Method for treating allergic rhinitis by Anti-il-4rα antibody

Abstract

Provided is a method for treating allergic rhinitis by an anti-IL-4Rα antibody, which comprises administering the anti-IL-4Rα antibody or an antigen-binding fragment thereof to a subject, wherein the allergic rhinitis is preferably seasonal allergic rhinitis.

Description

Methods of treating allergic rhinitis with anti-IL-4Rα antibodies Technical Field

[0001] This disclosure pertains to the field of biomedicine and specifically relates to a method for treating allergic rhinitis by administering an anti-IL-4Rα antibody or its antigen-binding fragment. Background Technology

[0002] Allergic rhinitis (AR) is a non-infectious, chronic inflammatory disease of the nasal mucosa, primarily mediated by immunoglobulin E (IgE), following exposure to allergens in atopic individuals. Typical symptoms include paroxysmal sneezing, clear nasal discharge, nasal itching, and nasal congestion; ocular symptoms may also be present, including itchy eyes, tearing, redness, and burning sensation, and are more common in patients with pollen allergies. AR can be classified into seasonal AR (SAR) and perennial AR based on the type of allergen. SAR symptoms occur seasonally, with common allergens being seasonal inhaled allergens such as pollen and fungi. Type 2 inflammation is part of a normal immune response triggered by specific types of allergens, caused by multiple factors, with Th2 cells being the core of the type 2 inflammatory response. Overactivation of the Th2 pathway can lead to severe allergic diseases (such as allergic rhinitis).

[0003] Interleukin-4 (IL-4) and IL-13 are key cytokines for inducing and maintaining type 2 inflammatory responses. They are essential for driving most key markers of type 2 inflammation, such as the production of immunoglobulin E and the recruitment of innate cells to inflammatory sites. IL-4 and IL-13 play important roles in the development and progression of type 2 inflammatory diseases by binding to IL-4Rα, triggering transphosphorylation and activation of JAK kinase, and inducing phosphorylation of the transcription factor STAT.

[0004] Numerous clinical studies have found that current conventional treatments for allergic rhinitis are ineffective and often lead to adverse reactions. Therefore, more effective treatments are still needed in clinical practice.

[0005] Invention Overview

[0006] In one aspect, this disclosure provides a method of treating allergic rhinitis in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In another aspect, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for treating allergic rhinitis in a subject. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with a further therapeutic agent.

[0007] In one aspect, this disclosure provides a method for improving one or more allergic rhinitis-related parameters in a subject with allergic rhinitis, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In another aspect, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for improving one or more allergic rhinitis-related parameters in a subject with allergic rhinitis. In some embodiments, in said method or use, the anti-IL-4Rα antibody or antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in said use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or antigen-binding fragment thereof. In some embodiments, in said method or use, the anti-IL-4Rα antibody or antigen-binding fragment thereof is co-administered with an additional therapeutic agent.

[0008] In one aspect, this disclosure provides a method for reducing dependence on standard treatments for allergic rhinitis (e.g., nasal corticosteroids and / or histamine receptor antagonists) in subjects with allergic rhinitis, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In another aspect, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for reducing dependence on standard treatments for allergic rhinitis (e.g., nasal corticosteroids and / or histamine receptor antagonists) in subjects with allergic rhinitis. In some embodiments, in said method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in said use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in said method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with a further therapeutic agent.

[0009] In some embodiments, this disclosure also provides pharmaceutical compositions comprising the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof for use in treating allergic rhinitis in subjects. In some embodiments, this disclosure also provides pharmaceutical compositions comprising the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof for improving one or more allergic rhinitis-related parameters in subjects with allergic rhinitis. In some embodiments, this disclosure also provides pharmaceutical compositions comprising the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof for reducing dependence on glucocorticoids and / or histamine receptor antagonists in subjects with allergic rhinitis.

[0010] In some embodiments, the allergic rhinitis is seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is moderate to severe seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is severe seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is seasonal allergic rhinitis that is poorly or unsuitably controlled by standard treatment (e.g., nasal corticosteroids and / or histamine receptor antagonists). In some embodiments, the allergic rhinitis is moderate to severe seasonal allergic rhinitis that is poorly or unsuitably controlled by standard treatment (e.g., nasal corticosteroids and / or histamine receptor antagonists).

[0011] In some implementations, the subject has a history of inadequate response to or intolerance to standard treatment for allergic rhinitis (e.g., nasal corticosteroids and / or histamine receptor antagonists).

[0012] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered every 2 weeks (q2w). In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered every 1 week (q1w or qw). In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered at a dose of 100-1200 mg each time. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered every 2 weeks (q2w) at a dose of 100-1200 mg each time.

[0013] Invention Details

[0014] Before describing this disclosure, it should be understood that this disclosure is not limited to the specific methods and experimental conditions described, as these methods and conditions can vary. Unless otherwise stated, the terminology used in this disclosure should not be considered uncertain or unclear unless specifically defined, but should be understood in accordance with its ordinary meaning in the art. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. When trade names appear in this disclosure, they are intended to refer to the corresponding product or its active ingredient.

[0015] As used herein, “about” means within an acceptable range of error 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, in accordance with art practice, mean within one or more standard deviations. Alternatively, “about” may mean a range of up to ±5%, such as fluctuations within ±2%, ±1%, or ±0.5% of a given specific numerical range. When a particular value is given in this disclosure or embodiments, unless otherwise stated, “about” should be understood as meaning within an acceptable range of error for that particular value. In this document, unless otherwise stated, all values ​​for drug dosage, time, procedure parameters, or conditions are implicitly modified by “about”.

[0016] Methods for treating allergic rhinitis

[0017] In one aspect, this disclosure provides a method of treating allergic rhinitis in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In another aspect, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for treating allergic rhinitis in a subject. In yet another aspect, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in treating allergic rhinitis in a 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 the subject. In some embodiments, in the method or use, the anti-IL-4Rα antibody or antigen-binding fragment thereof or the pharmaceutical composition is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or antigen-binding fragment thereof is co-administered with a further therapeutic agent.

[0018] This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, and other therapeutic agents, in the preparation of a medicament for treating allergic rhinitis in a subject. This disclosure further provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for treating allergic rhinitis in a subject in combination with other therapeutic agents.

[0019] In some embodiments, the allergic rhinitis in the method or use is seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is moderate to severe seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is severe seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is seasonal allergic rhinitis poorly or unsuitably controlled by standard treatment (e.g., nasal corticosteroids and / or histamine receptor antagonists). In some embodiments, the allergic rhinitis is moderate to severe seasonal allergic rhinitis poorly or unsuitably controlled by standard treatment (e.g., nasal corticosteroids and / or histamine receptor antagonists).

[0020] In some implementations, the subject has a history of inadequate response to or intolerance to standard treatment for allergic rhinitis (e.g., nasal corticosteroids and / or histamine receptor antagonists).

[0021] The terms “allergic rhinitis,” “hypersensitivity rhinitis,” and “deformity rhinitis” are used interchangeably.

[0022] The terms “administration,” “application,” or “giving” indicate the introduction of a therapeutic agent into a physical body using any of a variety of methods and delivery systems known to those skilled in the art.

[0023] In this document, 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.

[0024] Methods to improve parameters related to allergic rhinitis

[0025] In one aspect, this disclosure provides a method for improving one or more allergic rhinitis-related parameters in a subject with allergic rhinitis, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In another aspect, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for improving one or more allergic rhinitis-related parameters in a subject with allergic rhinitis. In yet another aspect, this disclosure provides the use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof in improving one or more allergic rhinitis-related parameters in a subject with allergic rhinitis. In some embodiments, the anti-IL-4Rα antibody or an antigen-binding fragment thereof may be formulated with one or more pharmaceutically acceptable excipients to form a suitable pharmaceutical composition for administration to the subject. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof or the pharmaceutical composition is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered in combination with another therapeutic agent in the method or use described herein.

[0026] This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, and other therapeutic agents, in the preparation of a medicament for improving one or more allergic rhinitis-related parameters in subjects with allergic rhinitis. This disclosure further provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for improving one or more allergic rhinitis-related parameters in combination with other therapeutic agents in subjects with allergic rhinitis.

[0027] In some embodiments, the allergic rhinitis in the method or use is seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is moderate to severe seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is severe seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is seasonal allergic rhinitis poorly or unsuitably controlled by standard treatment (e.g., nasal corticosteroids and / or histamine receptor antagonists). In some embodiments, the allergic rhinitis is moderate to severe seasonal allergic rhinitis poorly or unsuitably controlled by standard treatment (e.g., nasal corticosteroids and / or histamine receptor antagonists).

[0028] In some implementations, the subject has a history of inadequate response to or intolerance to standard treatment for allergic rhinitis (e.g., nasal corticosteroids and / or histamine receptor antagonists).

[0029] Examples of "parameters related to allergic rhinitis" include, but are not limited to: (1) Total Nasal Symptom Score (TNSS), (2) Total Ocular Symptom Score (TOSS), (3) Quality of Life Questionnaire for Patients with Allergic Rhinitis (RQLQ), (4) Visual Analogue Scale (VAS), and (5) Olfactory Function Score. TNSS is the sum of scores for four symptoms: runny nose, nasal congestion, nasal itching, and sneezing, and is divided into retrospective total nasal symptom score (rTNSS) and transient total nasal symptom score (iTNSS). TOSS is the sum of scores for three symptoms: itchy / burning eyes, tearing / watering eyes, and red eyes, and is divided into retrospective total ocular symptom score (rTOSS) and transient total ocular symptom score (iTOSS).

[0030] "Improvement of allergic rhinitis-related parameters," "Improvement of allergic rhinitis-related parameters," and "Improvement of one or more allergic rhinitis-related parameters" refer to a reduction in one or more of the following parameters relative to baseline: TNSS, rTNSS, iTNSS, TOSS, rTOSS, iTOSS, Allergic Rhinitis Patient Quality of Life Questionnaire score, individual nasal symptom score (i.e., runny nose, nasal congestion, nasal itching, or sneezing), individual ocular symptom score (i.e., itchy / burning eyes, watery / dribbling eyes, or red eyes), VAS, and olfactory function score. "Improvement of allergic rhinitis-related parameters" can be expressed as a percentage, for example, an improvement of 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 in its ordinary sense as understood by those skilled in the art, for example, in relation to allergic rhinitis-related parameters, meaning the value of such allergic rhinitis-related parameter in a subject before or at the time of administration of the anti-IL-4Rα antibody or its antigen-binding fragment of the present disclosure; for example, “baseline” is the average of all measurements taken 7 days prior to administration of the anti-IL-4Rα antibody or its antigen-binding fragment of the present disclosure, or the most recent non-missing measurement prior to administration of the anti-IL-4Rα antibody or its antigen-binding fragment of the present disclosure.

[0031] To determine whether a certain allergic rhinitis-related parameter has "improved," the parameter is quantified at baseline and at a time point following administration of the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein. For example, it can be quantified on days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 14, or at weeks 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 14, following initial treatment with the subject using the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein. Allergic rhinitis-related parameters are measured at weeks 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, or longer. In some implementations, parameters are measured daily (e.g., including but not limited to once or twice daily), weekly, bi-weekly, or monthly.

[0032] The difference between the value of a certain allergic rhinitis-related parameter at a specific time point after the start of treatment and the value of that allergic rhinitis-related parameter at baseline is used to demonstrate whether the allergic rhinitis-related parameter has "improved" (e.g., increased or decreased depending on the specific parameter being measured).

[0033] (1) Total Nasal Symptom Score (TNSS)

[0034] Nasal symptoms were scored, including runny nose, nasal congestion, nasal itching, and sneezing. Each symptom was assessed using a 0-3 category scale, where 0 indicates no symptoms, 1 indicates mild symptoms (i.e., signs / symptoms are clearly present but only very mild and easily tolerated), 2 indicates moderate symptoms (i.e., noticeable signs / symptoms are bothersome but tolerable), and 3 indicates severe symptoms (i.e., signs / symptoms are unbearable and interfere with daily activities and / or sleep). The TNSS (Total Nasal Symptom Score) is the sum of the scores for the four symptom categories, ranging from 0 to 12.

[0035] In some embodiments, this disclosure provides a method for reducing TNSS in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In some embodiments, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for reducing TNSS in a subject. In some embodiments, administering the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof to the subject results in a reduction of TNSS relative to baseline (i.e., achieving a lower number on a scale). In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with a further therapeutic agent.

[0036] In some embodiments, this disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, in combination with additional therapeutic agents, in the preparation of a medicament for reducing TNSS in a subject. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with additional therapeutic agents to reduce TNSS in a subject.

[0037] The retrospective total nasal symptom score (rTNSS) is a score of nasal symptoms described over the past 12 hours, administered twice daily: the daytime retrospective total nasal symptom score (AM rTNSS) and the nighttime retrospective total nasal symptom score (PM rTNSS). The AM rTNSS is administered in the morning, and the PM rTNSS is administered in the evening. The rTNSS is the mean of the AM and PM rTNSS for the current day, or the mean of the PM rTNSS for the current day and the AM rTNSS for the following day.

[0038] In some embodiments, this disclosure provides a method for reducing rTNSS in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In some embodiments, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for reducing rTNSS in a subject. In some embodiments, administration to the subject of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof results in a reduction of rTNSS relative to baseline (i.e., achieving a lower number on a scale). In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with a further therapeutic agent.

[0039] In some embodiments, this disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, in combination with additional therapeutic agents, in the preparation of a medicament for reducing rTNSS in a subject. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with additional therapeutic agents to reduce rTNSS in a subject.

[0040] In some embodiments, the method of this disclosure can reduce a subject's rTNSS score by 0.1 to 12 points relative to baseline. In some embodiments, the method of this disclosure can reduce a subject's rTNSS score by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, or 12 points, or any two of the above values, relative to baseline. In some embodiments, the method of this disclosure can reduce a subject's rTNSS 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 any two of the above values. In some implementations, the methods of this disclosure can reduce a subject's rTNSS score to 11 or lower, 10 or lower, 9 or lower, 8 or lower, 7 or lower, 6 or lower, 5 or lower, 4 or lower, 3 or lower, 2 or lower, or 1 or lower.

