Use of Anti-il-17rb antibody or antigen-binding fragment thereof or composition

Abstract

The present application discloses an isolated anti-IL-17RB antibody, or an antigen binding fragment thereof, or a pharmaceutical composition comprising the same, for treating FLG-associated diseases, which is capable of reversing the down-regulation of Th2-driven filaggrin expression, and thus can effectively treat FLG-associated diseases.

Description

(12) International publication published under the Patent Cooperation Treaty (19) World Intellectual Property Organization International Bureau (43) International Publication Date June 12, 2025 (12.06.2025) WIPO I PCT 關酮關__ _1關1 (10) International Publication Number WO 2025 / 118126 A1 (51) International Classification for Patents: A61K39 / 395 (2006.01) C07K16 / 24 (2006.01) Cfl7JT / rtZ2«(2006.01) (21) International Application Number: PCT / CN2023 / 136312 (22) International Filing Date: December 5, 2023 (05.12.2023) (25) Filing Language: Chinese (26) Publication Language: Chinese (71) Applicant: Sínomab Bioscience Limited [CN / CN]: Rooms 303 and 305-307, 15 Science Park West Avenue, Hong Kong Science Park, Pak Shek Kok, New Territories, Hong Kong Special Administrative Region, China (CN). (72) Inventors: HUI, Chin Wai; Rooms 303 and 305-307, 15 Science Park West Avenue, Hong Kong Science Park, Pak Shek Kok, New Territories, Hong Kong Special Administrative Region, China (CN). LAM, Lik Hang, Rooms 303 and 305-307, 15 Science Park West Avenue, Hong Kong Science Park, Pak Shek Kok, New Territories, Hong Kong Special Administrative Region, China (CN). LI, Weimin; Rooms 303 and 305-307, 15 Science Park West Avenue, Hong Kong Science Park, Pak Shek Kok, New Territories, Hong Kong Special Administrative Region, China (CN). WU, Wai Chung; Rooms 303 and 305-307, 15 Science Park West Avenue, Hong Kong Science Park, Pak Shek Kok, New Territories, Hong Kong Special Administrative Region, China (CN). CHOW, Kai Cheung; Rooms 303 and 305-307, 15 Science Park West Avenue, Hong Kong Science Park, Pak Shek Kok, New Territories, Hong Kong Special Administrative Region, China (CN). LEUNG, Shui On; Rooms 303 and 305-307, 15 Science Park West Avenue, Hong Kong Science Park, Pak Shek Kok, New Territories, Hong Kong Special Administrative Region, China (CN). (74) Agent: Beijing Sunhope Intellectual Property Ltd.; Room 1106, Kunxun Building, No. 9 Zhichun Road, Haidian District, Beijing, China 100191 (CN). (81) Designated States (unless otherwise indicated, claim for all available national protection): AE, AG, AL, AM, AO, AT, AU, AZ,BA, BB, BG, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IQ, IR, IS, IT, JM, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, MG, MK, MN, MU, MW, MX, MY, MZ, NA, NG, NI, KP, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, WS, ZA, ZM, ZW. (^) Designated States (unless otherwise indicated, claim all available types of regional protection): ARIPO (BW, CV, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SC, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, ME, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TO, TG). This international publication: — includes the international search report (Article 21(3) of the Treaty). — includes the sequence listing part of the specification (Rule 5.2(a)). BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CV, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, (54) Title: USE OF ANTI-IL-17RB ANTIBODY OR ANTIGEN-BINDING FRAGMENT THEREOF OR COMPOSITION(54) Title of Invention: Use of Anti-IL-17RB Antibody, or Antigen-Binding Fragment thereof or Composition thereof (57) Abstract: Disclosed in the present application are an isolated anti-IL-17RB antibody or antigen-binding fragment thereof, or a pharmaceutical composition containing sanic, which are used for treating FLG-associated diseases. The anti-IL-17RB antibody or antigen-binding fragment thereof or the pharmaceutical composition containing sanic can reverse Th2-driven downregulation of filaggrin ^2 expression, and can thus effectively treat FLG-associated diseases. J (57) Abstract: This invention discloses an isolated anti-IL-17RB antibody, or antigen-binding fragment thereof, or pharmaceutical composition containing sanic, for the treatment of FLG-associated diseases. The anti-IL-17RB antibody, or antigen-binding fragment thereof, or pharmaceutical composition containing sanic can reverse Th2-driven downregulation of filaggrin ^2 expression, and can thus effectively treat FLG-associated diseases. WO 2025 / 118126 PCT / CN2023 / 136312 Use of Anti-n,-17RR Antibody, or its Antigen-Binding Fragment or Composition Technical Field This application belongs to the field of immunopharmaceuticals, specifically relating to the use of IL-17RB antibody or its antigen-binding fragment, or pharmaceutical compositions containing the same, in the preparation of a pharmaceutical medicament for treating FLG-related diseases. Background Art The skin covers the entire human body, protecting humans from various external stimuli. Damage to the barrier can lead to increased penetration of external antigens, easily inducing skin inflammation. Persistent skin inflammation, in turn, can further weaken the skin barrier function, thus creating a "vicious cycle" between the skin barrier and skin immunity. Filagrin (FLG) and its metabolites are key components for maintaining skin barrier function. For example, FLG deficiency is a major pathogenic factor in many skin diseases such as atopic dermatitis. Atopic dermatitis (Atopic dermatitis,Atopic dermatitis (AD) is a chronic inflammatory skin disease that typically appears in childhood and can persist into adulthood. Over the past few decades, the prevalence and incidence of atopic dermatitis have been steadily increasing. Research data indicates that the prevalence in children is approximately 15% to 30%, and in adults it can reach as high as 10%, making atopic dermatitis the skin disease with the highest disease burden. The pathogenesis of atopic dermatitis involves genetic susceptibility, immune and epidermal barrier dysfunction, and environmental factors. Itching is the primary symptom, and skin lesions range from mild erythema to severe lichenification characteristic of erythroderma. Traditional treatments for atopic dermatitis include topical corticosteroids, phototherapy, JAK inhibitors (such as ruxolitmib and upadacilimb), calcineurin inhibitors, and PDE4 inhibitors. While corticosteroids provide good relief, their numerous side effects make them unsuitable for long-term use, and atopic dermatitis often recurs after discontinuation. Therefore, combining corticosteroids with other treatments is necessary. The availability of utpatinib extended-release tablets has provided more treatment options for atopic dermatitis patients. After two weeks of use, patients showed improvement in skin lesions, and after 16 weeks, more patients achieved high levels of lesion clearance. Dupilumab (Dupixent™), co-developed by Sanofi and Regeneron, is a fully human anti-IL-4 / IL-13 monoclonal antibody. It was first approved by the FDA in March 2017 and first approved for marketing in China in June 2020. It works by specifically binding to IL-4Ra, thereby inhibiting the signal transduction of IL-4 and IL-13, blocking the IL-4 and IL-13-mediated inflammatory response, and can therefore be used to treat atopic dermatitis. Furthermore, the results of the T1T phase clinical trial (NCT037 or 397) of utpatinib reported that utpatinib demonstrated efficacy advantages over dupilumab in both the primary endpoint and all secondary endpoints, and that utpatinib had a faster onset of action. In addition, the US FDA approved Tezepelumab (Tezspire™), an anti-TSLP antibody jointly developed by AstraZeneca and Amgen, in 2021 as a treatment for severe asthma. A phase 2a randomized, double-blind clinical trial (NCT02525094) using Tezepelumab in adult patients with moderate to severe atopic dermatitis was initiated in August 2015. Although the Tezepelumab + TCS group achieved EASI50 (50 Percent (%) Reduction From Baseline in Eczema Area and Severity) compared to the placebo + TCS (topical corticosteroids) group, the results showed improvement.The proportion of FLG (64.7% w. 48.2%) was higher, but the treatment difference was not statistically significant (Eric L Simpson et al., JAAD, 2019 Apr. 80(4): 10L3-1021). More options are still needed for the treatment of diseases related to filaggrin downregulation. The inventors of this application discovered in their research that anti-IL-17RB antibodies can restore FLG expression in the skin of patients with allergic diseases or conditions (e.g., dermatitis), thereby improving skin barrier function and thus achieving treatment of related diseases and conditions. This application relates to the use of an isolated anti-IL-17RB antibody, or its antigenic fragment, or a pharmaceutical composition containing the same, in the preparation of a medicament for treating FLG-related diseases, wherein the antibody comprises: HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:2 and HCDR3 shown in SEQ ID NO:3; and LCDR1 shown in SEQ ID NO:4, and LCDR3 shown in SEQ ID NO:5. The LCDR2 shown is illustrated in SEQ ID NO: 6, and the LCDR3 shown in SEQ ID NO: 6. Alternatively, this application relates to isolated anti-IL-17RB antibodies, or antigen-binding fragments thereof, or pharmaceutical compositions comprising the same for the treatment of FLG-associated disease, wherein the antibodies comprise: HCDR1 shown in SEQ ID NO: 1, HCDR2 shown in SEQ ID NO: 2, and HCDR3 shown in SEQ ID NO: 3; and LCDR1 shown in SEQ ID NO: 4, LCDR2 shown in SEQ ID NO: 5, and LCDR3 shown in SEQ ID NO: 6. Alternatively, this application relates to a method of treating FLG-associated disease, comprising administering to a subject in need an isolated anti-IL-17RB antibody, or antigen-binding fragments thereof, or a pharmaceutical composition comprising the same, wherein the antibodies comprise: HCDR1 shown in SEQ ID NO: 1, HCDR2 shown in SEQ ID NO: 2, and HCDR3 shown in SEQ ID NO: 3; and / or LCDR1 shown in SEQ ID NO: 4, LCDR2 shown in SEQ ID NO: 5, and LCDR3 shown in SEQ ID NO: 6. The LCDR1 shown is illustrated in SEQ ID NO: 5, the LCDR2 shown in SEQ ID NO: 6, and the LCDR3 shown in SEQ ID NO: 7. Alternatively, this application relates to a