Systems and methods for treating lymphatic channels

Abstract

Some non-limiting examples of the disclosure provide a medical device. The medical device can include a tube. The tube can include a wire scaffold coupled to and surrounding a carrier. The wire scaffold can structurally support the carrier. The carrier can include a therapeutic agent. The wire scaffold can be radiopaque and can be biodegradable. When the medical device is positioned in a lymphatic channel of a subject, the wire scaffold can dissolve, exposing the carrier to the lymph fluid of the lymphatic channel to release the therapeutic agent from the carrier. The therapeutic agent can be configured to treat a condition.

Description

Quarles 125141.04916SYSTEMS AND METHODS FOR TREATING LYMPHATIC CHANNELSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Patent Application No. 63 / 713,511 filed October 29, 2024, “Self-degrading Biohybrid Wire for Delivery into the Lymphatic System,” which is hereby incorporated by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0002] N / A.BACKGROUND

[0003] The lymphatic system is an open organ system of the body where fluids, antigens, lipids, cholesterol, wastes, nutrients, and other materials continuously flux into the lymphatic system and out of the lymphatic system. The lymphatic system also serves a critical immune system function, including generating and maturing lymphocytes and other immune system cells. Since the lymphatic system functions as the body’s fluid highway, sometimes the lymphatic system can transport undesirable materials including cells (e.g., metastatic cancerous cells). Further, tissues of the lymphatic system itself can become cancerous. Thus, it would be desirable to have improved systems and methods for treating lymphatic channels.SUMMARY OF THE DISCLOSURE

[0004] Some non-limiting examples of the disclosure provide a medical device. The medical device can include a tube. The tube can include a wire scaffold coupled to and surrounding a carrier. The wire scaffold can structurally support the carrier. The carrier can include a therapeutic agent. The wire scaffold can be radiopaque and can be biodegradable. When the medical device is positioned in a lymphatic channel of a subject, the wire scaffold can dissolve, exposing the carrier to the lymph fluid of the lymphatic channel to release the therapeutic agent from the carrier. The therapeutic agent can be configured to treat a condition.

[0005] In some non-limiting examples, a carrier can be embedded with a therapeutic agent.

[0006] In some non-limiting examples, a carrier can include a hydrogel.

[0007] In some non-limiting examples, a condition can be a lymphatic system condition. The lymphatic system condition can include at least one of: a lymphatic disease, lymphoma,- 1 -QB\99086149.3Quarles 125141.04916 lymphangitis, lymphedema, lymphadenopathy, lymphangioma, lymphocytosis, lymphatic filariasis, castleman disease, lymphangioleiomyomatosis, autoimmune lymphoproliferative syndrome, or mesenteric lymphadenitis

[0008] In some non-limiting examples, a thickness of a wire scaffold can be configured to dissolve completely after a medical device has been placed in the subject for a predetermined amount of time.

[0009] In some non-limiting examples, a predetermined amount of time can be twelve hours.

[0010] In some non-limiting examples, a thickness of the wire scaffold can be less than or equal to 1 millimeter.

[0011] In some non-limiting examples, a wire scaffold can seal a carrier, such that an outer surface of the carrier can be prevented from being exposed to an environment surrounding a medical device.

[0012] In some non-limiting examples, a wire scaffold can include a plurality of filaments.

[0013] In some non-limiting examples, a plurality of filaments can include a first filament and a second filament. The first filament can be coupled to the second filament at one or more locations to define one or more vertices.

[0014] In some non-limiting examples, a plurality of filaments can form a mesh.

[0015] In some non-limiting examples, a wire scaffold can include one or more filaments.The one or more filaments can be coiled.

[0016] In some non-limiting examples, a carrier can include a solution that has a therapeutic agent.

[0017] In some non-limiting examples, a carrier can include a polymer loaded with a therapeutic agent.

[0018] In some non-limiting examples, a polymer can be a hydrogel.

[0019] In some non-limiting examples, a carrier can release a therapeutic agent in a lymphatic channel over time.

[0020] In some non-limiting examples, a carrier can include a polymer. A rate that a carrier releases a therapeutic agent in a lymphatic channel can depend on a number of crosslinks of the polymer.- 2 -QB\99086149.3Quarles 125141.04916

[0021] In some non-limiting examples, a wire scaffold can include a polymer. The polymer can be at least one of polylactic acid (PLA), poly-l-lactic acid (PLLA),polyglycolic acid (PGA), polydioxanone (PDO), or chromic catgut.

[0022] In some non-limiting examples, a wire scaffold can include a metal. The metal can be magnesium.

[0023] In some non-limiting examples, a wire scaffold can include at least one of iodine, barium, iodine, tungsten, or calcium.

[0024] In some non-limiting examples, a medical device can include one or more radiopaque markers coupled to a wire scaffold. The one or more radiopaque markers providing a radiopacity of the wire scaffold.

[0025] In some non-limiting examples, one or more radiopaque markers can include a plurality of radiopaque markers distributed along a length of a tube.

[0026] In some non-limiting examples, a therapeutic agent can include a cytotoxic agent, chemotherapeutic agent, or a radiotherapy isotope.

[0027] Some non-limiting examples of the disclosure provide a medical device. The medical device can include a tube comprising a wire scaffold coupled to and surrounding a carrier. The wire scaffold can be radiopaque and biodegradable. The carrier can include a therapeutic agent. Thee therapeutic agent can be configured to treat a condition. The wire scaffold can isolate the carrier from contact with the internal environment surrounding the medical device.

[0028] Some non-limiting examples of the disclosure provide a device in accordance with any non-limiting example disclosed herein, alone or in combination with any other device or system.

[0029] Some non-limiting examples of the disclosure provide a method of manufacturing a device.

[0030] Some non-limiting examples of the disclosure provide a method of treating a patient using any of the devise described herein, alone or in combination with any other method.

[0031] The foregoing and other aspects and advantages of the present disclosure will appear from the following description. In the description, reference is made to the accompanying drawings that form a part hereof, and in which there is shown by way of- 3 -QB\99086149.3Quarles 125141.04916 illustration one or more exemplary versions. These versions do not necessarily represent the full scope of the disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The following drawings are provided to help illustrate various features of nonlimiting examples of the disclosure, and are not intended to limit the scope of the disclosure or exclude alternative implementations.

[0033] FIG. 1 shows a block diagram of a system including an imaging system, and a medical device.

[0034] FIG. 2 shows an example of an imaging system.

[0035] FIG. 3 A shows an isometric schematic illustration of a medical device.

[0036] FIG. 3B shows a cross-sectional view of the medical device of FIG. 3A taken along line 3B-3B of FIG. 3 A.

[0037] FIG. 4A show an isometric schematic illustration of a medical device.

[0038] FIG. 4B shows a cross-sectional view of the medical device of FIG. 4A taken along lines 4B-4B of FIG. 4A.

[0039] FIG. 5 shows an isometric schematic illustration of a medical device.

[0040] FIG. 6 shows an isometric schematic illustration of a medical device.

[0041] FIG. 7 shows a flowchart of a process for treating a lymphatic condition or a lymphatic disease.

