# US 10,308,649 B2 · Compounds and methods to suppress autoimmune response

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- Number: US 10,308,649 B2
- Document ID: US10308649B2
- Status: Granted
- Kind: B2
- Application number: 15/522,241
- Filed: 2015-10-28
- Published: 2018-02-01
- Granted: 2019-06-04
- Earliest claimed: 2014-10-28
- Assignees: Oregon State University
- Applicants: Oregon State University
- Inventors: Nancy I. Kerkvliet; Siva Kumar Kolluri
- Web page: https://patentgrep.com/patent/US10308649B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

## Abstract

A composition and method for treating autoimmune disease includes administering an effective amount of an aryl hydrocarbon receptor (AhR) ligand. The AhR ligand includes 11-Cl-BBQ, 10-Cl-BBQ, an analog of 11-Cl-BBQ, or combination thereof. The AhR ligand is administered topically, orally, transdermally, intravenously, subcutaneously, or with a nanoparticle. The AhR ligand induces regulatory T cells (AhR-Tregs). AhR-Treg cells block the differentiation of cytotoxic T-lymphocytes (CTL). The AhR ligand activates AhR in CD4+ T cells to induce CD4+ AhR-Tregs that suppress the development of effector CTL, thereby suppressing the development of CTL that attack host cells in graft versus host disease (GVHD) or β-cells in the pancreas in diabetes mellitus type 1 (T1DM). The AhR ligand can also suppress development of CTL independently of Foxp3+ regulatory T cell induction. The AhR ligand can therefore be used to treat autoimmune diseases characterized by an absence of functional Foxp3+ regulatory T cell.

## Claims

### Claim 1

A method of treating an autoimmune disease treatable through induction of regulatory T-cells comprising administering a therapeutically effective amount of an aryl hydrocarbon receptor (AhR) ligand to a subject in need thereof, wherein the aryl hydrocarbon receptor (AhR) ligand is 11-chloro-7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (11-Cl-BBQ), 7H-benzimidazo[2,1-a]benzo[de]isoquinolin-7-one, 4,11-dichloro-7H-benzimidazo[2,1-a]benzo[de]isoquinolin-7-one, 7-oxo-7H-benzimidazo[2,1-a]benzo[de]-isoquinoline-3-carboxylic acid, 11-trifluoro-7H-benzimidazo[2,1-a]benzo[de]isoquinolin-7-one, or 10-chloro-7H-benzimidazo[2,1-a]benzo[de]isoquinolin-7-one.

### Claim 2 (depends on 1)

The method of claim 1, wherein the autoimmune disease is diabetes mellitus type 1.

### Claim 3 (depends on 1)

The method of claim 1, wherein the autoimmune disease is graft versus host disease.

### Claim 4 (depends on 1)

The method of claim 1, wherein the autoimmune disease is Celiac disease, autoimmune hepatitis, autoimmune pancreatitis, Crohn's disease, interstitial cystitis, microscopic colitis, or ulcerative colitis.

### Claim 5 (depends on 1)

The method of claim 1, wherein the autoimmune disease is alopecia areata, atopic dermatitis, cicatricial pemphigoid, dermatomyositis, dermatitis herpetiformis, lichen planus, pemphigus vulgaris, or psoriasis.

### Claim 6 (depends on 1)

The method of claim 1, wherein the aryl hydrocarbon receptor (AhR) ligand is administered topically.

### Claim 7 (depends on 1)

The method of claim 1, wherein the aryl hydrocarbon receptor (AhR) ligand is administered orally, transdermally, intravenously, subcutaneously, or with a nanoparticle.

### Claim 8 (depends on 1)

The method of claim 1, wherein the aryl hydrocarbon receptor (AhR) ligand is 11-chloro-7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (11-Cl-BBQ).

### Claim 9 (depends on 1)

The method of claim 1, further including administering the AhR ligand with a pharmaceutically acceptable carrier.