# US 12,109,225 B2 · Methods for potentiating cancer treatment using ionizing radiation

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- Number: US 12,109,225 B2
- Document ID: US12109225B2
- Status: Granted
- Kind: B2
- Application number: 17/293,103
- Filed: 2019-11-11
- Published: 2021-12-30
- Granted: 2024-10-08
- Earliest claimed: 2018-11-13
- Assignees: Glycomira Therapeutics, Inc.
- Applicants: Glycomira Therapeutics, Inc.
- Inventors: Won Yong Lee; Thomas P. Kennedy; Glenn D. Prestwich
- Web page: https://patentgrep.com/patent/US12109225B2

## CPC

- A61K 31/737: Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate (A61K31/727 takes precedence)
- A61K 41/0038: {Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10)}
- A61N 5/1001: {using radiation sources introduced into or applied onto the body; brachytherapy}
- A61N 5/1077: {Beam delivery systems}
- A61N 5/1084: {for delivering multiple intersecting beams at the same time, e.g. gamma knives}
- A61P 35/00: Antineoplastic agents
- A61N 2005/1024: {Seeds}
- A61N 2005/1087: {Ions; Protons}
- A61N 2005/109: {Neutrons}
- A61N 2005/1091: {Kilovoltage or orthovoltage range photons}
- A61N 2005/1098: {Enhancing the effect of the particle by an injected agent or implanted device}
- 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)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Described herein are methods for reducing or maintaining the size of a tumor in a subject, where the method involves exposing the tumor to ionizing radiation and administering to the subject a modified hyaluronan or a pharmaceutically acceptable salt or ester. The use of the modified hyaluronan enhances or potentiates the effect of ionizing radiation used in cancer treatment. Additionally, the methods described herein prevent or reduces tumor regrowth in the subject after exposing the tumor to ionizing radiation and administration of the modified hyaluronan to the subject.

## Claims

### Claim 1

A method for reducing or maintaining the size of a tumor in a subject, the method comprising exposing the tumor to ionizing radiation and administering subcutaneously or intravenously to the subject a pharmaceutical composition comprising a modified hyaluronan or a pharmaceutically acceptable salt or ester, wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester comprises hyaluronan with at least one primary C-6 hydroxyl position of an N-acetylglucosamine residue substituted with a methyl group, and at least one C-2 hydroxyl proton, at least one hydroxyl proton, or at least one C-3 hydroxyl proton and at least one hydroxyl proton is substituted with a sulfate group, and the modified hyaluronan or its pharmaceutically acceptable salt or ester has an average molecular weight of 2 kDa to 10 kDa.

### Claim 2 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable salt is selected from the group consisting of NH4+, Na+, Li+, K+, Ca+2, Mg+2, Fe+2, Fe+3, Cu+2, Al+3, Zn+2, 2-trimethylethanolammonium cation, or a quaternary salt of isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, lysine, arginine, and histidine.

### Claim 3 (depends on 1)

The method of claim 1, wherein the modified hyaluronan is administered to the subject after the tumor is exposed to ionizing radiation, before the tumor is exposed to ionizing radiation, or a combination thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the modified hyaluronan is administered to the subject while the tumor is exposed to ionizing radiation.

### Claim 5 (depends on 1)

The method of claim 1 wherein the ionizing radiation comprises external beam radiation, brachytherapy radiation, or a combination thereof.

### Claim 6 (depends on 5)

The method of claim 5, wherein the external beam radiation comprises radiation delivered from an ortho-voltage X-ray machine, a Cobalt-60 machine, a linear accelerator, a proton beam machine, a betatron radiation, a neutron beam machine, a gamma knife, spray radiation, stereotactic radiation, or any combination thereof.

### Claim 7 (depends on 5)

The method of claim 5, wherein the brachytherapy radiation comprises interstitial radiation, intracavitary radiation, intraluminal radiation, radioligand tagged molecules administered intravenously, or any combination thereof.

### Claim 8 (depends on 1)

The method of claim 1 wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester has a degree of methylation from 0.03 to 0.50.

### Claim 9 (depends on 1)

The method of claim 1 wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester has from 50% to 100% of the primary C-6 hydroxyl protons of the N-acetyl-glucosamine residue of the modified hyaluronan are replaced with a methyl group.

### Claim 10 (depends on 1)

The method of claim 1 wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester has a degree of sulfation of 3.0 to 4.0 sulfate groups per disaccharide unit.

### Claim 11 (depends on 1)

The method of claim 1 wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester has an average molecular weight from 3 kDa to 7 kDa.

### Claim 12 (depends on 1)

The method of claim 1 wherein the modified hyaluronan or its pharmaceutically acceptable salt or ester has an average molecular weight of 3 kDa to 7 kDa, a degree of methylation from 0.03 to 0.30, and a degree of sulfation of 3.0 to 4.0.