TW202541839A - Il-13 antibodies for the treatment of chronic rhinosinusitis with nasal polyps - Google Patents

Abstract

Provided herein are methods and uses of antibodies that specifically bind human IL-13 (“anti-IL-13 antibodies”) for treating chronic rhinosinusitis with nasal polyps.

Description

IL-13 antibodies used to treat chronic sinusitis with nasal polyps

This invention relates to a method and application of using an antibody that specifically binds to human interleukin (IL)-13 ("anti-IL-13 antibody") for the treatment of chronic sinusitis with nasal polyps (CRSwNP).

Chronic sinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition with a significant incidence, estimated to affect 1-4% of the general population and 25-30% of patients with chronic sinusitis (Stevens et al., Chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract. 2016;4(4):565-572; Fokkens et al., European position paper on rhinosinusitis and nasal polyps (2020). Rhinology. 58(Suppl S29):1-464). CRSwNP is characterized by loss of the immune barrier in the nasal passages and increased or chronic inflammation. These conditions lead to increased nasal congestion and polyp formation. IL-4 and IL-13 induce the activation of M2 macrophages, which may contribute to the pathogenesis of CRSwNP (Maspero et al., Type 2 inflammation in asthma and other airway diseases. ERJ Open Res. (2022); 8(3):00576-2021). The exact etiology of nasal polyps (NP) is unknown, but allergies, asthma, infection, and aspirin sensitivity are associated with this complex and refractory disease in adults (Stevens et al., 2016).

Nasal congestion is a major symptom of CRSwNP, which is directly caused by the physical obstruction of nasal polyps, but can also be caused by inflammation of the mucosa or by irritants (e.g., smoke, exhaust fumes, or perfumes) or allergens. Inflammation induced by IL-13 can lead to nasal congestion (Naclerio et al., 2010, Pathophysiology of nasal congestion. Int J Gen Med. (2010); 3:47-57).

Systemic corticosteroids (SCS) and surgery have been used to treat CRSwNP. Although these treatments do provide short-term relief, a recent meta-analysis reported that 18.6% of patients have undergone more than one polyp removal surgery (Loftus et al., 2020, Revision surgery rates in chronic rhinosinusitis with nasal polyps: meta-analysis of risk factors. Int Forum Allergy Rhinol. 2020; 10(2):199-207), and 35% of patients who underwent polyp removal surgery experienced polyp recurrence after 6 months (DeConde, A.S. et al., Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017:127(3):550-555). Currently, dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP. However, not all patients respond to these treatments, and rapid disease rebound has been observed after some discontinuation of these antibody therapies (Bachert et al., Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. (2019); 394(10209);1638-50).

There is still a need for effective alternatives to CRSwNP treatment. There is also a need to provide patients with more tolerable, convenient, and lower-risk treatment and medication regimens to improve patient compliance and satisfaction.

This article provides methods and uses for the treatment of chronic sinusitis with nasal polyps using anti-IL-13 antibodies (i.e., antibodies that specifically bind to human IL-13) (e.g., lebrikizumab) or pharmaceutical compositions including anti-IL-13 antibodies.

In one embodiment, this article provides a method for treating chronic sinusitis with nasal polyps in patients in need, the method comprising administering a therapeutically effective dose of anti-IL-13 antibodies to the patient. In some embodiments, this article provides a method for treating chronic sinusitis with nasal polyps, the method comprising: selecting a patient with chronic sinusitis with nasal polyps and administering a therapeutically effective dose of anti-IL-13 antibodies to the patient.

In another embodiment, this document provides for the use of anti-IL-13 antibodies or pharmaceutical compositions including anti-IL-13 antibodies for the treatment of chronic sinusitis with nasal polyps. This document also provides for the use of anti-IL-13 antibodies in the manufacture of medicaments for the treatment of chronic sinusitis with nasal polyps.

In some embodiments, the anti-IL-13 antibody includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes HCDR1 containing SEQ ID NO:1, HCDR2 containing SEQ ID NO:2, and HCDR3 containing SEQ ID NO:3, and the VL includes LCDR1 containing SEQ ID NO:4, LCDR2 containing SEQ ID NO:5, and LCDR3 containing SEQ ID NO:6. In some embodiments, the anti-IL-13 antibody includes a VH containing SEQ ID NO:7 and a VL containing SEQ ID NO:8. In some embodiments, the anti-IL-13 antibody includes a VH containing SEQ ID NO:11 and a VL containing SEQ ID NO:12. In some embodiments, the anti-IL-13 antibody includes a heavy chain containing SEQ ID NO:9 and a light chain containing SEQ ID NO:10. In some embodiments, the anti-IL-13 antibody includes a heavy chain containing SEQ ID NO:13 and a light chain containing SEQ ID NO:14. In some embodiments, the anti-IL-13 antibody is a levozo monoclonal antibody. In some embodiments, the anti-IL-13 antibody includes the VH sequence described in SEQ ID NO:11, the VL sequence described in SEQ ID NO:12, and the human IgG sequence described in SEQ ID NO:15. In some embodiments, the anti-IL-13 antibody includes the VH sequence described in SEQ ID NO:11, the VL sequence described in SEQ ID NO:12, the human Fc region including the human IgG sequence described in SEQ ID NO:15, and the constant light chain sequence described in SEQ ID NO:16.

In some practices, the anti-IL-13 antibody system is administered subcutaneously to the patient. In some practices, the anti-IL-13 antibody is administered at doses ranging from 250 mg to 500 mg. In some practices, the anti-IL-13 antibody system is administered subcutaneously to the patient every two weeks at a dose of 250 mg. In some practices, the patient is further treated with a loading dose of 500 mg of the anti-IL-13 antibody. In some practices, the patient is given one or two loading doses. In some practices, the patient is given a loading dose at week 0 (baseline) and week 2. In some practices, the patient is treated with anti-IL-13 antibodies for approximately 24 weeks.

In some practices, patients were further treated for a maintenance period of approximately 32 weeks. In some practices, patients were treated with a maintenance dose of 250 mg of anti-IL-13 antibody every 4 weeks during the maintenance period. In some practices, patients were treated with a maintenance dose of 250 mg of anti-IL-13 antibody every 8 weeks during the maintenance period.

In some practices, patients were treated with a loading dose of 500 mg of anti-IL-13 antibody at week 0 (baseline) and week 2, followed by a dose of 250 mg every two weeks for 24 weeks, and then a maintenance dose of 250 mg every four weeks for 32 weeks.

In some embodiments, the methods and uses described herein further include measuring the severity of nasal congestion symptoms (NCS) in patients before, during, and after treatment. In some embodiments, the methods and uses described herein further include measuring the endoscopic nasal polyp score (NPS) in patients before, during, and after treatment.

In some embodiments, the methods and uses described herein further include administering nasal endothelial steroids to patients. In some embodiments, the nasal endothelial steroid is mometasone furoate. In some embodiments, the nasal endothelial steroid is administered simultaneously, concurrently, or sequentially with anti-IL-13 antibodies.

In some practices, the patient had bilateral nasal polyps. In some practices, the patient's bilateral endoscopic NPS score for each nasal cavity prior to treatment was at least 5 (out of 8), with a minimum score of 2. In some practices, the patient had nasal congestion and at least one other symptom selected from olfactory dullness, anosmia, anterior nasal discharge, or posterior nasal discharge. In some practices, the patient was 18 years of age or older. In some practices, the patient was 12-18 years of age and weighed at least 40 kg.

This application claims the interests in U.S. Provisional Application No. 63/610,071, filed December 14, 2023, and U.S. Provisional Application No. 63/648,932, filed May 17, 2024, pursuant to 35 U.S.C. §119(e); the entire disclosure of those provisional applications is incorporated herein by reference.

This application is filed together with the sequence list in ST.26 XML format. The sequence list is provided as a file titled "30943_WO_000 Sequence List ST26" created on December 11, 2024, and is 20 kilobytes in size. The full contents of the sequence list information in ST.26 XML format are incorporated herein by reference.

This article provides methods and uses for the treatment of chronic sinusitis with nasal polyps using anti-IL-13 antibodies (e.g., lerizobactam) or pharmaceutical compositions including anti-IL-13 antibodies (e.g., lerizobactam).

In one embodiment, this article provides a method for treating chronic sinusitis with nasal polyps in patients in need, the method comprising administering a therapeutically effective dose of anti-IL-13 antibodies to the patient. In some embodiments, this article provides a method for treating chronic sinusitis with nasal polyps, the method comprising: selecting a patient with chronic sinusitis with nasal polyps and administering a therapeutically effective dose of anti-IL-13 antibodies to the patient.

In another embodiment, this document provides for the use of anti-IL-13 antibodies or pharmaceutical compositions including anti-IL-13 antibodies for the treatment of chronic sinusitis with nasal polyps. This document also provides for the use of anti-IL-13 antibodies in the manufacture of medicaments for the treatment of chronic sinusitis with nasal polyps.