pharmaceutical product for treating FLG-related diseases, comprising an isolated anti-IL-17RB antibody, or an antigen-binding fragment thereof, or a pharmaceutical composition comprising thereto, wherein the antibody comprises: HCDR1 shown in SEQ ID NO: 1, HCDR2 shown in SEQ ID NO: 2, and HCDR3 shown in SEQ ID NO: 3; and a domain, as shown in SEQ ID NO: 6.LCDR1 shown in NO:4, LCDR2 shown in SEQ ID NO:5 WO 2025 / 118126 PCT / CN2023 / 136312, and LCDR3 shown in SEQ ID NO:6 are described in this application. The anti-IL-17RB antibody described in this application exhibits good affinity for IL-17RB (interleukin-17 receptor B), can reverse the downregulation of Th2-driven filaggrin expression, reduce the LLC2 population in submental lymph nodes, weaken the secretion of IL-4, IL-5, and IL-13 by lymph node cells, significantly reduce epidermal hyperplasia, inhibit the infiltration of mast cells and eosinophils, and thereby restore the skin barrier, achieving the treatment of FLG-related diseases. Furthermore, the inventors have also found through preclinical in vivo animal experiments that the anti-IL-17RB antibody described in this application is more effective than utpatinib in treating atopic dermatitis, especially in reducing itching and improving skin pathology, and is more effective and faster in this regard. Figure 1: Table of filaggrin in terminally differentiated HaCaT cells after treatment with cytokines and anti-IL-17RB antibody hD9043. A) Illustration of direct treatment of mature HaCaT cells with different reagents; B) Illustration of co-culture between PBMCs and mature HaCaT cells; C) Quantification of the band intensity of filaggrin expression after direct treatment of mature HaCaT cells; D) Representative protein blot of filaggrin expression after co-culture; E) Quantitative analysis showing that 5 μg / mL anti-IL-17RB antibody hD9043 can significantly restore filaggrin levels in the presence of total alarmins. ***p<0.001, **p<0.01. *p<0.05, analyzed by Student's t-test. N=3c. Figure 2: Animal model of atopic dermatitis developed using DNFB. A) Treatment modalities of topical DNFB administration and antibody therapy within one month; B) Representative images of dorsal skin from different groups of mice; C) Determination of dermatitis scores showed that anti-IL-17RB antibody hD9043 significantly restored dermatitis symptoms in DNFB-treated mice on days 14 and 21. ***p<0.001, by two-way ANOVA with post-hoc test. N=9. Figure 3: Anti-IL-17RB antibody hD9043 significantly reduced IL-17RB immunity in submental lymph nodes. A) Dry weight of four submental lymph nodes from different groups of mice; B) ILC2 population in single isolated cells from lymph nodes; C) Levels of IL-4, IL-5, and IL-13 in the supernatant after culturing lymph nodes for 1 day in the presence of DNFB restimulation. Student's t-test analysis showed that, compared with the physiological saline control, for A and B, ***p<0.001, *p<0.05, N=7-9. One-way ANOVA with post-hoc tests was also performed. Compared with IgG4-DNFB ffl, for CE...**p<0.01, * p<0.05. N = 6. Figure 4: Anti-IL-17RB antibody hD9043 significantly improves skin health by reducing epidermal thickness. A-B) Representative images obtained from paraffin sections of back skin and ears after hematoxylin-eosin staining. Signs of perivascular vasculitis, conventional acanthosis and spongiotic elongation of epidermal rete ridges were observed in DNFB-treated mice, and these pathologies can be suppressed by anti-IL-17RB antibody hD9043. C-D) Quantification shows that anti-IL-17RB antibody hD9043 can suppress DNFB-induced epidermal hyperplasia in back skin and ears. Analysis by Student's t-test, compared with the normal saline control, ***p<0.001. By one-way analysis of variance with post-hoc test, compared with the IgG4+DNFB group, ** p<0.01, * p<0.05. N=8-9. Figure 5: Under DNFB sensitization, anti-IL-17RB antibody hD9043 significantly suppresses the infiltration of eosinophils and mast cells into the back skin and ear layers. A) Representative images of eosinophil and mast cell infiltration into back skin and ear layers after DNFB treatment; B-C) Quantification of mast cell number and eosinophil intensity in back skin; D-E) Quantification of mast cell number and eosinophil intensity in ears. Analysis by Student's t-test, compared with the normal saline control, **p<0.01. By one-way analysis of variance with post-hoc test, compared with the IgG4+DNFB group, **p<0.01, *p<0.05. N=6. Figure 6: Anti-IL-17RB antibody hD9043 attenuates Th2 inflammation in ear sections of DNFB-treated animals. A) Representative images of IL-4 expression in different layers; B) Representative images of IL-13 expression in different layers; C-D) Quantification of IL-4 and IL-13 intensity in the epidermal layer and back dermal layer. Analysis by Student's t-test, compared with the normal saline control, ***p<0.001. By one-way analysis of variance with post-hoc test, compared with the IgG4+DNFB group, **p<0.01. N = 6. Figure 7: Anti-IL-17RB antibody hD9043 restores filaggrin expression in DNFB-treated animals. A) Representative images show that administration of DNFB significantly reduces filaggrin levels, and anti-IL-17RB antibody hD9043 can restore its expression. B) Quantification confirms that 5 mg / kg anti-IL-17RB antibody hD9043 can rescue filaggrin levels. Analysis by Student's t-test, compared with the normal saline control, *p <0.05. By one-way analysis of variance with post-hoc test, compared with the IgG4+DNFB group, *p<0.05. N=5-6.Figure 8: Summary of how administration of anti-IL-17RB antibodies (e.g., hD9043) salvages skin disease during AD progression. Detailed Description Unless otherwise stated, the following terms and phrases as used herein are intended to have the following definitions, and a particular term or phrase should not be considered uncertain or unclear unless specifically defined, but should be understood in accordance with its general meaning as commonly defined in the art. The term "antibody" herein refers to any protein or polypeptide capable of heterologously recognizing and binding to an antigen, encompassing both natural and artificial antibodies, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies, sclerosing antibodies, single-domain antibodies, etc., exhibiting the desired biological activity, and can be classified into five isotypes according to their chain type: IgG, IgM, IgD, IgA, and IgE. The term "isolated" means that the target product (e.g., antibody, or antigen-binding fragment) has been isolated from its natural environment. An "antigen-binding fragment" or "antigen-binding moiety" of an antibody refers to one or more fragments of an antibody that retain the function of specifically binding to antigens. Examples of antigen-binding fragments include, but are not limited to, Fab fragments, Fab' fragments, F(ab')2 fragments, Fd fragments, Fv fragments, dAb fragments, isolated CDR regions, single-chain Fv molecules (scFv), etc. When referring to antibodies, the term "isolated" as used herein means that the antibody is substantially free of other cellular components that bind to it in its native state; for example, an isolated antibody may be an antibody removed from its natural or natural environment. "Humanized antibody" refers to an antibody containing a complementarity-determining region (CDR) derived from a non-human animal, as well as a backbone region and constant regions derived from a human. The term "variable region (V)" as used herein... "Variants" refers to regions in the antibody light and heavy chains where the amino acid sequence varies considerably, including the light chain variable region (VL) and the heavy chain variable region (VH). The term "constant region (C)" refers to the region located at the carboxyl terminus of the antibody peptide S, where the amino acid sequence is relatively conserved in the antibody light and heavy chains, including the light chain constant region (CL) and the heavy chain constant region (CHL). The term "CDR" (complementarity-determining region), also known as "hypervariant region (HVR)," refers to regions in the heavy and light chain variable regions where the sequence is highly variable. This may include three CDRs located in the heavy chain variable region (i.e., HCDR1 to HCDR3) and three CDRs located in the light chain variable region (i.e., LCDRI to LCDR3). Regions in the heavy and light chain variable regions other than the CDRs are called "backbone regions (FR)." Various numbering systems known in the art can be used to number the CDRs of the heavy and light chains starting from the N-terminus, for example, Kabat, Chothia, Aho, IMGT. and Contact (see, Kabat et al., Sequences ofProteins of Immunological Interest 1991, 5th Edition, US Department of Health and Human Services, NIH Publication No. 91-3242; Johnson et al., Nucleic Acids Res 2001, 29:205-206; Chothia & Lesk, J Mol Biol 1987, 196:901-917; ChotWa et al., Nature 1989, 342:877-885; Chothia et al., J Mol Biol 1992, 227:799-817; Al-Lazikani et al., J Mol Biol 1997, 273:927-748; Lefranc MP et al., Nucleic Acids Research 1999, 27:209-212; MacCallum RM et al., J Mol Biol 1996, 262:732-745; http: / / imgt.cines.ft; Dunbar J, Deane CM. ANARCI: antigen receptor numbering and receptor classification. Bioinformatics. 