Methods for treating nasal polyposis by administering an IL-4R antagonist

Patent metadata

Field	Value
Publication number	US-10059771-B2
Application number	US-201414310419-A
Country	US
Kind code	B2
Filing date	Jun 20, 2014
Priority date	Jun 21, 2013
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

Abstract

The present invention provides methods for treating nasal polyposis. The methods include administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist such as an anti-IL-4R antibody or antigen binding fragment thereof.

First claim

What is claimed is:

1. A method for treating nasal polyposis, the method comprising administering to a subject having nasal polyposis characterized by the presence of one or more polyps in a nasal cavity, a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that specifically binds an interleukin-4 receptor (IL-4R), wherein the antibody or antigen-binding fragment thereof comprises three light chain complementarity determining region (CDR) sequences of SEQ ID NOs:6, 7 and 8, and three light chain complementarity determining region (CDR) sequences of SEQ ID NOs:3, 4 and 5, thereby treating nasal polyposis in the subject.

2. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID NO:1 and a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO:2.

3. The method of claim 1 , wherein the subject exhibits one or more symptoms associated with nasal polyposis.

4. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is administered at a dose of 0.1 mg to 600 mg.

5. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is administered at a dose of 100 mg to 400 mg.

6. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is administered at a dose of 300 mg.

7. The method of claim 1 , wherein
the pharmaceutical composition is administered to the subject systemically.

8. The method of claim 1 , the pharmaceutical composition is administered to the subject locally.

9. The method of claim 1 , the pharmaceutical composition is administered to the subject subcutaneously, intravenously or intranasally.

10. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is administered to the subject subcutaneously at a dose of about 300 mg.

11. The method of claim 1 , wherein a second therapeutic agent is administered to the subject
before, after or concurrent with the pharmaceutical composition.

12. The method of claim 11 , wherein the second therapeutic agent is selected from the group consisting of an IgE inhibitor, an antibiotic agent, and an anti-fungal agent.

13. The method of claim 11 , wherein the second therapeutic agent comprises an intranasal corticosteroid.

14. The method of claim 13 , wherein the intranasal corticosteroid is mometasone furoate nasal spray (MFNS).

15. The method of claim 11 , wherein the second therapeutic agent comprises an inhaled corticosteroid.

16. The method of claim 15 , wherein the inhaled corticosteroid is fluticasone or budesonide.

17. The method of claim 11 , wherein the second therapeutic agent comprises a long-acting beta2 agonist.

18. The method of claim 17 , wherein the long-acting beta 2 agonist is salmeterol or formoterol.

19. The method of claim 1 , wherein administration of the antibody or antigen-binding fragment thereof is followed by a decrease in nasal polyp score in the subject.

20. The method of claim 1 , wherein administration of the antibody or antigen-binding fragment thereof is followed by an improvement in one or more nasal polyposis-associated parameters selected from the group consisting of:
a) 22-item SinoNasal Outcome Test (SNOT-22) score;
b) Nasal Symptom Score;
c) number of nocturnal awakenings;
d) five-item Asthma Control Questionnaire (ACQ5) score;
e) Nasal Peak Inspiratory Flow (NPIF);
f) University of Pennsylvania Smell Identification Test (UPSIT);
g) Lund-McKay Score;
h) three-dimensional volumetric measurement of the maxillary sinus; and
i) subject-assessed nasal congestion/obstruction score.

21. The method of claim 1 , wherein the method treats bilateral nasal polyposis.

22. The method of claim 11 , wherein the method treats moderate-to-severe bilateral nasal polyposis.

23. A method for treating nasal polyposis, said method comprising: sequentially administering to a subject having nasal polyposis characterized by the presence of one or more polyps in a nasal cavity, a single initial dose of a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that specifically binds an interleukin-4 receptor (IL-4R), followed by one or more secondary doses of the antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises three light chain complementarity determining region (CDR) sequences of SEQ ID NOs:6, 7 and 8, and three heavy chain complementarity determining region (CDR) sequences of SEQ ID NOs:3, 4 and 5, thereby treating nasal polyposis in the subject.

24. The method of claim 23 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID NO:1 and a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO:2.

25. The method of claim 23 , wherein the subject exhibits one or more symptoms associated with nasal polyposis.

26. The method of claim 25 , wherein the subject further has one or more of asthma, aspirin hypersensitivity, or non-steroidal anti-inflammatory drug (NSAID) hypersensitivity.

27. The method of claim 23 , wherein
the initial dose and the one or more secondary doses each comprise 50 mg to 600 mg of the antibody or antigen-binding fragment thereof.

28. The method of claim 23 , wherein the initial dose and the one or more secondary doses each comprise 100 mg to 400 mg of the antibody or antigen-binding fragment thereof.

29. The method of claim 23 , wherein the initial dose and the one or more secondary doses each comprise 300 mg of the antibody or antigen-binding fragment thereof.

30. The method of claim 23 , wherein
the initial dose comprises a first amount of the antibody or antigen-binding fragment thereof, and the one or more secondary doses each comprise a second amount of the antibody or antigen-binding fragment thereof.

31. The method of claim 23 , wherein the initial dose and the one or more secondary doses each comprise the same amount of the antibody or antigen-binding fragment thereof.

32. The method of claim 23 , wherein the initial dose comprises a first amount of the antibody or antigen-binding fragment thereof, and the one or more secondary doses each comprise a second amount of the antibody or antigen-binding fragment thereof, wherein the first amount of the antibody or antigen-binding fragment thereof is 1.5×, 2×, 2.5×, 3×, 3.5× or 5× the second amount of antibody or antigen-binding fragment thereof.

33. The method of claim 23 , wherein each secondary dose is administered 1 to 15 weeks after the immediately preceding dose.

34. The method of claim 23 , wherein at least 3 secondary doses of the antibody or antigen-binding fragment thereof are administered to the subject, and wherein each secondary dose is administered one week after the immediately preceding dose.

35. The method of claim 23 , wherein at least 3 secondary doses of the antibody or antigen-binding fragment thereof are administered to the subject, and wherein each secondary dose is administered two weeks after the immediately preceding dose.

36. The method of claim 23 , wherein at least 3 sec

Assignees

• Sanofi Biotechnology
• Regeneron Pharma

Inventors

• Mannent Leda
• Pirozzi Gianluca
• Radin Allen
• Gandhi Namita A
• Evans Robert

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P11/02

  Nasal agents, e.g. decongestants · CPC title