8-14(N); Con 1 (N), as well as including antibodies to Ang2 and compositions based on them, such as those described in PCT Publication No. WO 2003/030833, which is incorporated herein by reference in its entirety with respect to the same, in specifically Ab526; Ab528; Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; ALH1C12; Ab1A1; Ab1F; Ab1K, Ab1P and

Ab1P with their various permutations as described therein, all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

NGF-specific antibodies, peptibodies and related proteins, and the like, including but not limited to those described in US Patent Application Publication No. 2005/0074821 and US Patent No. 6,919,426, which are incorporated herein by the references in their entirety to NGF-specific antibodies and related proteins as used herein, including, but not limited to, NGF-specific antibodies referred to therein as 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11, all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

CD22-specific antibodies, peptibodies and related proteins, and the like, such as those described in US Pat. , specific for human CD22 antibodies, such as, without limitation, humanized and fully human antibodies, including, without limitation, humanized and fully human monoclonal antibodies, in particular, including, without limitation, specific for human CD22 IgG antibodies, such as, for example, , a dimer from the gamma chain of a humanized murine mAb hLL2 disulfide-linked to the kappa chain of a humanized murine mAb hLL2, including but not limited to, e.g., the human CD22-specific fully humanized antibody epratuzumab having the CAS registration number 501423-23-0;

IGF-1 receptor-specific antibodies, peptibodies and related proteins, and the like, such as those described in PCT Publication No. WO 06/069202, which is incorporated herein by reference in its entirety with respect to IGF receptor-specific -1 antibodies and related proteins, including, but not limited to, IGF-1 specific antibodies referred to herein as 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, L31H31, L32H32, L33H33,

L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44,

L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1R binding fragments and derivatives thereof, all of which are individually and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication .

Also non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the present invention include any and all of those described in:

(i) U.S. Patent Application Publication No. 2006/0040358 (published February 23, 2006), 2005/0008642 (published January 13, 2005), 2004/0228859 (published November 18, 2004), including without limitation , for example, antibody 1A (DSMZ deposit no. DSM ACC 2586), antibody 8 (DSMZ deposit no. DSM ACC 2589), antibody 23 (DSMZ deposit no. DSM ACC 2588), and antibody 18 described therein;

(ii) PCT 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 2F8, A12, and IMC-A12 antibodies described therein;

(iii) PCT Publication Nos. 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);

(iv) U.S. Patent Application Publication No. 2005/0084906 (published April 21, 2005), including, but not limited to, 7C10 antibody, C7C10 chimeric antibody, h7C10 antibody, 7H2M antibody, *7C10 chimeric antibody, GM 607 antibody, humanized antibody 7C10 version 1, humanized 7C10 antibody version 2, humanized 7C10 antibody version 3, and 7H2HM antibody described therein;

(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 25 December 2003) and Maloney et al. (2003), Cancer Res. 63:5073-5083, in

- 8 042893 including but not limited to EM164, EM164 surface modified antibody, humanized

EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2 and huEM164 v1.3 described therein;

(vi) U.S. Patent No. 7,037,498 (issued May 2, 2006), U.S. Patent Application Publications No. 2005/0244408 (published November 30, 2005) and 2004/0086503 (published May 6, 2004) and Cohen, et al. . (2005), Clinical Cancer Res. 11:2063-2073, for example, the CP-751871 antibody, including, without limitation, each of the antibodies produced by hybridomas having ATCC accession numbers PTA2792, 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 described therein;

(vii) U.S. Patent Application Publication Nos. 2005/0136063 (published June 23, 2005) and 2004/0018191 (published January 29, 2004), including, without limitation, the 19D12 antibody and an antibody containing a heavy chain encoded by a polynucleotide in plasmid 15H12/19D12 HCA (γ4) deposited with ATCC under number PTA-5214, and the light chain encoded by the polynucleotide in plasmid 15H12/19D12 LCF (j) deposited with ATCC under number PTA-5220 described therein; and (viii) U.S. Patent Application Publication No. 2004/0202655 (published October 14, 2004), including but not limited to 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, PINT12A1, PINT-12A2, PINT-12A3, PINT-12A4 and PINT- 12A5 described therein; each and every one of which is incorporated herein by reference in its entirety, in particular with respect to the aforementioned antibodies, peptocytes and related proteins, and the like, which target IGF-1 receptors;

