Methods of treating chronic sinusitis with anti-IL-4Ralpha antibodies

Abstract

The present disclosure belongs to the field of biomedicine, and provides a method of treating chronic sinusitis with an anti-IL-4R [alpha] antibody, the method comprising administering to a subject in need thereof an anti-IL-4R [alpha] antibody or an antigen-binding fragment thereof, the chronic sinusitis including chronic sinusitis accompanied with nasal polyp and chronic sinusitis not accompanied with nasal polyp.

Description

Technical Field

[0001] The present disclosure belongs to the field of biomedicine, and specifically relates to a method for treating chronic sinusitis by administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof. Background Art

[0002] Chronic rhinosinusitis (CRS) is a highly heterogeneous disease characterized by chronic inflammation of the sinus mucosa. Common symptoms include nasal congestion, sticky or mucopurulent nasal discharge, facial pain, and decreased or lost sense of smell. Symptoms lasting for more than 12 weeks are defined as chronic. CRS is closely related to asthma, allergic rhinitis, etc. CRS can be clinically divided into chronic sinusitis with nasal polyps (CRSwNP) and chronic sinusitis without nasal polyps (CRSsNP). Type 2 inflammation is the main pathophysiological mechanism leading to refractory CRSwNP and CRSsNP.

[0003] Nasal polyps (NP) are proliferative masses of tissue that grow on the nasal or sinus mucosa and protrude from the nasal mucosa surface. Common symptoms of NP include nasal obstruction and congestion, reduced or lost olfactory perception, anterior and posterior rhinorrhoea, and facial pain. NP is a Th2 cell-driven inflammatory process that affects the mucosa of the nose and paranasal sinuses. Nasal polyp tissue often has high levels of IL-5, eosinophil cationic protein (ECP), and eotaxin, which attract and activate eosinophils, and therefore eosinophils and their products are considered to be hallmarks of nasal polyp-associated inflammation. Eosinophils are the main inflammatory cells found in nasal polyps, and nasal polyps are also associated with elevated levels of IgE.

[0004] Interleukin 4 (IL-4) and IL-13 are key cytokines that induce and maintain type 2 inflammatory responses. They are required to drive most key markers associated with type 2 inflammation, such as the production of immunoglobulin E and the recruitment of innate cells to the site of inflammation. IL-4 and IL-13 bind to IL-4Rα, triggering the transphosphorylation and activation of JAK kinases, inducing the phosphorylation of transcription factors STAT, and thus playing an important role in the occurrence and development of type 2 inflammatory diseases. The current treatment of chronic sinusitis focuses on inflammation control, and treatment methods include local or systemic broad-spectrum anti-inflammatory drugs, such as glucocorticoids and macrolides. If drug treatment is ineffective, endoscopic sinus surgery is used. However, some patients still have postoperative recurrence. Therefore, more effective treatment methods are still needed. SUMMARY OF THE INVENTION

[0006] In one aspect, the present disclosure provides a method for treating chronic sinusitis in a subject in need thereof, comprising administering to the subject an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure. In one aspect, the present disclosure provides a method for treating chronic sinusitis in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure. In one aspect, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for treating chronic sinusitis in a subject in need thereof. In one aspect, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the treatment of chronic sinusitis in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure.

[0007] In one aspect, the present disclosure provides a method for improving one or more sinusitis-related parameters in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure. In one aspect, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for improving one or more sinusitis-related parameters in a subject in need thereof. In one aspect, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in improving one or more sinusitis-related parameters in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure.

[0008] In some embodiments, the present disclosure also provides a pharmaceutical composition comprising an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure, which is used to treat chronic sinusitis in a subject in need thereof. In some embodiments, the present disclosure also provides a pharmaceutical composition comprising an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure, which is used to improve one or more sinusitis-related parameters in a subject in need thereof.

[0009] In some embodiments, the chronic sinusitis is bilateral chronic sinusitis.

[0010] In some embodiments, the chronic sinusitis is chronic sinusitis with nasal polyps (CRSwNP). In some embodiments, the chronic sinusitis is bilateral chronic sinusitis with nasal polyps. In some embodiments, the chronic sinusitis is eosinophilic chronic sinusitis with nasal polyps.

[0011] In some embodiments, the chronic sinusitis is chronic sinusitis without nasal polyps (CRSsNP). In some embodiments, the chronic sinusitis is bilateral chronic sinusitis without nasal polyps. In some embodiments, the chronic sinusitis is eosinophilic chronic sinusitis without nasal polyps.

[0012] In some embodiments, the subject with chronic sinusitis further suffers from asthma. In some embodiments, the subject with bilateral chronic sinusitis further suffers from asthma. In some embodiments, the subject with chronic sinusitis with nasal polyps further suffers from asthma. In some embodiments, the subject with bilateral chronic sinusitis with nasal polyps further suffers from asthma. In some embodiments, the subject with eosinophilic chronic sinusitis with nasal polyps further suffers from asthma. In some embodiments, the subject with chronic sinusitis without nasal polyps further suffers from asthma. In some embodiments, the subject with bilateral chronic sinusitis without nasal polyps further suffers from asthma. In some embodiments, the subject with eosinophilic chronic sinusitis without nasal polyps further suffers from asthma.

[0013] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered once every 2 weeks (Q2W). In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at a dose of 100-1200 mg each time. DETAILED DESCRIPTION OF THE INVENTION

[0015] Before describing the present disclosure, it should be understood that the present disclosure is not limited to the specific methods and experimental conditions described, because these methods and conditions can be varied. Unless otherwise specified, the terms used in the present disclosure should not be considered to be uncertain or unclear in the absence of special definitions, but should be understood according to the common meanings in the art. It should also be understood that the terms used herein are only for the purpose of describing specific embodiments, and are not intended to be limiting. When a trade name appears in the present disclosure, it is intended to refer to the corresponding commodity or its active ingredient.

[0016] As used herein, "about" means within the acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" may mean within 1 or more than 1 standard deviation as practiced in the art. Alternatively, "about" may mean a range of up to ±5%, such as fluctuations within ±2%, within ±1%, or within ±0.5% of a given specific numerical range. When a specific value is given in the present disclosure or claims, unless otherwise indicated, the meaning of "about" should be considered to be within the acceptable error range for that specific value. In this document, unless otherwise indicated, all values ​​of drug doses, times, step parameters, or conditions are modified by "about" by default.

[0017] Treatments for chronic sinusitis

[0018] In one aspect, the present disclosure provides a method for treating chronic sinusitis in a subject in need thereof, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In one aspect, the present disclosure provides a method for treating chronic sinusitis in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In one aspect, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for treating chronic sinusitis in a subject in need thereof. In one aspect, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the treatment of chronic sinusitis in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof may be formulated with one or more pharmaceutically acceptable excipients to form a suitable pharmaceutical composition for administration to a subject in need thereof.

[0019] The terms "administering" or "administering" refer to the physical introduction of a therapeutic agent into a subject using any of a variety of methods and delivery systems known to those skilled in the art.

[0020] As used herein, the terms "subject," "patient," or "subject" are used interchangeably. The terms "subject," "patient," or "subject" include any human or non-human animal. The term "non-human animal" includes, but is not limited to, vertebrates such as non-human primates, sheep, dogs, and rodents such as mice, rats, and guinea pigs. In some embodiments, the terms "subject," "patient," or "subject" are mammals. In some embodiments, the subject, patient, or subject is a mouse. In some embodiments, the subject, patient, or subject is a human.

[0021] As used herein, "sinusitis" refers to inflammation of the paranasal sinuses, including inflammation of the maxillary sinus, frontal sinus, ethmoid sinus and sphenoid sinus. As used herein, "chronic sinusitis" ("CRS") is a chronic inflammatory disease of the sinus mucosa, with a course of 8 weeks or longer (e.g., more than 12 weeks). CRS is characterized by a combination of any specific symptoms, including but not limited to nasal congestion, sticky or mucopurulent nasal discharge, nasal discharge, nasal itching, dyspnea, reduced or lost sense of smell, anterior and / or posterior epistaxis, headache and / or facial pain and its consequences. The formal diagnosis is based on a sinus computed tomography (CT) scan and / or sinus endoscopy. Based on endoscopic evaluation, CRS can be clinically divided into chronic sinusitis with nasal polyps and chronic sinusitis without nasal polyps. In addition, "sinusitis" described herein also includes conditions with symptoms of rhinitis.

[0022] In some embodiments, the chronic sinusitis is chronic sinusitis with nasal polyps. In some embodiments, the chronic sinusitis is bilateral chronic sinusitis with nasal polyps.

[0023] In some embodiments, the chronic sinusitis is chronic sinusitis without nasal polyps. In some embodiments, the chronic sinusitis is bilateral chronic sinusitis without nasal polyps. In some embodiments, the chronic sinusitis is eosinophilic chronic sinusitis without nasal polyps.

[0024] As used herein, "nasal polyps" are overgrowths of tissue in one or more nasal cavities. About 80% of nasal polyps are highly edematous and filled with eosinophils. Nasal polyps can also exist as fibers, glands, or cysts. Nasal polyps are teardrop-shaped growths that usually form in the nose and / or sinuses, blocking the sinuses and nasal passages.

[0025] Methods to improve sinusitis-related parameters

[0026] In one aspect, the present disclosure provides a method for improving one or more sinusitis-related parameters in a subject in need thereof, comprising administering an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject. In one aspect, the present disclosure provides a method for improving one or more sinusitis-related parameters in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject. In one aspect, the present disclosure provides the use of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for improving one or more sinusitis-related parameters in a subject in need thereof. In one aspect, the present disclosure provides the use of an anti-IL-4Rα antibody or antigen-binding fragment thereof in improving one or more sinusitis-related parameters in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof may be formulated with one or more pharmaceutically acceptable excipients to form a suitable pharmaceutical composition for administration to a subject in need thereof.

[0027] Examples of "sinusitis-related parameters" include, but are not limited to: (1) Nasal Polyp Score (NPS), (2) Lund Mackay Score, (3) Modified Lund Mackay Score, Kennedy score, (4) total sinus symptom score (sTSS), including nasal congestion, rhinorrhea (mean of anterior and posterior rhinorrhea), and facial pain / pressure, (5) nasal sinus outcome test (SNOT-22) score, (6) anosmia score, (7) UPSIT score, (8) nasal congestion score (NCS), (9) nasal / posterior rhinorrhea score, (10) facial pain / pressure score, (11) sinusitis visual analog scale (VAS) score, (12) health-related quality of life (HRQoL), (13) nasal peak inspiratory flow (NPIF), (14) proportion of patients receiving systemic corticosteroid (SCS) rescue or surgical treatment during treatment, (15) asthma control questionnaire (ACQ-6) score, (16) pulmonary ventilation function, including FEV1, FVC, and FEF 25-75, (17) sinusitis-related biomarkers, and (18) nasal secretion microorganisms. "Improvement of sinusitis-related parameters", "improvement of sinusitis-related parameters", and "improvement of one or more sinusitis-related parameters" means an increase in one or more of the following parameters relative to baseline: nasal peak inspiratory flow (NPIF), UPSIT score, and / or a decrease in one or more of the following parameters relative to baseline: nasal polyp score (NPS), Lund Mackay score, modified Lund Kennedy score, total sinus symptom score (sTSS), nasal congestion score (NCS), rhinorrhea score, facial pain / pressure score, anosmia score, nasal / postnasal discharge score, SNOT-22 score, VAS score, proportion of patients receiving systemic corticosteroid (SCS) rescue or surgical treatment during treatment, ACQ-6 score for patients with asthma. "Improvement in a sinusitis-related parameter" can be expressed as a percentage, for example, the score can be improved by 1% or more, 3% or more, 5% or more, 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, or 80% or more. As used herein, the term "baseline" is used herein in its ordinary sense as understood by those skilled in the art, for example, with respect to a sinusitis-related parameter, it refers to the value of the sinusitis-related parameter of the patient before or at the time of administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure; for example, "baseline" is the average of all measurements for 7 days before administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure, or the most recent non-missing measurement before administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure.

[0028] To determine whether a certain sinusitis-related parameter has been "improved," the parameter is quantified at baseline and at a certain time point after administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. For example, the parameter can be quantified at day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 8, day 9, day 10, day 11, day 12, day 14, or week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12, week 13, week 14, or week 15 after the subject is initially treated with the anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. At 4 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, or longer, the sinusitis-related parameter is measured. In certain embodiments, the parameter is measured daily (e.g., including but not limited to once or twice daily), weekly, biweekly, or monthly.

[0029] The difference between the value of a sinusitis-related parameter at a specific time point after the start of treatment and the value of the sinusitis-related parameter at baseline is used to demonstrate whether the sinusitis-related parameter has "improved" (e.g., increased or decreased, as appropriate, depending on the specific parameter measured).

[0030] (1) Nasal Polyp Score (NPS)

[0031] In some embodiments, the present disclosure provides a method for reducing NPS in a subject in need thereof, comprising administering to the subject a disclosed anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, the present disclosure provides a method for reducing NPS in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing NPS in a subject in need thereof. NPS is the sum of the scores of the left and right nostrils assessed by nasal endoscopy. NPS is scored from 0 to 4 points according to the grading of polyps, with 0 indicating that no polyps are present, 1 indicating that a small polyp is present in the middle nasal meatus but does not reach below the lower edge of the middle turbinate, 2 indicating that the polyp reaches below the lower edge of the middle turbinate, 3 indicating that a large polyp reaches the lower edge of the inferior turbinate or the inner side of the middle turbinate, and 4 indicating that a large polyp completely blocks the inferior nasal cavity. The NPS score ranges from 0 to 8 points (4 points per nasal cavity).

[0032] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in NPS relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in NPS relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in NPS relative to baseline of 0.1 to 8 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in NPS relative to baseline of 1 to 8 points, for example, resulting in a decrease in NPS of at least 1 point, 2 points, or 3 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in NPS relative to baseline of at least 1 point, 1.5 points, 2 points, 2.5 points, 3 points, 3.5 points, 4 points, 4.5 points, 5 points, 5.5 points, 6 points, 6.5 points, 7 points, 7.5 points, or 8 points, or a range formed by any of the foregoing values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in NPS relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values. In some embodiments, administering an anti-IL-4Rα antibody or antigen-binding fragment thereof of the disclosure to the subject results in a decrease in NPS to less than 4 points (eg, 3 points or less).

[0033] In some embodiments, treatment of the subject with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles results in a decrease in NPS relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in NPS relative to baseline of at least 1 point, 1.5 points, 2 points, 2.5 points, 3 points, 3.5 points, 4 points, 4.5 points, 5 points, 5.5 points, 6 points, 6.5 points, 7 points, 7.5 points, or 8 points, or a range formed by any of the foregoing values. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in NPS of at least 1 point, 2 points, or 3 points relative to baseline.

[0034] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in NPS to less than 4 points (e.g., 3 points or less).

[0035] (2) LundMackay score

[0036] In some embodiments, the present disclosure provides a method for reducing the Lund Mackay score in a subject in need thereof, comprising administering to the subject an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides a method for reducing the Lund Mackay score in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing the Lund Mackay score in a subject in need thereof. Using a sinus CT scan, a Lund Mackay score is performed based on the degree of local opacity (including the maxillary sinus, the anterior ethmoid sinus, the posterior ethmoid sinus, the sphenoid sinus, the frontal sinus, and the ostiomeatal complex). For the Lund Mackay score of the maxillary sinus, the anterior ethmoid sinus, the posterior ethmoid sinus, the sphenoid sinus, or the frontal sinus, 0 = normal, 1 = partial opacity, 2 = complete opacity; for the Lund Mackay score of the ostiomeatal complex, 0 = non-occluded, 2 = occluded. The left and right sinus systems were scored, with scores for each side ranging from 0 to 12, and the Lund Mackay score ranged from 0 to 24. For patients with a current loss of the ostiomeatal complex (OC) due to previous surgery, a comprehensive score was given based on the location of the previous OC.

