Treatment of chronic rhinosinusitis with Anti-tslp antibody

Abstract

The present disclosure, relates, in general, to methods of treating chronic rhinosinusitis, with or without nasal polyps, using an antibody specific for thymic stromal lymphopoietin (TSLP).

Description

Abstract This disclosure generally relates to a method for treating chronic sinusitis with or without nasal polyps using an antibody specific to thymic stromal lymphopoietin (TSLP).

Claims

WHAT IS CLAIMED:

1. A method for treating chronic rhinosinusitis in a subject comprising selecting a subject in need of treatment for chronic rhinosinusitis, and administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant to the subject, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising:

1. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

2. A method for treating chronic rhinosinusitis in a subject comprising selecting a subject in need of treatment for chronic rhinosinusitis, and administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant to the subject, wherein the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO: 12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11; and b. a heavy chain variable domain selected from the group consisting of:i. a sequence of amino acids that is at least 80% identical to SEQ ID NO: 10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

3. The method of claim 1 or 2, wherein the antibody is administered every 2 weeks or every 4 weeks.

4. The method of any one of claims 1 to 3, wherein the antibody is an lgG2 antibody.

5. The method of any one of claims 1 to 4, wherein the antibody is administered at a dose of between 140 and 420 mg.

6. The method of any one of claims 1 to 5, wherein the antibody is administered at a dose of 210 mg.

7. The method of any one of claims 1 to 6, wherein the antibody is administered at a dose of 420 mg.

8. A method for treating chronic rhinosinusitis in a subject comprising selecting a subject in need of treatment for chronic rhinosinusitis, and administering a composition comprising an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising:i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

9. A method for treating chronic rhinosinusitis in a subject comprising selecting a subject in need of treatment for chronic rhinosinusitis, and administering a composition comprising an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO: 12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO: 10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

10. The method of any one of the preceding claims wherein the light chain variable domain is set out in SEQ ID NO:12 and the heavy chain variable domain is set out in SEQ ID NQ:10.

11. The method of any one of the preceding claims, wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year or more.

12. The method of any one of the preceding claims, wherein said anti-TSLP antibody is selected from the group consisting of a monoclonal antibody, a recombinant antibody, an lgG1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

13. The method of any one of claims 9-12, wherein the antibody is an lgG2 antibody.

14. The method of any one of the preceding claims, wherein the antibody is a human antibody.

15. The method of any one of the preceding claims, comprising administering to a patient a pharmaceutical composition comprising the antibody or antibody variant and further comprising a pharmaceutically acceptable carrier or excipient.

16. The method of any one of the preceding claims, wherein the chronic rhinosinusitis is severe or moderate chronic rhinosinusitis.

17. The method of any one of the preceding claims, wherein the chronic rhinosinusitis is with nasal polyps.

18. The method of any one of the preceding claims, wherein the subject has moderate asthma.

19. The method of any one of the preceding claims, wherein the subject is an adult.

20. The method any one of the preceding claims, wherein the subject is a child or adolescent.

21. The method any one of the preceding claims, wherein the administration improves one or more measures of chronic rhinosinusitis including Nasal Polyp Score (NSP), Nasal Congestion Score (NCS), loss of smell, SinoNasal Outcome Test 22 Item (SNOT-22), EuroQOL quality of life 5-dimensions 3-level version (EQ-5D-3L), Asthma Control Questionnaire (ACQ-6), Lund-Mackay score, modified Lund-Mackay Score, incidence of nasal polyp surgery and / or systemic corticosteroids (SCS).

22. The method any one of the preceding claims, wherein the administration improves one or more symptoms of chronic rhinosinusitis as measured by a patient symptom diary.

23. The method of any one of the preceding claims, wherein the administration improves one or more symptoms of chronic rhinosinusitis selected from the group consisting of nasal blockage, nasal congestion, runny nose, post-nasal drip, mucus drainage down the throat, prominent nasal obstruction, nasal discharge, loss of smell, asthma symptoms, headache, facial pain, facial pressure, difficulty with sense of smell, difficulty with sleeping due to nasal symptoms, difficulty with daily activities due to nasal symptoms.

24. A method for treating chronic rhinosinusitis in a subject comprising selecting a subject in need of treatment for chronic rhinosinusitis, and administering a composition comprising an anti-TSLP antibody to the subject in a dose of 140 to 420 mg at an interval of every 2 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, wherein the antibody is an lgG2 antibody.

25. The method of claim 24, wherein the light chain variable domain is set out in SEQ ID NO:12 and the heavy chain variable domain is set out in SEQ ID NQ:10.

