JP-2026514305-A - Multiple-dose antibody drugs using phenol or benzyl alcohol

Abstract

This specification provides a method for stabilizing Fc-containing protein preparations in aqueous solution. The disclosed method can stabilize Fc-containing proteins in pharmaceuticals, particularly liquid formulations, by using phenol or benzyl alcohol as a preservative. [Selection Diagram] Figure 1A

Inventors

• タン、 シャオリン
• ブレイド、 レオニード
• ポーター、 ジュリー

Assignees

• リジェネロン・ファーマシューティカルズ・インコーポレイテッド

Dates

Publication Date

20260508

Application Date

20240501

Priority Date

20230501

Claims (20)

1. A multi-dose container containing a parenteral Fc-containing protein preparation, wherein the preparation is in an aqueous solution. A multi-dose container comprising (a) at least one Fc-containing protein, and (b) phenol or benzyl alcohol.
2. The multi-dose container according to claim 1, wherein the Fc-containing protein is concentrated at a concentration of 0.1 mg/mL to 500 mg/mL.
3. The container for multiple doses according to claim 1, wherein the preparation contains phenol at a concentration of 1 mg/mL to 10 mg/mL.
4. The container for multiple doses according to claim 3, wherein the preparation contains phenol at a concentration of 2 mg/mL to 5 mg/mL.
5. The container for multiple doses according to claim 4, wherein the preparation contains phenol at a concentration of 3 mg/mL.
6. The container for multiple doses according to claim 1, wherein the preparation contains benzyl alcohol at a concentration of 1 mg/mL to 15 mg/mL.
7. The multi-dose container according to claim 3, wherein the preparation contains benzyl alcohol at a concentration of 3 mg/mL to 12 mg/mL.
8. The multi-dose container according to claim 4, wherein the preparation contains benzyl alcohol at a concentration of 10 mg/mL.
9. The container for multiple doses according to claim 1, wherein the container is a single-patient container.
10. The container for multiple doses according to claim 1, wherein the container has a capacity of 1 mL to 100 mL.
11. The container for multiple doses according to claim 1, wherein the container has a capacity of 5 mL to 100 mL.
12. The container for multiple doses according to claim 1, wherein the container has a capacity of 10 mL to 50 mL.
13. The container for multiple doses according to claim 1, wherein the container has a capacity of 20 mL to 40 mL.
14. The container for multiple doses according to claim 1, wherein the container has a capacity of 30 mL.
15. The container for multiple doses according to claim 1, wherein the Fc-containing protein is a monoclonal antibody.
16. The container for multiple doses according to claim 12, wherein the monoclonal antibody is a bispecific antibody.
17. The container for multiple doses according to claim 1, wherein the container contains two or more types of Fc-containing proteins.
18. The container for multiple doses according to claim 1, wherein the Fc-containing protein is a receptor Fc fusion protein.
19. The container for multiple doses according to claim 1, wherein the Fc-containing protein is a trap protein.
20. The container for multiple doses according to claim 1, wherein the preparation contains phenol.

Description

Reference to Related Applications This application claims the benefit and priority of U.S. Provisional Application No. 63/463,179, filed on 1 May 2023. The above referenced application is incorporated herein by reference in its entirety. This invention provides an improved method for stabilizing Fc-containing protein preparations in aqueous solution using a preservative. Multidose antibody drugs are often supplied in lyophilized form to extend their shelf life. Some antibody products are supplied in solution, requiring preservatives. However, preservatives can destabilize antibodies. Furthermore, while various antimicrobial preservatives are used in commercially available biological products, they are rarely used in monoclonal antibodies (mAbs). Therefore, considering the effect of typical antimicrobial preservatives on the stability of several mAb liquid formulations, an object of the present invention is to provide an improved method for stabilizing and preserving Fc-containing protein preparations in aqueous solution. Another object of the present invention is to provide an improved method for developing formulations containing a preservative along with a stable Fc-containing protein in a multi-dose Fc-containing protein pharmaceutical. A method for stabilizing an Fc-containing protein preparation in an aqueous solution is provided. For example, a multi-dose container may contain a parenteral Fc-containing protein preparation. The preparation may contain at least one Fc-containing protein in the aqueous solution. The preparation may also contain phenol or benzyl alcohol in the aqueous solution. One or more of the following exemplary features may be included: The Fc-containing protein may be at a concentration of approximately 0.1 mg/mL to approximately 500 mg/mL. The phenol may be at a concentration of approximately 1 mg/mL to approximately 10 mg/mL. The phenol may also be at a concentration of approximately 2 mg/mL to approximately 5 mg/mL. Furthermore, the phenol may be at a concentration of, for example, approximately 3 mg/mL (approximately 0.3%). The benzyl alcohol may be at a concentration of approximately 1 mg/mL to approximately 15 mg/mL. Benzyl alcohol may further be at a concentration of approximately 3 mg/mL to approximately 12 mg/mL. Benzyl alcohol may further be at a concentration of, for example, approximately 10 mg/mL (approximately 1%). The container may be a single-patient container. The container may have a capacity of 1 mL to 100 mL. The container may also have a capacity of 0.5 mL to 100 mL. Furthermore, the container may have a capacity of 5 mL to 50 mL. The container may even have a capacity of 20 mL to 40 mL. The container may also have a capacity of 30 mL. The Fc-containing protein may be a monoclonal antibody. The monoclonal antibody may be a bispecific antibody. The container may contain one, two, three, or more types of Fc-containing proteins. The Fc-containing protein may be a receptor Fc fusion protein. The Fc-containing protein may also be a trap protein. In another exemplary implementation, the parenteral Fc-containing protein preparation may contain at least one Fc-containing protein in aqueous solution. The parenteral Fc-containing protein preparation may also contain phenol or benzyl alcohol in aqueous solution. The preparation may include one or more of the following exemplary features: The Fc-containing protein may be at a concentration of approximately 0.1 mg/mL to approximately 500 mg/mL. The phenol may be at a concentration of approximately 1 mg/mL to approximately 10 mg/mL. The phenol may also be at a concentration of approximately 2 mg/mL to approximately 5 mg/mL. Furthermore, the phenol may be at a concentration of, for example, approximately 3 mg/mL (approximately 0.3%). The benzyl alcohol may be at a concentration of approximately 1 mg/mL to approximately 15 mg/mL. The benzyl alcohol may also be at a concentration of approximately 3 mg/mL to approximately 12 mg/mL. Furthermore, the benzyl alcohol may be at a concentration of, for example, approximately 10 mg/mL (approximately 1%). The Fc-containing protein may be a monoclonal antibody. The monoclonal antibody may be a bispecific antibody. The preparation may contain one, two, three, or more types of Fc-containing proteins. The Fc-containing protein may be a receptor Fc fusion protein. The Fc-containing protein may also be a trap protein. Further exemplary embodiments provide a method for stabilizing an Fc-containing protein preparation, which may include the step of providing the Fc-containing protein in an aqueous solution containing phenol or benzyl alcohol. The method for stabilizing an Fc-containing protein preparation may also include the step of filling a container with the Fc-containing protein in an aqueous solution containing phenol or benzyl alcohol. One or more of the following exemplary features may be included. Phenol or benzyl alcohol may be added to an aqueous solution containing an Fc-containing