[0037] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in Lund Mackay score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in Lund Mackay score relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in Lund Mackay score relative to baseline of 0.1 to 24 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in Lund Mackay score of at least 0.2, 0.4, 0.6, 0.8, 1, 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.2, 3.4, 3.6, 3.8, 4, 5, 6, 7, 8, 9, 10, 11, or 12 points relative to baseline, or a range formed by any of the above values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in Lund Mackay score of at least 1, 2, or 3 points relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in Lund Mackay score relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values. In some embodiments, administering an anti-IL-4Rα antibody or antigen-binding fragment thereof of the disclosure to the subject results in a decrease in the Lund Mackay score to less than 2 points (eg, 1 point or less).

[0038] In some embodiments, treatment of the subject with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles results in a decrease in Lund Mackay score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in Lund. A decrease in Mackay score relative to baseline of at least 0.2, 0.4, 0.6, 0.8, 1, 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.2, 3.4, 3.6, 3.8, 4, 5, 6, 7, 8, 9, 10, 11, or 12 points, or a range formed by any of the foregoing values. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in Lund Mackay score of at least 1, 2, or 3 points relative to baseline.

[0039] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in Lund Mackay score to less than 2 points (e.g., 1 point or less).

[0040] (3) Modified LundKennedy score

[0041] In some embodiments, the present disclosure provides a method for reducing a modified Lund Kennedy score in a subject in need thereof, comprising administering to the subject an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides a method for reducing a modified Lund Kennedy score in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides a use of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing a modified Lund Kennedy score in a subject in need thereof. The modified Lund Kennedy score is performed using nasal endoscopy, and the nasal mucosal manifestations are divided into 3 categories: (1) polyps: 0 = none, 1 = polyps only in the middle nasal meatus, 2 = polyps beyond the middle nasal meatus; (2) secretions: 0 = none, 1 = clear, thin secretions, 2 = thick, purulent secretions; (3) edema: 0 = none, 1 = mild, 2 = severe. The left and right nasal cavities were scored separately, with scores for each side ranging from 0 to 6 points, and the modified Lund Kennedy score ranged from 0 to 12 points.

[0042] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the modified Lund Kennedy score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the modified Lund Kennedy score relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the modified Lund Kennedy score relative to baseline of 0.1 to 12 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in the modified Lund Kennedy score of at least 0.2, 0.4, 0.6, 0.8, 1, 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.2, 3.4, 3.6, 3.8, 4, 5, 6, 7, 8, 9, 10, 11, or 12 points relative to baseline, or a range formed by any of the above values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in the modified Lund Kennedy score of at least 1, 2, or 3 points relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in modified Lund Kennedy score of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values, relative to baseline. In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the disclosure to the subject results in a decrease in the modified Lund Kennedy score to less than 2 points (eg, 1 point or less).

[0043] In some embodiments, treatment of the subject with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles results in a decrease in the modified Lund Kennedy score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in improved Lund Cysts. Kennedy score is decreased by at least 0.2, 0.4, 0.6, 0.8, 1, 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.2, 3.4, 3.6, 3.8, 4, 5, 6, 7, 8, 9, 10, 11, or 12 points relative to baseline, or a range formed by any of the above values. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in the modified Lund Kennedy score of at least 1, 2, or 3 points relative to baseline.

[0044] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a reduction in the modified Lund Kennedy score to less than 2 points (e.g., 1 point or less).

[0045] (4) Total sinus symptom score (sTSS)

[0046] In some embodiments, the present disclosure provides a method for reducing sTSS in a subject in need thereof, comprising administering to the subject an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides a method for reducing sTSS in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing sTSS in a subject in need thereof. Scoring is performed for three types of symptoms: nasal congestion, rhinorrhoea (average of anterior and posterior rhinorrhoea), and facial pain or pressure, each of which adopts a 0-3 categorical scale (where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, and 3 = severe symptoms). sTSS is the sum of the scores for nasal congestion, rhinorrhoea, and facial pain or pressure, and the sTSS score ranges from 0 to 9 points. Nasal symptoms can be measured at a fixed time in the morning.

[0047] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in sTSS relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in sTSS relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in sTSS relative to baseline of 0.1 to 9 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in sTSS relative to baseline of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, 3 points, 3.5 points, 4 points, 4.5 points, 5 points, 5.5 points, 6 points, 6.5 points, 7 points, 7.5 points, 8 points, 8.5 points, or 9 points or a range formed by any of the foregoing values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in sTSS relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values.

[0048] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in sTSS relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in sTSS relative to baseline of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, 3 points, 3.5 points, 4 points, 4.5 points, 5 points, 5.5 points, 6 points, 6.5 points, 7 points, 7.5 points, 8 points, 8.5 points, or 9 points, or a range formed by any of the foregoing values.

[0049] In some embodiments, the present disclosure provides a method for reducing a nasal congestion score in a subject in need thereof, comprising administering to the subject an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides a method for reducing a nasal congestion score in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides a use of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing a nasal congestion score in a subject in need thereof.

[0050] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the nasal congestion score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the nasal congestion score relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the nasal congestion score of 0.1 to 3 points relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the nasal congestion score of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, or 3 points relative to baseline, or a range formed by any of the above values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the nasal congestion score of at least 0.5 points relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in nasal congestion score relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values. In some embodiments, administering an anti-IL-4Rα antibody or antigen-binding fragment thereof of the disclosure to the subject results in a reduction in the nasal congestion score to less than 2 points (eg, 1 point or less).

[0051] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in nasal congestion score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in nasal congestion score of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, or 3 points relative to baseline, or a range formed by any of the foregoing values. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in nasal congestion score of at least 0.5 points relative to baseline.

[0052] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a reduction in the nasal congestion score to less than 2 points (e.g., 1 point or less).

[0053] In some embodiments, the present disclosure provides a method for reducing rhinorrhea scores in a subject in need thereof, comprising administering to the subject an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides a method for reducing rhinorrhea scores in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing rhinorrhea scores in a subject in need thereof.

[0054] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the rhinorrhea score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the rhinorrhea score relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the rhinorrhea score relative to baseline of at least 0.1 to 3 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the rhinorrhea score relative to baseline of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, or 3 points, or a range formed by any of the above values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the rhinorrhea score relative to baseline of at least 0.5 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in rhinorrhea score relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values.

[0055] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in rhinorrhoea score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in rhinorrhea score of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, or 3 points relative to baseline, or a range formed by any of the foregoing values. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in rhinorrhea score of at least 0.5 points relative to baseline.

[0056] In some embodiments, the present disclosure provides a method for reducing facial pain / stress scores in a subject in need thereof, comprising administering to the subject an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides a method for reducing facial pain / stress scores in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing facial pain / stress scores in a subject in need thereof.

[0057] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in facial pain / stress score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in facial pain / stress score relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in facial pain / stress score of 0.1 to 3 points relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in facial pain / stress score of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, or 3 points relative to baseline, or a range formed by any of the foregoing values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in facial pain / stress score of at least 0.5 points relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in facial pain / stress score relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values.

[0058] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in facial pain / stress score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in facial pain / stress score of at least 0.5, 1, 1.5, 2, 2.5, or 3 points relative to baseline, or a range formed by any of the foregoing values. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in facial pain / stress score of at least 0.5 points relative to baseline.

[0059] (5) Nasal Sinus Outcome Test (SNOT-22)

[0060] In some embodiments, the present disclosure provides a method for reducing the SNOT-22 score in a subject in need, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides a method for reducing the SNOT-22 score in a subject in need, comprising administering a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing the SNOT-22 score in a subject in need. SNOT-22 is used to assess the impact of CRS on the quality of life of patients, and the scale has a total of 22 questions, including three dimensions: physiological problems, functional limitations, and emotional outcomes. The SNOT-22 score ranges from 0 to 110 points, and the higher the score, the greater the impact of CRS on health-related quality of life (HRQoL) (Hopkins et al 2009, Clin. Otolaryngol. 34: 447-454).

[0061] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the SNOT-22 score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the SNOT-22 score relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in the SNOT-22 score relative to baseline of 0.1 to 110 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in the SNOT-22 score of at least 1 point relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in SNOT-22 score relative to baseline by at least 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, 10 points, 11 points, 12 points, 13 points, 14 points, 15 points, 16 points, 17 points, 18 points, 19 points, 20 points, 21 points, 22 points, 23 points, 24 points, 25 points, 26 points, 27 points, 28 points, 29 points, 30 points, or 40 points, or a range formed by any of the above values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in SNOT-22 score relative to baseline by at least 8.9 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in SNOT-22 score relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values. In some embodiments, administering an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the SNOT-22 score to less than 30 points.

[0062] In some embodiments, treatment of the subject with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles results in a decrease in SNOT-22 score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in SNOT-22 score of at least 1 point relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, 21 treatment cycles, 22 treatment cycles, 23 treatment cycles, 24 treatment cycles, 25 treatment cycles, 26 treatment cycles, 27 treatment cycles, 28 treatment cycles, 29 treatment cycles, 30 treatment cycles, 31 treatment cycles, 32 treatment cycles, 33 treatment cycles, 34 treatment cycles, 35 treatment cycles, 36 treatment cycles, 37 treatment cycles, 38 treatment cycles, 39 treatment cycles, 40 treatment cycles, 41 treatment cycles, 42 treatment cycles, 43 treatment cycles, 44 treatment cycles, 45 treatment cycles, 46 treatment cycles, 47 treatment cycles, 48 ​​treatment cycles, 49 treatment cycles, 50 treatment cycles, 51 treatment cycles, 52 treatment cycles, After 9 treatment cycles, 20 treatment cycles, or more treatment cycles, the SNOT-22 score is reduced by at least 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, 10 points, 11 points, 12 points, 13 points, 14 points, 15 points, 16 points, 17 points, 18 points, 19 points, 20 points, 21 points, 22 points, 23 points, 24 points, 25 points, 26 points, 27 points, 28 points, 29 points, 30 points, or 40 points, or a range formed by any of the above values, relative to baseline.In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in SNOT-22 score of at least 8.9 points relative to baseline.

[0063] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in SNOT-22 score to less than 30 points.

[0064] (6) Olfactory loss score

[0065] In some embodiments, the present disclosure provides a method for reducing a loss of smell score in a subject in need thereof, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides a method for reducing a loss of smell score in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing a loss of smell score in a subject in need thereof. The loss of smell score ranges from 0 to 3 points, with 0 points indicating no symptoms, 1 point indicating mild symptoms, 2 points indicating moderate symptoms, and 3 points indicating severe symptoms.

[0066] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the loss of smell score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the loss of smell score relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the loss of smell score relative to baseline of 0.1 to 3 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the loss of smell score relative to baseline of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, or 3 points, or a range formed by any of the foregoing values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the loss of smell score relative to baseline of at least 0.5 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in anosmia score of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values, relative to baseline.

[0067] In some embodiments, treatment of the subject with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles results in a decrease in loss of smell score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in the loss of smell score of at least 0.5, 1, 1.5, 2, 2.5, or 3 points relative to baseline, or a range formed by any of the foregoing values. In some embodiments, treatment of the subject with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles results in a decrease in anosmia score of at least 0.5 points relative to baseline.

[0068] (7) University of Pennsylvania Smell Identification Test (UPSIT) score

[0069] In some embodiments, the present disclosure provides a method for increasing the UPSIT score in a subject in need thereof, comprising administering to the subject an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides a method for increasing the UPSIT score in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for increasing the UPSIT score in a subject in need thereof. The UPSIT score ranges from 0 to 40 points, with 35 to 40 points indicating normal sense of smell, 15 to 34 points indicating decreased sense of smell, and <15 points indicating loss of smell.

[0070] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in the UPSIT score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in the UPSIT score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in the UPSIT score relative to baseline of 0.1 to 40 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in the UPSIT score relative to baseline of at least 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, 10 points, 11 points, 12 points, 13 points, 14 points, 15 points, 16 points, 17 points, 18 points, 19 points, 20 points, or a range formed by any of the above values. In some embodiments, administering a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in UPSIT score of at least 4 points relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in UPSIT score relative to baseline by at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values.

[0071] In some embodiments, treatment of the subject with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles results in an increase in UPSIT score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in an increase in UPSIT score of at least 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, 10 points, 11 points, 12 points, 13 points, 14 points, 15 points, 16 points, 17 points, 18 points, 19 points, 20 points, or a range formed by any of the foregoing values ​​relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in an increase in UPSIT score of at least 4 points relative to baseline.

[0072] (8) Rhinorrhoea / postnasal discharge score

[0073] In some embodiments, the present disclosure provides a method for reducing the nasal discharge / post-nasal discharge score in a subject in need thereof, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides a method for reducing the nasal discharge / post-nasal discharge score in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing the nasal discharge / post-nasal discharge score in a subject in need thereof. Symptoms are divided into 4 levels from mild to severe, which are scored as 0 points, 1 point, 2 points and 3 points respectively.

[0074] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the nasal discharge / post-nasal discharge score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the nasal discharge / post-nasal discharge score relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the nasal discharge / post-nasal discharge score relative to baseline of 0.1 to 3 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the nasal discharge / post-nasal discharge score relative to baseline of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, or 3 points, or a range formed by any of the above values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the nasal discharge / post-nasal discharge score relative to baseline of at least 0.5 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in nasal discharge / post-nasal discharge score relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values.

[0075] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in nasal discharge / post-nasal discharge score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in the nasal discharge / post-nasal discharge score of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, or 3 points, or a range formed by any of the foregoing values, relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in the runny nose / post-runny nose score of at least 0.5 points relative to baseline.

[0076] (9) Sinusitis Visual Analog Scale (VAS) score

[0077] In some embodiments, the present disclosure provides a method for reducing the VAS score in a subject in need thereof, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides a method for reducing the VAS score in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing the VAS score in a subject in need thereof. VAS is used to evaluate the severity of sinusitis symptoms in patients, and the VAS score ranges from 0 to 10 points. The lower the score, the less impact sinusitis has on the subject's quality of life. 0 points ≤ VAS score ≤ 3 points indicates mild symptoms, 3 < VAS score ≤ 7 indicates moderate symptoms, and 7 < VAS score ≤ 10 indicates severe symptoms.

[0078] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the VAS score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the VAS score relative to baseline (i.e., a lower number is achieved on the scale). In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the VAS score relative to baseline of 0.1 to 10 points, 0.5 to 10 points, or 0.5 to 5 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in the VAS score relative to baseline of at least 0.5 points, 1 point, 1.5 points, 2 points, 2.5 points, 3 points, 3.5 points, 4 points, 4.5 points, or 5 points, or a range formed by any of the foregoing values. In some embodiments, administering a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in VAS score of at least 2 points (eg, 3 points or more) relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in VAS score relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values. In some embodiments, administering an anti-IL-4Rα antibody or antigen-binding fragment thereof of the disclosure to the subject results in a decrease in the VAS score to less than 5 points (eg, 4 points or less).

[0079] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in VAS score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in VAS score of at least 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 points relative to baseline, or a range formed by any of the foregoing values. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in VAS score of at least 2 points (e.g., 3 points or more) relative to baseline.

[0080] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in the VAS score to less than 5 points (e.g., 4 points or less).

[0081] (10) Health quality of life (HRQoL)

[0082] A variety of HRQoL can be used to monitor the efficacy of anti-IL-4Rα antibodies or antigen-binding fragments thereof, including the Short-Form-36 (SF-36) and the European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) scale.