[0042] FIG. 8 shows a schematic illustration of deploying a medical device along a guidewire to a target site within a lymphatic channel.DETAILED DESCRIPTION OF THE PRESENT DISCLOSURE

[0043] The lymphatic system is an open organ system of the body where fluids, antigens, lipids, cholesterol, wastes, nutrients, and other materials continuously flux into the lymphatic system and out of the lymphatic system. The lymphatic system also serves a critical immune system function, including generating and maturing lymphocytes and other immune system cells. Since the lymphatic system functions as the body’s fluid highway, sometimes the lymphatic system can transport undesirable materials including cells (e.g., metastatic cancerous cells). Further, tissues of the lymphatic system itself can become cancerous.- 4 -QB\99086149.3Quarles 125141.04916

[0044] Some approaches indirectly treat the lymphatic system or indirectly use the lymphatic system. For example, for non-lymphoma cancer treatments, chemotherapeutic agents (e.g., anti-cancer drugs) are introduced into the blood stream (e.g., intravenously) with the hope that a sufficient amount of the active agent will permeate to a lymph site (e.g., a lymph node). As another example, for lymphoma cancer treatments, a similar approach is used, where chemotherapeutic agents are also introduced into the blood stream, again, with the hope that a sufficient amount of the active agent will permeate to the lymph site. As yet another example, lymphangitis — an inflammation of your lymph vessels — is also treated globally, by the intravenous injection of antibodies. These global approaches to treatments have a number of downsides. First, the global approach can prevent a therapeutically effective dose of a therapeutic agent from reaching a target lymph site. This can undesirably lead to a wait-and- see approach, where a practitioner may not be able to determine whether a site has been treated, leading to delays (or sometimes inability in time) to actually treat a target lymph site. This can be especially problematic for aggressive forms of cancer where time is of the essence. Second, the global approach can lead to undesirable side effects, which can wreak havoc on patient general well-being. For example, chemotherapeutic agents, while targeting quickly dividing cancerous cells to a greater extent, still undesirably affect all cells in the body resulting in side effects including fatigue, hair loss, anemia, nausea, vomiting, etc. Third, in some cases, the types of agents may be limited by the global approach. For example, some therapeutic agents may not be able to safely be administered into the body (e.g., the blood stream), or some may not even be able to permeate into the lymphatic system.

[0045] Some non-limiting examples of the disclosure provide advantages to these issues (and others) by providing improved systems and methods for treating lymphatic channels. For example, some non-limiting examples of the disclosure provide a medical device that can include a wire scaffold coupled to and surrounding a carrier. The wire scaffold can structurally support the carrier so that the carrier can be actually manipulated (e.g., being guided by a guidewire or being advanced through a catheter or other tube). The carrier can be include the therapeutic agent, which can treat a condition or a disease at the lymph site or a site outside the lymphatic system (e.g., but delivered by the lymphatic channel and the broader lymphatic system). In some cases, the therapeutic agent can be impregnated within, embedded within, etc., the carrier, while in other cases, the therapeutic agent can be coupled to an outer surface- 5 -QB\99086149.3Quarles 125141.04916 of the carrier. The wire scaffold can be radiopaque, such that the medical device can be visible under x-ray guidance and the medical device can accordingly be guided to a target lymph site (e.g., within a lymphatic channel) during an interventional radiology procedure. Similarly, the wire scaffold can be biodegradable and can further be bioresorbable (e.g., formed out a biodegradable material, formed out of a bioresorbable material, etc.). In this way, once the medical device is guided to the lymph target site, the wire scaffold can begin degrading (e.g., after a sheath is removed from around medical device). Once the wire scaffold is degraded, thereby exposing the underlying carrier, the carrier releases the therapeutic agent all at once, or over a period of time (e.g., extended release, timed release, etc.). The therapeutic agent can treat a disease or condition at or near the target lymph site, or the therapeutic agent can use the lymphatic channel in which the medical device is located and other channels to treat lymphatic tissue away from the lymphatic channel. In this way, delivery of the therapeutic agent within the lymphatic channel can leverage the highway nature of the lymphatic system to treat multiple lymph sites (e.g., lymph nodes) that are away from the medical device. This targeted approach — as opposed to a global approach — can not only ensure that a therapeutic effective dose of the therapeutic agent actually reaches the target lymphatic site, but also can prevent large doses of the therapeutic agent from having to be administered and negatively impact the individual with undesirable side effects (e.g., the global approach).

[0046] FIG. 1 shows a block diagram of a system 100 including an imaging system 102, and a medical device 104. The imaging system 102 can acquire one or more images of the medical device 104 positioned within the subject to guide the medical device 104 to a lymphatic channel 106, which can include a target lymphatic site within or coupled to the lymphatic channel (e.g., a lymph node). In some cases, the imaging system 102 can be an x- ray imaging system (e.g., a fluoroscopy imaging system) so that the medical device 104 can be guided to the lymphatic target site under x-ray imaging guidance.

[0047] The medical device 104 can include a wire scaffold 108, a carrier 110, and a therapeutic agent 112. As shown in FIG. 1, the wire scaffold 108 is coupled to and surrounds the carrier 110, and the carrier 110 is coupled to and surrounds the therapeutic agent 112. The wire scaffold 108 can include one or more filaments, and more specifically a plurality of filaments. The plurality of filaments can include a first filament and a second filament. The first filament can be coupled to the second filament at a first location to define a first vertex,- 6 -QB\99086149.3Quarles 125141.04916 the first filament can be coupled to the second filament at a second location to define second vertex, and so on (e.g., three, four, five, etc., vertices). Further, the plurality of filaments can include three, four, five, etc., filaments, where each filament of the plurality of filaments can be coupled to some or all of the other filaments of the plurality of filaments. Each filament can have different shapes. For example, each filament can be flat (e.g., have one or more planar surfaces), can be cylindrical (e.g., have a cylindrical shape), etc. In some cases, the wire scaffold 108 can form a mesh, where the plurality of filaments form a mesh. In other cases, the plurality of filaments can be interwoven together, in which respective filaments can be coupled together in the location where the respective filaments overlap.

[0048] The wire scaffold 108 can be biodegradable and can be bioresorbable. For example, the wire scaffold 108, when exposed to the internal environment of the subject (e.g., the lymph fluid) at or above a specific temperature (e.g., body temperature, about 37°C) can begin degrading. In some cases, the wire scaffold 108 can degrade after a predetermined period of time when in the internal aera of the subject at or above the specific temperature. For example, the material or materials of the wire scaffold 108 (e.g., of the filament), a thickness of the wire scaffold (e.g., the thickness of the filament), a width of the wire scaffold 108 (e.g., a width of the filament), etc., a length of the wire scaffold 108 (e.g., length of the filament), etc., can be selected so that the wire scaffold 108 can completely degrade at or about the predetermined period of time which can be exactly or about 12 hours. Once completely degraded, the carrier 110 is exposed to the internal environment of the subject to release the therapeutic agent 112. In some cases, only a portion of a thickness of the wire scaffold 108 degrades after the period of time, exposing only the underlying portion of the carrier 110. In other words, after the predetermined period of time, the area of the carrier 110 under the portion of the wire scaffold 108 is exposed to the internal environment. In some cases, the thickness of the wire scaffold and specifically the thickness of each filament can be less than or equal to about (or exactly) 1 millimeter, 0.9 millimeters, 0.889 millimeters, etc. In some cases, this relatively small thickness can permit the timed degradation of the filament (or wire scaffold 108 more broadly) with the predetermined period of time.

[0049] The wire scaffold 108 can also be radiopaque. That is, the wire scaffold 108 can appear in an x-ray image to, for example, guide the medical device 104 during an interventional radiology procedure to the lymphatic target site. In some cases, the one or more filaments of- 7 -QB\99086149.3Quarles 125141.04916 the wire scaffold 108 can be radiopaque (e.g., formed of a relatively high density material). In other cases, the wire scaffold 108 can be loaded with a radiopaque material (e.g., calcium, tungsten, iodine, barium, iron, etc.), so that at least portions of the wire scaffold 108 is visible from the radiopaque material. In some cases, each radiopaque material can be charged (e.g., derived from a salt), or can be in an uncharged state (e.g., a natural state). In other cases, the wire scaffold 108 (and the medical device 104 more generally) can be radiopaque from one or more radiopaque markers coupled to the medical device 104, such as at the wire scaffold 108. For example, the medical device 104 can include a plurality of radiopaque markers distributed along the length of the medical device 104 (e.g., substantially or exactly evenly spaced along the length of the medical device).

[0050] The wire scaffold 108 can be formed out of various materials. For example, the wire scaffold 108, and more specifically the one or more filaments, can include a metal, a polymer, etc. The metal can include iron, steel, calcium, tungsten, magnesium, etc. The polymer can be polylactic acid (“PLA”), poly-l-lactic acid (“PLLA”), polyglycolic acid (“PGA”), polydioxanone (“PDO”), chromic catgut, hydroxyapatite (“HA”), poly(methyl methacrylate) (“PMMA”), poly (L-lactide-co-D,L4actide)(“PLDLLA”), etc. In some cases, the polymer can be a hydrogel (e.g., a natural hydrogel or a synthetic hydrogel), such as, for example, collagen, elastin, silk fibronin, bacterial cellulose, poly(ethylene glycol) (“PEG”), alginate, gelatin, etc. In some cases, the hydrogel can have a number of chemical crosslinks (e.g., by polymerization) or a number of physical crosslinks. In some cases, for example, to provide the radi opacity of the wire scaffold 108 and when the wire scaffold 108 includes a hydrogel, the hydrogel can be loaded with a radiopaque material (e.g., calcium ions, such as Ca2+).

