EP-4736865-A1 - COMPOSITION FOR INHIBITING DENATURATION OF PROTEIN

Abstract

The present invention provides a composition for inhibiting protein denaturation, capable of inhibiting denaturation of a wide range of proteins. The present invention relates to a composition for inhibiting protein denaturation, containing at least one saccharide selected from the group consisting of trehalose, sucrose, maltitol, and isomaltitol and at least one amine compound selected from the group consisting of glutamic acid, aspartic acid, arginine, proline, serine, choline, and salts thereof.

Inventors

• KONO, KEIZO
• KUSANO, HAJIME
• MITSUKAWA, Yuki
• HASHIMOTO, KOTARO
• HOJO, Yukiko

Assignees

• Nagase Viita Co., Ltd.

Dates

Publication Date

20260506

Application Date

20240705

Claims (17)

1. A composition for inhibiting protein denaturation, comprising: at least one saccharide selected from the group consisting of trehalose, sucrose, maltitol, and isomaltitol; and at least one amine compound selected from the group consisting of glutamic acid, aspartic acid, arginine, proline, serine, choline, and salts thereof.
2. The composition for inhibiting protein denaturation according to claim 1, which inhibits protein denaturation caused by heating or freeze-thawing.
3. The composition for inhibiting protein denaturation according to claim 1 or 2, which inhibits protein aggregation.
4. The composition for inhibiting protein denaturation according to claim 1 or 2, wherein the protein is at least one selected from the group consisting of antibodies, cytokines, allergens, and enzymes.
5. The composition for inhibiting protein denaturation according to claim 1 or 2, wherein the protein is at least one selected from the group consisting of anti-IFNα antibodies, anti-IFNγ antibodies, anti-TNFα antibodies, anti-IL-17A antibodies, and anti-IL-18 antibodies.
6. The composition for inhibiting protein denaturation according to claim 1 or 2, wherein the protein is at least one selected from the group consisting of IFNα, IFNγ, IL-18, and TNFα.
7. The composition for inhibiting protein denaturation according to claim 1 or 2, wherein the protein is a cedar pollen allergen.
8. The composition for inhibiting protein denaturation according to claim 1 or 2, wherein the protein is at least one selected from the group consisting of lactate dehydrogenases, glycosyltransferases, saccharide-degrading enzymes, malate dehydrogenases, and protein-degrading enzymes.
9. The composition for inhibiting protein denaturation according to claim 1 or 2, wherein the protein is a virus-derived protein or a bacteria-derived protein.
10. The composition for inhibiting protein denaturation according to claim 1 or 2, wherein the protein is a blood coagulation factor or albumin.
11. The composition for inhibiting protein denaturation according to claim 1 or 2, wherein a molar ratio of the saccharide to the amine compound is from 40:1 to 1:40.
12. The composition for inhibiting protein denaturation according to claim 1 or 2, wherein the composition is in liquid form, and a total concentration of the saccharide and the amine compound is from 0.20 mol/L to 3.50 mol/L.
13. The composition for inhibiting protein denaturation according to claim 1 or 2, which inhibits protein denaturation synergistically compared to a protein denaturation inhibitory effect of the saccharide and a protein denaturation inhibitory effect of the amine compound.
14. A method for inhibiting protein denaturation, comprising allowing a protein to coexist with the composition for inhibiting protein denaturation according to claim 1 or 2.
15. A protein formulation, comprising a protein and the composition for inhibiting protein denaturation according to claim 1 or 2.
16. A method for inhibiting protein denaturation, comprising allowing a protein to coexist with: at least one saccharide selected from the group consisting of trehalose, sucrose, maltitol, and isomaltitol, and at least one amine compound selected from the group consisting of glutamic acid, aspartic acid, arginine, proline, serine, choline, and salts thereof.
17. A protein formulation, comprising: at least one saccharide selected from the group consisting of trehalose, sucrose, maltitol, and isomaltitol; at least one amine compound selected from the group consisting of glutamic acid, aspartic acid, arginine, proline, serine, choline, and salts thereof; and a protein.

