# US 10,500,157 B2 · Nanoparticle-mediated delivery of cytokines for maintenance of the regulatory T cell phenotype

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- Number: US 10,500,157 B2
- Document ID: US10500157B2
- Status: Granted
- Kind: B2
- Application number: 16/019,704
- Filed: 2018-06-27
- Published: 2018-12-27
- Granted: 2019-12-10
- Earliest claimed: 2012-04-12
- Assignees: Yale University
- Applicants: Yale University
- Inventors: Tarek M. Fahmy
- Web page: https://patentgrep.com/patent/US10500157B2

## CPC

- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911})
- A61K 9/1273: Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances
- A61K 9/1277: Preparation processes; Proliposomes
- A61K 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 31/343: condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
- A61K 38/1841: {Transforming growth factor [TGF]}
- A61K 38/2013: {IL-2}
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/40: Cyclodextrins; Derivatives thereof
- A61K 47/58: obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6937: {the polymer being PLGA, PLA or polyglycolic acid}
- A61K 47/6951: {using cyclodextrin (cyclodextrins used as simple excipients A61K47/40)}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- C07K 16/2812: {against CD4}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Compositions for delivery of growth factors needed for stable Tregs and methods of use thereof are provided. In preferred embodiments, the compositions can induce, increase, or enhance a functionally robust induced CD4 Treg population (e.g., Foxp3+ Treg) in vivo or ex vivo. The compositions generally include delivery vehicles including TGF-β and IL-2. Delivery vehicles include, for example, polymeric particles, silica particles, liposomes, or multilamellar vesicles. The TGF-β and IL-2 are typically co-loaded into, attached to the surface of, and/or enclosed within the delivery vehicle into the same particle for simultaneous co-delivery to cells such as T cells. Preferably the delivery vehicles are targeted to CD4. The compositions and cells treated therewith can be used in various methods of treating, for example, inflammation, inflammatory and autoimmune diseases and disorders, and inducing or maintaining tolerance including graft and transplant tolerance.

## Claims

### Claim 1

A method of increasing donor specific Treg comprising treating isolated cells ex vivo with a composition comprising CD4-targeted nanoparticles loaded with a combination of TGF-β and IL-2.