[0051] Although the term wire scaffold 108 may insinuate gaps (e.g., between filaments), the wire scaffold 108 need not have gaps (but can include gaps). For example, the plurality of filaments can be coupled to each other tightly, leaving no gaps between adjacent filaments. Further, the wire scaffold 108 can include a plurality of different layers (e.g., with each layer having a plurality of filaments), in which adjacent layers (e.g., the filaments thereof) are coupled together. In this way, the plurality of layers collectively can mitigate gaps and otherwise prevent the internal environment (e.g., the lymph fluid) from contacting the carrier 110. As another example, the wire scaffold 108 can be a tubular block of material (e.g., when- 8 -QB\99086149.3Quarles 125141.04916 each of the plurality of filaments is a polymer chain). As yet another example, the wire scaffold 108 can function as a structural frame (e.g., like a skeleton) in which a different material (e.g., than the structural frame) can surround and can envelop or encapsulate the wire scaffold 108. In this way, the structural frame can be formed of a first material (e.g., PLA), and a second material can encapsulate the structural frame (e.g., a hydrogel). The first material can be stronger, more rigid, etc., than the second material, while the second material can degrade faster than the first material. In this way, the second material can adequately decompose and biodegrade completely within the predetermined period of time (e.g., within twelve hours), exposing the carrier 110 to the internal environment (e.g., at locations between the gaps or apertures in the structural frame), while the first material of the structural frame remains (e.g., for a longer period of time). This can ensure that the position of the medical device 104 does not move from the placement location, and can ensure that the medical device 104 is structurally sound during placement (e g., being deployed, the medical device 104 will not, for example, collapse).

[0052] The carrier 110 can be coupled to the wire scaffold 108, and as shown in FIG. 1, the carrier 110 can be positioned within the wire scaffold 108, where the wire scaffold 108 surrounds the carrier 110. The carrier 110 can include the therapeutic agent 112. For example, the therapeutic agent 112 can be embedded within the carrier 110, the therapeutic agent 112 can be impregnated within the carrier 110, etc. As another example, the therapeutic agent 112 can be coupled to a surface of the carrier 110 (e.g., an outer surface of the carrier 110). In some cases, the therapeutic agent 112 can be evenly, or uniformly distributed within the carrier 110. In other cases, the therapeutic agent 112 can be encapsulated within the carrier 110. For example, a pocket within the carrier 110 can include the therapeutic agent 112 (e.g., the pocket including a solution of the therapeutic agent 112). In this case, when the carrier 110 degrades, the pocket exposes and releases the contents of the pocket including the therapeutic agent 112 therein. In some cases, the carrier 110 can include more than one pockets, each of which can be at different depths within the carrier 110. Accordingly, each pocket can include a different therapeutic agent positioned therein.

[0053] In some cases, the carrier 110 can biodegrade or bioresorb more quickly than the wire scaffold 108 under the same conditions (e.g., when placed in the subject, at the same temperature, etc ). In some cases, the carrier 110 can be formed out of various materials- 9 -QB\99086149.3Quarles 125141.04916 including polymers, such as, for example, a hydrogel. The hydrogel can be loaded with the therapeutic agent. In some configurations, the carrier 110 can deliver a payload of the therapeutic agent 112 where the carrier 110 purges or otherwise unloads all of the therapeutic agent 112 contained by the carrier 110. In other cases, the carrier 110 can release the therapeutic agent 112 over time (e.g., an extended release of the therapeutic agent 112 over a period of time). For example, the therapeutic agent 112 elutes out of the carrier 110 over time. In some cases, this extended release of the therapeutic agent 112, such as, a therapeutically effective dose (or amount) of the therapeutic agent 112 delivered to a target site within a lymphatic channel over a period of time (e.g., days, weeks, etc.) can advantageously limit the number of surgical interventions needed. For example, long after the procedure is completed, the medical device 104 and specifically the carrier 110 can continue eluting the therapeutic agent 112 to treat the subject. In some cases, the rate of eluting of the therapeutic agent 112 from the carrier 110 can depend on a number of factors. For example, the permeability of the carrier 110 can dictate the rate of elution of the therapeutic agent 112 out of the carrier 110. In some cases, the number of crosslinks of a polymer (e.g., a hydrogel) can determine the permeability of the carrier 110 (e.g., with a higher number of crosslinks decreasing the rate of elution of the therapeutic agent 112 out of the carrier 110 and vice versa). In some cases, when the carrier 110 includes a hydrogel, the hydrogel (e.g., a natural hydrogel or a synthetic hydrogel), can be, for example, collagen, elastin, silk fibronin, bacterial cellulose, poly(ethylene glycol) (“PEG”), alginate, gelatin, etc. In some cases, the hydrogel can have a number of chemical crosslinks (e.g., by polymerization) or a number of physical crosslinks.

[0054] As described above, the release of the therapeutic agent 112 by the carrier 110 can be at a therapeutically effective dose required to treat a condition or a disease. In some configurations, the disease (e g., a disease state) can be chronic, acute, can be single or multi- symptomatic, etc. The condition or the disease can be a lymphatic system condition or a lymphatic system disease. For example, the lymphatic system condition can be a lymphatic disease, lymphoma, lymphangitis, lymphedema, lymphadenopathy, lymphangioma, lymphocytosis, lymphatic filariasis, castleman disease, lymphangioleiomyomatosis, autoimmune lymphoproliferative syndrome, or mesenteric lymphadenitis. In some cases, the term “therapeutic agent” can include any molecule, or groups of molecules intended to provide a particular level of therapy for a condition or a disease. For example, a therapeutic agent can- 10 -QB\99086149.3Quarles 125141.04916 include an antagonist, alkaloid, antibiotic, enzyme inhibitor, anti metabolite, growth factor inhibitor, enzyme, carbohydrate, lipid, protein, peptide, amino acid, peptide, miRNA, nucleic acid, drug, antibody, cell receptor molecule, biological response modifier, combinations thereof, etc. In some cases, the therapeutic agent can include a cytotoxic agent. The cytotoxic agent can include a chemotherapeutic agent, radiotherapy isotopes such as 213Bi, 223Ra, 177Lu, 225Act. 212Pb, 211At, I66H0, 89Sr, 153Sm, 105Rh, 1251, 1311, 90Y, 47Sc, 77Br, 67Cu, 149Pr, 199Ag and 186Re, alkylating agents, antagonists, plant alkaloids, intercalating antibiotics, enzyme inhibitors, antimetabolites, mitotic inhibitors, growth factor inhibitors, cell cycle inhibitors, enzymes, biological response modifiers, and combinations thereof. In some configurations, the therapeutic agent 112 can include other pharmaceuticals. In some nonlimiting examples, the bioactive agent can include DNA, RNA, or other gene(s), lipid(s), carbohydrate(s), protein(s), amino acid(s), peptide based therapeutics, etc.

[0055] Although FIG. 1 shows the carrier 110 includes a therapeutic agent 112, the carrier 110 can include multiple therapeutic agents. For example, as described above, the carrier 110 can include multiple pockets, with each pocket containing a different (or the same) therapeutic agent therein. As another example, the medical device 104 can include multiple carriers 110, each with the same or different therapeutic agent. More specifically, a first carrier can include a first therapeutic agent, and a second carrier can include a second therapeutic agent, with the first carrier surrounding the second carrier. The first therapeutic agent and the second therapeutic agent can treat the same disease (e g., lymphoma), in which the first therapeutic agent and the second therapeutic agent can be the same or substantially the same drug, molecule, etc. The first carrier can be loaded with a higher concentration of the first therapeutic as compared to the concentration of the second therapeutic agent in the second carrier. In this way, when the first carrier is exposed and releases the first therapeutic agent, the first therapeutic agent (e.g., due to the higher concentration) can treat an acute version of the disease. Then, when the second carrier is exposed and releases the second therapeutic agent, the second therapeutic agent can treat a chronic version of the disease (or provide a maintenance drug delivery to treat the disease, an extended release of the therapeutic agent over a period of time). This can provide an even higher tailored and targeted approach to treating a disease state. In some cases, therefore, the first carrier can provide a payload of a- 11 -QB\99086149.3Quarles 125141.04916 first therapeutic agent, while the second carrier can include an extended release of the second therapeutic agent.