2016; 32(2):298-300). Table 1. CDRs Determined Using Different Numbering Systems CDR Kabat AbM Chothia Contact IMGT LCDR1 L24-L34 L24-L34 L26-L32 L30-L36 L27-L32 LCDR2 L50-L56 L50-L56 L50-L52 L46-L55 L50-L52 LCDR3 L89-L97 L89-L97 L91-L96 L89-L96 L89-L96 HCDR1 H31-H35B H26-H35B H26-H32 H30-H35B H26-H35B HCDR1 H31-H35 H26-H35 H26-H32 H30-H35 H26-H35 HCDR2 H50-H65 H50-H58 H53-H55 The "percentage of identity" of the amino acid sequences (H47-H58, H51-H57, HCDR3, H95-H102, H95-H102, H96-H101, H93-H101, H93-H102) refers to the alignment of the candidate sequence with the reference sequence and, if necessary, to achieve [a certain percentage of identity].The percentage of sequence identity of an amino acid sequence is the percentage of S-amino acid residues in a candidate sequence that are identical to a reference sequence, excluding any conserved substitutions as part of the sequence identity. This percentage can be determined by aligning two or more sequences using tools known in the art, such as BLASTp, ClustalW2 (see SI Higgins DG et al., Methods Enzymol 1996, 266:383-402; Larkin MA et al., Biomformatics 2007, 23:2947-2948), ALIGN gfc Megalign (UNAS I'AR) software, etc. In this document, the terms “X” and “Xaa” are equivalent and refer to unspecified amino acids (Jr. specified Amino Acids). Their scope is defined by the relevant descriptions. To distinguish multiple “X”s in the same amino acid sequence, sequentially appearing Xs are numbered (i.e., written as X…) and their scope is defined separately. The terms “subject,” “patient,” and “individual” are used interchangeably herein and include mammals or non-mammalian vertebrates (e.g., chickens, pheasants, fish), including but not limited to domesticated animals (e.g., cattle, sheep, cats, dogs, pigs, and horses), primates (e.g., humans, non-human primates such as monkeys), rabbits, and rodents (e.g., mice, rats, guinea pigs, hamsters), preferably humans. The term “affinity” or “binding affinity” refers to the intrinsic binding capacity between members of a binding pair. The affinity between one molecule and another in a binding pair is typically expressed as the equilibrium dissociation constant (Kd). The term "treatment" (or "treatment") used herein encompasses preventative treatment, which refers to the reduction, improvement, relief, or delay of a disease or its related symptoms; the slowing or delaying of the onset or development of a disease or its related symptoms; the reduction of the risk of developing a disease or its related symptoms; the maintenance of a disease or its related symptoms; the complete or partial reversal of a disease or its related symptoms; or the cure of a disease or its related symptoms. The term "pharmaceutically acceptable" refers to compounds, materials, compositions, and / or dosage forms that, within the limits of reliable scientific judgment, are suitable for use in contact with human and animal tissues without undue toxicity, irritation, allergic reactions, or other problems or complications, in proportion to a reasonable benefit / risk ratio. Unless the context clearly indicates otherwise, singular terms encompass the plural objects referred to, and vice versa. Similarly, unless the context clearly indicates otherwise (WO 2025 / 118126 PCT / CN2023 / 136312), the word "or" is intended to include "and".In this document, unless otherwise stated, the terms “comprise”, “comprise”, “comprising”, or their equivalents (contain, contain, containing, include, includes, including) are open-ended expressions meaning that, in addition to the listed elements, components, and steps, they may also encompass other unspecified elements, components, and steps. Unless otherwise stated, all figures used herein to represent amounts of components, measurements, or reaction conditions should be understood to be modified by the term "about" in all cases, and the meaning of the term "about" herein should be considered as within an acceptable margin of error for the corresponding value. When associated with percentages, the term "about" may mean, for example, ±1%, preferably ±0.5%, more preferably ±0.1%. The anti-IL-17RB antibody of this application can specifically recognize and bind to human IL-17RB, inhibit signal transduction downstream of the IL-17RB signaling pathway, and can reverse the regulation of Th2-driven FLG expression, reducing the [LC2 population in lymph nodes. Next, the technical solution of this application will be described in more detail through exemplary embodiments, but the scope of protection of this application is not limited thereto. 1. Use In some embodiments, this application relates to the use of an isolated anti-IL-17RB antibody, or its antigen-binding fragment, or a pharmaceutical composition containing the thereof in the preparation of a medicament for treating FLG-related diseases, wherein the antibody comprises: HCDR1 as specified in SEQ ID NO: 1, and as specified in SEQ ID NO: 2 The HCDR2 shown is shown in SEQ ID NO:3 and HCDR3 shown in SEQ ID NO:4, LCDR1 shown in SEQ ID NO:5 and LCDR3 shown in SEQ ID NO:6. In some embodiments, this application relates to isolated anti-IL-17RB antibodies, or antigen-binding fragments thereof, or pharmaceutical compositions containing them for treating FLG-associated disease, wherein the antibodies comprise: HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:2 and HCDR3 shown in SEQ ID NO:3; and LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5 and LCDR3 shown in SEQ ID NO:6. In some embodiments, this application relates to a pharmaceutical product for treating FLG-associated disease, comprising isolated anti-IL-17RB antibodies, Or its antigen-binding fragment, or a pharmaceutical composition containing it, wherein the antibody comprises: HCDR1 as shown in SEQ ID NO: 1, H as shown in SEQ ID NO: 2IICDR2 and IICDR3 shown in SEQ ID NO:3; and / or LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5, and LCDR3 shown in SEQ ID NO:6. In some embodiments, the FLG-associated disease is at least one of atopic dermatitis, allergic rhinitis, eczema (e.g., herpetic eczema), contact dermatitis (e.g., allergic contact dermatitis), urticaria, angioedema, psoriasis, herpetic dermatitis, bullous pemphigoid, pemphigus, epidermolysis bullosa, rosacea, ichthyosis, photodermatitis, or related symptoms thereof. In some embodiments, the FLG-associated disease is atopic dermatitis or related symptoms thereof. In some specific embodiments, the atopic dermatitis is infantile atopic dermatitis, childhood atopic dermatitis, or adolescent and adult atopic dermatitis. In some specific embodiments, the atopic dermatitis is mild, moderate, or severe. Various methods for evaluating the severity of atopic dermatitis are known in the art, such as the Scoring for Atopic Dermatitis (SCORAD), the Area and Severity Index for Eczema (EASI), the Investigator Global Assessment (IGA), and the Visual Analogue Scale (VAS) for itching. Alternatively, simple and easy-to-use indicators can be used clinically to determine the severity of atopic dermatitis, such as: mild atopic dermatitis is characterized by a rash area of ​​less than 5%; moderate atopic dermatitis is characterized by 5%–10% of the rash, or recurrent rashes; severe atopic dermatitis is characterized by lesions covering more than 10% of the body surface area, or persistent dermatitis with severe itching affecting sleep. In some specific embodiments, the symptoms associated with atopic dermatitis include dry skin, itchy skin, eczematous lesions (including erythema, papules, redness, vesicles, skin erosion, and epidermal thickening), xeroderma-related symptoms, dermatographia-related symptoms, white dermatographia, Hertoghe's sign, infraorbital folds, periorbital hyperpigmentation (darkening around the eyes), pityriasis alba, and low hairline. In some embodiments, the anti-IL-17RB antibody includes: HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:12 or 13, and HCDR3 shown in SEQ ID NO:3; and LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5, and LCDR3 shown in SEQ ID NO:6. In some embodiments, the anti-IL-17RB antibiotic comprises: HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:12, and HCDR3 shown in SEQ ID NO:3; and / or, LCDR1 shown in SEQ ID NO:4, and HCDR3 shown in SEQ ID NO:5.LCDR2 is shown and LCDR3 is shown in SEQ ID NO. 6. In some embodiments, the anti-IL-17RB antibody comprises: a VH region having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and at least 99% identity with the amino acid sequence shown in SEQ ID NO: 7; and a region having at least 80%, at least 85%, rarely 90%, at least 91%, rarely 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and at least 99% identity with the amino acid sequence shown in SEQ ID NO: 11. 2025 / 118126 PCT / CN2O23 / 136312 VL with at least 99% identity. In some embodiments of the H body, the amino acid sequence with at least 80% identity with the amino acid sequence shown in SEQ ID NO: 7 has predominantly (or all) different amino acids in the FR region (backbone region). In some specific embodiments, the amino acid sequence with at least 80% identity with the amino acid sequence shown in SEQ ID NO: 11 has predominantly (or all) different amino acids in the FR region (backbone region). In some specific embodiments, the VH comprises the amino acid sequence shown in SEQ ID NO: 7, optionally having up to four (e.g., 1, 2, 3, 4) additional amino acid substitutions in the framework region. In some specific embodiments, the VH comprises the amino acid sequence shown in SEQ ED NO: 7, where X3 is N. Further, X+ is 5G, and further, X5 is D. Further, XtlQ. Further, X2 is A. Further, X6 is M. In some specific embodiments, the VH comprises the amino acid sequence shown in SEQ ID NO: 7, wherein X1 is E. Further, X2 is T. Further, X6 is L. In some specific embodiments, the VH comprises the amino acid sequence shown in SEQ ID NO: 7, wherein X3 is A. Further, X4 is Q. Further, X5 is G0. Further, X6 is E0. Further, X2 is T. Further, X5 is L. In some embodiments, the anti-IL-17RB antibody comprises: amino acids shown in any one of SEQ ID NO: 8, 9, or 10.The sequence has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with VH: and / or has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with VL. In some specific embodiments, the amino acids differing from those shown in any of SEQ ID NO: 8, 9, 10, or 11 are predominantly (or all) present in the FR region (backbone region). In some embodiments, the anti-IL-17RB antibody comprises: a VH having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence shown in SEQ ID NO: 8; and / or a VL having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence shown in SEQ ID NO: 11. Preferably, the amino acids differing in the amino acid sequence with at least 80% identity with the amino acid sequence shown in SEQ ID NO: 8 or 11 are mainly present (or all present) in the FR region (backbone region). In some embodiments, the anti-IL-17RB antibody comprises: a VH having an amino acid sequence shown in SEQ ID NO: 8, and an amino acid sequence shown in SEQ ID NO: 11. In some embodiments, the anti-IL-17RB antibody further comprises a heavy chain constant region (CHL) having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, 96%, 97%, 98%, or 99% identity with the amino acid sequence shown in SEQ ID NO: 14 or 18. In some specific embodiments, the anti-IL-17RB antibody further comprises