IP Library › Granted Patent US 12,286,481
Granted Patent B2
US 12,286,481 · App. 18/929,510 · Granted Apr 29, 2025

Methods for the treatment of thyroid eye disease

Inventors: David Madden (Mount Kisco, NY); Kathleen Gabriel (Voorhees, NJ); Guido Magni (Basel, CH); Richard Woodward (Phoenixville, PA)
Assignee: Horizon Therapeutics Ireland DAC
C07K16/2863A61K39/3955A61K45/06A61P27/02A61K2039/505A61K2039/545A61K2039/55C07K2317/21C07K2317/92
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Quick Facts
Patent No.
US 12,286,481
App. No.
18/929,510
Granted
Apr 29, 2025
Kind
B2
Abstract

The invention provides a method of reducing the severity of, or treating, thyroid-associated ophthalmopathy (TAO), also known as thyroid eye disease (TED) or Graves' ophthalmopathy or orbitopathy (GO), as well as antibodies, or antigen binding fragments thereof, and pharmaceutical compositions comprising them, useful in the methods.

Claims (38)

1. A method of treating a subject with thyroid eye disease, comprising:

reducing proptosis in the subject with thyroid eye disease by administering to the subject an antibody comprising a heavy chain comprising CDRH1, CDRH2, and CDRH3 and a light chain comprising CDRL1, CDRL2, and CDRL3, as set forth in SEQ ID NOs: 1-6, respectively, wherein the antibody specifically binds and inhibits insulin-like growth factor I receptor,

wherein the antibody is administered at a dosage of about 5 mg/kg to about 10 mg/kg antibody as a first dose, and

wherein the proptosis is reduced by at least 3 mm.

2. The method of claim 1 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8.

3. The method of claim 2 , wherein the antibody is a human monoclonal antibody.

4. The method of claim 3 , wherein the antibody is IgG.

5. The method of claim 4 , wherein the antibody is IgG1.

6. The method of claim 5 , wherein the antibody is teprotumumab.

7. The method of claim 1 , wherein the antibody is administered at a dosage of about 5 mg/kg to about 20 mg/kg in subsequent doses.

8. The method of claim 7 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8.

9. The method of claim 7 , wherein the antibody is administered in the following amounts:

about 10 mg/kg as a first dose; and

about 20 mg/kg in subsequent doses.

10. The method of claim 9 , wherein the antibody is teprotumumab.

11. The method of claim 9 , wherein the subsequent doses are administered every three weeks for at least 21 weeks.

12. The method of claim 11 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8.

13. The method of claim 11 , wherein the antibody is teprotumumab.

14. The method of claim 7 , wherein the subsequent doses are administered every three weeks for at least 21 weeks.

15. The method of claim 1 , wherein the antibody is administered by intravenous infusion.

16. A method of treating a subject with thyroid eye disease, comprising:

reducing proptosis in the subject with thyroid eye disease by administering to the subject a course of intravenous infusions of an antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8, wherein the antibody specifically binds and inhibits insulin-like growth factor I receptor,

wherein the course of intravenous infusions comprises an initial intravenous infusion of the antibody at a dosage of about 5 mg/kg to about 10 mg/kg and subsequent intravenous infusions of the antibody at a dosage of about 5 mg/kg to about 20 mg/kg, and

wherein after administration of the course of intravenous infusions proptosis is reduced by at least 3 mm.

17. The method of claim 16 , wherein the antibody is a human monoclonal antibody.

18. The method of claim 17 , wherein the antibody is IgG.

19. The method of claim 18 , wherein the antibody is IgG1.

20. The method of claim 19 , wherein the antibody is teprotumumab.

21. The method of claim 16 , wherein the intravenous infusions are administered every three weeks.

22. The method of claim 21 , wherein the course of intravenous infusions consists of 8 intravenous infusions.

23. The method of claim 16 , wherein the initial intravenous infusion comprises a dose of about 10 mg/kg of the antibody and the subsequent intravenous infusions comprise a dose of about 20 mg/kg of the antibody.

24. The method of claim 23 , wherein the antibody is teprotumumab.

25. The method of claim 23 , wherein the subsequent intravenous infusions are administered every three weeks.

26. The method of claim 25 , wherein the course of intravenous infusions consists of 8 intravenous infusions.

27. The method of claim 26 , wherein the antibody is teprotumumab.

28. A method of reducing proptosis by at least 2 mm in a subject with thyroid eye disease (TED),

comprising administering to the subject an effective amount of an antibody, comprising a heavy chain comprising CDR1, CDR2 and CDR3 and a light chain comprising CDR1, CDR2 and CDR3, as set forth in SEQ ID NOs: 1-6, respectively, wherein the antibody specifically binds and inhibits insulin-like growth factor I receptor (IGF-IR),

wherein the antibody is administered at a dosage of about 5 mg/kg to about 10 mg/kg antibody as a first dose.

Assignments (2)
CHANGE OF ADDRESS OF ASSIGNEE Recorded Oct 22, 2025
From: HORIZON THERAPEUTICS IRELAND DAC
To: HORIZON THERAPEUTICS IRELAND DAC
Reel/Frame 073156/0404 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 30, 2025
From: MADDEN, DAVID; GABRIEL, KATHLEEN; MAGNI, GUIDO; WOODWARD, RICHARD
To: HORIZON THERAPEUTICS IRELAND DAC
Reel/Frame 070066/0393 →
Continuity (6)
Continuation 17531365 · Nov 19, 2021
Continuation 16256221 · Jan 24, 2019
Provisional Application 62716194 · Aug 8, 2018
Provisional Application 62635342 · Feb 26, 2018
Provisional Application 62621201 · Jan 24, 2018
Related Publication 20250051461A1 · Feb 13, 2025
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