High concentration antibody-containing liquid formulation

Patent metadata

Field	Value
Publication number	US-11008394-B2
Application number	US-201916390197-A
Country	US
Kind code	B2
Filing date	Apr 22, 2019
Priority date	Dec 27, 2007
Publication date	May 18, 2021
Grant date	May 18, 2021

Abstract

The problem to be solved is to provide an antibody-containing formulation which is stable and suited for subcutaneous administration, wherein dimerization and deamidation is prevented during long-term storage. The present application is directed to a stable antibody-containing liquid formulation characterized by containing arginine and methionine.

First claim

The invention claimed is:

1. A method of inhibiting deamidation of a humanized anti-IL-6 receptor antibody MRA in a concentrated liquid formulation of 150 to 200 mg/mL of the antibody, comprising including in the liquid formulation 50 to 300 mM arginine and histidine buffer, pH 6.0.

2. The method of claim 1 , wherein dimerization is also inhibited.

3. The method of claim 1 , wherein the arginine concentration is selected from the group consisting of 50 mM, 1.00 mM, 150 mM, 200 mM, and 300 mM.

4. The method of claim 3 , wherein the arginine concentration is 100 mM.

5. The method of claim 1 , wherein the antibody concentration in the formulation is 180 mg/mL.

6. The method of claim 1 , wherein the formulation further comprises polysorbate 20 or polysorbate 80 at a concentration from 0.005 to 3%.

7. A method of inhibiting deamidation of a humanized anti-IL-6 receptor antibody MRA in a concentrated liquid formulation of 150 to 200 mg/mL, of the antibody, comprising including in the liquid formulation 50 to 300 mM arginine, 0.005 to 3% polysorbate 80, and histidine buffer, pH 6.0.

8. The method of claim 7 , wherein dimerization is also inhibited.

9. The method of claim 7 , wherein the arginine concentration is 100 mM.

10. The method of claim 7 , wherein the antibody concentration in the formulation is 180 mg/mL.

11. A method for formulating humanized anti-IL-6 receptor antibody MRA for use for subcutaneous administration, comprising combining 150 to 200 mg/mL of the antibody with 50 to 300 mM arginine and a histidine buffer pH 6.0 to prepare a liquid formulation, wherein the arginine inhibits dimerization or deamidation of the antibody in the formulation.

12. The method of claim 11 , wherein the arginine concentration is 100 mM.

13. The method of claim 11 , wherein the antibody concentration is 180 mg/mL.

14. A method for formulating humanized anti-IL-6 receptor antibody MRA for use for subcutaneous administration, comprising combining 150 to 200 mg/mL of the antibody with 50 to 300 mM arginine, 0.005 to 3% polysorbate 80 and a histidine buffer pH 6.0 to prepare a liquid formulation, wherein the arginine inhibits dimerization or deamidation of the antibody in the formulation.

15. The method of claim 14 , wherein the arginine concentration is 100 mM.

16. The method of claim 14 , wherein the antibody concentration is 180 mg/mL.

Assignees

• Chugai Pharmaceutical Co Ltd
• F Hoffmann—La Roche Ag
• Hoffmann La Roche

Inventors

• Morichika Toshiyuki
• Kameoka Daisuke
• Imaeda Yoshimi
• Maeda Terutoshi
• Stauch Oliver Boris

Classifications

• C07K16/2866 Primary

  against receptors for cytokines, lymphokines, interferons · CPC title

• A61K39/39591

  Stabilisation, fragmentation · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title