[0056] In some configurations, the medical device 104 can include a bore directed entirely therethrough. The bore can be directed along a longitudinal axis of the medical device 104. The bore can provide for delivery of the medical device 104 via a guidewire. For example, a guidewire can first be placed at a desired location (e.g., a distal end of the guidewire), via image guidance. Then, the medical device 104 can be advanced along the guidewire (e.g., by pushing the medical device 104) until the medical device 104 reaches a desired location (e.g., via image guidance). As another example, the guidewire can be inserted into the bore of the medical device 104 and the guidewire and the medical device 104 can be advanced together, until the medical device 104 reaches the desired location. In some cases, the medical device 104 can include a barrier that can define the bore, or the barrier can line the bore (e.g., the carrier 110 can surround the barrier). The barrier can be formed out of various materials such as described herein, but the barrier can be made of a stronger material than the carrier 110. Regardless, the barrier can protect the carrier 110 from being exposed to the internal environment (e.g., from inadvertently releasing the therapeutic agent 112 before the medical device 104 reaches the target site), and the barrier can protect the carrier 110 from being punctured, worn, etc. (e.g., since the carrier 110 may be formed out of a more fragile material, such as a hydrogel). In some cases, the barrier can be biodegradable and bioresorbable. In some configurations, the barrier can not only extend within the region of the medical device 104 that defines the bore, but can also extend upwardly along longitudinal ends (e.g., opposing axial ends). In this way, the barrier can encapsulate otherwise exposed regions of the carrier 110, and the wire scaffold 108, to avoid unwanted degradation of the carrier 110 and the wire scaffold 108 (e.g., during positioning and deployment of the medical device 104). In some cases, rather than the barrier encapsulating opposing ends of the carrier 110 (e.g., axial surfaces thereof), the wire scaffold 108 can extend along those surfaces of the carrier 110 to encapsulate those ends of the carrier 110. In some specific cases, the barrier can be a wire scaffold.

[0057] In some non-limiting examples, the medical device 104 can include a sheath surrounding the wire scaffold and the carrier 110 (e.g., the sheath surrounding the medical device 104). The sheath can be slideably engaged with the medical device 104, such that once the medical device 104 reaches a desired target site, the sheath can be slid off (e.g., by an- 12 -QB\99086149.3Quarles 125141.04916 instrument) and the wire scaffold 108 can then be exposed to the internal environment (and therefore begin degrading). Similarly to the barrier, the sheath, which covers a top surface of the wire scaffold 108, can prevent unwanted exposure of the wire scaffold 108 to the internal environment (and therefore prevent unwanted degrading), such as, for example, during deployment and positioning of the medical device 104. In some configurations, the medical device 104 can lack the wire scaffold 108, where the sheath can be positioned over a top surface of the carrier 110. This can be desirable, for example, to decrease the overall size of the medical device 104.

[0058] In some configurations, as described above, the wire scaffold 108 can seal the carrier 110 (and the therapeutic agent 112) from being exposed to the internal environment of the subject to degrade, until the wire scaffold 108 degrades and exposes a top surface of the carrier 110 to the internal environment. In operation, the medical device 104 can be advanced, such as along a guidewire and under image guidance using the imaging system 102, until the medical device 104 reaches a target site (e.g., a lymph node) within the lymphatic channel 106 (e.g., entirely within the lymphatic channel). Once the placement of the medical device 104 has been confirmed using the imaging system 102, the guidewire can be removed, and the sheath can be removed from the medical system 104 exposing the wire scaffold 108 to the internal environment and therefore to begin degrading. After the wire scaffold 108 has degraded and exposed a top surface of the carrier 110, the carrier 110 begins releasing the therapeutic agent 112 within the lymphatic channel 106 to treat the condition or the disease, which can include the target site.

[0059] In some configurations, a portion 114 of the medical device 104 can be decoupled or otherwise removed. For example, a series of notches, perforations, etc., can be disposed around the medical device 104 to provide a location to decouple that portion from the medical device 104. In this way, during placement, the medical device 104 can be adjusted in size to, for example, account for different patient lymphatic channel anatomies, sizes, etc. In some configurations, the medical device 104 can include a coupler 120, which can be coupled to the medical device 104 including the wire scaffold 108, the carrier 110, etc. The coupler 120 can extend away from the medical device 104. In some cases, the coupler 120 can be coupled to a proximal end of the medical device 104. In this way, as described below, the coupler 120 when coupled to an instrument, guide, etc., can push and advance the medical device 104 to a desired- 13 -QB\99086149.3Quarles 125141.04916 location. Then, once the medical device 104 is at the desired location, the instrument, guide, etc., can decouple, detach, etc., from the coupler 120 to leave the medical device 104 at the desired location and retract the instrument, guide, etc., to be removed from the patient.

[0060] The coupler 120 can be coupled to and decoupled from an instrument 122 (e.g., in the form of a guidewire). For example, the instrument 122 can also include a coupler 124, where the couplers 120, 124 can be coupled together to position the medical device 104 and can be decoupled to leave the medical device 104 in the desired position and retract the instrument 122 back out of the patient. The couplers 120, 124 can be implemented in different ways. For example, as shown in FIG. 1, the coupler 120 can include a bore 126 that is threaded, while the coupler 124 can include a shaft 128 that is threaded. The couplers 120, 124 can be engaged by threadingly engaging the shaft 128 with the bore 126 (e.g., by rotating the shaft 128 in a first direction) to advance the medical device 104 to a desired position. Similarly the couplers 120, 124 can be disengaged by threadingly disengaging the shaft 128 from the bore 126 to decouple the instrument 122 from the medical device 104 (e.g., by rotating the shaft 128 in a second direction). Although the instrument 122 is shown including the shaft 128, the coupler 120 can include the shaft 128 and the instrument 122 can include the bore 126. Further, other coupling mechanisms are contemplated to couple the couplers 120, 124 together (e.g., friction fitting the components together, magnetically coupling the components together, using a temporary adhesive, etc.). In some cases, the coupler 120 can have similar material properties as the other features of the medical device 104. For example, the coupler 120 can be biodegradable and bioresorbable. Further, the coupler 120 can also be radiopaque. In some configurations, the coupler 128 is not biodegradable and bioresorbable, at least because the coupler 124 and instrument 122 are withdrawn from the patient after positioning the medical device 104.

[0061] In some embodiments, when the medical device 104 includes the coupler 120 the medical device does not include a bore directed through the medical device 104 (e.g., entirely through the medical device), since for example, the instrument (e.g., guidewire) already can attach to the medical device 104 at the coupler 120 to move the medical device 104 into position.

[0062] FIG. 2 shows an example of an imaging system 200, which can be a specific implementation of the imaging system 102. Accordingly, the description of the imaging- 14 -QB\99086149.3Quarles 125141.04916 system 200 pertains to the imaging system 102 and vice versa. The imaging system 200 can be used with the systems and methods of the present disclosure. The imaging system 200 can be a so-called “C-arm” x-ray imaging system. In other configurations, however, the imaging system 200 can be a fixed-position, a single-source, a bi-plane, or other architecture. The imaging system 200 can guide the medical device 104 (or other medical devices) to a target site within a lymphatic channel.

[0063] In the non-limiting example of FIG. 2, the C-arm x-ray imaging system 200 includes a gantry 202 having a C-arm to which an x-ray source assembly 204 is coupled on one end and an x-ray detector array assembly 206 is coupled at its other end. The gantry 202 enables the x-ray source assembly 204 and detector array assembly 206 to be oriented in different positions and angles around a subject 208, such as a medical patient or an object undergoing examination that is positioned on a table 210. When the subject 208 is a medical patient, this configuration enables a physician access to the subject 208.