CH as shown in SEQ ID NO: 14 or 18. In some specific embodiments, the anti-IL-17RB antibody further comprises CH as shown in SEQ ID NO: 18. In some embodiments, the anti-IL-17RB antibody further comprises a light chain constant region (CL), the light chain constant region being selected from the human α chain and β chain, preferably the constant region of the human α chain.In some embodiments, the anti-IL-17RB antibody further comprises: a CL having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, 96%, 97%, 98%, or 99% identity with the amino acid sequence shown in SEQ ID NO: 16. In some specific embodiments, the anti-IL-17RB antibody further comprises the CL of SEQ ID NO: 16. In some embodiments, the anti-IL-17RB antibody comprises: a heavy chain having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, 96%, 97%, 98%, or 99% identity with the amino acid sequence shown in SEQ ID NO: 15, 19, 20, or 21. In another specific embodiment, the anti-IL-17RB antibody comprises: a heavy chain shown in SEQ ID NO: 15, 19, 20, or 21. In some specific embodiments, the anti-IL-17RB antibody comprises the heavy chain shown in SEQ ID NO: 19. In one specific embodiment, the anti-IL-17RB antibody comprises a light chain having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, 96%, 97%, 98%, or 99% identity with the amino acid sequence shown in SEQ ID NO: 17. In some specific embodiments, the anti-IL-17RB antibody comprises the light chain shown in SEQ ID NO: 17. In some embodiments, the anti-IL-17RB antibody is of type IgG1, IgG2, IgG3, or IgG4, preferably type IgG4. In some embodiments, the antigen fragment of the isolated anti-IL-17RB antibody described in this application is selected from Fab fragments, Fab' fragments, F(ab')2 fragments, Fd fragments, Fv fragments, dAb fragments, isolated CDR|x, scFv, and nanobodies. 5 WO 2025 / 118126 PCT / CN2023 / 136312 In this document, various variants of the isolated anti-IL47RB antibody or its antigen-binding fragment described above retain the ability to specifically bind to the antigen IL-17RB. In some embodiments, the pharmaceutical composition further comprises pharmaceutically acceptable excipients. The excipients described herein may be any pharmaceutically acceptable excipient, such as, but not limited to, solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, flow aids, flavoring agents, preservatives, suspending agents, antioxidants, penetration enhancers, pH adjusters, surfactants, diluents, etc. Regarding other available pharmaceutically acceptable excipients...For information on excipients, please refer to, for example, "Pharmaceutical Excipients Handbook" (4th Edition), by RC Luo et al., translated by Zheng Junmin, Chemical Industry Press, 2005. In some embodiments, the pharmaceutical composition further includes additional therapeutic agents, including but not limited to anti-allergic drugs, analgesics, anti-inflammatory drugs, anesthetic drugs, and drugs that lower body temperature. In some embodiments, the pharmaceutical composition further includes additional specific dermatitis treatment agents, such as glucocorticoids (e.g., hydrocortisone butyrate, mometasone furoate, econazole / triamcinolone), calcineurin inhibitors (e.g., tacrolimus, semamoxine), antibiotics (e.g., amoxicillin-clavulanate, levofloxacin hydrochloride), antipruritic agents (e.g., doxepin hydrochloride, diclofenac diethylamine, ketoprofen), antihistamines (e.g., loratadine, dietirizine hydrochloride, ebastine, chlorpheniramine maleate), JAK inhibitors (e.g., ruxotetinib, utpatinib), PDE4 inhibitors (e.g., criborone, roxithromycin), calamine lotion, etc. In some embodiments, the anti-TL-I7RB antibody, or its antigen-binding fragment, or pharmaceutical composition containing it described herein may be in the form of an aqueous solution, suspension, emulsion, liposome formulation, or powder. In some implementations, the anti-IL-17RB antibody, its antigen-binding fragment, or pharmaceutical composition comprising it described herein may be in unit dose form to facilitate administration to the patient at the desired dose. The dosage range of the anti-IL-17RB antibody, its antigen-binding fragment, or pharmaceutical composition comprising it described herein may be determined empirically by the clinician based on the route of administration (including administration time, dosing interval, and route of administration), the patient's age, weight, sex, or pathological condition, diet, excretion rate, and drug sensitivity. The anti-IL-17RB antibody, its antigen-binding fragment, or pharmaceutical composition comprising it described herein may be prepared in any dosage form known in the art, such as injections, suspensions, solutions, powders, emulsions, sprays, tablets, pills, capsules, granules, ointments, suppositories, gels, etc. The anti-IL-17RB antibody, its antigen-binding fragment, or pharmaceutical composition comprising it described herein may be suitable for intravenous, intramuscular, or other administration. Intra-arterial, intra-articular, subcapsular, subarachnoid, orbital, intracardiac, subcutaneous, extraintestinal, intraperitoneal, intraspinal, intranasal, or epidermal administration, for example, by injection or infusion. 2. Treatment Method This application relates to a method of treating FLG-associated disease, comprising administering to a subject in need: • an isolated anti-IL-17RB antibody, or an antigen-containing fragment thereof, or a pharmaceutical composition containing the thereof, wherein the antibody comprises: HCDR1 shown in SEQ ID NO: 1; HCDR2 shown in SEQ ID NO: 2; and HCDR3 shown in SEQ ID NO: 3; and LCDR1 shown in SEQ ID NO: 4; and LCDR2 shown in SEQ ID NO: 5.And LCDR3 shown in SEQ ID NO: 6. In some embodiments, a therapeutically effective or preventatively effective amount of anti-IL-17RB anti-ILR3 or its antigen-binding fragment, or a pharmaceutical composition containing it, is administered to a subject in need. The therapeutically effective or preventatively effective amount may be determined by a clinician using conventional methods or experience based on the subject's individual condition, disease severity, sex, age, body type, administration method, etc. In some embodiments, the FLG-associated disease is at least one of atopic dermatitis, allergic rhinitis, eczema (e.g., herpetic eczema), contact dermatitis (e.g., allergic contact dermatitis), urticaria, angioedema, psoriasis, herpetic dermatitis, bullous bullous dermatitis, bullous epidermolysis bullosa, rosacea, ichthyosis, photodermatitis, or related symptoms thereof. In some embodiments, the FLG-associated disease is atopic dermatitis or related symptoms thereof. In some specific embodiments, the atopic dermatitis is infantile atopic dermatitis, childhood atopic dermatitis, or adolescent and adult atopic dermatitis. In some specific embodiments, the atopic dermatitis is mild, moderate, or severe. In some specific embodiments, the related symptoms of atopic dermatitis include dry skin, itchy skin, eczematous lesions (including erythema, papules, redness, vesicles, skin erosion, and epidermal thickening), xeroderma-related symptoms, palmar dermatographia-related symptoms, white dermatographia, Hcrtoghe's sign, infraorbital folds, periorbital hyperpigmentation (darkness around the eyes), pityriasis alba, and low hairline, etc. In some embodiments, the anti-IL-17RB antibody comprises: HCDRR shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:12 or 13, and HCDR3 shown in SEQ ID NO:3; and, or, LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5, and LCDR3 shown in SEQ ID NO:6. In some embodiments, the anti-IL-17RB antibody comprises: IICDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:12, and HCDR3 shown in SEQ ID NO:3; and / or, LCDR1 shown in SEQ ID NO:4, IICDR2 shown in SEQ ID NO:5, and TICDR3 shown in SEQ ID NO:6. In some embodiments, the anti-IL-17RB antibody comprises: having at least 80% of the amino acid sequence shown in SEQ ID NO:7. At least 85%, at least 90%, at least 91%, rarely 92%, at least 93%, rarely 94%, at least 95%, at least 96%, at least 97%, WO 2025 / 118126PCT / CN2023 / 136312 A VH with at least 98% or at least 99% identity; and / or a VL with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 97%, at least 98%, or at least 99% identity to the amino acid sequence shown in SEQ ID NO: 11. In some specific embodiments, amino acids differing from the amino acid sequence shown in SEQ ID NO: 7 are predominantly (or all) present in the FR region (backbone region). In some specific embodiments, amino acids differing from the amino acid sequence shown in SEQ ID NO: 11 are predominantly (or all) present in the FR region (backbone region). In some specific embodiments, the VH comprises the amino acid sequence shown in SEQ ID NO: 7, optionally having up to four additional amino acid substitutions in the framework region. In some specific embodiments, the VH comprises an amino acid sequence as shown in SEQ ID NO: 7, where X3 is N. Further, & is &=, further, X5 is D. Further, | is (3). Further, 2 is human. Further, X6 is... In some specific embodiments, the VH comprises an amino acid sequence as shown in SEQ ID NO: 7, where X^F,. Further, 2 is 1, further, X6 is L. In some specific embodiments, the VH comprises an amino acid sequence as shown in SEQ ID NO: 7, where X3 is A. Further, + is <3. Further, X5 is G. Further, , is £. Further, X2 is T. Further, X6 is L. In some embodiments, the anti-IL-17RB antibody comprises: with SEQ ID NO: 8, The amino acid sequence shown in any of SEQ ID NO: 9 or 10 has at least 80%, rarely 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence shown in SEQ ID NO: 11. The VH sequence has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence shown in SEQ ID NO: 11. In some specific embodiments, amino acids differing from the amino acid sequence shown in any of SEQ ID NO: 8, 9, 10, or 11 are predominantly (or all) present in the FRIZ (backbone region).In some embodiments, the anti-IL-17RB antibody comprises: a VH having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence shown in SEQ ID NO: 8; and a VL having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence shown in SEQ ID NO: 11. Preferably, the amino acids differing from the amino acid sequence shown in SEQ ID NO: 8 or 11 are predominantly (or all) present in FR|x (backbone