[0083] The EQ-5D-5L questionnaire includes 5 aspects: mobility, self-care, daily activities, pain / discomfort, and anxiety / depression, and each aspect has 5 levels: no problems, slight problems, some problems, serious problems, and extremely serious problems. Subjects are asked to indicate their current health status by selecting the most appropriate level in the 5 aspects. The questionnaire also includes a visual analog scale, which requires subjects to rate their current health status using a 0-100 scale, where 100 is the best health state imaginable and 0 is the worst health state imaginable.

[0084] SF-36 is a questionnaire used to assess the health status of subjects, including 8 aspects: physical function (PF, a total of 10 items), physical role (RP, a total of 4 items), bodily pain (BP, a total of 2 items), general health (GH, a total of 5 items), vitality (VT, a total of 4 items), social function (SF, a total of 2 items), emotional role (RE, a total of 3 items) and mental health (MH, a total of 5 items). The total physical health measurement (PCS) includes PF, RP, BP and GH, and the total mental health measurement (MCS) includes: VT, SF, RE, MH. For each aspect, the score of each item is coded, summed, and converted to a scale from 0 to 100. The average of the converted scores of the 8 aspects is the total score, and the PCS score and MCS score are averaged by the scores of the corresponding 4 aspects. The high or low score directly reflects the quality of health status. The higher the score, the better the functional status of this aspect and the higher the quality of life.

[0085] (11) Nasal peak inspiratory flow (NPIF)

[0086] In some embodiments, the present disclosure provides a method for increasing NPIF in a subject in need thereof, comprising administering to the subject an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides a method for increasing NPIF in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for increasing NPIF in a subject in need thereof. NPIF monitors the subject's nasal flow rate and assesses the patient's nasal resistance by measuring the maximum inspiratory flow rate of both nostrils, and is most relevant to the subject's subjective feeling of nasal congestion.

[0087] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in NPIF relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in NPIF relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in NPIF relative to baseline of at least 0.10 L / min, 0.15 L / min, 0.20 L / min, 0.25 L / min, 0.30 L / min, 0.35 L / min, 0.40 L / min, 0.45 L / min, 0.50 L / min, 0.55 L / min, 0.60 L / min, 0.65 L / min, 0.70 L / min, 0.75 L / min, 0.80 L / min, 0.85 L / min, 0.90 L / min, 0.95 L / min, or 1 L / min, or a range formed by any of the foregoing values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in NPIF relative to baseline by at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values.

[0088] In some embodiments, treatment of the subject with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles results in an increase in NPIF relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in NPIF-related An increase from baseline of at least 0.10 L / min, 0.15 L / min, 0.20 L / min, 0.25 L / min, 0.30 L / min, 0.35 L / min, 0.40 L / min, 0.45 L / min, 0.50 L / min, 0.55 L / min, 0.60 L / min, 0.65 L / min, 0.70 L / min, 0.75 L / min, 0.80 L / min, 0.85 L / min, 0.90 L / min, 0.95 L / min, or 1 L / min, or a range formed by any of the foregoing values.

[0089] (12) Asthma Control Questionnaire (ACQ-6)

[0090] In some embodiments, the present disclosure provides a method for reducing an ACQ-6 score in a subject in need thereof, comprising administering an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides a method for reducing an ACQ-6 score in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for reducing an ACQ-6 score in a subject in need thereof. The ACQ-6 measures the adequacy of asthma control and changes in asthma control that occur spontaneously or as a result of treatment. Subjects record five asthma symptoms (nighttime awakening, symptoms when awakening, activity limitation, shortness of breath, and wheezing) and the use of bronchodilators (e.g., short-acting β2 receptor agonists) in the ACQ-6 according to a 7-point scale (scoring ranges from 0 points for complete control to 6 points for severe poor control), and the ACQ-6 score is a weighted average of the five asthma symptom scores. Only subjects with comorbid asthma were assessed with the ACQ-6.

[0091] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in ACQ-6 score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in ACQ-6 score relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in ACQ-6 score relative to baseline of at least 0.1 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in ACQ-6 score relative to baseline of at least 0.5 points. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in ACQ-6 score relative to baseline of at least 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 2, or 3 points, or a range formed by any of the foregoing values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in a decrease in ACQ-6 score relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values.

[0092] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in ACQ-6 score relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in ACQ-6 score of at least 0.1 point relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in a decrease in ACQ-6 score of at least 0.5 points relative to baseline.In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles. The invention further provides that the ACQ-6 score is decreased by at least 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 2, or 3 points, or a range formed by any of the above values, relative to baseline after 1 treatment cycle, 19 treatment cycles, 20 treatment cycles, or more treatment cycles.

[0093] (13) Pulmonary ventilation function measurement

[0094] In some embodiments, the present disclosure provides a method for improving pulmonary ventilation function in a subject in need thereof, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides a method for improving pulmonary ventilation function in a subject in need thereof, comprising administering a therapeutically effective amount of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure to the subject. In some embodiments, the present disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof of the present disclosure in the preparation of a medicament for improving pulmonary ventilation function in a subject in need thereof. Pulmonary ventilation function measurements include forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF 25-75 ), where FEF 25-75 It refers to the average expiratory flow rate when 25%-75% of vital capacity is exhaled forcefully.

[0095] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FEV1 relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FEV1 relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FEV1 relative to baseline of at least 10 mL. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FEV1 relative to baseline of at least 20 mL, 40 mL, 60 mL, 70 mL, 80 mL, 90 mL, 100 mL, 110 mL, 120 mL, 130 mL, 140 mL, 150 mL, 160 mL, 170 mL, 180 mL, 190 mL, 200 mL, 210 mL, 220 mL, 230 mL, 240 mL, 250 mL, 260 mL, 270 mL, 280 mL, 290 mL, 300 mL, 320 mL, 340 mL, 360 mL, 380 mL, or 400 mL, or a range formed by any of the foregoing values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FEV1 relative to baseline by at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FEV1 of at least 100-200 mL relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FEV1 of at least 100 mL relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FEV1 of at least 150 mL relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FEV1 of at least 200 mL relative to baseline.

[0096] In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in an increase in FEV1 relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in an increase in FEV1 of at least 10 mL relative to baseline. In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in an increase in FEV1. For an increase from baseline of at least 20 mL, 40 mL, 60 mL, 70 mL, 80 mL, 90 mL, 100 mL, 110 mL, 120 mL, 130 mL, 140 mL, 150 mL, 160 mL, 170 mL, 180 mL, 190 mL, 200 mL, 210 mL, 220 mL, 230 mL, 240 mL, 250 mL, 260 mL, 270 mL, 280 mL, 290 mL, 300 mL, 320 mL, 340 mL, 360 mL, 380 mL, or 400 mL, or a range formed by any of the foregoing values.In some embodiments, the subject is treated with an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, 5 treatment cycles, 6 treatment cycles, 7 treatment cycles, 8 treatment cycles, 9 treatment cycles, 10 treatment cycles, 11 treatment cycles, 12 treatment cycles, 13 treatment cycles, 14 treatment cycles, 15 treatment cycles, 16 treatment cycles, 17 treatment cycles, 18 treatment cycles, 19 treatment cycles, 20 treatment cycles, or more treatment cycles, resulting in an increase in FEV1 of at least 100-200 mL relative to baseline.

[0097] In some embodiments, administration of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FVC relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FVC relative to baseline. In some embodiments, administration of a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in an increase in FVC relative to baseline of at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or a range formed by any of the foregoing values.

[0098] In some embodiments, administering the anti-IL-4Rα antibodies or antigen-binding fragments thereof of the present disclosure to the subject results in FEF 25-75 In some embodiments, administering a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in FEF 25-75 In some embodiments, administering a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject results in FEF 25-75%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% increase relative to baseline.

[0099] (14) Biomarkers related to sinusitis

[0100] Sinusitis-related biomarkers include biomarkers of blood and nasal exfoliated cells, including but not limited to one or any combination of IgE, eosinophil count, eotaxin-3 (CCL26), cystatin 1 (CST1), Charcot-Leyden crystal protein (CLC) and arachidonic acid-15-lipoxygenase (ALOX15). In some embodiments of the present disclosure, one or more sinusitis-related biomarkers can be detected from a biological sample derived from a subject. Biological samples include but are not limited to one or any combination of the following materials taken from a subject: culture, cells, tissues, blood (e.g., peripheral blood), saliva, nasal secretions, nasal exfoliated cells, cerebrospinal fluid, pleural fluid, milk, lymph, sputum, semen, needle aspirates, etc. Any method known in the art can be used to obtain biological samples. For example, nasal secretion samples can be obtained from smears, blown secretions, prints, lavages, wipes, washes, etc.

[0101] In some embodiments, after administering the anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject, one or more of the following of the subject is reduced relative to baseline: IgE level, eosinophil count, CCL26 level, CST1 level, CLC level, and ALOX15 level. In some embodiments, after administering a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject, one or more of the following of the subject is reduced relative to baseline: IgE level, eosinophil count, CCL26 level, CST1 level, CLC level, and ALOX15 level. In some embodiments, after administering the anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject, one or more of the following in the subject's peripheral blood is reduced relative to baseline: IgE level, eosinophil count, CCL26 level, CST1 level, CLC level, and ALOX15 level. In some embodiments, after administering a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject, one or more of the following in the subject's peripheral blood is reduced relative to baseline: IgE level, eosinophil count, CCL26 level, and CST1 level. In some embodiments, after administering an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject, one or more of the following in the subject's nasal exfoliated cells is reduced relative to baseline: CCL26 level, CST1 level, CLC level, and ALOX15 level. In some embodiments, after administering a therapeutically effective amount of an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure to the subject, one or more of the following in the subject's nasal exfoliated cells is reduced relative to baseline: CCL26 level, CST1 level, CLC level, and ALOX15 level.

[0102] Anti-IL-4Rα antibody or antigen-binding fragment thereof

[0103] As used herein, the term "antibody" refers to an antigen binding protein having at least one antigen binding domain. The antibodies and fragments thereof disclosed herein may be whole antibodies or any fragments thereof. Therefore, the antibodies and fragments thereof disclosed herein include monoclonal antibodies or fragments thereof and antibody variants or fragments thereof. Examples of antibody and antigen binding fragment fragments thereof include monospecific antibodies, bispecific antibodies, multispecific antibodies, Fab fragments, Fab' fragments, F(ab)'2 fragments, Fv fragments, isolated CDR regions, single-chain Fv molecules (scFv) and other antibody fragments known in the art. The anti-IL-4Rα antibodies and antigen binding fragments thereof disclosed herein may be IgG1, IgG2, IgG3 or IgG4 isotypes. The term "isotype" refers to the type of antibody encoded by the heavy chain constant region gene. The anti-IL-4Rα antibodies and antigen binding fragments thereof disclosed herein may be derived from any species, including but not limited to mice, rats, rabbits, primates, llamas and humans. The anti-IL-4Rα antibodies and antigen binding fragments thereof disclosed herein may be murine antibodies, chimeric antibodies, humanized antibodies or fully human antibodies. Unless otherwise specified, the "antibodies" of the present disclosure include whole antibodies and any antigen-binding fragments or single chains thereof. Conventional "whole antibodies" are glycoproteins comprising two heavy (H) chains and two light (L) chains, and the heavy chains and light chains are connected by disulfide bonds. Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region consists of three domains, namely CH1, CH2 and CH3. Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL). The light chain constant region consists of one domain CL. The VH and VL regions can also be divided into hypervariable regions, namely complementary determining regions (CDRs), and framework regions (FRs) with relatively conservative sequences. Each VH and VL consists of three CDRs and four FRs, respectively, from the amino terminus to the carboxyl terminus, respectively: FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. The variable regions of the heavy and light chains contain binding domains that interact with antigens. The constant region of the antibody can mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. At the same time, as those skilled in the art will appreciate, a special "whole antibody", such as a nanobody, has only a heavy (H) chain and no light (L) chain.

[0104] An "antigen-binding fragment" of an antibody refers to one or more fragments of an antibody that retain the function of specifically binding to an antigen (e.g., IL-4Rα). It has been demonstrated that the antigen-binding function of an antibody can be performed by a fragment of the entire antibody. Examples encompassed by the term "antigen-binding fragment" of an antibody include: (i) Fab fragment: a fragment consisting of V L 、V HThe invention relates to a monovalent fragment consisting of a single variable domain and a heavy chain variable region comprising a single variable domain and two constant domains. The invention relates to a monovalent fragment consisting of a single variable domain and a single constant domain comprising a Fab fragment; a monovalent fragment consisting of a CL and CH1 domain; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments connected by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody; (v) a dAb fragment consisting of the VH domain (see Ward et al., Nature. 341:544-546 (1989)); (vi) an isolated complementarity determining region (CDR); and (vii) a nanobody, a heavy chain variable region comprising a single variable domain and two constant domains. In addition, although the two domains VL and VH of the Fv fragment are encoded by different genes, VH and VL can be connected into a single protein chain by a synthetic linker using a recombinant method, wherein VL and VH are paired to form a monovalent molecule (called single-chain Fv (scFv); see, for example, Bird et al., Science. 242: 423-426 (1988); Huston et al., Proc. Natl. Acad. Sci. 85: 5879-5883 (1988)). These single-chain antibodies are also encompassed in the term antigen-binding fragment. In addition, recombinant polypeptides, fusion proteins, and immunoconjugates comprising the antigen-binding fragment are also encompassed in the term antigen-binding fragment.

[0105] A "chimeric antibody" is an antibody having at least a portion of a heavy chain variable region and at least a portion of a light chain variable region derived from one species; and at least a portion of a constant region derived from another species. For example, in one embodiment, a chimeric antibody may comprise a murine variable region and a human constant region.

[0106] "Humanized antibodies" are antibodies that contain complementary determining regions (CDRs) derived from non-human antibodies and framework regions and constant regions derived from human antibodies. For example, an anti-IL-4Rα antibody may comprise CDRs derived from one or more murine antibodies and human framework regions and human constant regions. Additional anti-IL-4Rα antibodies or variants thereof comprising the HCDRs and LCDRs provided herein may be produced using any human framework sequence and are also included in the present disclosure. In one embodiment, framework sequences suitable for use in the present disclosure include those that are structurally similar to the framework sequences provided herein. Additional modifications may be made in the framework region to improve the properties of the antibodies provided herein. Such additional framework modifications may include chemical modifications, point mutations to reduce immunogenicity or remove T cell epitopes, or mutations back to residues in the original germline sequence.

[0107] The term "identity" is also known as consistency. The "percentage (%) identity" of an amino acid sequence refers to the percentage of amino acid residues in the sequence to be compared that are identical to the amino acid residues in the specific amino acid sequence shown in this article, after comparing the sequence to be compared with the specific amino acid sequence shown in this article and introducing spaces if necessary to achieve the maximum sequence identity percentage, and not considering any conservative substitutions as part of the sequence identity. The amino acid sequence alignment of identity can be carried out in a variety of ways within the scope of the art, such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine the appropriate parameters for comparing sequences, including any algorithm required to obtain the maximum alignment in the full length of the comparison sequence.

[0108] According to some embodiments of the present disclosure, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a complementarity determining region (CDR), a heavy chain variable region and / or a light chain variable region contained in any amino acid sequence of the anti-IL-4Rα antibody or its antigen-binding fragment involved in the patent application document with publication number WO2021170020A1 or CN115087673A.

[0109] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain CDR1 (HCDR1), a heavy chain CDR2 (HCDR2), a heavy chain CDR3 (HCDR3), a light chain CDR1 (LCDR1), a light chain CDR2 (LCDR2), and a light chain CDR3 (LCDR3), wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO: 7, 17, or 21, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO: 7, 17, or 21, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO: 7, 17, or 21, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO: 8, 18, or 22, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO: 8, 18, or 22, and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO: 8, 18, or 22, wherein SEQ ID NO: NO: 7 X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, SEQ ID NO: 8 X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I, SEQ ID NO: 17 X5 is A or V. In some embodiments, SEQ ID NO: 7 X1 is W and X2 is A, SEQ ID NO: 8 X3 is F and X4 is V, and SEQ ID NO: 17 X5 is A or V.