In some embodiments, the methods and uses described herein further include measuring the severity of nasal congestion symptoms (NCS) in patients before, during, and after treatment. In some embodiments, the methods and uses described herein further include measuring the endoscopic nasal polyp score (NPS) in patients before, during, and after treatment.

In some embodiments, the methods and uses described herein further include administering nasal endothelial steroids to patients. In some embodiments, the nasal endothelial steroid is mometasone furoate. In some embodiments, the nasal endothelial steroid is administered simultaneously, concurrently, or sequentially with anti-IL-13 antibodies.

In some practices, the patient had bilateral nasal polyps. In some practices, the patient's bilateral endoscopic NPS score for each nasal cavity prior to treatment was at least 5 (out of 8), with a minimum score of 2. In some practices, the patient had nasal congestion and at least one other symptom selected from olfactory dullness, anosmia, anterior nasal discharge, or posterior nasal discharge. In some practices, the patient was 18 years of age or older. In some practices, the patient was 12-18 years of age and weighed at least 40 kg.

Anti-IL-13 antibodies suitable for the methods and uses provided herein have been previously described, for example, WO2005/062967. In some embodiments, the anti-IL-13 antibody includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes HCDR1 containing SEQ ID NO:1, HCDR2 containing SEQ ID NO:2, and HCDR3 containing SEQ ID NO:3, and the VL includes LCDR1 containing SEQ ID NO:4, LCDR2 containing SEQ ID NO:5, and LCDR3 containing SEQ ID NO:6. In some embodiments, the anti-IL-13 antibody includes VH containing SEQ ID NO:7 and VL containing SEQ ID NO:8. In some embodiments, the anti-IL-13 antibody includes VH containing SEQ ID NO:11 and VL containing SEQ ID NO:12. In some embodiments, the anti-IL-13 antibody includes a heavy chain containing SEQ ID NO:9 and a light chain containing SEQ ID NO:10. In some embodiments, the anti-IL-13 antibody includes a heavy chain containing SEQ ID NO:13 and a light chain containing SEQ ID NO:14. In some embodiments, the anti-IL-13 antibody includes the VH sequence described in SEQ ID NO:11, the VL sequence described in SEQ ID NO:12, and the human IgG sequence described in SEQ ID NO:15. In some embodiments, the anti-IL-13 antibody includes the VH sequence described in SEQ ID NO:11, the VL sequence described in SEQ ID NO:12, the human Fc region including the human IgG sequence described in SEQ ID NO:15, and the constant light chain sequence described in SEQ ID NO:16. In some embodiments, the anti-IL-13 antibody system is lerizocumab (CAS No.: 953400-68-5). Lerizocumab is a humanized monoclonal IgG4 antibody that specifically binds to IL-13 with high affinity and blocks signal transduction via an active IL-4Rα/IL-13Rα1 heterodimer. The amino acid sequence of lerizocumab is provided in Table 1. C-terminal cleavage of the IgG antibody can occur when one or two C-terminal amino acids are removed from the heavy chain of the IgG antibody. For example, if a C-terminal lysine (K) is present, it can be truncated or cleaved from the heavy chain. The penultimate glycine (G) can also be truncated or cleaved from the heavy chain. Modification of the N-terminal amino acids of IgG can also occur. For example, the N-terminal glutamic acid (Q) or glutamic acid (E) can spontaneously cyclize into pyroxine (pE). SEQ ID NO:9 reflects such potential modifications to the lerezo monoclonal antibody heavy chain. Similarly, SEQ ID NO:11, 13, and 15 reflect such potential modifications to the lerezo monoclonal antibody variant VH, lerezo monoclonal antibody variant HC, and the human IgG1 Fc region, respectively. Table 1. Anti- IL-13 antibody sequences SEQ ID NO: instruction sequence 1 Lerui monoclonal antibody HCDR1 AYSVN 2 Lerui monoclonal antibody HCDR2 MIWGDGKIVYNSALKS 3 Lerui monoclonal antibody HCDR3 DGYYPYAMDN 4 Lerui monoclonal antibody LCDR1 RASKSVDSYGNSFMH 5 Lerui monoclonal antibody LCDR2 LASNLES 6 Lerui monoclonal antibody LCDR3 QQNNEDPRT 7 Levofloxacin monoclonal antibody heavy chain variable region (VH) VTLRESGPALVKPTQTLTLTCTVSGFSLSAYSVNWIRQPPGKALEWLAMIWGDGKIVYNSALKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCAGDGYYPYAMDNWGQGSLVTVSS 8 Levozo monoclonal antibody light chain variable region (VL) DIVMTQSPDSLSVSLGERATINCRASKSVDSYGNSFMHWYQQKPGQPPKLLIYLASNLESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQNNEDPRTFGGGTKVEIK 9 Levitra monoclonal antibody heavy chain (HC) Xaa1VTLRESGPALVKPTQTLTLTCTVSGFSLSAYSVNWIRQPPGKALEWLAMIWGDGKIVYNSALKSRLTISKDTSKNQVVLTTMTNMDPVDTATYYCAGDGYYPYAMDNWGQ GSLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPC PPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLXaa2Xaa3 Where Xaa1 is Q, pE or does not exist; Xaa2 is G or does not exist; Xaa3 is K or does not exist. 10 Levitra monoclonal antibody light chain (LC) DIVMTQSPDSLSVSLGERATINCRASKSVDSYGNSFMHWYQQKPGQPPKLLIYLASNLESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQNNEDPRTFGGGTKVE IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 11 Levofloxacin monoclonal antibody variant with variable heavy chain region (VH) Xaa1VQLQESGPGLVKPSETLSLTCTVSGFSLNAYSVNWIRQPPGKGLEWLGMIWGDGKIVYNSALKSRLTISKDSSKNQVSLKLSSVTAADTAVYYCAGDGYYPYAMDNWGQGTTVTVSS Where Xaa1 is E, pE, or does not exist. 12 Levofloxacin monoclonal antibody variant with variable light chain region (VL) DIQLTQSPSSSLSASVGDRVTITCRASKSVDSYGNSFMHWYQQKPGKAPKLLIYLASNLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQNNEDPRTFGGGTKVEIK 13 Levozo monoclonal antibody variant heavy chain (HC) Xaa1VQLQESGPGLVKPSETLSLTCTVSGFSLNAYSVNWIRQPPGKGLEWLGMIWGDGKIVYNSALKSRLTISKDSSKNQVSLKLSSVTAADTAVYYCAGDGYYPYA MDNWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTUSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSXaa2Xaa3 Where Xaa1 is E, pE, or does not exist; Xaa2 is P or does not exist; Xaa3 is G or does not exist. 14 Levofloxacin monoclonal antibody variant light chain (LC) DIQLTQSPSSSLSASVGDRVTITCRASKSVDSYGNSFMHWYQQKPGKAPKLLIYLASNLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQNNEDPRTFGGGTKVE IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 15 hlgGI-LALA-YTE HC constant structural domain ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTUSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSXaa1Xaa2 where Xaa1 is P or does not exist; Xaa2 is G or does not exist 16 LC Human κ LC RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

In some embodiments, the anti-IL-13 antibody system includes lerejib antibody variants with the same HCDR and LCDR sequences as lerejib. In some embodiments, the anti-IL-13 antibody system includes lerejib antibody variants described in WO2023245187, such as structures 133, 134, 136, and 141. In some embodiments, the anti-IL-13 antibody system is APG777. The amino acid sequences of lerejib antibody variants are also provided in Table 1.

Other exemplary anti-IL-13 antibodies include (but are not limited to) IMA-026, IMA-638 (also known as anrukinzumab, QAX-576, CAS No.: 910649-32-0), tralokinumab (also known as CAT-354, CAS No.: 1044515-88-9); cendakimab (also known as CC-93538, RPC4046, ABT-308, CAS No.: 2151032-62-9), AER-001, and ABT-308 (also known as humanized 13C5.5 antibody). Examples of such anti-IL-13 antibodies and other inhibitors of IL-13 are disclosed (for example) in WO2008/086395, WO2006/085938, US 7,615,213, US 7,501,121, US 7,935,343, US 7,829,090, US7,947,273, WO2007/036745, WO2010/073119, WO2007/045477 and WO 2014/165771. In some embodiments, the anti-IL-13 antibody system is trarorumab. In some embodiments, the anti-IL-13 antibody system is sendazumab.

Anti-IL-13 antibodies can be formulated with suitable carriers or excipients into a pharmaceutical composition suitable for administration to a patient. For example, as described in WO 2013/066866, an anti-IL-13 antibody (e.g., lerizobactam) can be formulated into a pharmaceutical composition. The pharmaceutical composition may include 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, or 500 mg of anti-IL-13 antibody. In some embodiments, the pharmaceutical composition includes 250 mg to 500 mg of anti-IL-13 antibody. In some embodiments, the concentration of the anti-IL-13 antibody in the pharmaceutical composition is between 100 mg/mL and 150 mg/mL, for example, 125 mg/mL. The pharmaceutical composition may also include a buffer, such as a 5 mM to 40 mM histidine acetate buffer, pH 5.4 to 6.0. In some embodiments, the pharmaceutical composition further includes a polyol (e.g., a sugar) at a concentration between 100 mM and 200 mM and/or a surfactant (e.g., polysorbate 20) at a concentration of 0.01% to 0.1%. In one embodiment, the pharmaceutical composition comprises 125 mg/mL of an anti-IL-13 antibody (e.g., lerizob), 20 mM histidine acetate buffer (pH 5.7), 175 mM sucrose, and 0.03% polysorbate 20. In some embodiments, this document provides pharmaceutical compositions comprising components for inhibiting IL-13 and pharmaceutically acceptable loading or excipients.

