Formulation of a protein molecule containing iduronate 2-sulfatase

Abstract

Certain embodiments provide pharmaceutical compositions comprising a protein molecule comprising an ERT enzyme-Fc fusion polypeptide and a modified Fc polypeptide, a buffer, an isotonicity agent, a surfactant, and a stabilizer, wherein the pharmaceutical composition has a pH of about 5.5 to 7.0, and methods for using the same are also provided. In certain embodiments, the buffer is selected from the group consisting of phosphate buffer, acetate buffer, arginine buffer, and histidine buffer. In certain embodiments, the phosphate buffer is sodium phosphate buffer or potassium phosphate buffer.

Claims

1. A pharmaceutical composition comprising: a. (i) Protein molecules comprising: a first Fc polypeptide comprising the amino acid sequence of SEQ ID NO: 42, and a fusion polypeptide comprising the amino acid sequence of SEQ ID NO: 40; and (ii) Protein molecules comprising: a first Fc polypeptide comprising the amino acid sequence of SEQ ID NO: 42, and a fusion polypeptide comprising the amino acid sequence of SEQ ID NO: 39; b. A buffer, and c. A salt wherein the pH of the pharmaceutical composition is 5.5 to 7.

0.

2. Further comprising: a. (iii) Protein molecules comprising: a first Fc polypeptide comprising the amino acid sequence of SEQ ID NO: 7, and a fusion polypeptide comprising the amino acid sequence of SEQ ID NO: 5; and / or a. (iv) Protein molecules comprising: a first Fc polypeptide comprising the amino acid sequence of SEQ ID NO: 7, and a fusion polypeptide comprising the amino acid sequence of SEQ ID NO: 4; The pharmaceutical composition according to claim 1.

3. The pharmaceutical composition according to claim 1 or 2, wherein the buffer is selected from the group consisting of phosphate buffer, acetate buffer, arginine buffer, and histidine buffer.

4. The pharmaceutical composition according to claim 3, wherein the buffer is sodium phosphate buffer or potassium phosphate buffer.

5. The pharmaceutical composition according to any one of claims 1 to 4, wherein the salt is a sodium salt.

6. The pharmaceutical composition according to claim 5, wherein the sodium salt is selected from the group consisting of sodium chloride, sodium sulfate, and sodium phosphate.

7. The pharmaceutical composition further comprises a surfactant and / or The pharmaceutical composition further comprises a stabilizer containing sugar, The pharmaceutical composition according to any one of claims 1 to 6.

8. The pharmaceutical composition according to claim 1, comprising a buffer containing sodium phosphate, sodium chloride, a surfactant, and a stabilizer containing sugar.

9. The pharmaceutical composition according to any one of claims 1 to 8, wherein the concentration of the protein molecule is 5 to 50 mg / mL, 10 to 30 mg / mL, 10 mg / mL ± 2 mg / mL, 20 mg / mL ± 2 mg / mL, or 30 mg / mL ± 2 mg / mL.

10. The pharmaceutical composition according to any one of claims 1 to 9, wherein the concentration of the buffer is 5 to 50 mM, 10 to 30 mM, or 20 mM.

11. The pharmaceutical composition according to any one of claims 1 to 10, wherein the concentration of the salt is 30 to 150 mM, 50 to 137 mM, 50 mM ± 2 mM, or 137 mM ± 2 mM.

12. The pharmaceutical composition according to any one of claims 7 to 11, wherein the pharmaceutical composition further contains a surfactant, and here, the concentration of the surfactant is 0.1 to 1.0 mg / mL, 0.2 to 0.6 mg / mL, 0.4 mg / mL ± 0.1 mg / mL, or 0.6 mg / mL ± 0.1 mg / mL.

13. The pharmaceutical composition according to any one of claims 7 to 12, wherein the pharmaceutical composition further contains a surfactant, and here, the surfactant contains polysorbate.

14. The pharmaceutical composition according to claim 13, wherein the surfactant is polysorbate-20 (PS-20) or polysorbate-80 (PS-80).

15. The pharmaceutical composition according to any one of claims 7 to 14, wherein the pharmaceutical composition further contains a stabilizer containing sugar, and here, the stabilizer contains a sugar selected from sucrose or trehalose.

16. The pharmaceutical composition according to claim 15, wherein the stabilizer contains sucrose.

17. The pharmaceutical composition according to any one of claims 7 to 16, wherein the pharmaceutical composition further contains a stabilizer containing sugar, and here, the concentration of the sugar is 100 to 250 mM.

18. The pharmaceutical composition according to claim 17, wherein the concentration of the sugar is 175 mM ± 2 mM.

19. The pharmaceutical composition according to any one of claims 1 to 18, wherein the composition further contains methionine.

20. The pharmaceutical composition according to claim 19, wherein the concentration of the methionine is 5 to 20 mM.

21. The pharmaceutical composition according to claim 20, wherein the concentration of the methionine is 10 mM ± 2 mM.

22. The pharmaceutical composition according to any one of claims 1 to 20, wherein the pH of the pharmaceutical composition is 5.5 to 6.5 or 6.5 ± 0.

5.

23. The pharmaceutical composition according to any one of claims 1 to 22, wherein the protein molecule remains intact at a pH of 5.5 to 7.

0.

24. The pharmaceutical composition according to any one of claims 1 to 23, wherein the pharmaceutical composition is provided as a liquid composition or a lyophilized composition.

25. The pharmaceutical composition according to any one of claims 1 to 24 for treating Hunter syndrome in a subject in need of treatment for Hunter syndrome.

26. The pharmaceutical composition according to claim 25, wherein the pharmaceutical composition is administered intravenously.

27. Use of the pharmaceutical composition according to any one of claims 1 to 24 in the preparation of a medicament for treating Hunter syndrome in a subject in need of treatment for Hunter syndrome.

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