[0041] In some embodiments, after the subject has been treated with the method of this disclosure for 1, 2, 3, 4, or more treatment cycles, the subject's rTNSS decreases relative to baseline. In some embodiments, after the subject has been treated with the method of this disclosure for 1, 2, 3, 4, or more treatment cycles, the subject's rTNSS decreases relative to baseline by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, or 12 points. In some implementations, after the subject is treated with the method of this disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, or more treatment cycles, the subject's rTNSS score is reduced to 11 points or less, 10 points or less, 9 points or less, 8 points or less, 7 points or less, 6 points or less, 5 points or less, 4 points or less, 3 points or less, 2 points or less, or 1 point or less.

[0042] In some implementations, after one, two, three, four, or more treatment cycles, the reduction in rTNSS relative to baseline in subjects administering the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 points, or any two of the above values, after one, two, three, four, or more treatment cycles, is greater than the reduction in rTNSS relative to baseline in subjects administering placebo. In some implementations, after one or two treatment cycles, the reduction in rTNSS relative to baseline in subjects administering the anti-IL-4Rα antibody or its antigen-binding fragment of this disclosure is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 points, or any two of the above values, after one or two treatment cycles.

[0043] The instantaneous nasal symptom score (iTNSS) is a score of the nasal symptoms at a specific point in time. In some embodiments, the iTNSS is performed before administration of the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the iTNSS is performed after administration of the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the iTNSS is performed at 4, 6, 8, 10, and / or 12 hours after administration of the anti-IL-4Rα antibody or its antigen-binding fragment.

[0044] In some embodiments, this disclosure provides a method for reducing iTNSS in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In some embodiments, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for reducing iTNSS in a subject. In some embodiments, administration to the subject of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof results in a reduction of iTNSS relative to baseline (i.e., achieving a lower number on a scale). In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with a further therapeutic agent.

[0045] In some embodiments, this disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, in combination with additional therapeutic agents, in the preparation of a medicament for reducing iTNSS in a subject. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with additional therapeutic agents to reduce iTNSS in a subject.

[0046] In some embodiments, the method of this disclosure can reduce a subject's iTNSS score by 0.1 to 12 points relative to baseline. In some embodiments, the method of this disclosure can reduce a subject's iTNSS score by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, or 12 points, or any two of the above values, relative to baseline. In some embodiments, the methods of this disclosure can reduce a subject's iTNSS 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 any two of the above values. In some implementations, the methods of this disclosure can reduce a subject's iTNSS to 11 points or less, 10 points or less, 9 points or less, 8 points or less, 7 points or less, 6 points or less, 5 points or less, 4 points or less, 3 points or less, 2 points or less, or 1 point or less.

[0047] In some embodiments, after the subject has been treated with the method of this disclosure for 1, 2, 3, 4, or more treatment cycles, the subject's iTNSS decreases relative to baseline. In some embodiments, after the subject has been treated with the method of this disclosure for 1, 2, 3, 4, or more treatment cycles, the subject's iTNSS decreases relative to baseline by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, or 12 points. In some implementations, after the subject is treated with the method of this disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, or more treatment cycles, the subject's iTNSS score is reduced to 11 points or less, 10 points or less, 9 points or less, 8 points or less, 7 points or less, 6 points or less, 5 points or less, 4 points or less, 3 points or less, 2 points or less, or 1 point or less.

[0048] In some implementations, after one, two, three, four, or more treatment cycles, the reduction in iTNSS relative to baseline in subjects administering the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 points, or any two of the above values, after one, two, three, four, or more treatment cycles, is greater than the reduction in iTNSS relative to baseline in subjects administering placebo. In some implementations, after one or two treatment cycles, the reduction in iTNSS relative to baseline in subjects receiving the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 points, or any two of the above values, is greater than the reduction in iTNSS relative to baseline in subjects receiving placebo.

[0049] In some embodiments, this disclosure provides a method for reducing a single nasal symptom score in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In some embodiments, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for reducing a single nasal symptom score in a subject. In some embodiments, administration of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof to the subject results in a reduction in the single nasal symptom score relative to baseline (i.e., achieving a lower number on the scale). In some embodiments, the single nasal symptom score is runny nose, nasal congestion, nasal itching, or sneezing. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with an additional therapeutic agent.

[0050] In some embodiments, this disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, and additional therapeutic agents, in the preparation of a medicament for reducing a single nasal symptom score in a subject. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with additional therapeutic agents to reduce a single nasal symptom score in a subject.

[0051] In some embodiments, the method of this disclosure can reduce a subject's individual nasal symptom score by 0.1 to 3 points relative to baseline. In some embodiments, the method of this disclosure can reduce a subject's individual nasal symptom score by at least 1, 1.5, 2, 2.5, or 3 points, or any two of the above values, relative to baseline. In some embodiments, the methods of this disclosure can reduce a subject's individual nasal symptom 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 any two of the above values. In some implementations, the methods of this disclosure can reduce a subject's individual nasal symptom score to 2.5 points or less, 2 points or less, 1.5 points or less, or 1 point or less.

[0052] In some embodiments, after the subject has been treated with the method of this disclosure for one, two, three, four, or more treatment cycles, the subject's individual nasal symptom score decreases relative to baseline. In some embodiments, after the subject has been treated with the method of this disclosure for one, two, three, four, or more treatment cycles, the subject's individual nasal symptom score decreases relative to baseline by at least 1, 1.5, 2, 2.5, or 3 points. In some embodiments, after the subject has been treated with the method of this disclosure for one, two, three, four, or more treatment cycles, the subject's individual nasal symptom score decreases to 2.5 points or less, 2 points or less, 1.5 points or less, or 1 point or less.

[0053] In some implementations, after one, two, three, four, or more treatment cycles, the reduction in a single nasal symptom score relative to baseline in subjects administering the anti-IL-4Rα antibody or its antigen-binding fragment of this disclosure is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, or any two of the above values, greater than the reduction in a single nasal symptom score relative to baseline in subjects administering placebo. In some implementations, after one or two treatment cycles, the reduction in a single nasal symptom score relative to baseline in subjects administering the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment is greater than the reduction in a single nasal symptom score relative to baseline in subjects administering placebo by 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, or any two of the above values.

[0054] (2) Total Ocular Symptom Score (TOSS)

[0055] Eye symptoms were scored, including itchy / burning eyes, tearing / watering eyes, and red eyes. Each symptom was assessed using a 0-3 category scale, where 0 indicates no symptoms, 1 indicates mild symptoms (i.e., signs / symptoms are clearly present but rarely noticed and easily tolerated), 2 indicates moderate symptoms (i.e., signs / symptoms are clearly noticed, bothersome but still tolerable), and 3 indicates severe symptoms (i.e., signs / symptoms are unbearable and interfere with daily activities and / or sleep). TOSS is the sum of the scores for the three symptom categories, ranging from 0 to 9.

[0056] In some embodiments, this disclosure provides a method for reducing TOSS in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In some embodiments, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for reducing TOSS in a subject. In some embodiments, administration to the subject of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof results in a reduction in TOSS relative to baseline (i.e., achieving a lower number on a scale). In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with a further therapeutic agent.

[0057] In some embodiments, this disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, in combination with additional therapeutic agents, in the preparation of a medicament for reducing TOSS in a subject. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with additional therapeutic agents to reduce TOSS in a subject.

[0058] The retrospective total ocular symptom score (rTOSS) is a score of the ocular symptoms described over the past 12 hours, administered twice daily: the daytime retrospective total ocular symptom score (AM rTOSS) and the nighttime retrospective total ocular symptom score (PM rTOSS). AM rTOSS is administered in the morning, and PM rTOSS is administered in the evening. rTOSS is the mean of the AM rTOSS and PM rTOSS for the current day; or the mean of the PM rTOSS for the current day and the AM rTOSS for the following day.

[0059] In some embodiments, this disclosure provides a method for reducing rTOSS in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In some embodiments, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for reducing rTOSS in a subject. In some embodiments, administration to the subject of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof results in a reduction of rTOSS relative to baseline (i.e., achieving a lower number on a scale). In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with an additional therapeutic agent.

[0060] In some embodiments, this disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, in combination with additional therapeutic agents, in the preparation of a medicament for reducing rTOSS in a subject. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with additional therapeutic agents to reduce rTOSS in a subject.

[0061] In some embodiments, the method of this disclosure can reduce a subject's rTOSS score by 0.1 to 9 points relative to baseline. In some embodiments, the method of this disclosure can reduce a subject's rTOSS score relative to baseline by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9 points, or any two of the above values. In some embodiments, the methods of this disclosure can reduce a subject's rTOSS 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 any two of the above values. In some implementations, the methods disclosed herein can reduce a subject's rTOSS score to 8 or below, 7 or below, 6 or below, 5 or below, 4 or below, 3 or below, 2 or below, or 1 or below.

[0062] In some embodiments, after the subject has been treated with the method of this disclosure for 1, 2, 3, 4, or more treatment cycles, the subject's rTOSS decreases relative to baseline. In some embodiments, after the subject has been treated with the method of this disclosure for 1, 2, 3, 4, or more treatment cycles, the subject's rTOSS decreases relative to baseline by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9 points. In some implementations, after the subject is treated with the method of this disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, or more treatment cycles, the subject's rTOSS score is reduced to 8 points or less, 7 points or less, 6 points or less, 5 points or less, 4 points or less, 3 points or less, 2 points or less, or 1 point or less.

[0063] In some implementations, after one, two, three, four, or more treatment cycles, the reduction in rTOSS relative to baseline in subjects administering the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 points, or any two of the above values, after one, two, three, four, or more treatment cycles, respectively. In some implementations, after one or two treatment cycles, the reduction in rTOSS relative to baseline in subjects administering the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 points, or any two of the above values, greater than the reduction in rTOSS relative to baseline in subjects administering placebo.

[0064] The transient total ocular symptom score (iTOSS) is a score of the ocular symptoms at a specific point in time. In some embodiments, iTOSS is performed before administration of the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, iTOSS is performed after administration of the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, iTOSS is performed at 4, 6, 8, 10, and / or 12 hours after administration of the anti-IL-4Rα antibody or its antigen-binding fragment.

[0065] In some embodiments, this disclosure provides a method for reducing iTOSS in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In some embodiments, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for reducing iTOSS in a subject. In some embodiments, administration to the subject of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof results in a reduction of iTOSS relative to baseline (i.e., achieving a lower number on a scale). In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with a further therapeutic agent.

[0066] In some embodiments, this disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, in combination with additional therapeutic agents, in the preparation of a medicament for reducing iTOSS in a subject. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with additional therapeutic agents to reduce iTOSS in a subject.

[0067] In some embodiments, the method of this disclosure can reduce a subject's iTOSS score by 0.1 to 9 points relative to baseline. In some embodiments, the method of this disclosure can reduce a subject's iTOSS score by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9 points, or any two of the above values, relative to baseline. In some embodiments, the methods of this disclosure can reduce a subject's iTOSS 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 any two of the above values. In some implementations, the methods disclosed herein can reduce a subject’s iTOSS score to 8 or below, 7 or below, 6 or below, 5 or below, 4 or below, 3 or below, 2 or below, or 1 or below.

[0068] In some embodiments, after the subject has been treated with the method of this disclosure for 1, 2, 3, 4, or more treatment cycles, the subject's iTOSS decreases relative to baseline. In some embodiments, after the subject has been treated with the method of this disclosure for 1, 2, 3, 4, or more treatment cycles, the subject's iTOSS decreases relative to baseline by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9 points. In some implementations, after the subject is treated with the method of this disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, or more treatment cycles, the subject's iTOSS score is reduced to 8 points or less, 7 points or less, 6 points or less, 5 points or less, 4 points or less, 3 points or less, 2 points or less, or 1 point or less.

[0069] In some implementations, after one, two, three, four, or more treatment cycles, the reduction in iTOSS relative to baseline in subjects administering the anti-IL-4Rα antibody or its antigen-binding fragment of this disclosure is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 points, or any two of the above values, after one, two, three, four, or more treatment cycles, is greater than the reduction in iTOSS relative to baseline in subjects administering placebo. In some implementations, after one or two treatment cycles, the reduction in iTOSS relative to baseline in subjects administering the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 points, or any two of the above values, greater than the reduction in iTOSS relative to baseline in subjects administering placebo.

[0070] In some embodiments, this disclosure provides a method for reducing a single ocular symptom score in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In some embodiments, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for reducing a single ocular symptom score in a subject. In some embodiments, administration of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof to the subject results in a reduction in the single ocular symptom score relative to baseline (i.e., achieving a lower number on the scale). In some embodiments, the single ocular symptom score is itchy / burning eye, watery / dribbling eye, or red eye. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with an additional therapeutic agent.

[0071] In some embodiments, this disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, and additional therapeutic agents, in the preparation of a medicament for reducing individual ocular symptom scores in subjects. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with additional therapeutic agents to reduce individual ocular symptom scores in subjects.

[0072] In some embodiments, the method of this disclosure can reduce a subject's individual ocular symptom score by 0.1 to 3 points relative to baseline. In some embodiments, the method of this disclosure can reduce a subject's individual ocular symptom score by at least 1, 1.5, 2, 2.5, or 3 points, or any two of the above values, relative to baseline. In some embodiments, the methods of this disclosure can reduce a subject's individual ocular symptom 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 any two of the above values. In some implementations, the methods of this disclosure can reduce a subject's individual ocular symptom score to 2.5 points or less, 2 points or less, 1.5 points or less, or 1 point or less.

