# US 2021/0275547 A1 · Methods of Modulating Activity of a Cyclic Dinucleotide (CDN) with a CDN Transporter-Modulating Agent

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- Number: US 2021/0275547 A1
- Document ID: US20210275547A1
- Status: Published application
- Kind: A1
- Application number: 17/053,963
- Filed: 2019-05-16
- Published: 2021-09-09
- Earliest claimed: 2018-05-17
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: David H. RAULET; Rutger D. LUTEIJN; Jacob E. CORN
- Web page: https://patentgrep.com/patent/US20210275547A1

## CPC

- A61K 31/635: having a heterocyclic ring, e.g. sulfadiazine
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- A61K 31/7084: Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
- 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)

## Abstract

Methods of modulating the activity of a cyclic dinucleotide (CDN) in a cell via membrane transporter are provided. Aspects of the methods may include contacting a cell with a CDN transporter-modulating agent to modulate transport of a CDN into the cell. In some cases, the CDN transporter-modulating agent modulates SLC19A1-mediated transport of the CDN into the cell. Also provided are compositions and kits for use in practicing the subject methods. The methods and compositions find use in a variety of applications, including therapeutic applications, such as methods of treating cancer or an inflammatory disease.

## Claims

### Claim 1

A method of modulating activity of a cyclic dinucleotide (CDN) in a cell, the method comprising:
contacting a cell with:
a CDN; and
an amount of a CDN transporter-modulating agent effective to modulate transport of the CDN into the cell;
to modulate activity of the CDN in the cell.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the CDN transporter-modulating agent modulates a transporter of folate or a folate derivative.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the CDN transporter-modulating agent modulates: SLC19A1-mediated transport of the CDN into the cell;
SLC46A1-mediated transport of the CDN into the cell and/or SLC46A3-mediated transport of the CDN into the cell.

### Claim 4 (depends on 1)

The method according to claim 1, wherein contacting the cell with the amount of the CDN transporter-modulating agent is effective to inhibit transport of the CDN into the cell.

### Claim 5 (depends on 1)

The method according to claim 1, wherein contacting the cell with the amount of the CDN transporter-modulating agent is effective to enhance transport of the CDN into the cell.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the cell is in vitro or
in vivo.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the contacting comprises administration of the CDN transporter-modulating agent to a subject.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the contacting comprises contacting the cell with composition comprising a CDN.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the CDN is a naturally occurring CDN or a non-naturally occurring or synthetic CDN.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the CDN comprises two 2′-5′ phosphodiester linkages.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the CDN comprises a 2′-5′ phosphodiester linkage and a 3′-5′ phosphodiester linkage.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the CDN has the formula:
wherein X and Y are each independently:
or a salt thereof.

### Claim 13 (depends on 1)

The method according to claim 1, wherein the CDN transporter-modulating agent is selected from small molecule, organic anion, inorganic anion, an antibody or fragment thereof and an RNAi agent.

### Claim 14 (depends on 1)

The method according to claim 1, wherein the CDN transporter-modulating agent is sulfasalazine or a salt thereof.

### Claim 15

A composition or kit comprising:
a CDN; and
a CDN transporter-modulating agent.