B-7 related protein-1 specific antibodies, peptibodies, related proteins, and the like. (B7RP-1 is also referred to in the literature as B7H2, ICOSL, B7h and CD275), in particular B7RP-specific fully human IgG2 monoclonal antibodies, in particular a fully human IgG2 monoclonal antibody that binds an epitope in the first immunoglobulin-like domain of B7RP-1, in the first in turn, those that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, on activated T cells, in particular, in the first place, all of the above refer to those disclosed in US Patent Application Publication No. 2008/0166352 and PCT- Publication No. WO 07/011941, which are incorporated herein by reference in their entirety with respect to such antibodies and related proteins, including, without limitation, antibodies designated as follows: 16H (having the light chain variable region and variable region sequences heavy chain under sequence identification number 1 and sequence identification number 7, respectively, described therein); 5D (having the light chain variable region and heavy chain variable region sequences of Sequence ID 2 and Sequence ID 9, respectively, described therein); 2H (having the light chain variable region and heavy chain variable region sequences of sequence identification number 3 and sequence identification number 10, respectively, described therein); 43H (having the light chain variable region and heavy chain variable region sequences of sequence identification number 6 and sequence identification number 14, respectively, described therein); 41H (having the light chain variable region and heavy chain variable region sequences of sequence identification number 5 and sequence identification number 13, respectively, described therein) and 15H (having the light chain variable region and heavy chain variable region sequences of sequence identification number 4 and sequence number 12, respectively, described therein), all of which are individually and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

IL-15 specific antibodies, peptibodies and related proteins, and the like, such as in particular humanized monoclonal antibodies, in particular antibodies such as those disclosed in US Patent Application Publication No. 2003/0138421; 2003/023586 and 2004/0071702; and US Pat. IL-15 HuMax and related proteins such as, for example, 146B7;

IFN-gamma specific antibodies, peptibodies and related proteins, and the like, in particular human IFN-gamma specific antibodies, in particular fully human anti-IFN-gamma antibodies such as, for example, those described in U.S. Patent Application Publication No. 2005/0004353, which is incorporated herein by reference in its entirety with respect to IFN-gamma specific antibodies, in particular, for example, antibodies referred to therein as 1118; 1118*; 1119; 1121 and 1121*. The complete sequences of the heavy and light chains of each of these antibodies, as well as the sequences of the variable regions and complementarity determining regions of their heavy and light chains, are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115. In addition, the description of the properties of these antibodies, presented in the above publication, is also incorporated into this document by reference in its entirety. Specific antibodies include those having a heavy chain with sequence identification number 17 and a light chain with sequence identification number 18; antibodies having a heavy chain variable region of sequence identification number 6 and a light chain variable region of sequence identification number 8; antibodies having a heavy chain with sequence identification number 19 and a light chain with sequence identification number 20; antibodies having a heavy chain variable region of sequence identification number 10 and a light chain variable region of sequence identification number 12; antibodies having a heavy chain with sequence identification number 32 and a light chain with sequence identification number 20; antibodies having a heavy chain variable region of sequence identification number 30 and a light chain variable region of sequence identification number 12; antibodies having a heavy chain sequence of sequence identification number 21 and a light chain sequence of sequence identification number 22; antibodies having a heavy chain variable region of sequence identification number 14 and a light chain variable region of sequence identification number 16; antibodies having a heavy chain with sequence identification number 21 and a light chain with sequence identification number 33; and antibodies having a heavy chain variable region of sequence identification number 14 and a light chain variable region of sequence identification number 31 disclosed in the above publication. The specific antibody in question is the 1119 antibody disclosed in the above US patent application publication and having the entire heavy chain sequence of sequence identification number 17 disclosed therein and having the entire light chain sequence of sequence identification number 18 disclosed therein;

