Anti-IL31RA antibody-containing formulations
In one non-limiting embodiment, the present disclosure relates to lyophilized formulations containing an IL-31 antagonist (for example, an anti-IL-31RA antibody) as an active ingredient, the lyophilized formulations further containing arginine and/or a salt thereof and sucrose and/or trehalose. In another non-limiting embodiment, the present disclosure relates to solution formulations containing an IL-31 antagonist as an active ingredient, the solution formulations further containing arginine and/or a salt thereof. In other non-limiting embodiments, the present disclosure relates to methods for stabilizing an antibody (for example, an anti-IL-31RA antibody) in an antibody-containing formulation, methods for suppressing antibody aggregation (aggregate formation) in an antibody-containing formulation, and methods for reducing components with charge heterogeneity in an antibody-containing formulation, the methods being characterized in that the formulation is prepared to contain arginine and/or a salt thereof, and/or sucrose and/or trehalose.
1. A solution formulation comprising
6 to 100 mg/mL of an IL-31 antagonist that is an anti-IL-31RA antibody comprising (i) an H chain variable region that comprises a CDR1 as set forth in SEQ ID NO: 1, a CDR2 as set forth in SEQ ID NO: 2, and a CDR3 as set forth in SEQ ID NO: 3; and (ii) an L chain variable region that comprises a CDR1 as set forth in SEQ ID NO: 4, a CDR2 as set forth in SEQ ID NO: 5, and a CDR3 as set forth in SEQ ID NO: 6,
6 to 20 mmol/L Tris buffer,
45 to 150 mmol/L arginine or a salt thereof,
75 to 250 mmol/L sucrose or trehalose, and
0.15 to 0.50 mg/mL poloxamer 188 or polysorbate 20,
wherein the solution formulation has a pH in the range of 6 to 8.
2. The solution formulation of claim 1 , wherein the H chain variable region comprises SEQ ID NO: 7 and the L chain variable region comprises SEQ ID NO: 8.
3. A lyophilized formulation produced by lyophilizing the solution formulation of claim 2 .
4. A method comprising lyophilizing the solution of claim 2 to produce a lyophilized formulation.
5. The solution formulation of claim 1 , wherein the anti-IL-31RA antibody comprises an H chain comprising SEQ ID NO: 9 and an L chain comprising SEQ ID NO: 10.
6. A lyophilized formulation produced by lyophilizing the solution formulation of claim 5 .
7. A method comprising lyophilizing the solution of claim 5 to produce a lyophilized formulation.
8. The solution formulation of claim 1 , wherein the molar ratio of the arginine or salt thereof to the anti-IL-31RA antibody is in the range of 220:1 to 1100:1 and the molar ratio of the sucrose or trehalose to the anti-IL-31RA antibody is in the range of 370:1 to 1840:1.
9. A lyophilized formulation produced by lyophilizing the solution formulation of claim 8 .
10. A method comprising lyophilizing the solution of claim 8 to produce a lyophilized formulation.
11. The solution formulation of claim 1 , wherein the arginine or salt thereof is arginine-hydrochloride, arginine-aspartate, or arginine-glutamate.
12. A lyophilized formulation produced by lyophilizing the solution formulation of claim 11 .
13. A method comprising lyophilizing the solution of claim 11 to produce a lyophilized formulation.
14. A method comprising lyophilizing the solution of claim 1 to produce a lyophilized formulation.
15. A lyophilized formulation produced by lyophilizing the solution formulation of claim 1 .
16. A kit comprising a container that contains the lyophilized formulation of claim 15 .
17. The kit of claim 16 , wherein the lyophilized formulation in the container comprises:
1 to 800 mg of the anti-IL-31RA antibody,
0.1 to 40 mg tris(hydroxymethyl)aminomethane,
0.8 to 400 mg arginine or a salt thereof,
3 to 1100 mg sucrose or trehalose, and
0.01 to 7 mg poloxamer 188 or polysorbate 20.
18. The kit of claim 17 , wherein the H chain variable region comprises SEQ ID NO: 7 and the L chain variable region comprises SEQ ID NO: 8.
19. The kit of claim 17 , wherein the anti-IL-31RA antibody comprises an H chain comprising SEQ ID NO: 9 and an L chain comprising SEQ ID NO: 10.
20. The kit of claim 17 , wherein the arginine or salt thereof is arginine-hydrochloride, arginine-aspartate, or arginine-glutamate.
21. A method of preparing a reconstituted solution, the method comprising providing the kit of claim 17 and contacting the lyophilized formulation with water to produce a reconstituted solution.
22. The kit of claim 16 , wherein the container is a syringe suitable for injecting a medicament.
23. The kit of claim 16 , further comprising a second container comprising water for injection.
24. A method of preparing a reconstituted solution, the method comprising providing the kit of claim 16 and contacting the lyophilized formulation with water to produce a reconstituted solution.
25. A lyophilized formulation comprising
an IL-31 antagonist that is an anti-IL-31RA antibody comprising (i) an H chain variable region that comprises a CDR1 as set forth in SEQ ID NO: 1, a CDR2 as set forth in SEQ ID NO: 2, and a CDR3 as set forth in SEQ ID NO: 3; and (ii) an L chain variable region that comprises a CDR1 as set forth in SEQ ID NO: 4, a CDR2 as set forth in SEQ ID NO: 5, and a CDR3 as set forth in SEQ ID NO: 6,
Tris buffer,
arginine or a salt thereof,
sucrose or trehalose, and
poloxamer 188 or polysorbate 20,
wherein the molar ratio of the arginine or salt thereof to the anti-IL-31RA antibody is in the range of 220:1 to 1100:1,
wherein the molar ratio of the sucrose or trehalose to the anti-IL-31RA antibody is in the range of 370:1 to 1840:1, and
wherein pH is 6 to 8 when the lyophilized formulation is reconstituted in water.
26. The lyophilized formulation of claim 25 , wherein the H chain variable region comprises SEQ ID NO: 7 and the L chain variable region comprises SEQ ID NO: 8.
27. The lyophilized formulation of claim 25 , wherein the anti-IL-31RA antibody comprises an H chain comprising SEQ ID NO: 9 and an L chain comprising SEQ ID NO: 10.
28. The lyophilized formulation of claim 25 , wherein the arginine or salt thereof is arginine-hydrochloride, arginine-aspartate, or arginine-glutamate.