Bispecific antibody and application thereof

Abstract

The invention provides a bispecific antibody targeting TSLP and IgE (Immunoglobulin E) and application of the bispecific antibody. The bispecific antibody targeting the TSLP and the IgE has high specificity and affinity for binding with the TSLP and the IgE, and can be used for treating allergic diseases and autoimmune inflammatory diseases related to the TSLP and the IgE.

Description

Technical Field

[0001] This invention relates to the field of biotechnology, and more particularly to a bispecific antibody and its applications. Background Technology

[0002] Allergic diseases and autoimmune inflammatory diseases (such as asthma, atopic dermatitis, and allergic rhinitis) have become significant public health issues worldwide. The core pathological mechanisms of these diseases involve the abnormal activation of multiple immune pathways, among which thymic stromal lymphopoietin (TSLP) and immunoglobulin E (IgE) are key molecules mediating disease development and progression, leading to tissue damage and clinical symptoms.

[0003] TSLP is a cytokine secreted by epithelial cells (such as airway epithelium and skin keratinocytes) in response to external stimuli (such as allergens, pollutants, and mechanical damage). Under physiological conditions, it participates in the early development and homeostasis regulation of the immune system, especially playing a role in initiating the initial immune response in mucosal immunity. However, under pathological conditions, overexpression of TSLP can induce inflammation through the following pathways: On the one hand, TSLP can directly activate immune cells such as dendritic cells and mast cells, promoting Th2 immune responses and inducing the release of Th2 cytokines such as IL-4, IL-5, and IL-13, leading to pathological changes such as eosinophil infiltration and increased mucus secretion; on the other hand, TSLP can upregulate the expression of IgE receptors on the surface of B cells, enhancing the synthesis and secretion of IgE, forming a positive amplification loop of "TSLP-Th2-IgE". Current research has confirmed that high expression of TSLP is closely related to the severity of diseases such as severe asthma, moderate to severe atopic dermatitis, and allergic rhinitis, and is one of the core driving factors for the progression of these diseases.

[0004] IgE is an immunoglobulin produced by B cells. Under physiological conditions, it mainly participates in anti-parasitic immunity, and its content in the normal human body is extremely low. However, in allergic diseases, allergens (such as pollen, dust mites, and food proteins) can activate Th2 cells through antigen-presenting cells, prompting B cells to undergo class switching and secrete large amounts of IgE. These pathological IgEs can induce allergic reactions through two pathways: First, they bind to high-affinity IgE receptors (FcεRI) on the surface of mast cells and basophils, putting the cells in a "sensitized" state. When exposed to the same allergen again, the allergen cross-binds with IgE, triggering cell degranulation and releasing bioactive mediators such as histamine and leukotrienes, rapidly inducing acute allergic symptoms such as skin itching, urticaria, and bronchospasm. Second, IgE can regulate the activation of B cells and T cells through low-affinity receptors (FcεRII), further promoting the release of inflammatory factors and participating in the maintenance of chronic inflammation. Therefore, IgE is a key mediator of the "immediate phase reaction" and "delayed phase reaction" in allergic diseases.

[0005] For the aforementioned targets, some single-target antibody drugs have been applied clinically or entered clinical trial stages, demonstrating certain therapeutic effects. However, existing single-target antibodies still have significant limitations and are insufficient to meet clinical needs:

[0006] Limitations of efficacy: The inflammatory network of allergic diseases has multi-pathway synergistic characteristics, and single-target blockade cannot comprehensively inhibit inflammation. For example, although anti-TSLP antibodies can inhibit the initiation of Th2 pathways, they cannot block the acute response mediated by already generated IgE; although anti-IgE antibodies can reduce acute symptoms, they cannot prevent TSLP-driven Th2 cell activation and new IgE synthesis, resulting in low response rates (only about 40%-60%) in some patients (especially severe patients with high TSLP expression) and a high relapse rate after drug withdrawal.

[0007] The drawbacks of combination therapy: Anti-TSLP and anti-IgE antibodies have different pharmacokinetic characteristics (such as half-life and tissue distribution differences), which may lead to difficulty in matching doses and increase the risk of adverse reactions (such as injection site reactions and increased risk of infection); at the same time, the multiple injections can reduce patient compliance, especially in children and adolescents.

[0008] Limited applicable population: Some patients have synergistic activation of the TSLP and IgE pathways (such as simultaneous elevation of TSLP and abnormal IgE levels), and single-target antibodies cannot cover these "dual-pathway driven" patients, resulting in a treatment gap.

[0009] Therefore, there is an urgent need to develop a treatment that synergistically blocks two key pathways to overcome the limitations of single-target antibodies, reduce the drawbacks of combination therapy, and provide more efficient and safer treatment options for patients with allergic diseases. This has significant clinical value and application prospects. Summary of the Invention

[0010] Through inventive research, the inventors have obtained a bispecific antibody targeting TSLP and IgE after multiple rounds of screening and optimization, comprising:

[0011] (a) Targeting the first binding functional region of TSLP; and

[0012] (b) Targeting the second binding functional region of IgE.

[0013] In one specific implementation, the first binding functional region of the targeted TSLP includes a heavy chain variable region (VH) and / or a light chain variable region (VL); wherein the heavy chain variable region includes heavy chain complementarity-determining region (HCDR)1, HCDR2, and HCDR3; and the light chain variable region includes light chain complementarity-determining region (LCDR)1, LCDR2, and LCDR3.

[0014] The bispecific antibody targeting TSLP and IgE has high specificity and affinity for binding to TSLP and IgE, and can be used to treat allergic diseases and autoimmune inflammatory diseases related to TSLP and IgE. Figure 1 The chromatogram of the purification of the TSLP×IgEκλ ​​bispecific antibody using Capto S ImpAct ion exchange chromatography is shown. Figure 2 The mass spectrum of the purified TSLP×IgEκλ001 sample is shown using mass spectrometry F(ab)2 molecular weight detection. Figure 3 The mass spectrum of the purified TSLP×IgEκλ002 sample is shown using mass spectrometry F(ab)2 molecular weight detection. Detailed Implementation

[0015] Terminology Definition

[0016] Unless otherwise defined, all technical terms used herein have the same meaning as understood by one of ordinary skill in the art.

[0017] Although the numerical ranges and parameter approximations shown in the broad scope of this invention are intended to be approximated, the values ​​described in the specific embodiments are recorded as accurately as possible. However, any numerical value inherently contains a certain degree of error due to the standard deviation present in their respective measurements. Furthermore, all ranges disclosed herein should be understood to encompass any and all subranges contained therein. For example, the stated range “1 to 10” should be considered to include any and all subranges between the minimum value 1 and the maximum value 10 (inclusive); that is, all subranges beginning with a minimum value of 1 or greater, such as 1 to 6.1, and subranges ending with a maximum value of 10 or less, such as 5.5 to 10. Additionally, any references marked “incorporated herein” should be understood to be incorporated herein in their entirety.

