Methods of using FIX polypeptides

Patent metadata

Field	Value
Publication number	US-11225650-B2
Application number	US-201715619196-A
Country	US
Kind code	B2
Filing date	Jun 9, 2017
Priority date	Sep 25, 2012
Publication date	Jan 18, 2022
Grant date	Jan 18, 2022

Abstract

The present invention provides methods of administering long-acting Factor IX; methods of administering long-acting, chimeric and hybrid polypeptides comprising Factor IX; and methods of producing such chimeric and hybrid polypeptides using cells.

First claim

What is claimed is:

1. A method of reducing or decreasing an annualized bleeding rate in a human subject with hemophilia B, comprising administering to the subject multiple doses of a pharmaceutical composition comprising:
(a) a chimeric Factor IX(FIX) polypeptide comprising human FIX and a first Fc region;
(b) sucrose;
(c) mannitol; and
(d) polysorbate 20 or polysorbate 80 ,

wherein each of the multiple doses comprises 10 IU/kg to 200 IU/kg of the chimeric FIX polypeptide wherein each of the multiple doses is administered at a dosing interval of about 7 days to about 14 days, wherein the annualized bleeding rate of the bleeding episodes is reduced to less than 5; and wherein the bleeding episodes are spontaneous bleeding episodes.

2. The method of claim 1 , wherein each of the multiple doses of the chimeric FIX polypeptide is 50 IU/kg to 100 IU/kg.

3. The method of claim 1 , wherein each of the multiple doses is about 50 IU/kg or about 100 IU/kg and the dosing interval is about 10 days to about 14 days.

4. The method of claim 1 , wherein each of the multiple doses is for individualized interval prophylaxis of one or more spontaneous bleeding episodes.

5. The method of claim 4 , wherein the annualized bleeding rate of the one or more spontaneous bleeding episodes is reduced to less than 4.

6. The method of claim 1 , wherein the dosing interval is every 7 days to 14 days.

7. The method of claim 1 , wherein each of the multiple doses is about 25 IU/kg to about 50 IU/kg and the dosing interval is about 7 days.

8. The method of claim 1 , wherein the chimeric FIX polypeptide further comprises a second Fc region.

9. The method of claim 1 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 1.

10. The method of claim 1 , wherein each of the multiple doses is 25 IU/kg to 50 IU/kg.

11. The method of claim 1 , wherein the chimeric FIX polypeptide comprises a first subunit comprising an amino acid sequence at least 99% identical to SEQ ID NO: 2, and a second subunit comprising an amino acid sequence at least 99% identical to SEQ ID NO: 4.

12. The method of claim 1 , wherein the chimeric FIX polypeptide comprises a first subunit comprising amino acids 1 to 641 of SEQ ID NO: 2, and a second subunit comprising amino acids 1 to 226 of SEQ ID NO: 4.

13. The method of claim 12 , wherein each of the multiple doses is about 50 IU/kg and the dosing interval is about 7 days.

14. The method of claim 12 , wherein each of the multiple doses is about 100 IU/kg and the dosing interval is about 10 days.

15. The method of claim 3 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 4.

16. The method of claim 3 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 3.

17. The method of claim 3 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 2.

18. The method of claim 7 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 4.

19. The method of claim 7 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 3.

20. The method of claim 7 , wherein the annualized bleeding rate of the spontaneous bleeding episodes is reduced to less than 2.

Assignees

• Bioverativ Therapeutics Inc

Inventors

• Pierce Glenn
• Truex Samantha
• Peters Robert T
• Jiang Haiyan
• Brader Mark

Classifications

• A61P7/04

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

• C12Y304/21022

  Coagulation factor IXa (3.4.21.22) · CPC title

• C07K14/745

  Blood coagulation or fibrinolysis factors · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title