region). In some embodiments, the anti-IL-17RB antibody comprises: VH, whose amino acid sequence is shown in SEQ ID NO: 8, and VL, whose amino acid sequence is shown in SEQ ID NO: 11. In some embodiments, the anti-IL-17RB antibody further comprises: a heavy chain constant region (CH) having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 97%, at least 98%, or at least 99% identity to the amino acid sequence shown in SEQ ID NO: 14 or 18. In some specific embodiments, the anti-IL-17RB antibody further comprises: CH, as shown in SEQ ID NO: 14 or 18. In some specific embodiments, the anti-IL-17RB antibody further comprises CH, as shown in SEQ ID NO: 18. In some embodiments, the anti-IL-17RB antibody further comprises a light chain constant region (CL), the light chain constant region being selected from the human K chain and X chain, preferably a constant region of the human K chain. In some embodiments, the anti-EL-17RB antibody further comprises: a CL having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% isotropic to the amino acid sequence shown in SEQ ID NO: 16 / 5. In some specific embodiments, the anti-IL-17RB antibody further comprises the CL shown in SEQ ID NO: 16. In some embodiments, the anti-IL-17RB antibody comprises: an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, or at least 96% isotropic to the amino acid sequence shown in SEQ ID NO: 15 / 19, 20, or 21.The anti-IL-17RB antibody comprises a heavy chain having at least 96%, at least 97%, at least 98%, or at least 99% identity with the amino acid sequence shown in SEQ ID NO: 15-19, 20, or 21. In some embodiments, the anti-IL-17RB antibody comprises a heavy chain having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the sequence shown in SEQ ID NO: 17. In some embodiments, the anti-IL-17RB antibody comprises a light chain having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the sequence shown in SEQ ID NO: 17. In some embodiments, the anti-IL-17RB antibody comprises a light chain having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the sequence shown in SEQ ID NO: 17. WO 2025 / 118126 PCT / CN2023 / 136312 In some embodiments, the anti-IL-17RB antibody is of type IgG1, IgG2, IgG3, or IgG4, preferably type IgG4. In some embodiments, the antigen-binding fragment of the isolated anti-IL-17RB antibody described in this application is selected from Fab fragments, Fab' fragments, F(ab')2 fragments, fd fragments, Fv fragments, dAb fragments, isolated CDR regions, scFv, and nanobodies. In this embodiment, the various variants of the isolated anti-IL-17RB antibody or its antigen-binding fragments described above retain the ability to specifically bind to the antigen IL-17RB. In some embodiments, the pharmaceutical composition further comprises pharmaceutically acceptable excipients. The excipients described herein may be any pharmaceutically acceptable excipient, such as, but not limited to, solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, flow aids, flavoring agents, preservatives, suspending agents, antioxidants, penetration enhancers, pH adjusters, surfactants, diluents, etc. For other pharmaceutically acceptable excipients, please refer to, for example, *Handbook of Pharmaceutical Excipients* (4th Edition), by R.C. Luo et al., translated by Zheng Junmin, 2005, Chemical Industry Press. In some embodiments, the pharmaceutical composition further includes additional therapeutic agents, including but not limited to anti-allergic drugs and analgesics. Anti-inflammatory drugs, anesthetic drugs, and drugs to lower body temperature, etc. In some embodiments, the pharmaceutical composition further includes additional specific dermatitis treatment agents, such as corticosteroids (e.g., hydrocortisone butyrate, mometasone furoate, triamcinolone acetonide / econazole), calcineurin inhibitors (e.g., tacrolimus, pimecrolimus), antibiotics (e.g., acyclovir clavulanate, levofloxacin hydrochloride), and antipruritic drugs (e.g., doxetine hydrochloride).The following are examples of drugs used in this application: diclofenac sodium, ketoprofen, antihistamines (such as loratadine, cetirizine hydrochloride, ebastine, chlorpheniramine maleate), JAK inhibitors (such as ruxolitinib, urobotinib), PDE4 inhibitors (such as criborone, roflumilast), calamine lotion, etc. In some embodiments, the subjects are selected from humans, non-human primates, or murines, preferably humans. Examples: The present application is described in detail below through examples, but this does not mean that the scope of protection of the present application is limited to this. This application has been described in detail, and specific embodiments thereof are disclosed herein. It will be apparent to those skilled in the art that various changes and modifications can be made to the specific embodiments of the present application without departing from the spirit and scope of the present application. Unless otherwise stated, the reagents, materials, instruments, etc. involved in the following examples are all known in the art and commercially available. Example 1: Preparation of anti-IL-17RB antibody. Humanized anti-IL-17RB antibodies hD9040, hD9041, and hD9042 were prepared according to the methods disclosed in the "Experiments" section of WO2020115319A1, and IgG4 antibody hD9043 was prepared according to the methods therein. EUSA testing showed that the humanized antibodies had similar EC50 values ​​for binding human IL-17RB. Biacore analysis showed that the humanized antibodies had good affinity for binding human IL-17RB. The humanized antibodies also exhibited good high-temperature thermal stability, no aggregation problem, low non-specific interaction tendency, and good solubility. (Table 2. Amino acid sequence of anti-IL-17RB antibody hD9040 hD9041 hD9042 hD9043 (IgG4) HCDR1 SYWMN (SEQ ID NO:1) SYWMN (SEQ ID NO:1) SYWMN (SEQ ID NO:1) SYWMN (SEQ ID NO:1) N0:l) SYWMN (SEQ ID NO: 1) HCDR2 RIDPYDSEIQYNQK FKD (SEQ1DNO:12) RIDPYDSEIQYAQK FQG (SEQLDN0:13) RIDPYDSEIQYNQK FKD (SEQ ID NO: 12) RIDPYDSEIQYNQKFKD (SEQ IDNO:12) HCDR3 SGGFDWFAY (SEQ ID NO:3) SGGFDWFAY (SEQ ID NO:3) SGGFDWFAY (SEQ ID NO:3) SGGFDWFAY (SEQ ID NO:3) VH EVQLVQSGAEVKK PGASVKVSCKTSG YTFISYWMNWVRQAPGQGLEWMGRID PYDSEIQWQKFKD RVTLTRDTSISTAY MELSRLRSDDTAV YYCARSGGFDWFA YWGQGTLVTVSS (SEQ ID NO: 9) EVQLVQSGAEVKK PGASVKVSCKTSG YTFISYWMNWVR QAPGQGLEWMGRI DPYDSEIQYAQKFQ GRVTLTRDTSISTA YMELSRLRSDDTA VYYCARSGGFDWF AYWGQGTLVTVSS (SEQ ID NO: 10) QVQLVQSGAEVKK PGASVKVSCKASG YTFISYWMNWVR QAPGQGLEWMGRI DPYDSEIQYNQKF KDRVTMTRDTSIS T AYMELSRLRSDDTA VYYCARSGGFDWF AYWGQGTLVTVSS (SEQ ID NO: " QVQLVQSGAEVKKPGA SVKVSCKASGYTFISYW MNWVRQAPGQGLEW MGRIDPYDSEIQWQKF KDRVTMTRDTSISTAYM ELSRLRSDDTAVYYCAR SGGFDWFAYWGQGTLV TVSS (SEQ ID NO: 8) LCDR1 RASENINSNLA (SEQ ID NO: 4) RASENINSNLA (SEQ ID NO: 4) RASENINSNLA (SEQ ID NO: 4) RASENINSNLA (SEQ ID NO: 4) LCDR2 DVTNLAD (SEQ ID NO: 5) DVTNLAD (SEQ ID NO: 5) DVTNLAD (SEQ ID NO: 5) DVTNLAD ( SEQ ID NO: 5) 3 WO 2025 / 118126 PCT / CN2023 / 136312 Unless otherwise stated, the anti-IL-17RB antibody used in the following examples is the humanized anti-IL-17RB antibody hD904 prepared above. LCDR3 QHFWGPPYT (SEQ ID NO: 6) QHFWGPPYT (SEQ ID NO: 6) QHFWGPPYT(SEQ ID NO: 6) QHFWGPPYT ( SEQ ID NO: 6) VL DIQMTQSPSSLSAS VGDRVTITCRASEN INSNLAWYQQKPG KAPKLLIYDVTNL ADGVPSRFSGSGSG TDYTLTISSLQPEDFATYYCQHFWGPPY TFGGGTKVEIK (SEQIDNO:11) DIQMTQSPSSLSAS VGDRVTITCRASEN INSNLAWYQQKPG KAPKLLLYDVTNL AIXiVPSRFSGSGSG TDYTLTISSLQPEDF ATYYCQHFWGPPY TFGGGTKVEIK (SEQIDNO:11) DIQMTQSPSSLSAS VGDRVTITCRASEN INSNLAWYQQKPG KAPKLLLYDVTNL ADGVPSRFSGSGSG TDYTLHSSLQPEDF ATYYCQHFWGPPY TFGGGTKVEIK (SEQIDNO:11) D1QMTQSPSSLSASVGD miTCRASENINSNLA WYQQKPGKAPKLLLYD VTNLADGVPSRFSGSGS GTOYTUTTSSLQPEDFAT YYCQHFWGPPYTFGGG TKVE1K (SEQIDNOrll) CH ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS^SGA LTSGVHTFPAX / TQSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS RTPE\TCVVVDVSHEDPEVKFNWYVDGVEVHN.\KTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPEEKTISKAKG QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV^EWESNGQ PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGK (SEQ1DNO:14) ASTKGPSVFPLAPCSRS TSESTAALGCLVKDYFP EPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSV VTVPSSSLGTKTYTCNV DHKPSNTKVDKRXTSK YGPPCPPCPAPEFLGGPS VFLFPPKPKDTLMISRTP EVTCVWDVSQEDPEV QFNWYVDGVEVHNAK TKPREEQFNSTYRVVSV LTVLHQDWLNGKEYKCKVSNKGLPSSIEKT1SKA KGQPREPQVYTLPPSQE EMTKNQVSLTCLVKGF YPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFL YSRLTVDKSRWQEGNV FSCSVMHEALHNHYTQ KSLSLSLGK (SEQ ID NO:18) CL RTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD STYSLSSTLTLSKADYEKHKWACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:16) Example 1: Role of anti-IL-17RB antibody in restoring filaggrin levels in vitro. Filaggrin is an important protein used to develop and maintain the skin barrier to protect the host from pathogens, allergens, and UV-induced damage. Clinical studies have clearly shown that clinical severity is associated with barrier impairment in filaggrin-associated eczema AD (Hasebe et al., Jinvest Dermatol., 2009; 129(3): 682-9), and filaggrin levels are downregulated in both unaffected and diseased skin in AD (Howel et al., J Allergy Clin Immunol., 2007; 120(1): 150-155). Furthermore, null mutations in FLG (the gene encoding filaggrin) are a strong genetic factor in Alzheimer's disease (AD). FLG null mutations have been shown to be associated with the severity of AD and its persistence in adulthood (Moosbrugger-Martinz et al., Int J Mol Sci., 2022; 23(10):5318'). During the activation of the helper T cell 2 (Th2) immune response, Th2 cells, due to secretion by Th2-associated immune cells, suppress the expression of filaggrin in keratinocytes, such as in vitro (Howell et al., J Allergy Clin Immunol., 2007; 120(1): 150-155; Howell et al., J Invest Dennatol., 2008; 128(9): 2248-58) and in vivo (H&nzke et al., J Invest Dermatol.