[0064] The x-ray source assembly 204 includes at least one x-ray source that projects an x-ray beam, which may be a fan-beam or cone-beam of x-rays, towards the x-ray detector array assembly 206 on the opposite side of the gantry 202. The x-ray detector array assembly 206 includes at least one x-ray detector, which may include a number of x-ray detector elements. Examples of x-ray detectors that may be included in the x-ray detector array assembly 206 include flat panel detectors, such as so-called “small flat panel” detectors, in which the detector array panel may be around centimeters in size. Such a detector panel allows the coverage of a field-of-view of approximately twelve centimeters.

[0065] Together, the x-ray detector elements in the one or more x-ray detectors housed in the x-ray detector array assembly 206 sense the projected x-rays that pass through a subject 208. Each x-ray detector element produces an electrical signal that may represent the intensity of an impinging x-ray beam and, thus, the attenuation of the x-ray beam as it passes through the subject 208. In some configurations, each x-ray detector element is capable of counting the number of x-ray photons that impinge upon the detector. During a scan to acquire x-ray projection data, the gantry 202 and the components mounted thereon rotate about an isocenter of the C-arm x-ray imaging system 200.

[0066] The gantry 202 includes a support base 212. A support arm 214 is rotatably fastened to the support base 212 for rotation about a horizontal pivot axis 216. The pivot axis 216 is- 15 -QB\99086149.3Quarles 125141.04916 aligned with the centerline of the table 210 and the support arm 214 extends radially outward from the pivot axis 216 to support a C-arm drive assembly 218 on its outer end. The C-arm gantry 202 is slidably fastened to the drive assembly 218 and is coupled to a drive motor (not shown) that slides the C-arm gantry 202 to revolve it about a C-axis, as indicated by arrows 220. The pivot axis 216 and C-axis are orthogonal and intersect each other at the isocenter of the C-arm x-ray imaging system 200, which is indicated by the black circle and is located above the table 210.

[0067] The x-ray source assembly 204 and x-ray detector array assembly 206 extend radially inward to the pivot axis 216 such that the center ray of this x-ray beam passes through the system isocenter. The center ray of the x-ray beam can thus be rotated about the system isocenter around either the pivot axis 216, the C-axis, or both during the acquisition of x-ray attenuation data from a subject 208 placed on the table 210. During a scan, the x-ray source and detector array are rotated about the system isocenter to acquire x-ray attenuation projection data from different angles. By way of example, the detector array is able to acquire thirty projections, or views, per second.

[0068] The C-arm x-ray imaging system 200 also includes an operator workstation 222, which typically includes a display 224; one or more input devices 226, such as a keyboard and mouse; and a computer processor 228. The computer processor 228 may include a commercially available programmable machine running a commercially available operating system. The operator workstation 222 provides the operator interface that enables scanning control parameters to be entered into the C-arm x-ray imaging system 200. In general, the operator workstation 222 is in communication with a data store server 230 and an image reconstruction system 232. By way of example, the operator workstation 222, data store sever 230, and image reconstruction system 232 may be connected via a communication system 234, which may include any suitable network connection, whether wired, wireless, or a combination of both. As an example, the communication system 234 may include both proprietary or dedicated networks, as well as open networks, such as the internet.

[0069] The operator workstation 222 is also in communication with a control system 236 that controls operation of the C-arm x-ray imaging system 200. The control system 236 generally includes a C-axis controller 238, a pivot axis controller 240, an x-ray controller 242, a data acquisition system (“DAS”) 244, and a table controller 246. The x-ray controller 242- 16 -QB\99086149.3Quarles 125141.04916 provides power and timing signals to the x-ray source assembly 204, and the table controller 246 is operable to move the table 210 to different positions and orientations within the C-arm x-ray imaging system 200.

[0070] The rotation of the gantry 202 to which the x-ray source assembly 204 and the x- ray detector array assembly 206 are coupled is controlled by the C-axis controller 238 and the pivot axis controller 240, which respectively control the rotation of the gantry 202 about the C-axis and the pivot axis 216. In response to motion commands from the operator workstation 222, the C-axis controller 238 and the pivot axis controller 240 provide power to motors in the C-arm x-ray imaging system 200 that produce the rotations about the C-axis and the pivot axis 216, respectively. For example, a program executed by the operator workstation 222 generates motion commands to the C-axis controller 238 and pivot axis controller 240 to move the gantry 202, and thereby the x-ray source assembly 204 and x-ray detector array assembly 206, in a prescribed scan path.

[0071] The DAS 244 samples data from the one or more x-ray detectors in the x-ray detector array assembly 206 and converts the data to digital signals for subsequent processing. For instance, digitized x-ray data is communicated from the DAS 244 to the data store server 230. The image reconstruction system 232 then retrieves the x-ray data from the data store server 230 and reconstructs an image therefrom. The image reconstruction system 232 may include a commercially available computer processor, or may be a highly parallel computer architecture, such as a system that includes multiple-core processors and massively parallel, high-density computing devices. Optionally, image reconstruction can also be performed on the processor 228 in the operator workstation 222. Reconstructed images can then be communicated back to the data store server 230 for storage or to the operator workstation 222 to be displayed to the operator or clinician.

[0072] The C-arm x-ray imaging system 200 may also include one or more networked workstations 248. By way of example, a networked workstation 248 may include a display 250; one or more input devices 252, such as a keyboard and mouse; and a processor 254. The networked workstation 248 may be located within the same facility as the operator workstation 222, or in a different facility, such as a different healthcare institution or clinic.

[0073] The networked workstation 248, whether within the same facility or in a different facility as the operator workstation 222, may gain remote access to the data store server 230,- 17 -QB\99086149.3Quarles 125141.04916 the image reconstruction system 232, or both via the communication system 234. Accordingly, multiple networked workstations 248 may have access to the data store server 230, the image reconstruction system 232, or both. In this manner, x-ray data, reconstructed images, or other data may be exchanged between the data store server 230, the image reconstruction system 232, and the networked workstations 248, such that the data or images may be remotely processed by the networked workstation 248. This data may be exchanged in any suitable format, such as in accordance with the transmission control protocol (“TCP”), the Internet protocol (“IP”), or other known or suitable protocols.

[0074] Although the disclosure below will described in reference to the use of a biplane fluoroscopy imaging system (e.g., the “C-arm” x-ray imaging system 200), in other nonlimiting examples other imaging systems can be utilized (e.g., a single-plane fluoroscopy imaging system).

[0075] FIG. 3A shows an isometric schematic illustration of a medical device 300, while FIG. 3B shows a cross-sectional view of the medical device 300 taken along line 3B-3B of FIG. 3A. The medical device 300 can be a specific implementation of the medical device 104. Accordingly, the description of the medical device 300 pertains to the medical device 104 and vice versa.

[0076] The medical device 300, which can be a tube (or have a tubular shape), can include a wire scaffold 302, a carrier 304, and a bore 306. As shown in FIG. 3A, the wire scaffold 302 is coupled to and surrounds the carrier 304 and the carrier 304 surrounds the bore 306. The bore 306 can be directed entirely though the medical device 300 so as to receive a guidewire for placement of the medical device 300. Although not shown in FIG. 3A, opposing longitudinal sides 308, 310 of the medical device 300 can include a barrier to seal or otherwise prevent axial surfaces of the carrier 304 from inadvertently being exposed to the internal environment (e.g., axial surface 312 of the carrier 304). In some cases, the barrier can be a part of the wire scaffold 302 (e.g., the wire scaffold 302 can cover those areas).

[0077] The medical device 300 can include a barrier 314. As shown in FIG. 3B, the barrier 314 can be coupled an inner surface of the carrier 304 (e.g., opposite an outer surface that is coupled to the wire scaffold 302). The barrier 314 can prevent the inner surface of the carrier 304 from being exposed to the internal environment. In some cases, a portion of the medical device 300 can be decoupled, severed, split, etc., from the medical device 300. For example,- 18 -QB\99086149.3Quarles 125141.04916 the medical device 300 can include one or more notches 316 to split a portion of the medical device (e.g., including a terminal distal end of the medical device 300) from the remaining medical device 300.