[0110] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain CDR1 (HCDR1), a heavy chain CDR2 (HCDR2), a heavy chain CDR3 (HCDR3), a light chain CDR1 (LCDR1), a light chain CDR2 (LCDR2), and a light chain CDR3 (LCDR3), wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:7, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:7, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:7, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:8, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:8, and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:8, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and SEQ ID NO:7 comprises the amino acid sequence of HCDR1 in SEQ ID NO:8, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:8, and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:8. NO: 8, X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I. In some embodiments, X1 of SEQ ID NO: 7 is W and X2 is A, and X3 of SEQ ID NO: 8 is F and X4 is V.

[0111] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:7, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:7, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:7, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:22, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:22, and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A.

[0112] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:21, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:21, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:21, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:8, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:8, and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:8, wherein X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I.

[0113] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:21, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:21, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:21, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:22, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:22 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:22.

[0114] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO: 17, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO: 17, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO: 17, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO: 18, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO: 18 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V.

[0115] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO:8, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I. In some embodiments, X1 of SEQ ID NO:7 is W and X2 is A, and X3 of SEQ ID NO:8 is F and X4 is V.

[0116] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A.

[0117] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region shown in SEQ ID NO:21, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO:8, wherein X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I.

[0118] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2, and HCDR3 of the heavy chain variable region shown in SEQ ID NO:21, and LCDR1, LCDR2, and LCDR3 of the light chain variable region shown in SEQ ID NO:22.

[0119] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region shown in SEQ ID NO: 17, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V.

[0120] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof described in the present disclosure comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence shown in SEQ ID NO:1 or 11, HCDR2 comprises the amino acid sequence shown in SEQ ID NO:2 or 12, HCDR3 comprises the amino acid sequence shown in SEQ ID NO:3 or 13, LCDR1 comprises the amino acid sequence shown in SEQ ID NO:4 or 14, LCDR2 comprises the amino acid sequence shown in SEQ ID NO:5 or 15, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO:6 or 16. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof described in the present disclosure comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence shown in SEQ ID NO:1, HCDR2 comprises the amino acid sequence shown in SEQ ID NO:2, HCDR3 comprises the amino acid sequence shown in SEQ ID NO:3, LCDR1 comprises the amino acid sequence shown in SEQ ID NO:4, LCDR2 comprises the amino acid sequence shown in SEQ ID NO:5, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO:6. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof described in the present disclosure comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence shown in SEQ ID NO:11, HCDR2 comprises the amino acid sequence shown in SEQ ID NO:12, HCDR3 comprises the amino acid sequence shown in SEQ ID NO:13, LCDR1 comprises the amino acid sequence shown in SEQ ID NO:14, LCDR2 comprises the amino acid sequence shown in SEQ ID NO:15, and LCDR3 comprises the amino acid sequence shown in SEQ ID NO:16.

[0121] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof described in the present disclosure comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 1 or 11, HCDR2 of the amino acid sequence shown in SEQ ID NO: 2 or 12, HCDR3 of the amino acid sequence shown in SEQ ID NO: 3 or 13, LCDR1 of the amino acid sequence shown in SEQ ID NO: 4 or 14, LCDR2 of the amino acid sequence shown in SEQ ID NO: 5 or 15, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 6 or 16. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof described in the present disclosure comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 1, HCDR2 of the amino acid sequence shown in SEQ ID NO: 2, HCDR3 of the amino acid sequence shown in SEQ ID NO: 3, LCDR1 of the amino acid sequence shown in SEQ ID NO: 4, LCDR2 of the amino acid sequence shown in SEQ ID NO: 5, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 6. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof described in the present disclosure comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO:11, HCDR2 of the amino acid sequence shown in SEQ ID NO:12, HCDR3 of the amino acid sequence shown in SEQ ID NO:13, LCDR1 of the amino acid sequence shown in SEQ ID NO:14, LCDR2 of the amino acid sequence shown in SEQ ID NO:15, and LCDR3 of the amino acid sequence shown in SEQ ID NO:16.

[0122] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises the above-mentioned HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises the above-mentioned HCDR1, HCDR2 and HCDR3.

[0123] The CDR sequences of anti-IL-4Rα antibodies or antigen-binding fragments thereof are shown in Table 1.

[0124] Table 1. CDR sequences of anti-IL-4Rα antibodies or antigen-binding fragments thereof

[0125]

[0126] It will be understood by those skilled in the art that, unless otherwise specified, the term "CDR" or "complementarity determining region" of a given antibody or region thereof (e.g., variable region) should be understood to encompass complementarity determining regions defined by any known scheme. Although Table 1 has shown CDR sequences defined by the Kabat numbering system, however, when referring to antibodies defined by specific CDR sequences in Table 1, the scope of the antibodies also encompasses antibodies defined by CDR sequences converted to other arbitrary numbering system definitions (e.g., a combination of one or more of the definitions of AbM, Chothia, IMGT, CCG or Contact, etc., which are well known in the art).

[0127] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:7, 17 or 21, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X5 of SEQ ID NO:17 is A or V. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:8, 18 or 22, wherein X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:7, 17, or 21, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:8, 18, or 22, wherein SEQ ID NO: NO: 7 X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, SEQ ID NO: 8 X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I, SEQ ID NO: 17 X5 is A or V. In some embodiments, SEQ ID NO: 7 X1 is W and X2 is A, SEQ ID NO: 8 X3 is F and X4 is V, and SEQ ID NO: 17 X5 is A or V.

[0128] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain variable region whose amino acid sequence is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:7, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:8, wherein X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I of SEQ ID NO:8. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:8, wherein SEQ ID NO: NO: 7 X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, SEQ ID NO: 8 X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I. In some embodiments, SEQ ID NO: 7 X1 is W and X2 is A, SEQ ID NO: 8 X3 is F and X4 is V.

[0129] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:22, wherein SEQ ID NO: In NO:7, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A.

[0130] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:21, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:8, wherein SEQ ID NO: In NO:8, X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I.

[0131] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:21, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:22.

[0132] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V.

[0133] In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-IL-4Rα antibody or antigen-binding fragment thereof is as shown in SEQ ID NO:7, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A. In some specific embodiments, the amino acid sequence of the light chain variable region of the anti-IL-4Rα antibody or antigen-binding fragment thereof is as shown in SEQ ID NO:8, wherein X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I. In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-IL-4Rα antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 7, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO: 8, wherein X1 of SEQ ID NO: 7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X3 of SEQ ID NO: 8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I. In some embodiments, X1 of SEQ ID NO: 7 is W and X2 is A, and X3 of SEQ ID NO: 8 is F and X4 is V.

[0134] In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-IL-4Rα antibody or its antigen-binding fragment is as shown in SEQ ID NO:7, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A.

[0135] In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-IL-4Rα antibody or its antigen-binding fragment is as shown in SEQ ID NO:21, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO:8, wherein X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I in SEQ ID NO:8.

[0136] In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-IL-4Rα antibody or antigen-binding fragment thereof is as shown in SEQ ID NO:21, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO:22.

[0137] In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-IL-4Rα antibody or its antigen-binding fragment is as shown in SEQ ID NO: 17, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V.

[0138] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain variable region of the amino acid sequence shown in SEQ ID NO:7, and a light chain variable region of the amino acid sequence shown in SEQ ID NO:8, wherein X1 of SEQ ID NO:7 is W and X2 is A, and X3 of SEQ ID NO:8 is F and X4 is V. In some specific embodiments, the amino acid sequence of the heavy chain variable region of the anti-IL-4Rα antibody or antigen-binding fragment thereof is as shown in SEQ ID NO:7, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO:8, wherein X1 of SEQ ID NO:7 is W and X2 is A, and X3 of SEQ ID NO:8 is F and X4 is V.

[0139] EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYGMSWVRQAPGKGLVX1VX2TINSNGGSTSYPDSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCARFFRFRNAMDYWGQGTLVTVSS (SEQ ID NO: 7, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A);

[0140] DIQMTQSPSSLSASVGDRVTITCRTSENIYSYLAWYQQKPGKAPKX3LX4YNAKTLAEGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQHYYGPPTWTFGQGTKVEIK (SEQ ID NO:8, wherein X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I);

[0141] EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYGMSWVRQSPDKRLEWVSTINSNGGSTSYPDSVKG RFTISRDNAKNTLYLQMRSLRAEDTAVYYCARFFRFRNAMDYWGQGTLVTVSS (SEQ ID NO:21);

[0142] DIQMTQSPSSLSASVGQRVTITCRTSENIYSYLAWYQQKQGKPPRFLIYNAKTLAEGVPSRFSGSGSGTEFTLTITSLQAEDFGVYYCQHYYGPPTWTFGPGTKLEIK (SEQ ID NO:22);

[0143] EVQLVQSGAEVKKPGATVKISCKX5SGFNIKDTYMHWVKQAPGKGLEWMGRIDPTNGYTIYASKFQ GKATITADTSSNTAYMELSSLRSEDTAVYHCVSRRPWFAYWGQGTLVTVSS (SEQ ID NO:17, wherein X5 is A or V);

[0144] DIVMTQTPLSLSVTPGQPASISCRSSQSIVHSNGNTYLEWYLQKPGQSPQLLIYKVTNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQGTKLEIK (SEQ ID NO:18).

[0145] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof may further comprise a constant region of an immunoglobulin, or a fragment, analog, variant or derivative of the constant region. The constant region comprises a heavy chain constant region and a light chain constant region. In some embodiments, the heavy chain constant region comprises the sequence of a human immunoglobulin heavy chain, such as a heavy chain of human IgG1, IgG2, IgG3 and IgG4 or other classes of immunoglobulins, preferably a heavy chain of human IgG1 and IgG4. In some embodiments, the light chain constant region comprises the sequence of a human immunoglobulin light chain, such as a κ light chain of a human immunoglobulin. In some embodiments, the constant region may comprise any modification described in the text, such as insertion, deletion, substitution or chemical modification of amino acids. The C-terminal lysine of the heavy chain constant region may be present or absent. In some embodiments, the constant region comprises a mutation that alters effector function. In some embodiments, any amino acid residue of the constant region may be substituted with an amino acid residue of any allotype.

[0146] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:9, 19 or 23, wherein X1 of SEQ ID NO:9 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X5 of SEQ ID NO:19 is A or V. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 10, 20 or 24, wherein X3 of SEQ ID NO: 10 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 9, 19, or 23, and a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 10, 20, or 24, wherein SEQ ID NO: NO: 9 X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, SEQ ID NO: 10 X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I, SEQ ID NO: 19 X5 is A or V. In some embodiments, SEQ ID NO: 9 X1 is W and X2 is A, SEQ ID NO: 10 X3 is F and X4 is V, and SEQ ID NO: 19 X5 is A or V.

[0147] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO:9, wherein X1 of SEQ ID NO:9 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 10, wherein X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I of SEQ ID NO: 10. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:9, and a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:10, wherein SEQ ID NO: NO: 9 X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, SEQ ID NO: 10 X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I. In some embodiments, SEQ ID NO: 9 X1 is W and X2 is A, SEQ ID NO: 10 X3 is F and X4 is V.

[0148] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:9, and a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:24, wherein SEQ ID NO: In NO:9, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A.

[0149] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:23, and a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:10, wherein SEQ ID NO: In NO:10, X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I.

[0150] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:23, and a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:24.

[0151] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19, and a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 20, wherein X5 of SEQ ID NO: 19 is A or V.

[0152] In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 9, wherein X1 of SEQ ID NO: 9 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A. In some specific embodiments, the amino acid sequence of the light chain of the anti-IL-4Rα antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 10, wherein X3 of SEQ ID NO: 10 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I. In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 9, and the amino acid sequence of the light chain is as shown in SEQ ID NO: 10, wherein X1 of SEQ ID NO: 9 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X3 of SEQ ID NO: 10 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I. In some embodiments, X1 of SEQ ID NO: 9 is W and X2 is A, and X3 of SEQ ID NO: 10 is F and X4 is V.

[0153] In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or its antigen-binding fragment is as shown in SEQ ID NO:9, and the amino acid sequence of the light chain is as shown in SEQ ID NO:24, wherein X1 of SEQ ID NO:9 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A.

[0154] In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or its antigen-binding fragment is as shown in SEQ ID NO:23, and the amino acid sequence of the light chain is as shown in SEQ ID NO:10, wherein X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I in SEQ ID NO:10.

[0155] In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or antigen-binding fragment thereof is as shown in SEQ ID NO:23, and the amino acid sequence of the light chain is as shown in SEQ ID NO:24.

[0156] In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or its antigen-binding fragment is as shown in SEQ ID NO: 19, and the amino acid sequence of the light chain is as shown in SEQ ID NO: 20, wherein X5 of SEQ ID NO: 19 is A or V.

[0157] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO:9, and a light chain having an amino acid sequence as shown in SEQ ID NO:10, wherein X1 of SEQ ID NO:9 is W and X2 is A, and X3 of SEQ ID NO:10 is F and X4 is V. In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or antigen-binding fragment thereof is as shown in SEQ ID NO:9, and the amino acid sequence of the light chain is as shown in SEQ ID NO:10, wherein X1 of SEQ ID NO:9 is W and X2 is A, and X3 of SEQ ID NO:10 is F and X4 is V.

[0158] EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYGMSWVRQAPGKGLVX1VX2TINSNGGSTSYPDSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCARFFRFRNAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK(SEQ ID NO:9, where X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A);

[0159] DIQMTQSPSSLSASVGDRVTITCRTSENIYSYLAWYQQKPGKAPKX3LX4YNAKTLAEGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQHYYGPPTWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEQ ID NO:10, where X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I));

[0160] EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYGMSWVRQSPDKRLEWVSTINSNGGSTSYPDSVKGRFTISRDNAKNTLYLQMRSLRAEDTAVYYCARFFRFRNAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK(SEQ ID NO:23);

[0161] DIQMTQSPSSLSASVGQRVTITCRTSENIYSYLAWYQQKQGKPPRFLIYNAKTLAEGVPSRFSGSGSGTEFTLTITSLQAEDFGVYYCQHYYGPPTWTFGPGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEQID NO:24);

[0162] EVQLVQSGAEVKKPGATVKISCKX5SGFNIKDTYMHWVKQAPGKGLEWMGRIDPTNGYTIYASKFQ GKATITADTSSNTAYMELSSLRSEDTAVYHCVSRRPWFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK(SEQ ID NO:19, where X5 is A or V);

[0163] DIVMTQTPLSLSVTPGQPASISCRSSQSIVHSNGNTYLEWYLQKPGQSPQLLIYKVTNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC(SEQ ID NO:20);

[0164] Pharmaceutical composition containing anti-IL-4Rα antibody or antigen-binding fragment thereof

[0165] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof may be formulated with one or more pharmaceutically acceptable excipients to form a suitable pharmaceutical composition. As used herein, "excipient" is used to describe any ingredient other than the active ingredient (e.g., the anti-IL-4Rα antibody or antigen-binding fragment thereof described in the present disclosure). The choice of excipient will depend to a large extent on factors such as the specific mode of administration, the efficacy of the excipient on solubility and stability, and the nature of the dosage form. As used herein, "pharmaceutically acceptable excipients" include any and all excipients, diluents, fillers, binders, disintegrants, solubilizers, stabilizers, colorants, flavorings, surfactants, emulsifiers, buffers, or encapsulating materials that are physiologically compatible. The amount of each excipient may vary within the conventional range in the art.

[0166] In some embodiments, the unit dose of the pharmaceutical composition containing the anti-IL-4Rα antibody or its antigen-binding fragment is 60-900 mg, 100-600 mg or 200-300 mg, for example, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, 150 mg, 160 mg, 180 mg, 200 mg, 220 mg, 240 mg, 260 mg, 280 mg, 300 mg, 320 mg, 340 mg, 360 mg, 380 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or a range formed by any of the above values.