[0018] It should also be noted that, as used in this specification, the singular form includes the plural form of the object it refers to, unless it is clearly and explicitly limited to a single object.

[0019] The terms used herein, such as “comprising,” “containing,” “containing,” and “including,” are not intended to be limiting. Furthermore, unless otherwise stated, “or” or “or” means “and / or.”

[0020] All patents, patent applications, publications cited in this document, or descriptions herein are incorporated herein by reference in their entirety.

[0021] Unless otherwise specifically stated otherwise, the practice of this invention will take place using conventional methods of virology, immunology, microbiology, molecular biology, and recombinant DNA techniques within the scope of the art, or in the same sense as commonly understood by one of ordinary skill in the art to which this invention pertains. Many of these are described below for illustrative purposes, and such techniques are well described in the literature.

[0022] As used in this invention, the term "antibody" refers to an antibody in its substantially intact form, as opposed to an antibody fragment. Specifically, the "antibody" involved in this invention is preferably an antibody in its intact form, having a symmetrical structure with four polypeptide chains, namely two heavy chains (H chains) and two light chains (L chains), which are linked by disulfide bonds and non-covalent bonds to form a monomer molecule consisting of four polypeptide chains.

[0023] As used in this invention, the term "antigen-binding fragment" encompasses a portion of a complete antibody, preferably the antigen-binding region and / or variable region of the complete antibody. Examples of antibody fragments include Fab, Fab′, F(ab′)2, and Fv fragments, etc.

[0024] As used herein, the term "humanized antibody or antigen-binding fragment" refers to a human immunoglobulin (receptor antibody) in which residues of the receptor's HVR are replaced by residues of the HVR from a non-human species (donor antibody) having the desired specificity, affinity, and / or ability, such as a mouse, rat, rabbit, or non-human primate. In some cases, the framework ("FR") residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, the humanized antibody or antigen-binding fragment may contain residues not present in the receptor or donor antibody. These modifications can be made to further improve antibody properties, such as binding affinity. Generally, the humanized antibody or antigen-binding fragment will contain at least one, and typically substantially all, of two variable domains, wherein all or substantially all of the hypervariable loops correspond to those of the non-human immunoglobulin sequence, and all or substantially all of the FR regions are those of the human immunoglobulin sequence, but the FR regions may include one or more individual FR residue substituents that improve antibody properties, such as binding affinity, isomerization, immunogenicity, etc. Humanized antibodies may optionally also contain at least a portion of the immunoglobulin constant region (Fc) that is typically found in human immunoglobulins. For further details, see, for example, Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992). See also, for example, Vaswani and Hamilton, Ann. Allergy, Asthma & Immunol. 1: 105-115 (1998); Harris, Biochem. Soc. Transactions 23: 1035-1038 (1995); Hurle and Gross, Curr. Op. Biotech. 5: 428-433 (1994); and U.S. Patents 6,982,321 and 7,087,409.

[0025] As used herein, the term "human antibody" is an antibody having an amino acid sequence corresponding to an antibody produced by a human and / or prepared using any of the techniques for preparing human antibodies. This definition of human antibody explicitly excludes humanized antibodies containing non-human antigen-binding residues. A variety of techniques known in the art, including phage display libraries, can be used to prepare human antibodies. Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991). Methods described in the following literature can also be used to prepare human monoclonal antibodies: Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boerner et al., J. Immunol., 147(1):86-95 (1991). See also van Dijk and van de Winkel, Curr. Opin. Pharmacol., 5:368-74 (2001). Human antibodies can be prepared by administering an antigen to a transgenic animal that has been modified to produce such antibodies in response to antigen attack, but whose endogenous loci have been disabled, for example, immunized heterologous mice (see, for example, U.S. Patents 6,075,181 and 6,150,584 relating to XENOMOUSE™ technology). See also, for example, Li et al., Proc. Natl. Acad. Sci. USA, 103:3557-3562 (2006), relating to human antibodies produced via human B-cell hybridoma technology.

[0026] As used in this invention, the term "CDR" (complementarity-determining region) refers to a hypervariable region, as defined by the Kabat system. See Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, Md. (1991). Other definitions of CDR exist, such as IMGT, Chothia, AbM, Contact, etc.

[0027] Unless otherwise specified, the immunoglobulin residues involved in this invention are numbered using the Kabat index.

[0028] As used in this application, the term "Fc region" refers to the heavy chain structure portion including the constant region CH1 domain, the hinge region, the heavy chain constant region CH2 domain, and the heavy chain constant region CH3 domain (i.e., CH1-Hinge-CH2-CH3). The hinge region, heavy chain constant region CH2 domain, and heavy chain constant region CH3 domain in the Fc region often form dimers via disulfide bonds. Currently, the most commonly used fusion partner is the Fc segment of immunoglobulin IgG, and the antibody Fc is part of the antibody constant region. Fusion with the Fc segment increases the stability of the fusion molecule and prolongs its in vivo half-life by increasing molecular weight and through FcRn-mediated recycling mechanisms. Simultaneously, the Fc segment can mediate various biological functions such as ADCC and CDC. However, such fusion proteins lack the variable region of the antibody, and their pharmacology and efficacy mainly depend on the functional molecule fused with the Fc segment. Human immunoglobulin G has four subtypes, and the biological activities of different immunoglobulin G subtypes vary. Currently, IgG1 antibodies are the most widely used. In recent years, with the expansion of new indications and the emergence of antibody drugs with new mechanisms of action, IgG2 and IgG4 subtypes with lower cytotoxicity have gained attention. In this invention, the "Fc region" is preferably the Fc region of an IgG1 antibody or an IgG4 antibody.

[0029] As used herein, the term "specificity" refers to an antigen-binding protein or antibody that selectively recognizes a specific epitope of an antigen. For example, natural antibodies are monospecific. As used herein, the terms "bispecific" or "multispecific" indicate that an antigen-binding protein or antibody has two or more antigen-binding sites, wherein at least two bind different antigens or different epitopes of the same antigen.

[0030] As used in this article, the terms "divalent," "trivalent," and "tetravalent" represent "valence," which indicates the specified number of binding sites present in an antigen-binding protein or antibody molecule. Therefore, the terms "divalent," "trivalent," and "tetravalent" indicate that there are two, three, and four binding sites, respectively, in an antigen-binding protein or antibody molecule.

[0031] As used herein, the term "identity" refers to the percentage of amino acid residues in a candidate sequence that are identical to amino acid residues in a specific peptide or polypeptide sequence after sequence alignment and cleavage introduction (if necessary) to achieve the maximum percentage of sequence identity, without considering any conserved substitutions as part of sequence identity. Alignments used to determine the percentage of amino acid sequence identity can be performed in various ways within the scope of the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or MEGALIGN™ (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignments, including any algorithms required to achieve maximum alignment across the full length of the sequences being compared.