In some embodiments, anti-IL-13 antibodies or pharmaceutical compositions comprising anti-IL-13 antibodies are administered to the patient subcutaneously. The dosing frequency may be approximately once weekly, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, or once every eight weeks. In some embodiments, anti-IL-13 antibodies or pharmaceutical compositions comprising anti-IL-13 antibodies are administered to the patient every two weeks, once every four weeks, or once every eight weeks. In some embodiments, anti-IL-13 antibodies or pharmaceutical compositions comprising anti-IL-13 antibodies are administered subcutaneously to the patient every two weeks at a dose of 250 mg. In some practices, the patient is given a subcutaneous dose of 250 mg of anti-IL-13 antibody or a pharmaceutical combination containing anti-IL-13 antibody every 4 weeks. In some practices, the patient is given a subcutaneous dose of 250 mg of anti-IL-13 antibody or a pharmaceutical combination containing anti-IL-13 antibody every 8 weeks. In some practices, the patient is given anti-IL-13 antibody or a pharmaceutical combination containing anti-IL-13 antibody every 8 weeks, every 12 weeks, every 24 weeks, every 36 weeks, or every 52 weeks. In some embodiments, anti-IL-13 antibodies or pharmaceutical combinations containing anti-IL-13 antibodies are administered to patients approximately every 8 weeks, approximately every 12 weeks, approximately every 24 weeks, approximately every 36 weeks, or approximately every 52 weeks. In some embodiments, anti-IL-13 antibodies or pharmaceutical combinations containing anti-IL-13 antibodies are administered subcutaneously every 8 weeks at a dose of 360 mg. In some embodiments, anti-IL-13 antibodies or pharmaceutical combinations containing anti-IL-13 antibodies are administered subcutaneously every 12 weeks at a dose of 360 mg. In some embodiments, anti-IL-13 antibodies or pharmaceutical combinations containing anti-IL-13 antibodies are administered subcutaneously every 24 weeks at a dose of 360 mg. In some embodiments, the patient's anti-IL-13 antibody or a pharmaceutical combination containing an anti-IL-13 antibody is administered subcutaneously at a dose of 360 mg every 36 weeks. In some embodiments, the patient's anti-IL-13 antibody or a pharmaceutical combination containing an anti-IL-13 antibody is administered subcutaneously at a dose of 360 mg every 52 weeks. In some embodiments, the patient's anti-IL-13 antibody or a pharmaceutical combination containing an anti-IL-13 antibody is administered subcutaneously at a dose of 360 mg approximately every 8 weeks. In some embodiments, the patient's anti-IL-13 antibody or a pharmaceutical combination containing an anti-IL-13 antibody is administered subcutaneously at a dose of 360 mg approximately every 12 weeks. In some embodiments, the patient's anti-IL-13 antibody or a pharmaceutical combination containing an anti-IL-13 antibody is administered subcutaneously at a dose of 360 mg approximately every 24 weeks. In some embodiments, the patient's anti-IL-13 antibody or a pharmaceutical combination containing an anti-IL-13 antibody is administered subcutaneously at a dose of 360 mg approximately every 36 weeks. In some embodiments, the patient's anti-IL-13 antibody or a pharmaceutical combination containing an anti-IL-13 antibody is administered subcutaneously at a dose of 360 mg approximately every 52 weeks.

In some embodiments, patients are treated with anti-IL-13 antibodies or pharmaceutical combinations containing anti-IL-13 antibodies for approximately 24 weeks or longer. In some embodiments, patients are further treated for a maintenance period of approximately 32 weeks or longer. In some embodiments, patients are treated with anti-IL-13 antibodies or pharmaceutical combinations containing anti-IL-13 antibodies for approximately 24 weeks, approximately 26 weeks, approximately 28 weeks, approximately 30 weeks, approximately 32 weeks, approximately 34 weeks, approximately 36 weeks, approximately 38 weeks, approximately 40 weeks, approximately 42 weeks, approximately 44 weeks, approximately 46 weeks, approximately 48 weeks, approximately 50 weeks, approximately 52 weeks, approximately 54 weeks, approximately 56 weeks, approximately 58 weeks, or approximately 60 weeks. In some embodiments, patients were treated with anti-IL-13 antibodies or medical conjugates containing anti-IL-13 antibodies for approximately 24 weeks. In some embodiments, patients were further treated with anti-IL-13 antibodies or medical conjugates containing anti-IL-13 antibodies for approximately 32 weeks of maintenance therapy. In some embodiments, patients were treated with anti-IL-13 antibodies or medical conjugates containing anti-IL-13 antibodies for approximately 56 weeks.

In some practices, patients are treated with a loading dose of anti-IL-13 antibody (e.g., a loading dose of 500 mg of anti-IL-13 antibody). Several loading doses may be administered to the patient at the start of treatment. For example, a loading dose of 500 mg of anti-IL-13 antibody may be administered in week 0 (baseline) and week 2. Following the loading dose, the patient may be administered 250 mg of anti-IL-13 antibody every two weeks, every four weeks, and every eight weeks.

In some practices, patients were treated with a loading dose of 500 mg of anti-IL-13 antibody at week 0 (baseline) and week 2, followed by a dose of 250 mg every two weeks for 24 weeks, and then a maintenance dose of 250 mg every four weeks for 32 weeks.

In some practices, patients were treated with a loading dose of 500 mg of anti-IL-13 antibody at week 0 (baseline) and week 2, followed by a dose of 250 mg every two weeks for 24 weeks, and then a maintenance dose of 250 mg every eight weeks for 32 weeks.

In some practices, patients were treated with a loading dose of 720 mg of anti-IL-13 antibody at weeks 0 and 2, followed by a 360 mg dose of anti-IL-13 antibody at weeks 4 and 12, and then a maintenance dose of 360 mg of anti-IL-13 antibody every 12 weeks for 32 weeks.

In some practices, patients were treated with a loading dose of 720 mg of anti-IL-13 antibody at weeks 0 and 2, followed by a 360 mg dose of anti-IL-13 antibody at weeks 4 and 12, and then a maintenance dose of 360 mg of anti-IL-13 antibody every 24 weeks for 32 weeks.

In some embodiments, a subcutaneous delivery device is used to administer anti-IL-13 antibodies or pharmaceutical compositions including anti-IL-13 antibodies to a patient. The subcutaneous delivery device may be selected from pre-filled syringes, disposable pen devices, microneedle devices, microinfusion devices, needle-free injection devices, or autoinjector devices. Various subcutaneous delivery devices (including autoinjector devices) are known in the industry and commercially available. Example devices include (but are not limited to) prefilled syringes (e.g., BD HYPAK SCF®, READYFILL ^™ and STERIFILL SCF ^™ from Becton Dickinson; CLEARSHOT ^™ copolymer prefilled syringes from Baxter; and Daikyo Seiko CRYSTAL ZENITH® prefilled syringes available from West Pharmaceutical Services); disposable injection pen devices, such as the BD Pen from Becton Dickinson; ultra-sharp and microneedle devices (e.g., INJECT-EASE ^™ and microinfusion devices from Becton Dickinson; and H-PATCH ^™ available from Valeritas); and needle-free injection devices (e.g., BIOJECTOR® and IJECT® available from Bioject; and SOF-SERTER® and patch devices available from Medtronic). In some embodiments, the subcutaneous delivery device is the automatic injector device described in WO 2008/112472, WO 2011/109205, WO 2014/062488 or WO 2016/089864.

Before, during, and after treatment, one or more characteristics of a patient can be evaluated, including certain signs, symptoms, features, or parameters that are relevant to chronic sinusitis with nasal polyps and can be evaluated quantitatively or qualitatively. These characteristics include (but are not limited to) the severity of NCS, endoscopic NPS, LMK score, _FEV1 , severity of olfactory impairment, postnasal drip score, taste impairment, facial pain/stress, VAS of CRS, SNOT-22, UPSIT, ACQ-6, NPIF, EQ-5D-5L, WPAI+CIQ:CRSwNP, PROMIS Anxiety Short Form v1.0 – Anxiety 8a, and PROMIS Depression Short Form v1.0 – Depression 8a. 8a) The most severe rhinorrhea in the first 24 hours, PGI-S, PGI-C, the proportion of participants receiving systemic corticosteroids and the time of event occurrence, approved biologics used for CRSwNP salvage and/or surgery on NP programs during study treatment.