[0073] In some embodiments, after the subject has undergone one, two, three, four, or more treatment cycles using the method of this disclosure, the subject's individual ocular symptom score decreases relative to baseline. In some embodiments, after the subject has undergone one, two, three, four, or more treatment cycles using the method of this disclosure, the subject's individual ocular symptom score decreases relative to baseline by at least 1, 1.5, 2, 2.5, or 3 points. In some embodiments, after the subject has undergone one, two, three, four, or more treatment cycles using the method of this disclosure, the subject's individual ocular symptom score decreases to 2.5 points or less, 2 points or less, 1.5 points or less, or 1 point or less.

[0074] In some implementations, after one, two, three, four, or more treatment cycles, the reduction in a single ocular symptom score relative to baseline in subjects administering the anti-IL-4Rα antibody or its antigen-binding fragment of this disclosure is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, or any two of the above values, greater than the reduction in a single ocular symptom score relative to baseline in subjects administering placebo. In some implementations, after one or two treatment cycles, the reduction in a single ocular symptom score relative to baseline in subjects administering the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment is greater than the reduction in a single ocular symptom score relative to baseline in subjects administering placebo by 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, or any two of the above values.

[0075] (3) Quality of Life Questionnaire for Patients with Allergic Rhinitis (RQLQ)

[0076] The RQLQ is a quality-of-life scale for allergic rhinitis, used by participants to assess their quality of life over a week. In the RQLQ, participants rate 28 items across seven areas: activity, sleep, non-nasal / eye symptoms, practical problems, nasal symptoms, eye symptoms, and emotional state, using a 7-point scale (ranging from 0 for no distress to 6 for extreme distress). The RQLQ score is either the average of all item scores or the total score.

[0077] In some embodiments, this disclosure provides a method for reducing RQLQ scores in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof. In some embodiments, this disclosure provides the use of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof in the preparation of a medicament for reducing RQLQ scores in a subject. In some embodiments, administration of the anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof to the subject results in a reduction in the RQLQ score relative to baseline (i.e., achieving a lower number on the scale). In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is administered to the subject in a therapeutically effective amount. In some embodiments, in the use, the medicament comprises a therapeutically effective amount of the anti-IL-4Rα antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the anti-IL-4Rα antibody or an antigen-binding fragment thereof is co-administered with an additional therapeutic agent.

[0078] In some embodiments, this disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof, and additional therapeutic agents, in the preparation of a medicament for reducing RQLQ scores in subjects. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with additional therapeutic agents to reduce RQLQ scores in subjects.

[0079] In some embodiments, the method of this disclosure can reduce the average RQLQ score of a subject by 0.1 to 6 points relative to baseline. In some embodiments, the method of this disclosure can reduce the average RQLQ score of a subject by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6 points, or any two of the above values, relative to baseline. In some embodiments, the method of this disclosure can reduce the mean RQLQ score of a subject 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 any two of the above values. In some implementations, the methods of this disclosure can reduce the average RQLQ score of subjects to 6 or less, 5 or less, 4 or less, 3 or less, 2 or less, 1 or less, or 0.5 or less.

[0080] In some embodiments, after the subjects have undergone one, two, three, four, or more treatment cycles using the method of this disclosure, their average RQLQ score decreases relative to baseline. In some embodiments, after the subjects have undergone one, two, three, four, or more treatment cycles using the method of this disclosure, their average RQLQ score decreases relative to baseline by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6 points. In some embodiments, after the subjects have undergone one, two, three, four, or more treatment cycles using the method of this disclosure, their average RQLQ score decreases to 6 points or less, 5 points or less, 4 points or less, 3 points or less, 2 points or less, or 1 point or less.

[0081] In some implementations, after one, two, three, four, or more treatment cycles, the mean reduction in RQLQ score relative to baseline in subjects receiving the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 points, or any two of the above values, after one, two, three, four, or more treatment cycles, is greater than the mean reduction in RQLQ score relative to baseline in subjects receiving placebo. In some implementations, after one or two treatment cycles, the mean reduction in RQLQ score relative to baseline in subjects receiving the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3 points, or any two of the above values, greater than the mean reduction in RQLQ score relative to baseline in subjects receiving placebo.

[0082] In some embodiments, the method of this disclosure can reduce a subject's total RQLQ score by 0.1 to 168 points relative to baseline. In some embodiments, the method of this disclosure can reduce a subject's total RQLQ score by at least 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, or 168 points, or any two of the above values, relative to baseline. In some embodiments, the method of this disclosure can reduce a subject's total RQLQ 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 any two of the above values. In some implementations, the method of this disclosure can reduce the total RQLQ score of the subject to 160 or less, 140 or less, 120 or less, 100 or less, 90 or less, 80 or less, 70 or less, 60 or less, 50 or less, 40 or less, 30 or less, 20 or less, 10 or less, or 1 or less.

[0083] In some embodiments, after the subject has been treated with the method of this disclosure for one, two, three, four, or more treatment cycles, the subject's total RQLQ score decreases relative to baseline. In some embodiments, after the subject has been treated with the method of this disclosure for one, two, three, four, or more treatment cycles, the subject's total RQLQ score decreases relative to baseline by at least 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, or 168 points. In some embodiments, after the subject has been treated with the method of this disclosure for 1 treatment cycle, 2 treatment cycles, 3 treatment cycles, 4 treatment cycles, or more treatment cycles, the subject's total RQLQ score is reduced to 160 points or less, 140 points or less, 120 points or less, 100 points or less, 90 points or less, 80 points or less, 70 points or less, 60 points or less, 50 points or less, 40 points or less, 30 points or less, 20 points or less, 10 points or less, or 1 point or less.

[0084] Anti-IL-4Rα antibody or its antigen-binding fragment

[0085] The term "antibody" is used in the broadest sense, including but not limited to various antibody structures such as monoclonal antibodies, polyclonal antibodies, and multispecific antibodies (e.g., bispecific antibodies, trispecific antibodies), as long as they exhibit the desired antigen-binding activity.

[0086] The term “antigen-binding fragment” refers to one or more fragments of an antibody that retain the function of specifically binding to an antigen. Examples covered by the term “antigen-binding fragment” include: (i) Fab fragments: monovalent fragments consisting of VL, VH, CL, and CH1 domains; (ii) F(ab')2 fragments, bivalent fragments containing two Fab fragments connected by disulfide bonds in the hinge region; (iii) Fd fragments consisting of VH and CH1 domains; (iv) Fv fragments consisting of VL and VH domains of an antibody single arm; (v) dAb fragments consisting of VH domains (see Ward et al., Nature. 341:544-546 (1989)); (vi) separated complementarity-determining regions (CDRs); (vii) nanobodies; and (viii) single-chain Fv (scFv).

[0087] 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.

[0088] "Humanized antibody" is an antibody containing a complementarity-determining region (CDR) derived from a non-human antibody and a frame region and constant region derived from a human antibody. For example, an anti-IL-4Rα antibody may contain a CDR derived from one or more murine antibodies, as well as a human frame region and a human constant region. Additional anti-IL-4Rα antibodies or variants thereof containing the HCDR and LCDR provided herein can be generated using any human frame sequence and are also included in this disclosure. In one embodiment, the frame sequences suitable for use in this disclosure include those that are structurally similar to the frame sequences provided herein. Further modifications can be made to the frame region to improve the properties of the antibodies provided herein. Such additional frame modifications may include chemical modifications, point mutations to reduce immunogenicity or remove T-cell epitopes, or mutation reversion to residues in the original germline sequence.

[0089] The term "identity," also known as consistency, refers to the percentage of amino acid residues in the sequence to be aligned that are identical to those in the specific amino acid sequence shown herein, after aligning the sequence to be aligned with it and, if necessary, introducing vacancies to achieve the maximum percentage of sequence identity, and without considering any conserved substitutions as part of sequence identity. Amino acid sequence alignment for identity can be performed using various methods within the art, such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Those skilled in the art can determine the appropriate parameters for the aligned sequences, including any algorithm required to achieve maximum alignment across the full length of the compared sequences.

[0090] According to some embodiments of this disclosure, the anti-IL-4Rα antibody or its antigen-binding fragment contains the complementarity-determining region (CDR), heavy chain variable region and / or light chain variable region contained in any amino acid sequence of the anti-IL-4Rα antibody or its antigen-binding fragment as disclosed in patent applications with publication numbers WO2021170020A1 or CN115087673A.

[0091] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), heavy chain CDR3 (HCDR3), light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and 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. In SEQ ID NO:7, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A; in 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; and in SEQ ID NO:17, X5 is A or V. In some embodiments, in SEQ ID NO:7, X1 is W and X2 is A, in SEQ ID NO:8, X3 is F and X4 is V, and in SEQ ID NO:17, X5 is A or V.

[0092] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), heavy chain CDR3 (HCDR3), light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and 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 in SEQ ID 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:7... In 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, 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.

[0093] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 in 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.

[0094] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 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.

[0095] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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.

[0096] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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.

[0097] In some embodiments, 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:7, and LCDR1, LCDR2, and LCDR3 of the light chain variable region shown in SEQ ID NO:8, wherein X1 in 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 in 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 in SEQ ID NO:7 is W and X2 is A, and X3 in SEQ ID NO:8 is F and X4 is V.

[0098] In some embodiments, 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:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO:22, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:7.

[0099] In some embodiments, 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: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.

[0100] In some embodiments, 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.

[0101] In some embodiments, 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: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.

[0102] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment described in this 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 its antigen-binding fragment described in this 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 its antigen-binding fragment described in this 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.

[0103] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment described in this 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 its antigen-binding fragment described in this 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 its antigen-binding fragment described herein 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.

[0104] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 as described above, and the light chain variable region comprises HCDR1, HCDR2 and HCDR3 as described above.

[0105] The CDR sequences of anti-IL-4Rα antibodies or their antigen-binding fragments are shown in Table 1.

[0106] Table 1. CDR sequences of anti-IL-4Rα antibodies or their antigen-binding fragments

[0107] Those skilled in the art will understand that, unless otherwise specified, the term "CDR" or "complementarity-determining region" for a given antibody or its region (e.g., variable region) should be understood to encompass complementarity-determining regions defined by any known scheme. While Table 1 has shown CDR sequences defined by the Kabat numbering system, when referring to antibodies defined by specific CDR sequences in Table 1, the scope of said antibodies also encompasses antibodies defined by CDR sequences converted to those defined by any other numbering system (e.g., one or more combinations of definitions such as AbM, Chothia, IMGT, CCG, or Contact, as is known in the art).

[0108] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in 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, and X5 is A or V in SEQ ID NO:17. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a light chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence 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. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:7, 17, or 21, and a light chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:8, 18, or 22. In SEQ ID NO:7, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A; in 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; and in SEQ ID NO:17, X5 is A or V. In some embodiments, in SEQ ID NO:7, X1 is W and X2 is A, in SEQ ID NO:8, X3 is F and X4 is V, and in SEQ ID NO:17, X5 is A or V.

[0109] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 shown in 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 in SEQ ID NO:7. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 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. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:7, and a light chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:8. In SEQ ID NO:7, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A; in 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, in SEQ ID NO:7, X1 is W and X2 is A, and in SEQ ID NO:8, X3 is F and X4 is V.

[0110] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:7, and a light chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:22, wherein SEQ ID NO:7... For NO:7, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A.

[0111] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:21, and a light chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:8, wherein SEQ ID NO:21 NO:8 has X3 as L and X4 as I, X3 as F and X4 as V, or X3 as F and X4 as I.

[0112] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:21, and a light chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:22.

[0113] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:17, and a light chain variable region having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:18, wherein X5 of SEQ ID NO:17 is A or V.

[0114] In some embodiments, the different amino acids in the amino acid sequences that have at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequences shown in SEQ ID NO: 7, 8, 17, 18, 21, or 22 are located in the frame region (FR).

[0115] 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, wherein X1 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 its antigen-binding fragment 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 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:8, wherein in SEQ ID NO:7, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A; and in 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, in SEQ ID NO:7, X1 is W and X2 is A, and in SEQ ID NO:8, X3 is F and X4 is V.

[0116] 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 shown in SEQ ID NO:7, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO:22, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:7.

[0117] 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 shown in SEQ ID NO:21, and the amino acid sequence of the light chain variable region is 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.

[0118] 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 shown in SEQ ID NO:21, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO:22.

[0119] 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 shown in SEQ ID NO:17, and the amino acid sequence of the light chain variable region is 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 its antigen-binding fragment 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 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: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.

[0121] EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYGMSWVRQAPGKGLVX1VX2TINSNGGSTSYPDSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCARFFRFRNAMDYWGQGTLVTVSS (SEQ ID NO:7, where X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A);

[0122] DIQMTQSPSSLSASVGDRVTITCRTSENIYSYLAWYQQKPGKAPKX3LX4YNAKTLAEGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQHYYGPPTWTFGQGTKVEIK(SEQ ID NO:8, where X3 is L and X4 is I, X3 is F and X4 is V, or X3 is F and X4 is I);

[0123] EVQLVQSGAEVKKPGATVKISCKX5SGFNIKDTYMHWVKQAPGKGLEWMGRIDPTNGYTIYASKFQGKATITADTSSNTAYMELSSLRSEDTAVYHCVSRRPWFAYWGQGTLVTVSS (SEQ ID NO: 17, where X5 is A or V);

[0124] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment may further comprise a constant region of an immunoglobulin, or a fragment, analog, variant, or derivative of said 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 a sequence of a human immunoglobulin heavy chain, such as the heavy chains of human IgG1, IgG2, IgG3, and IgG4, or other classes of immunoglobulins, preferably the heavy chains of human IgG1 and IgG4. In some embodiments, the light chain constant region comprises a sequence of a human immunoglobulin light chain, such as the κ light chain of human immunoglobulin. In some embodiments, the constant region may comprise any modifications described herein, such as the 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 any allotype amino acid residue.