TALL-1 specific antibodies, peptibodies and related proteins, and the like. and other binding proteins specific for TALL, such as those described in US Patent Application Publication Nos. 2003/0195156 and 2006/0135431, each of which is incorporated herein by reference in its entirety with respect to TALL-1 binding proteins, in particular molecules from the table. 4 and 5B, all of which are individually and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publications;

parathyroid hormone (PTH) specific antibodies, peptibodies and related proteins, and the like, such as those described in US Pat. proteins that bind PTH;

thrombopoietin receptor (TPO-R) specific antibodies, peptibodies and related proteins, and the like, such as those described in US Pat. No. 6,835,809, which is incorporated herein by reference in its entirety, in particular relating to proteins that bind TPO-R;

hepatocyte growth factor (HGF) specific antibodies, peptibodies and related proteins, etc., including those that target the HGF/SF:cMet (HGF/SF:c-Met) signaling pathway axis, such as fully human monoclonal antibodies that neutralize hepatocyte growth factor/scattering factor (HGF/SF) described in US Patent Application Publication No. 2005/0118643 and PCT Publication No. WO 2005/017107, huL2G7 described in US Patent No. 7220410, and OA -5d5, as described in US Pat.

TRAIL-R2 specific antibodies, peptibodies, related proteins, and the like, such as those described in US Pat. that bind TRAIL-R2;

Activin A-specific antibodies, peptibodies, related proteins, and the like, including, without limitation, those described in U.S. Patent Application Publication No. 2009/0234106, which is incorporated herein by reference in its entirety, to in particular, in parts relating to proteins that bind Activin A;

TGF-beta-specific antibodies, peptibodies, related proteins, and the like, including, without limitation, those described in US Patent No. 6,803,453 and US Patent Application Publication No. 2007/0110747, all of which are incorporated herein by reference in its entirety, in particular in parts relating to proteins that bind TGF-beta;

beta-amyloid protein-specific antibodies, peptibodies, related proteins and

- 10 042893

etc., including without limitation those described in PCT Publication No. WO 2006/081171, which is incorporated herein by reference in its entirety, in particular in parts relating to proteins that bind beta-amyloid proteins. One contemplated antibody is an antibody having a heavy chain variable region having a sequence identification number of 8 and a light chain variable region having a sequence identification number of 6 as disclosed in the above publication;

c-Kit specific antibodies, peptibodies, related proteins, and the like, including, without limitation, those described in U.S. Patent Application Publication No. 2007/0253951, which is incorporated herein by reference in its entirety, in particular, in parts relating to proteins that bind c-Kit and/or other stem cell factor receptors;