[0167] The pharmaceutical composition containing the anti-IL-4Rα antibody or antigen-binding fragment thereof disclosed herein may be in a suitable dosage form, including but not limited to tablets, lozenges, pills, capsules (e.g., hard capsules, soft capsules, enteric-coated capsules, microcapsules), elixirs, granules, syrups, injections (e.g., preparations suitable for intramuscular, intravenous, intraperitoneal, or subcutaneous injections), granules, emulsions, suspensions, solutions, dispersions, and sustained-release preparations for oral or parenteral administration. In some embodiments, the pharmaceutical composition containing the anti-IL-4Rα antibody or antigen-binding fragment thereof is an injection (e.g., a preparation suitable for intramuscular, intravenous, intraperitoneal, or subcutaneous injections).

[0168] The term "pharmaceutically acceptable" refers to those compounds, materials, compositions and / or dosage forms which, within the scope of sound medical judgment, are suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response or other problems or complications, commensurate with a reasonable benefit / risk ratio.

[0169] The term "pharmaceutical composition" refers to a mixture of one or more active ingredients (e.g., the anti-IL-4Rα antibodies or antigen-binding fragments thereof disclosed herein) and pharmaceutically acceptable excipients. The purpose of a pharmaceutical composition is to facilitate administration of the active ingredient (e.g., the anti-IL-4Rα antibodies or antigen-binding fragments thereof disclosed herein) to a subject. As used herein, the terms "pharmaceutical composition" and "preparation" have the same meaning and are used interchangeably.

[0170] In a specific embodiment, the pharmaceutical composition containing the anti-IL-4Rα antibody or its antigen-binding fragment is a water-soluble injection. The water-soluble injection includes but is not limited to a water-soluble preparation that has not been lyophilized or a water-soluble preparation reconstituted with a lyophilized powder. In other embodiments, the pharmaceutical composition containing the anti-IL-4Rα antibody or its antigen-binding fragment is a lyophilized preparation. The lyophilized preparation refers to a preparation prepared by a lyophilization process in which the aqueous solution is first frozen, and then the amount of solvent is reduced by sublimation (primary drying process), and then the amount of solvent is reduced by desorption (secondary drying process) until the amount of solvent is a value that no longer supports biological activity or chemical reaction. The lyophilized preparation of the present disclosure can also be dried by other methods known in the art, such as spray drying and bubbling drying (bubbledrying).

[0171] In some embodiments, the concentration of the anti-IL-4Rα antibody or its antigen-binding fragment in the pharmaceutical composition containing the anti-IL-4Rα antibody or its antigen-binding fragment is 30-300 mg / mL, 50-250 mg / mL, 70-200 mg / mL, 100-180 mg / mL, 120-180 mg / mL, 120-150 mg / mL, or 150-180 mg / mL. In some embodiments, the concentration of the anti-IL-4Rα antibody or antigen-binding fragment thereof is 70 mg / mL, 80 mg / mL, 90 mg / mL, 100 mg / mL, 110 mg / mL, 120 mg / mL, 125 mg / mL, 130 mg / mL, 135 mg / mL, 140 mg / mL, 145 mg / mL, 150 mg / mL, 155 mg / mL, 160 mg / mL, 165 mg / mL, 170 mg / mL, 175 mg / mL, 180 mg / mL, 190 mg / mL, or 200 mg / mL. In some specific embodiments, the concentration of the anti-IL-4Rα antibody or antigen-binding fragment thereof is 150 mg / mL. In some specific embodiments, the concentration of the anti-IL-4Rα antibody or antigen-binding fragment thereof is 175 mg / mL.

[0172] In some embodiments, the pharmaceutical composition containing an anti-IL-4Rα antibody or an antigen-binding fragment thereof comprises an anti-IL-4Rα antibody or an antigen-binding fragment thereof, a buffer, an isotonicity regulator / stabilizer, and a surfactant. In a specific embodiment, the pharmaceutical composition containing an anti-IL-4Rα antibody or an antigen-binding fragment thereof is in the form of a liquid pharmaceutical composition (e.g., an injection), which comprises an anti-IL-4Rα antibody or an antigen-binding fragment thereof, a histidine salt buffer, proline, sodium chloride, and polysorbate 80. In some embodiments, the histidine salt buffer includes a histidine-hydrochloric acid buffer, a histidine-acetic acid buffer, a histidine-histidine hydrochloride buffer, or a histidine hydrochloride buffer. In some embodiments, the histidine salt buffer is a histidine-hydrochloric acid buffer.

[0173] dose

[0174] The amount of the anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure administered to a subject is generally a therapeutically effective amount. The term "treatment" refers to an attempt to alter the natural course of a disease in a treated individual, and may be for the purpose of preventing, ameliorating or eliminating a disease or one or more symptoms associated with the disease, including but not limited to preventing the occurrence or recurrence of a disease, alleviating symptoms, reducing any direct or indirect pathological consequences of a disease, preventing metastasis of a disease, slowing the rate of progression of a disease, improving or relieving the state of a disease, prolonging the frequency and duration of symptom-free periods, and regressing or improving the prognosis of a disease. The term "therapeutically effective amount" means an amount of a compound of the present disclosure that (i) treats a particular disease, condition or disorder, (ii) alleviates, ameliorates or eliminates one or more symptoms of a particular disease, condition or disorder, or (iii) prevents or delays the onset of one or more symptoms of a particular disease, condition or disorder. The amount of active substance (e.g., an anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure) that constitutes a "therapeutically effective amount" may vary according to factors such as the disease state, age, sex and weight of the individual, and the ability of the therapeutic agent or combination of therapeutic agents to elicit a desired response in the individual. The therapeutically effective amount can also be routinely determined by one skilled in the art based on his or her own knowledge and this disclosure.

[0175] Administration regimen

[0176] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In some specific embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered once every 2 weeks. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at a dose of 100-1200 mg, 120-900 mg, 150-800 mg, 200-600 mg, or 300-600 mg each time. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg, 400 mg, 410 mg, 420 mg, 430 mg, 440 mg, 450 mg, 460 mg, In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at a dose of 200 mg, 300 mg, 400 mg, or 600 mg per administration. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at a dose of 300 mg or 600 mg per administration.

[0177] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of 300-600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of 300 mg or 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment. In some specific embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 2 weeks, each time at a dose of 300 mg or 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment. In other embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of 200-400 mg of the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of 200 mg or 400 mg of the anti-IL-4Rα antibody or antigen-binding fragment thereof. In some specific embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered once every 2 weeks, each time at a dose of 200 mg or 400 mg of the anti-IL-4Rα antibody or antigen-binding fragment thereof.

[0178] In some embodiments, every 2 weeks is a treatment cycle, and the anti-IL-4Rα antibody or its antigen-binding fragment is administered in each treatment cycle. In some embodiments, every 2 weeks is a treatment cycle, and the anti-IL-4Rα antibody or its antigen-binding fragment is administered once in each treatment cycle. In some embodiments, every 2 weeks is a treatment cycle, and the anti-IL-4Rα antibody or its antigen-binding fragment is administered on the first day of each treatment cycle. In some embodiments, every 2 weeks is a treatment cycle, and the anti-IL-4Rα antibody or its antigen-binding fragment is administered once on the first day of each treatment cycle. In some embodiments, every 2 weeks is a treatment cycle, and the anti-IL-4Rα antibody or its antigen-binding fragment is administered for a total of 1-20, 8-12 or 8-20 treatment cycles. In some embodiments, every 2 weeks is a treatment cycle, and the anti-IL-4Rα antibody or its antigen-binding fragment is administered for a total of 8, 9, 10, 11 or 12 treatment cycles. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered for a total of 16, 17, 18, 19 or 20 treatment cycles every 2 weeks. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered for a total of 8 treatment cycles every 2 weeks. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered for a total of 20 treatment cycles every 2 weeks.

[0179] In some specific embodiments, every 2 weeks is a treatment cycle, and 300-600 mg of anti-IL-4Rα antibody or its antigen-binding fragment is administered in each treatment cycle. In some specific embodiments, every 2 weeks is a treatment cycle, and 300 mg or 600 mg of anti-IL-4Rα antibody or its antigen-binding fragment is administered in each treatment cycle. In some specific embodiments, every 2 weeks is a treatment cycle, and 300 mg or 600 mg of anti-IL-4Rα antibody or its antigen-binding fragment is administered on the first day of each treatment cycle. In other specific embodiments, every 2 weeks is a treatment cycle, and 200-400 mg of anti-IL-4Rα antibody or its antigen-binding fragment is administered in each treatment cycle. In other specific embodiments, every 2 weeks is a treatment cycle, and 200 mg or 400 mg of anti-IL-4Rα antibody or its antigen-binding fragment is administered in each treatment cycle. In other specific embodiments, every 2 weeks is a treatment cycle, and 200 mg or 400 mg of anti-IL-4Rα antibody or its antigen-binding fragment is administered on the first day of each treatment cycle.

[0180] The term "flat dose" is used to refer to the dose administered to a patient regardless of the patient's weight or body surface area (BSA). A flat dose is thus specified as an absolute amount of an agent (e.g., an anti-IL-4Rα antibody or antigen-binding fragment thereof) rather than as a mg / kg dose. For example, a 60 kg person and a 100 kg person would receive the same dose of antibody (e.g., 300 mg IL-4Rα antibody).

[0181] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered to the subject at a uniform dose of 100-1200 mg, 120-900 mg, 150-800 mg, 200-600 mg, or 300-600 mg. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg, 400 mg, 410 mg, 420 mg, 430 mg, 440 mg, 450 mg, 460 mg, 470 mg, 480 mg, 490 mg, 500 mg, 510 mg, 520 mg, 530 mg, 540 mg, 550 mg, 560 mg, 570 mg, 580 mg, 590 mg, 70 mg, 480 mg, 490 mg, 500 mg, 510 mg, 520 mg, 530 mg, 540 mg, 550 mg, 560 mg, 570 mg, 580 mg, 590 mg, 600 mg, 610 mg, 620 mg, 630 mg, 640 mg, 650 mg, 660 mg, 670 mg, 680 mg, 690 mg, 700 mg, 710 mg, 720 mg, 730 mg, 740 mg, 750 mg, 760 mg, 770 mg, 780 mg, 790 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, or a uniform dose formed by any value above is administered to a subject. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered to a subject at a uniform dose of 200 mg, 300 mg, 400 mg, or 600 mg. In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered to a subject at a uniform dose of 300 mg or 600 mg.

[0182] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered to a subject at a dose of 0.01 to 20 mg / kg, 0.1 to 15 mg / kg, 1 to 15 mg / kg, 2 to 15 mg / kg, 1 to 10 mg / kg, 2 to 10 mg / kg, or 3 to 10 mg / kg of the subject's body weight.

[0183] In some embodiments, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered in multiple doses or in a single dose.

[0184] As used herein, the term "single dose" refers to the smallest packaging unit containing a certain amount of medicine, for example, if a box of medicine contains seven tablets, then one tablet is a single dose; or a bottle of injection is a single dose. The term "multiple doses" consists of multiple single doses.

[0185] "Unit dose" refers to the dose of active ingredient contained in the smallest packaging unit containing a certain amount of drug. For example, the dose of antibody contained in a bottle of antibody injection is a unit dose.

[0186] Combination therapy

[0187] In some embodiments, the subject is administered one or more additional therapeutic agents before, after, or simultaneously with the anti-IL-4Rα antibody or antigen-binding fragment thereof. In some embodiments, the subject has been administered or is being administered one or more additional therapeutic agents before receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof. For example, when an additional therapeutic agent is administered "before" the anti-IL-4Rα antibody or antigen-binding fragment thereof, the additional therapeutic agent can be administered at least 72 hours, at least 60 hours, at least 48 hours, at least 36 hours, at least 24 hours, at least 12 hours, at least 10 hours, at least 8 hours, at least 6 hours, at least 4 hours, at least 2 hours, at least 1 hour, at least 30 minutes, at least 15 minutes, or at least 10 minutes before the administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof. When the additional therapeutic agent is administered "after" the anti-IL-4Rα antibody or antigen-binding fragment thereof, the additional therapeutic agent can be administered at least 10 minutes, at least 15 minutes, at least 30 minutes, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, at least 10 hours, at least 12 hours, at least 24 hours, at least 36 hours, at least 48 hours, at least 60 hours, or at least 72 hours after the administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof. Administration "concurrently" with the anti-IL-4Rα antibody or antigen-binding fragment thereof means that the additional therapeutic agent is administered to the subject within less than 10 minutes (before, after, or simultaneously with) the administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof.

[0188] Additional therapeutic agents can be, for example, IL-1 inhibitors, IL-5 inhibitors, IL-5Rα inhibitors, IL-13 inhibitors, TNF inhibitors, IgE inhibitors, nonsteroidal anti-inflammatory drugs, antibiotics, antihistamines, antifungal agents, local decongestants, long-acting β2 receptor agonists, short-acting β2 receptor agonists, long-acting muscarinic antagonists, leukotriene antagonists and / or glucocorticoids. The glucocorticoids can be, for example, nasal glucocorticoids (INCS), inhaled glucocorticoids and / or systemic glucocorticoids. In some embodiments, the additional therapeutic agent is a nasal glucocorticoid, such as furoate mometasone nasal spray (MFNS). In some embodiments, the additional therapeutic agent is an inhaled glucocorticoid, such as fluticasone or budesonide. In some embodiments, the additional therapeutic agent is a long-acting β2 receptor agonist, such as salmeterol or formoterol.

[0189] In some embodiments, the additional therapeutic agent is mometasone furoate nasal spray, which is administered once a day. In some embodiments, the additional therapeutic agent is mometasone furoate nasal spray, which is administered twice a day. In some embodiments, the additional therapeutic agent is mometasone furoate nasal spray, which is administered once a day at a daily dose of 200 μg. In some embodiments, the additional therapeutic agent is mometasone furoate nasal spray, which is administered once a day at a daily dose of 100 μg.

[0190] In some embodiments, the subject has been or is being administered a nasal glucocorticoid prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof. In some embodiments, the subject has been or is being administered mometasone furoate nasal spray prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof.

[0191] In some embodiments, the subject has been or is being administered mometasone furoate nasal spray prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof, the mometasone furoate nasal spray being administered once daily. In some embodiments, the subject has been or is being administered mometasone furoate nasal spray prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof, the mometasone furoate nasal spray being administered twice daily. In some embodiments, the subject has been or is being administered mometasone furoate nasal spray prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof, the mometasone furoate nasal spray being administered once daily at a daily dose of 200 μg. In some embodiments, the subject has been or is being administered mometasone furoate nasal spray prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof, the mometasone furoate nasal spray being administered once daily at a daily dose of 100 μg.

[0192] Mode of administration

[0193] The following does not limit the administration method of the anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure.

[0194] The anti-IL-4Rα antibodies or antigen-binding fragments thereof of the present disclosure can be administered in various suitable routes, including but not limited to oral, parenteral (by intravenous, intramuscular, topical or subcutaneous) routes. In some embodiments, the anti-IL-4Rα antibodies or antigen-binding fragments thereof of the present disclosure can be administered by injection, such as intravenous or subcutaneous injection, preferably subcutaneous injection. In some embodiments, the anti-IL-4Rα antibodies or antigen-binding fragments thereof of the present disclosure can also be absorbed through the epithelium or mucosa (such as oral mucosa, rectal and intestinal mucosa, etc.). In some embodiments, the anti-IL-4Rα antibodies or antigen-binding fragments thereof of the present disclosure can also be administered, for example, once, multiple times, and / or over one or more extended time periods. In some embodiments, the anti-IL-4Rα antibodies or antigen-binding fragments thereof of the present disclosure can also be administered by various known drug delivery systems, including liposome encapsulation, microparticles, microcapsules, controlled release systems, and the like.