[0125] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 shown in SEQ ID NO:9, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A, and X5 is A or V in SEQ ID NO:19. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 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. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 9, 19, or 23, and a light chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 10, 20, or 24, wherein SEQ ID NO: 9, 19, or 23, wherein SEQ ID NO: 9, 19, or 23, is a heavy chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 10, 20, or 24, wherein SEQ ID NO: 9, 19, or 23, is a heavy chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 98%, 99%, or 100% with In SEQ ID NO:9, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A; in 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; and in SEQ ID NO:19, X5 is A or V. In some embodiments, in SEQ ID NO:9, X1 is W and X2 is A, in SEQ ID NO:10, X3 is F and X4 is V, and in SEQ ID NO:19, X5 is A or V.

[0126] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 shown in SEQ ID NO:9, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:9. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 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. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:9, and a light chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:10, wherein SEQ ID NO:9... In SEQ ID NO:9, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A; in 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, in SEQ ID NO:9, X1 is W and X2 is A, and in SEQ ID NO:10, X3 is F and X4 is V.

[0127] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:9, and a light chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:24, wherein SEQ ID NO:9... For NO:9, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A.

[0128] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:23, and a light chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:10, wherein SEQ ID NO:23... NO:10 has X3 as L and X4 as I, X3 as F and X4 as V, or X3 as F and X4 as I.

[0129] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:23, and a light chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO:24.

[0130] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 19, and a light chain having an amino acid sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% with respect to the amino acid sequence shown in SEQ ID NO: 20, wherein X5 of SEQ ID NO: 19 is A or V.

[0131] In some embodiments, the different amino acids in the amino acid sequences that have at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the amino acid sequences shown in SEQ ID NO: 9, 10, 19, 20, 23, or 24 are located in the FR or constant region.

[0132] 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, wherein X1 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 its antigen-binding fragment 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 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:10, wherein in SEQ ID NO:9, X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A; and in 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, X1 is W and X2 is A in SEQ ID NO:9, and X3 is F and X4 is V in SEQ ID NO:10.

[0133] In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or its antigen-binding fragment is shown in SEQ ID NO:9, and the amino acid sequence of the light chain is shown in SEQ ID NO:24, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:9.

[0134] In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or its antigen-binding fragment is shown in SEQ ID NO:23, and the amino acid sequence of the light chain is 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.

[0135] In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or its antigen-binding fragment is shown in SEQ ID NO:23, and the amino acid sequence of the light chain is shown in SEQ ID NO:24.

[0136] In some specific embodiments, the amino acid sequence of the heavy chain of the anti-IL-4Rα antibody or its antigen-binding fragment is shown in SEQ ID NO:19, and the amino acid sequence of the light chain is shown in SEQ ID NO:20, wherein X5 of SEQ ID NO:19 is A or V.

[0137] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment comprises a heavy chain of the amino acid sequence shown in SEQ ID NO:9 and a light chain of the amino acid sequence 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 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: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.

[0138] In some embodiments, the C-terminal lysine residue of the amino acid sequence shown in SEQ ID NO:9 is deleted. In some embodiments, the C-terminal lysine residue of the amino acid sequence shown in SEQ ID NO:19 is deleted. In some embodiments, the C-terminal lysine residue of the amino acid sequence shown in SEQ ID NO:23 is deleted.

[0139] 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);

[0140] 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));

[0141] EVQLVQSGAEVKKPGATVKISCKX5SGFNIKDTYMHWVKQAPGKGLEWMGRIDPTNGYTIYASKFQGKATITADTSSNTAYMELSSLRSEDTAVYHCVSRRPWFAYWGQGTL VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCP PCPAPEFLGGGSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKA KGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK(SEQ ID NO: 19, where X5 is A or V);

[0142] Pharmaceutical compositions containing anti-IL-4Rα antibodies or their antigen-binding fragments

[0143] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment may be formulated with one or more pharmaceutically acceptable excipients to form a suitable pharmaceutical composition. As used herein, “excipient” refers to any component other than the active ingredient (e.g., the anti-IL-4Rα antibody or its antigen-binding fragment described in this disclosure). The selection of excipients will largely depend on factors such as the specific route of administration, the excipient’s efficacy in solubility and stability, and the nature of the dosage form. As used herein, “pharmaceuticalally acceptable excipients” include any and all physiologically compatible excipients, diluents, fillers, binders, disintegrants, solubilizers, stabilizers, colorants, flavoring agents, surfactants, emulsifiers, buffers, or encapsulating materials. The amount of each excipient may vary within the conventional range in the art.

[0144] 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 two of the above values.

[0145] The pharmaceutical compositions containing anti-IL-4Rα antibodies or their antigen-binding fragments disclosed herein may be in suitable dosage forms, 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., formulations suitable for intramuscular, intravenous, intraperitoneal, or subcutaneous injection), granules, emulsions, suspensions, solutions, dispersants, and sustained-release formulations for oral or non-oral administration. In some embodiments, the pharmaceutical compositions containing anti-IL-4Rα antibodies or their antigen-binding fragments are injections (e.g., formulations suitable for intramuscular, intravenous, intraperitoneal, or subcutaneous injection).

[0146] The term "pharmaceutical acceptable" refers to compounds, materials, compositions, and / or dosage forms that, within the bounds of reliable medical judgment, are suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, in proportion to a reasonable benefit / risk ratio.

[0147] The term "pharmaceutical composition" refers to a mixture of one or more active ingredients (such as the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein) with pharmaceutically acceptable excipients. The purpose of a pharmaceutical composition is to facilitate the administration of the active ingredient (such as the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein) to a subject. In this document, the terms "pharmaceutical composition" and "formulation" have the same meaning and are used interchangeably.

[0148] In one specific embodiment, the pharmaceutical composition containing an anti-IL-4Rα antibody or its antigen-binding fragment is a water-soluble injection. The water-soluble injection includes, but is not limited to, un-lyophilized water-soluble formulations or water-soluble formulations reconstituted from lyophilized powder. In other embodiments, the pharmaceutical composition containing an anti-IL-4Rα antibody or its antigen-binding fragment is a lyophilized formulation. The lyophilized formulation refers to a formulation prepared by lyophilizing an aqueous solution, in which the substance is first frozen, then the solvent quantity is reduced by sublimation (primary drying process), and then by desorption (secondary drying process), until the solvent quantity is at a value that no longer supports biological activity or chemical reaction. The lyophilized formulations of this disclosure can also be dried by other methods known in the art, such as spray drying and bubble drying.

[0149] 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 its antigen-binding fragment 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 its antigen-binding fragment is 150 mg / mL. In some specific embodiments, the concentration of the anti-IL-4Rα antibody or its antigen-binding fragment is 175 mg / mL.

[0150] In some embodiments, the pharmaceutical composition containing an anti-IL-4Rα antibody or its antigen-binding fragment comprises an anti-IL-4Rα antibody or its antigen-binding fragment, a buffer, an isotonic regulator / stabilizer, and a surfactant. In one specific embodiment, the pharmaceutical composition containing an anti-IL-4Rα antibody or its antigen-binding fragment is in the form of a liquid pharmaceutical composition (e.g., an injection) comprising an anti-IL-4Rα antibody or its antigen-binding fragment, a histidine buffer, proline, sodium chloride, and polysorbate 80. In some embodiments, the histidine buffer comprises a histidine-hydrochloride buffer, a histidine-acetate buffer, a histidine-histidine hydrochloride buffer, or a histidine hydrochloride buffer. In some embodiments, the histidine buffer is a histidine-hydrochloride buffer.

[0151] dose

[0152] The amount of the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein administered to a subject is generally a therapeutically effective amount. The term "treatment" means an attempt to alter the natural course of an individual's disease and can be for the purpose of preventing, improving, or eliminating the disease or one or more symptoms associated with said disease, including but not limited to preventing the onset or recurrence of the disease, relieving symptoms, reducing any direct or indirect pathological consequences of the disease, preventing the metastasis of the disease, slowing the rate of disease progression, improving or alleviating the state of the disease, prolonging the frequency and duration of asymptomatic periods, and resolving or improving the prognosis of the disease. The term "therapeutically effective amount" means (i) the amount of the compound disclosed herein used to treat a specific disease, condition, or disorder, (ii) reduce, improve, or eliminate one or more symptoms of a specific disease, condition, or disorder, or (iii) prevent or delay the onset of one or more symptoms of a specific disease, condition, or disorder. The amount of active substance constituting a "therapeuticly effective amount" (e.g., the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein) can vary depending on factors such as an individual's disease state, age, sex, and weight, and the ability of the therapeutic agent or combination of therapeutic agents to elicit the desired response in the individual. The effective therapeutic dose can also be routinely determined by those skilled in the art based on their own knowledge and the contents of this disclosure.

[0153] Application plan

[0154] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 its antigen-binding fragment is administered once every 1 week. In other specific embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 2 weeks. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 its antigen-binding fragment is administered at doses of 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, or 460 mg per dose. Administer a dose of 470mg, 480mg, 490mg, 500mg, 510mg, 520mg, 530mg, 540mg, 550mg, 560mg, 570mg, 580mg, 590mg, 600mg, 610mg, 620mg, 630mg, 640mg, 650mg, 660mg, 670mg, 680mg, 690mg, 700mg, 710mg, 720mg, 730mg, 740mg, 750mg, 760mg, 770mg, 780mg, 790mg, 800mg, 900mg, 1000mg, 1100mg, 1200mg, or any two of the above values ​​within a range. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered at a dose of 200 mg, 300 mg, 400 mg, or 600 mg each time. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered at a dose of 300 mg or 600 mg each time. In some specific embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is initially administered at a dose of 600 mg (also known as the “initial dose”), followed by subsequent administrations at a dose of 300 mg (also known as the “maintenance dose”).

[0155] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 1 week, 2 weeks, 3 weeks, or 4 weeks, at a dose of 300-600 mg each time. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 1 week, 2 weeks, 3 weeks, or 4 weeks, at a dose of 300 mg or 600 mg each time. In some specific embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 2 weeks, at a dose of 300 mg or 600 mg each time. In some specific embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 2 weeks, at a dose of 300 mg each time. In some specific embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered every two weeks, with an initial dose of 600 mg (also known as the "initial dose") followed by 300 mg (also known as the "maintenance dose"). In some specific embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered every week, with an initial dose of 600 mg (also known as the "initial dose") followed by 300 mg (also known as the "maintenance dose"). In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered a total of two times. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered a total of four times.

[0156] In some embodiments, a treatment cycle is defined as every 2 weeks, with the anti-IL-4Rα antibody or its antigen-binding fragment administered during each treatment cycle. In some embodiments, a treatment cycle is defined as every 2 weeks, with the anti-IL-4Rα antibody or its antigen-binding fragment administered once during each treatment cycle. In some embodiments, a treatment cycle is defined as every 2 weeks, with the anti-IL-4Rα antibody or its antigen-binding fragment administered on day 1 of each treatment cycle. In some embodiments, a treatment cycle is defined as every 2 weeks, with the anti-IL-4Rα antibody or its antigen-binding fragment administered once on day 1 of each treatment cycle. In some specific embodiments, a treatment cycle is defined as every 2 weeks, with 300-600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment administered during each treatment cycle. In some specific embodiments, a treatment cycle is defined as every 2 weeks, with 300 mg or 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment administered on day 1 of each treatment cycle. In some specific implementations, a treatment cycle is defined as 2 weeks, with 300 mg of anti-IL-4Rα antibody or its antigen-binding fragment administered on day 1 of each treatment cycle. In some specific implementations, a treatment cycle is defined as 2 weeks, with 600 mg of anti-IL-4Rα antibody or its antigen-binding fragment administered on day 1 of the first treatment cycle, and 300 mg of anti-IL-4Rα antibody or its antigen-binding fragment administered on day 1 of each subsequent treatment cycle. In some specific implementations, a treatment cycle is defined as 2 weeks, with 600 mg of anti-IL-4Rα antibody or its antigen-binding fragment administered on day 1 of the first treatment cycle, and 300 mg of anti-IL-4Rα antibody or its antigen-binding fragment administered on day 1 of each subsequent treatment cycle.

[0157] In some embodiments, a treatment cycle is one week, and an anti-IL-4Rα antibody or its antigen-binding fragment is administered during each treatment cycle. In some embodiments, a treatment cycle is one week, and an anti-IL-4Rα antibody or its antigen-binding fragment is administered once during each treatment cycle. In some embodiments, a treatment cycle is one week, and an anti-IL-4Rα antibody or its antigen-binding fragment is administered on day 1 of each treatment cycle. In some embodiments, a treatment cycle is one week, and an anti-IL-4Rα antibody or its antigen-binding fragment is administered once on day 1 of each treatment cycle. In some specific embodiments, a treatment cycle is one week, and 300-600 mg of an anti-IL-4Rα antibody or its antigen-binding fragment is administered during each treatment cycle. In some specific embodiments, a treatment cycle is one week, and 300 mg or 600 mg of an anti-IL-4Rα antibody or its antigen-binding fragment is administered on day 1 of each treatment cycle. In some specific implementations, a treatment cycle is one week. During the first treatment cycle, 600 mg of anti-IL-4Rα antibody or its antigen-binding fragment is administered, followed by 300 mg of anti-IL-4Rα antibody or its antigen-binding fragment on the first day of each subsequent treatment cycle.

[0158] The term "flat dose" is used to describe the dose administered to a subject regardless of their weight or body surface area (BSA). Therefore, the flat dose is specified as the absolute amount of the drug (e.g., anti-IL-4Rα antibody or its antigen-binding fragment), rather than as a mg / kg dose. For example, a 60kg person and a 100kg person would receive the same dose of antibody (e.g., 300 mg of IL-4Rα antibody).