26. The method of claim 24, wherein the antibody is administered every 4 weeks.

27. The method of claim 24 or 25, wherein the antibody is administered at a dose of 210 mg.

28. The method of any one of claims 24 to 27, wherein the antibody is administered at a dose of 420 mg.

29. The method of any one of the preceding claims, wherein the antibody is tezepelumab.

30. The method of claim 29, wherein the antibody is an lgG2 antibody, and has the full length heavy and light chain sequences set out in SEQ ID NOs: 13 and 14, respectively.

31. The method of any one of the preceding claims, wherein the antibody variant has substantially similar pK characteristics as tezepelumab in humans.

32. A method of reducing the frequency of chronic rhinosinusitis exacerbation in a subject comprising selecting a subject in need of treatment for chronic rhinosinusitis, and administering a composition comprising an anti-TSLP antibody to the subject in a dose of 140 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

33. A method of reducing the frequency of chronic rhinosinusitis exacerbation in a subject comprising selecting a subject in need of treatment for chronic rhinosinusitis, and administering a composition comprising an anti-TSLP antibody to the subject in a dose of 140 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein the antibody comprisesa. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO: 12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO: 10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

34. The method of claim 32 or 33, wherein the light chain variable domain is set out in SEQ ID NO:12 and the heavy chain variable domain is set out in SEQ ID NQ:10.

35. The method of any one of claims 32 to 34, wherein the antibody is administered every 4 weeks.

36. The method of any one of claims 32 to 34, wherein the antibody s administered at a dose of 210 mg.

37. The method of any one of claims 32 to 34, wherein the s administered at a dose of 420 mg.

38. The method of any one of claims 32 to 37, wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year or more.

39. The method of any one of claims 32 to 38, wherein said anti-TSLP antibody is selected from the group consisting of a monoclonal antibody, a recombinant antibody, an lgG1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

40. The method any one of claims 32 to 39, wherein the antibody is an lgG2 antibody.

41. The method of any one of claims 32 to 40, wherein the is a human antibody.

42. The method of any one of claims 32 to 41 wherein the antibody is tezepelumab.

43. The method of any one of claims 32 to 42, comprising administering to a patient a pharmaceutical composition comprising the antibody or antibody variant and further comprising a pharmaceutically acceptable carrier or excipient.

44. The method of any one of claims 32 to 43, wherein the administration delays the time to a chronic rhinosinusitis exacerbation compared to a subject not receiving the anti- TSLP antibody.

45. The method any one of claims 32 to 45, wherein the administration reduces frequency of or levels of co-administered therapy in the subject.

46. The method of claim 45, wherein the co-administered therapy is selected from the group consisting of dupilumab, immunosuppressive or immunomodulating drugs, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon (IFN)-gamma, Janus kinase inhibitors, azathioprine, methotrexate, anti-IL-13 antibodies, anti-IL-5 pathway antibodies, or combinations thereof.

47. The method of claim 45, wherein the administration reduces or eliminates the need for corticosteroid therapy.

48. A method for reducing SNOT-22 and / or Lund-Mackay score in a subject comprising administering a composition comprising of an anti-TSLP antibody in a dose of 140 mg to 420 mg at an interval of every 2 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, andiii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

49. A method for reducing SNOT-22 and / or Lund-Mackay score in a subject comprising administering a composition comprising an anti-TSLP antibody in a dose of 140 mg to 420 mg at an interval of every 2 weeks, wherein the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO: 12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO: 10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

50. A method for reducing SNOT-22 and / or Lund-Mackay score in a subject comprising administering a composition comprising an anti-TSLP antibody in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising:i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

51. A method for reducing SNOT-22 and / or Lund-Mackay score in a subject comprising administering a composition comprising an anti-TSLP antibody in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO: 12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO: 10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

52. The method of any one of claims 48 to 51 , wherein the light chain variable domain is set out in SEQ ID NO:12 and the heavy chain variable domain is set out in SEQ ID NQ:10.

53. The method of any one of claims 48 to 52 wherein the subject has a nasal polyp score (NPS) of 0 or 1 after 52 weeks of treatment.

54. The method of any one of claims 32 to 53, wherein the anti-TSLP antibody is tezepelumab.

55. The method of claim 54, wherein the antibody is an lgG2 antibody, and has the full length heavy and light chain sequences set out in SEQ ID NOs: 13 and 14, respectively.

