MÉTODOS PARA TRATAR DOENÇA PULMONAR OBSTRUTIVA CRÔNICA (DPOC) ADMINISTRANDO UM ANTAGONISTA DE IL-4R

Abstract

Methods for treating or preventing chronic obstructive pulmonary disease (COPD) in a subject are provided. Methods comprising 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, are provided.

Claims

1. A method for treating an individual with chronic obstructive pulmonary disease (COPD), characterized by the fact that it comprises administering to the individual an antibody or an antigen-binding fragment thereof that binds specifically to the interleukin-4 receptor (IL-4R).

2. A method for treating an individual with moderate to severe chronic obstructive pulmonary disease (COPD), characterized by the fact that it comprises administering to the individual an antibody or an antigen-binding fragment thereof that binds specifically to the interleukin-4 receptor (IL-4R).

3. A method for treating an individual with chronic obstructive pulmonary disease (COPD) with Type 2 inflammation, characterized by the fact that it comprises administering to the individual an antibody or an antigen-binding fragment thereof that binds specifically to the interleukin-4 receptor (IL-4R). 4.Method for treating an individual with moderate to severe chronic obstructive pulmonary disease (COPD) with Type 2 inflammation, characterized in that it comprises administering to the individual an antibody or an antigen-binding fragment thereof that specifically binds to the interleukin-4 receptor (IL-4R).

5. Method for treating an individual with chronic obstructive pulmonary disease (COPD) not adequately controlled with background therapy, characterized in that it comprises administering to the individual an antibody or an antigen-binding fragment thereof that specifically binds to the interleukin-4 receptor (IL-4R).

6. Method for treating an individual with chronic obstructive pulmonary disease (COPD) with closed airway disease (UAD), characterized in that it comprises administering to the individual Petition 870250084888, dated 09 / 19 / 2025, p.265 / 455 2 / 15 an antibody or an antigen-binding fragment thereof that specifically binds to the interleukin-4 receptor (IL-4R).

7. Method for treating an individual with chronic obstructive pulmonary disease (COPD), wherein the COPD is comorbid with at least one Type 2 inflammatory disease, characterized in that it comprises administering to the individual an antibody or an antigen-binding fragment thereof that specifically binds to the interleukin-4 receptor (IL-4R).

8. Method, according to any one of claims 1 to 7, characterized in that the individual has a baseline blood eosinophil count of >300 cells / l, >350 cells / l, >400 cells / l, >450 cells / l or >500 cells / l.

9. Method, according to any one of claims 1 to 7, characterized in that the individual has a baseline blood eosinophil count below 300 cells / µL. 10.

10. A method according to any one of claims 1 to 9, characterized in that the individual has a baseline fractional exhaled nitric oxide (FeNO) level of > 20 ppb, > 25 ppb, > 30 ppb, > 35 ppb, or > 40 ppb.

11. A method according to any one of claims 1 to 9, characterized in that the individual has a baseline fractional exhaled nitric oxide (FeNO) level below 20 ppb.

12. A method according to any one of claims 1 to 11, characterized in that the individual has a baseline immunoglobulin E (IgE) level > 100 kU / L.

13. A method according to any one of claims 1 to 11, characterized in that the individual has a baseline immunoglobulin E (IgE) level below 100 kU / L. Petition 870250084888, dated 09 / 19 / 2025, page 266 / 455 3 / 15 14. Method, according to any of claims 1 to 13, characterized in that COPD is oxygen-dependent COPD. 15.Method, according to any one of claims 1 to 14, characterized in that the individual has chronic bronchitis.

16. Method, according to any one of claims 1 to 15, characterized in that the individual has emphysema.

17. Method, according to any one of claims 1 to 16, characterized in that the individual is a smoker.

18. Method, according to any one of claims 1 to 16, characterized in that the individual is a former smoker.

19. Method, according to any one of claims 1 to 18, wherein the method is characterized in that it additionally comprises a basic therapy in addition to the antibody or an antigen-binding fragment thereof. 20.Method according to claim 19, characterized in that the baseline therapy comprises an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), a leukotriene receptor antagonist (LTRA), a long-acting muscarinic antagonist (LAMA), a methylxanthine, a phosphodiesterase inhibitor which is optionally roflumilast or theophylline or a mixture thereof.

21. Method according to claim 20, characterized in that the baseline therapy comprises a LABA, a LAMA and an ICS, and optionally COPD is not controlled at baseline despite baseline therapy alone.

22. Method according to any one of claims 20 and 21, characterized in that the baseline therapy with Petition 870250084888, dated 19 / 09 / 2025, p. 267 / 455 4 / 15 involves a high dose of ICS.