OX40L-specific antibodies, peptibodies, related proteins, and the like, including, without limitation, those described in US Patent Application Publication No. 2006/0002929, which is incorporated herein by reference in its entirety, in particular, in parts relating to proteins that bind OX40L and/or other OX40 receptor ligands; and other illustrative proteins, including Activase® (alteplase, tPA); Aranesp® (darbepoetinalfa); Epogen® (epoetin-alpha or erythropoietin); GLP-1, Avonex® (interferon-beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonal antibody); Betaseron® (interferon-beta); Campath® (alemtuzumab, an anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (CCR2 chemokine receptor mAb); Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNF blocker); Eprex® (epoetin-alpha); Erbitux® (cetuximab, anti-EGFR/HER1/c-ErbB-1 antibody); Genotropin® (somatropin, human growth hormone); Herceptin® (trastuzumab, HER2/neu receptor (erbB2) mAb); Humatrope® (somatropin, human growth hormone); Humira® (adalimumab); insulin in solution; Infergen® (interferon alfacon-1); Natrecor® (nesiritide; recombinant human B natriuretic peptide (hBNP); Kineret® (anakinra); Leukine® (sargramostim, rhuGM-CSF); LymphoCide® (epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat-B, belimumab, mAb to BlyS); Metalyse® (tenecteplase, t-PA analogue); Mircera® (methoxy polyethylene glycol-epoetin-beta); Mylotarg® (gemtuzumab ozogamicin); Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris ™ (eculizumab); pexelizumab (complement C5 antibody); Numax® (MEDI-524); Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio® (lerdelimumab); TheraCim hR3 (nimotuzumab) ; Omnitarg (pertuzumab, 2C4); Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (visilizumab); cantuzumab mertansin (huC242-DM1); NeoRecormon® (epoetin-beta); Neumega® (oprelvekin , human interleukin-11); Neulasta® (pegylated filgrastim, pegylated GCSF, pegylated hu-Met-G-CSF); Neupogen® (filgrastim, G-CSF, hu-MetG-CSF); Orthoclone OKT3® (muromonab-CD3, monoclonal antibody to CD3); Procrit® (epoetin-alpha); Remicade® (infliximab, anti-TNFa monoclonal antibody); Reopro® (abciximab, anti-GP lIb/Ilia monoclonal antibody); Actemra® (mAb for IL6 receptor); Avastin® (bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20 mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2a); Simulect® (basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO (anti-IL15 antibody, see US Pat. No. 7,153,507); Tysabri® (natalizumab, anti-integrin a4 mAb); Valortim® (MDX-1303, B. anthracis protective antigen mAb); ABthrax™; Vectibix® (panitumumab); Xolair® (omalizumab); ETI211 (mAb to MRSA); IL-1 decoy (Fc portion of human IgG1 and extracellular domains of both components of the IL-1 receptor (type I receptor and receptor accessory protein)); VEGF trap (VEGFR1 Ig domains fused to IgG1 Fc); Zenapax® (daclizumab); Zenapax® (daclizumab, anti-IL-2Ra mAb); Zevalin® (ibritutomab tiuxetan); Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); monoclonal antibody to CD80 (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3/huFc fusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFa mAb); HGS-ETR1 (mapatumumab; human TRAIL receptor mAb); HuMax-CD20 (ocrelizumab, anti-human CD20 mAb); HuMax-EGFR (zalutumumab); M200 (volociximab, mAb to integrin α5β 1); MDX-010 (ipilimumab, anti-CTLA-4 and VEGFR-1 (IMC18F1) mAb; anti-BR3 mAb; C. difficile C toxin A and toxin B mAb, MDX-066 (CDA-1) and MDX-1388); dsFv conjugates to CD22-PE38 (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401); adecatumumab; mAb to CD30 (MDX-060); MDX-1333 (anti-IFNAR antibody); anti-CD38 mAb (HuMax CD38); mAb to CD40L; mAb to Crypto; anti-CTGF antibody for use in idiopathic pulmonary fibrosis in a phase I study (FG-3019) from Fibrogen; mAb to CTLA4; mAb to eotaxin-1 (CAT-213); mAb to FGF8; mAb to ganglioside GD2; mAb to ganglioside GM2; anti-human GDF-8 mAb (MYO-029); mAb to the GMCSF receptor (CAM-3001); mAb to HepC (HuMax HepC); mAb to IFNa (MEDI-545, MDX-1103); mAb to IGF1R; anti-IGF-1R mAb (HuMax-Inflam); mAb to IL12 (AWT-874); mAb to IL12/IL23 (CNTO 1275); mAb to IL13 (CAT-354); mAb to IL2Ra (HuMax-TAC); mAb to the IL5 receptor; mAb for integrin receptors (MDX-018, CNTO 95); mAb to IP10 used in ulcerative colitis (MDX-1100); anti-LLY antibody; BMS-66513; mannose receptor/hCGP mAb (MDX-1307); dsFv conjugate to mesothelin-PE38 (CAT-5001); mAb to PD1 (MDX-1106 (ONO-4538)); anti-PDGFRa antibody (IMC-3G3); mAb to TGFe (GC-1008); mAb for human TRAIL receptor-2 (HGS-ETR2); mAb to TWEAK; mAb to VEGFR/Flt-1; mAb to ZP3 (HuMax-ZP3); NVS antibody #1 and

NVS antibody #2.