[0032] As used in this invention, the term "treatment" refers to a clinical intervention designed to alter the natural course of a treatment in an individual or cell during a clinicopathological process. Desired therapeutic effects include reducing the rate of disease progression, improving or alleviating the disease state, and alleviating or improving prognosis. For example, if one or more symptoms associated with the treated disease or condition (such as cancer, inflammation, or an autoimmune disease) are reduced or eliminated.

[0033] As used in this invention, "effective amount" refers to the amount of a drug or pharmaceutical agent that is effective in treating a subject's disease or symptom. In the case of cancer, the effective amounts of the anti-VEGF single-domain antibody-binding fragment, bispecific antibody, multispecific antigen-binding construct, pharmaceutical composition, and immunoconjugate provided in this application may reduce the number of cancer cells; reduce tumor size; inhibit (i.e., slowly to a certain extent and preferably prevent) cancer cell infiltration into surrounding organs; inhibit (i.e., slowly to a certain extent and preferably prevent) tumor cancer cell metastasis; inhibit tumor growth to a certain extent; and / or alleviate one or more symptoms associated with cancer to a certain extent. As understood in the clinical setting, an effective amount of a drug, compound, or pharmaceutical composition may or may not be combined with another drug, compound, or pharmaceutical composition. Therefore, an "effective amount" may be considered in the context of administration of one or more therapeutic agents, and if combined with one or more other pharmaceutical agents, it may be considered that an effective amount of a single agent can achieve or realize the desired result.

[0034] As used in this invention, the "subject" is preferably a mammal, including but not limited to humans, cattle, horses, felines, canines, rodents, or primates. In some embodiments, the individual is a human.

[0035] Specifically, this application discloses the following implementation scheme:

[0036] Antigen binding region combination

[0037] Implementation Scheme 1. This application provides a bispecific antibody targeting TSLP and IgE, comprising:

[0038] (a) Targeting the first binding functional region of TSLP; and

[0039] (b) Targeting the second binding functional region of IgE.

[0040] Implementation Scheme 2. The bispecific antibody targeting TSLP and IgE according to Implementation Scheme 1, wherein the first binding functional region targeting TSLP includes a heavy chain variable region (VH) and / or a light chain variable region (VL); wherein the heavy chain variable region includes heavy chain complementarity-determining regions (HCDR)1, HCDR2, and HCDR3; and / or the light chain variable region includes light chain complementarity-determining regions (LCDR)1, LCDR2, and LCDR3.

[0041] Implementation Scheme 3. A bispecific antibody targeting TSLP and IgE according to Implementation Scheme 1 or 2, wherein the first binding functional region targeting TSLP includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four or five heavy chain variable regions and / or one, two, three, four or five light chain variable regions.

[0042] Implementation Scheme 4. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 3, wherein the first binding functional region targeting TSLP includes one or more heavy chain variable regions, and the more than one heavy chain variable regions are connected by linkers; and / or

[0043] The first binding functional region of the targeted TSLP includes one or more light chain variable regions, which are connected by connectors; and / or

[0044] The heavy chain variable region and the light chain variable region of the first binding functional region of the targeted TSLP are connected by a connector.

[0045] Implementation Scheme 5. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 4, wherein the first binding functional region targeting TSLP includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:1; the first binding functional region targeting TSLP includes a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:5.

[0046] Implementation Scheme 6. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 5, wherein the first binding functional region targeting TSLP includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:9; the first binding functional region targeting TSLP includes a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:13.

[0047] Implementation Scheme 7. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 6, wherein the first binding functional region targeting TSLP includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:17; the first binding functional region targeting TSLP includes a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:21.

[0048] Implementation Scheme 8. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 7, wherein the first binding functional region targeting TSLP includes a heavy chain variable region, wherein the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region are HCDR1, HCDR2 and HCDR3 of VH with the sequence SEQ ID NO:25.

[0049] Implementation Scheme 9. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 8, wherein the first binding functional region targeting TSLP includes a heavy chain variable region, wherein the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region are HCDR1, HCDR2 and HCDR3 of VH with the sequence SEQ ID NO:26.

[0050] Implementation Scheme 10. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 9, wherein the first binding functional region targeting TSLP includes two heavy chain variable regions, wherein the HCDR1, HCDR2 and HCDR3 of the first heavy chain variable region are HCDR1, HCDR2 and HCDR3 of VH with the sequence SEQ ID NO:25, and the HCDR1, HCDR2 and HCDR3 of the second heavy chain variable region are HCDR1, HCDR2 and HCDR3 of VH with the sequence SEQ ID NO:26.

[0051] Implementation Scheme 11. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 10, wherein the first binding functional region targeting TSLP includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:39; the first binding functional region targeting TSLP includes a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:43.

[0052] Implementation Scheme 12. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 11, wherein the first binding functional region targeting TSLP includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:47; the first binding functional region targeting TSLP includes a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:51.

[0053] Implementation Scheme 13. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 12, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:55; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:59.

[0054] Implementation Scheme 14. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 13, wherein the first binding functional region targeting TSLP includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:63; the first binding functional region targeting TSLP includes a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:67.

[0055] Implementation Scheme 15. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 14, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:71; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:75.

[0056] Implementation Scheme 16. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 15, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:79; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:83.

[0057] Implementation Scheme 17. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 16, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:87; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:91.

[0058] Implementation Scheme 18. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 17, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:95; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:96.

[0059] Implementation Scheme 19. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 18, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:97; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:98.

[0060] Implementation Scheme 20. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 19, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:119; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:120.

[0061] Implementation Scheme 21. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 20, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:123; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:124.

[0062] Implementation Scheme 22. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 21, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:198; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:202.

[0063] Implementation Scheme 23. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 22, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO: 2-4, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO: 6-8, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0064] Implementation Scheme 24. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 23, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:10-12, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:14-16, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0065] Implementation Scheme 25. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 24, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:18-20, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:22-24, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0066] Implementation Scheme 26. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 25, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:27-29, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0067] Implementation Scheme 27. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 26, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:30-32, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0068] Implementation Scheme 28. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 27, wherein the first binding functional region targeting TSLP includes two heavy chain variable regions, wherein HCDR1, HCDR2 and HCDR3 of the first heavy chain variable region respectively contain the amino acid sequences shown in SEQ ID NO:27-29, or amino acid sequences having 1-2 amino acid mutations compared to them, and HCDR1, HCDR2 and HCDR3 of the second heavy chain variable region respectively contain the amino acid sequences shown in SEQ ID NO:30-32, or amino acid sequences having 1-2 amino acid mutations compared to them.