[0078] FIG. 4A show an isometric schematic illustration of a medical device 350, while FIG. 4B shows a cross-sectional view of the medical device 350 taken along lines 4B-4B of FIG. 4A. The medical device 350 can be a specific implementation of the medical device 104. Accordingly, the description of the medical device 350 pertains to the medical device 104 and vice versa.

[0079] The medical device 350 generally shows an inverted configuration of the wire scaffold and the carrier. For example, the medical device 350, which can be a tube (or have a tubular shape), can also include a wire scaffold 352, a carrier 354, and a bore 356. However, the carrier 354 surrounds the wire scaffold 352, and the wire scaffold 352 surrounds the bore 356. In this way, the structural integrity provided by the wire scaffold 352 closer to the bore 356 can ensure that the carrier 354 does not inadvertently move during placement. In other words, the wire scaffold 352 being placed closer to a centroid of the medical device 300 can provide better structural support of the medical device 350 during placement thereof. In some non-limiting examples, the medical device 350 can include a sheath 358 that surrounds the carrier 354. As described above, the sheath 358 can be slideably engaged to the carrier 354 (and more broadly the medical device 350), such that the carrier 354 does not degrade during, for example, placement of the medical device 350 at the target site.

[0080] FIG. 5 shows an isometric schematic illustration of a medical device 400, which can be a specific implementation of the medical device 104. Accordingly, the description of the medical device 400 pertains to the medical device 104 and vice versa. In some cases, such as illustrated with respect to the medical devices 300, 350, a wire scaffold can be formed as a mesh. In other cases, however, a wire scaffold can have other shapes. For example, the wire scaffold can be coiled, spiraled, helically wound, etc. The medical device 400 can include a wire scaffold 402 including one or more filaments 404. Each filament of the one or more filaments 404 can be wound around a longitudinal axis 406 of the medical device 400. In this way, the wire scaffold 402 can have a shape like a coiled spring. In some cases, the spacing between adjacent segments of the same or different filament can be the same or substantially the same. That is, the wire scaffold 402 can have a substantially constant pitch spacing. In- 19 -QB\99086149.3Quarles 125141.04916 other cases, the spacing between adjacent segments can be variable (e.g., the wire scaffold 402 can be variably pitched). In some cases, adjacent segments of the same or different fdament along the longitudinal axis 406 can be coupled together or otherwise can be in contact (e.g., to create a seal between the carrier and the surrounding environment).

[0081] FIG. 6 shows an isometric schematic illustration of a medical device 450, which can be a specific implementation of the medical device 104. Accordingly, the description of the medical device 450 pertains to the medical device 104 and vice versa. The medical device 450 can include one or more markers 452 distributed along a longitudinal axis of the medical device 450. Each marker 452 can be radiopaque (e.g., the one or more makers being radiopaque markers), such that each marker 452 is visible in an x-ray image (e.g., from the imaging system 102). The radiopaque markers can be encapsulated with a radiopaque material (e.g., a high density material), each of which can be biodegradable and bioresorbable. Specifically, the material that encapsulates the radiopaque material can be biodegradable and bioresorbable and the radiopaque material itself can be biodegradable and bioresorbable. For example, a calcium loaded hydrogel can be radiopaque (e.g., from the calcium), biodegradable, and bioresorbable.

[0082] The one or more markers 452 can be substantially evenly spaced apart along the medical device 450 (e.g., the distance between adjacent markers is substantially the same along the longitudinal axis 454). In other cases, the one or more markers 452 can be substantially unevenly spaced along the medical device 450. Each marker of the one or more markers 452 can have different shapes, such as, for example, spheres, cubes, rectangular prisms, etc. Accordingly in some cases, the one or more markers 452 can be flat (e.g., following the outer curvature of the medical device 450, such as the outer curvature of the wire scaffold) or can have a three-dimensional shape. In some cases, each marker of the one or more markers 452 being spherical can be advantageous in that a projection (or slice) of the sphere, regardless of imaging angle, will yield a circle in the image(and each circle being the same size in the image irrespective of the imaging angle).

[0083] FIG. 7 shows a flowchart of a process 500 for treating a lymphatic condition or a lymphatic disease. The process 500 can be implemented using any of the medical devices (e.g., 104, 300, 350, 400, etc.), any of the imaging systems (e.g., imaging system 102, 200), described herein.- 20 -QB\99086149.3Quarles 125141.04916

[0084] At block 502, the process 500 can include guiding a medical device to a target site of a lymphatic channel. For example, this block 502 can include inserting a guidewire into a subject until a distal end of the guidewire reaches the target site (e.g., under image guidance using one or more acquired images of the guidewire deployed in the subject). In some cases, once the guidewire is placed, the medical device can be advanced along the guidewire until the medical device reaches the target site. This can include acquiring one or more images of the medical device (e.g., on the guidewire) to guide the medical device until the medical device reaches the target site (e.g., where the wire scaffold, the markers, etc., appear on the images). Once the medical device has been placed, a sheath (if present) can be removed, and the guidewire can be retrieved (e.g., in some cases, a stop can prevent the medical device from being retracted along with the guidewire when the guidewire is retreated). In some cases, when placed, the medical device can be located entirely within the lymphatic channel (e.g., or lymph node, or other structure of the lymphatic system) of the subject.

[0085] FIG. 8 shows a schematic illustration of deploying a medical device 550 along a guidewire 552 to a target site 554 within a lymphatic channel 556. As shown in FIG. 8, the medical device 550 is positioned at the target site 554. In some cases, the therapeutic agent released by the medical device 550 can treat a lymph node 558 that is fluidly coupled to the lymphatic channel 556. That is, the released therapeutic agent is emitted into the lymphatic channel 556 and travels to the lymph node 558 to treat the lymph node 558.

[0086] Referring back to FIG. 7, at block 504, the process 500 can include dissolving a wire scaffold of the medical device. As described above, the wire scaffold can dissolve over predetermined amount of time, such as, for example, at about 12 hours (e.g., when the wire scaffold is exposed to the internal environment). Once the wire scaffold dissolves, the carrier is exposed and comes in contact with the internal environment. In some cases, including when the medical device includes multiple carriers, the block 504 can include dissolving the multiple carriers.

[0087] At block 506, the process 500 can include releasing a therapeutic agent from the carrier, which can include releasing each therapeutic agent from each carrier. In some cases, the therapeutic agent is released into the lymphatic channel of the lymphatic system. In some cases, each amount released of the therapeutic agent can be a therapeutically effective dose of the therapeutic agent (e.g., for each therapeutic agent, as applicable).- 21 -QB\99086149.3Quarles 125141.04916

[0088] At block 508, the process 500 can include treating a lymphatic disease or a lymphatic condition with the therapeutic agent (or multiple therapeutic agents) with the therapeutic agent (e.g., the therapeutically effective dose thereof). Further, including when there are multiple therapeutic agents, each therapeutic agent can treat the same or a different lymphatic condition or lymphatic disease.

[0094] The therapeutically effective amount (or therapeutically effective dose) can vary depending upon the intended application or the subject and disease condition being treated, for example, the weight and age of the subject, the severity of the disease condition, the manner of administration and the like, which can readily be determined such as by a board-certified physician.

[0095] As used herein, the terms “treat,” “treatment,” “treating” refer to therapeutic treatments, wherein the object is to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a disorder. The term “treating” includes reducing or alleviating at least one adverse effect or symptom of a condition, disease, or disorder. Treatment is generally “effective” if one or more symptoms or clinical markers are reduced. Alternatively, treatment is “effective” if the progression of a disorder is reduced or halted. That is, “treatment” includes not just the improvement of symptoms or markers, but also a cessation of, or at least slowing of, progress or worsening of symptoms compared to what would be expected in the absence of treatment. Beneficial clinical results include, but are not limited to, alleviation of one or more symptom(s), diminishment of extent of disease, stabilized (e.g., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, remission (whether partial or total), decreased mortality, whether detectable or undetectable, etc. The term “treatment” of a disease also includes providing relief from the symptoms or side-effects of the disease (including palliative treatment).