An anti-sclerostin antibody such as, but not limited to, romosozumab, blososumab, or BPS 804 (Novartis) may also be included. In addition, therapeutic agents such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesaniba diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA may be included. In addition, the device may contain a monoclonal antibody (IgG) that binds human subtilisin-kexin type 9 (PCSK9) proprotein convertase. Such antibodies specific for PCSK9 include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab), as well as molecules, variants, analogs, or derivatives thereof, disclosed in the following patents or patent applications, all of which are included herein by reference in its entirety: US Pat. Wo 2009/100297, Wo 2009/100318, Wo 2011/037791, Wo 2011/053759, Wo 2011/053783, Wo 2008/125623, Wo 2011/072263, Wo 2009/055783, Wo 2012/05444438, Wo 2010/029513, Wo 2010/029513, WO 2011/111007, WO 2010/077854, WO 2012/088313, WO 2012/101251, WO 2012/101252, WO 2012/101253, WO 2012/109530 and WO2001/031007.

The talimogen lagerparepvec or other oncolytic HSV for the treatment of melanoma or other types of cancer may also be included. Examples of oncolytic HSV include, without limitation, the talimogen lagerparepvec (US Pat. Nos. 7,223,593 and 7,537,924); OncoVEXGALV/CD (US Pat. No. 7981669); 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).

Also included are TIMP. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) and play an important role in many natural processes. TIMP-3 is expressed by various cells and/or present in the extracellular matrix; it inhibits all major cartilage-degrading metalloproteases and may be involved in the development of many destructive connective tissue diseases, 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 the DNA molecule that encodes TIMP-3 are disclosed in US Pat. No. 6,562,596 issued May 13, 2003, the disclosure of which is incorporated herein by reference. A description of mutations in TIMP can be found in US Patent Application Publication No. 2014/0274874 and PCT Publication No. WO 2014/152012.

Also included are antibodies that antagonize the human calcitoningen-related peptide (CGRP) receptor and a bispecific antibody molecule that targets the CGRP receptor and other targets associated with the development of headache. Additional information regarding these molecules can be found in PCT Application No. WO 2010/075238.

In addition, a bispecific T-cell recruiter antibody (BiTE®) such as BLINCYTO® (blinatumomab) can be used in the device. Alternatively, a high molecular weight APJ agonist such as apelin or analogues thereof may be included in the device. Information related to such molecules can be found in PCT Publication No. WO 2014/099984.

In certain embodiments, the drug formulation comprises a therapeutically effective amount of an antibody to thymic stromal lymphopoietin (TSLP) or TSLP receptor. Examples of anti-TSLP antibodies that can be used in such embodiments include, without limitation, those described in US Pat. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in US Pat. No. 8,101,182. In particularly preferred embodiments, the drug formulation contains a therapeutically effective amount of an anti-TSLP antibody designated as A5 in US Pat. No. 7,982,016.

Although the methods, drug delivery devices, and components thereof have been described by way of the exemplary embodiments, they are not limited thereto. The detailed description is to be interpreted as being by way of example only and does not set forth every possible embodiment of the present invention, since it would be impractical, if not impossible, to set forth every possible embodiment. Numerous alternative embodiments can be implemented using current technology or technology developed after the filing date of this patent, which nevertheless fall within the scope of the claims that define the scope of the present invention. For example, the components described herein with reference to certain types of drug delivery devices, such as underbody drug delivery devices or other types of drug delivery devices, may also be used in other types of drug delivery devices, such as drug delivery devices in the form of an autoinjector.

Those skilled in the art will appreciate that numerous modifications, changes

-

Claims (20)

