Low ph pharmaceutical formulation

Abstract

This disclosure describes a low-pH formulation comprising, for example, an antigen-binding protein that binds to CD3, at least one buffer, at least one sugar, and at least one surfactant.

Claims

1. A liquid pharmaceutical composition comprising (a) a heterodimeric antibody comprising three antigen-binding domains and an Fc, wherein the three antigen-binding domains comprise (i) two Fab domains binding a first target and (ii) a scFv domain binding a second target, wherein the second target is CD3; (b) a glutamate in an amount of 10 to 50 mM; (c) a surfactant in an amount of 0.004 to 0.01% (w / v), wherein the surfactant is polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or a combination thereof; and (d) a sugar in an amount of 9 to 12% (w / v), wherein the pH range of the pharmaceutical composition is from 4 to 5.

2. The liquid pharmaceutical composition of claim 1, wherein the glutamate is present in a concentration range of 10 mM to 30 mM.

3. The liquid pharmaceutical composition of claim 1 or 2, wherein the sugar is present in a concentration range of 9% to 11% (w / V).

4. The liquid pharmaceutical composition of claim 1 or 2, wherein the sugar is present in a concentration range of 9% to 10.5% (w / V).

5. The liquid pharmaceutical composition of claim 4, wherein the sugar is present in a concentration range of 9% to 10% (w / V).

6. The liquid pharmaceutical composition of claim 1 or 2, wherein the surfactant is present in a concentration range of 0.005% to 0.01% (w / V).

7. The liquid pharmaceutical composition of claim 1 or 2, wherein the surfactant is present in a concentration range of 0.007% to 0.01% (w / V).

8. The liquid pharmaceutical composition of claim 7, wherein the surfactant is present at a concentration of 0.01% (w / V).

9. A liquid pharmaceutical composition as claimed in claim 1 or 2, wherein the pH range of the composition is from 4.2 to 4.

6.

10. The liquid pharmaceutical composition of claim 9, wherein the pH of the composition is 4.

2.

11. The liquid pharmaceutical composition of claim 1 has an osmotic pressure range of 150 mOsm to 500 mOsm.

12. The liquid pharmaceutical composition of claim 1 further comprises excipients selected from the group consisting of polyols and amino acids.

13. The liquid pharmaceutical composition of claim 12, wherein the excipient is present in a concentration range of 0.1% to 15% (m / V).

14. The liquid pharmaceutical composition of claim 1, wherein the composition comprises 10 mM glutamic acid, 9% (w / v) sucrose and 0.01% (w / v) polysorbate 80, and wherein the pH of the liquid pharmaceutical composition is 4.

2.

15. The liquid pharmaceutical composition of claim 1, wherein the heterodimeric antibody is present in a concentration range of 0.1 mg / ml to 8 mg / ml.

16. The liquid pharmaceutical composition of claim 1, wherein the heterodimeric antibody is present in a concentration range of 0.1 mg / mL to 20 mg / mL.

17. The liquid pharmaceutical composition of claim 1, wherein the heterodimeric antibody is present in an amount ranging from 50 µg to 200 mg.

18. The liquid pharmaceutical composition of claim 1, wherein the heterodimeric antibody is present at 1 mg / mL.

19. The liquid pharmaceutical composition of claim 1, wherein the heterodimeric antibody is present at 5 mg / mL.

20. The liquid pharmaceutical composition of claim 1, wherein the heterodimeric antibody is present at 20 mg / mL.

21. The liquid pharmaceutical composition of claim 1, wherein the heterodimeric antibody is present at 10 mg / mL.

22. Use of a composition as claimed in any one of claims 1 to 21 for the preparation of a medicament for treating cancer.

23. As claimed in claim 22, wherein the cancer is multiple myeloma.

24. As requested in claim 22, wherein the cancer is prostate cancer.

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