[0069] Implementation Scheme 29. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 28, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:33-35, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0070] Implementation Scheme 30. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 29, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:36-38, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0071] Implementation Scheme 31. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 30, wherein the first binding functional region targeting TSLP includes two heavy chain variable regions, wherein HCDR1, HCDR2 and HCDR3 of the first heavy chain variable region respectively contain the amino acid sequence shown in SEQ ID NO:33-35, or an amino acid sequence having 1-2 amino acid mutations compared to it, and HCDR1, HCDR2 and HCDR3 of the second heavy chain variable region respectively contain the amino acid sequence shown in SEQ ID NO:36-38, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0072] Implementation Scheme 32. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 31, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:40-42, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:44-46, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0073] Implementation Scheme 33. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 32, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:48-50, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:52-54, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0074] Implementation Scheme 34. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 33, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:56-58, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:60-62, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0075] Implementation Scheme 35. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 34, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:64-66, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:68-70, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0076] Implementation Scheme 36. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 35, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:72-74, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:76-78, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0077] Implementation Scheme 37. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 36, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:80-82, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:84-86, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0078] Implementation Scheme 38. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 37, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:88-90, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:92-94, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0079] Implementation Scheme 39. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 38, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO: 99-101, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO: 108-110, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0080] Implementation Scheme 40. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 39, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:102-104, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:111-113, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0081] Implementation Scheme 41. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 40, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:105-107, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:114-116, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0082] Implementation Scheme 42. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 41, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequences shown in SEQ ID NO:130-132; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequences shown in SEQ ID NO:141-143.

[0083] Implementation Scheme 43. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 42, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region respectively comprise the amino acid sequences shown in SEQ ID NO: 133, 134 and 230, or amino acid sequences having 1-2 amino acid mutations compared to them; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region respectively comprise the amino acid sequences shown in SEQ ID NO: 144-146, or amino acid sequences having 1-2 amino acid mutations compared to them.

[0084] Implementation Scheme 44. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 43, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:135-137, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:147-149, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0085] Implementation Scheme 45. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 44, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:153-155, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:165-167, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0086] Implementation Scheme 46. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 45, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:156-158, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:168-170, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0087] Implementation Scheme 47. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 46, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:159-161, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:171-173, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0088] Implementation Scheme 48. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 47, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:177-179, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:189-191, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0089] Scheme 49. A bispecific antibody targeting TSLP and IgE according to any one of Schemes 1 to 48, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:199-201, or an amino acid sequence having 1-2 amino acid mutations compared to it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:203-205, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0090] Implementation Scheme 50. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 49, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:1, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:5, or an amino acid sequence having 90% or more identity with it.

[0091] Implementation Scheme 51. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 50, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:9, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:13, or an amino acid sequence having 90% or more identity with it.

[0092] Implementation Scheme 52. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 51, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:17, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:21, or an amino acid sequence having 90% or more identity with it.

[0093] Implementation Scheme 53. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 52, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25, or an amino acid sequence having 90% or more identity with it.

[0094] Implementation Scheme 54. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 53, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:26, or an amino acid sequence having 90% or more identity with it.

[0095] Implementation Scheme 55. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 54, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, wherein the first heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25, or an amino acid sequence having 90% or more identity with it; and the second heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:26, or an amino acid sequence having 90% or more identity with it.

[0096] Implementation Scheme 56. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 55, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:39, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:43, or an amino acid sequence having 90% or more identity with it.

[0097] Implementation Scheme 57. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 56, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:47, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:51, or an amino acid sequence having 90% or more identity with it.

[0098] Implementation Scheme 58. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 57, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:55, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:59, or an amino acid sequence having 90% or more identity with it.

[0099] Implementation Scheme 59. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 58, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:63, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:67, or an amino acid sequence having 90% or more identity with it.

[0100] Implementation Scheme 60. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 59, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:71, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:75, or an amino acid sequence having 90% or more identity with it.

[0101] Implementation Scheme 61. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 60, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:79, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:83, or an amino acid sequence having 90% or more identity with it.

[0102] Implementation Scheme 62. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 61, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:87, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:91, or an amino acid sequence having 90% or more identity with it.

[0103] Implementation Scheme 63. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 62, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:95, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:96, or an amino acid sequence having 90% or more identity with it.

[0104] Implementation Scheme 64. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 63, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:97, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:98, or an amino acid sequence having 90% or more identity with it.

[0105] Implementation Scheme 65. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 64, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 119, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 120, or an amino acid sequence having 90% or more identity with it.

[0106] Implementation Scheme 66. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 65, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:123, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:124, or an amino acid sequence having 90% or more identity with it.

[0107] Implementation Scheme 67. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 66, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:198, or an amino acid sequence having 90% or more identity with it; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:202, or an amino acid sequence having 90% or more identity with it.

[0108] Implementation Scheme 68. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 67, wherein the heavy chain variable region and the light chain variable region of the first binding functional region targeting TSLP, or the heavy chain variable region and the heavy chain variable region are linked by a linker.

[0109] Implementation Scheme 69. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 68, wherein the second binding functional region targeting IgE includes a heavy chain variable region (VH) and / or a light chain variable region (VL); wherein the heavy chain variable region includes heavy chain complementarity-determining regions (HCDR)1, HCDR2, and HCDR3; and / or the light chain variable region includes a light chain complementarity-determining region (HL). complementarity-determining region, LCDR)1, LCDR2 and LCDR3.

[0110] Implementation Scheme 70. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 69, wherein the second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four or five heavy chain variable regions and / or one, two, three, four or five light chain variable regions.

[0111] Implementation Scheme 71. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 70, wherein the second binding functional region targeting IgE comprises one or more heavy chain variable regions, and the more than one heavy chain variable regions are connected by linkers; and / or

[0112] The second binding functional region targeting IgE includes one or more light chain variable regions, which are connected by connectors; and / or;

[0113] The heavy chain variable region and the light chain variable region of the second binding functional region targeting IgE are connected by a connector.

[0114] Implementation Scheme 72. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 71, wherein the second binding functional region targeting IgE comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:206; and the second binding functional region targeting IgE comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:210.

[0115] Implementation Scheme 73. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 72, wherein the second binding functional region targeting IgE comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:214; and the second binding functional region targeting IgE comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:218.

[0116] Implementation Scheme 74. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 73, wherein the second binding functional region targeting IgE comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:222; and the second binding functional region targeting IgE comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:226.

[0117] Implementation Scheme 75. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 74, wherein the second binding functional region targeting IgE comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:207-209, or an amino acid sequence having 1-2 amino acid mutations compared to it; the second binding functional region targeting IgE comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:211-213, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0118] Implementation Scheme 76. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 75, wherein the second binding functional region targeting IgE comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:215-217, or an amino acid sequence having 1-2 amino acid mutations compared to it; the second binding functional region targeting IgE comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:219-221, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0119] Implementation Scheme 77. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 76, wherein the second binding functional region targeting IgE comprises a heavy chain variable region, wherein HCDR1, HCDR2 and HCDR3 of the heavy chain variable region each comprise the amino acid sequence shown in SEQ ID NO:223-225, or an amino acid sequence having 1-2 amino acid mutations compared to it; the second binding functional region targeting IgE comprises a light chain variable region, wherein LCDR1, LCDR2 and LCDR3 of the light chain variable region each comprise the amino acid sequence shown in SEQ ID NO:227-229, or an amino acid sequence having 1-2 amino acid mutations compared to it.