[0104] “Effective amount” or “therapeutically effective amount” or “therapeutically effective dose” means a dosage sufficient to alleviate one or more symptoms of the condition being treated, or to otherwise provide a pharmacological effect, physiologic effect, etc., as may be determined by an objective measure or a patient derived subjective measure. In certain nonlimiting examples, an “effective amount” refers to the optimal amount of a dose adsorbed at a site needed to elicit a clinically significant improvement in the symptoms, pathological state, etc., associated with a disease state, infection, or disorder to be treated. In certain non-limiting- 22 -QB\99086149.3Quarles 125141.04916 examples, the disease state, infection, or disorder to be treated a is a lymphatic disease, lymphatic disorder, lymphatic condition, etc.EXAMPLES

[0089] The following examples have been presented in order to further illustrate aspects of the disclosure, and are not meant to limit the scope of the disclosure in any way. The examples below are intended to be examples of the present disclosure and these (and other aspects of the disclosure) are not to be bounded by theory.

[0090] Some non-limiting examples of the disclosure are described herein with reference to the accompanying figures. The description and figures make apparent to a person having ordinary skill in the art how some non-limiting examples of the disclosure may be practiced. The figures are for the purpose of illustrative discussion and no attempt is made to show structural details of an non-limiting example in more detail than is necessary for a fundamental understanding of the teachings of the disclosure. Nor are the figures herein shown to scale. Where dimensions are given in the text or figures, these dimensions are merely exemplary and do not limit the scope or spirit of the disclosed invention.

[0091] The invention comprises, consists of, or consists essentially of the following features, in any combination.

[0092] Disclosed herein is the LymphoWire, comprising a platform conformable delivery wire for delivering endolymphatic therapeutic agents via traditional endolymphatic interventional radiologic methods. By accessing lymphatics via image-guided and interventional radiology methods, this wire could be visible under radiographic guidance. This wire would be ultra-thin, on the order of less than <O.O35" inches with properties that allow it to track along the lymphatics and be visible under x ray-guidance. The wire is designed to be self-degrading within a 12 hour period when reaching core body temperature, leaving behind the inner therapeutic agent for delivery. The radiopaque wire is manufactured around a hollow chamber for therapeutic agent, for which the inner component may be retained or left behind at the site of delivery. The free end of the LymphoWire may be detachable, which means that once the wire is in a confirmed position, the part outside the patient's body can be detached and disposed of. The wire can be composed of biologically compatible hydrogels or made by means of tissue engineering.- 23 -QB\99086149.3Quarles 125141.04916

[0093] Radiopaque markers along the LymphoWire will allow the user / operator to target delivery along lymphatic channels. The wire also features a detachable end so excess redundant length outside the patient can be detached via a detachment mechanism.

[0094] An exemplary non-limiting example of a Lymphowire in cross section can be provided. Hollow chamber inner component for therapeutic delivery. Outer component wire fortrackability through the lymphatic system. Cross section demonstrates the radiopaque outer component which will degrade within a 12-hour period following delivery, leaving the inner component (therapeutic agent) behind.

[0095] The Lymphowire can inlcude a detachment mechanism. Sagittal cut demonstrates the Lymphowire being inserted into the patient’s lymphatic channel with the free end detachable component outside of the patient. The detachment mechanism is designed for manual removal, leaving the LymphoWire (outer trackable component and inner therapeutic component) inside the patient for therapeutic delivery.

[0096] The Lymphowire can include exemplary components. There is a radioopaque outer biocompatible component which is used to track the wire into the lymphatic system for delivery. This component will also degrade with time, leaving behind the inner therapeutic component in place. There is an outer detachable component for delivery which is removed at the time the wire is in good position / in place. The detachment mechanism is designed for manual removal, leaving the LymphoWire (outer trackable component and inner therapeutic component) inside the patient for therapeutic delivery.

[0097] It will be appreciated by those skilled in the art that while the disclosed subject matter is described above in connection with particular non-limiting examples and examples, the invention is not necessarily so limited, and that numerous other non-limiting examples, examples, uses, modifications and departures from the non-limiting examples, examples and uses are intended to be encompassed by the claims attached hereto. Each reference cited herein is incorporated by reference in its entirety.

[0098] Various features and advantages of the invention are set forth in the following claims.

[0099] The present disclosure has described one or more preferred non-limiting examples, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.- 24 -QB\99086149.3Quarles 125141.04916

[0100] It is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the accompanying description or illustrated in the accompanying drawings. The disclosure is capable of other non-limiting examples and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “mounted,” “connected,” “supported,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings. Further, “connected” and “coupled” are not restricted to physical or mechanical connections or couplings.

[0101] As used herein, unless otherwise limited or defined, discussion of particular directions is provided by example only, with regard to particular non-limiting examples or relevant illustrations. For example, discussion of “top,” “front,” or “back” features is generally intended as a description only of the orientation of such features relative to a reference frame of a particular example or illustration. Correspondingly, for example, a “top” feature may sometimes be disposed below a “bottom” feature (and so on), in some arrangements or nonlimiting examples. Further, references to particular rotational or other movements (e.g., counterclockwise rotation) is generally intended as a description only of movement relative a reference frame of a particular example of illustration.

[0102] In some non-limiting examples, aspects of the disclosure, including computerized implementations of methods according to the disclosure, can be implemented as a system, method, apparatus, or article of manufacture using standard programming or engineering techniques to produce software, firmware, hardware, or any combination thereof to control a processor device (e.g., a serial or parallel general purpose or specialized processor chip, a single- or multi-core chip, a microprocessor, a field programmable gate array, any variety of combinations of a control unit, arithmetic logic unit, and processor register, and so on), a computer (e.g., a processor device operatively coupled to a memory), or another electronically operated controller to implement aspects detailed herein. Accordingly, for example, nonlimiting examples of the disclosure can be implemented as a set of instructions, tangibly- 25 -QB\99086149.3Quarles 125141.04916 embodied on a non-transitory computer-readable media, such that a processor device can implement the instructions based upon reading the instructions from the computer-readable media. Some non-limiting examples of the disclosure can include (or utilize) a control device such as an automation device, a special purpose or general purpose computer including various computer hardware, software, firmware, and so on, consistent with the discussion below. As specific examples, a control device can include a processor, a microcontroller, a field- programmable gate array, a programmable logic controller, logic gates etc., and other typical components that are known in the art for implementation of appropriate functionality (e.g., memory, communication systems, power sources, user interfaces and other inputs, etc.).

[0103] The term “article of manufacture” as used herein is intended to encompass a computer program accessible from any computer-readable device, carrier (e.g., non-transitory signals), or media (e.g., non-transitory media). For example, computer-readable media can include but are not limited to magnetic storage devices (e.g., hard disk, floppy disk, magnetic strips, and so on), optical disks (e.g., compact disk (CD), digital versatile disk (DVD), and so on), smart cards, and flash memory devices (e.g., card, stick, and so on). Additionally it should be appreciated that a carrier wave can be employed to carry computer-readable electronic data such as those used in transmitting and receiving electronic mail or in accessing a network such as the Internet or a local area network (LAN). Those skilled in the art will recognize that many modifications may be made to these configurations without departing from the scope or spirit of the claimed subject matter.

[0104] Certain operations of methods according to the disclosure, or of systems executing those methods, may be represented schematically in the FIGS, or otherwise discussed herein. Unless otherwise specified or limited, representation in the FIGS, of particular operations in particular spatial order may not necessarily require those operations to be executed in a particular sequence corresponding to the particular spatial order. Correspondingly, certain operations represented in the FIGS., or otherwise disclosed herein, can be executed in different orders than are expressly illustrated or described, as appropriate for particular non-limiting examples of the disclosure. Further, in some non-limiting examples, certain operations can be executed in parallel, including by dedicated parallel processing devices, or separate computing devices configured to interoperate as part of a large system.- 26 -QB\99086149.3Quarles 125141.04916

[0105] As used herein in the context of computer implementation, unless otherwise specified or limited, the terms “component,” “system,” “module,” and the like are intended to encompass part or all of computer-related systems that include hardware, software, a combination of hardware and software, or software in execution. For example, a component may be, but is not limited to being, a processor device, a process being executed (or executable) by a processor device, an object, an executable, a thread of execution, a computer program, or a computer. By way of illustration, both an application running on a computer and the computer can be a component. One or more components (or system, module, and so on) may reside within a process or thread of execution, may be localized on one computer, may be distributed between two or more computers or other processor devices, or may be included within another component (or system, module, and so on).

