Factor IX polypeptide formulations

Patent metadata

Field	Value
Publication number	US-10588949-B2
Application number	US-201414776125-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Mar 17, 2020
Grant date	Mar 17, 2020

Abstract

The present invention provides formulations comprising a Factor IX-FcRn Binding Partner (FIXFBP) polypeptide, and methods of administering FIXFBP.

First claim

What is claimed is:

1. A pharmaceutical composition comprising:
(a) a rFIXFc polypeptide comprising human FIX fused to a Fc domain of a human antibody;
(b) between about 10 mg/ml and about 20 mg/ml of sucrose;
(c) between about 20 mg/ml and about 40 mg/ml of mannitol
(d) between about 3 mg/ml and about 4 mg/ml of sodium chloride (NaCl);
(e) between about 3 mg/ml and about 6 mg/ml of L-histidine; and
(f) between about 0.08 mg/ml and about 0.2 mg/ml of polysorbate 20 or polysorbate 80.

2. The pharmaceutical composition of claim 1 , comprising about 11.9 mg/ml of sucrose.

3. The pharmaceutical composition of claim 1 , comprising about 16.7 mg/ml of sucrose.

4. The pharmaceutical composition of claim 1 , comprising about 23.8 mg/ml of mannitol.

5. The pharmaceutical composition of claim 1 , comprising about 33.3 mg/ml of mannitol.

6. The pharmaceutical composition of claim 1 , comprising about 3.25 mg/ml of NaCl.

7. The pharmaceutical composition of claim 1 , comprising about 3.88 mg/ml of L-histidine.

8. The pharmaceutical composition of claim 1 , comprising about 5.43 mg/ml of L-histidine.

9. The pharmaceutical composition of claim 1 , comprising 0.10 mg/ml of polysorbate 20 or polysorbate 80.

10. The pharmaceutical composition of claim 1 , comprising about 0.14 mg/ml of polysorbate 20 or polysorbate 80.

11. The pharmaceutical composition of claim 1 , comprising:
(a) about 50 IU/ml of the rFIXFc polypeptide;
(b) about 11.9 mg/ml of sucrose;
(c) about 23.8 mg/ml of mannitol;
(d) about 3.25 mg/ml of NaCl;
(e) about 3.88 mg/ml of L-histidine; and
(f) about 0.10 mg/ml of polysorbate 20 or polysorbate 80.

12. The pharmaceutical composition of claim 1 , comprising:
(a) about 100 IU/ml of the rFIXFc polypeptide;
(b) about 11.9 mg/ml of sucrose;
(c) about 23.8 mg/ml of mannitol;
(d) about 3.25 mg/ml of NaCl;
(e) about 3.88 mg/ml of L-histidine; and
(f) about 0.10 mg/ml of polysorbate 20 or polysorbate 80.

13. The pharmaceutical composition of claim 1 , comprising:
(a) about 200 IU/ml of the rFIXFc polypeptide;
(b) about 11.9 mg/ml of sucrose;
(c) about 23.8 mg/ml of mannitol;
(d) about 3.25 mg/ml of NaCl;
(e) about 3.88 mg/ml of L-histidine; and
(f) about 0.10 mg/ml of polysorbate 20 or polysorbate 80.

14. The pharmaceutical composition of claim 1 , comprising:
(a) about 400 IU/ml of the rFIXFc polypeptide;
(b) about 11.9 mg/ml of sucrose;
(c) about 23.8 mg/ml of mannitol;
(d) about 3.25 mg/ml of NaCl;
(e) about 3.88 mg/ml of L-histidine; and
(f) about 0.10 mg/ml of polysorbate 20 or polysorbate 80.

15. The pharmaceutical composition of claim 1 , comprising:
(a) about 600 IU/ml of the rFIXFc polypeptide;
(b) about 16.7 mg/ml of sucrose;
(c) about 33.3 mg/ml of mannitol;
(d) about 3.25 mg/ml of NaCl;
(e) about 5.43 mg/ml of L-histidine; and
(f) about 0.14 mg/ml of polysorbate 20 or polysorbate 80.

16. A pharmaceutical kit comprising:
(a) a first container comprising a lyophilized powder, where the powder comprises
(i) about 200 IU to about 4000 IU of a rFIXFc polypeptide comprising human Factor IX fused to a Fc domain of a human antibody;
(ii) about 59.5 mg or about 83.3 mg of sucrose;
(iii) about 119 mg or about 167 mg of mannitol;
(iv) about 19.4 mg or about 27.2 mg of L-histidine; and
(v) about 0.50 mg or about 0.7 mg of polysorbate 20 or polysorbate 80; and

(b) a second container comprising 0.325% (w/v) NaCl to be combined with the lyophilized powder of the first container.