[0159] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment 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 its antigen-binding fragment is administered in doses of 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, etc. A uniform dose of 480mg, 490mg, 500mg, 510mg, 520mg, 530mg, 540mg, 550mg, 560mg, 570mg, 580mg, 590mg, 600mg, 610mg, 620mg, 630mg, 640mg, 650mg, 660mg, 670mg, 680mg, 690mg, 700mg, 710mg, 720mg, 730mg, 740mg, 750mg, 760mg, 770mg, 780mg, 790mg, 800mg, 900mg, 1000mg, 1100mg, 1200mg, or any two of the above values, shall be administered to the subject. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered to the subject at a uniform dose of 200 mg, 300 mg, 400 mg, or 600 mg. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered to the subject at a uniform dose of 300 mg or 600 mg.

[0160] In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment is administered to the 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, 3 to 10 mg / kg, or 5 to 10 mg / kg of the subject's body weight.

[0161] In some implementations, the anti-IL-4Rα antibody or its antigen-binding fragment is administered in multiple doses or a single dose.

[0162] As used herein, the term "single dose" refers to the smallest packaged unit containing a certain amount of medicine, such as a box of medicine containing seven tablets, in which case one tablet is a single dose; or a vial of injection is a single dose. The term "multiple doses" consists of multiple single doses.

[0163] "Unit dose" refers to the dose of active ingredient contained in the smallest packaging unit containing a certain amount of medicine. For example, the dose of antibody contained in a bottle of antibody injection is the unit dose.

[0164] combination therapy

[0165] In some embodiments, the subject is administered an additional therapeutic agent before, after, or simultaneously with receiving the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the subject has already been administered or is being administered an additional therapeutic agent before receiving the anti-IL-4Rα antibody or its antigen-binding fragment. For example, when the additional therapeutic agent is administered "before" the anti-IL-4Rα antibody or its antigen-binding fragment, the additional therapeutic agent may 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 administering the anti-IL-4Rα antibody or its antigen-binding fragment. When an additional therapeutic agent is administered “after” the anti-IL-4Rα antibody or its antigen-binding fragment, the additional therapeutic agent may 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 administration of the anti-IL-4Rα antibody or its antigen-binding fragment. Administering “simultaneously” with the anti-IL-4Rα antibody or its antigen-binding fragment means administering the additional therapeutic agent to the subject within 10 minutes (before, after, or simultaneously) of administration of the anti-IL-4Rα antibody or its antigen-binding fragment.

[0166] Other therapeutic agents may include, for example, IL-1 inhibitors, IL-5 inhibitors, IL-5Rα inhibitors, IL-13 inhibitors, TNF inhibitors, IgE inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, histamine receptor antagonists, antifungal agents, topical decongestants, long-acting β2 receptor agonists, short-acting β2 receptor agonists, long-acting muscarinic antagonists, leukotriene receptor antagonists, and / or glucocorticoids. The glucocorticoids may be, for example, nasal glucocorticoids (INCS), inhaled glucocorticoids, and / or systemic glucocorticoids. The histamine receptor antagonists may be H1 receptor antagonists or H2 receptor antagonists. The terms "histamine receptor antagonist" and "antihistamine" are used interchangeably.

[0167] In some embodiments, the additional therapeutic agent is a nasal corticosteroid, such as mometasone furoate, fluticasone propionate, fluticasone furoate, budesonide, triamcinolone acetonide, and / or beclomethasone dipropionate. In some embodiments, the additional therapeutic agent is an H1 receptor antagonist, such as fexofenadine, cetirizine, azelastine, levocabastine, ebastine, olopatadine, rupatadine, levocetirizine, loratadine, desloratadine, and / or cetiratadine. In some specific embodiments, the additional therapeutic agent is a nasal corticosteroid and a histamine receptor antagonist. In some specific embodiments, the additional therapeutic agent is a nasal corticosteroid and an H1 receptor antagonist. In some specific embodiments, the additional therapeutic agent is mometasone furoate nasal spray (MFNS) and loratadine.

[0168] In some embodiments, the MFNS is administered once daily. In some embodiments, the MFNS is administered once daily at a dose of 200 μg. In some embodiments, the loratadine is administered once daily. In some embodiments, the loratadine is administered once daily at a dose of 10 mg.

[0169] In some specific embodiments, the additional therapeutic agents are MFNS and loratadine, wherein the MFNS is administered once daily and the loratadine is administered once daily. In some embodiments, the additional therapeutic agents are MFNS and loratadine, wherein the MFNS is administered once daily at a dose of 200 μg, and the loratadine is administered once daily at a dose of 10 mg.

[0170] In some embodiments, the subject is administered a nasal corticosteroid before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the subject is administered MFNS before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment.

[0171] In some embodiments, the subject is administered a histamine receptor antagonist before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the subject is administered an H1 receptor antagonist before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the subject is administered loratadine before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment.

[0172] In some embodiments, the subject is administered a nasal corticosteroid and a histamine receptor antagonist before, after, or simultaneously with the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the subject is administered a nasal corticosteroid and an H1 receptor antagonist before, after, or simultaneously with the anti-IL-4Rα antibody or its antigen-binding fragment. In some embodiments, the subject is administered MFNS and loratadine before, after, or simultaneously with the anti-IL-4Rα antibody or its antigen-binding fragment.

[0173] This disclosure also provides a method for treating allergic rhinitis in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof, a nasal corticosteroid, and a histamine receptor antagonist. This disclosure also provides a method for treating allergic rhinitis in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof, a nasal corticosteroid, and an H1 receptor antagonist. This disclosure also provides a method for treating allergic rhinitis in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof, MFNS, and loratadine.

[0174] This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment thereof, nasal corticosteroids, and histamine receptor antagonists of this disclosure in the preparation of a medicament for treating allergic rhinitis in a subject. This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment thereof, nasal corticosteroids, and H1 receptor antagonists of this disclosure in the preparation of a medicament for treating allergic rhinitis in a subject. This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment thereof, MFNS, and loratadine of this disclosure in the preparation of a medicament for treating allergic rhinitis in a subject.

[0175] This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment thereof, nasal corticosteroids, and histamine receptor antagonists of this disclosure in the preparation of medicaments for improving one or more allergic rhinitis-related parameters in subjects with allergic rhinitis. This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment thereof, nasal corticosteroids, and H1 receptor antagonists of this disclosure in the preparation of medicaments for improving one or more allergic rhinitis-related parameters in subjects with allergic rhinitis. This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment thereof, MFNS, and loratadine of this disclosure in the preparation of medicaments for improving one or more allergic rhinitis-related parameters in subjects with allergic rhinitis.

[0176] This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment in the preparation of a medicament for the treatment of allergic rhinitis in a subject in combination with nasal corticosteroids and histamine receptor antagonists. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment in the preparation of a medicament for the treatment of allergic rhinitis in a subject in combination with nasal corticosteroids and H1 receptor antagonists. This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment in the preparation of a medicament for the treatment of allergic rhinitis in a subject in combination with MFNS and loratadine.

[0177] This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with nasal corticosteroids and histamine receptor antagonists to improve one or more allergic rhinitis-related parameters in subjects with allergic rhinitis. This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with nasal corticosteroids and H1 receptor antagonists to improve one or more allergic rhinitis-related parameters in subjects with allergic rhinitis. This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with MFNS and loratadine to improve one or more allergic rhinitis-related parameters in subjects with allergic rhinitis.

[0178] In some embodiments, the allergic rhinitis is seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is moderate to severe seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is severe seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is seasonal allergic rhinitis that is poorly or unsuitably controlled by standard treatment (e.g., nasal corticosteroids and / or histamine receptor antagonists). In some embodiments, the allergic rhinitis is moderate to severe seasonal allergic rhinitis that is poorly or unsuitably controlled by standard treatment (e.g., nasal corticosteroids and / or histamine receptor antagonists).

[0179] This disclosure also provides a method for treating seasonal allergic rhinitis in a subject, comprising administering to the subject an anti-IL-4Rα antibody of this disclosure or an antigen-binding fragment thereof, a nasal corticosteroid, and a histamine receptor antagonist.

[0180] This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment, nasal corticosteroids, and histamine receptor antagonists of this disclosure in the preparation of medicaments for the treatment of seasonal allergic rhinitis in subjects.

[0181] This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment, nasal corticosteroids, and histamine receptor antagonists of this disclosure in the preparation of medicaments for improving one or more allergic rhinitis-related parameters in subjects with seasonal allergic rhinitis.

[0182] This disclosure also provides the use of the anti-IL-4Rα antibody of this disclosure or its antigen-binding fragment in the preparation of a medicament for use in treating seasonal allergic rhinitis in subjects in combination with nasal corticosteroids and histamine receptor antagonists.

[0183] This disclosure also provides the use of the anti-IL-4Rα antibody or its antigen-binding fragment thereof in the preparation of a medicament for use in combination with nasal corticosteroids and histamine receptor antagonists to improve one or more allergic rhinitis-related parameters in subjects with seasonal allergic rhinitis.

[0184] Improving parameters related to allergic rhinitis includes, but is not limited to: reducing TNSS, reducing rTNSS (including AM rTNSS and / or PM rTNSS), reducing iTNSS, reducing TOSS, reducing rTOSS (including AM rTOSS and / or PM rTOSS), reducing iTOSS, reducing RQLQ scores, reducing individual nasal symptom scores (i.e., runny nose, nasal congestion, nasal itching, or sneezing), and reducing individual eye symptom scores (i.e., itchy / burning eyes, watery / dribbling eyes, or red eyes).

[0185] In some implementations, the combination therapy reduces dependence on standard treatment for allergic rhinitis (e.g., nasal corticosteroids and / or histamine receptor antagonists) in subjects with allergic rhinitis. In some implementations, the combination therapy reduces adverse reactions to standard treatment for allergic rhinitis (e.g., nasal corticosteroids and / or histamine receptor antagonists) in subjects with allergic rhinitis.

[0186] Application method

[0187] The following content is not intended to limit the administration of the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein.

[0188] The anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein can be administered via a variety of suitable routes, including but not limited to oral, parenteral (intravenous, intramuscular, local, or subcutaneous) routes. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein can be administered by injection, such as intravenous or subcutaneous injection, preferably subcutaneous injection. In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein can also be absorbed via epithelial or mucosal routes (e.g., oral mucosa, rectal and intestinal mucosa). In some embodiments, the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein 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 antibody or its antigen-binding fragment disclosed herein can also be administered via a variety of known drug delivery systems, including liposome encapsulation, microparticles, microcapsules, controlled-release systems, etc.

[0189] Treatment group

[0190] In some implementations, the allergic rhinitis is seasonal allergic rhinitis.

[0191] In some embodiments, the subject with allergic rhinitis also has allergic conjunctivitis. In some embodiments, the subject with allergic rhinitis does not have allergic conjunctivitis.

[0192] In some embodiments, the subject with seasonal allergic rhinitis also has allergic conjunctivitis. In some embodiments, the subject with seasonal allergic rhinitis does not have allergic conjunctivitis. In some embodiments, the subject with seasonal allergic rhinitis has a history of seasonal allergic rhinitis for at least 2 years.

[0193] In some embodiments, the allergic rhinitis is eosinophilic allergic rhinitis. In some embodiments, the allergic rhinitis is eosinophilic seasonal allergic rhinitis.

[0194] In some embodiments, the allergic rhinitis is moderate to severe seasonal allergic rhinitis. In some embodiments, the allergic rhinitis is severe seasonal allergic rhinitis.

[0195] In some embodiments, the allergic rhinitis is seasonal allergic rhinitis that is poorly or unsuitably controlled by standard treatment (e.g., nasal corticosteroids and / or histamine receptor antagonists). In some embodiments, the allergic rhinitis is moderate to severe seasonal allergic rhinitis that is poorly or unsuitably controlled by standard treatment (e.g., nasal corticosteroids and / or histamine receptor antagonists).

[0196] In some embodiments, the allergic rhinitis subject has previously received standard treatment for allergic rhinitis (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the allergic rhinitis subject has previously received glucocorticoid treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the allergic rhinitis subject has previously received nasal glucocorticoid treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the allergic rhinitis subject has previously received MFNS treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the allergic rhinitis subject has previously received histamine receptor antagonist treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the allergic rhinitis subject has previously received leukotriene receptor antagonist treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the allergic rhinitis subject has previously received oral glucocorticoid treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the allergic rhinitis subject has previously received mast cell stabilizer treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the allergic rhinitis subject has previously received topical decongestant treatment (e.g., no response, insufficient response, and / or intolerance).

[0197] In some embodiments, the subject with seasonal allergic rhinitis has previously received standard treatment for seasonal allergic rhinitis (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the subject with seasonal allergic rhinitis has previously received glucocorticoid treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the subject with seasonal allergic rhinitis has previously received nasal glucocorticoid treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the subject with seasonal allergic rhinitis has previously received MFNS treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the subject with seasonal allergic rhinitis has previously received histamine receptor antagonist treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the subject with seasonal allergic rhinitis has previously received leukotriene receptor antagonist treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the subject with seasonal allergic rhinitis has previously received oral glucocorticoid treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the subject with seasonal allergic rhinitis has previously received mast cell stabilizer treatment (e.g., no response, insufficient response, and / or intolerance). In some embodiments, the subject with seasonal allergic rhinitis has previously received topical decongestant treatment (e.g., no response, insufficient response, and / or intolerance).

[0198] Standard treatment for allergic rhinitis and seasonal allergic rhinitis, as is generally understood in the art, includes nasal corticosteroids, histamine receptor antagonists, leukotriene receptor antagonists, oral corticosteroids, mast cell stabilizers, and / or topical decongestants.