[0106] In some implementations, devices or systems disclosed herein can be utilized or installed using methods embodying aspects of the disclosure. Correspondingly, description herein of particular features, capabilities, or intended purposes of a device or system is generally intended to inherently include disclosure of a method of using such features for the intended purposes, a method of implementing such capabilities, and a method of installing disclosed (or otherwise known) components to support these purposes or capabilities. Similarly, unless otherwise indicated or limited, discussion herein of any method of manufacturing or using a particular device or system, including installing the device or system, is intended to inherently include disclosure, as non-limiting examples of the disclosure, of the utilized features and implemented capabilities of such device or system.

[0107] As used herein, unless otherwise defined or limited, ordinal numbers are used herein for convenience of reference based generally on the order in which particular components are presented for the relevant part of the disclosure. In this regard, for example, designations such as “first,” “second,” etc., generally indicate only the order in which the relevant component is introduced for discussion and generally do not indicate or require a particular spatial arrangement, functional or structural primacy or order.

[0108] As used herein, unless otherwise defined or limited, directional terms are used for convenience of reference for discussion of particular figures or examples. For example, references to downward (or other) directions or top (or other) positions may be used to discuss- 27 -QB\99086149.3Quarles 125141.04916 aspects of a particular example or figure, but do not necessarily require similar orientation or geometry in all installations or configurations.

[0109] This discussion is presented to enable a person skilled in the art to make and use non-limiting examples of the disclosure. Various modifications to the illustrated examples will be readily apparent to those skilled in the art, and the generic principles herein can be applied to other examples and applications without departing from the principles disclosed herein. Thus, non-limiting examples of the disclosure are not intended to be limited to non-limiting examples shown, but are to be accorded the widest scope consistent with the principles and features disclosed herein and the claims below. The accompanying detailed description is to be read with reference to the figures, in which like elements in different figures have like reference numerals. The figures, which are not necessarily to scale, depict selected examples and are not intended to limit the scope of the disclosure. Skilled artisans will recognize the examples provided herein have many useful alternatives and fall within the scope of the disclosure.

[0110] Also as used herein, unless otherwise limited or defined, “or” indicates a nonexclusive list of components or operations that can be present in any variety of combinations, rather than an exclusive list of components that can be present only as alternatives to each other. For example, a list of “A, B, or C” indicates options of: A; B; C; A and B; A and C; B and C; and A, B, and C. Correspondingly, the term “or” as used herein is intended to indicate exclusive alternatives only when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” Further, a list preceded by “one or more” (and variations thereon) and including “or” to separate listed elements indicates options of one or more of any or all of the listed elements. For example, the phrases “one or more of A, B, or C” and “at least one of A, B, or C” indicate options of: one or more A; one or more B; one or more C; one or more A and one or more B; one or more B and one or more C; one or more A and one or more C; and one or more of each of A, B, and C. Similarly, a list preceded by “a plurality of’ (and variations thereon) and including “or” to separate listed elements indicates options of multiple instances of any or all of the listed elements. For example, the phrases “a plurality of A, B, or C” and “two or more of A, B, or C” indicate options of: A and B; B and C; A and C; and A, B, and C. In general, the term “or” as used herein only indicates exclusive alternatives (e.g.- 28 -QB\99086149.3Quarles 125141.04916“one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.”

[0111] Also as used herein, unless otherwise specified or limited, the terms “about” and “approximately,” as used herein with respect to a reference value, refer to variations from the reference value of ± 15% or less (e.g., ± 10%, ± 5%, etc.), inclusive of the endpoints of the range. Similarly, the term “substantially equal” (and the like) as used herein with respect to a reference value refers to variations from the reference value of less than ± 30% (e.g., ± 20%, ± 10%, ± 5%) inclusive. Where specified, “substantially” can indicate in particular a variation in one numerical direction relative to a reference value. For example, “substantially less” than a reference value (and the like) indicates a value that is reduced from the reference value by 30% or more, and “substantially more” than a reference value (and the like) indicates a value that is increased from the reference value by 30% or more.

[0112] Various features and advantages of the disclosure are set forth in the following claims.- 29 -QB\99086149.3

Claims

Quarles 125141.04916CLAIMSWhat is claimed is:

1. A medical device comprising: a tube comprising a wire scaffold coupled to and surrounding a carrier, the wire scaffold to structurally support the carrier, the carrier including a therapeutic agent; wherein the wire scaffold is radiopaque and biodegradable; and wherein when the medical device is positioned in a lymphatic channel of a subject, the wire scaffold dissolves, exposing the carrier to the lymph fluid of the lymphatic channel to release the therapeutic agent from the carrier; and wherein the therapeutic agent is configured to treat a condition.

2. The medical device of claim 1, wherein the carrier is embedded with the therapeutic agent.

3. The medical device of claim 2, wherein the carrier includes a hydrogel.

4. The medical device of claim 1, wherein the condition is a lymphatic system condition; and wherein the lymphatic system condition includes at least one of: a lymphatic disease, lymphoma, lymphangitis, lymphedema, lymphadenopathy, lymphangioma, lymphocytosis, lymphatic filariasis, castleman disease, lymphangioleiomyomatosis, autoimmune lymphoproliferative syndrome, or mesenteric lymphadenitis5. The medical device of claim 1, wherein a thickness of the wire scaffold is configured to dissolve completely after the medical device has been placed in the subject for a predetermined amount of time.

6. The medical device of claim 5, wherein the predetermined amount of time is twelve hours.- 30 -QB\99086149.3Quarles 125141.049167. The medical device of claim 5, wherein a thickness of the wire scaffold is less than or equal to 1 millimeter.

8. The medical device of claim 1, wherein the wire scaffold seals the carrier, such that an outer surface of the carrier is prevented from being exposed to the environment surrounding the medical device.

9. The medical device of claim 1, wherein the wire scaffold includes a plurality of filaments.

10. The medical device of claim 9, wherein the plurality of filaments include a first filament and a second filament; and wherein the first filament is coupled to the second filament at one or more locations to define one or more vertices.

11. The medical device of claim 9, wherein the plurality of filaments form a mesh.

12. The medical device of claim 1, wherein the wire scaffold includes one or more filaments; and wherein the one or more filaments are coiled.

13. The medical device of claim 1, wherein the carrier includes a solution that has the therapeutic agent.

14. The medical device of claim 1, wherein the carrier includes a polymer loaded with the therapeutic agent.

15. The medical device of claim 13, wherein the polymer is a hydrogel.

16. The medical device of claim 1, wherein the carrier releases the therapeutic agent in the lymphatic channel over time.- 31 -QB\99086149.3Quarles 125141.0491617. The medical device of claim 16, wherein the carrier includes a polymer; and wherein the rate that the carrier releases the therapeutic agent in the lymphatic channel depends on a number of crosslinks of the polymer.

18. The medical device of claim 1, wherein the wire scaffold includes a polymer; and wherein the polymer is at least one of polylactic acid (PLA), poly-l-lactic acid(PLLA),polyglycolic acid (PGA), polydioxanone (PDO), or chromic catgut.

19. The medical device of claim 1, wherein the wire scaffold includes a metal; and wherein the metal is magnesium.

20. The medical device of claim 1, wherein the wire scaffold includes at least one of iodine, barium, iodine, tungsten, or calcium.

21. The medical device of claim 1, further comprising one or more radiopaque markers coupled to the wire scaffold, the one or more radiopaque markers providing the radiopacity of the wire scaffold.

22. The medical device of claim 1, wherein the one or more radiopaque markers include a plurality of radiopaque markers distributed along the length of the tube.

23. The medical device of claim 1, wherein the therapeutic agent includes a cytotoxic agent, chemotherapeutic agent, or a radiotherapy isotope.

24. A medical device comprising: a tube comprising a wire scaffold coupled to and surrounding a carrier, the wire scaffold being radiopaque and biodegradable, the carrier including a therapeutic agent, the therapeutic agent configured to treat a condition; wherein the wire scaffold isolates the carrier from contact with the internal environment surrounding the medical device.- 32 -QB\99086149.3

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