- 2016; As shown in 136(3):631-639), since anti-IL-17RB antibodies have previously demonstrated anti-Th2 immune function in PBMC cultures, it is necessary to test the efficacy of anti-IL-17RB antibodies in reversing Th2-driven filaggrin downregulation.HaCaT cells, immortalized human keratinocytes, were used to test the above phenomena in vitro. HaCaT cells were first terminally fractionated into mature keratinocytes and maintained in a medium containing 1.8 mM calcium chloride. Through Western blot analysis, a proof-of-concept (POC) study demonstrated for the first time that direct administration of 50 ng / mL of Hedysarum mongolicum (HDM) extract (Jeon et al., Front Immunol., 2021 Oct 8:12:646316) and an IL-4 / IL-13 mixture (50 ng / mL) to mature HaCaT cells resulted in a significant decrease in filaggrin expression after 24 hours (Figure 1C). These numerical validations are an in vitro system used in our laboratory to study keratinocyte homeostasis. Since IL-25 has no effect on filaggrin levels in mature HaCaT cells, a co-culture system was developed using PBMCs to investigate how an anti-IL-17RB antibody can regulate filaggrin expression in mature HaCaT cells. In short, transwcll WO 2025 / 118126 PCT / CN2023 / 136312 coated with PBMCs was placed on top of each 12-well plate coated with mature HaCaT cells. Total alamins (IL-25-IL-33+TSLP, 20 ng / mL each) and the stated antibody were administered to the whole PBMCs, and the plates were co-cultured with the bottom HaCaT cells for 6 days. Protein was harvested from the HaCaT cells for Western blot analysis. The results showed that the anti-IL-17RB antibody could restore filaggrin water in HaCaT cells in an agonistic-dependent manner (Figure 1D-Figure 1IE), indicating a reduction in TH2-driven downregulation of filaggrin in keratinocytes. Example 2: Development of an animal model for AD research. To investigate the efficacy of the anti-IL-17RB antibody in vivo, 1-fluoro-2,4-dinitrophenyl (DNFB) (a hapten that induces contact dermatitis) was topically applied to female BALB / c mice (Feng et al., Front Med (Lausanne)). In short, prior to topical application, 0.15% DNFB was prepared in a 3:1 mixture of acetone and olive oil. After anesthesia, the skin on the back of mice was shaved and peeled off with tape to disrupt the skin barrier. 0.15% DNFB was applied to the back skin (1cm x 1cm) and ears of mice weekly for 4 weeks, as shown in Figure 2A. Antibodies (anti-IL-17RB antibody or isotype IgG4 control) were administered intraperitoneally to mice in each group using the same administration modality as DNFB. Tissue was harvested from mice 24 hours after the last antibody treatment. Simultaneously, a control group of healthy mice (also known as the non-disease saline group) was established, and these mice were administered physiological saline (100 pL) intraperitoneally using the same administration modality as DNFB.Each mouse was scored for dermatitis based on the severity of erythema, edema, dryness / scarring, and abrasions / erosions observed on the dorsal skin. Each symptom was scored as 0 (none), 1 (mild), 2 (moderate), or 3 (severe), and the total dermatitis score was the sum of these individual scores (Feng et al., Front Med (Lausanne)., 2022:9:843230). Data showed a peak in dermatitis on day 14, with mice recovering by day 2, characterized by reduced inflammation and erosion, and increased hair regrowth (Figure 2B). Quantitative analysis of the dermatitis score confirmed that all doses of anti-IL-17RB antibody significantly improved skin symptoms compared to the IgG4 control group (Figure 2C), and no dermatitis symptoms were observed in any mice in the non-diabetic saline group. Example 3: Inhibition of Th2 Immune Response by Anti-IL-17RB Antibody in AD The overall regulation of the immune response was studied using submental lymph nodes obtained from mice after blood collection. One month later, DNFB significantly induced lymph node swelling, while anti-IL-17RB antibody partially reduced the swelling (Figure 3A). Single cells were isolated from the lymph nodes by trypsin digestion and seeded into 48-well plates for a 1-day DNFB restimulation experiment. The supernatant was collected for ELISA analysis, and the remaining cells were fixed with 4% paraformaldehyde for flow cytometry analysis. Type 2 innate lymphocytes (ILC2) are one of the main cell types driving the Th2 immune response during AD (Salind et al., J Exp Med., 2013: 210(13): 2939-50). (The LC2 population was phylogeneticly classified as Lin- / CD45WST2+ / TCOS+ cells. Results showed that the anti-TL-17RR antibody exhibited a significant trend in reducing the TLC2 population in the submental lymph nodes (Figure 3B). Consistent with the ILC2 results, after DNFB restimulation for one day, the secretion of IL-4, IL-5, and IL-13 by lymph node cells in the anti-IL-17RB antibody treatment group was reduced (Figures 3C-3E). Example 4: Improvement in Skin and Ear Pathology after Anti-IL-17RB Antibody Administration. Histological studies of the prepared ear and skin paraffin sections further demonstrated the efficacy of the anti-IL-17RB antibody in reducing DNFB-induced dermatitis. Briefly, after blood collection, ear and back skin were isolated from the animals, fixed in 4% paraformaldehyde, dehydrated in elevated concentrations of ethanol, and embedded in paraffin. Five-micron sections were cut from the tissue blocks using a microtome and mounted on pre-coated glass slides.) Tissue sections were stained with hematoxylin and eosin to assess structural changes in the skin and ear layer following treatment with DNFB and anti-IL-17RB antibody. Sections were dewaxed twice in xylene and rehydrated in diluted ethanol. After washing several times in water, sections were stained with hematoxylin and eosin.Stain in seminal solution for 1–2 minutes, wash in water to remove overstaining, and incubate in Scott tap water for 1 minute. Dehydrate the sections. Stain in eosin solution for 1–2 minutes, and wash in 100% ethanol to remove overstaining. Wash the stained sections twice in xylene and then mount with DPX mounting medium. Impaired skin barrier function and epidermal thickening are often caused by Th2 inflammation and are used as an indicator of the severity of AD (Kim et al., Allergy Asthma Proc., 2019; 40(2):84–92). Epidermal thickness was calculated in random regions in each image for quantification, and three to four images were analyzed for each animal. Representative images show that one month of DNFB treatment altered the dorsal and auricular skin layers in the following ways: increased epidermal and dorsal thickening, signs of peripheral vasculitis—regular acanthosis—and spongiosis elongation of rete ridges; these symptoms were improved by anti-IL-17RB antibody (Fig. 4A-Fig. 4B), and quantitative analysis further confirmed that anti-IL-17RB antibody significantly reduced DNFB-induced epidermal hyperplasia in the dorsal and auricular skin layers (Fig. 4C-Fig. 4D), indicating that the severity of the disease was significantly reduced with anti-IL-17RB antibody treatment. Example 5: Inhibition of Immune Cell Infiltration after Anti-IL-17RB Antibody Administration. Eosinophils and mast cells are two important cell types involved in the initiation and progression of Alzheimer's disease (AD) (Kawakami et al., Curr Opm Immunol., 2009; 21(6): 666-678; Radonjic-Hoesli et al., Semin ImmunopathoL., 2021; 43(3): 393-409). Eosinophils and mast cells can form a positive circuit, further enhancing the activation of Th2 and Th17, causing AD to transition from the acute phase to the chronic phase. Therefore, it is necessary to elucidate the role of anti-IL-17RB antibody in mast cells and eosinophils. To study mast cell infiltration, skin sections from the ear and back were stained with 0.1% toluidine blue for 2-3 minutes to label mast cells, and then encapsulated in DPX mounting medium for microscopic analysis. Mast cells were labeled as light to dark purple cells under a microscope. 10 WO 2025 / 118126 PCT / CN2023 / 136312 To study eosinophil infiltration, immunohistochemistry was performed on skin sections from the ear and back. Briefly, after dewaxing and rehydration, the sections were quenched in 3% hydrogen peroxide. After washing several times in P3S, the sections were washed in 8% PBS diluted with 0.3% Triton X-100.Blocked in FBS at room temperature for 1 hour. The anti-PRG2 primary antibody was diluted in the same blocking buffer and used to incubate the sections overnight at 4°C. The next day, the sections were washed and stained with HRP-conjugated secondary antibody under RT for 1 hour. Eosinophils appeared brown after DAR substrate application and were mounted on slides using DPX mounting medium. Quantification was performed using ImageJ software. Representative images show that DNFB can significantly induce mast cells and eosinophils to infiltrate the back skin and ear layer, with anti-TL-17RB antibody suppressing these two phenomena in a dose-dependent manner (Fig. 5Ah). Quantification of mast cell number and eosinophil signal intensity further confirms the observations in the back skin (Fig. 5B-5C) and ear (Fig. 5D-5E). Example 6: Inhibition of Th2 inflammation by anti-antibody leads to filaggrin recovery. As previously described, the expansion of TK2 cells leads to Th2 inflammation through increased secretion of TH2 cytokines (such as IL-4 and IL-13), ultimately resulting in downregulation of filaggrin levels in the skin layer. To realize this in our model, tissue sections were again stained by immunohistochemistry with anti-IL-4, anti-IL-13, and anti-filaggrin antiserum. Reactive signaling of IL-4 and IL-13 was confirmed in the epidermis and dorsal layer, consistent with results from submental lymph node cultures. DNFB increased the secretion of IL-4 and IL-3, while anti-IL-17RB antibody, in turn, suppressed their expression in the ear (Fig. 6). Filament expression in the epidermis and dorsal layer was also visualized and characterized, consistent with a reduction in Th2 inflammation in the skin layer. Anti-IL-17RB antibody restored filaggrin levels and may have improved the skin peptide status in DNFB-treated mice (Fig. 7). Overall, Fig. 8 summarizes the beneficial effects of anti-IL-17RB antibody. Anti-IL-17RB antibody can restore the skin peptide barrier and reduce epidermal proliferation by inhibiting Th2 immune responses, reducing eosinophil / mast cell infiltration, and restoring filaggrin expression in the skin layer. For the purposes of describing and disclosing 3, all patents, patent applications and other publications are expressly incorporated herein by reference, provided only because their publication predates application H of this application. All statements regarding the dates of these documents or descriptions of their contents are based on information available to the applicant and do not constitute any admission of the dates of these documents or the accuracy of their contents. Those skilled in the art can make various combinations, modifications, constructs, etc., of embodiments of this application within the spirit and concept of this application, and the resulting solutions also fall within the protection scope of this application. 