[0199] In some embodiments, the allergic rhinitis subject has an iTNSS score of at least 4. In some embodiments, the allergic rhinitis subject has an iTNSS score of at least 4 on the morning of the screening day. In some embodiments, the allergic rhinitis subject has an iTNSS score of at least 4 in the morning at the baseline visit. In some embodiments, the allergic rhinitis subject has an iTNSS score of at least 4 in the morning on day 1 of the first treatment cycle. In some embodiments, the allergic rhinitis subject has an average rTNSS score of at least 6 over the most recent 6 days at the baseline visit. In some embodiments, the allergic rhinitis subject has an iTNSS score of at least 4 in the morning and an average rTNSS score of at least 6 over the most recent 6 days at the baseline visit. In some embodiments, the allergic rhinitis subject has an average rTNSS score of at least 6 over the most recent 6 days on day 1 of the first treatment cycle. In some embodiments, the allergic rhinitis subject has an iTNSS score of at least 4 in the morning and an average rTNSS score of at least 6 over the most recent 6 days on day 1 of the first treatment cycle. In some embodiments, the allergic rhinitis subject has a nasal congestion score of at least 2 and a runny nose, nasal itching, or sneezing score of at least 2 at the baseline visit. In some embodiments, the allergic rhinitis subject has a morning iTNSS score of at least 4 and an average rTNSS score of at least 6 over the most recent 6 days at the baseline visit; wherein the nasal congestion score is at least 2 and the runny nose, nasal itching, or sneezing score is at least 2. In some embodiments, the allergic rhinitis subject has a nasal congestion score of at least 2 and a runny nose, nasal itching, or sneezing score of at least 2 on day 1 of the first treatment cycle. In some embodiments, the allergic rhinitis subject has a morning iTNSS score of at least 4 and an average rTNSS score of at least 6 over the most recent 6 days at the first treatment cycle; wherein the nasal congestion score is at least 2 and the runny nose, nasal itching, or sneezing score is at least 2.

[0200] In some embodiments, the subject with seasonal allergic rhinitis has an iTNSS score of at least 4. In some embodiments, the subject with seasonal allergic rhinitis has an iTNSS score of at least 4 on the morning of the screening day. In some embodiments, the subject with seasonal allergic rhinitis has an iTNSS score of at least 4 on the morning of the baseline visit. In some embodiments, the subject with seasonal allergic rhinitis has an iTNSS score of at least 4 on the morning of day 1 of the first treatment cycle. In some embodiments, the subject with seasonal allergic rhinitis has an average rTNSS score of at least 6 over the most recent 6 days at the baseline visit. In some embodiments, the subject with seasonal allergic rhinitis has an iTNSS score of at least 4 on the morning of the baseline visit and an average rTNSS score of at least 6 over the most recent 6 days. In some embodiments, the subject with seasonal allergic rhinitis has an average rTNSS score of at least 6 over the most recent 6 days on day 1 of the first treatment cycle. In some embodiments, the subject with seasonal allergic rhinitis has an iTNSS score of at least 4 on the morning of day 1 of the first treatment cycle and an average rTNSS score of at least 6 over the most recent 6 days. In some embodiments, the subject with seasonal allergic rhinitis has a nasal congestion score of at least 2 and a runny nose, nasal itching, or sneezing score of at least 2 at the baseline visit. In some embodiments, the subject with seasonal allergic rhinitis has a morning iTNSS score of at least 4 and an average rTNSS score of at least 6 over the most recent 6 days at the baseline visit; wherein the nasal congestion score is at least 2 and the runny nose, nasal itching, or sneezing score is at least 2. In some embodiments, the subject with seasonal allergic rhinitis has a nasal congestion score of at least 2 and a runny nose, nasal itching, or sneezing score of at least 2 on day 1 of the first treatment cycle. In some embodiments, the subject with seasonal allergic rhinitis has a morning iTNSS score of at least 4 and an average rTNSS score of at least 6 over the most recent 6 days at the first treatment cycle; wherein the nasal congestion score is at least 2 and the runny nose, nasal itching, or sneezing score is at least 2.

[0201] In some embodiments, the allergic rhinitis subject further suffers from asthma. In some embodiments, the allergic rhinitis subject who further suffers from asthma has received inhaled corticosteroid treatment prior to the screening period. In some embodiments, the allergic rhinitis subject who further suffers from asthma has received inhaled corticosteroid treatment for at least 4 weeks prior to the screening period.

[0202] In some embodiments, the subject with seasonal allergic rhinitis further suffers from asthma. In some embodiments, the subject with seasonal allergic rhinitis who further suffers from asthma has received inhaled corticosteroid treatment prior to the screening period. In some embodiments, the subject with seasonal allergic rhinitis who further suffers from asthma has received inhaled corticosteroid treatment for at least 4 weeks prior to the screening period.

[0203] Technical effect

[0204] Typically, the anti-IL-4Rα antibody or its antigen-binding fragment disclosed herein, in combination with the therapy, has one or more of the following effects:

[0205] (1) It provides benefit to subjects with allergic rhinitis, especially seasonal allergic rhinitis (e.g., seasonal allergic rhinitis that is poorly or unsuitably controlled by nasal corticosteroids and / or antihistamines);

[0206] (2) It has good safety (e.g., low incidence and severity of adverse events and serious adverse events, and low risk of adverse reactions);

[0207] (3) Provide treatment that is well tolerated in subjects with allergic rhinitis, especially seasonal allergic rhinitis (e.g., seasonal allergic rhinitis that is poorly controlled or unsuitable for nasal corticosteroids and / or antihistamines);

[0208] (4) Improve one or more allergic rhinitis-related parameters in subjects;

[0209] (5) To provide improvement and control of lung function in subjects with allergic rhinitis combined with asthma, especially seasonal allergic rhinitis (e.g., seasonal allergic rhinitis that is poorly or unsuitable for nasal corticosteroids and / or antihistamines).

[0210] (6) Reduced dependence on standard treatments for allergic rhinitis (e.g., nasal corticosteroids and / or histamine receptor antagonists).

[0211] The disclosed anti-IL-4Rα antibody or its antigen-binding fragment and combination therapy have good efficacy and safety in the treatment of allergic rhinitis (e.g., seasonal allergic rhinitis).

[0212] For purposes of description and disclosure, all patents, patent applications, and other identified publications are expressly incorporated herein by reference. These publications are provided solely because their publications predate the filing date of this disclosure. All statements regarding the dates of these documents or representations of their contents are based on information available to the applicant and do not constitute any acknowledgment of the accuracy of the dates or contents of these documents. Furthermore, in any country, any reference to these publications herein does not constitute an endorsement that such publications are part of the general knowledge in the art.

[0213] This disclosure also provides the following specific implementation schemes, but the scope of protection of this disclosure is not limited thereto:

[0214] Implementation Scheme 1. A method for treating seasonal allergic rhinitis, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof to a subject, wherein:

[0215] (1) The anti-IL-4Rα antibody or its antigen-binding fragment 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 in 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 in 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;

[0216] (2) The anti-IL-4Rα antibody or its antigen-binding fragment 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;

[0217] (3) The anti-IL-4Rα antibody or its antigen-binding fragment 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 in 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;

[0218] (4) The anti-IL-4Rα antibody or its antigen-binding fragment 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 in 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;

[0219] (5) The anti-IL-4Rα antibody or its antigen-binding fragment 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;

[0220] (6) 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:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region 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;

[0221] (7) 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: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;

[0222] (8) 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:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO:22, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:7;

[0223] (9) 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:8, wherein X3 in 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

[0224] (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.

[0225] Implementation Scheme 2. A method for treating seasonal allergic rhinitis, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof to a subject, wherein the anti-IL-4Rα antibody or the antigen-binding fragment thereof comprises:

[0226] (1) HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6; or

[0227] (2) HCDR1 containing the amino acid sequence shown in SEQ ID NO:11, HCDR2 containing the amino acid sequence shown in SEQ ID NO:12, HCDR3 containing the amino acid sequence shown in SEQ ID NO:13, LCDR1 containing the amino acid sequence shown in SEQ ID NO:14, LCDR2 containing the amino acid sequence shown in SEQ ID NO:15, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:16.

[0228] Implementation Scheme 3. The method according to Implementation Scheme 1 or 2, wherein the seasonal allergic rhinitis is moderate to severe seasonal allergic rhinitis; optionally, the seasonal allergic rhinitis is seasonal allergic rhinitis that is poorly or unsuitably controlled by nasal corticosteroids and / or histamine receptor antagonists; optionally, the seasonal allergic rhinitis is moderate to severe seasonal allergic rhinitis that is poorly or unsuitably controlled by nasal corticosteroids and / or histamine receptor antagonists.

[0229] Implementation Scheme 4. The method according to any one of Implementation Schemes 1-3, wherein the subject further suffers from asthma.

[0230] Implementation Scheme 5. The method according to any one of Implementation Schemes 1-4, wherein the anti-IL-4Rα antibody or its antigen-binding fragment 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 its antigen-binding fragment is administered at a dose of 300 mg or 600 mg each time.

[0231] Implementation Scheme 6. The method according to any one of Implementation Schemes 1-5, wherein 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; preferably, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 1 week or every 2 weeks.

[0232] Implementation Scheme 7. The method according to any one of Implementation Schemes 1-4, wherein:

[0233] (1) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once every 2 weeks, each time at a dose of 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment;

[0234] (2) The anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 2 weeks. The first administration is 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, and the subsequent administrations are 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment.

[0235] (3) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once a week, with the first administration being 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, and thereafter 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment each time.

[0236] (4) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once every 2 weeks, with each administration of 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, for a total of 2 administrations.

[0237] (5) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once every two weeks, with the first administration being 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, followed by each administration of 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, for a total of two administrations; or

[0238] (6) The anti-IL-4Rα antibody or its antigen-binding fragment is administered once a week. The first administration is 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, and the subsequent administrations are 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, for a total of 4 administrations.

[0239] Implementation Scheme 8. The method according to any one of Implementation Schemes 1-7, wherein the subject is administered an additional therapeutic agent before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment.

[0240] Implementation Scheme 9. The method according to Implementation Scheme 8, wherein the additional therapeutic agent is selected from one or more combinations 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, nonsteroidal anti-inflammatory drugs, antibiotics, histamine receptor antagonists, antifungal agents, topical decongestants, long-acting muscarinic antagonists, and leukotriene receptor antagonists.

[0241] Implementation Scheme 10. The method according to Implementation Scheme 9, wherein the glucocorticoid includes nasal glucocorticoids, inhaled glucocorticoids, and / or systemic glucocorticoids; optionally, the histamine receptor antagonist includes an H1 receptor antagonist and / or an H2 receptor antagonist.

[0242] Implementation Scheme 11. The method according to Implementation Scheme 8, wherein the additional therapeutic agent is a nasal corticosteroid and a histamine receptor antagonist, or the additional therapeutic agent is a nasal corticosteroid and an H1 receptor antagonist; preferably, the additional therapeutic agent is MFNS and loratadine.

[0243] Implementation Scheme 12. The method according to any one of Implementation Schemes 1-7, wherein the subject is administered MFNS before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment, and is administered loratadine before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment.

[0244] Implementation Scheme 13. The method according to any one of Implementation Schemes 1-12, wherein the anti-IL-4Rα antibody or its antigen-binding fragment comprises:

[0245] (1) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:7, and the light chain variable region having at least 95% identity with the amino acid sequence 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; preferably, 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;

[0246] (2) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:17, and the light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:18, wherein X5 of SEQ ID NO:17 is A or V;

[0247] (3) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:7, and the light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:22, wherein X1 in 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;

[0248] (4) A heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:21, and a light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:8, wherein X3 in 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

[0249] (5) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:21, and the light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:22.

[0250] Implementation Scheme 14. The method according to any one of Implementation Schemes 1-13, wherein the anti-IL-4Rα antibody or its antigen-binding fragment comprises:

[0251] (1) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:9, and a light chain having at least 95% identity with the amino acid sequence 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; preferably, 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;

[0252] (2) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:19, and a light chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:20, wherein X5 of SEQ ID NO:19 is A or V;

[0253] (3) A heavy chain whose amino acid sequence is at least 95% identical to the amino acid sequence shown in SEQ ID NO:9, and a light chain whose amino acid sequence is at least 95% identical to the amino acid sequence shown in SEQ ID NO:24, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:9;

[0254] (4) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:23, and a light chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:10, wherein X3 in 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; or

[0255] (5) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:23, and a light chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:24.

[0256] Implementation Scheme 15. The method according to any one of Implementation Schemes 1-14, wherein the anti-IL-4Rα antibody or its antigen-binding fragment is formulated together with pharmaceutically acceptable excipients.

[0257] Implementation Scheme 16. Use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof in the preparation of a medicament for use in combination with an additional therapeutic agent to treat seasonal allergic rhinitis in a subject, wherein the anti-IL-4Rα antibody or the antigen-binding fragment thereof is as described in any one of Implementation Schemes 1-15, and the additional therapeutic agent is as described in any one of Implementation Schemes 8-12.

[0258] Implementation Scheme 17. A method for improving one or more allergic rhinitis-related parameters in a subject with seasonal allergic rhinitis, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof to said subject, wherein:

[0259] (1) The anti-IL-4Rα antibody or its antigen-binding fragment 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 in 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 in 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;

[0260] (2) The anti-IL-4Rα antibody or its antigen-binding fragment 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;

[0261] (3) The anti-IL-4Rα antibody or its antigen-binding fragment 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 in 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;

[0262] (4) The anti-IL-4Rα antibody or its antigen-binding fragment 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 in 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;

[0263] (5) The anti-IL-4Rα antibody or its antigen-binding fragment 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;

[0264] (6) 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:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region 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;

[0265] (7) 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: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;

[0266] (8) 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:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO:22, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:7;

[0267] (9) 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:8, wherein X3 in 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

[0268] (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.

[0269] Implementation Scheme 18. A method for improving one or more allergic rhinitis-related parameters in a subject with seasonal allergic rhinitis, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof to the subject, wherein the anti-IL-4Rα antibody or the antigen-binding fragment thereof comprises:

[0270] (1) HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6; or

[0271] (2) HCDR1 containing the amino acid sequence shown in SEQ ID NO:11, HCDR2 containing the amino acid sequence shown in SEQ ID NO:12, HCDR3 containing the amino acid sequence shown in SEQ ID NO:13, LCDR1 containing the amino acid sequence shown in SEQ ID NO:14, LCDR2 containing the amino acid sequence shown in SEQ ID NO:15, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:16.