[0120] Implementation Scheme 78. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 77, wherein the second binding functional region targeting IgE comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 206, or an amino acid sequence having 90% or more identity with it; the second binding functional region targeting IgE comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 210, or an amino acid sequence having 90% or more identity with it.

[0121] Implementation Scheme 79. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 78, wherein the second binding functional region targeting IgE comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 214, or an amino acid sequence having 90% or more identity with it; the second binding functional region targeting IgE comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 218, or an amino acid sequence having 90% or more identity with it.

[0122] Implementation Scheme 80. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 79, wherein the second binding functional region targeting IgE comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 222, or an amino acid sequence having 90% or more identity with it; the second binding functional region targeting IgE comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 226, or an amino acid sequence having 90% or more identity with it.

[0123] Implementation Scheme 81. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 80, wherein the heavy chain variable region and the light chain variable region of the second binding functional region targeting IgE are linked by a linker.

[0124] Implementation Scheme 82. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 81, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are the HCDR1, HCDR2, and HCDR3 of VH as shown in SEQ ID NO:1; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are the LCDR1, LCDR2, and LCDR3 of VL as shown in SEQ ID NO:5; and

[0125] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0126] Implementation Scheme 83. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 82, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:9; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:13; and

[0127] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0128] Implementation Scheme 84. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 83, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:17; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:21; and

[0129] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0130] Implementation Scheme 85. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 84, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:25; and

[0131] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0132] Implementation Scheme 86. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 85, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:26; and

[0133] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0134] Implementation Scheme 87. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 86, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, wherein the HCDR1, HCDR2, and HCDR3 of the first heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:25, and the HCDR1, HCDR2, and HCDR3 of the second heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:26; and

[0135] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0136] Implementation Scheme 88. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 87, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:25; and

[0137] The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four, or five, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable regions are independently selected from the VH shown in SEQ ID NO:206, SEQ ID NO:214, and SEQ ID NO:222; and / or the LCDR1, LCDR2, and LCDR3 of the light chain variable regions are independently selected from the VH shown in SEQ ID NO:210, SEQ ID NO:218, and SEQ ID NO:226.

[0138] Implementation Scheme 89. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 88, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:26; and

[0139] The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four, or five, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable regions are independently selected from the VH shown in SEQ ID NO:206, SEQ ID NO:214, and SEQ ID NO:222; and / or the LCDR1, LCDR2, and LCDR3 of the light chain variable regions are independently selected from the VH shown in SEQ ID NO:210, SEQ ID NO:218, and SEQ ID NO:226.

[0140] Implementation Scheme 90. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 89, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, wherein the HCDR1, HCDR2, and HCDR3 of the first heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:25, and the HCDR1, HCDR2, and HCDR3 of the second heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:26; and

[0141] The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four, or five, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable regions are independently selected from the VH shown in SEQ ID NO:206, SEQ ID NO:214, and SEQ ID NO:222; and / or the LCDR1, LCDR2, and LCDR3 of the light chain variable regions are independently selected from the VH shown in SEQ ID NO:210, SEQ ID NO:218, and SEQ ID NO:226.

[0142] Implementation Scheme 91. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 90, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:39; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:43; and

[0143] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0144] Implementation Scheme 92. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 91, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:47; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:51; and

[0145] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0146] Implementation Scheme 93. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 92, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:55; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:59; and

[0147] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0148] Implementation Scheme 94. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 93, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:63; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:67; and

[0149] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0150] Implementation Scheme 95. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 94, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:71; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:75; and

[0151] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0152] Implementation Scheme 96. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 95, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:79; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:83; and

[0153] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0154] Implementation Scheme 97. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 96, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:87; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:91; and

[0155] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0156] Implementation Scheme 98. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 97, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:95; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:96; and

[0157] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0158] Implementation Scheme 99. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 98, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:97; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:98; and

[0159] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0160] Implementation Scheme 100. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 99, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO: 119; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO: 120; and

[0161] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0162] Implementation Scheme 101. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 100, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO: 123; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO: 124; and

[0163] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0164] Implementation Scheme 102. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 101, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:198; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:202; and

[0165] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:210.

[0166] Implementation Scheme 103. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 102, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH in sequence SEQ ID NO:1; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL in sequence SEQ ID NO:5; and

[0167] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0168] Implementation Scheme 104. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 103, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:9; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:13; and

[0169] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0170] Implementation Scheme 105. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 104, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:17; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:21; and

[0171] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0172] Implementation Scheme 106. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 105, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:25; and

[0173] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0174] Implementation Scheme 107. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 106, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:26; and

[0175] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0176] Implementation Scheme 108. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 107, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, wherein the HCDR1, HCDR2, and HCDR3 of the first heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:25, and the HCDR1, HCDR2, and HCDR3 of the second heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:26; and

[0177] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0178] Implementation Scheme 109. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 108, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:39; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:43; and

[0179] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0180] Implementation Scheme 110. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 109, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:47; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:51; and

[0181] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0182] Implementation Scheme 111. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 110, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:55; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:59; and

[0183] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0184] Implementation Scheme 112. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 111, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:63; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:67; and

[0185] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0186] Implementation Scheme 113. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 112, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:71; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:75; and

[0187] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0188] Implementation Scheme 114. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 113, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:79; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:83; and

[0189] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0190] Implementation Scheme 115. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 114, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:87; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:91; and

[0191] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0192] Implementation Scheme 116. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 115, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:95; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:96; and

[0193] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0194] Implementation Scheme 117. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 116, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:97; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:98; and

[0195] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0196] Implementation Scheme 118. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 117, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO: 119; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO: 120; and

[0197] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0198] Implementation Scheme 119. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 118, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO: 123; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO: 124; and

[0199] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0200] Implementation Scheme 120. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 119, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:198; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:202; and

[0201] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218.

