# US 12,109,222 B2 · Methods and compositions for treating mucositis

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- Number: US 12,109,222 B2
- Document ID: US12109222B2
- Status: Granted
- Kind: B2
- Application number: 17/175,258
- Filed: 2021-02-12
- Published: 2021-08-05
- Granted: 2024-10-08
- Earliest claimed: 2018-08-14
- Assignees: Tosk, Inc.
- Applicants: Tosk, Inc.
- Inventors: William A. Garland; Brian D. Frenzel; Philip Liaw
- Web page: https://patentgrep.com/patent/US12109222B2

## CPC

- A61K 31/7072: having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
- A61P 35/00: Antineoplastic agents
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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

Methods for treating a subject for mucositis are provided. Aspects of the methods include administering an effective amount of a cancer therapy toxicity-reducing adjuvant in combination with uridine or a prodrug thereof to the subject. In certain embodiments, the cancer therapy toxicity-reducing adjuvant is a 2,2′-anhydropyrimidine, or a derivative thereof. Also provided are compositions for use in practicing the subject methods. The subject methods and compositions find use in a variety of different cancer therapy applications.

## Claims

### Claim 1

A method of treating a subject for mucositis, the method comprising:
administering to a subject known to be suffering from mucositis an effective amount of a 2,2′-anhydropyrimidine or derivative thereof in combination with an effective amount of uridine to treat the subject for mucositis.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the 2,2′-anhydropyrimidine or derivative thereof is a compound of formula (I):
or the pharmaceutically acceptable salts, solvates, hydrates, and prodrug forms thereof, and stereoisomers thereof,
wherein:
each R1, R2, R3 and R4 is independently selected from the group consisting of hydrogen, substituted or unsubstituted heteroatom, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, halogen or pseudohalogen, carbohydrate, nucleic acid, amino acid, peptide, dye, fluorophore and polypeptide.

### Claim 3 (depends on 2)

The method according to claim 2, wherein each R1, R2, R3 and R4 is independently selected from the group consisting of hydrogen, hydroxyl, sulfhydryl, amino, hydroxymethyl, methoxy, halogen, pseudohalogen, and a substituted or unsubstituted lower hydrocarbon containing 1 to 20 carbons.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the lower hydrocarbon is selected from the group consisting of alkyl, alkenyl, alkanoyl, aryl, aroyl, aralkyl and alkylamino, and esters thereof.

### Claim 5 (depends on 2)

The method according to claim 2, wherein R1 is hydrogen, fluorine, methyl, ethyl, propyl, benzyl, or 2-bromovinyl; R2 is hydrogen, hydroxyl fluorine, methyl, ethyl, propyl, benzyl, benzoyl, benzoyloxy, or 2-bromovinyl; and each R3 and R4 is independently selected from the group consisting of hydroxyl and benzoyloxy.

### Claim 6 (depends on 5)

The method according to claim 5, wherein R1 is hydrogen or methyl; R2 is hydrogen; and each R3 and R4 is independently selected from the group consisting of hydroxyl and benzoyloxy.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the 2,2′-anhydropyrimidine or derivative thereof is selected from the group consisting of: 2,2′-anhydro-5-methyluridine; 3′-O-benzoyl-2,2′-anhydrouridine; 3′-O-benzoyl-2,2′-anhydro-5-methyluridine; 5′-O-benzoyl-2,2′-anhydrouridine; and 5′-O-benzoyl-2,2′-anhydro-5-methyluridine.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the 2,2′-anhydropyrimidine or derivative thereof is 2,2′-anhydro-5-methyluridine.

### Claim 9 (depends on 7)

The method according to claim 7, wherein the 2,2′-anhydropyrimidine or derivative thereof is 3′-O-benzoyl-2,2′-anhydro-5-methyluridine.

### Claim 10 (depends on 7)

The method according to claim 7, wherein the 2,2′-anhydropyrimidine or derivative thereof is 5′-O-benzoyl-2,2′-anhydro-5-methyluridine.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the 2,2′-anhydropyrimidine or derivative thereof comprises a stereoisomer.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the stereoisomer is selected from the group consisting of 2,2′-anhydro-1-(β-D-arabinofuranosyl)-5-methyluracil; 3′-O-benzoyl-2,2′-anhydro-1-(β-D-arabinofuranosyl)-uracil; 3′-O)-benzoyl-2,2′-anhydro-1-(β-D-arabinofuranosyl)-5-methyluracil; 5′-O-benzoyl-2,2′-anhydro-1-(β-D-arabinofuranosyl)-uracil; and 5′-O-benzoyl-2,2′-anhydro-1-(β-D-arabinofuranosyl)-5-methyluracil.

### Claim 13 (depends on 1)

The method according to claim 1, wherein the 2,2′-anbydropyrimidine or derivative thereof and the uridine are administered at the same time.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the 2,2′-anhydropyrimidine or derivative thereof and the uridine are administered as separate formulations.

### Claim 15 (depends on 13)

The method according to claim 13, wherein the 2,2′-anhydropyrimidine or derivative thereof and the uridine are administered in a single formulation.

### Claim 16 (depends on 1)

The method according to claim 1, wherein the 2,2′-anbydropyrimidine or derivative thereof and the uridine are administered sequentially.

### Claim 17 (depends on 1)

The method according to claim 1, wherein the method further comprises administering a second UPase inhibitor.

### Claim 18 (depends on 1)

The method according to claim 1, wherein the mucositis is stomatitis.

### Claim 19 (depends on 1)

The method according to claim 1, wherein the subject is undergoing cancer therapy.

### Claim 20 (depends on 19)

The method according to claim 19, wherein in the cancer therapy is selected from the group consisting of radiation therapy, chemotherapy and combinations thereof.