# US 10,308,938 B2 · Compositions and methods to activate or inhibit toll-like receptor signaling

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- Number: US 10,308,938 B2
- Document ID: US10308938B2
- Status: Granted
- Kind: B2
- Application number: 15/319,132
- Filed: 2015-06-18
- Published: 2017-05-11
- Granted: 2019-06-04
- Earliest claimed: 2014-06-20
- Assignees: Yale University
- Applicants: Yale University
- Inventors: Margarita Dominguez-Villar; David A. Hafler
- Web page: https://patentgrep.com/patent/US10308938B2

## CPC

- C12N 15/1132: {against retroviridae, e.g. HIV}
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 31/708: having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 39/39541: {against normal tissues, cells}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- G01N 33/56972: {White blood cells}
- A61K 2039/505: {comprising antibodies}
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/31: Combination therapy
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention includes compositions and methods of inhibiting or activating TLR7 signaling. In one aspect, a composition includes an inhibitor of TLR7 signaling is described, where the inhibitor of TLR7 signaling is a TLR7 inhibitory oligonucleotide, a TLR7 antibody, or a TLR7 antagonist. In another aspect, a composition and method are described for preventing and treating viral infection of a T cell in a subject. Methods for decreasing T cell proliferation by administering a composition with a TLR7 ligand or agonist or inducing T cell anergy in a subject by stimulating T cells with a TLR7 ligand or agonist are also described.

## Claims

### Claim 1

A method of preventing a viral infection of a T cell in a subject in need thereof comprising administering a composition comprising an inhibitor of TLR7 signaling selected from the group consisting of dual-iODN, IMO-3100, DV056, DV1179, chloroquine, hydroxychloroquine, quinacrine, and any combination thereof and further comprising administering a CD3 antibody, an ICOS antibody, or a CD28 antibody to the subject, wherein viral infection of the T cell is prevented following administration of the composition.

### Claim 2

A method of treating a viral infection in a subject in need thereof comprising administering a composition comprising an inhibitor of TLR7 signaling to the subject, wherein the viral infection is reduced in the subject following administration of the TLR7 inhibitor.

### Claim 3 (depends on 1)

The method of claim 1, wherein the inhibitor of TLR7 signaling is capable of decreasing expression of TLR7.

### Claim 4 (depends on 1)

The method of claim 1, wherein administering the composition increases secretion of at least one selected from the group consisting of IL-2, IFNγ and IL-17.

### Claim 5 (depends on 1)

The method of claim 1, wherein the composition is capable of preventing viral infection of a CD4+ T cell.

### Claim 6 (depends on 1)

The method of claim 1, wherein the subject is exposed to a virus prior to or after administration of the composition.

### Claim 7 (depends on 1)

The method of claim 1, wherein the viral infection is selected from the group consisting of a hepatitis B virus (HBV), a hepatitis C virus (HCV), human T-lymphotropic virus (HTLV) and a human immunodeficiency virus (HIV) infection.