23. Method, according to any of claims 20 and 21, characterized in that the basic therapy comprises a non-high dose of ICS. 24.Method according to claim 20, characterized in that the baseline therapy comprises a LABA and a LAMA, and optionally COPD is not controlled at baseline despite baseline therapy alone.

25. Method according to any one of claims 19 to 24, characterized in that an inhaled corticosteroid (ICS) is contraindicated in the individual.

26. Method according to any one of claims 19 to 25, characterized in that the baseline therapy comprises roflumilast.

27. Method according to any one of claims 19 to 26, characterized in that the baseline therapy comprises theophylline.

28. Method according to any one of claims 1 to 27, characterized in that one or more parameters associated with COPD are improved in the individual. 29.Method according to claim 28, characterized in that one or more parameters associated with COPD are selected from the group consisting of: (1) annualized rate of moderate or severe acute COPD exacerbations (ACOPD exacerbations); (2) annualized rate of severe AECOPD; (3) time until first moderate or severe COPD episode; (4) forced expiratory volume in 1 second (FEV1) (pre-bronchodilator or post-bronchodilator); Petition 870250084888, dated 09 / 19 / 2025, page 268 / 455 5 / 15 (5) forced vital capacity (FVC); (6) forced expiratory flow (FEF) 25% to 75%; (7) fractionated exhaled nitric oxide (FeNO); (8) Chronic Obstructive Pulmonary Disease Exacerbation Tool (EXACT); (9) St.George (SGRQ); (10) Respiratory Symptom Assessment in COPD (ERS:COPD); (11) Body mass index, airflow obstruction, dyspnea, exercise capacity (BODE); (12) Euro 5-Dimensional Quality of Life Questionnaire (EQ-5D); (13) Modified British Medical Research Council Questionnaire (mMRC); (14) Health-Related Quality of Life Questionnaire (HRQoL); (15) Steroid courses in days (e.g., systemic corticosteroid); (16) Antibiotic courses in days; and (17) Resting respiratory rate, (18) FEVi / FVC ratio, (19) Mucus obstruction, or any combination thereof. 30.A method, according to any one of claims 1 to 29, characterized in that the treatment reduces the level of one or more biomarkers in the individual selected from the group consisting of blood eosinophil count (Eos), fractionated exhaled nitric oxide (FeNO) level, serum immunoglobulin E (IgE) level, eotaxin level (e.g., eotaxin-3), and pulmonary activation-regulated chemokine (PARC) level. Petition 870250084888, dated 09 / 19 / 2025, p. 269 / 455 6 / 15 31. Method, according to any one of claims 1 to 30, characterized in that the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs: 3, 4 and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs: 6, 7 and 8, respectively. 32.A method according to any of the preceding claims, characterized in that the antibody or antigen-binding fragment thereof is administered to the individual as an initial dose followed by one or more secondary doses.

33. A method according to claim 32, characterized in that the initial dose is about 300 mg, and one or more secondary doses are each about 300 mg.

34. A method according to claim 33, characterized in that the secondary doses are administered every two weeks (q2w).

35. A method according to any of the preceding claims, characterized in that the individual is at least 40 years of age. 36.Method, according to any of the preceding claims, characterized in that, prior to the start of treatment, the individual has a baseline Medical Research Council (MRC) Dyspnea Scale Grade score of >2 or a baseline modified Medical Research Council (mMRC) Dyspnea Scale Grade score of >2.

37. Method, according to any of the preceding claims, characterized in that the individual has a history of high risk of exacerbation.

38. Method, according to any of the preceding claims, characterized in that the individual has two or more severe exacerbations annually, leading to hospital admission. 39.A method, according to any of the preceding claims, characterized in that the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) sequence of SEQ ID NO: 1 and a light chain variable region (LCVR) sequence of SEQ ID NO:

2.

40. A method, according to claim 39, characterized in that the antibody is Dupilumab.

41. A method, according to any of the preceding claims, characterized in that the antibody or the antigen-binding fragment thereof is administered using an autoinjector, a needle and syringe, or a pen.

42. A method, according to claim 41, characterized in that the antibody or the antigen-binding fragment thereof is administered using a pre-loaded device. 43.

43. Method, according to any of the preceding claims, characterized in that the antibody or antigen-binding fragment thereof is administered subcutaneously.

44. Method, according to any of the preceding claims, wherein the method is characterized in that it comprises the step of determining the baseline level of a biomarker selected from the group consisting of PARC, eotaxin-3, FeNO (post-bronchodilator), total IgE, fibrinogen and any mixture thereof in the individual.

