Claims for Patent: 10,066,017

Summary for Patent: 10,066,017

Title:	Methods for treating chronic sinusitis with nasal polyps by administering an IL-4R antagonist
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.
Inventor(s):	Mannent; Leda (Paris, FR), Pirozzi; Gianluca (Bridgewater, NJ), Swanson; Brian (Bridgewater, NJ), Radin; Allen (New York, NY), Gandhi; Namita A. (New York, NY), Evans; Robert (New York, NY), Hamilton; Jennifer (Hopewell Junction, NY)
Assignee:	SANOFI BIOTECHNOLOGY (Paris, FR) REGENERON PHARMACEUTICALS, INC (Tarrytown, NY)
Application Number:	14/940,431
Patent Claims:	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 treating CSwNP in the subject. 21. The method of claim 20, wherein the antibody or antigen binding fragment thereof is administered in an initial dose of between about 400 mg and about 600 mg, and in one or more maintenance doses of between about 200 mg and about 300 mg each. 22. A method for treating chronic sinusitis with bilateral nasal polyps in a subject in need thereof, wherein the subject has persistent signs and symptoms of bilateral nasal polyposis despite treatment with INCS, 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 doses of INCS, such that one or more symptoms of chronic sinusitis with bilateral nasal polyps is treated in the subject. 23. The method of claim 22, wherein one or more nasal polyposis-associated parameters selected from the group consisting of nasal congestion/obstructions (NC) severity, endoscopic nasal polyp score (NPS), computed tomography (CT) scan opacification of the sinuses, total symptoms score (TSS), sinonasal outcome test-22 (SNOT-22) score, loss of smell, runny nose, post nasal drip, and NPIF and/or 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, are improved in the subject. 24. The method of claim 22, wherein a need for treatment with oral corticosteroids is reduced and/or a need for nasal polyp surgery is reduced in the subject. 25. The method of claim 22, wherein administration of the antibody or the antigen binding fragment thereof is performed subcutaneously. 26. The method of claim 25, wherein administration of the antibody or the antigen binding fragment thereof is performed with a syringe. 27. The method of claim 26, wherein the syringe is a prefilled syringe or an autoinjector. 28. The method of claim 22, wherein the antibody or antigen binding fragment thereof is administered in one or more doses of about 300 mg. 29. The method of claim 28, wherein the antibody or antigen binding fragment thereof is administered in an initial dose of about 300 mg and one or more secondary doses of about 300 mg once every two weeks. 30. The method of claim 22, wherein the light chain CDR sequences are set forth in SEQ ID NOs: 6, 7, and 8, and the heavy chain CDR sequences are set forth in SEQ ID NOs: 3, 4 and 5. 31. The method of claim 22, wherein the antibody or antigen binding fragment thereof comprises an HCVR having the amino acid sequence of SEQ ID NO: 1, and an LCVR having the amino acid sequence of SEQ ID NO: 2. 32. The method of claim 22, wherein the antibody comprises a heavy chain sequence of SEQ ID NO:9 and a light chain sequence of SEQ ID NO:10. 33. The method of claim 22, wherein the antibody comprises dupilumab or an antigen-binding fragment thereof.

Details for Patent 10,066,017

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	03/28/2017		2034-11-14
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	10/19/2018		2034-11-14
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	06/18/2020		2034-11-14
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	06/14/2021		2034-11-14