[0202] Implementation Scheme 121. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 120, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH in sequence SEQ ID NO:1; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL in sequence SEQ ID NO:5; and

[0203] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0204] Implementation Scheme 122. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 121, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:9; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:13; and

[0205] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0206] Implementation Scheme 123. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 122, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:17; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:21; and

[0207] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0208] Implementation Scheme 124. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 123, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:25; and

[0209] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0210] Implementation Scheme 125. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 124, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:26; and

[0211] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0212] Implementation Scheme 126. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 125, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, wherein the HCDR1, HCDR2, and HCDR3 of the first heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:25, and the HCDR1, HCDR2, and HCDR3 of the second heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:26; and

[0213] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0214] Implementation Scheme 127. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 126, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:39; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:43; and

[0215] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0216] Implementation Scheme 128. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 127, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:47; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:51; and

[0217] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0218] Implementation Scheme 129. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 128, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:55; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:59; and

[0219] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0220] Implementation Scheme 130. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 129, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:63; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:67; and

[0221] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0222] Implementation Scheme 131. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 130, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:71; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:75; and

[0223] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0224] Implementation Scheme 132. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 131, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:79; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:83; and

[0225] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0226] Implementation Scheme 133. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 132, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:87; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:91; and

[0227] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0228] Implementation Scheme 134. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 133, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:95; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:96; and

[0229] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0230] Implementation Scheme 135. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 134, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:97; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:98; and

[0231] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0232] Implementation Scheme 136. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 135, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO: 119; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO: 120; and

[0233] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0234] Implementation Scheme 137. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 136, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO: 123; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO: 124; and

[0235] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0236] Implementation Scheme 138. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 137, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:198; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:202; and

[0237] The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:226.

[0238] Implementation Scheme 139. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 138, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:1; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:5; and

[0239] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0240] Implementation Scheme 140. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 139, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:9; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:13; and

[0241] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0242] Implementation Scheme 141. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 140, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:17; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:21; and

[0243] The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or light chain variable regions, wherein the heavy chain variable region includes an amino acid sequence independently selected from the amino acid sequences shown in SEQ ID NO:206, SEQ ID NO:214 and SEQ ID NO:222; and / or the light chain variable region includes an amino acid sequence independently selected from the amino acid sequences shown in SEQ ID NO:210, SEQ ID NO:218 and SEQ ID NO:226.

[0244] Implementation Scheme 142. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 141, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:17; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:21; and

[0245] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0246] Implementation Scheme 143. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 142, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25; and

[0247] The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four, or five, wherein the heavy chain variable region includes an amino acid sequence independently selected from the amino acid sequences shown in SEQ ID NO:206, SEQ ID NO:214, and SEQ ID NO:222; and / or the light chain variable region includes an amino acid sequence independently selected from the amino acid sequences shown in SEQ ID NO:210, SEQ ID NO:218, and SEQ ID NO:226.

[0248] Implementation Scheme 144. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 143, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25; and

[0249] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0250] Implementation Scheme 145. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 144, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:26; and

[0251] The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four, or five, wherein the heavy chain variable region includes an amino acid sequence independently selected from the amino acid sequences shown in SEQ ID NO:206, SEQ ID NO:214, and SEQ ID NO:222; and / or the light chain variable region includes an amino acid sequence independently selected from the amino acid sequences shown in SEQ ID NO:210, SEQ ID NO:218, and SEQ ID NO:226.

[0252] Implementation Scheme 146. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 145, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:26; and

[0253] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0254] Implementation Scheme 147. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 146, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, wherein the first heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25, and the second heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:26; and

[0255] The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four, or five, wherein the heavy chain variable region includes an amino acid sequence independently selected from the amino acid sequences shown in SEQ ID NO:206, SEQ ID NO:214, and SEQ ID NO:222; and / or the light chain variable region includes an amino acid sequence independently selected from the amino acid sequences shown in SEQ ID NO:210, SEQ ID NO:218, and SEQ ID NO:226.

[0256] Implementation Scheme 148. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 147, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, wherein the first heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25, and the second heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:26; and

[0257] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0258] Implementation Scheme 149. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 148, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:39; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:43; and

[0259] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0260] Implementation Scheme 150. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 149, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:47; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:51; and

[0261] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0262] Implementation Scheme 151. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 150, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 55; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 59; and

[0263] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0264] Implementation Scheme 152. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 151, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:63; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:67; and

[0265] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0266] Implementation Scheme 153. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 152, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:71; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:75; and

[0267] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0268] Implementation Scheme 154. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 153, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:79; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:83; and

[0269] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0270] Implementation Scheme 155. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 154, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:87; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:91; and

[0271] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0272] Implementation Scheme 156. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 155, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:95; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:96; and

[0273] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0274] Implementation Scheme 157. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 156, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:97; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:98; and

[0275] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0276] Implementation Scheme 158. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 157, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 119; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 119. The amino acid sequence shown in 120; and

[0277] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0278] Implementation Scheme 159. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 158, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 123; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: The amino acid sequence shown in 124; and

[0279] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0280] Implementation Scheme 160. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 159, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 198; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 202; and

[0281] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:210.

[0282] Implementation Scheme 161. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 160, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:1; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:5; and

[0283] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0284] Implementation Scheme 162. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 161, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:9; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:13; and

[0285] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0286] Implementation Scheme 163. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 162, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:17; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:21; and

[0287] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0288] Implementation Scheme 164. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 163, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25; and

[0289] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0290] Implementation Scheme 165. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 164, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:26; and

[0291] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0292] Implementation Scheme 166. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 165, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, wherein the first heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25, and the second heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:26; and

[0293] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0294] Implementation Scheme 167. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 166, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:39; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:43; and

[0295] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0296] Implementation Scheme 168. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 167, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:47; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:51; and

[0297] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0298] Implementation Scheme 169. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 168, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:55; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:59; and

[0299] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0300] Implementation Scheme 170. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 169, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:63; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:67; and

[0301] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0302] Implementation Scheme 171. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 170, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:71; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:75; and

[0303] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0304] Implementation Scheme 172. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 171, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:79; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:83; and

[0305] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0306] Implementation Scheme 173. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 172, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:87; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:91; and

[0307] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0308] Implementation Scheme 174. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 173, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:95; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:96; and

[0309] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0310] Implementation Scheme 175. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 174, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:97; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:98; and

[0311] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0312] Implementation Scheme 176. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 175, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 119; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: The amino acid sequence shown in 120; and

[0313] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0314] Implementation Scheme 177. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 176, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 123; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: The amino acid sequence shown in 124; and

[0315] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0316] Implementation Scheme 178. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 177, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 198; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 202; and

[0317] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:218.

[0318] Implementation Scheme 179. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 178, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:1; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:5; and

[0319] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0320] Implementation Scheme 180. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 179, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:9; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:13; and

[0321] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0322] Implementation Scheme 181. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 180, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:17; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:21; and

[0323] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0324] Implementation Scheme 182. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 181, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25; and

[0325] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0326] Implementation Scheme 183. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 182, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:26; and

[0327] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0328] Implementation Scheme 184. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 183, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, wherein the first heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:25, and the second heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:26; and

[0329] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0330] Implementation Scheme 185. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 184, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:39; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:43; and

[0331] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0332] Implementation Scheme 186. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 185, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:47; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:51; and

[0333] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0334] Implementation Scheme 187. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 186, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:55; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:59; and

[0335] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0336] Implementation Scheme 188. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 187, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:63; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:67; and

[0337] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0338] Implementation Scheme 189. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 188, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:71; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:75; and

[0339] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0340] Implementation Scheme 190. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 189, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:79; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:83; and

[0341] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0342] Implementation Scheme 191. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 190, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:87; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:91; and

[0343] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0344] Implementation Scheme 192. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 191, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:95; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:96; and

[0345] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0346] Implementation Scheme 193. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 192, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:97; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:98; and

[0347] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0348] Implementation Scheme 194. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 193, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 119; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: The amino acid sequence shown in 120; and

[0349] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0350] Implementation Scheme 195. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 194, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 123; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: The amino acid sequence shown in 124; and

[0351] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0352] Implementation Scheme 196. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 195, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 198; and the first binding functional region targeting TSLP comprises a light chain variable region, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 202; and

[0353] The second binding functional region targeting IgE includes a heavy chain variable region, wherein the heavy chain variable region includes the amino acid sequence shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein the light chain variable region includes the amino acid sequence shown in SEQ ID NO:226.