45. Method for improving one or more symptoms characterized in that it is intended for an individual selected from the group consisting of: Petition 870250084888, dated 19 / 09 / 2025, p. 271 / 455 8 / 15 (1) an individual who has chronic obstructive pulmonary disease (COPD); (2) an individual who has moderate to severe COPD; (3) an individual who has COPD with Type 2 inflammation; (4) an individual who has moderate to severe COPD with Type 2 inflammation; (5) an individual who has COPD that is not adequately controlled on baseline therapy; (6) an individual who has COPD with joined airway disease (UAD); and (7) an individual who has COPD, wherein the COPD is comorbid with at least one Type 2 inflammatory disease, wherein the method comprises administering to the individual an antibody or an antigen-binding fragment thereof that binds specifically to the interleukin-4 receptor (IL-4R).

46. Method for reducing or preventing moderate to severe exacerbations characterized in that it is intended for an individual selected from the group consisting of: (1) an individual who has chronic obstructive pulmonary disease (COPD); (2) an individual who has moderate to severe COPD; (3) an individual who has COPD with Type 2 inflammation; (4) an individual who has moderate to severe COPD with Type 2 inflammation; (5) an individual who has COPD not adequately controlled on baseline therapy; (6) an individual who has COPD with joined airway disease (UAD); and Petition 870250084888, dated 09 / 19 / 2025, page.272 / 455 9 / 15 (7) an individual who has COPD, wherein the COPD is comorbid with at least one Type 2 inflammatory disease, wherein the method comprises administering to the individual an antibody or an antigen-binding fragment thereof that binds specifically to the interleukin-4 receptor (IL-4R). 47.A method for delaying the progression of lung function decline characterized in that it is intended for an individual selected from the group consisting of: (1) an individual who has chronic obstructive pulmonary disease (COPD); (2) an individual who has moderate to severe COPD; (3) an individual who has COPD with Type 2 inflammation; (4) an individual who has moderate to severe COPD with Type 2 inflammation; (5) an individual who has COPD not adequately controlled on baseline therapy; (6) an individual who has COPD with united airway disease (UAD); and (7) an individual who has COPD, wherein the COPD is comorbid with at least one Type 2 inflammatory disease, wherein the method comprises administering to the individual an antibody or an antigen-binding fragment thereof that binds specifically to the interleukin-4 receptor (IL-4R). 48.A method for improving health-related quality of life characterized in that it is intended for an individual selected from the group consisting of: (1) an individual who has chronic obstructive pulmonary disease (COPD); (2) an individual who has moderate to severe COPD; Petition 870250084888, dated 09 / 19 / 2025, page 273 / 455 10 / 15 (3) an individual who has COPD with Type 2 inflammation; (4) an individual who has moderate to severe COPD with Type 2 inflammation; (5) an individual who has COPD that is not adequately controlled on baseline therapy; (6) an individual who has COPD with joined airway disease (UAD); and (7) an individual with COPD, in which COPD is comorbid with at least one Type 2 inflammatory disease, wherein the method comprises administering to the individual an antibody or an antigen-binding fragment thereof that binds specifically to the interleukin-4 receptor (IL-4R). 49.Method for delaying the time to the first moderate or severe exacerbation characterized in that it is intended for an individual selected from a group consisting of: (1) an individual who has chronic obstructive pulmonary disease (COPD); (2) an individual who has moderate to severe COPD; (3) an individual who has COPD with Type 2 inflammation; (4) an individual who has moderate to severe COPD with Type 2 inflammation; (5) an individual who has COPD not adequately controlled on baseline therapy; (6) an individual who has COPD with united airway disease (UAD); and (7) an individual who has COPD, wherein the COPD is comorbid with at least one Type 2 inflammatory disease, wherein the method comprises administering to the individual a Petition 870250084888, dated 19 / 09 / 2025, p. 274 / 455 11 / 15 antibody or an antigen-binding fragment thereof that binds specifically to the interleukin-4 receptor (IL-4R). 50.A method for treating an individual with uncontrolled chronic obstructive pulmonary disease (COPD), characterized in that it comprises administering to the individual an antibody or an antigen-binding fragment thereof that specifically binds to the interleukin-4 receptor (IL-4R).

51. A method according to claim 50, characterized in that the individual is an adult.

52. A method according to claim 50, characterized in that the individual receives triple therapy in addition to the antibody or antigen-binding fragment thereof.