11 WO 2025 / 118126 PCT / CN2023 / 136312 Claims 1.Use of an isolated anti-IL-17RB antibody, or an antigen-binding fragment thereof, or a pharmaceutical composition comprising thereof, in the preparation of a medicament for treating FLG-related diseases, wherein the antibody comprises: HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:2, and HCDR3 shown in SEQ ID NO:3; and / or, LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5, and LCDR3 shown in SEQ ID NO:6. 2. The use according to claim 1, wherein the FLG-related disease is at least one of atopic dermatitis, allergic rhinitis, eczema, contact dermatitis, urticaria, angioedema, psoriasis, herpetic dermatitis, bullous pemphigoid, bullous epidermolysis bullosa, acne erythematosus, ichthyosis, photodermatitis, or related symptoms thereof. 3. The use as described in claim 1 or 2, wherein the FLG-associated disease is atopic dermatitis or its related symptoms. 4. The use as described in claim 2 or 3, wherein the atopic dermatitis is infantile atopic dermatitis, childhood atopic dermatitis, or adolescent and adult atopic dermatitis. 5. The use as described in any one of claims 2-4, wherein the atopic dermatitis is mild, moderate, or severe atopic dermatitis. 6. The use as described in any one of claims 2-5, wherein the related symptoms of the atopic dermatitis include dry skin, itchy skin, eczematous lesions, xeroderma-related symptoms, palmar dermatographia-related symptoms, white dermatographia, Henoghe's sign, infraorbital folds, periorbital hyperpigmentation (darkness around the eyes), white papules, and low hairline. 7. The use according to any one of claims 1-6, wherein the anti-IL-17RB antibody comprises: HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:12 or 13, and HCDR3 shown in SEQ ID NO:3; and LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5, and LCDR3 shown in SEQ ID NO:6. 8. The use according to any one of claims 1-7, wherein the anti-IL-17RB antibody comprises: HCDR1 shown in SEQ ID NO:1, HCDR2 shown in SEQ ID NO:12, and HCDR3 shown in SEQ ID NO:3; and LCDR1 shown in SEQ ID NO:4, LCDR2 shown in SEQ ID NO:5, and LCDR3 shown in SEQ ID NO:6. 9.10. The use of any one of claims 1-8, wherein the anti-IL-17RB antibody comprises: a VH having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 7; and / or a VL having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 11. 11. The use of any one of claims 1-8, wherein the amino acids differing in the amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 7 are mainly or entirely present in the FR region; and / or, the amino acids differing in the amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 11 are mainly or entirely present in the FR region. 12. The use of any one of claims 1-8, wherein the VH comprises the amino acid sequence shown in SEQ ID NO: 7, optionally the amino acid sequence having amino acid substitutions in up to four additional frame regions. 12. The use of claim 11, wherein the VH comprises the amino acid sequence shown in SEQ ID NO: 7, wherein X1 is N, X4 is K, X5 is D, X6 is Q, X2 is A, and X7 is L. 13. The use of claim 11, wherein the VH comprises the amino acid sequence shown in SEQ ID NO: 7, wherein X1 is E, X2 is T, and / or X7 is L. 14. The use of claim 11, wherein the VH comprises the amino acid sequence shown in SEQ ID NO: 7, wherein X1 is A, X4 is Q, X5 is G, X6 is E, X2 is T, and / or X7 is 1 / 2. 15. The use of any one of claims 1-10, wherein the anti-IL-17RB antibody comprises: a VH having at least 80% identity with the amino acid sequence shown in any one of SEQ ID NO: 8, 9, or 10; and a VL having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 11. 16. The use of claim 15, wherein the amino acids differing in the amino acid sequence having at least 80% identity with any one of SEQ ID NO: 8, 9, 10, or 11 are predominantly or entirely present in the FR region. 17. The use as claimed in claim 15 or 16, wherein the anti-IL-17RB antibody comprises: VH having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 8; and VL having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 11. 18. The use as claimed in any one of claims 1-17, wherein the anti-IL-17RB antibody comprises: its amino acid sequence shown in SEQ ID NO: 8.8. VH, and its amino acid sequence shown in SEQ ID NO: 11, VL. 19. The use of any one of claims 1-18, wherein the anti-IL-17RB antibody further comprises: a heavy chain constant region having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 18 12 WO 2025 / 118126 PCT / CN2023 / 136312 or 14. 20. The use of claim 19, wherein the anti-IL-17RB antibody further comprises the i-chain constant region shown in SEQ ID NO: 18. 21. The use of any one of claims 1-20, wherein the anti-IL-17RB antibody further comprises a human k-chain constant region. 22. The use of claim 21, wherein the anti-IL-17RB antibody further comprises: CL, having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 16. 23. The use of any one of claims 1-22, wherein the anti-IL-17RB antibody comprises: a heavy chain having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 19, 15, 20 or 21; and a light chain having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 17. 24. The use of claim 23, wherein the anti-IL-17RB antibody comprises: a heavy chain having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 19; and a light chain having at least 80% identity with the amino acid sequence shown in SEQ ID NO: 17. 25. The use of claim 24, wherein the anti-IL-17RB antibody comprises: the heavy chain shown in SEQ ID NO: 19; and the light chain shown in SEQ ID NO: 17. 26. The use of any one of claims 1-25, wherein the anti-IL-17RB antibody is of type IgG1, IgG2, IgG3 or IgG4. 27. The use as described in any one of claims 1-26, wherein the antigen-binding fragment is selected from Fab fragments, Fab' fragments, F(ab')2 fragments, Fd fragments, Fv fragments, dAb fragments, isolated CDR regions, scFv, and nano-antibodies. 28. The use as described in any one of claims 1-27, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient. 29. The use as described in any one of claims 1-28, wherein the pharmaceutical composition further comprises an additional therapeutic agent, said additional therapeutic agent comprising: an anti-allergic drug, an analgesic drug, an anti-inflammatory drug, an anesthetic drug, or a drug that lowers body temperature. 30.The use as described in any one of claims 1-29, wherein the pharmaceutical composition further comprises an additional specific dermatitis treatment agent, said additional specific dermatitis treatment agent comprising at least one of glucocorticoids, calcineurin inhibitors, antibiotics, antipruritic drugs, antihistamines, JAK inhibitors, PDE4 inhibitors, and calamine lotion. WO 2025 / 118126 PCT / CN2023 / 136312 B << Western blot 8 Armins ■' « * / « z / ?:々- h»W43ir -----------> ■ V ', HaOaT c Filaggrin D Filagg rin Mediutn —$ 5 35 125 J§G4 ,,,,,',',ww •^,,-',,,,,, ......... . ■ N.sxxs . •' ..V.\x -xw.xxx- .'■■..X'SSSs. WsvSS.sx- ww SAPDH ® 1 to! a <armfn WO 2025 / 118126 PCT / CN2023 / 136312 in A 29 3022Dayl 158 ♦ ♦} t Endpoint * Saiine ★ lgG4 ,.■ hi)9W-10mpk ,>,. hDms-Smpk hD9iM3-2.5mpk DNF8 DAY ffl2 WO 2025 / 118126 PCT / CN2023 / 136312 3 / 7 WO 2025 / 118126 PCT / CN2023 / 136312 4 / 7 WO 2025 / 118126 PCT / CN2023 / 136312 5 / 7 A Shift Wait ceHEosinophil ED T T IWui^ne (nn> $t <e<Q TOJuitfin** (m*5t iiSii} WS2 ...... •、•■'<> *>■■ *': Mast ce^l u' hD904.M@mpk MHW-5mpk hD9«M ?-2.5mpk X / 'i>-.,..<>... ___ ,1,.. .Illi 3 々MWWfwpiJdSfb / z ±^rx~— / / ■» :_、、—L、. I):NFB ULUl:liiiii ', ; V ;• x;.:>- ■ . ■ * ■ . ̂ • / :*': r ». 、, '■.:• : J 'J • 、‘、 ■• : • ■ 、\ f. / . ...:.;v、...〜 •< . 、 」:■ WK? V X . V ^ . .:•:: :: ,:: .s: .D • *t * .• *..*** • ’•• ' x > ** . ffl5 WO 2025 / 118126 PCT / CN2023 / 136312 A -V*:- Y. '• ' !ty*)W &D9043 tWi C iL4 jn ear cterwai B tgS canwiri 、.《'、»■"< *、、 ■>,•、,- hlWW ^O|WP& U3 ift ear dermal S:;、、 、,• 0》、: Saittx? WO 2025 / 118126 PCT / CN2023 / 136312 A Saline IgG control hD9043lOmpk hD9043 5mpk B Filaggrin expression :’*»■ S8 INTERNATIONAL SEARCH REPORT International application No. PCT / CN2023 / 136312 A. CLASSIFICATION OF SUBJECT MATTER A61K39 / 395(2006.01)i; C07K 16 / 28(2006.01)i; C07K 16 / 24(2006.01)i According to International Patent ClassificatioD (IPC) or to both national classification and IPC B. FIELDS SEARCHED Minimum documentation searched (classification system followed by classification symbols) IPC: A61K C07K Documentation searched other than minimum documentation to the extent that suchDocuments are included in the fields searched. Electronic database consulted during the international search (name of database and, where practicable, search terms used): CNABS, CNTXT, WPABS, WPABSC, DWP1, VEN, ENTXT, ENTXTC, CNK1, CJFD, 1S1. Web of Science, GenBank, STNext, China Patents Biological Sequence Search System: Search based on sequences 1-21. Search on sequences 1-21. China Antibody Pharmaceutical Co., Ltd., Xu Zhanwei, Lin Qieheng, Li Weimin, Hu Weicong, Zhou Qixiang, Liang Ruian. Antibody, atopic dermatitis, filaggrin. Interleukin-17 receptor β, EL-17RB, IL17RB, FLG, filaggrin, atopic dermatitis. AD, hD9043, antibody C. DOCUMENTS CONSIDERED TO BE RELEVANT Category* Cilulion of document, with indiuaiioo, where appropriate, of the relevani passages Relevani to claim No. A CN 113260631 A (LIFEARC) 13 August 2021 (2021-08-13) description, paragraphs

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[0013] and

[0129] 1-30 A WO 2023160610 Al (SINOMAB BIOSCEENCE LTD.) 31 August 2023 (2023-08-31) claims 1-22 1-30 A CN 116802210 A (UNITED KINGDOM RESEARCH AND rNNOVATTON) 22 September 2023 (2023-09-22) desenption, paragraphs

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[0032] 1-30 A US2012020985 Al (MCKENZIE ANDREW NEIL JAMES et al.) 26 January 2012 (2012-01-26) description, paragraphs