[0272] Implementation Scheme 19. The method according to Implementation Scheme 17 or 18, wherein the seasonal allergic rhinitis is moderate to severe seasonal allergic rhinitis; optionally, the seasonal allergic rhinitis is seasonal allergic rhinitis that is poorly or unsuitably controlled by nasal corticosteroids and / or histamine receptor antagonists; optionally, the seasonal allergic rhinitis is moderate to severe seasonal allergic rhinitis that is poorly or unsuitably controlled by nasal corticosteroids and / or histamine receptor antagonists.

[0273] Implementation Scheme 20. The method according to any one of Implementation Schemes 17-19, wherein the subject further suffers from asthma.

[0274] Implementation Scheme 21. The method according to any one of Implementation Schemes 17-20, wherein the allergic rhinitis-related parameters include TNSS, rTNSS, iTNSS, TOSS, rTOSS, iTOSS and / or RQLQ.

[0275] Implementation Scheme 22. The method according to any one of Implementation Schemes 17-21, wherein administering the anti-IL-4Rα antibody or its antigen-binding fragment to the subject results in a reduction of TNSS, rTNSS, iTNSS, TOSS, rTOSS, iTOSS and / or RQLQ relative to baseline.

[0276] Implementation Scheme 23. The method according to any one of Implementation Schemes 17-21, wherein administering the anti-IL-4Rα antibody or its antigen-binding fragment to the subject results in a reduction of rTNSS by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, or 12 points relative to baseline.

[0277] Implementation Scheme 24. The method according to any one of Implementation Schemes 17-21, wherein administering the anti-IL-4Rα antibody or its antigen-binding fragment to the subject results in a reduction of at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, or 12 points in iTNSS relative to baseline.

[0278] Implementation Scheme 25. The method according to any one of Implementation Schemes 17-21, wherein administering the anti-IL-4Rα antibody or its antigen-binding fragment to the subject results in a reduction of rTOSS by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9 points relative to baseline.

[0279] Implementation Scheme 26. The method according to any one of Implementation Schemes 17-21, wherein administering the anti-IL-4Rα antibody or its antigen-binding fragment to the subject results in a reduction of at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9 points in iTOSS relative to baseline.

[0280] Implementation Scheme 27. The method according to any one of Implementation Schemes 17-21, wherein administration of the anti-IL-4Rα antibody or its antigen-binding fragment to the subject results in a reduction of at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6 points in the mean RQLQ score relative to baseline; and / or

[0281] Administration of the anti-IL-4Rα antibody or its antigen-binding fragment to the subject resulted in a reduction of at least 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, or 168 points in the total RQLQ score relative to baseline.

[0282] Implementation Scheme 28. The method according to any one of Implementation Schemes 17-27, wherein the anti-IL-4Rα antibody or its antigen-binding fragment 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 its antigen-binding fragment is administered at a dose of 300 mg or 600 mg each time.

[0283] Implementation Scheme 29. The method according to any one of Implementation Schemes 17-28, wherein 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; preferably, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 1 week or every 2 weeks.

[0284] Implementation Scheme 30. The method according to any one of Implementation Schemes 17-27, wherein:

[0285] (1) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once every 2 weeks, each time at a dose of 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment;

[0286] (2) The anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 2 weeks. The first administration is 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, and the subsequent administrations are 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment.

[0287] (3) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once a week, with the first administration being 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, and thereafter 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment each time.

[0288] (4) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once every 2 weeks, with each administration of 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, for a total of 2 administrations.

[0289] (5) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once every two weeks, with the first administration being 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, followed by each administration of 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, for a total of two administrations; or

[0290] (6) The anti-IL-4Rα antibody or its antigen-binding fragment is administered once a week. The first administration is 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, and the subsequent administrations are 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, for a total of 4 administrations.

[0291] Implementation Scheme 31. The method according to any one of Implementation Schemes 17-30, wherein the subject is administered an additional therapeutic agent before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment.

[0292] Implementation Scheme 32. The method according to Implementation Scheme 31, wherein the additional therapeutic agent is selected from one or more combinations 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, nonsteroidal anti-inflammatory drugs, antibiotics, histamine receptor antagonists, antifungal agents, topical decongestants, long-acting muscarinic antagonists, and leukotriene receptor antagonists.

[0293] Implementation Scheme 33. The method according to Implementation Scheme 32, wherein the glucocorticoid includes nasal glucocorticoids, inhaled glucocorticoids, and / or systemic glucocorticoids; optionally, the histamine receptor antagonist includes an H1 receptor antagonist and / or an H2 receptor antagonist.

[0294] Implementation Scheme 34. The method according to Implementation Scheme 31, wherein the additional therapeutic agent is a nasal corticosteroid and a histamine receptor antagonist, or the additional therapeutic agent is a nasal corticosteroid and an H1 receptor antagonist; preferably, the additional therapeutic agent is MFNS and loratadine.

[0295] Implementation Scheme 35. The method according to any one of Implementation Schemes 17-30, wherein the subject is administered MFNS before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment, and is administered loratadine before, after, or simultaneously with receiving an anti-IL-4Rα antibody or its antigen-binding fragment.

[0296] Implementation Scheme 36. The method according to any one of Implementation Schemes 17-35, wherein the anti-IL-4Rα antibody or its antigen-binding fragment comprises:

[0297] (1) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:7, and the light chain variable region having at least 95% identity with the amino acid sequence 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; preferably, 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;

[0298] (2) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:17, and the light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:18, wherein X5 of SEQ ID NO:17 is A or V;

[0299] (3) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:7, and the light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:22, wherein X1 in 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;

[0300] (4) A heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:21, and a light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:8, wherein X3 in 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

[0301] (5) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:21, and the light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:22.

[0302] Implementation Scheme 37. The method according to any one of Implementation Schemes 17-36, wherein the anti-IL-4Rα antibody or its antigen-binding fragment comprises:

[0303] (1) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:9, and a light chain having at least 95% identity with the amino acid sequence 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; preferably, 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;

[0304] (2) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:19, and a light chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:20, wherein X5 of SEQ ID NO:19 is A or V;

[0305] (3) A heavy chain whose amino acid sequence is at least 95% identical to the amino acid sequence shown in SEQ ID NO:9, and a light chain whose amino acid sequence is at least 95% identical to the amino acid sequence shown in SEQ ID NO:24, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:9;

[0306] (4) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:23, and a light chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:10, wherein X3 in 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; or

[0307] (5) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:23, and a light chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:24.

[0308] Implementation Scheme 38. The method according to any one of Implementation Schemes 17-37, wherein the anti-IL-4Rα antibody or its antigen-binding fragment is formulated together with pharmaceutically acceptable excipients.

[0309] Implementation Scheme 39. Use of an anti-IL-4Rα antibody or an antigen-binding fragment thereof in the preparation of a medicament for use in combination with an additional therapeutic agent to improve one or more allergic rhinitis-related parameters in subjects with seasonal allergic rhinitis, wherein the anti-IL-4Rα antibody or the antigen-binding fragment thereof is as described in any one of Implementation Schemes 17-38, and the additional therapeutic agent is as described in any one of Implementation Schemes 31-35. Example

[0310] For clarity, this disclosure is further illustrated by examples, but these examples are not intended to limit the scope of this disclosure. All reagents used in this disclosure are commercially available and can be used without further purification.

[0311] The entire contents of patent applications with publication numbers WO2021170020A1 or CN115087673A are incorporated herein by reference. In the following examples, the heavy chain amino acid sequence of the anti-IL-4Rα antibody is shown in SEQ ID NO:9 of this disclosure, and the light chain amino acid sequence is shown in SEQ ID NO:10 of this 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. The C-terminal lysine in SEQ ID NO:9 may be present or absent.

[0312] Example 1: Clinical trial of allergic rhinitis

[0313] 1. Experimental Design

[0314] This clinical trial included a 1-week screening / induction period, a 4-week treatment period, and an 8-week post-treatment follow-up period. Subjects diagnosed with SAR who did not respond well to standard treatment were randomly assigned to four groups in a 1:1:1:1 ratio. A baseline requirement was an absolute peripheral blood eosinophil count (EOS) <0.3 × 10⁻⁶. 9 / L or ≥0.3×10 9 " / L" was used as a stratification factor to ensure that at least 60% of subjects entering randomization had an absolute eosinophil count ≥0.3 × 10⁻⁶ at baseline. 9 / L. During the treatment period, subjects will receive mometasone furoate nasal spray (MFNS) and loratadine as background therapy. The specific dosing regimen is shown in Table 2 below:

[0315] Table 2. Dosing Regimen

[0316] 2. Selection Criteria

[0317] Participants in this study must meet all of the following inclusion criteria:

[0318] (1) Age between 18 and 75 years old (inclusive), gender not limited;

[0319] (2) Seasonal allergic rhinitis (SAR) that meets the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (2022, Revised Edition), with or without allergic conjunctivitis, and with a history of SAR in the same season for at least 2 years.

[0320] (3) Subjects exhibit immunoglobulin E (IgE)-mediated hypersensitivity reactions to at least one pollen allergen in their current environment, which can be confirmed based on the results of a skin prick test or specific IgE test performed within the year prior to screening. For skin prick tests: a positive reaction is defined as a wheal diameter at least 3 mm larger than that of a negative control. (A skin prick test (SPT) report or serum allergen-specific immunoglobulin E (sIgE) test report issued by a tertiary-level Class A medical institution within the year prior to screening is required.)

[0321] (4) Subjects have sufficient pollen exposure during pollen season: Subjects are expected to be in the pollen season throughout the treatment period and have no travel plans to leave the area for 48 hours or more (Note: Pollen season refers to a three-day consecutive period with a local pollen count of more than 20 pollen / 1000 mm). 2 This is considered the start of pollen season. If the local pollen count is below 20 pollens per 1000 mm for three consecutive days, it is considered the start of pollen season. 2 (This is considered the end of the pollen season);

[0322] (5) The subject’s medical history suggests that during the same pollen season in the past, the subject used nasal corticosteroids or other drugs for treating SAR (antihistamines, leukotriene receptor antagonists, etc.) and the SAR symptoms were poorly controlled or the subject’s subjective symptoms were not well controlled (based on the subject’s complaints or medical records, the subject still has at least one moderate or higher SAR symptom).

[0323] (6) On the day of screening, the subject’s instantaneous nasal symptom score (iTNSS) in the morning is ≥4; at the baseline visit (i.e. D1), the morning iTNSS is ≥4, and the average score of the past 6 retrospective nasal symptom scores (rTNSS) is ≥6 (i.e., within the past 3 24-hour time periods, 3 daytime assessments and 3 nighttime assessments, including the daytime assessment of the baseline visit), of which nasal congestion is ≥2, and one of the three symptoms of runny nose, nasal itching and sneezing is ≥2;

[0324] (7) At the baseline visit, the absolute value of peripheral blood eosinophils was ≥0.15×10⁻⁶. 9 / L;

[0325] (8) During the screening / introduction period, subjects completed at least 80% of the assessments on the diary cards and showed good compliance;

[0326] (9) Subjects with asthma were treated with a stable dose of inhaled corticosteroids for at least 4 weeks before the screening period and were assessed to have maintained the same dose of inhaled corticosteroids throughout the study period. The inhaled corticosteroid dose was ≤1000 μg / day of fluticasone propionate or equivalent dose of other inhaled corticosteroids and the subject’s asthma was assessed to be stable by the investigator or specialist.

[0327] (10) The participants voluntarily joined the study, signed informed consent forms, and had good compliance;

[0328] (11) Subjects and their partners agreed to use effective contraception throughout the study period (from signing the informed consent form to 3 months after the last dose of the investigational drug).

[0329] 3. Medications and Treatment Plan

[0330] 3.1 Test drug: Anti-IL-4Rα antibody injection (specification: 300mg (2mL) / vial): The low-dose group was injected subcutaneously with anti-IL-4Rα antibody once every 2 weeks, the medium-dose group was injected subcutaneously with anti-IL-4Rα antibody once every 2 weeks, and the high-dose group was injected subcutaneously with anti-IL-4Rα antibody once every week.

[0331] 3.2 Control drug: Placebo (specification: 2mL / vial, which does not contain anti-IL-4Rα antibody compared with anti-IL-4Rα antibody injection).

[0332] 3.3 Background Treatment Drugs:

[0333] (1) Mometasone furoate nasal spray (Nasonex) ): Apply 2 puffs per nostril each time (each puff contains 50 μg of mometasone furoate), once a day (total daily dose is 200 μg).

[0334] (2) Loratadine: 10 mg once a day (total daily dose is 10 mg).

[0335] 4. Safety Evaluation Standards

[0336] The severity of adverse events is determined using the NCI-CTC AE 5.0 standard.

[0337] 5. Effectiveness evaluation indicators

[0338] (1) Total Nasal Symptom Score (TNSS)

[0339] The TNSS is the sum of scores for four symptoms: runny nose, nasal congestion, nasal itching, and sneezing, with each symptom scored from 0 to 3.

[0340] ● The retrospective total nasal symptom score (rTNSS) is a rating of the severity of nasal symptoms over the past 12 hours, administered in the morning (AM rTNSS) and evening (PM rTNSS). The daily rTNSS is the mean of the PM rTNSS for the current day and the AM rTNSS for the following day;

[0341] ●The Instantaneous Nasal Symptom Score (iTNSS) is a rating of the severity of instantaneous nasal symptoms at a specific point in time.

[0342] (2) Total Ocular Symptom Score (TOSS)

[0343] The Total Eye Symptom Score (TOSS) is the sum of scores for three symptoms: itchy / burning eyes, tearing / watering eyes, and red eyes, with each symptom scored from 0 to 3.

[0344] ● The retrospective total ocular symptom score (rTOSS) is a rating of the severity of ocular symptoms over the past 12 hours, administered in the morning (AM rTOSS) and evening (PM rTOSS). Daily rTOSS is the average of the PM rTOSS for the current day and the AM rTOSS for the following day.