The Nasal Congestion Score (NCS) was assessed by study participants using a 4-point scale (range 0 to 3), where 0 corresponds to no symptoms and 3 corresponds to severe symptoms, and the data was collected in an electronic diary. Participants were instructed to record the severity of their nasal congestion symptoms in their daily electronic diary at approximately the same time each day (preferably in the morning). The NCS at each assessment point was the average score over the previous 14 days. Participants were required to complete the NCS for at least 4 out of 7 days in each of the 2 weeks prior to randomization.

Endoscopic nasal polyp scoring (NPS) is evaluated through a centralized, blinded, and independent review of video recordings from endoscopic sinus surgery. The total score is the sum of the scores from the right and left nasal cavities. Otolaryngologists or allergy specialists with clinical research experience are certified to perform flexor endoscopic sinus surgery and can conduct interpretable lung volume measurements. Alternatively, allergy specialists can classify otolaryngologists as Sub-I for flexor endoscopic sinus surgery to perform NPS assessments. For each nasal cavity, the endoscopic NPS is graded based on a polyp size scale of 0 to 4, where 0 = no polyp and 4 = large polyp (Department of Health and Human Services (DHHS), Food and Drug Administration, Center for Drug Evaluation and Research (USA). Guidance for Industry. Chronic rhinosinusitis with nasal polyps: Developing drugs for treatment. June 2023. Access: www.fda.gov/media/154724/download). The endoscopic NPS is calculated as an average of scores from two trained physicians reviewing nasal endoscopy records, with the evaluators remaining blind to the participants' research treatment assignments. In cases where two evaluators disagree, a ruling process is required.

Nasal sinus opacity can be assessed as follows: A central readout of a CT scan of the sinus tract is performed to obtain a Lund Mackay (LMK) score. The CT scan should be performed at a predetermined time. In countries where specific approval procedures for CT scans require approval from different committees rather than the local IEC/IRB, participants can be recruited using CT scans performed in the previous year or MRI of the sinus tract performed between Visit 1 and Visit 2. These countries may exempt all planned research CT scans until approval from those committees is received. Review of CT scans of the right and left anterior sinuses includes the use of a scoring system. The LMK scoring system is a 3-point scale, where 0 = normal, 1 = partially cloudy, and 2 = completely cloudy. The total score is the sum of the scores from each side and ranges from 0 to 24, where 0 indicates no disease and 24 indicates the most severe disease (Lund, V.J., Kennedy, D.W. Staging for rhinosinusitis. Otolaryngol Head Neck Surg. (1997); 117(3 Pt 2):S35-40). The LMK scoring system assesses each side (right and left) of each sinus tract separately: anterior sinus, maxillary sinus, sphenoid sinus, meatus-sinusoidal complex, anterior ethmoid sinus, and posterior ethmoid sinus.

Spirometry was used to measure physiological airflow during forced expiratory volume in one second ( _FEV1 ). Spirometry was performed on all participants at screening (interview 1) using a spirometer supplied for research purposes that met the recommendations of the American Thoracic Society/European Respiratory Society. At subsequent interviews, spirometry was performed only on participants with asthma at selected time points. Normal _FEV1 values are typically ≥80% (Barriero, TJ, An approach to interpreting spirometry. Am Fam Physician. (2004); 69(5):1107-14). Lower _FEV1 values may indicate more severe asthma or other causes of airway restriction or obstruction. According to the procedures specified in the research reference manual, lung volume measurements shall be performed by trained and qualified personnel. Lung volume measurements should be performed at the research site whenever possible within ±1 hour of the baseline value.

The severity of olfactory impairment can be assessed as follows. Through qualitative interviews with individuals with CRS, participants’ reported olfactory impairment was identified as an important and distressing symptom (Hall, R. et al., Understanding the patient experience of severe, recurrent, bilateral nasal polyps: a qualitative interview study in the United States and Germany. Value Health. (2020); 23(5):632-41; O’Quinn, S. et al., Measuring the patient experience of chronic rhinosinusitis with nasal polyposis: qualitative development of a novel symptom diary. Int Forum Allergy Rhinol. (2022); 12(8):996-1005) and recommended as a secondary endpoint in FDA Guidance (DHHS 2023). Olfactory impairment was assessed by study participants using a 4-point scale, where 0 corresponded to no symptoms and 3 to severe symptoms. Participants were asked to record the most severe level of olfactory impairment within the previous 24 hours. The severity of olfactory impairment was collected in an electronic diary.

Postnasal drip was assessed by study participants using a 4-point scale, with 0 corresponding to no symptoms and 3 to severe symptoms. Participants were asked to record the most severe postnasal drip within the previous 24 hours. This assessment was collected in participants' electronic diaries.

Loss of taste, facial pain/stress, and nasal discharge were assessed by study participants using a 4-point scale, where 0 corresponded to no symptoms and 3 to severe symptoms. Participants were asked to record their most severe loss of taste, facial pain/stress, and nasal discharge within the first 24 hours using an electronic diary. The severity scores for loss of taste, facial pain/stress, and nasal discharge at each assessment time point were the average scores over the previous 14 days. Data on loss of taste, facial pain/stress, and nasal discharge were collected in the electronic diary.

The Visual Analogue Scale (VAS) for Chronic Sinusitis (CRS) assesses overall disease severity and can be collected on a notebook at the study site. Participants are asked to complete the following question on a 10 cm chronic sinusitis symptom VAS: "How troublesome have your chronic sinusitis symptoms been in the past 7 days?", where 0 corresponds to "not troublesome at all" and 10 corresponds to "the most troublesome I can imagine". The CRS VAS is assessed at the selected study visit. The critical values for disease severity are defined as mild = 0 – 3, moderate = >3 – 7 and severe = >7 – 10 (Fokkens WJ et al., European position paper on rhinosinusitis and nasal polyps 2020. Rhinology. 2020;58(Supplement S29):1-464).

The Sino-Nasal Outcome Test (SNOT-22) is an empirical participant-reported questionnaire that assesses the impact of nasal, sinus, and ear function, psychological effects, productivity, and sleep quality on a notebook at the study site. Participants are asked to recall their experiences over the past two weeks and rate their symptoms on a scale ranging from 0 (no problem) to 5 (worst-case). The scores for each question are summed to create an overall score ranging from 0 (no disease) to 110 (worst-case). Lower scores indicate less impact. A change in score of 8.9 was considered the least clinically significant difference (Hopkins, C. et al., Psychometric validity of the 22-item Sinonasal Outcome Test. Clinical Otolaryngology. (2009); https://doi.org/10.1111/j.1749-4486.2009.01995.x.).

The University of Pennsylvania Smell Identification Test (UPSIT) is an evaluation of participants' reported olfactory function, which uses a "sniffing" test with 10 different odorants. The scoring range is 0-40, where <18 is equivalent to anosmia (complete loss of smell), 19-25 = severe anosmia, 26-30 = moderate anosmia, 31-34 = mild anosmia and 35-40 = no anosmia (normal olfactory assessment) (Doty, R.L., Olfactory dysfunction and its measurement in the clinic. World J. Otorhinolaryngol Head Neck Surg. (2015); 1(1):28-33；Doty, R.L., Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test:a standardized microencapsulated test of olfactory function. Physiol. Behav. (1984); 32(3):489-502).

The Asthma Control Questionnaire-6 (ACQ-6) is a 6-question participant-reported questionnaire that assesses the most common asthma symptoms and was collected on a notepad only from participants with asthma at the study site. The questions included: awakening due to asthma; symptoms of awakening; activity limitation; shortness of breath; wheezing; and use of inhalers/inhalers. Participants with a history of asthma were asked to recall how their asthma had been in the previous week and answer questions on a 7-point scale, where 0 corresponds to no difficulty and 6 corresponds to maximum difficulty. The ACQ-6 score was calculated by averaging the self-reported scores and expressed as a total control value within 6 points, where 0 corresponds to complete asthma control and 6 corresponds to severe uncontrolled asthma. The minimum clinically significant difference in ACQ-6 is defined as a change of 0.5 points (Juniper, E.F., et al., Development and validation of a questionnaire to measure asthma control. Eur Respir J. (1999); 14(4):902-7; Juniper, E.F., et al., Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir Med. (2005); 99(5):553-8).

Nasal peak inspiratory flow (NPIF) was measured as the maximum inspiratory flow rate through both nostrils during inspiration, expressed in L/min. Participants with an NPIF result >120 L/min were considered to have no nasal obstruction (Mo, S. et al., Nasal peak inspiratory flow in healthy and obstructed patients: systematic review and meta-analysis. Laryngoscope. (2021); 131(2):260-7). NPIF was performed at defined time points, using the highest three readings. NPIF measurements were performed by trained and qualified personnel according to the procedures specified in the study reference manual.

The European Quality of Life – 5 Dimensions – 5 Levels (EQ-5D-5L) is a universal questionnaire for assessing health status, collected on notebooks at research sites. It comprises a descriptive system of 5 dimensions (mobility, self-care, routine activities, pain/discomfort, and anxiety/depression), with each dimension having 5 levels: no problem, minor problem, moderate problem, serious problem, and very serious problem. The questionnaire also includes the VAS scale, in which respondents self-assess their health on the vertical VAS, with endpoints for "the best health you can imagine" and "the worst health you can imagine" (EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. (1990); 16(3):199-208; Herdman, M. et al., Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. (2011); 20(10):1727-36; Remenschneider, A.K. et al., The EQ-5D:a new tool for studying clinical outcomes in chronic rhinosinusitis. Laryngoscope. (2015); 125(1):7-15).

