# US 10,864,163 B2 · Therapeutic agents and delivery with microspheres

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- Number: US 10,864,163 B2
- Document ID: US10864163B2
- Status: Granted
- Kind: B2
- Application number: 15/107,802
- Filed: 2014-12-22
- Published: 2016-10-13
- Granted: 2020-12-15
- Earliest claimed: 2013-12-23
- Assignees: UCL Business PLC
- Applicants: UCL Business PLC
- Inventors: Richard Michael Day
- Web page: https://patentgrep.com/patent/US10864163B2

## CPC

- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 9/1676: {having a drug-free core with discrete complete coating layer containing drug (adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921)}
- A61K 9/1682: {Processes}
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- A61K 35/15: Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells (presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00)
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 35/30: Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
- A61K 35/34: Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44)
- A61K 35/39: Pancreas; Islets of Langerhans (Langerhans cells of epidermis A61K35/36)
- A61K 35/44: Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
- 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 31/022: {Metals or alloys}
- A61L 31/10: Macromolecular materials
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- B01J 13/06: by phase separation
- A61L 2300/64: Animal cells
- A61L 2420/02: Methods for coating medical devices
- 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)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS

## Abstract

The invention relates to methods for attaching therapeutic agents to structures produced by thermally induced phase separation as well as methods for coating devices and producing multi-layered microspheres.

## Claims

### Claim 1

A method for attaching a therapeutic agent to a hydrophobic microsphere structure produced by thermally induced phase separation comprising:
i) at least partly submerging the hydrophobic microsphere structure in a culture medium;
ii) subsequently contacting the hydrophobic microsphere structure with a wetting agent that wets the hydrophobic microsphere structure, wherein the wetting agent is ethanol which is added to the culture medium to a concentration of from 10% to 30%; and
iii) attaching the therapeutic agent to the hydrophobic microsphere structure.

### Claim 2 (depends on 1)

The method of claim 1 which results in the hydrophobic microsphere structure being fully submerged in the culture medium.

### Claim 3 (depends on 1)

The method of claim 1 wherein the hydrophobic microsphere structure comprises poly(lactide-co-glycolide) (PLGA).

### Claim 4 (depends on 1)

The method of claim 1 wherein the culture medium is Dulbecco's Modified Eagle's Medium (DMEM).

### Claim 5 (depends on 1)

The method of claim 1 wherein the culture medium is tissue culture medium comprising serum.

### Claim 6 (depends on 1)

The method of claim 1 wherein the hydrophobic microsphere structure is mixed with the culture medium before and after the contacting with the wetting agent.

### Claim 7 (depends on 1)

The method of claim 1 further comprising incubating the hydrophobic microsphere structure at about 30° C. to about 40° C.

### Claim 8 (depends on 1)

The method of claim 1 wherein the therapeutic agent is a cell.

### Claim 9 (depends on 1)

The method of claim 1 wherein the therapeutic agent is an active pharmaceutical ingredient (API).

### Claim 10 (depends on 1)

The method of claim 1 further comprising periods of static incubation interspersed with agitation.

### Claim 11 (depends on 10)

The method of claim 10 comprising about 1 minute of agitation at about 300 rpm per hour of static incubation.

### Claim 12 (depends on 5)

The method of claim 5 wherein the serum is fetal bovine serum (FBS) or fetal calf serum (FCS).