# US 2022/0031817 A1 · Enhanced therapeutic usage of a purine nucleoside phosphorylase or nuceloside hydrolase prodrug

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- Number: US 2022/0031817 A1
- Document ID: US20220031817A1
- Status: Published application
- Kind: A1
- Application number: 17/502,101
- Filed: 2021-10-15
- Published: 2022-02-03
- Earliest claimed: 2011-02-18
- Assignees: The UAB Research Foundation; Southern Research Institute
- Applicants: The UAB Research Foundation; Southern Research Institute
- Inventors: William B. Parker; Eric J. Sorscher
- Web page: https://patentgrep.com/patent/US20220031817A1

## CPC

- A61K 38/47: acting on glycosyl compounds (3.2), e.g. cellulases, lactases
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 9/1641: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers}
- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 31/7076: containing purines, e.g. adenosine, adenylic acid
- A61K 38/45: Transferases (2)
- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61P 35/00: Antineoplastic agents
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The use of a purine nucleoside phosphorylase or nucleoside hydrolase or a vector encoding expression of one of these enzymes is detailed along with the use of a prodrug cleaved by the purine nucleoside phosphorylase or nucleoside hydrolase for the preparation of a direct injection inhibition of replicating or non-replicating targeted cells. The targeted cells do not normally express the introduced purine nucleoside phosphorylase or nucleoside hydrolase. The enzyme and prodrug are amenable to intermixing and injection as a single dose or as separate injection or administration to the targeted cells. The substance and prodrug efficacy are enhanced through exposure of the targeted cells to X-ray radiation. Administration of a prodrug regardless of administration route to the targeted cells is effective in combination with X-ray radiation therapy to kill or inhibit function of the targeted cells.

## Claims

### Claim 1

A process to sequentially destroy large regions of a solid tumor comprising:
delivering a purine nucleoside phosphorylase or nucleoside hydrolase or a vector encoding expression thereof directly into the solid tumor; and
injecting intratumorally a prodrug cleaved by said purine nucleoside phosphorylase or nucleoside hydrolase directly into the solid tumor to release a purine base cytotoxic into a portion of the solid tumor to sequentially destroy large regions of the solid tumor.

### Claim 2 (depends on 1)

The process of claim 1 wherein said purine nucleoside phosphorylase or nucleoside hydrolase is delivered with a viral vector containing a nucleic acid encoding said purine nucleoside phosphorylase.

### Claim 3 (depends on 2)

The process of claim 2 wherein said viral vector is an adenoviral vector.

### Claim 4 (depends on 1)

The process of claim 1 wherein said purine nucleoside phosphorylase is present and is a mutant of E. coli.

### Claim 5 (depends on 1)

The process of claim 1 wherein said purine nucleoside phosphorylase is present and is a tailed mutant.

### Claim 6 (depends on 1)

The process of claim 1 further comprising exposing the targeted cells to X-ray radiation.

### Claim 7 (depends on 1)

The process of claim 1 wherein said purine nucleoside phosphorylase is present and said prodrug is fludarabine phosphate.

### Claim 8 (depends on 1)

The process of claim 1 further comprising a sustained release carrier of a gel, paste, or a microparticle.

### Claim 9 (depends on 1)

The process of claim 1 wherein said purine base is a purine base of 2-fluoroadenine.

### Claim 10 (depends on 1)

The process of claim 1 wherein said prodrug is injected directly into proximity to the solid tumor in multiple doses.

### Claim 11 (depends on 1)

The process of claim 1 wherein said prodrug is injected directly into proximity to the targeted cells in at least three consecutive doses.

### Claim 12

A process of performing a tissue ablation procedure without granulation or scarification comprising:
delivering a purine nucleoside phosphorylase or nucleoside hydrolase or a vector encoding expression thereof directly into proximity to the tissue; and
injecting intratumorally a prodrug cleaved by said purine nucleoside phosphorylase or nucleoside hydrolase directly into proximity to the tissue to release a purine base cytotoxic to the tissue to induce chemical ablation.

### Claim 13 (depends on 12)

The procedure of claim 12 wherein the procedure is treatment of one of: cardiac arrhythmia, cyst, reduction, ganglion treatment, male sterilization, cosmetic dermatological procedures, or melanoma.