Work productivity and activity impairment + classroom impairment: The CRSwNP (WPAI+CIQ:CRSwNP) is a patient-reported assessment tool used to evaluate the impairment of work, classroom, and routine activities in patients with CRSwNP; it is also collected on notebooks at the study site. It contains measurements of the following 10 items: employment status; hours of work lost due to CRSwNP; hours of work lost due to other reasons; actual hours worked; the degree of impact of CRSwNP on productivity at work; school attendance in academic situations; hours of classroom time lost due to CRSwNP; hours of school/class attendance; the degree of impact of CRSwNP on productivity in the classroom; and the degree of impact of CRSwNP on regular daily activities. WPAI+CIS:CRSwNP generates four sub-scores: Absence (time lost in work or class); Pseudo-attendance (work or class impairment/reduced work productivity); Work productivity impairment (overall work or class impairment/absence + pseudo-attendance); and Activity impairment. The scores are calculated as percentage of impairment (Reilly, M.C., Zbrozek, A.S., Dukes, E.M. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. (1993); 4(5):353-65), with higher values indicating greater impairment and lower efficiency, i.e., a worse result.

The PROMIS Anxiety Scale version 1.0 – Anxiety 8a is suitable for the general population and individuals with chronic conditions. The PROMIS Anxiety Item Scale assesses self-reported fears (fear, panic), anxiety distress (worry, apprehension), hyperarousal (tension, nervousness, restlessness), and arousal-related physical symptoms (rapid heartbeat, dizziness). PROMIS Anxiety Scale 8a (version 1.0) includes eight questions assessing the participant's symptoms over the previous seven days. Response options range from 1 = Never; 2 = Rarely; 3 = Sometimes; 4 = Often; 5 = Always. The total raw score was converted into a T-score, with higher scores indicating higher anxiety (PROMIS Anxiety 2019, published March 1, 2019, available March 8, 2021. Access: https://www.healthmeasures.net/images/PROMIS/manuals/PROMIS_Anxiety_Scoring_Manual.pdf).

The PROMIS Depression Short Form 1.0 – Depression 8a is available for the general population and individuals with chronic conditions. The PROMIS Depression Item Scale assesses self-reported negative emotions (sadness, guilt), self-perception (self-criticism, feelings of worthlessness), and social cognition (loneliness, social isolation), as well as positive impacts and decreased engagement (loss of interest, meaning, and purpose). PROMIS Depression Short Form 8a (version 1.0) includes eight questions assessing the participant's symptoms over the previous seven days. Response options range from 1 = Never; 2 = Rarely; 3 = Sometimes; 4 = Often; 5 = Always. The total raw score was converted into a T-score, with higher scores representing higher depression (PROMIS Depression 2019, released on February 18, 2019, and available on March 8, 2021. Access: https://www.healthmeasures.net/images/PROMIS/manuals/PROMIS_Depression_Scoring_Manual.pdf).

To facilitate the assessment of clinically significant intra-partner changes in nasal congestion, loss of smell, and postnasal drip, we collected patient general impressions of severity (PGI-S) and patient general impressions of change (PGI-C).

PGI-S: Nasal Congestion requires participants to assess the overall severity of nasal congestion due to chronic sinusitis in the past 14 days, with response options including: asymptomatic, mild, moderate, severe, and very severe.

PGI-S: The sense of smell loss requires participants to assess the overall severity of their sense of smell loss due to chronic sinusitis in the past 14 days, and the response options are: asymptomatic, mild, moderate, severe, and very severe.

PGI-S: Postnasal drip requires participants to assess the overall severity of postnasal drip due to chronic sinusitis in the past 14 days, with response options including: asymptomatic, mild, moderate, severe, and very severe.

PGI-C: Nasal Congestion requires participants to describe the overall changes in nasal congestion due to chronic sinusitis since they started taking the new medication, and the response options are: greatly improved, more improved, very little improved, no change, very little worsened, more worsened, and greatly worsened.

PGI-C: The olfactory loss assessment requires participants to describe the overall changes in their olfactory loss due to chronic sinusitis since they started taking the new medication, and the response options are: greatly improved, more improved, very little improved, no change, very little worsened, more worsened, and greatly worsened.

PGI-C: Postnasal drip requires participants to describe the overall changes in their postnasal drip due to chronic sinusitis since they started taking the new medication, and the response options are: greatly improved, more improved, very little improved, no change, very little worsened, more worsened, and greatly worsened.

The proportion of participants receiving systemic corticosteroids and the timing of events, the approved biologics used for salvage treatment of CRSwNP, and/or the evaluation of planned surgeries for NP during the study treatment period are as follows. Systemic corticosteroids (SCS) will be prescribed on-site to participants, as needed, depending on local legislation/regulation, for salvage treatment of nasal polyps or another cause. Patient-reported outcomes (PROs) and nasal endoscopy should be performed before initiation of SCS treatment. The investigator (or designated person) will record the date and medication information on the appropriate page of the eCRF. The indication for SCS use will be recorded as the relevant AE or medical history. Approved biologics for CRSwNP will be prescribed on-site to participants, as needed, depending on local legislation/regulation, for salvage treatment or another cause. PRO and nasal endoscopy should be performed before initiating treatment with the approved biologic. The investigator (or assigned person) should record the date and administration information (daily dose, duration, international non-patent name) on the appropriate page of the eCRF. Indications for biologic use should be recorded as relevant AEs or medical history. For participants who have undergone or are planning NP nasal and sinus surgery, the decision date and surgery date should be recorded (if applicable). PRO and endoscopy should be performed before surgical intervention. Surgical data should be collected via participant safety follow-up (SFU) visits.

After administration of anti-IL-13 antibodies or pharmaceutical compositions including anti-IL-13 antibodies, the described properties can be measured at baseline and at one or more time points. For example, it can be measured at the end of week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12, week 13, week 14, week 15, week 16, week 17, week 18, week 19, week 20, week 21, week 22, week 23, or at the end of week 24, or after a longer period of initial treatment with anti-IL-13 antibodies or medical combinations including anti-IL-13 antibodies. The difference between the value at a specific time point after the start of treatment and the baseline value is used to determine whether there is an improvement in the characteristic (e.g., relief).

In another embodiment, this document provides for the use of anti-IL-13 antibodies or pharmaceutical compositions including anti-IL-13 antibodies for the treatment of chronic sinusitis with nasal polyps. This document also provides for the use of anti-IL-13 antibodies in the manufacture of medicaments for the treatment of chronic sinusitis with nasal polyps.

Unless otherwise indicated herein or the context clearly contradicts it, the terms “a”, “the” and similar terms used herein in the context of this invention (especially in the context of the claims) shall be understood to cover both the singular and the plural.

As used in this article, the term "about" refers to a reasonable near-range of a stated value, such as a stated value of + or -10%.

As used herein, the term "antibody" refers to an immunoglobulin molecule that binds to an antigen. Examples of antibodies include monoclonal antibodies, multiclonal antibodies, human antibodies, humanized antibodies, chimeric antibodies, or conjugated antibodies. Antibodies can be of any class (e.g., IgG, IgE, IgM, IgD, IgA) or any subclass (e.g., IgG1, IgG2, IgG3, IgG4).

An example antibody system is an immunoglobulin G (IgG) type antibody, comprising four polypeptide chains: two heavy chains (HC) and two light chains (LC) cross-linked by inter-chain disulfide bonds. Each amino-terminal portion of the four polypeptide chains contains a variable region of approximately 100-125 or more amino acids, primarily responsible for antigen recognition. Each carboxyl-terminal portion of the four polypeptide chains contains a constant region primarily responsible for the therapeutic effect. Each heavy chain includes a heavy chain variable region (VH) and a heavy chain constant region. Each light chain includes a light chain variable region (VL) and a light chain constant region. IgG isotypes can be further subdivided into subtypes (e.g., IgG1, IgG2, IgG3, and IgG4).

The VH and VL regions can be further subdivided into hypervariable regions (called complementary determinant regions (CDRs)) and more conserved regions (called framework regions (FRs)). CDRs are exposed on the protein surface and are important regions for the antigen-binding specificity of the antibody. Each VH and VL consists of 3 CDRs and 4 FRs, arranged in the following order from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. In this paper, the three CDRs of the heavy chain are referred to as "HCDR1, HCDR2, and HCDR3," and the three CDRs of the light chain are referred to as "LCDR1, LCDR2, and LCDR3." CDRs contain most of the residues that form specific interactions with the antigen. The amino acid residues of CDRs can be assigned according to well-known schemes, including the following: Kabat (Kabat et al., Sequences of Proteins of Immunological Interest, National Institutes of Health, Bethesda, Md. (1991)), Chothia (Chothia et al., Canonical structures for the hypervariable regions of immunoglobulins, Journal of Molecular Biology, 196, 901-917 (1987); Al-Lazikani et al., Standard conformations for the canonical structures of immunoglobulins, Journal of Molecular Biology, 273, 927-948 (1997)), North (North et al., A New Clustering of Antibody CDR Loop Conformations, Journal of Molecular Biology, 406, 228-256 (2011)), or IMGT. (The international ImMunoGeneTics database is available at www.imgt.org; see Lefranc et al., Nucleic Acids Res. (1999); 27:209-212).

