# US 11,898,180 B2 · Compositions and methods for amino acid depletion therapy

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- Number: US 11,898,180 B2
- Document ID: US11898180B2
- Status: Granted
- Kind: B2
- Application number: 16/639,078
- Filed: 2018-08-16
- Published: 2021-06-24
- Granted: 2024-02-13
- Earliest claimed: 2017-08-16
- Assignees: Avalon Polytom (HK) Limited
- Applicants: Avalon Polytom (Hk) Limited
- Inventors: Johnson Yiu-Nam Lau; Yun Chung Leung; Kuo-Ming Yu; Yuk-Keung Yeung; Pui Shi Pang; Qui-Lim Choo
- Web page: https://patentgrep.com/patent/US11898180B2

## CPC

- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- C12N 9/78: acting on carbon to nitrogen bonds other than peptide bonds (3.5)
- A61K 38/50: acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
- A61P 35/00: Antineoplastic agents
- C07K 1/16: by chromatography
- C07K 1/18: Ion-exchange chromatography
- C12Y 305/03001: Arginase (3.5.3.1)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- C12Y: ENZYMES

## Abstract

Compositions and methods for the preparation of high purity arginase and high efficiency preparation of monosubstituted polyethylene glycol conjugation of arginase are provided, as are methods for using arginase in combination with asparaginase to inhibit cancer cells. High purity arginase is provided by applying an initial high temperature precipitation step, followed by ion exchange to provide arginase at a purity of 90% or greater. Conjugation with either linear or branched polyethylene glycol is performed using a maleimide-derivatized polyethylene glycol at low molar excess relative to arginase and at reduced temperature. Such polyethylene glycol-derivatized arginase is useful in combination with asparaginase in inhibiting the growth of cancer cells, particularly cells that have low endogenous asparaginase expression.

## Claims

### Claim 1

A method of selectively inhibiting a cancer cell having low asparaginase expression, comprising:
introducing an arginase to a media in contact with the cancer cell to reduce arginine concentration in the media to a concentration effective to inhibit growth of the cancer cell; and
introducing an asparaginase to the media to reduce asparagine concentration in the media to a concentration effective to inhibit growth of the cancer cell,
wherein the arginase and the asparaginase in combination provide a synergistic effect in reducing viability of the cancer cell, wherein the synergistic effect exceeds additive effects of monotherapies with the arginase and the asparaginase in inhibition of growth of the cancer cell having low asparaginase expression.

### Claim 2 (depends on 1)

The method of claim 1, comprising reducing glutamine concentration in the media.

### Claim 3 (depends on 2)

The method of claim 2, comprising supplying an aminotransferase inhibitor to reduce the glutamine concentration.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cancer cell is a breast cancer cell.