[0195] Treatment population

[0196] In some embodiments, the chronic sinusitis patient has previously been treated with corticosteroids (e.g., treatment failed, unsuitable, and / or intolerant). In some embodiments, the chronic sinusitis patient has previously been treated with systemic corticosteroids (e.g., treatment failed, unsuitable, and / or intolerant). In some embodiments, the chronic sinusitis patient has previously been treated with glucocorticoids (e.g., treatment failed, unsuitable, and / or intolerant). In some embodiments, the chronic sinusitis patient has previously been treated with systemic glucocorticoids (e.g., treatment failed, unsuitable, and / or intolerant).

[0197] In some embodiments, the chronic sinusitis patient has previously received surgical treatment (e.g., treatment failure, unsuitability and / or intolerance). In some embodiments, the chronic sinusitis patient has previously received nasal sinus surgery (e.g., treatment failure, unsuitability and / or intolerance).

[0198] In some embodiments, the chronic sinusitis patient has previously received corticosteroid treatment (e.g., treatment failure, unsuitable and / or intolerance) and sinus surgery (e.g., treatment failure, unsuitable and / or intolerance). In some embodiments, the chronic sinusitis patient has previously received systemic corticosteroid treatment (e.g., treatment failure, unsuitable and / or intolerance) and sinus surgery (e.g., treatment failure, unsuitable and / or intolerance). In some embodiments, the chronic sinusitis patient has previously received glucocorticoid treatment (e.g., treatment failure, unsuitable and / or intolerance) and sinus surgery (e.g., treatment failure, unsuitable and / or intolerance). In some embodiments, the chronic sinusitis patient has previously received systemic glucocorticoid treatment (e.g., treatment failure, unsuitable and / or intolerance) and sinus surgery (e.g., treatment failure, unsuitable and / or intolerance). In some embodiments, the chronic sinusitis patient has previously received systemic glucocorticoid treatment (e.g., treatment failure, unsuitable and / or intolerance) and sinus surgery (e.g., treatment failure, unsuitable and / or intolerance). In some embodiments, the chronic sinusitis is bilateral chronic sinusitis.

[0199] In some such embodiments, the chronic sinusitis is chronic sinusitis with nasal polyps. In some such embodiments, the chronic sinusitis is bilateral chronic sinusitis with nasal polyps. In some such embodiments, the chronic sinusitis is eosinophilic chronic sinusitis with nasal polyps.

[0200] In some embodiments, the chronic sinusitis is chronic sinusitis without nasal polyps. In some embodiments, the chronic sinusitis is bilateral chronic sinusitis without nasal polyps. In some embodiments, the chronic sinusitis is eosinophilic chronic sinusitis without nasal polyps.

[0201] In some embodiments, patients with chronic sinusitis further suffer from asthma. In some embodiments, patients with bilateral chronic sinusitis further suffer from asthma. In some embodiments, patients with chronic sinusitis with nasal polyps further suffer from asthma. In some embodiments, patients with bilateral chronic sinusitis with nasal polyps further suffer from asthma. In some embodiments, patients with eosinophilic chronic sinusitis with nasal polyps further suffer from asthma. In some embodiments, patients with chronic sinusitis without nasal polyps further suffer from asthma. In some embodiments, patients with bilateral chronic sinusitis without nasal polyps further suffer from asthma. In some embodiments, patients with eosinophilic chronic sinusitis without nasal polyps further suffer from asthma.

[0202] In some specific embodiments, the patient with chronic sinusitis with nasal polyps has previously received systemic glucocorticoid treatment (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the patient with chronic sinusitis with nasal polyps has previously received at least one course of systemic glucocorticoid treatment, but still has bilateral chronic sinusitis.

[0203] In some specific embodiments, the patient with eosinophilic chronic sinusitis with nasal polyps has previously received systemic glucocorticoid treatment (e.g., treatment failure, inappropriateness and / or intolerance). In some specific embodiments, the patient with eosinophilic chronic sinusitis with nasal polyps has previously received at least one course of systemic glucocorticoid treatment, but still has bilateral chronic sinusitis.

[0204] In some specific embodiments, the patient with chronic sinusitis without nasal polyps has previously received systemic glucocorticoid treatment (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the patient with chronic sinusitis without nasal polyps has previously received at least one course of systemic glucocorticoid treatment, but still has bilateral chronic sinusitis.

[0205] In some specific embodiments, the patient with eosinophilic chronic sinusitis without nasal polyps has previously received systemic glucocorticoid treatment (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the patient with eosinophilic chronic sinusitis without nasal polyps has previously received at least one course of systemic glucocorticoid treatment, but still has bilateral chronic sinusitis.

[0206] In some specific embodiments, the patient with chronic sinusitis with nasal polyps has previously received sinus surgery (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the patient with chronic sinusitis with nasal polyps has previously received sinus surgery (e.g., treatment failure, unsuitability and / or intolerance) 6 months before the administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof.

[0207] In some specific embodiments, the patient with eosinophilic chronic sinusitis with nasal polyps has previously received sinus surgery (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the patient with eosinophilic chronic sinusitis with nasal polyps has previously received sinus surgery (e.g., treatment failure, unsuitability and / or intolerance) 6 months before the administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof.

[0208] In some specific embodiments, the patient with chronic sinusitis with nasal polyps has previously received sinus surgery (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the patient with chronic sinusitis with nasal polyps has previously received sinus surgery (e.g., treatment failure, unsuitability and / or intolerance) 6 months before the administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof.

[0209] In some specific embodiments, the patient with eosinophilic chronic sinusitis without nasal polyps has previously received sinus surgery (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the patient with eosinophilic chronic sinusitis without nasal polyps has previously received sinus surgery (e.g., treatment failure, unsuitability and / or intolerance) 6 months before the administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof.

[0210] In some specific embodiments, the chronic sinusitis with nasal polyps patient has previously received systemic glucocorticoid treatment (e.g., treatment failure, unsuitability and / or intolerance) and / or sinus surgery (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the chronic sinusitis with nasal polyps patient has previously received systemic glucocorticoid treatment, but the treatment failed. In some specific embodiments, the chronic sinusitis with nasal polyps patient is not suitable for and / or intolerant of systemic glucocorticoid treatment. In some specific embodiments, the eosinophilic chronic sinusitis with nasal polyps patient has previously received systemic glucocorticoid treatment (e.g., treatment failure, unsuitability and / or intolerance) and / or sinus surgery (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the eosinophilic chronic sinusitis with nasal polyps patient has previously received systemic glucocorticoid treatment, but the treatment failed. In some specific embodiments, the eosinophilic CRSwNP patient is not suitable for and / or is intolerant to systemic glucocorticoid treatment.

[0211] In some specific embodiments, the patient with chronic sinusitis without nasal polyps has previously received systemic glucocorticoid treatment (e.g., treatment failure, unsuitability and / or intolerance) and / or sinus surgery (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the patient with chronic sinusitis without nasal polyps has previously received systemic glucocorticoid treatment, but the treatment failed. In some specific embodiments, the patient with chronic sinusitis without nasal polyps is not suitable for and / or intolerant of systemic glucocorticoid treatment. In some specific embodiments, the patient with eosinophilic chronic sinusitis without nasal polyps has previously received systemic glucocorticoid treatment (e.g., treatment failure, unsuitability and / or intolerance) and / or sinus surgery (e.g., treatment failure, unsuitability and / or intolerance). In some specific embodiments, the patient with eosinophilic chronic sinusitis without nasal polyps has previously received systemic glucocorticoid treatment, but the treatment failed. In some specific embodiments, the eosinophilic CRSwNP patient is not suitable for and / or is intolerant to systemic glucocorticoid treatment.

[0212] As used herein, "treatment failure" is defined as the persistence or presence, progression, or recurrence of disease during or after the last treatment.

[0213] In some embodiments, the bilateral NPS of a CRSwNP patient is at least 5 out of a maximum of 8, with at least 2 points in each nostril. The presence of nasal polyps can be confirmed by endoscopy.

[0214] In some embodiments, the CRSwNP patient has an NCS of at least 2 points.

[0215] In some embodiments, the CRS patients have had symptoms of (1) nasal congestion and (2) runny nose and / or decreased or loss of smell for at least 8 weeks.

[0216] In some embodiments, the CRSNP patient has a Lund Mackay score of at least 8.

[0217] In some embodiments, the CRSNP patient has an anosmia score of at least 2.

[0218] In some embodiments, the sTSS of a CRSwNP patient is at least 2. In some embodiments, the sTSS of a CRSwNP patient is at least 5.

[0219] In some embodiments, the patient with CRSwNP has symptoms such as nasal discharge and / or loss of smell for at least 4 weeks. In some embodiments, the patient with CRSwNP has symptoms such as nasal discharge and / or loss of smell for at least 12 weeks.

[0220] In some embodiments, the eosinophil count in the blood of a CRSNP patient is at least 250 cells / mm 3 .

[0221] In some embodiments, the patient has been treated for chronic sinusitis with a regimen of nasal glucocorticoids (e.g., mometasone furoate nasal spray) for at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, or longer. In some embodiments, the patient has been treated for chronic sinusitis with a regimen of nasal glucocorticoids (e.g., mometasone furoate nasal spray) for at least 4 weeks.

[0222] In some embodiments, the patient has been or is being administered one or more additional therapeutic agents (i.e., "background therapy") prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof. The "background therapy" includes, but is not limited to, administering to the patient IL-1 inhibitors, IL-5 inhibitors, IL-5Rα inhibitors, IL-13 inhibitors, TNF inhibitors, IgE inhibitors, nonsteroidal anti-inflammatory drugs, antibiotics, antihistamines, antifungal agents, local decongestants, long-acting β2 receptor agonists, short-acting β2 receptor agonists, long-acting muscarinic antagonists, leukotriene antagonists, and / or glucocorticoids. A non-limiting example of the "background therapy" is administering to the patient glucocorticoids, including nasal glucocorticoids, inhaled glucocorticoids, and systemic glucocorticoids. In some embodiments, the patient has been or is being administered nasal glucocorticoids prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof. In some embodiments, the patient has been administered or is being administered mometasone furoate nasal spray prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof. In some embodiments, the patient has been administered mometasone furoate nasal spray for at least 4 weeks prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof. In some embodiments, the patient continues background therapy after receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof. In some embodiments, the patient continues to be administered mometasone furoate nasal spray after receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof. In some embodiments, the patient stops receiving background therapy (e.g., immediately or gradually) prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof.

[0223] In some embodiments, the patient further suffers from asthma. In some embodiments, the patient has been administered glucocorticoids, or is being administered glucocorticoids, before receiving the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the patient has been administered inhaled glucocorticoids, or is being administered inhaled glucocorticoids, before receiving the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the patient has been administered inhaled glucocorticoids before receiving the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the patient has been administered inhaled glucocorticoids for at least 4 weeks before receiving the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the patient has been administered INCS before receiving the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the patient has been administered INCS for at least 4 weeks before receiving the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the patient has been administered intranasal glucocorticoids and / or bronchodilators, or is being administered intranasal glucocorticoids and / or bronchodilators prior to receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof. Non-limiting examples of bronchodilators include short-acting β2 receptor agonists, long-acting β2 receptor agonists, and long-acting muscarinic antagonists.

[0224] Technical Effects

[0225] Generally, administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof of the present disclosure has one or more of the following effects:

[0226] (1) Benefit patients with chronic sinusitis;

[0227] (2) have a good safety profile (e.g., low incidence and severity of adverse events and serious adverse events, and low risk of adverse reactions);

[0228] (3) provide treatments that are well tolerated in patients with CRSsNP and / or CRSwNP;

[0229] (4) improving one or more sinusitis-related parameters in the subjects (e.g., continuous treatment for 1-20 treatment cycles, NPS decreases by ≥1 point relative to baseline, Lund Mackay score decreases by ≥1 point relative to baseline, modified Lund Kennedy score decreases by ≥1 point relative to baseline, NCS decreases by ≥0.5 point relative to baseline, anosmia score decreases by ≥0.5 point relative to baseline, SNOT-22 score decreases by ≥8.9 points relative to baseline, VAS score decreases by ≥2 points relative to baseline, the proportion of subjects requiring nasal polyp surgery decreases significantly, and / or the proportion of subjects requiring systemic glucocorticoids for remediation decreases significantly; for example, continuous treatment for 1 treatment cycle, NPS decreases by 2 points relative to baseline; for example, continuous treatment for 8 treatment cycles, modified Lund Mackay decreases by 2 points relative to baseline);

[0230] (5) Provide improvement and control of lung function in patients with chronic sinusitis and asthma.

[0231] The anti-IL-4Rα antibody or antigen-binding fragment thereof and treatment regimen disclosed herein have good efficacy and safety in the treatment of chronic sinusitis (eg, CRSwNP or CRSsNP).

[0232] For the purpose of description and disclosure, all patents, patent applications and other identified publications are expressly incorporated herein by reference. These publications are provided only because their disclosure precedes the filing date of the present disclosure. All statements regarding the dates of these documents or the representations of the contents of these documents are based on the information available to the applicant and do not constitute any admission as to the correctness of the dates of these documents or the contents of these documents. Furthermore, any reference to these publications herein does not constitute an admission that the publications are part of the common general knowledge in the art in any country.

[0233] The present disclosure also provides the following specific implementation schemes, but the protection scope of the present disclosure is not limited thereto:

[0234] Embodiment 1. Use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof in the preparation of a medicament for treating chronic sinusitis in a subject in need thereof, characterized in that:

[0235] (1) The anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:7, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:7, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:7, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:8, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:8 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:8, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I;

[0236] (2) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO: 17, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO: 17, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO: 17, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO: 18, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO: 18 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V;

[0237] (3) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:7, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:7, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:7, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:22, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:22 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A;

[0238] (4) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:21, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:21, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:21, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:8, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:8 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:8, wherein X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I;

[0239] (5) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:21, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:21, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:21, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:22, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:22 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:22;

[0240] (6) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO:8, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I;

[0241] (7) The anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO: 17, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V;

[0242] (8) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A;

[0243] (9) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO:21, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO:8, wherein X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I; or

[0244] (10) The anti-IL-4Rα antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region shown in SEQ ID NO:21, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO:22.

[0245] Embodiment 2. Use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof in the preparation of a medicament for treating chronic sinusitis in a subject in need thereof, wherein the anti-IL-4Rα antibody or the antigen-binding fragment thereof comprises:

[0246] (1) a HCDR1 comprising the amino acid sequence of SEQ ID NO:1, a HCDR2 comprising the amino acid sequence of SEQ ID NO:2, a HCDR3 comprising the amino acid sequence of SEQ ID NO:3, a LCDR1 comprising the amino acid sequence of SEQ ID NO:4, a LCDR2 comprising the amino acid sequence of SEQ ID NO:5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:6; or

[0247] (2) HCDR1 comprising the amino acid sequence shown in SEQ ID NO:11, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:12, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:13, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:14, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:15, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:16.

[0248] Embodiment 3. The use according to embodiment 1 or 2, wherein the chronic sinusitis is chronic sinusitis with nasal polyps or chronic sinusitis without nasal polyps; or the chronic sinusitis is bilateral chronic sinusitis; or the chronic sinusitis is eosinophilic chronic sinusitis with nasal polyps or eosinophilic chronic sinusitis without nasal polyps.

[0249] Embodiment 4. The use according to any one of embodiments 1-3, wherein the subject further suffers from asthma.

[0250] Embodiment 5. The use according to any one of embodiments 1-4, wherein the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at a dose of 100-1200 mg, 120-900 mg, 150-800 mg, 200-600 mg, or 300-600 mg each time; preferably, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at a dose of 300 mg or 600 mg each time.

[0251] Embodiment 6. The use according to any one of Embodiments 1-5, wherein the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks; preferably, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered once every 2 weeks.