Example embodiments of the antibodies of the present invention also include antibody fragments or antigen-binding fragments, including at least a portion of the antibody that retains the ability to specifically interact with an antigen, such as Fab, Fab’, F(ab’)2, Fv fragments, scFv, scFab, disulfide-linked Fvs (sdFv), Fd fragments, and linear antibodies.

As used herein, the term "anti-IL-13 antibody" refers to an antibody that specifically binds to human IL-13. In some embodiments, the dissociation constant (KD) of the anti-IL-13 antibody to human IL-13 is ≤ 1 μM, ≤ 100 nM, ≤ 10 nM, ≤ 1 nM, ≤ 0.1 nM, or ≤ 0.01 nM (e.g., ^10⁻⁸ M or less or ^10⁻⁹ M or less).

As used in this article, the term "baseline" means at or before the administration of the first dose of anti-IL-13 antibody (week 0) or a pharmaceutical combination that includes anti-IL-13 antibody.

Unless otherwise indicated, the term “bind” as used herein is intended to refer to the ability of a protein or molecule to form a chemical bond or attractive interaction with another protein or molecule, as determined by commonly used methods known in the industry, to result in the proximity of the two proteins or molecules.

The "effective dose" of a drug refers to the effective dose that achieves the desired therapeutic effect within the required time period and at the required dosage.

As used herein, unless otherwise indicated, the term "IL-13" refers to any human isoform of interleukin-13. The term encompasses untreated "full-length" IL-13 and any form of IL-13 produced during cellular treatment. The term also encompasses naturally occurring IL-13 variants, such as splice variants or paired variants. Exemplary human IL-13 amino acid sequences are known, for example, NCBI Registries NP_002179.2, NP_001341920.1, NP_001341921.1, NP_001341922.1; UniProtKB Registry P35225.

The term "load dose" refers to the dose of a drug given at the beginning of treatment, which is higher than the doses given subsequently and the doses given in each part of the treatment.

The term "maintenance dose" refers to the follow-up dose of a drug administered to a patient to maintain or continue the therapeutic effect.

The term "patient" used in this article refers to human patients.

As used herein, "treatment" refers to any process that slows, controls, delays, or stops the progression of the condition or disease described herein or that improves the symptoms of the condition or disease, but does not necessarily mean the complete elimination of all symptoms of the condition or disease. Treatment includes administering proteins or nucleic acids or vectors or compounds to treat the disease or condition of a patient (especially a human).

Example 1. A phase 3 , multicenter, randomized, double-blind, placebo-controlled, parallel cohort study evaluating the efficacy and safety of lerizobactam in participants with chronic sinusitis and nasal polyps in the context of nasal endothelial steroids . This was a phase 3 , multinational, multicenter, double-blind, placebo-controlled, parallel cohort, randomized clinical study to evaluate the efficacy and safety of lerizobactam in participants with chronic sinusitis (CRS) and bilateral nasal polyps (NP) receiving background therapy with nasal endothelial steroids (INCS).

We recruited approximately 510 adult participants (≥18 years old) with CRS and bilateral NP.

This study has four study periods: screening (maximum 30 days), induction (4 weeks), randomized treatment (56 weeks, including an induction period (24 weeks; week 0 to week 24) and a maintenance period (32 weeks; week 24 to week 56)), and safety follow-up (SFU) (8 weeks) starting after the study site visit at week 56. The maximum program duration of study participation for each participant is approximately 72 weeks.

Goals and End Points :

The primary, secondary, and exploratory objectives and endpoints of this study are presented in Table 2. Table 2 Objectives and Endpoints Target Finish line Primary : • Evaluate the efficacy of leveti monoclonal antibody 250 mg Q2W against placebo in reducing nasal congestion severity and endoscopic nasal polyp score at week 24 in the context of INCS. • Mean change from baseline (CFBL) of participant-reported nasal congestion score (NCS) severity at week 24 • Mean CFBL of endoscopic nasal polyp score (NPS) at week 24 Key secondary objectives : • To evaluate the efficacy of the levofloxacin monoclonal antibody in reducing participants' signs and symptoms. • Mean CFBL of endoscopic NPS at week 56. • Mean CFBL of NCS reported by participants at week 56. • Mean change in sinus opacity from baseline to weeks 24 and 56 as measured by LMK assessment. • Mean change in forced expiratory volume in one second ( _FEV1 ) from baseline to weeks 24 and 56. • Mean CFBL of olfactory impairment severity at weeks 4, 24, and 56. • Mean CFBL of postnasal drip at weeks 24 and 56. • Proportion of participants receiving systemic corticosteroids and time of event occurrence and/or approved biologics used for CRSwNP salvage and/or planned NP procedures during the study treatment period. Other minor aspects : • Efficacy of the levofloxacin monoclonal antibody compared to placebo, as measured by clinician evaluations and by patient-reported outcomes (PROs) and participant quality of life assessments. The following mean changes from baseline to visit: • Severity of NCS reported by participants. • Endoscopic NPS. • Nasal sinus turbidity as measured by the Lund Mackay scale (LMK scale). • Severity of olfactory impairment as assessed by the participant's daily electronic diary (eDiary). • Postnasal drip as assessed by the participant's daily electronic diary (FEV1 ₎ . • Severity of taste impairment as assessed by the participant's daily electronic diary. • Severity of facial pain/stress as assessed by the participant's daily electronic diary. • Severity of nasal discharge as assessed by the participant's daily electronic diary. • Severity of chronic sinusitis symptoms (Visual Analogue Scale) • 22-Item Nasal and Sinus Outcomes Test (SNOT-22) • University of Pennsylvania Olfactory Identification Test (UPSIT) • Asthma Control Questionnaire-6 (ACQ-6) • Peak Nasal Inspiratory Flow (NPIF) • EuroQol 5-Dimensional 5-Point Scale (EQ-5D-5L) • WPAI+CIQ: CRSwNP (Work Performance and Activity Disorders + Classroom Disorders: Chronic Sinusitis with Nasal Polyps) • Patient's Overall Impression of Severity (PGI-S) • Patient's Overall Impression of Change (PGI-C) • Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety Scale Version 1.0 – Anxiety 8a • PROMIS Depression Summary Version 1.0 – Depression 8a Exploratory : • PK of the levodopa monoclonal antibody during the characterization study • Immunogenicity and changes of exploratory biomarkers during the characterization study • Analysis of gene changes related to drug response (optional) • Serum concentration of the levodopa monoclonal antibody at the identification visit • Immunogenicity (antidrug-resistant antibody), total immunoglobulin E (IgE), and nasal and blood biomarkers at the identification visit • Pharmacogenomic analysis Safety : • Describe the safety and tolerability of the levozo monoclonal antibody. • Incidence of adverse events (AEs) and serious adverse events (SAEs); baseline values and changes over time for clinical laboratory assessments and vital signs.

The following sections describe the inclusion and exclusion criteria for recruiting participants in this study. Inclusion Criteria : Each participant to be recruited for this study must meet all of the following criteria: 1. Adult participants must be ≥18 years of age at the time of signing the informed consent form (ICF), and adolescent participants must be ≥12 to <18 years of age and weigh ≥40 kg at Visit 1. 2. CRS with bilateral NPs diagnosed by a physician. 3. Prior treatment with SCS for CRS or CRSwNP within the past 2 years (or medical contraindication or poor tolerance to systemic corticosteroids), prior nasal polyp surgery, or both. 4. The bilateral NPS score of each nasal cavity endoscopic examination performed in screening (Visit 1) and baseline (Visit 3) must be at least 5 points (out of 8), and the minimum score must be 2 points. 5. Progressive symptoms lasting for at least 8 weeks prior to entry into the study (screening [Interview 1]) include: a. Nasal congestion of moderate or severe severity (rated 2 or 3) at screening (Interview 1) (one day of Interview 1) and a weekly average severity score of at least 1 (range 0 to 3) on a randomized basis (average of the 14 days prior to Interview 3 [baseline]); and b. At least one other symptom, such as (but not limited to) partial anosmia (dullness of smell), complete anosmia (loss of smell), or anterior or posterior nasal discharge. 6. Patients with asthma must have achieved stable asthma treatment using permitted routine methods for 3 months prior to screening. 7. Two weeks prior to the randomized follow-up (Follow-line 3), participants must complete an electronic diary for at least 4 out of 7 days per week. 8. Women of childbearing potential (WOCBP) must use at least one highly effective contraceptive or a combination of two effective contraceptive methods consistent with local regulations regarding contraceptive methods for clinical study participants. 9. Parents/legal guardians of adult or adolescent participants must understand the exploratory nature of the study and sign a written informed consent form approved by the Institutional Ethics Committee (IEC)/Institutional Review Board (IRB) before undergoing any research-related procedures. If required by local regulations, adolescent participants must also understand the nature of the study and sign an informed consent form before undergoing any research-related procedures. 10. Willingness and ability to fulfill all clinical visits, research-related procedures, and questionnaires, including, importantly, necessary background therapy and completion of daily electronic journaling.

