Granted Patent B2

US 12,653,871 · App. 18/184,821 · Granted Jun 16, 2026

Inventor: Mark Brader (Lexington, MA)

Assignee: BIOVERATIV THERAPEUTICS INC.

A61K38/4846A61K9/0019A61K9/19A61K47/02A61K47/10A61K47/22A61K47/26A61M5/158A61M5/178A61M5/19C12Y304/21022C07K2319/30

Abstract

Claims (45)

1 . A pharmaceutical kit comprising:

(a) a first container comprising a lyophilizate, where the lyophilizate comprises

i) a chimeric polypeptide comprising a Factor IX (FIX) polypeptide and an Fc region,

ii) sucrose;

iii) mannitol;

iv) L-histidine; and

v) polysorbate 20 or polysorbate 80; and

(b) a second container comprising a 0.325% (w/v) NaCl diluent solution at a volume sufficient to produce, when combined with the lyophilized powder of the first container, a solution comprising:

i) between about 10 mg/ml and about 20 mg/ml of sucrose;

ii) between about 20 mg/ml and about 40 mg/ml of mannitol;

iii) between about 3 mg/ml and about 4 mg/ml of sodium chloride (NaCl);

iv) between about 3 mg/ml and about 6 mg/ml of L-histidine; and

v) between about 0.08 mg/ml and about 0.2 mg/ml of polysorbate 20 or polysorbate 80.

2 . The kit of claim 1 , wherein the first container is a glass vial comprising a rubber stopper.

3 . The kit of claim 1 , wherein the second container is a syringe body, and wherein the syringe body is associated with a plunger.

4 . The kit of claim 3 , further comprising infusion tubing associated with a needle to be connected to the syringe, suitable for intravenous infusion.

5 . A vial comprising a pharmaceutical composition, the composition comprising:

(i) about 250 IU, about 500 IU, about 1000 IU, about 2000 IU, about 3000 IU, or about 4000 IU of a chimeric polypeptide comprising a Factor IX (FIX) polypeptide and an Fc region;

(ii) about 59.5 mg of sucrose

(iii) about 119 mg of mannitol;

(iv) about 0.325% (w/v) sodium chloride (NaCl);

(v) about 19.4 mg of L-histidine; and

(vi) about 0.50 mg of polysorbate 20 or polysorbate 80.

6 . A syringe comprising a pharmaceutical composition comprising:

i) about 50 IU/ml, about 100 IU/ml, about 200 IU/ml, about 400 IU/ml, about 600 IU/ml, or about 800 IU/ml of a chimeric polypeptide comprising a Factor IX (FIX) polypeptide and an Fc region,

ii) about 11.9 mg/mL of sucrose;

iii) about 23.8 mg/ml of mannitol;

iv) about 3.88 mg/ml of L-histidine; and

v) about 0.10 mg/ml of polysorbate 20 or polysorbate 80; and

vi) about 0.325% (w/v) NaCl.

7 . The kit of claim 1 , wherein the second container comprises a preservative in an amount sufficient to provide antimicrobial activity.

8 . The kit of claim 7 , wherein the preservative is selected from the group consisting of phenol, m-cresol, benzyl alcohol, chlorobutanol, methyl paraben, propylparaben, phenoxyethanol, any other pharmaceutically acceptable preservative, and any combinations thereof.

9 . The vial of claim 5 , wherein the vial is a single-use vial.

10 . The vial of claim 5 , wherein the pharmaceutical composition is a lyophilizate.

11 . The syringe of claim 6 , wherein the pharmaceutical composition is a liquid pharmaceutical composition.

12 . The pharmaceutical kit of claim 1 , wherein the lyophilizate comprises about 250 IU, about 500 IU, about 1000 IU, about 2000 IU, about 3000 IU, or about 4000 IU of the chimeric polypeptide.

13 . The pharmaceutical kit of claim 1 , wherein the polysorbate 20 or polysorbate 80 is polysorbate 20.

14 . The pharmaceutical kit of claim 1 , wherein the polysorbate 20 or polysorbate 80 is polysorbate 80.

15 . The pharmaceutical kit of claim 13 , wherein the chimeric polypeptide is a human FIX covalently linked to the Fc domain of human immunoglobulin G1.

16 . The vial of claim 5 , wherein the chimeric polypeptide is a human FIX covalently linked to the Fc domain of human immunoglobulin G1.

17 . The syringe of claim 6 , wherein the chimeric polypeptide is a human FIX covalently linked to the Fc domain of human immunoglobulin G1.

18 . The pharmaceutical kit of claim 12 , wherein the lyophilizate comprises 3000 IU of the chimeric polypeptide and the solution comprises 600 IU/ml of the chimeric polypeptide, or wherein the lyophilizate comprises 4000 IU of the chimeric polypeptide and the solution comprises 800 IU/ml of the chimeric polypeptide.

19 . The pharmaceutical kit of claim 1 , wherein the chimeric polypeptide comprises a first subunit comprising an amino acid sequence at least 95% identical to amino acids 1 to 642 of SEQ ID NO:2, and a second subunit comprising an amino acid sequence at least 95% identical to amino acids 1 to 227 of SEQ ID NO:4.

20 . The pharmaceutical kit of claim 19 , wherein the chimeric polypeptide comprises a first subunit comprising amino acids 1 to 642 of SEQ ID NO:2, and a second subunit comprising amino acids 1 to 227 of SEQ ID NO:4.

21 . The pharmaceutical kit of claim 20 , wherein the first subunit and the second subunit are bound together through two disulfide bonds in the hinge region of Fc.

Assignments (2)

Continuity (4)

References Cited (400)