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[0026] 1-30 I I Further documents are listed in the continuation of Box C. See patent family annex. * Special categories of cited documents: ‘t’ later document published after the international filing date or priority ‘.A” document defining the general state of the art which is not considered date and not in conflict with the application but cited to understand the to be of particular relevance principle or theory underlying the invention • D” document cited by the applicant in the intemationai application “X” document of particular relevance; the claimed invention canaot be “E” earlier appOcation or patent but pubUshed on or after the international considered novel or cannot be considered to involve aa inventive step filing dnrp when Che document is taken alone “L” document which may throw doubts oa priority claim(s) or which is “Y1’ docuineal of particular relevance; theclaimed invention cannot be cited to establish the nuhlication date of another citation or other considered to involve an inventive step when the document is special reason (as specified) combined with oae or more other such documeats, such combination “0” document referring to an oral disclosure, use, exhibition or other being obvious to a person skilled in the art means •‘&” document member of the same patent family •T” document published prior to the international filing date but later than the priority date claimed Date of the actual completion of the international search 30 July 2024 Date of mailing of the international search report 05 August 2024 Name and mailing address of the ISA / CN China National Inteilectual Property Administration (ISA / CN) China No. 6, Xitucheag Road. Jimenqiao, Haidian District, Beijing 100088 Authorized officer Telephone No. Form PCT / ISA / 210 (.second sheet) (July 2022) INTERNATIONAL SEARCH REPORT International application No. PCT / CN2023 / 136312 Box No. INucleotide and / or amino acid sequence(s) (Continuation of item l.c of the first sheet) 1. With regard to any nucleotide and / or amino acid sequence disclosed in the international application, the international search was carried out ou the basis of a sequence listing: a. b. / forming part of the international application as filed. _ furnished subsequent to the international filing date for the purposes of international search (Rule 13rer.l(a)), accompanied by a statement to the effect that the sequence listing does not go heyond the disclosure in the international application as filed. 2. With regard to any nucleotide and / or amino acid sequence disclosed in the international application, this report has been established to the extent that a meaningful search could be carried out without a WIPO Standard ST.26 compliant sequence listing. 3. Additional comments: Form PCT / ISA / 210 (continuation of first sheet) (July 2022) INTERNATIONAL SEARCH REPORT Informatiou on patent family membersInternational application No. PCL7CN2023 / 136312 Patent docunieat cited in search report CN 113260631 A WO 2023160610 Al CN 116802210 A US 2012020985 Al Publication date (day / month / year) Patent family member(s) Publication date (day / month / year) 13 August 2021 EP 3891180 Al 13 October 2021 CA 3122039 Al 11 Juue 2020 WO 2020115319 Al 11 June 2020 JP 2022511062 A 28 January 2022 US 2022041740 Al 10 February 2022 GB 201820006 DO 23 January 2019 AU 2019394099 Ai 22 July 2021 31 August 2023 None 22 September 2023 WO 2022101489 Al 19 May 2022 GB 202018015 DO 30 December 2020 EP 4244250 Al 20 September 2023 JP 2023550554 A 01 December 2023 26 January 2012 CA 2757104 Al 14 October 2010 CA 2757104 C 24 July 2018 EP 2417161 Al 15 February 2012 EP 2417161 Bl 24 May 2017 DK 2417161 T3 31 July 2017 WO 2010116123 Al 14 October 2010 US 2014044718 Al 13 February 2014 US 8852589 B2 07 October 2014 AU 2010233535 Al 03 November 2011 AU 2010233535 B2 27 February 2014 JP 2012522531 A 27 September 2012 .TP5767625 B2 19 August 2015 US 8586037 B2 19 November 2013 ES 2633767 T3 25 September 2017 GB 0905972 DO 20 May 2009 HK 1170745 A1 08 March 2013 Form PCT / ISA / 210 (parent family aanex) (July 2022) International Search Report International Application Number PCT / CN2023 / 136312 A. Subject Classification A61K39 / 395(2006.01)i; C07K 16 / 28(2006.01)i; C07K 16 / 24(2006.01)i According to the International Patent Classification (ITC) or simultaneously according to both the ITC and PC classifications B. Search field (minimum; limit literature classification system and classification number) IPC: A61K C07K ft contains search literature in the right search field other than the minimum limit literature. The databases consulted during international searches (database name and search terms used (if used)) CNABS; CNTXT; WPABS; WPABSC; DWP[; VEN:ENTXT; ENTXTC; CNKI; CJFD; ISI Web of Science; GenBank; STNext; China 3 Patent Biological Sequence Search System:. Search based on sequence 1-21, China Antibody Pharmaceutical Co., Ltd., Xu Zhanwei. Lin Liheng, Li Weimin, Hu Huicong, Zhou Qixiang. Liang Ruian. Antibody. Atopic dermatitis. Filamentin, interleukin-17 receptor B. IL-17RB. IL17RB. FLG, Glaggriri. atopic dermatitis, AD, HD9043, antibody C. Related document type* Referenced document, if necessary, refers to the relevant paragraph Related claims A CN 113260631 A (Life Arc Company) August n, 2021 (2021-08-13) Specification No.

[0009]

[0013] ,

[0129] Paragraphs 1-30 A WO 2023160610 A1 (SINOMAB BfOSCIFNCF (.TD) August 31, 2023 (2023-08-31) Claims 1-22 1-30 A CN 116802210 A (Institute for Research and Innovation) September 22, 2023 (2023-09-22) Specification No. 1

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[0032] Paragraphs 1-30 A US 2012020985 A1(MCKENZIE ANDREW NEIL JAMES et al) January 26, 2012 (2012-01-26) Paragraphs 1-30 of description 1 [00111-(0026] □ The rest of the documents are listed on the continuation page in Column C. □ See the family patent attachment. *Specific types of cited documents: "A" documents representing the general state of the prior art that are not considered particularly relevant "D" documents cited by the applicant in the international application "E" earlier applications or patents published on or after the international filing date "O" documents relating to oral disclosure, use, exhibition or other means of disclosure "P" documents published before the international filing date but after the claimed priority date "T" documents for the understanding of prior art when cited, where the application claims that the disclosure does not go beyond the originally filed content "&" documents of the same patent family Date of actual completion of international search Date of mailing of international search report July 30, 2024 August 5, 2024 Name and mailing address of ISA / CN Authorized Officer China National Intellectual Property Administration 6 Xitucheng Road, Jimenqiao, Haidian District, Beijing, China, 100088 Ping Guan Telephone (+86) 0512-88996446 Form PCT / ISA / 210 (Page 2) (July 2022) International application number International Search Report PCT / CN2023 / 136312 1. With respect to any nucleotide and / or amino acid sequences disclosed in the international application, the international search is carried out based on the sequence listing as follows: 2. b. ☐ Submitted as part of the international application: ☐ Submitted after the international application for the purpose of international search (Rule 13ter.1(a)), ☐ Accompanied by a statement that the sequence listing does not go beyond the scope of the disclosure of the international application as filed. 2. ☐ This report is made to the extent that meaningful search can be conducted, without receiving a sequence listing complying with WIPO ST.26 standard, and taking into account any nucleotide and / or amino acid sequences disclosed in the international application. 3. Additional comments: Column I Nucleotide and / or amino acid sequence (continuation of item 1.c on page 1) Form PCT / ISA / 210 (continuation of page 1) (July 2022) PCT / CN2023 / 136312 ^0 ( / 0) CN 113260631 A August 13, 2021 EP 3891180 A1 October 13, 2021 CA 3122039 A1 June 11, 2020 WO 2020115319 A1 June 11, 2020 JP 2022511062 A January 28, 2022 US 2022041740 A1 February 1, 2022 GB 2018200-06 January 23, 2019 AU 2019394099Al 2021^7^220 WO 2023160610 Al 2023^8^310 CN 116802210 A 2023^9^220 WO 2022101489 Al 2022^5^190 GB 202018G15 DO 2020^12^300 EP 4244250 Al 2023^9^200 JP 202355055^ A 2023^12^10 US 2012020985 Al 2012^1^260 CA 27571(X Al 2010^10^140 CA 27571(XC 2018^7 / ]24td FP 2417161 A1 2012^2^150 EP 2417161 Bl 2017^5^240 DK 2417161 T3 2017^7^310 WO 2010116123 A1 2010^10^140 US 2014044718 Al 2014^2^130 US 8852589 B2 2014^10^70 AU 2010233535 Al 201l^llJ]3S AU 2010233535 B2 2014^2^270 JP 2012522531 A 2012^9^270 JP 5767625 B2 2015^8^190 US 8586C-37 B2 2013^11^190 ES 2633767 T3 2017^9^250 GB 0905972 DO 2009^5^200 HK 1170745 Al 2013^3^80 PCT / ISA / 210 (2022^7^) (19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number CN 122396504 A (43) Application Publication Date 2026. 07. 14 (21) Application Number 202380104593.3 (22) Application Date 2023.12.05 (85) PCT International Application Entering National Phase Date 2026.06.05 (86) Application Data of PCT International Application PCT / CN2023 / 136312 2023.12.05 (87) Publication data of PCT international application W02025 / 118126 ZH 2025.06.12 (74) Patent agency Beijing Xinhui Yongguang Intellectual Property Agency Co., Ltd. 11290 Patent attorney Dong Shihao Yang Guoqiang (51) Int. CI. A61K 39 / 395(2006.01) C07K )6 / 28(2006.01) C07K76 / 24 (2006.01) (71) Applicant: China Antibody Pharmaceutical Co., Ltd. Address: 303 & 305-307, 15 Science Park West, Hong Kong Science Park, Pak Shek Kok, New Territories, Hong Kong (72) Inventors: Xu Zhanwei, Lin Liheng, Li Weimin, Hu Weicong, Zhou Qixiang, Liang Rui'an (54) Invention Title: Use of Anti-IL-17RB Antibody, or its Antigen-Binding Fragment or Composition (57) Abstract: This application discloses an isolated anti-IL-17RB antibody, or its antigen-binding fragment, or a pharmaceutical composition containing the same for the treatment of FLG-related diseases, wherein the anti-IL-17RB antibody, or its antigen-binding fragment, or the pharmaceutical composition containing the same can reverse the downregulation of Th2-driven filaggrin expression, thereby effectively treating FLG-related diseases. VS g 9 6 s - 3

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