[0252] Embodiment 7. The use according to any one of Embodiments 1-6, wherein the subject is administered one or more additional therapeutic agents before, after or simultaneously with the anti-IL-4Rα antibody or antigen-binding fragment thereof; preferably, the subject has been administered or is being administered one or more additional therapeutic agents before receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof.

[0253] Embodiment 8. The use according to embodiment 7, wherein the additional therapeutic agent is selected from one or more of glucocorticoids, long-acting β2 receptor agonists, short-acting β2 receptor agonists, IL-1 inhibitors, IL-5 inhibitors, IL-5Rα inhibitors, IL-13 inhibitors, TNF inhibitors, IgE inhibitors, non-steroidal anti-inflammatory drugs, antibiotics, antihistamines, antifungal agents, local decongestants, long-acting muscarinic antagonists and leukotriene antagonists; preferably, the glucocorticoid is selected from one or more of nasal glucocorticoids, inhaled glucocorticoids and systemic glucocorticoids.

[0254] Embodiment 9. The use according to embodiment 7, wherein the subject has been or is being administered a nasal glucocorticoid before receiving the anti-IL-4Rα antibody or its antigen-binding fragment; preferably, the subject has been or is being administered a mometasone furoate nasal spray before receiving the anti-IL-4Rα antibody or its antigen-binding fragment.

[0255] Embodiment 10. The use according to any one of embodiments 1 to 9, wherein the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises:

[0256] (1) a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:8, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A of SEQ ID NO:7, and X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I of SEQ ID NO:8;

[0257] (2) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 17, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V;

[0258] (3) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A;

[0259] (4) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:21, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:8, wherein X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I in SEQ ID NO:8; or

[0260] (5) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:21, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:22.

[0261] Embodiment 11. The use according to any one of embodiments 1-10, wherein the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises:

[0262] (1) a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:9, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:10, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A of SEQ ID NO:9, and X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I of SEQ ID NO:10;

[0263] (2) a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 19, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 20, wherein X5 of SEQ ID NO: 19 is A or V;

[0264] (3) a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:9, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:24, wherein X1 of SEQ ID NO:9 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A;

[0265] (4) a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:23, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:10, wherein X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I of SEQ ID NO:10; or

[0266] (5) a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:23, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:24.

[0267] Embodiment 12. The use according to any one of Embodiments 1-11, wherein the anti-IL-4Rα antibody or antigen-binding fragment thereof is formulated together with a pharmaceutically acceptable excipient.

[0268] Embodiment 13. Use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof in the preparation of a medicament for improving one or more sinusitis-related parameters in a subject in need thereof, characterized in that:

[0269] (1) The anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:7, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:7, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:7, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:8, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:8 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:8, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I;

[0270] (2) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO: 17, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO: 17, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO: 17, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO: 18, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO: 18 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V;

[0271] (3) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:7, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:7, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:7, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:22, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:22 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A;

[0272] (4) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:21, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:21, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:21, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:8, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:8 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:8, wherein X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I;

[0273] (5) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:21, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:21, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:21, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:22, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:22 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:22;

[0274] (6) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO:8, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I;

[0275] (7) The anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO: 17, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V;

[0276] (8) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A;

[0277] (9) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO:21, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO:8, wherein X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I; or

[0278] (10) The anti-IL-4Rα antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region shown in SEQ ID NO:21, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO:22.

[0279] Embodiment 14. Use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof in the preparation of a medicament for improving one or more sinusitis-related parameters in a subject in need thereof, wherein the anti-IL-4Rα antibody or the antigen-binding fragment thereof comprises:

[0280] (1) a HCDR1 comprising the amino acid sequence of SEQ ID NO:1, a HCDR2 comprising the amino acid sequence of SEQ ID NO:2, a HCDR3 comprising the amino acid sequence of SEQ ID NO:3, a LCDR1 comprising the amino acid sequence of SEQ ID NO:4, a LCDR2 comprising the amino acid sequence of SEQ ID NO:5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:6; or

[0281] (2) HCDR1 comprising the amino acid sequence shown in SEQ ID NO:11, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:12, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:13, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:14, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:15, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:16.

[0282] Embodiment 15. The use according to embodiment 13 or 14, wherein the subject suffers from chronic sinusitis; or the subject suffers from bilateral chronic sinusitis; or the subject suffers from chronic sinusitis with nasal polyps or chronic sinusitis without nasal polyps; or the subject suffers from eosinophilic chronic sinusitis with nasal polyps or eosinophilic chronic sinusitis without nasal polyps.

[0283] Embodiment 16. The use according to any one of embodiments 13-15, wherein the subject further suffers from asthma.

[0284] Embodiment 17. The use according to any one of embodiments 13-16, wherein the sinusitis-related parameters include NPS, Lund-Mackay score, modified Lund-Kennedy score, sTSS, SNOT-22 score, nasal congestion score, rhinorrhoea score, anosmia score, nasal discharge / postnasal discharge score, facial pain / pressure score, VAS score, UPSIT score, NPIF, ACQ-6 score and / or the proportion of patients receiving systemic glucocorticoid rescue or surgical treatment during treatment.

[0285] Embodiment 18. The use according to Embodiment 17, wherein administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in an increase in NPIF and / or UPSIT score relative to baseline.

[0286] Embodiment 19. The use according to embodiment 17, wherein administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in NPS, Lund-Mackay score, Lund-Kennedy score, sTSS, SNOT-22 score, nasal congestion score, rhinorrhea score, anosmia score, runny nose / post-rhinorrhea score, facial pain / stress score, VAS score and / or ACQ-6 relative to baseline.

[0287] Embodiment 20. The use according to embodiment 19, wherein administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in NPS of at least 1 point, 1.5 points, 2 points, 2.5 points, 3 points, 3.5 points, 4 points, 4.5 points, 5 points, 5.5 points, 6 points, 6.5 points, 7 points, 7.5 points, or 8 points relative to baseline.

[0288] Embodiment 21. The use according to embodiment 19, wherein administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject results in a decrease in Lund-Mackay score of at least 0.2, 0.4, 0.6, 0.8, 1, 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.2, 3.4, 3.6, 3.8, 4, 5, 6, 7, 8, 9, 10, 11, or 12 points relative to baseline.

[0289] Embodiment 22. The use according to any one of Embodiments 13-21, wherein after administration of the anti-IL-4Rα antibody or antigen-binding fragment thereof to the subject, one or more of the following is reduced: IgE level, eosinophil count, CCL26 level, CST1 level, CLC level, and ALOX15 level.

[0290] Embodiment 23. The use according to any one of Embodiments 13-22, wherein the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at a dose of 100-1200 mg, 120-900 mg, 150-800 mg, 200-600 mg, or 300-600 mg each time; preferably, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at a dose of 300 mg or 600 mg each time.

[0291] Embodiment 24. The use according to any one of Embodiments 13-23, wherein the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks; preferably, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered once every 2 weeks.

[0292] Embodiment 25. The use according to any one of Embodiments 13-24, wherein the subject is administered one or more additional therapeutic agents before, after or simultaneously with receiving the anti-IL-4Rα antibody or its antigen-binding fragment; preferably, the subject has been administered or is being administered one or more additional therapeutic agents before receiving the anti-IL-4Rα antibody or its antigen-binding fragment.

[0293] Embodiment 26. The use according to embodiment 25, wherein the additional therapeutic agent is selected from one or more of glucocorticoids, long-acting β2 receptor agonists, short-acting β2 receptor agonists, IL-1 inhibitors, IL-5 inhibitors, IL-5Rα inhibitors, IL-13 inhibitors, TNF inhibitors, IgE inhibitors, non-steroidal anti-inflammatory drugs, antibiotics, antihistamines, antifungal agents, local decongestants, long-acting muscarinic antagonists and leukotriene antagonists; preferably, the glucocorticoid is selected from one or more of nasal glucocorticoids, inhaled glucocorticoids and systemic glucocorticoids.

[0294] Embodiment 27. The use according to Embodiment 25, wherein the subject has been or is being administered a nasal glucocorticoid before receiving the anti-IL-4Rα antibody or its antigen-binding fragment; preferably, the subject has been or is being administered a mometasone furoate nasal spray before receiving the anti-IL-4Rα antibody or its antigen-binding fragment.

[0295] Embodiment 28. The use according to any one of embodiments 13-27, wherein the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises:

[0296] (1) a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:8, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A of SEQ ID NO:7, and X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I of SEQ ID NO:8;

[0297] (2) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 17, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V;

[0298] (3) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A;

[0299] (4) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:21, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:8, wherein X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I in SEQ ID NO:8; or

[0300] (5) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:21, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:22.

[0301] Embodiment 29. The use according to any one of embodiments 13-28, wherein the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises:

[0302] (1) a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:9, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:10, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A of SEQ ID NO:9, and X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I of SEQ ID NO:10;

[0303] (2) a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 19, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 20, wherein X5 of SEQ ID NO: 19 is A or V;

[0304] (3) a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:9, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:24, wherein X1 of SEQ ID NO:9 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A;

[0305] (4) a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:23, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:10, wherein X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I of SEQ ID NO:10; or

[0306] (5) a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:23, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:24.

[0307] Embodiment 30. The use according to any one of Embodiments 13-29, wherein the anti-IL-4Rα antibody or antigen-binding fragment thereof is formulated together with a pharmaceutically acceptable excipient. Example

[0308] For the sake of clarity, the present disclosure is further illustrated with examples, but the examples do not limit the scope of the present disclosure. All reagents used in the present disclosure are commercially available and can be used without further purification.

[0309] The entire contents of the patent application documents with publication numbers WO2021170020A1 or CN115087673A are incorporated into the present disclosure. The heavy chain amino acid sequence of the anti-IL-4Rα antibody in the following embodiments is shown in SEQ ID NO:9 of the present disclosure, and the light chain amino acid sequence is shown in SEQ ID NO:10 of the present disclosure, wherein X1 of SEQ ID NO:9 is W and X2 is A, and X3 of SEQ ID NO:10 is F and X4 is V.

[0310] Example 1: Clinical trial A for chronic sinusitis

[0311] 1. Experimental Design

[0312] This clinical trial includes a 1-week screening period, a 2-4-week lead-in period, a 16-week treatment period, and an 8-week post-treatment follow-up period. For cohort 1, subjects were randomly divided into stratified groups based on whether they had previous asthma and whether the absolute value of eosinophils in nasal polyp tissue was ≥55 / HPF (high-power field of view); for cohort 2, subjects were randomly divided into stratified groups based on whether they had previous asthma. During the treatment period, subjects were given the trial drug or placebo on days 1, 15, 29, 43, 57, 71, 85, and 99.

[0313] Mometasone furoate nasal spray As a basic medication. During the lead-in period, the subjects began to use mometasone furoate nasal spray until the clinical trial is completed.

[0314] 2. Selection criteria

[0315] Subjects for this study must meet all of the following inclusion criteria:

[0316] (1) Aged 18-75, regardless of gender;

[0317] (2) Bilateral chronic sinusitis (with or without nasal polyps) that meets the diagnostic criteria of the "Guidelines for the Diagnosis and Treatment of Chronic Sinusitis in China (2018)"; (3) Receiving systemic glucocorticoid treatment within 2 years before screening (at least 1 course of prednisone 0.5-1 mg / kg / day, 15-30 mg / day, or equivalent)

[0318] effective dose for at least 3 days), but still have bilateral chronic sinusitis; and / or have contraindications or intolerance to systemic glucocorticoids, and / or have undergone sinus surgery within 6 months before the screening period;

[0319] (4) Subjects had used a stable dose of nasal corticosteroids (INCS) for more than 4 weeks before the screening period (for subjects who used INCS alternative products instead of mometasone furoate nasal spray (MFNS) before screening, the subjects were willing to switch to MFNS during the study);

[0320] (5) Subjects with combined asthma should have started stable inhaled glucocorticoid treatment at least 4 weeks before screening and can accept the unchanged inhaled glucocorticoid dose throughout the study;

[0321] (6) During the run-in period, subjects were willing to conduct daily symptom assessments in a diary and maintain a stable dose of MFNS with compliance greater than or equal to 70%;

[0322] (7) Be able to read and understand, and be willing to sign the informed consent form;

[0323] (8) Subjects and their partners agree to take effective contraceptive measures throughout the study (from the screening or run-in period to 3 months after the last medication). (9) For Cohort 1 (Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) subjects):

[0324] i. At screening and randomization, the bilateral nasal polyp score (NPS) assessed by nasal endoscopy was ≥5 (maximum score was 8), and the score of each nostril was ≥2;

[0325] ii. Nasal Congestion Score (NCS) ≥ 2 during the screening period and randomization; and

[0326] iii. The following symptoms persisted for at least 8 weeks before screening: ① nasal congestion; ② any other symptom such as decreased or loss of smell, or runny nose.

[0327] For Cohort 2 (eosinophilic chronic rhinosinusitis without nasal polyps (CRSsNP) subjects):

[0328] i. Prior to randomization, the subject must have bilateral sinus inflammation and bilateral Lund Mackay total score ≥ 8 points on CT scan, and bilateral ethmoid opacification;

[0329] ii. No nasal polyps confirmed by nasal endoscopy during the screening period and randomization;

[0330] iii. Subjects must have persistent symptoms of hyposmia for at least 4 consecutive weeks before the screening period;

[0331] iv. During the screening period, the subject had moderate or severe anosmia symptoms (anosmia score ≥ 2 points) and the weekly average severity at randomization was ≥ 2 points;

[0332] v. Subjects must have an sTSS score of ≥ 2 during screening and randomization; and

[0333] vi. Participants who have at least one blood test within 2 years before screening or at screening showing blood eosinophils meeting any of the following conditions:

[0334] 1) Blood eosinophil count ≥ 0.25 × 10 9 / L;

[0335] 2) The blood eosinophil percentage was ≥6.9% and the subjects did not have asthma;

[0336] 3) The blood eosinophil percentage is ≥3.7% and the subject has asthma.

[0337] 3. Drugs and treatment options

[0338] 3.1 Experimental drug: Anti-IL-4Rα antibody injection (specification: 300 mg (2 mL) / bottle): During the trial, one treatment cycle was every 2 weeks. The drug was administered subcutaneously at a dose of 300 mg or 600 mg of anti-IL-4Rα antibody on the first day of each treatment cycle, for a total of 8 doses.

[0339] 3.2 Control drug: Placebo (specification: 2 mL / bottle): During the trial, 2 weeks was a treatment cycle, and the drug was administered subcutaneously once on the first day of each treatment cycle, for a total of 8 times.

[0340] 3.3 Basic medication: mometasone furoate nasal spray (Specification: 140 presses / bottle, each press contains 50 μg of mometasone furoate): During the trial, 2 presses are administered in each nostril once a day (total daily dose is 200 μg). If the subject cannot tolerate the drug, the dose can be adjusted to 1 press in each nostril once a day (total daily dose is 100 μg).

[0341] 4. Safety evaluation standards

[0342] The NCI-CTC AE 5.0 standard was used to determine the incidence and severity of adverse events.