[0345] ●The Instantaneous Total Ocular Symptom Score (iTOSS) is a rating of the severity of transient ocular symptoms at a specific point in time.

[0346] (3) Individual nasal symptom score

[0347] ● Retrospective individual nasal symptom scoring assesses the severity of ocular symptoms (i.e., runny nose, nasal congestion, nasal itching, or sneezing) over the past 12 hours, conducted in the morning and evening.

[0348] (4) Individual ocular symptom score

[0349] ● The retrospective individual ocular symptom score is a rating of the severity of ocular symptoms (i.e., itchy / burning eyes, watery / dribbling eyes, or red eyes) over the past 12 hours, conducted in the morning and evening.

[0350] (5) Quality of Life Questionnaire for Patients with Allergic Rhinitis (RQLQ)

[0351] The Allergic Rhinitis Quality of Life Questionnaire (RQLQ) is a 28-item, self-administered quality of life scale for allergic rhinitis patients, used to assess their quality of life over a week. Each question is scored from 0 to 6, with higher scores indicating a greater impact on quality of life. The overall quality of life score is calculated by averaging all scores.

[0352] (6) Onset time

[0353] (7) Time to reach peak efficacy

[0354] (8) Number of days without symptoms or with mild symptoms

[0355] For (1)-(4), subjects will use log cards to record their allergy symptoms. Subjects will use the following 0 to 3 scale on the log cards to assess the severity of each symptom in the study:

[0356] 0 = None (no symptoms)

[0357] 1 = Mild (Signs / symptoms are clearly present, but only very slight; easily tolerable)

[0358] 2 = Moderate (obvious signs / symptoms, bothersome but tolerable)

[0359] 3 = Severe (unbearable signs / symptoms; interfering with daily activities and / or sleep)

[0360] Retrospective scoring (rTNSS, rTOSS) represents the subject's symptoms over the past 12 hours. This assessment provides information on the effectiveness of treatment over the past day and is performed twice daily: morning scoring (AM rTNSS, AM rTOSS) and evening scoring (PM rTNSS, PM rTOSS). AM scoring must be performed before morning medication to assess the subject's feelings throughout the past night. PM scoring must be performed approximately 12 hours after medication (before bedtime) to assess the subject's feelings during the day.

[0361] The transient symptom score (iTNSS, iTOSS) is a rating of the severity of transient symptoms at a specific point in time. iTNSS and iTOSS are evaluated during the screening visit; on the day of the baseline visit, the transient symptom score is evaluated before medication administration and at 4, 6, 8, 10, and 12 hours after medication administration; after the baseline visit, the transient symptom score is evaluated every morning before medication administration.

[0362] 6. Results

[0363] Statistical analysis was performed using a per-protocol set (PPS). For the mean daily change in rTNSS from baseline over 2 weeks of treatment, a baseline absolute EOS value ≥ 0.3 × 10⁻⁶ was considered acceptable. 9Among subjects taking the medium-dose regimen (L), the least squares mean (SE) was -4.594 (0.4475) in the medium-dose group and -3.191 (0.4371) in the placebo group. The change in the medium-dose group was greater than that in the placebo group, with an inter-group difference (95% CI) of -1.403 (-2.678, -0.129) (p < 0.05). Among all subjects, the least squares mean (SE) was -3.621 (0.3910) in the medium-dose group and -2.563 (0.3674) in the placebo group. The change in the medium-dose group was greater than that in the placebo group, with an inter-group difference (95% CI) of -1.057 (-2.118, 0.003). Here, LS mean is the least squares mean, and SE is the standard error, calculated based on ANCOVA.

[0364] Table 3. Mean change from baseline in daily retrospective total nasal symptom score (rTNSS) over 2 weeks of treatment (baseline absolute EOS value ≥ 0.3 × 10⁻⁶). 9 / L of subjects)

[0365] Table 4. Mean change from baseline in daily retrospective total nasal symptom score (rTNSS) during 2 weeks of treatment (all subjects)

[0366] In Tables 3 and 4, N(nmiss) represents the number of subjects (number of missing individuals), Mean±Std represents the arithmetic mean ± standard deviation, Median(Q1,Q3) represents the median (first quartile, third quartile), and LS mean Diff. represents the difference between the medium-dose group and the placebo group in LS mean.

[0367] In addition, the changes in the medium-dose group were greater than those in the placebo group for the following indicators: mean daily rTNSS change from baseline at 4 weeks of treatment; mean daily iTNSS change from baseline before morning medication at 2 weeks of treatment; mean daily rTOSS change from baseline at 2 weeks of treatment; mean daily rTOSS change from baseline at 4 weeks of treatment; mean daily iTOSS change from baseline before morning medication at 2 weeks of treatment; mean daily retrospective nasal single symptom score change from baseline at 2 weeks of treatment; mean daily retrospective nasal single symptom score change from baseline at 4 weeks of treatment; mean daily retrospective ocular single symptom score change from baseline at 2 weeks of treatment; mean daily retrospective ocular single symptom score change from baseline at 4 weeks of treatment; mean daily RQLQ score change from baseline at 2 weeks of treatment; and / or mean daily RQLQ score change from baseline at 4 weeks of treatment.

[0368] The results showed that the anti-IL-4α antibody disclosed herein had good efficacy in subjects with seasonal allergic rhinitis, especially those whose seasonal allergic rhinitis was poorly controlled or unsuitable with nasal corticosteroids and / or other medications (e.g., antihistamines), and demonstrated good safety in clinical trials.

[0369] The scope of this disclosure is not limited to the specific embodiments described herein. In fact, many modifications beyond those described herein will become apparent to those skilled in the art from the foregoing description and drawings. Such modifications are also intended to fall within the scope of the appended embodiments.

Claims

A method for treating seasonal allergic rhinitis, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof to a subject, wherein: (1) The anti-IL-4Rα antibody or its antigen-binding fragment 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 in 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 in 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 its antigen-binding fragment 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 its antigen-binding fragment 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 in 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 its antigen-binding fragment 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 in 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 its antigen-binding fragment 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 its antigen-binding fragment 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: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 its antigen-binding fragment 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; (8) 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:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO:22, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:7; (9) 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:8, wherein X3 in 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. A method for treating seasonal allergic rhinitis includes administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof to a subject, wherein, The anti-IL-4Rα antibody or its antigen-binding fragment comprises: (1) HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6; or (2) HCDR1 containing the amino acid sequence shown in SEQ ID NO:11, HCDR2 containing the amino acid sequence shown in SEQ ID NO:12, HCDR3 containing the amino acid sequence shown in SEQ ID NO:13, LCDR1 containing the amino acid sequence shown in SEQ ID NO:14, LCDR2 containing the amino acid sequence shown in SEQ ID NO:15, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:

16. A method for improving one or more allergic rhinitis-related parameters in subjects with seasonal allergic rhinitis, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof to the subject, wherein: (1) The anti-IL-4Rα antibody or its antigen-binding fragment 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 in 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 in 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 its antigen-binding fragment 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 its antigen-binding fragment 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 in 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 its antigen-binding fragment 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 in 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 its antigen-binding fragment 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 its antigen-binding fragment 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: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 its antigen-binding fragment 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; (8) 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:7, and LCDR1, LCDR2 and LCDR3 of the light chain variable region shown in SEQ ID NO:22, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:7; (9) 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:8, wherein X3 in 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. A method for improving one or more allergic rhinitis-related parameters in subjects with seasonal allergic rhinitis, comprising administering an anti-IL-4Rα antibody or an antigen-binding fragment thereof to the subject, wherein, The anti-IL-4Rα antibody or its antigen-binding fragment comprises: (1) HCDR1 containing the amino acid sequence shown in SEQ ID NO:1, HCDR2 containing the amino acid sequence shown in SEQ ID NO:2, HCDR3 containing the amino acid sequence shown in SEQ ID NO:3, LCDR1 containing the amino acid sequence shown in SEQ ID NO:4, LCDR2 containing the amino acid sequence shown in SEQ ID NO:5, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:6; or (2) HCDR1 containing the amino acid sequence shown in SEQ ID NO:11, HCDR2 containing the amino acid sequence shown in SEQ ID NO:12, HCDR3 containing the amino acid sequence shown in SEQ ID NO:13, LCDR1 containing the amino acid sequence shown in SEQ ID NO:14, LCDR2 containing the amino acid sequence shown in SEQ ID NO:15, and LCDR3 containing the amino acid sequence shown in SEQ ID NO:

16. The method according to any one of claims 1-4, wherein, The seasonal allergic rhinitis is moderate to severe seasonal allergic rhinitis; optionally, the seasonal allergic rhinitis is seasonal allergic rhinitis that is poorly or unsuitably controlled by nasal corticosteroids and / or histamine receptor antagonists; optionally, the seasonal allergic rhinitis is moderate to severe seasonal allergic rhinitis that is poorly or unsuitably controlled by nasal corticosteroids and / or histamine receptor antagonists. Optionally, the subject further suffers from asthma. The method according to any one of claims 3-5, wherein, The parameters related to allergic rhinitis include TNSS, rTNSS, iTNSS, TOSS, rTOSS, iTOSS, and / or RQLQ. The method according to any one of claims 3-6, wherein, Administration of the anti-IL-4Rα antibody or its antigen-binding fragment to the subject resulted in a reduction of TNSS, rTNSS, iTNSS, TOSS, rTOSS, iTOSS and / or RQLQ relative to baseline; Preferably, (1) Administration of the anti-IL-4Rα antibody or its antigen-binding fragment to the subject resulted in a reduction of rTNSS by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, or 12 points relative to baseline; (2) Administration of the anti-IL-4Rα antibody or its antigen-binding fragment to the subject resulted in a reduction of at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, or 12 points in iTNSS relative to baseline; (3) Administration of the anti-IL-4Rα antibody or its antigen-binding fragment to the subject resulted in a reduction of rTOSS by at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9 points relative to baseline; (4) Administration of the anti-IL-4Rα antibody or its antigen-binding fragment to the subject resulted in a reduction of at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, or 9 points in iTOSS relative to baseline; (5) Administration of the anti-IL-4Rα antibody or its antigen-binding fragment to the subject resulted in a reduction of at least 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6 points in the mean RQLQ score relative to baseline; and / or (6) Administration of the anti-IL-4Rα antibody or its antigen-binding fragment to the subject resulted in a reduction of at least 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, or 168 points in the total RQLQ score relative to baseline. The method according to any one of claims 1-7, wherein, The anti-IL-4Rα antibody or its antigen-binding fragment 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 its antigen-binding fragment is administered at a dose of 300 mg or 600 mg each time. The method according to any one of claims 1-8, wherein, The anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 1 week, 2 weeks, 3 weeks, or 4 weeks; preferably, the anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 1 week or 2 weeks. The method according to any one of claims 1-9, wherein: (1) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once every 2 weeks, each time at a dose of 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment; (2) The anti-IL-4Rα antibody or its antigen-binding fragment is administered once every 2 weeks. The first administration is 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, and the subsequent administrations are 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment. (3) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once a week, with the first administration being 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, and thereafter 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment each time. (4) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once every 2 weeks, with each administration of 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, for a total of 2 administrations. (5) The anti-IL-4Rα antibody or its antigen-binding fragment shall be administered once every two weeks, with the first administration being 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, followed by each administration of 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, for a total of two administrations; or (6) The anti-IL-4Rα antibody or its antigen-binding fragment is administered once a week. The first administration is 600 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, and the subsequent administrations are 300 mg of the anti-IL-4Rα antibody or its antigen-binding fragment, for a total of 4 administrations. The method according to any one of claims 1-10, wherein, The subjects were given additional therapeutic agents before, after, or simultaneously with receiving anti-IL-4Rα antibody or its antigen-binding fragment. The method according to claim 11, wherein, The additional therapeutic agents are selected from one or more of the following: 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, nonsteroidal anti-inflammatory drugs, antibiotics, histamine receptor antagonists, antifungal agents, topical decongestants, long-acting muscarinic antagonists, and leukotriene receptor antagonists. Preferably, the additional therapeutic agent is a nasal corticosteroid and a histamine receptor antagonist, or the additional therapeutic agent is a nasal corticosteroid and an H1 receptor antagonist; more preferably, the additional therapeutic agent is MFNS and loratadine. The method according to any one of claims 1-12, wherein, The anti-IL-4Rα antibody or its antigen-binding fragment comprises: (1) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:7, and the light chain variable region having at least 95% identity with the amino acid sequence 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; preferably, 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; (2) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:17, and the light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:18, wherein X5 of SEQ ID NO:17 is A or V; (3) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:7, and the light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:22, wherein X1 in 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 at least 95% identity with the amino acid sequence shown in SEQ ID NO:21, and a light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:8, wherein X3 in 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 (5) The heavy chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:21, and the light chain variable region having at least 95% identity with the amino acid sequence shown in SEQ ID NO:

22. The method according to any one of claims 1-13, wherein, The anti-IL-4Rα antibody or its antigen-binding fragment comprises: (1) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:9, and a light chain having at least 95% identity with the amino acid sequence 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; preferably, 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; (2) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:19, and a light chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:20, wherein X5 of SEQ ID NO:19 is A or V; (3) A heavy chain whose amino acid sequence is at least 95% identical to the amino acid sequence shown in SEQ ID NO:9, and a light chain whose amino acid sequence is at least 95% identical to the amino acid sequence shown in SEQ ID NO:24, wherein X1 is W and X2 is S, X1 is L and X2 is A, or X1 is W and X2 is A in SEQ ID NO:9; (4) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:23, and a light chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:10, wherein X3 in 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; or (5) A heavy chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:23, and a light chain having at least 95% identity with the amino acid sequence shown in SEQ ID NO:

24. The method according to any one of claims 1-14, wherein, The anti-IL-4Rα antibody or its antigen-binding fragment is formulated together with pharmaceutically acceptable excipients.

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