Virus inactivation method, method for manufacturing protein drug, and system for purifying solution

Patent metadata

Field	Value
Publication number	US-12533413-B2
Application number	US-202318212087-A
Country	US
Kind code	B2
Filing date	Jun 20, 2023
Priority date	Dec 24, 2020
Publication date	Jan 27, 2026
Grant date	Jan 27, 2026

Abstract

A virus inactivation method is provided. The method includes irradiating a solution containing an artificially expressed antibody or antibody fragment with ultraviolet rays in the presence of a radical scavenger. The irradiating only aggregates 5% or less of the antibody or antibody fragment. A wavelength of the ultraviolet rays is 200 nm or longer and 315 nm or shorter. An irradiation amount of the ultraviolet rays is 300 mJ/cm 2 or more. An irradiation time of the ultraviolet rays is 3 minutes or less. A concentration of the radical scavenger in the solution is 0.03 mM or more.

First claim

What is claimed is:

1 . A virus inactivation method comprising irradiating a solution containing an artificially expressed antibody or antibody fragment with ultraviolet rays in the presence of a radical scavenger, wherein
the irradiating only aggregates 5% or less of the antibody or antibody fragment, a wavelength of the ultraviolet rays is 200 nm or longer and 315 nm or shorter, an irradiation amount of the ultraviolet rays is 300 mJ/cm 2 or more, an irradiation time of the ultraviolet rays is 3 minutes or less, and a concentration of the radical scavenger in the solution is 0.03 mM or more.

2 . The inactivation method according to claim 1 , wherein the antibody or antibody fragment has been expressed in transgenic cells.

3 . The inactivation method according to claim 1 , wherein the radical scavenger is ascorbic acid, edaravone, or polyphenols.

4 . The inactivation method according to claim 1 , wherein the radical scavenger is ascorbic acid, edaravone, or epigallocatechin gallate.

5 . The inactivation method according to claim 1 , wherein a concentration of the antibody or antibody fragment in the solution is 20 mg/mL or less.

6 . The inactivation method according to claim 1 , wherein the irradiating includes irradiating the solution flowing in a channel with the ultraviolet rays.

7 . The inactivation method according to claim 1 , further comprising:
purifying the solution containing the antibody or antibody fragment by chromatography; and further purifying, by chromatography, the solution containing the antibody or antibody fragment purified by chromatography and then irradiated with the ultraviolet rays.

8 . The inactivation method according to claim 7 , wherein the irradiating includes irradiating the solution containing the antibody or antibody fragment flowing in a channel for supplying a solution purified by chromatography for the further purifying with the ultraviolet rays.

9 . The inactivation method according to claim 1 , wherein the irradiating inactivates 99% or more of viruses.

10 . A method for manufacturing an antibody drug or an antibody fragment drug comprising:
artificially expressing an antibody drug or an antibody fragment drug; and inactivating viruses contained in a solution containing the artificially expressed antibody drug or antibody fragment drug by irradiating the solution with ultraviolet rays in the presence of a radical scavenger, wherein the irradiating only aggregates 5% or less of the antibody or antibody fragment, a wavelength of the ultraviolet rays is 200 nm or longer and 315 nm or shorter, an irradiation amount of the ultraviolet rays is 300 mJ/cm 2 or more, an irradiation time of the ultraviolet rays is 3 minutes or less, and a concentration of the radical scavenger in the solution is 0.03 mM or more.

11 . The inactivation method according to claim 1 , wherein the irradiating comprises irradiation with ultraviolet rays using an apparatus for inactivating viruses, wherein the apparatus comprises:
a channel having an inlet and an outlet for a solution containing a protein and an ultraviolet-transmitting portion provided in at least a portion between the inlet and the outlet; and a light source for emitting ultraviolet rays to the ultraviolet-transmitting portion.

12 . A system for purifying a solution containing an artificially expressed antibody or antibody fragment, comprising:
a first purification unit configured to purify the solution containing the artificially expressed antibody or antibody fragment by chromatography; a virus inactivation unit configured to irradiate the solution containing the antibody or antibody fragment resulting from the first purification unit with ultraviolet rays in the presence of a radical scavenger, the virus inactivation unit comprising:
a channel having an inlet and an outlet for the solution and an ultraviolet-transmitting portion provided in at least a portion between the inlet and the outlet; and
a light source configured to emit ultraviolet rays to the ultraviolet-transmitting portion; and
a second purification unit configured to further purify, by chromatography, the solution containing the antibody or antibody fragment irradiated with the ultraviolet rays by the inactivation unit, wherein the irradiation of the solution containing the antibody or antibody fragment by the inactivation unit only aggregates 5% or less of the antibody or antibody fragment, a wavelength of the ultraviolet rays is 200 nm or longer and 315 nm or shorter, an irradiation amount of the ultraviolet rays is 300 mJ/cm 2 or more, an irradiation time of the ultraviolet rays is 3 minutes or less, and a concentration of the radical scavenger in the solution is 0.03 mM or more, and the outlet of the channel of the inactivation unit is connected to an inlet of a column for the chromatography which the second purification unit comprises.

Assignees

• Univ Kobe Nat Univ Corp
• Able Corp

Inventors

• Uchida Kazuhisa
• Ishikawa Shutaro
• Tomita Satoshi
• Kanada Kensaku

Classifications

• C12M47/16

  Sterilization (autoclaves in general B01J3/04) · CPC title

• C12M47/10

  Separation or concentration of fermentation products (bioreactors combined with means for distillation or extraction of liquid fuel C12M43/02) · CPC title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• A61K41/17 Primary

  by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays · CPC title