# US 12,178,881 B2 · Filterable duocarmycin-containing antibody-drug conjugate compositions and related methods

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,178,881 B2
- Document ID: US12178881B2
- Status: Granted
- Kind: B2
- Application number: 17/291,141
- Filed: 2019-11-04
- Published: 2021-12-16
- Granted: 2024-12-31
- Earliest claimed: 2018-11-09
- Assignees: Byondis B.V.
- Applicants: Byondis B.V.
- Inventors: Carolus Johannes Edgar Van Den Hoef
- Web page: https://patentgrep.com/patent/US12178881B2

## CPC

- A61K 47/6809: {Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/16: containing nitrogen, {e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates}
- A61K 47/6803: {Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates}
- A61K 47/6855: {the tumour determinant being from breast cancer cell}
- 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)

## Abstract

Duocarmycin-based antibody-drug conjugates can be readily separated from non-conjugated duocarmycin linker-drug in a composition that contains a solvent system of water and acetonitrile and that has 30% to 60% acetonitrile.

## Claims

### Claim 1

A method, which comprises:
(a) combining (i) an aqueous solution or a lyophilized product of an antibody-drug conjugate of formula (I):
Ab-(L-D)m (I),
wherein Ab is an IgG antibody, L-D is a duocarmycin linker-drug, wherein the duocarmycin linker-drug in non-conjugated form is represented by formula (IV):
wherein n is 0-3; R5 is selected from
y is 1-16; and
R6 is selected from
m represents an average DAR of from 1 to 12, and optionally further comprising the duocarmycin linker-drug in non-conjugated form, with (ii) a dilution medium that comprises water, acetonitrile, and acid to form a filterable composition, wherein said filterable composition comprises 30% to 60% (v/v) of said acetonitrile; and
(b) filtering said filterable composition across a filter having a molecular weight cutoff within the range of 3 kDa to 50 kDa to form a filtrate.

### Claim 2 (depends on 1)

The method according to claim 1, wherein said non-conjugated duocarmycin linker-drug is represented by the formula

### Claim 3 (depends on 1)

The method according to claim 1, wherein said filtrate is formed with less than 0.5% of the amount of said antibody-drug conjugate that was present in said filterable composition.

### Claim 4 (depends on 3)

The method according to claim 3, wherein said filtering is centrifugal filtering.

### Claim 5 (depends on 4)

The method according to claim 4, wherein said filter comprises a modified polyethersulfone filter media.

### Claim 6 (depends on 1)

The method according to claim 1, which further comprises subjecting said filtrate to a chromatographic separation process suitable for isolating said duocarmycin linker-drug in non-conjugated form and measuring the amount, if any, of said duocarmycin linker-drug in non-conjugated form present in said filtrate.

### Claim 7 (depends on 1)

The method according to claim 1, wherein said filterable composition comprises 35% to 55% of said acetonitrile.

### Claim 8 (depends on 1)

The method according to claim 1, wherein said antibody-drug conjugate is contained in a concentration of from 0.5 to 50 mg/ml.

### Claim 9 (depends on 8)

The method according to claim 8, wherein said antibody-drug conjugate is contained in a concentration of from 1.0 to 10 mg/ml.

### Claim 10 (depends on 1)

The method according to claim 1, wherein said acid in said filterable composition has a concentration of from 0.05% to 2%.

### Claim 11 (depends on 10)

The method according to claim 10, wherein said acid in said filterable composition has a concentration of from 0.1% to 1%.

### Claim 12 (depends on 11)

The method according to claim 11, wherein said acid is selected from the group consisting of trifluoroacetic acid, formic acid, and hydrochloric acid.

### Claim 13 (depends on 9)

The method according to claim 9, wherein said filtrate is formed with less than 0.2% of the amount of said antibody-drug conjugate that was present in said filterable composition.

### Claim 14 (depends on 13)

The method according to claim 13, wherein said filtrate is formed with less than 0.1% of the amount of said antibody-drug conjugate that was present in said filterable composition.

### Claim 15 (depends on 1)

The method according to claim 1, wherein said filter has a molecular weight cutoff within the range of 10 kDa to 30 kDa.