[0354] Those skilled in the art should understand that the specificity of antibody-antigen binding depends on the CDR region. Currently, various software programs exist for analyzing the CDR region, and the resulting sequence information may differ. However, when both the VH and VL sequences of the antibody are determined, its specificity for antigen binding is fixed. Those skilled in the art should know that the CDR sequences of the antibodies in this application, defined using different numbering systems such as KABAT, IMGT, Chothia, AbM, and Contact, should all be included within the scope of protection of this application.

[0355] Implementation Scheme 197. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 196, wherein the first binding functional region targeting TSLP can be obtained from antibodies Bosakitug, PF-07275315, Ecleralimab, Lunsekimig, Solrikitug, Verekitug, HBM-9378, MG-014, SHR-1905, GR-2002, IBI-3002, APG333, and QX-008N.

[0356] Implementation Scheme 198. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 197, wherein the second binding functional region targeting IgE can be obtained from antibodies Omalizumab, Ligelizumab, and JYB-1904.

[0357] Bosakitug antibody, originally developed by Bio-Sensing Biotechnology (Nanjing) Co., Ltd., is a monoclonal antibody targeting TSLP and is currently in Phase III clinical trials (see CN113423733B for details). PF-07275315 antibody, developed by Pfizer Inc., is a trispecific antibody targeting IL-13, IL-4, and TSLP simultaneously and is currently in Phase II clinical trials (see WO2023166420A1 for details). Ecleralimab antibody, developed by Novartis Pharma AG, is a Fab fragment antibody targeting TSLP and is currently in Phase II clinical trials (see WO2017042701A1 for details). Lunsekimig antibody, originally developed by Sanofi, is a nanobispecific antibody targeting both IL-13 and TSLP simultaneously and is currently in Phase II clinical trials (see CN114980974A for details). Solrikitug antibody, originally developed by Merck & Co., Inc., is a monoclonal antibody targeting TSLP and is currently in Phase II clinical trials (see WO2011056772A1 for details). Verekitug antibody, developed by UpstreamBio, Inc., is a monoclonal antibody targeting TSLPR and is currently in Phase II clinical trials (see US12150991B2 for details). HBM-9378 antibody, developed by Sichuan Kelun Pharmaceutical Co., Ltd. and Platinum Pharmaceuticals (Shanghai) Co., Ltd., is a monoclonal antibody targeting TSLP and is currently in Phase II clinical trials (see CN114729037A for details). MG-014 antibody, developed by Hunan Maiji Biotechnology Co., Ltd., is a monoclonal antibody targeting TSLP and is currently in Phase II clinical trials (see CN114437212B for details). SHR-1905 antibody is a monoclonal antibody targeting TSLP developed by Shanghai Hengrui Medicine Co., Ltd., and it is currently in Phase II clinical trials (see CN113853387B for details). GR-2002 is a bispecific antibody targeting TSLP developed by Chongqing Zhixiang Jintai Biopharmaceutical Co., Ltd., and it is currently in Phase I clinical trials (see CN113501878B for details). IBI-3002 antibody is a bispecific antibody targeting both IL-4Rα and TSLP developed by Innovent Biologics (Suzhou) Co., Ltd., and it is currently in Phase I clinical trials (see WO2025077822A1 for details). APG333 antibody is a monoclonal antibody targeting TSLP developed by Apogee Therapeutics, Inc., and it is currently in Phase I clinical trials (see WO2024264002A2 for details).QX-008N antibody is a monoclonal antibody targeting TSLP developed by Jiangsu Quanxin Biopharmaceutical Co., Ltd. It has entered Phase I clinical trials. For details, please refer to CN113683694B.

[0358] Omalizumab antibody, originally developed by Novartis Pharma AG, is a monoclonal antibody targeting IgE and has been approved for marketing (see US6914129B2). Ligelizumab antibody, originally developed by Genentech, Inc., is a monoclonal antibody targeting IgE and is currently in Phase 3 clinical trials (see US 7531169B2 and CN1771338B). JYB-1904 antibody, originally developed by Jiangsu Jiye Biopharmaceutical Co., Ltd., is a monoclonal antibody targeting IgE and is currently in Phase 2 clinical trials (see WO2022007965A1).

[0359] The contents of the aforementioned patent documents are incorporated herein by reference in their entirety.

[0360] Bispecific antibody structure design

[0361] Implementation Scheme 199. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 198, wherein the bispecific antibody targeting TSLP and IgE is any form of bispecific antibody, such as those described by Labrijn et al. 2019 in Nat Rev Drug Discov 18:585–608 and Madsen et al. 2024 in Front Bioeng Biotechnol 12:135 2014, including symmetrical or asymmetric antibodies containing an Fc region, antibody fragment conjugates without an Fc region, single-domain antibody conjugates, etc.

