Methods for treating chronic sinusitis with nasal polyps by administering an IL-4R antagonist

Patent metadata

Field	Value
Publication number	US-10066017-B2
Application number	US-201514940431-A
Country	US
Kind code	B2
Filing date	Nov 13, 2015
Priority date	Nov 14, 2014
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

Abstract

The present invention provides methods for decreasing a nasal polyp score in a subject. 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:

1. A method for treating chronic sinusitis with nasal polyps (CSwNP) in a subject in need thereof comprising
administering to the subject 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 heavy chain and light chain CDR sequences from the heavy chain variable region (HCVR) and light chain variable region (LCVR) sequence pair of SEQ ID NOs:1 and 2, and
administering to the subject one or more maintenance doses of intranasal corticosteroid (INCS), thereby treating CSwNP in the subject.

2. The method of claim 1 , wherein the subject has a total of at least 5 nasal polyps, with two or more nasal polyps present in each nostril prior to the administering steps.

3. The method of claim 1 , wherein the antibody or antigen binding fragment thereof is administered in an initial dose of between about 200 mg and about 600 mg, in one or more subsequent doses of between about 200 mg and about 400 mg each, and wherein the one or more subsequent doses are administered once every seven days or once every two weeks.

4. The method of claim 1 , wherein the antibody or antigen binding fragment thereof comprises light chain CDR sequences of SEQ ID NOs: 6, 7 and 8, and heavy chain CDR sequences of SEQ ID NOs: 3, 4 and 5.

5. The method of claim 1 , wherein the administering steps are followed by an improvement in one or more nasal polyposis-associated parameters selected from the group consisting of loss of smell, runny nose, post nasal drip, and nasal peak inspiratory flow (NPIF) that occur in the day (AM), at night (PM) or both in the AM and in the PM, and/or an improvement in one or more chronic sinusitis-associated parameters selected from the group consisting of nasal congestion, decreased or lost sense of smell, anterior nasal discharge, posterior nasal discharge, facial pain, and headache.

6. The method of claim 1 , wherein the antibody or antigen binding fragment thereof is dupilumab or an antigen binding fragment thereof.

7. A method for treating CSwNP in a subject in need thereof comprising
administering to the subject a loading dose of about 400 to about 600 mg of an antibody or antigen binding fragment thereof that specifically binds an IL-4R, wherein the antibody or antigen binding fragment thereof comprises heavy chain and light chain CDR sequences from the HCVR and LCVR sequence pair of SEQ ID NOs:1 and 2,
administering to the subject one or more maintenance doses of about 200 to about 300 mg each of the antibody or antigen binding fragment thereof, and
administering to the subject one or more doses of INCS, thereby treating CSwNP in the subject.

8. The method of claim 7 , wherein the subject has a total of at least 5 nasal polyps, with two or more nasal polyps present in each nostril prior to the administering steps.

9. The method of claim 7 , wherein the one or more maintenance doses are about 300 mg each, and the one or more maintenance doses are administered once every seven days or once every two weeks.

10. The method of claim 7 , wherein the antibody or antigen binding fragment thereof comprises light chain CDR sequences of SEQ ID NOs: 6, 7 and 8, and heavy chain CDR sequences of SEQ ID NOs: 3, 4 and 5.

11. The method of claim 7 , wherein the administering steps are followed by an improvement in one or more nasal polyposis-associated parameters selected from the group consisting of loss of smell, runny nose, post nasal drip, and NPIF that occur in the AM, in the PM or both in the AM and in the PM, and/or an improvement in one or more chronic sinusitis-associated parameters selected from the group consisting of nasal congestion, decreased or lost sense of smell, anterior nasal discharge, posterior nasal discharge, facial pain, and headache.

12. A method for treating CSwNP in a subject in need thereof comprising
administering to the subject one or more maintenance doses of an INCS,
administering to the subject a loading dose of about 400 to about 600 mg of an antibody or antigen binding fragment thereof that specifically binds an IL-4R, wherein the antibody or antigen binding fragment thereof comprises heavy chain and light chain CDR sequences from the HCVR and LCVR sequence pair of SEQ ID NOs:1 and 2, and
administering to the subject one or more maintenance doses of about 200 to about 300 mg each of the antibody or antigen binding fragment thereof,
wherein the INCS is administered for the duration of administration of the antibody or antigen binding fragment thereof, thereby treating CSwNP in the subject.

13. The method of claim 12 , wherein the subject has a total of at least 5 nasal polyps, with two or more nasal polyps present in each nostril prior to the administering steps.

14. The method of claim 12 , wherein the loading dose is about 300 mg and the one or more maintenance doses are about 300 mg each.

15. The method of claim 12 , wherein the antibody or antigen binding fragment thereof comprises light chain CDR sequences of SEQ ID NOs: 6, 7 and 8, and heavy chain CDR sequences of SEQ ID NOs: 3, 4 and 5.

16. The method of claim 12 , wherein the administering steps are followed by an improvement in one or more nasal polyposis-associated parameters selected from the group consisting of loss of smell, runny nose, post nasal drip, and NPIF that occur in the AM, in the PM or both in the AM and in the PM, and/or an improvement in one or more chronic sinusitis-associated parameters selected from the group consisting of nasal congestion, decreased or lost sense of smell, anterior nasal discharge, posterior nasal discharge, facial pain, and headache.

17. The method of claim 12 , wherein the one or more maintenance doses are administered once every seven days or once every two weeks.

18. The method of claim 12 , wherein the INCS is mometasone furoate nasal spray (MFNS).

19. A method for treating CSwNP in a subject in need thereof comprising
administering to the subject one or more maintenance doses of an INCS,
administering to the subject a loading dose of about 400 to about 600 mg of an antibody or antigen binding fragment thereof that specifically binds an IL-4R, wherein the antibody or antigen binding fragment thereof comprises heavy chain and light chain CDR sequences from the HCVR and LCVR sequence pair of SEQ ID NOs:1 and 2, and
administering to the subject one or more maintenance doses of about 200 to about 300 mg each of the antibody or antigen binding fragment thereof,
wherein the INCS is administered for the duration of administration of the antibody or antigen binding fragment thereof, thereby treating CSwNP in the subject, and improving one or more additional nasal polyposis-associated parameters of the subject selected from the group consisting of loss of smell, runny nose, post nasal drip, and NPIF, and/or improving one or more chronic sinusitis-associated parameters selected from the group consisting of nasal congestion, decreased or lost sense of smell, anterior nasal discharge, posterior nasal discharge, facial pain, and headache.

20. A method for treating CSwNP in a subject in need thereof comprising administering to the subject a pharmaceutical composition comprising an antibody or antigen binding fragment thereof that specifically binds IL-4R, wherein the antibody or antigen binding fragment thereof comprises the HCVR and LCVR sequence pair of SEQ ID NOs: 1 and 2, and administering to the subject one or more doses of INCS, thereby

Assignees

• Sanofi Biotechnology
• Regeneron Pharma
• Regeneron Pharma

Inventors

• Mannent Leda
• Pirozzi Gianluca
• Swanson Brian
• Radin Allen
• Gandhi Namita A
• Evans Robert
• Hamilton Jennifer

Classifications

• A61P37/08

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P11/02

  Nasal agents, e.g. decongestants · CPC title

• A61P11/06

  Antiasthmatics · CPC title