# US 12,515,027 B2 · Subcutaneous biodegradable reservoir device

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- Number: US 12,515,027 B2
- Document ID: US12515027B2
- Status: Granted
- Kind: B2
- Application number: 17/284,989
- Filed: 2019-10-16
- Published: 2021-11-11
- Granted: 2026-01-06
- Earliest claimed: 2018-10-16
- Assignees: Research Triangle Institute
- Applicants: Research Triangle Institute
- Inventors: Leah Marie Johnson; Ariane Van Der Straten; Ginger Denison Rothrock; Linying Alice Li; Ellen Luecke; Natalie Girouard; Zach Richard Demkovich; Sai Archana Krovi
- Web page: https://patentgrep.com/patent/US12515027B2

## CPC

- A61M 31/002: {Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time (artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50)}
- A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)}
- A61K 31/138: Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377)
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 31/553: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
- A61K 31/567: substituted in position 17 alpha, e.g. mestranol, norethandrolone
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 31/683: Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/58: Materials at least partially resorbable by the body
- A61P 31/18: for HIV
- A61L 2300/43: Hormones, e.g. dexamethasone
- A61L 2300/434: of enzymes
- A61L 2300/802: Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
- A61M 2205/02: characterised by a particular materials
- A61M 2205/04: implanted
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A reservoir device comprising an active agent formulation contained within a reservoir is described. The reservoir is defined by a biodegradable, permeable polymer membrane having a thickness of at least 45 μm. The membrane allows for diffusion of an active agent of the formulation there through when positioned subcutaneously in a body of a subject.

## Claims

### Claim 1

A reservoir device comprising an active agent formulation contained within a reservoir, the reservoir defined by a biodegradable, permeable polymer membrane having a thickness of 100 μm to 300 μm, wherein the active agent formulation comprises an active agent and an excipient, wherein the excipient includes castor oil, wherein a mass ratio of active agent to excipient in the reservoir ranges from 1:1 to 3:1, wherein the active agent dissolves in the excipient to form an active agent solution, wherein a formation rate of the active agent solution is greater than a diffusion rate of the active agent solution through the polymer membrane, wherein the polymer membrane comprises polycaprolactone (PCL) at a molecular weight ranging from 15,000-140,000 Da, the polymer membrane allowing for diffusion of the active agent solution there through when positioned subcutaneously in a body of a subject, wherein the reservoir device is configured for an average release rate of the active agent ranging from 15 to 30 μg/day; and wherein the active agent comprises tenofovir alafenamide fumarate (TAF), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), levonorgestrel (LNG); etonogestrel (ENG), emtricitabine (FTC), tenofovir (TFV), tenofovir disoproxil fumarate (TDF), EFdA-alafenamide, bictegravir (BIC), tamoxifen citrate, naltrexone or combinations thereof.

### Claim 2 (depends on 1)

The device of claim 1, wherein the permeable polymer membrane has a thickness of 200 μm to 300 μm.

### Claim 3 (depends on 1)

The device of claim 1, wherein the reservoir comprises a first segment and a second segment, and wherein the first segment contains a first active agent formulation and the second segment contains a second active agent formulation, which is different from the first active agent formulation.

### Claim 4 (depends on 1)

The device of claim 1, wherein the device has a cylindrical shape with a length between 10 mm and 50 mm.

### Claim 5 (depends on 1)

The device of claim 1, wherein the polymer membrane has an initial molecular weight at implantation and wherein the membrane is configured such that the molecular weight of the membrane is reduced to a molecular weight ranging from 8 kDa to 3 kDa after the active agent is depleted from the device.

### Claim 6 (depends on 1)

The device of claim 1, wherein the biodegradable, permeable polymer membrane is configured for the average release rate of the active agent ranging from 15 to 49 μg/day for at least 90 days, wherein the biodegradable, permeable polymer membrane is configured to substantially or fully degrade within a time period of 4 months to 2 years.

### Claim 7 (depends on 1)

The device of claim 1, comprising LNG as the active agent in the formulation, wherein the device has a release profile of 30 μg/day for a time period of 90 days to 24 months in in-vitro conditions.

### Claim 8 (depends on 1)

The device of claim 1, comprising ENG as the active agent, wherein the polymer membrane allows for diffusion of the active agent there through with zero-order release kinetics for a time period of at least 100 days when positioned subcutaneously in a body of a subject.

### Claim 9 (depends on 1)

The device of claim 1, comprising 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) as the active agent in the formulation, wherein the device has a length of 40 mm, a width of 2.5 mm, and a wall thickness of 100 μm.