IP Library › Granted Patent US 12667606
Granted Patent B2
US 12667606 · App. 17/600,527 · Granted Jun 30, 2026

Formulations of protein molecules comprising iduronate 2-sulfatase

Inventors: Dana Andersen (South San Francisco, CA); Adam Catherman (South San Francisco, CA); Tina Giese (South San Francisco, CA); Gunasekaran Kannan (South San Francisco, CA); Mihalis S. Kariolis (South San Francisco, CA); Cathal S. Mahon (South San Francisco, CA); Ankit Patel (South San Francisco, CA)
Assignee: DENALI THERAPEUTICS INC.
A61K38/465A61K47/183A61K47/26C12Y301/06013
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Quick Facts
Patent No.
US 12667606
App. No.
17/600,527
Granted
Jun 30, 2026
Kind
B2
Abstract

Certain embodiments provide a pharmaceutical composition 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 pH of the pharmaceutical composition is about 5.5 to 7.0, as well as methods of use thereof.

Claims (61)

1 . A pharmaceutical composition comprising:

a. (i) a protein molecule 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) a protein molecule 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 about 5.5 to 7.0.

2 . The pharmaceutical composition of claim 1 , wherein the buffer is selected from the group consisting of: a phosphate buffer, an acetate buffer, an arginine buffer, and a histidine buffer.

3 . The pharmaceutical composition of claim 2 , wherein the buffer is a phosphate buffer, and wherein the phosphate buffer is a sodium phosphate buffer or a potassium phosphate buffer.

4 . The pharmaceutical composition of claim 1 , wherein the salt is a sodium salt selected from the group consisting of: sodium chloride, sodium sulfate, and sodium phosphate.

5 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a surfactant.

6 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a stabilizer comprising a sugar.

7 . The pharmaceutical composition of claim 1 , wherein the protein molecule concentration is about 5-50 mg/mL.

8 . The pharmaceutical composition of claim 1 , wherein the buffer concentration is about 5-50 mM.

9 . The pharmaceutical composition of claim 1 , wherein the salt concentration is about 30-150 mM.

10 . The pharmaceutical composition of claim 5 , wherein the surfactant concentration is about 0.1-1.0 mg/mL.

11 . The pharmaceutical composition of claim 5 , wherein the surfactant comprises polysorbate.

12 . The pharmaceutical composition of claim 11 , wherein the surfactant is selected from the group consisting of: polysorbate-20 (PS-20) and polysorbate-80 (PS-80).

13 . The pharmaceutical composition of claim 6 , wherein the stabilizer comprises a sugar selected from sucrose or trehalose.

14 . The pharmaceutical composition of claim 6 , wherein the sugar concentration is about 100-250 mM.

15 . The pharmaceutical composition of claim 1 , wherein the composition further comprises methionine.

16 . The pharmaceutical composition of claim 15 , wherein the methionine concentration is about 5-20 mM.

17 . The pharmaceutical composition of claim 1 , wherein the pH of the pharmaceutical composition is about 6.5±0.5.

18 . A method of treating Hunter syndrome in a subject in need thereof, comprising providing and administering the pharmaceutical composition of claim 1 to the subject.

19 . The pharmaceutical composition of claim 1 , further comprising:

a. (iii) a protein molecule 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) a protein molecule 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.

20 . The pharmaceutical composition of claim 1 , comprising: a buffer comprising sodium phosphate; sodium chloride; a surfactant; and a stabilizer comprising a sugar.

21 . A pharmaceutical composition comprising:

a. (i) a protein molecule 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) a protein molecule 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. about 10-30 mM of sodium phosphate buffer;

c. about 30-100 mM sodium chloride;

d. about 0.4-0.7 mg/mL of a polysorbate surfactant;

e. about 150-200 mM of sucrose; and

f. about 5-25 mM methionine;

wherein the pH of the pharmaceutical composition is 6.5±0.5.

22 . The pharmaceutical composition of claim 21 , further comprising:

a. (iii) a protein molecule 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

 (iv) a protein molecule 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.

23 . The pharmaceutical composition of claim 21 , wherein the sodium phosphate buffer concentration is about 15-25 mM.

24 . The pharmaceutical composition of claim 21 , wherein the sodium phosphate buffer concentration is about 20 mM.

25 . The pharmaceutical composition of claim 21 , wherein the sodium chloride concentration is about 40-100 mM.

26 . The pharmaceutical composition of claim 21 , wherein the sodium chloride concentration is about 50 mM.

27 . The pharmaceutical composition of claim 21 , wherein the polysorbate surfactant concentration is about 0.6 mg/mL.

28 . The pharmaceutical composition of claim 21 , wherein the polysorbate surfactant is polysorbate-20 (PS-20).

29 . The pharmaceutical composition of claim 21 , wherein the sucrose concentration is about 175 mM.

30 . The pharmaceutical composition of claim 21 , wherein the methionine concentration is about 5-15 mM.

31 . The pharmaceutical composition of claim 21 , wherein the methionine concentration is about 10 mM.

32 . The pharmaceutical composition of claim 21 , wherein the protein molecule concentration is about 5-50 mg/mL.

33 . The pharmaceutical composition of claim 21 , wherein the protein molecule concentration is about 10-40 mg/mL.

34 . The pharmaceutical composition of claim 21 , wherein the protein molecule concentration is about 30 mg/mL.

35 . The pharmaceutical composition of claim 22 , comprising:

b. about 20 mM of sodium phosphate buffer;

c. about 50 mM sodium chloride;

d. about 0.6 mg/mL of polysorbate-20 (PS-20);

e. about 175 mM of sucrose; and

f. about 10 mM methionine;

wherein the protein molecule concentration is about 5-50 mg/mL; and

wherein the pH of the pharmaceutical composition is 6.5±0.2.

36 . The pharmaceutical composition of claim 35 , wherein the protein molecule concentration is about 10-40 mg/mL.

37 . The pharmaceutical composition of claim 35 , wherein the protein molecule concentration is about 30 mg/mL.