Exclusion Criteria : Participants were excluded from the study if they met any of the following criteria: 1. They had received a dose of lerezab. 2. They were currently enrolled in any other clinical study involving the investigational product or any other type of medical study deemed scientifically or medically incompatible with this study. 3. They had received treatment with the investigational drug within 8 weeks or 5 half-lives (if known) prior to randomization, whichever was longer. 4. They had a known allergy to lerezab or its excipients. 5. They had contraindications or poor tolerance to mometasone furoate. 6. They had taken a leukotriene receptor antagonist within 4 weeks prior to screening (Visit 1). 7. Received any salvage therapy and/or required NP surgery during the screening and/or induction period. 8. Allergen immunotherapy (subcutaneous immunotherapy [SCIT]/sublingual immunotherapy [SLIT]) occurring within 6 months prior to screening, with unstable dosage (3 months prior to screening [Visit 1]) or dosage changes required during the study. 9. Previous or current biologic therapy for CRSwNP and/or asthma and/or AD, including (but not limited to) omalizumab, dupilumab, mepolizumab, reslizumab, and benalizumab. 10. Prior to baseline visits (Visit 3; randomization), the patient had received any biologic or systemic immunosuppressant treatment for an inflammatory or autoimmune disease (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis). a. B-cell depletion biologics, including rituximab, within 6 months. b. Other biologics within 5 half-lives (if known) or 8 weeks, using the longer of the two. c. Systemic immunosuppressants within 4 weeks prior to baseline (Visit 3). 11. Prior to screening (Visit 1), the patient had undergone any intranasal sinus surgery (including nasal polyp removal surgery). 12. Previous nasal or sinus surgery that alters the lateral nasal wall structure, making endoscopic NPS difficult to evaluate. 13. History of severe asthma exacerbation in recent years and documented use of SCS for asthma treatment within the past 12 months. 14. Presence of any of the following conditions that could affect endpoint evaluation during screening (Visit 1) or baseline (Visit 3): a. Nasal septal deviation obstructing at least one nostril. b. Posterior maxillary sinus polyps. c. Acute sinusitis, acute nasal infection, or acute upper respiratory tract infection. d. Progressive drug-induced rhinitis. e. The presence of another diagnosis associated with nasal polyps (i.e., eosinophilic granuloma with polyangiitis, granuloma with polyangiitis, Young's syndrome, primary pilomotor disorder, cystic fibrosis). f. Nasal tumor (malignant or benign). g. Signs of fungal sinusitis. 15. Having received any live or live attenuated vaccine (including Bacillus Calmette-Guerin vaccine or treatment) within 4 weeks prior to baseline (visit 3), or intending to receive a live attenuated vaccine (or Bacillus Calmette-Guerin treatment) during the study or within 4 weeks after receiving the final dose of the investigational product (IP). The following vaccines are not considered live vaccines: messenger RNA vaccines, vaccines containing inert viral elements, and/or non-replicating viral vector vaccines. Before recruiting participants for the study, investigators should assess whether adolescent participants have followed local vaccination guidelines for immunization to date. For unvaccinated adolescents, investigators should document the benefits/risks for recruitment purposes. 16. History of HIV infection or HIV serological positivity. 17. Current or chronic HBV infection (in other words, positive hepatitis B surface antigen (HBsAg) and/or positive polymerase chain reaction). 18. Current hepatitis C virus (HCV) infection (HCV RNA positive). 19. Known cirrhosis and/or chronic hepatitis of any cause. 20. Diagnosed with an active endoparasitic infection or at high risk of such infection. 21. Known or suspected history of immunosuppression, including a history of invasive opportunistic infections (e.g., tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, Pneumocystis jirovecii infection, and aspergillosis) despite remission; or unusually frequent, recurrent, or prolonged infections according to the investigator's opinion. 22. Having any of the following types of infection within 3 months prior to screening, or having any of these infections during the screening or induction period: a. Severe (requiring hospitalization and/or IV or equivalent oral antibiotic treatment). b. Opportunistic. c. Symptomatic herpes zoster infection not resolved at screening. Note: Herpes zoster is considered active and progressive until all vesicles are dry and crusted. d. Chronic (6 weeks or longer duration of symptoms, signs, and/or treatment). e. Recurrent (including (but not limited to) recurrent cellulitis, chronic osteomyelitis). Note: Participants with only recurrent, mild, and uncomplicated oral herpes and/or genital herpes may be admitted based on medical monitoring. 23. Active or acute infection requiring systemic antibiotics, antivirals, antiparasitics, antiprotozoal, or antifungal treatment within 2 weeks prior to baseline (Visit 3). Note: Participants may be rescreened after infection resolution. If other study eligibility criteria are met, recruitment of participants with vaginal or oral candidiasis who are symptomatically treated and do not require systemic anti-infective agents may be considered. Recruitment of participants with other non-complicated local infections should be discussed by a medical monitor designated by the client. 24. History of malignancy within 5 years prior to screening (excluding adequately treated basal cell or squamous cell carcinoma, cervical carcinoma in situ). 25. Any other medical or psychological condition that, according to the investigator's opinion, indicates a novel and/or poorly understood disease, poses an unreasonable risk to the study participant due to their participation, could lead to unreliable participation, or could interfere with the study evaluation. 26. A serious comorbidity that, according to the investigator, would adversely affect participation in the study. 27. Loss of smell due to COVID or any cause other than CRSwNP. 28. A participant who recently had a nasal perforation that has not fully recovered at screening (Visit 1) and could cause nasal symptoms, or who plans to have a new nasal perforation during study participation. 29. A participant with 50% or less of _FEV1 (relative to the normal predicted value) at screening (Visit 1). 30. A laboratory result that, according to the investigator, is clinically significant at screening (Visit 1) or (baseline [Visit 3]). 31. Female participants who are pregnant, breastfeeding, or planning to become pregnant or breastfeeding during the study period. 32. Employees of Lilly, relatives of Lilly employees, or employees of any third party whose employees need to be excluded from the study. 33. Personnel directly affiliated with the study site and/or their immediate family members, defined as spouses, parents, children, or siblings, whether biological or legally adopted. 34. Participants or caregivers who are unable or unwilling to participate in the duration of the study or to comply with study restrictions and procedures (including subcutaneous administration of study drugs). 35. A history of chronic alcohol abuse, intravenous drug abuse, or other illicit drug abuse within the two years prior to screening. 36. According to the researcher, it is not suitable for inclusion in the study in other respects.

Investigational drug : A pharmaceutical conjugate containing 125 mg/mL lerezab or placebo was administered subcutaneously to patients in the form of a sterile, prefilled syringe with a pre-assembled needle safety device (PFS-NSD). Table 1 provides the lerezab sequence. The placebo solution has the same appearance and volume as the active solution, except that it does not contain lerezab.

Administer INCS mometasone furoate nasal spray at a dose of 200 μg twice daily (2 sprays per nostril).

Research Design: The research design for this experiment is shown in Figure 1.

Following the screening and induction period, at baseline (visit 3), individuals meeting the inclusion and exclusion criteria were randomly assigned 1:1:1 to the following treatment arms: • Lerezab Q2W/Q4W arm: Lerezab 500 mg loading dose in weeks 0 and 2, followed by Lerezab 250 mg Q2W for 24 weeks (induction period) and then Lerezab 250 mg Q4W for 56 weeks (maintenance period). • Lerezab Q2W/Q8W arm: Lerezab 500 mg loading dose at weeks 0 and 2, followed by 250 mg Q2W for 24 weeks (induction period) and then 250 mg Q8W for 56 weeks (maintenance period). • PBO arm: Placebo Q2W for 24 weeks (induction period) and then placebo Q4W for 56 weeks (maintenance period). Adolescents were recruited on an open-label basis, and all adolescents were assigned to the lerezab Q2W/Q4W treatment arm.

Randomization of adult participants was performed using block randomization with fixed block size and stratified according to the following factors: asthma and/or aspirin-exacerbated respiratory disease (AERD) vs. no asthma/no AED; prior nasal polyp surgery vs. no prior nasal polyp surgery; geographic region (North America, Europe, the rest of the world).

Participants, researchers, and on-site staff remained completely blind to the treatment arm.

All participants received intranasal mometasone furoate at the start of the 4-week induction period and throughout the randomized treatment period (week 0 to week 56). Participants may continue to receive mometasone furoate during the SFU period at the investigator's discretion.

Statistical analysis was performed on primary, secondary, and exploratory endpoints.