Description

TECHNICAL FIELD The present invention relates to a composition for inhibiting protein denaturation. BACKGROUND ART Proteins are widely used in fields such as therapeutic agents, diagnostic agents, vaccines, and food. However, proteins alone are prone to denaturation, and when subjected to heating, long-term storage, multiple freeze-thaw cycles, or other processes, they become denatured and lose their function. Efforts to improve protein-containing compositions are being made to inhibit protein denaturation. Carbohydrates and amino acids have been known to inhibit protein denaturation. For example, Patent Literature 1 discloses a method for stabilizing a Fc-mutant protein using a carbohydrate, a cationic amino acid, an anion, and a polysorbate. Patent Literature 2 discloses a method for stabilizing an anti-TNFα antibody using a polyol, a surfactant, and arginine. These methods can stabilize only limited types of proteins. CITATION LIST - Patent Literature Patent Literature 1: JP 2009-525986 TPatent Literature 2: JP 2022-097600 A SUMMARY OF INVENTION - Technical Problem An object of the present invention is to provide a composition for inhibiting protein denaturation, capable of inhibiting denaturation of a wide range of proteins. - Solution to Problem The present inventors have found that a combination of a specific saccharide and a specific amine compound enables the inhibition of protein denaturation. Based on this finding, the present invention has been completed. Specifically, the present invention relates to a composition for inhibiting protein denaturation, containing at least one saccharide selected from the group consisting of trehalose, sucrose, maltitol, and isomaltitol and at least one amine compound selected from the group consisting of glutamic acid, aspartic acid, arginine, proline, serine, choline, and salts thereof. Preferably, the composition for inhibiting protein denaturation inhibits protein denaturation caused by heating or freeze-thawing. Preferably, the composition for inhibiting protein denaturation inhibits protein aggregation. Preferably, the protein is at least one selected from the group consisting of antibodies, cytokines, allergens, and enzymes. Preferably, the protein is at least one selected from the group consisting of anti-IFNα antibodies, anti-IFNγ antibodies, anti-TNFα antibodies, anti-IL-17A antibodies, and anti-IL-18 antibodies. Preferably, the protein is at least one selected from the group consisting of IFNα, IFNγ, IL-18, and TNFα. Preferably, the protein is a cedar pollen allergen. Preferably, the protein is at least one selected from the group consisting of lactate dehydrogenases, glycosyltransferases, saccharide-degrading enzymes, malate dehydrogenases, and protein-degrading enzymes. Preferably, the protein is a virus-derived protein or a bacteria-derived protein. Preferably, the protein is a blood coagulation factor or albumin. Preferably, a molar ratio of the saccharide to the amine compound in the composition for inhibiting protein denaturation is from 40:1 to 1:40. Preferably, the composition for inhibiting protein denaturation is in liquid form, and a total concentration of the saccharide and the amine compound in the composition is from 0.20 mol/L to 3.50 mol/L. Preferably, the composition for inhibiting protein denaturation inhibits protein denaturation synergistically compared to a protein denaturation inhibitory effect of the saccharide and a protein denaturation inhibitory effect of the amine compound. The present invention also relates to a method for inhibiting protein denaturation, including allowing a protein to coexist with the composition for inhibiting protein denaturation. The present invention also relates to a protein formulation, containing a protein and the composition for inhibiting protein denaturation. The present invention also relates to a method for inhibiting protein denaturation, including allowing a protein to coexist with: at least one saccharide selected from the group consisting of trehalose, sucrose, maltitol, and isomaltitol, andat least one amine compound selected from the group consisting of glutamic acid, aspartic acid, arginine, proline, serine, choline, and salts thereof. The present invention also relates to a protein formulation, containing: at least one saccharide selected from the group consisting of trehalose, sucrose, maltitol, and isomaltitol;at least one amine compound selected from the group consisting of glutamic acid, aspartic acid, arginine, proline, serine, choline, and salts thereof; anda protein. - Advantageous Effects of Invention The composition for inhibiting protein denaturation according to the present invention can inhibit denaturation of a wide range of proteins. DESCRIPTION OF EMBODIMENTS <<Composition for inhibiting protein denaturation>> The present invention relates to a composition for inhibiting protein denaturation, containing at least one saccharide selected from the group consisting of trehalose