[0343] 5. Effectiveness evaluation indicators

[0344] 5.1 Main indicators:

[0345] (1) Queue 1:

[0346] The change in the nasal polyp score (NPS) of the subjects at week 16 relative to baseline, where: NPS is the sum of the scores of the left and right nostrils assessed by nasal endoscopy, with a total score range of 0 to 8. NPS is scored according to the grade of polyps, with 0 being no polyps, 1 being a small polyp in the middle nasal meatus that does not reach below the lower edge of the middle turbinate, 2 being a polyp that reaches below the lower edge of the middle turbinate, 3 being a large polyp that reaches the lower edge of the inferior turbinate or the inner side of the middle turbinate, and 4 being a large polyp that completely blocks the inferior nasal cavity;

[0347] (2) Queue 2:

[0348] The change in Lund Mackay score from baseline at week 16, where: Lund Mackay score was performed using sinus CT scans, divided into left and right sinus systems, with each side scored from 0 to 12 points, and a total score of 0 to 24 points; for patients who currently have a missing ostiomeatal complex (OC) due to previous surgery, a comprehensive score was given based on the location of the previous OC;

[0349] 5.2 Secondary indicators:

[0350] (1) Queue 1:

[0351] Changes from baseline in Lund Mackay scores on sinus CT scans at week 16;

[0352] Changes in the nasal congestion score (NCS) of the subjects at week 16 relative to baseline, where: NCS uses a 0-3 classification scale, with 0 for no symptoms, 1 for mild symptoms, 2 for moderate symptoms, and 3 for severe symptoms, determined by the subjects based on the severity of nasal congestion in the past 24 hours; for the determination of baseline values, if the subjects collected 4 or more measurements within 7 days before randomization, the average of all collected values ​​was taken as the baseline value; if the patient subjects collected less than 4 measurements within 7 days before randomization, the baseline was the average of the 4 most recent measurements before randomization, and the average score of week 15 was used for the determination of NCS at week 16;

[0353] (2) Queues 1 and 2:

[0354] The change in the modified Lund Kennedy score of the subjects under nasal endoscopy relative to the baseline at week 16, where: the modified Lund Kennedy score is based on the mucosal morphology of the subjects, with the main items being polyps, edema, and secretions. Each item is classified into three categories (0, 1, and 2 points respectively). The two sides of the nasal cavity are scored separately, and the total score is the sum of the scores of both sides;

[0355] The change in the subject's total sinus symptom score (sTSS) relative to baseline at week 16, where: the subjects scored nasal congestion, facial pain or pressure, and rhinorrhea (the average of anterior and posterior rhinorrhea) at a fixed time every morning, and each symptom was classified into three categories, with 0 for no symptoms, 1 for mild symptoms, 2 for moderate symptoms, and 3 for severe symptoms. The sTSS is composed of the sum of the above items, with a score range of 0-9. For the determination of baseline values, if the subject collected 4 or more measurements within 7 days before randomization, the average of all collected values ​​was taken as the baseline value; if the subject collected less than 4 measurements within 7 days before randomization, the baseline was the average of the 4 most recent measurements before randomization. For the determination of sTSS at week 16, the average score of week 15 will be used;

[0356] The change in the 22-item nasal sinus outcome test (SNOT-22) of the subjects at week 16 relative to baseline, including: The SNOT-22 scoring scale has a total of 22 questions, including three dimensions: physiological problems, functional limitations, and emotional outcomes. The subjects make an assessment based on their situation in the past two weeks. The total score of SNOT-22 ranges from 0 to 110 points, and the lower the score, the less impact sinusitis has on quality of life;

[0357] The relative baseline change value of the University of Pennsylvania Smell Identification Test (UPSIT) at week 16. The test method is: 40 bromines are placed in capsules of 10-50μm, and then divided into 4 booklets arranged according to different odors. Each booklet includes 10 pages, and each page has 1 odor capsule with 4 answers printed on it. The subject scratches the capsule with a pencil, sniffs it and chooses from the 4 options. 1 point is scored for each correct answer to the odor. The olfactory function is evaluated according to the subject's score, 35-40 points for normal olfaction, 15-34 points for hyposmia, and <15 points for anosmia;

[0358] The change in the subjects' smell loss score relative to the baseline at week 16, where the smell loss score ranges from 0 to 3 points, with 0 being no symptoms, 1 being mild symptoms, 2 being moderate symptoms, and 3 being severe symptoms, and is assessed by the subjects based on the severity of their own smell loss on that day;

[0359] Changes in the subjects' nasal discharge or postnasal discharge scores relative to baseline at week 16;

[0360] Changes in the subjects' facial pain or stress scores relative to baseline at week 16;

[0361] The change in the subjects' sinusitis visual analogue scale (VAS) score relative to baseline at week 16, where: the VAS score range is 0-10 points, and the higher the score, the greater the impact of sinusitis on the subject's quality of life. According to the score range, the condition is divided into mild (0-3 points), moderate (3-7 points, excluding 3 points) and severe (7-10 points, excluding 7 points);

[0362] The impact value of the subjects’ health-related quality of life (HRQoL) at week 16;

[0363] The change in the subject's nasal peak inspiratory flow (NPIF) relative to baseline at week 16, where: NPIF monitors the subject's nasal flow and assesses the subject's nasal resistance by measuring the maximum inspiratory flow rate of both nostrils, and is most relevant to the subject's subjective feeling of nasal congestion. The subject needs to measure the nasal peak inspiratory flow rate before using MFNS for each test. The subject should rest for at least 5 minutes before the operation. During the operation, the subject stands and returns the indicator dial of the nasal peak inspiratory flow meter to zero. The subject holds the inspiratory peak flow meter connected to a sealed mask horizontally, exhales to the residual breath position, the mask fits tightly against the cheek without leaking, inhales explosively, removes the mask and reads the reading, and repeats the measurement 3 times. The highest value will be used for evaluation. The baseline NPIF value is defined as the highest NPIF value measured at the randomization visit. After treatment, the NPIF uses the highest value measured at week 16 and the end-of-treatment (EOT) visit;

[0364] The proportion of subjects who received systemic corticosteroid (SCS) rescue or surgical treatment during the treatment period;

[0365] 5.3 Exploration Indicators:

[0366] (1) Queues 1 and 2:

[0367] Changes from baseline in ACQ-6 scores of subjects with asthma at week 16;

[0368] At week 16, the relative changes in the subjects' peripheral blood total IgE, blood eosinophil count, blood eosinophil activation chemokine-3 (CCL26), and cysteine ​​protease inhibitor 1 (CST1) relative to baseline;

[0369] Changes from baseline in CST1, CCL26, Charcot-Leyden crystallin (CLC), and arachidonic acid-15-lipoxygenase (ALOX15) in nasal exfoliated cells of subjects at week 16;

[0370] Changes in nasal secretion cytokines and microorganisms relative to baseline at week 16;

[0371] (2) Queue 2:

[0372] The change in nasal congestion score (NCS) of subjects at week 16 relative to baseline.

[0373] Example 2: Clinical trial B for chronic sinusitis

[0374] 1. Experimental Design

[0375] This clinical trial includes a 1-week screening period, a 24-week treatment period, and an 8-week post-treatment follow-up period. During the treatment period, randomization will begin on day 1 and trial drugs or placebo will be administered until week 24, with no medication at week 24.

[0376] Mometasone furoate nasal spray As a basic medication. Subjects began to use mometasone furoate nasal spray on the day of randomization. until the clinical trial is completed.

[0377] 2. Selection criteria

[0378] Subjects for this study must meet all of the following inclusion criteria:

[0379] (1) Sign the informed consent form before the trial and fully understand the purpose, process and possible adverse reactions of the trial;

[0380] (2) Aged 18-75 (inclusive), regardless of gender;

[0381] (3) Participating in the clinical study described in Example 1 and meeting the following criteria "a" or "b":

[0382] a. The subjects completed the prescribed treatment as required and completed the end-of-study (EOS) visit;

[0383] b. The subject withdraws early and completes the early withdrawal visit according to the protocol, and the factors that lead to the subject's early termination have disappeared or no longer affect the subject's participation in this study as assessed by the investigator and the sponsor;

[0384] (4) Subjects had used a stable dose of nasal corticosteroids (INCS) for more than 4 weeks before the screening period (for subjects who used INCS alternative products instead of mometasone furoate nasal spray (MFNS) before screening, the subjects were willing to switch to MFNS during the study);

[0385] (5) The subjects agree not to have any fertility plans from the date of signing the informed consent form to 6 months after the last dose, and must take effective non-drug contraceptive measures with their sexual partners of childbearing age.

[0386] 3. Drugs and treatment options

[0387] 3.4 Trial drug: Anti-IL-4Rα antibody injection (Specification: 300 mg (2 mL) / bottle): During the trial, one treatment cycle was every 2 weeks, and the anti-IL-4Rα antibody was administered once on the first day of each treatment cycle by subcutaneous injection at a dose of 300 mg or 600 mg, for a total of

[0388] 12 times.

[0389] 3.5 Control drug: Placebo (specification: 2 mL / bottle): During the trial, one treatment cycle was 2 weeks, and the drug was administered subcutaneously once on the first day of each treatment cycle, for a total of 12 times.

[0390] 3.6 Basic medication: mometasone furoate nasal spray (Specification: 140 presses / bottle, each press contains 50 μg of mometasone furoate): During the trial, 2 presses are administered in each nostril once a day (total daily dose is 200 μg). If the subject cannot tolerate the drug, the dose can be adjusted to 1 press in each nostril once a day (total daily dose is 100 μg).

[0391] 4. Safety evaluation standards

[0392] The NCI-CTC AE 5.0 standard was used to determine the incidence and severity of adverse events.

[0393] 5. Effectiveness evaluation indicators

[0394] (1) Main indicators: frequency of treatment-emergent adverse events (TEAEs);

[0395] (2) Secondary indicators: For CRSwNP subjects:

[0396] The frequency of serious adverse events (SAEs) that occurred during treatment;

[0397] Abnormal laboratory test indicators during treatment;

[0398] The change in nasal polyp score from the baseline (the baseline values ​​of the clinical study described in Example 1 and the present study, respectively);

[0399] Change from baseline in Lund Mackay score assessed by CT;

[0400] The change in UPSIT score relative to the baseline (the baseline values ​​of the clinical study described in Example 1 and this study were used respectively);

[0401] The change value of sTSS relative to baseline;

[0402] Change in SNOT-22 from baseline;

[0403] Change value of NCS relative to baseline;

[0404] change from baseline in nasal discharge / postnasal discharge score;

[0405] change in smell loss score from baseline;

[0406] VAS change value relative to baseline;

[0407] Immunogenicity: the incidence and titer of anti-drug antibodies (ADA), the incidence of neutralizing antibodies (Nab).

[0408] For CRSsNP subjects:

[0409] The frequency of serious adverse events (SAEs) that occurred during treatment;

[0410] Abnormal laboratory test indicators during treatment;

[0411] Change from baseline in Lund Mackay score assessed by CT;

[0412] The change in UPSIT score relative to the baseline (the baseline values ​​of the clinical study described in Example 1 and this study were used respectively);

[0413] change in smell loss score from baseline;

[0414] The relative baseline of the modified Lund Kennedy score under nasal endoscopy (respectively using the clinical study described in Example 1 and the baseline in this study)

[0415] Line value) change value;

[0416] The change in sTSS relative to the baseline (the baseline values ​​of the clinical study described in Example 1 and this study were used respectively);

[0417] Change in SNOT-22 from baseline;

[0418] The change value of VAS relative to the baseline (the baseline values ​​of the clinical study described in Example 1 and this study were used respectively);

[0419] Immunogenicity: the incidence and titer of anti-drug antibodies (ADA), the incidence of neutralizing antibodies (Nab).

[0420] The scoring methods for the above indicators are carried out with reference to Example 1.

Claims

1. Use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof in the preparation of a medicament for treating chronic sinusitis in a subject in need thereof, characterized in that: (1) The anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:7, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:7, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:7, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:8, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:8 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:8, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I; (2) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO: 17, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO: 17, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO: 17, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO: 18, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO: 18 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V; (3) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:7, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:7, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:7, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:22, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:22 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A; (4) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:21, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:21, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:21, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:8, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:8 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:8, wherein X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I; (5) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of HCDR1 in SEQ ID NO:21, HCDR2 comprises the amino acid sequence of HCDR2 in SEQ ID NO:21, HCDR3 comprises the amino acid sequence of HCDR3 in SEQ ID NO:21, LCDR1 comprises the amino acid sequence of LCDR1 in SEQ ID NO:22, LCDR2 comprises the amino acid sequence of LCDR2 in SEQ ID NO:22 and LCDR3 comprises the amino acid sequence of LCDR3 in SEQ ID NO:22; (6) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO:8, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I; (7) The anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO: 17, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V; (8) The anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A; (9) the anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region as shown in SEQ ID NO:21, and LCDR1, LCDR2 and LCDR3 of the light chain variable region as shown in SEQ ID NO:8, wherein X3 of SEQ ID NO:8 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I; or (10) The anti-IL-4Rα antibody or its antigen-binding fragment comprises: HCDR1, HCDR2 and HCDR3 of the heavy chain variable region shown in SEQ ID NO:21, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO:

22.

2. Use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof in the preparation of a medicament for treating chronic sinusitis in a subject in need thereof, wherein: The anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: (1) a HCDR1 comprising the amino acid sequence of SEQ ID NO:1, a HCDR2 comprising the amino acid sequence of SEQ ID NO:2, a HCDR3 comprising the amino acid sequence of SEQ ID NO:3, a LCDR1 comprising the amino acid sequence of SEQ ID NO:4, a LCDR2 comprising the amino acid sequence of SEQ ID NO:5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:6; or (2) HCDR1 comprising the amino acid sequence shown in SEQ ID NO:11, HCDR2 comprising the amino acid sequence shown in SEQ ID NO:12, HCDR3 comprising the amino acid sequence shown in SEQ ID NO:13, LCDR1 comprising the amino acid sequence shown in SEQ ID NO:14, LCDR2 comprising the amino acid sequence shown in SEQ ID NO:15, and LCDR3 comprising the amino acid sequence shown in SEQ ID NO:

16.

3. The use according to claim 1 or 2, wherein The chronic sinusitis is chronic sinusitis with nasal polyps or chronic sinusitis without nasal polyps; or the chronic sinusitis is bilateral chronic sinusitis; or the chronic sinusitis is eosinophilic chronic sinusitis with nasal polyps or eosinophilic chronic sinusitis without nasal polyps.

4. The use according to any one of claims 1 to 3, wherein The subject further suffers from asthma.

5. The use according to any one of claims 1 to 4, wherein The anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at a dose of 100-1200 mg, 120-900 mg, 150-800 mg, 200-600 mg, or 300-600 mg each time; preferably, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered at a dose of 300 mg or 600 mg each time.

6. The use according to any one of claims 1 to 5, wherein The anti-IL-4Rα antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks; preferably, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered once every 2 weeks.

7. The use according to any one of claims 1 to 6, wherein The subject is administered one or more additional therapeutic agents before, after or simultaneously with the anti-IL-4Rα antibody or antigen-binding fragment thereof; preferably, the subject has been administered or is being administered one or more additional therapeutic agents before the anti-IL-4Rα antibody or antigen-binding fragment thereof.

8. The use according to claim 7, wherein The additional therapeutic agent is selected from one or more of glucocorticoids, long-acting β2 receptor agonists, short-acting β2 receptor agonists, IL-1 inhibitors, IL-5 inhibitors, IL-5Rα inhibitors, IL-13 inhibitors, TNF inhibitors, IgE inhibitors, non-steroidal anti-inflammatory drugs, antibiotics, antihistamines, antifungal agents, local decongestants, long-acting muscarinic antagonists and leukotriene antagonists; preferably, the glucocorticoid is selected from one or more of nasal glucocorticoids, inhaled glucocorticoids and systemic glucocorticoids.

9. The use according to claim 7, wherein: The subject has been or is being administered nasal glucocorticoids before receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof; preferably, the subject has been or is being administered mometasone furoate nasal spray before receiving the anti-IL-4Rα antibody or antigen-binding fragment thereof.

10. The use according to any one of claims 1 to 9, wherein The anti-IL-4Rα antibody or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:8, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A of SEQ ID NO:7, and X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I of SEQ ID NO:8; (2) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 17, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 18, wherein X5 of SEQ ID NO: 17 is A or V; (3) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:7, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:22, wherein X1 of SEQ ID NO:7 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A; (4) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:21, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:8, wherein X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I in SEQ ID NO:8; or (5) a heavy chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:21, and a light chain variable region having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:22.

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