Figure 1 is a schematic diagram of the phase 3 study design described in Example 1. Abbreviations: CFBL = Change from baseline; INCS = Nasal endothelial steroid; Lebri = Lebri monoclonal antibody; PBO = Placebo; Q2W = every 2 weeks; Q4W = every 4 weeks; Q8W = every 8 weeks.

TW202541839A_113148727_SEQL.xml

Claims (51)

A method for treating chronic sinusitis with nasal polyps in patients in need, the method comprising administering to the patient a therapeutically effective amount of an anti-IL-13 antibody, wherein the anti-IL-13 antibody includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes HCDR1 containing SEQ ID NO:1, HCDR2 containing SEQ ID NO:2, and HCDR3 containing SEQ ID NO:3, and the VL includes LCDR1 containing SEQ ID NO:4, LCDR2 containing SEQ ID NO:5, and LCDR3 containing SEQ ID NO:6. A method for treating chronic sinusitis with nasal polyps, the method comprising: selecting a patient with chronic sinusitis with nasal polyps and administering to the patient a therapeutically effective amount of an anti-IL-13 antibody, wherein the anti-IL-13 antibody includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes HCDR1 containing SEQ ID NO:1, HCDR2 containing SEQ ID NO:2 and HCDR3 containing SEQ ID NO:3, and the VL includes LCDR1 containing SEQ ID NO:4, LCDR2 containing SEQ ID NO:5 and LCDR3 containing SEQ ID NO:6. The method of claim 1 or 2, wherein the anti-IL-13 antibody includes VH containing SEQ ID NO:7 and VL containing SEQ ID NO:8. The method of any one of claims 1 to 3, wherein the anti-IL-13 antibody comprises a heavy chain containing SEQ ID NO:9 and a light chain containing SEQ ID NO:10. The method of any of claims 1 to 4, wherein the anti-IL-13 antibody system is lebrikizumab. The method described in any of claims 1 to 5, wherein the anti-IL-13 antibody system is administered subcutaneously to the patient. The method of any one of claims 1 to 6, wherein the anti-IL-13 antibody system is administered at a dose of 250 mg to 500 mg. The method described in any of claims 1 to 7, wherein the anti-IL-13 antibody system is administered subcutaneously to the patient at a dose of 250 mg every two weeks. The method described in claim 8, wherein the patient is further treated with the anti-IL-13 antibody at a loading dose of 500 mg. The method of claim 9, wherein the loading dose is administered to the patient in week 0 and week 2. The method described in any of claims 1 to 10, wherein the patient is treated with the anti-IL-13 antibody for approximately 24 weeks. The method described in any of the requests 1 to 11, wherein the patient is further treated for a maintenance period of approximately 32 weeks. The method of claim 12, wherein the patient is treated with a maintenance dose of the anti-IL-13 antibody at a dose of 250 mg every 4 weeks during the maintenance period. The method of claim 12, wherein the patient is treated with a maintenance dose of 250 mg of anti-IL-13 antibody every 8 weeks during the maintenance period. The method described in any of claims 1 to 14 further includes measuring the severity score of the patient’s nasal congestion symptoms (NCS) before, during and after the treatment. The method described in any of claims 1 to 14 further includes measuring the patient’s endoscopic nasal polyp score (NPS) before, during and after the treatment. The method of any of claims 1 to 16, wherein the anti-IL-13 antibody is administered to the patient using a subcutaneous delivery device. The method of claim 17, wherein the subcutaneous delivery device is selected from a pre-filled syringe, a disposable injection pen device, a microneedle device, a microinfusion device, a needle-free injection device, or an automatic syringe device. The method of any of claims 1 to 18 further includes administering nasal endothelial steroids to the patient. The method of claim 19, wherein the nasal endothelial steroid is mometasone furoate. The method of claim 19 or 20, wherein the nasal endothelial steroid is administered simultaneously, concurrently, or sequentially with the anti-IL-13 antibody. The method of any of the requests 1 to 21, wherein the patient has bilateral nasal polyps. The method of any of claims 1 to 22, wherein prior to the treatment, the patient's bilateral endoscopic NPS score for each nasal cavity is at least 5 out of 8, and the minimum score is 2. The method described in any of claims 1 to 23, wherein the patient suffers from nasal congestion and at least one other symptom selected from dullness of smell, anosmia, anterior nasal discharge, or posterior nasal discharge. If any of the methods requested in items 1 to 24 are used, the patient is 18 years of age or older. An anti-IL-13 antibody for treating chronic sinusitis with nasal polyps, wherein the anti-IL-13 antibody includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes HCDR1 containing SEQ ID NO:1, HCDR2 containing SEQ ID NO:2 and HCDR3 containing SEQ ID NO:3, and the VL includes LCDR1 containing SEQ ID NO:4, LCDR2 containing SEQ ID NO:5 and LCDR3 containing SEQ ID NO:6. A pharmaceutical composition comprising an anti-IL-13 antibody for treating chronic sinusitis with nasal polyps, wherein the anti-IL-13 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises HCDR1 containing SEQ ID NO:1, HCDR2 containing SEQ ID NO:2 and HCDR3 containing SEQ ID NO:3, and the VL comprises LCDR1 containing SEQ ID NO:4, LCDR2 containing SEQ ID NO:5 and LCDR3 containing SEQ ID NO:6. The use of an anti-IL-13 antibody in the manufacture of a medicament for treating chronic sinusitis with nasal polyps, wherein the anti-IL-13 antibody includes a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH includes HCDR1 containing SEQ ID NO:1, HCDR2 containing SEQ ID NO:2 and HCDR3 containing SEQ ID NO:3, and the VL includes LCDR1 containing SEQ ID NO:4, LCDR2 containing SEQ ID NO:5 and LCDR3 containing SEQ ID NO:6. The anti-IL-13 antibody used in claim 26 includes VH containing SEQ ID NO:7 and VL containing SEQ ID NO:8. The anti-IL-13 antibody used in claims 26 or 29 includes a heavy chain containing SEQ ID NO:9 and a light chain containing SEQ ID NO:10. The anti-IL-13 antibody used in any of the requests 26, 29 or 30, wherein the anti-IL-13 antibody is a levozo monoclonal antibody. The anti-IL-13 antibody used in any of claims 26 or 29 to 31, wherein the anti-IL-13 antibody is administered subcutaneously. The anti-IL-13 antibody used in any of claims 26 or 29 to 32, wherein the anti-IL-13 antibody is administered at a dose of 250 mg to 500 mg. The anti-IL-13 antibody used in any of claims 26 or 29 to 33 is administered subcutaneously at a dose of 250 mg every two weeks. The anti-IL-13 antibody used in any of claims 34, wherein the anti-IL-13 antibody is further administered at a loading dose of 500 mg. For example, the anti-IL-13 antibody used in claim 35, wherein the loading dose is administered in week 0 and week 2. The anti-IL-13 antibody used in any of claims 26 or 29 to 36, wherein the anti-IL-13 antibody is administered for approximately 24 weeks. The anti-IL-13 antibody used in any of claims 26 or 29 to 37, wherein the anti-IL-13 antibody is further administered for a maintenance period of approximately 32 weeks. The anti-IL-13 antibody used in claim 38, wherein the anti-IL-13 antibody is administered at a dose of 250 mg every 4 weeks during the maintenance period. The anti-IL-13 antibody used in claim 38, wherein the anti-IL-13 antibody is administered at a dose of 250 mg every 8 weeks during the maintenance period. The anti-IL-13 antibody used in any of the requests 26 or 29 to 40 further includes measuring the severity score of the patient's nasal congestion symptoms (NCS) before, during and after the treatment. The anti-IL-13 antibody used in any of claims 26 or 29 to 41 further includes measuring the patient’s endoscopic nasal polyp score (NPS) before, during and after the treatment. The anti-IL-13 antibody used in any of claims 26 or 29 to 42, wherein the anti-IL-13 antibody is administered using a subcutaneous administration device. The anti-IL-13 antibody used in claim 43, wherein the subcutaneous delivery device is selected from a pre-filled syringe, a disposable injection pen device, a microneedle device, a microinfusion device, a needle-free injection device, or an automatic syringe device. The anti-IL-13 antibody used in any of claims 26 or 29 to 44 may further include administration of nasal endothelial steroids. For example, the anti-IL-13 antibody used in claim 45, wherein the nasal endothelial steroid is mometasone furoate. The anti-IL-13 antibody used in claims 45 or 46, wherein the nasal endothelial steroid is administered simultaneously, concurrently, or sequentially with the anti-IL-13 antibody. The anti-IL-13 antibody used in any of claims 26 or 29 to 47, where the patient has bilateral nasal polyps. If the anti-IL-13 antibody used in any of the requests 26 or 29 to 48 is provided, the patient's bilateral endoscopic NPS score in each nasal cavity prior to the treatment is at least 5 out of 8, and the minimum score is 2. The anti-IL-13 antibody used in any of claims 26 or 29 to 49 is used in patients who have nasal congestion and at least one other symptom selected from dullness of smell, anosmia, anterior nasal discharge or posterior nasal discharge. If the anti-IL-13 antibody is used in any of the requests 26 or 29 to 49, the patient is 18 years of age or older.