and combinations may be made with respect to the embodiments described above without departing from the scope of the present invention, and that such modifications, changes, and combinations are to be considered as falling within the scope of the teachings of the present invention. CLAIM 1. A method for assembling a platform device (100) for drug delivery, wherein the method includes: providing a set of basic components (104) for the drug delivery device; determining, based on at least one target characteristic of the drug delivery device, a rear assembly (108) for a drug delivery device from a group of rear assemblies, each of the rear assemblies in the group of rear assemblies including a different drive mechanism, each of these drive mechanisms is compatible with each base component (104) of the specified set of base components (104) and has a different characteristic; selecting said specific rear assembly unit; determining, based on at least one target characteristic of the drug delivery device, the front assembly (106) for the drug delivery device from the group of front assemblies, each front assembly (106) from the specified group of front assemblies is compatible with each base component (104) from the specified set of basic components (104); selecting said particular front assembly; and assembling the drug delivery device using the set of base components, the back assembly, and the front assembly. 2. The method of claim 1, wherein the at least one target property comprises at least one of drug viscosity or drug volume. 3. The method according to claim 1 or 2, characterized in that each front assembly contains another assembly in the form of a syringe. 4. Method according to claim 3, characterized in that the syringe assembly is constructed from one of glass or polymeric material. 5. The method according to any one of claims 1 to 4, characterized in that the set of basic components is geometrically identical in the configurations of the drug delivery device. 6. The method according to any one of claims 1 to 5, further comprising applying an outer coating (112) to the drug delivery device. 7. The method according to claim 6, characterized in that the outer cover is selected based on at least one attribute of the implied user group. 8. A method for assembling a platform device (100) for drug delivery, wherein the method includes: providing a set of base components (104) for the drug delivery device; determining, based on at least one target characteristic of the drug delivery device, the first assembly (106) for the drug delivery device from the first group of selectable assembly units, each first assembly unit (106) from the specified first group of selectable assembly units is compatible with each base component (104) of the specified set of base components (104); selecting said specific first assembly unit; determining, based on said at least one target characteristic, a second drug delivery device assembly (108) from a second group of selectable assemblies, each of the second group of selectable assemblies including a different drive mechanism, each of these drive mechanisms is compatible with each of the basic components (104) of the specified set of basic components (104) and has a different characteristic; selecting said specific second assembly unit; determining, based on said at least one target characteristic, a third assembly unit (110) for the drug delivery device from the third group of selectable assembly units; selecting said specific third assembly unit; assembling the drug delivery device using the set of base components, the first assembly, the second assembly, and the third assembly. 9. The method of claim 8, wherein at least one characteristic includes at least one of drug viscosity or drug volume. 10. The method according to claim 8 or 9, characterized in that the first group of selectable assembly units - 13 042893 includes a set of pre-filled assemblies in the form of a syringe. 11. Method according to any one of claims 8 to 10, characterized in that the plurality of drive assemblies includes a plurality of torsion springs, wherein each of the torsion springs collectively has different characteristics. 12. The method according to any one of claims 8-11, characterized in that the third group of selectable assembly units includes a set of adapters for different volumes. 13. The method according to any one of claims 8 to 12, further comprising applying an outer coating to the drug delivery device. 14. The method of claim 13, wherein the outer cover is selected based on at least one attribute of the intended user group. 15. The method according to any one of claims 8-14, characterized in that the set of basic components is geometrically identical in the configurations of the drug delivery device. 16. A platform system for assembling a platform device (100) for drug delivery by the method of any one of claims 1 to 7, wherein the system comprises: a set of base components (104) for a drug delivery device; a first group of selectable assemblies (106) for a drug delivery device, each selectable assembly (106) from said first group of selectable assemblies (106) being compatible with each base component (104) from said set of base components (104); a second group of selectable assemblies (108) for the drug delivery device, each of this second group of selectable assemblies including a different drive mechanism, each of these drive mechanisms being compatible with each base component (104) from the specified set of base components ( 104) and has a different characteristic; and a third group of selectable assemblies (110) for the drug delivery device; wherein the drug delivery device is assembled using at least one target characteristic of the drug delivery device to determine and select the first assembly from the first group of selectable assemblies, the second assembly from the second group of selectable assemblies, and the third assembly from the third group of selectable assemblies. assembly units, and attaching a set of basic components to the first group of selectable assembly units, the second group of selectable assembly units and the third group of selectable assembly units. 17. The platform system of claim 16, wherein at least one characteristic includes at least one of drug viscosity or drug volume. 18. Platform system according to claim 16 or 17, characterized in that the first group of selectable assembly units includes a set of pre-filled syringe-shaped assemblies. 19. The platform system of claim 18, wherein the set of springs includes a set of torsion springs, each of the torsion springs collectively having different characteristics. 20. Platform system according to any one of claims 16-19, characterized in that the third group of selectable assembly units includes a set of adapters for different volumes. -