56. The method of any one of claims 48-55, wherein the antibody is administered every 4 weeks.

57. The method of any one of claims 24 to 56, wherein the subject has chronic rhinosinusitis.

58. The method of claim 57, wherein the chronic rhinosinusitis is severe or moderate chronic rhinosinusitis.

59. The method any one of the preceding claims, wherein the administration is subcutaneous or intravenous.

60. A method for treating chronic rhinosinusitis with nasal polyps in a subject comprising selecting a subject in need of treatment for chronic rhinosinusitis with nasal polyps, and administering a composition comprising an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8;61. A method for treating chronic rhinosinusitis with nasal polyps in a subject comprising selecting a subject in need of treatment for chronic rhinosinusitis with nasalpolyps, and administering a composition comprising an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO: 12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO: 10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

62. The method of claim 60 or 61 , wherein the light chain variable domain is set out in SEQ ID NO:12 and the heavy chain variable domain is set out in SEQ ID NQ:10.

63. The method of claim 62, wherein the antibody is an lgG2 antibody, and has the full length heavy and light chain sequences set out in SEQ ID NOs: 13 and 14, respectively.

64. The method of any one of claims 60 to 63, wherein the antibody or antibody variant is administered for a period of at least 4 months, 6 months, 9 months, 1 year or more.

65. The method of any one of claims 60 to 64, wherein said anti-TSLP antibody is selected from the group consisting of a monoclonal antibody, a recombinant antibody, an lgG1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

66. The method any one of claims 60 to 65, wherein the antibody is an lgG2 antibody.

67. The method of any one of claims 60 to 66, wherein the antibody is a human antibody.

68. The method of any one of claims 60 to 67 wherein the antibody is tezepelumab.

69. A method for treating chronic rhinosinusitis in a subject comprising selecting a subject in need of treatment for chronic rhinosinusitis, and administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant to the subject, wherein the anti-TSLP antibody or antibody variant is described in WO 20220226342A1, WO 20220226339A1, WO2023098491A1 , WO2021155634A1, WO2022166072A1 ,WO2021043221A1, WO2022184074A1, WO2021104053A1 , WO2023116925A1, WO2021155861 A1, WO2022116858A1, WO2022117079A1 , WO2020244544A1, WO2021152488A1, WO2022253147A1, W02023070948A1 , WO2023142309A1, WO2022095689A1, W02021115240A1, WO2022166739A1 and W02019100111A1 or set out in Table A.

70. The method of any one of claims 60 to 69, comprising administering to a patient a pharmaceutical composition comprising the antibody or antibody variant and further comprising a pharmaceutically acceptable carrier or excipient.

71. The method of any one of claims 60 to 70, wherein the administration delays the time to a chronic rhinosinusitis exacerbation compared to a subject not receiving the anti- TSLP antibody.

72. The method any one of claims 60 to 71, wherein the administration reduces frequency of or levels of co-administered therapy in the subject.

73. The method of claim 72, wherein the co-administered therapy is selected from the group consisting of dupilumab, immunosuppressive or immunomodulating drugs, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon (IFN)-gamma, Janus kinase inhibitors, azathioprine, methotrexate, anti-IL-13 antibodies, anti-IL-5 pathway antibodies, or combinations thereof.

74. The method of claim 72 or 73, wherein the administration reduces or eliminates the need for corticosteroid therapy.

75. The method of any one of claims 60 to 74 wherein the subject has a nasal polyp score (NPS) of 0 or 1 after 52 weeks of treatment.

76. The method any one of claims 60 to 75, wherein the administration improves one or more measures of chronic rhinosinusitis including Nasal Polyp Score (NSP), NasalCongestion Score (NCS), loss of smell, SinoNasal Outcome Test 22 Item (SNOT-22), EuroQOL quality of life 5-dimensions 3-level version (EQ-5D-3L), Asthma Control Questionnaire (ACQ-6), Lund-Mackay score, modified Lund-Mackay Score, incidence of nasal polyp surgery and / or systemic corticosteroids (SCS).

77. The method any one of claims 60 to 76, wherein the administration improves one or more symptoms of chronic rhinosinusitis as measured by a patient symptom diary.

78. The method of any one of claims 60 to 77, wherein the administration improves one or more symptoms of chronic rhinosinusitis selected from the group consisting of nasal blockage, nasal congestion, runny nose, post-nasal drip, mucus drainage down the throat, prominent nasal obstruction, nasal discharge, loss of smell, asthma symptoms, headache, facial pain, facial pressure, difficulty with sense of smell, difficulty with sleeping due to nasal symptoms, difficulty with daily activities due to nasal symptoms.

79. The method of any one of claims 60 to 78, wherein the chronic rhinosinusitis, is severe or moderate chronic rhinosinusitis.

80. The method any one of claims 60 to 79, wherein the administration is subcutaneous or intravenous.

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