53. A method according to claim 52, characterized in that the triple therapy comprises treatment with an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), and a long-acting muscarinic antagonist (LAMA). 54.Method according to claim 50, characterized in that ICS is contraindicated, and the individual receives dual therapy in addition to the antibody or antigen-binding fragment thereof.

55. Method according to claim 54, characterized in that the dual therapy comprises LABA and LAMA.

56. Method according to any one of claims 50 to 55, characterized in that the antibody or an antigen-binding fragment thereof is an additional treatment.

57. Method according to any one of claims 50 to 55, characterized in that the antibody or an antigen-binding fragment thereof is a maintenance treatment.

58. Method according to any one of claims Petition 870250084888, dated 19 / 09 / 2025, p. 275 / 455 12 / 15 tions 50 to 55, characterized by the fact that the antibody or an antigen-binding fragment thereof is an additional maintenance treatment. 59.Method according to claim 50, characterized in that the individual has a history of COPD exacerbations.

60. Method according to claim 50, characterized in that the individual has an elevated level of a Type 2 inflammation biomarker relative to a control.

61. Method according to claim 60, characterized in that the biomarker is the blood eosinophil count.

62. Method according to any one of claims 50 to 61, characterized in that the individual has a baseline blood eosinophil count of >300 cells / l, >350 cells / l, >400 cells / l, >450 cells / l or >500 cells / l.

63. Method, according to any one of claims 50 to 61, characterized in that the individual has a baseline blood eosinophil count below 300 cells / pl. 64.Method, according to any one of claims 50 to 63, characterized in that the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) sequence of SEQ ID NO: 1 and a light chain variable region (LCVR) sequence of SEQ ID NO:

2.

65. Method, according to claim 64, characterized in that the antibody is Dupilumab.

66. Combination therapy characterized in that it comprises: i) an antibody or an antigen-binding fragment Petition 870250084888, dated 19 / 09 / 2025, p. 276 / 455 13 / 15 of the same which specifically binds to the interleukin-4 receptor (IL4R) and ii) a baseline therapy for COPD, for use in a method to treat uncontrolled chronic obstructive pulmonary disease (COPD) with Type 2 inflammation.

67. Combination therapy, according to claim 66, characterized in that uncontrolled COPD is associated with a history of exacerbations. 68.Combination therapy, according to any one of claims 66 or 67, characterized in that the treatment reduces the individual's dependence on systemic steroids in the baseline therapy for COPD.

69. Combination therapy, according to any one of claims 66 to 68, characterized in that the individual is an adult.

70. Combination therapy, according to any one of claims 66 to 69, characterized in that the individual is a human being.

71. Combination therapy, according to any one of claims 66 to 70, characterized in that the baseline therapy for COPD is triple therapy.

72. Combination therapy, according to claim 71, characterized in that the triple therapy comprises treatment with an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), and a long-acting muscarinic antagonist (LAMA). 73.Combination therapy, according to claim 72, characterized in that ICS is contraindicated and the individual receives dual therapy.

74. Combination therapy, according to claim 73, characterized in that the dual therapy comprises LABA and LAMA.

75. Combination therapy, according to any of claims 66 to 74, characterized in that the individual has a history of COPD exacerbations.

76. Combination therapy, according to any of claims 66 to 75, characterized in that the individual has an elevated level of a Type 2 inflammation biomarker relative to a control.

77. Combination therapy, according to claim 76, characterized in that the biomarker is the blood eosinophil count. 78.Combination therapy according to claim 77, characterized in that the individual has a baseline blood eosinophil count of >300 cells / l, >350 cells / l, >400 cells / l, >450 cells / l or >500 cells / pl.

79. Combination therapy according to claim 78, characterized in that the individual has a baseline blood eosinophil count below 300 cells / pl.

80. Combination therapy according to any one of claims 66 to 79, characterized in that the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) sequence of SEQ ID NO: 1 and a light chain variable region (LCVR) sequence of SEQ ID NO:

2.

81. Combination therapy according to claim 80, characterized in that the antibody is Dupilumab. 82.Combination therapy, according to any one of claims 66 to 81, characterized in that the individual has a fractional exhaled nitric oxide (FeNO) baseline level of > 20 ppb, > 25 ppb, > 30 ppb, > 35 ppb, or > 40 ppb.

83. Combination therapy, according to any one of claims 66 to 82, characterized in that the antibody or antigen-binding fragment thereof is administered to the individual as an initial dose followed by one or more secondary doses.

84. Combination therapy, according to claim 83, characterized in that the initial dose is about 300 mg, and one or more secondary doses are each about 300 mg.

85. Combination therapy, according to claim 84, characterized in that secondary doses are administered every two weeks (q2w).

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