Claims for Patent: 10,059,771

Summary for Patent: 10,059,771

Title:	Methods for treating nasal polyposis by administering an IL-4R antagonist
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.
Inventor(s):	Mannent; Leda (Paris, FR), Pirozzi; Gianluca (Bridgewater, NJ), Radin; Allen (Tarrytown, NY), Gandhi; Namita A. (Tarrytown, NY), Evans; Robert (Tarrytown, NY)
Assignee:	SANOFI BIOTECHNOLOGY (Paris, FR) REGENERON PHARMACEUTICALS, INC. (Tarrytown, NY)
Application Number:	14/310,419
Patent Claims:	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.sub.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.times., 2.times., 2.5.times., 3.times., 3.5.times. or 5.times. 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 secondary doses of the antibody or antigen-binding fragment thereof are administered to the subject, and wherein each secondary dose is administered four weeks after the immediately preceding dose. 37. The method of claim 23, wherein the initial dose and the secondary doses are administered by the same or different routes of administration. 38. The method of claim 23, wherein the initial dose and the secondary doses are administered subcutaneously, intravenously, or intranasally. 39. The method of claim 23, wherein a second therapeutic agent is administered to the subject before, after or concurrent with the initial dose or the one or more secondary doses. 40. The method of claim 23, wherein a second therapeutic agent selected from the group consisting of an IgE inhibitor, an antibiotic agent, an anti-fungal agent, and an intranasal corticosteroid is administered to the subject before, after or concurrent with the initial dose or the one or more secondary doses. 41. The method of claim 40, wherein the intranasal corticosteroid is mometasone furoate nasal spray (MFNS). 42. The method of claim 23, wherein a second therapeutic agent comprises an inhaled corticosteroid administered to the subject before, after or concurrent with the initial dose or the one or more secondary doses. 43. The method of claim 42, wherein the inhaled corticosteroid is fluticasone or budesonide. 44. The method of claim 23, wherein a second therapeutic agent comprises a long-acting beta2 agonist administered to the subject before, after or concurrent with the initial dose or the one or more secondary doses. 45. The method of claim 44, wherein the long-acting beta.sub.2 agonist is salmeterol or formoterol. 46. The method of claim 23, wherein administration of the antibody or antigen-binding fragment thereof is followed by a decrease in nasal polyp score in the subject. 47. The method of claim 23, wherein administration of the initial dose and the one or more secondary doses 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. 48. The method of claim 23, wherein the method treats bilateral nasal polyposis. 49. The method of claim 39, wherein the method treats moderate-to-severe bilateral nasal polyposis. 50. A method for treating nasal polyposis, the method comprising: a) selecting a patient having nasal polyposis characterized by the presence of one or more polyps in a nasal cavity, and further based on one or more of the following standards: i) a minimum bilateral nasal polyp score of 5; ii) an elevated level of one or more genes selected from the group consisting of: thymus and activation-regulated chemokine (TARC), eotaxin-3, periostin, carcinoembryonic antigen (CEA), and YKL-40; or iii) an elevated level of blood eosinophils or sputum eosinophils; and b) administering to the selected patient two or more doses of 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 (CDR) sequences of SEQ ID NOs:6, 7 and 8, and three heavy chain complementarity determining (CDR) sequences of SEQ ID NOs:3, 4 and 5. 51. The method of claim 50, wherein the patient's nasal polyp score is reduced. 52. The method of claim 50, wherein level of one or more genes selected from the group consisting of thymus and activation-regulated chemokine (TARC), eotaxin-3, periostin, carcinoembryonic antigen (CEA), and YKL-40 is reduced when compared to the pre-administration level. 53. The method of claim 50, wherein the level of blood eosinophils or sputum eosinophils is reduced when compared to the pre-administration level. 54. The method of claim 50, wherein the method treats bilateral nasal polyposis. 55. A method for treating bilateral nasal polyposis, the method comprising administering to a subject having bilateral 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 the three light chain complementarity determining region (CDR) sequences set forth in SEQ ID NOs:6, 7, and 8, and three heavy chain complementarity determining region (CDR) sequences set forth in SEQ ID NOs:3, 4 and 5, thereby treating bilateral nasal polyposis in the subject. 56. The method of claim 55, wherein the antibody is dupilumab. 57. A method for treating nasal polyposis, the method comprising administering to an adult subject having nasal polyposis that is characterized by the presence of one or more polyps in a nasal cavity and is inadequately controlled with intranasal corticosteroids (INCS), a pharmaceutical composition comprising an antibody that specifically binds an interleukin-4 receptor (IL-4R), wherein the antibody comprises the heavy chain variable region (HCVR) set forth in SEQ ID NO: 1 and the light chain variable region (LCVR) set forth in SEQ ID NO: 2, and wherein the antibody is dupilumab, and wherein the pharmaceutical composition is administered as an add-on treatment at a dose of 300 mg every two weeks, thereby treating nasal polyposis in the adult subject.

Details for Patent 10,059,771

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	03/28/2017		2034-05-07
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	10/19/2018		2034-05-07
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	06/18/2020		2034-05-07
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	06/14/2021		2034-05-07
Regeneron Pharmaceuticals, Inc.	DUPIXENT	dupilumab	Injection	761055	10/20/2021		2034-05-07