Solution preparation containing stabilized antibody
An objective of the present invention is to provide stable antibody-containing formulations which are suitable for subcutaneous administration and in which aggregation formation is suppressed during long-term storage. The present inventors discovered that a significant stabilization effect was achieved by using an acidic amino acid, aspartic acid or glutamic acid as a counter ion species in histidine buffer or tris(hydroxymethyl)aminomethane, specifically by using histidine-aspartate buffer or histidine-glutamate buffer, or tris(hydroxymethyl)aminomethane-aspartate or tris(hydroxymethyl)aminomethane-glutamate as a buffer. The present inventors also discovered that a significant stabilization effect was achieved by using an acidic amino acid, aspartic acid or glutamic acid, as a counter ion species to a basic amino acid such as arginine, specifically by using arginine-aspartate or arginine-glutamate.
1. A stable antibody-comprising formulation comprising basic amino acid-aspartate or basic amino acid-glutamate, wherein the antibody concentration is 100 mg/ml or more, and the basic amino acid is selected from the group consisting of histidine, arginine and tris(hydroxymethyl)aminomethane.
2. The formulation of claim 1 comprising histidine-aspartate buffer or histidine-glutamate buffer, wherein the basic amino acid is histidine.
3. The formulation of claim 1 comprising arginine-aspartate or arginine-glutamate, wherein the basic amino acid is arginine.
4. A stable antibody-comprising formulation comprising histidine-aspartate buffer or histidine-glutamate buffer, and arginine-aspartate or arginine-glutamate, wherein the antibody concentration is 100 mg/ml or more.
5. A stable antibody-comprising formulation comprising tris(hydroxymethyl)aminomethane-aspartate buffer or tris(hydroxymethyl) aminomethane-glutamate buffer, wherein the antibody concentration is 100 mg/ml or more.
6. A stable antibody-comprising formulation comprising tris(hydroxymethyl) aminomethane-aspartate buffer and tris(hydroxymethyl) aminomethane-glutamate buffer, wherein the antibody concentration is 100 mg/ml or more.
7. The formulation according to claim 1 , which consists of less than 1 mM chloride ion and acetate ion.
8. The formulation according to claim 1 , which additionally comprises a sugar.
9. The formulation according to claim 1 , wherein the antibody is a humanized antibody or a human antibody.
10. The formulation according to claim 1 , wherein the antibody has been modified to have an isoelectric point (pI) of 5 to 8.
11. The formulation according to claim 1 , wherein the antibody concentration is 100 to 250 mg/ml.
12. The formulation according to claim 1 , which is a liquid formulation.
13. The formulation according to claim 12 , wherein the viscosity of the liquid formulation is 30 mPas or less.
14. The formulation according to claim 12 , wherein the liquid formulation is stable at 2° C. to 8° C. for at least six months.
15. The formulation according to claim 1 , which has not been subjected to lyophilization during preparation of the formulation.
16. The formulation according to claim 12 , which is frozen stored at −30° C. to −10° C.
17. The formulation according to claim 1 , wherein the formulation is a lyophilized formulation.
18. The formulation according to claim 2 , wherein the buffer concentration is 5 to 100 Mm.
19. The formulation according to claim 3 , wherein the arginine concentration is 5 to 300 mM.
20. The formulation according to claim 1 , wherein the antibody is an anti-IL-6 receptor antibody.
21. The formulation according to claim 2 , wherein the buffer consists essentially of amino acid(s).
22. The formulation according to claim 1 , which is for subcutaneous administration.
23. The formulation according to claim 1 , wherein the antibody comprises heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and light chain comprising the amino acid sequence of SEQ ID NO: 2.
24. The formulation according to claim 1 , wherein the antibody comprises heavy chain comprising the amino acid sequence of SEQ ID NO: 3 and light chain comprising the amino acid sequence of SEQ ID NO: 4.
25. The formulation according to claim 1 , wherein the antibody is a bispecific antibody against factor IX and factor X.
26. The formulation according to claim 1 , wherein the antibody is an anti-NR10 antibody.
27. The formulation according to claim 1 , wherein the antibody is an anti-glypican-3 antibody.