17. A pharmaceutical composition comprising:
(a) between about 25 IU/ml and about 700 IU/ml of a rFIXFc polypeptide comprising human Factor IX fused to a Fc domain of a human antibody;
(b) between about 10 mg/ml and about 20 mg/ml of sucrose;
(c) between about 20 mg/ml and about 40 mg/ml of mannitol;
(d) between about 3 mg/ml and about 4 mg/ml of NaCl;
(e) between about 3 mg/ml and about 6 mg/ml of L-histidine; and
(f) between about 0.08 mg/ml and about 0.15 mg/ml of polysorbate-20 or polysorbate-80.

18. The pharmaceutical composition of claim 17 , comprising:
(a) about 50 IU/ml, about 100 IU/ml, about 200 IU/ml, or about 400 IU/ml of the rFIXFc polypeptide;
(b) about 11.9 mg/ml of sucrose;
(c) about 23.8 mg/ml of mannitol;
(d) about 3.25 mg/ml of NaCl;
(e) about 3.88 mg/ml of L-histidine; and
(f) about 0.10 mg/ml of polysorbate-20 or polysorbate-80.

19. The pharmaceutical composition of claim 17 , comprising:
(a) about 600 IU/ml of the rFIXFc polypeptide;
(b) about 16.7 mg/ml of sucrose;
(c) about 33.3 mg/ml of mannitol;
(d) about 3.25 mg/ml of NaCl;
(e) about 5.43 mg/ml of L-histidine; and
(f) about 0.14 mg/ml of polysorbate-20 or polysorbate-80.

20. The pharmaceutical composition of claim 1 , which is a liquid formulation.

21. A vial comprising the pharmaceutical composition of claim 20 .

22. The pharmaceutical kit of claim 16 , wherein the rFIXFc polypeptide comprises a first subunit comprising an amino acid sequence at least 90% identical to amino acids 1 to 642 of SEQ ID NO:2, and a second subunit comprising an amino acid sequence at least 90% identical to amino acids 1 to 227 of SEQ ID NO:4.

23. The pharmaceutical kit of claim 16 , wherein the rFIXFc polypeptide is a rFIXFc 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.

24. The pharmaceutical kit of claim 22 , wherein the powder comprises
(i) about 250 IU of the rFIXFc polypeptide,
(ii) about 59.5 mg of sucrose;
(iii) about 119 mg of mannitol;
(iv) about 19.4 mg of L-histidine; and
(v) about 0.50 mg of polysorbate 20 or polysorbate 80.

25. The pharmaceutical kit of claim 22 , wherein the powder comprises
(i) about 500 IU of the rFIXFc polypeptide,
(ii) about 59.5 mg of sucrose;
(iii) about 119 mg of mannitol;
(iv) about 19.4 mg of L-histidine; and
(v) about 0.50 mg of polysorbate 20 or polysorbate 80.

26. The pharmaceutical kit of claim 22 , wherein the powder comprises
(i) about 1000 IU of the rFIXFc polypeptide,
(ii) about 59.5 mg of sucrose;
(iii) about 119 mg of mannitol;
(iv) about 19.4 mg of L-histidine; and
(v) about 0.50 mg of polysorbate 20 or polysorbate 80.

27. The pharmaceutical kit of claim 22 , wherein the powder comprises
(i) about 2000 IU of the rFIXFc polypeptide,
(ii) about 59.5 mg of sucrose;
(iii) about 119 mg of mannitol;
(iv) about 19.4 mg of L-histidine; and
(v) about 0.50 mg of polysorbate 20 or polysorbate 80.

28. The pharmaceutical kit of claim 22 , wherein the powder comprises
(i) about 3000 IU of the rFIXFc polypeptide,
(ii) about 83.3 mg of sucrose;
(iii) about 167 mg of mannitol;
(iv) about 27.2 mg of L-histidine; and
(v) about 0.7 mg of polysorbate 20 or polysorbate 80.

29. The pharmaceutical composition of claim 16 , wherein the rFIXFc polypeptide comprises a first subunit comprising an amino acid sequence at least 90% identical to amino acids 1 to 642 of SEQ ID NO:2, and a second subunit comprising an amino acid sequence at least 90% identical to amino acids 1 to 227 of SEQ ID NO:4.

30. The pharmaceutical composition of claim 16 , wherein the rFIXFc 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 N

Assignees

• Bioverativ Therapeutics Inc

Inventors

• Brader Mark

Classifications

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title