[0362] Specifically, for example, those forms described in Brinkmann and Kontermann MAbs (2017) 9(2): 182-212, which are incorporated herein by reference in their entirety. Suitable forms include those from Brinkmann and Kontermann MAbs (2017) 9(2): 182-212. Figure 2The forms shown are: antibody conjugates, such as IgG2, F(ab')2, or CovX-antibodies; IgG or IgG-like molecules, such as IgG, chimeric IgG, kλ-antibodies, and common HC antibodies; CH1 / CL fusion proteins, such as scFv2-CH1 / CL, VHH2-CH1 / CL; "variable domain-only" bispecific antigen-binding molecules, such as tandem scFv (taFV), triantibodies, biantibodies (Db), dsDb, Db (kih), DART, scDB, dsFv-dsFv, tandAb, trihead antibodies, and tandem dAb / VHH. Trivalent dAb.VHH; non-Ig fusion proteins, such as scFv2-albumin, scDb-albumin, taFv-albumin, taFv-toxin, microantibodies, DNL-Fab2, DNL-Fab2-scFv, DNL-Fab2-IgG-cytokine 2, ImmTAC (TCR-scFv); modified Fc and CH3 fusion proteins, such as scFv-Fc (kih), scFv-Fc (CH3 charge pair), scFv-Fc (EW-RVT), scFv-fc (HA-TF), scFv-Fc (S SEED antibody), taFv-Fc(kih), scFv-Fc(kih)-Fv, Fab-Fc(kih)-scFv, Fab-scFv-Fc(kih), Fab-scFv-Fc(BEAT), Fab-scFv-Fc(SEED antibody), DART-Fc, scFv-CH3(kih), TriFabs; Fc fusions, such as biantibodies, scDb-Fc, taFv-Fc, scFv-Fc-scFv, HCAb-VHH, Fab-scFv-Fc, scFv4 -Ig, scFv2-Fcab; CH3 fusion proteins, such as biantibodies, scDb-CH3; IgE / IgMCH2 fusions, such as scFv-EHD2-scFv, scFvMHD2-scFv; Fab fusion proteins, such as Fab-scFv (biantibody), Fab-scFv2 (triantibody), Fab-Fv, Fab-dsFv, Fab-VHH, orthogonal Fab-Fab; non-Ig fusion proteins, such as DNL-Fab3, DNL-Fab2-scFv, DNL-Fab2-IgG-cytokine 2;Asymmetric IgG or IgG-like molecules, such as IgG(kih), IgG(kih) universal LC, ZW1 IgG universal LC, Biclonics universal LC, CrossMab, CrossMab(kih), scFab-IgG(kih), Fab-scFab-IgG(kih), orthogonal Fab IgG(kih), DuetMab, CH3 charge pair + CH1 / CL charge pair, hinge / CH3 charge pair, SEED-antibody, bispecific antibody, four-in-one CrossMab(kih), LUZ-Y universal LC; LUZ-Y scFab-IgG, FcFc*; additional and Fc-modified IgG, such as IgG(kih)-Fv, IgG HA-TF-Fv, IgG(kih)scFab, scFab-Fc(kih)-scFv2, scFab-Fc(kih)-scFv, half-DVD-Ig, DVI-Ig (quadruple), CrossMab-Fab; modified Fc and CH3 fusion proteins, such as Fab-Fc(kih)-scFv, Fab-scFv-Fc(kih), Fab-scFv-Fc(BEAT), Fab-scFv-Fc-SEED antibody, TriFab; additional IgG-HC fusion proteins, such as IgG-HC, scFv, IgG-dAb, IgG-taFV, IgG-CrossFab, IgG-orthogonal Fab, IgG-(CaCβ)Fab, scFv-HC-IgG, tandem Fab-IgG (orthogonal Fab-CrossFab), IgG-orthogonal Fab, IgG-(CaCβ)Fab, scFv-HC-IgG, tandem Fab-IgG (orthogonal Fab-CrossFab), IgG-orthogonal Fab, IgG-(CaCβ)Fab, scFv-HC-IgG, tandem Fab-IgG (orthogonal Fab-CrossFab), IgG-(CaCβ)Fab, IgG-CrossFab, ... Fab-Fab-IgG (CaCβFab), Fab-IgG (CR3), Fab-hinge-IgG (CR3); IgG-LC fusions, such as IgG-scFv(LC), scFv(LC)-IgG, dAb-IgG; IgG-HC and LC fusions, such as DVD-Ig, TVD-Ig, CODV-Ig, scFv4-IgG, Zy antibody; Fc fusions, such as Fab-scFv-Fc, scFv4-Ig; F(ab')2 fusions, such as F(ab')2-scFv2; CH1 / CL fusion protein scFv2-CH1-hinge / CL; modified IgG, such as DAF (dual IgG), DutaMab, Mab2; and non-Ig fusions, such as DNL-Fab4-IgG.

[0363] Symmetrical bispecific antibodies containing the Fc region

[0364] Implementation Scheme 200. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 199, wherein the bispecific antibody targeting TSLP and IgE is a symmetrical bispecific antibody.

[0365] Symmetrical bispecific antibodies are bispecific antibodies with a symmetrical molecular structure. Their molecular structure features two symmetrically distributed antigen-binding arms (or functional domains), exhibiting overall spatial conformational symmetry. These symmetrical bispecific antibodies can be designed based on the symmetrical structure of natural antibodies (such as the Y-shaped symmetrical structure of IgG antibodies). Through techniques such as genetic engineering, the antigen-binding region of the antibody can be modified to produce two symmetrical binding arms. For example, based on a monoclonal antibody targeting one target, two functional domains binding to another target can be further linked to its variable or constant regions via a linker.

[0366] Implementation Scheme 201. The bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 200, wherein the symmetrical bispecific antibody targeting TSLP and IgE comprises an Fc region, for example, the Fc region of the symmetrical bispecific antibody targeting TSLP and IgE is any Fc region in the prior art.

[0367] Implementation Scheme 202. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 201, wherein the Fc region of the symmetrical bispecific antibody targeting TSLP and IgE is the Fc region of IgG1, the Fc region of IgG2, the Fc region of IgG3 or the Fc region of IgG4.

[0368] Implementation Scheme 203. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 202, wherein the Fc region of the symmetrical bispecific antibody targeting TSLP and IgE is the Fc region disclosed in Li et al. 2018, Molecular cancer therapeutics 17(5):1039-1050, Lacy et al. 2015, mAbs 7(3):605-19, Schaefer et al. 2011, Cancer Cell 20(4):472-–486, WO2008082651, WO2014071074, WO2014144280 and WO2009052081.

[0369] Implementation Scheme 204. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 203, wherein the Fc region is any one of the Fc regions disclosed in US6914129B2, CN1771338B, CN113423733B, WO2023166420A1, WO2017042701A1, CN114980974A, WO2011056772A1, US12150991B2, CN114729037A, CN113853387B, CN113501878B, CN113683694B, CN114729037A, etc. The entire contents of the above-mentioned documents are incorporated herein by reference.

[0370] Implementation Scheme 205. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 204, wherein the first binding functional region targeting TSLP forms a homodimer with the Fc region, and the second binding functional region targeting IgE is connected to and / or fused to: the C-terminus of the Fc region, and / or the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the first binding functional region targeting TSLP, forming a symmetrical bispecific antibody.

[0371] Implementation Scheme 206. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 205, wherein the second binding functional region targeting IgE forms a homodimer with the Fc region, and the first binding functional region targeting TSLP is connected to and / or fused to: the C-terminus of the Fc region, and / or the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the second binding functional region targeting IgE, forming a symmetrical bispecific antibody.

[0372] Implementation Scheme 207. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 85 to 90, 106 to 108 and 124 to 126, wherein the second binding functional region targeting IgE forms a homodimer with the Fc region, and the first binding functional region targeting TSLP is connected to and / or fused to: the C-terminus of the Fc region, and / or the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the second binding functional region targeting IgE, forming a symmetrical bispecific antibody.

[0373] Implementation Scheme 208. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 143 to 148, 164 to 166 and 182 to 184, wherein the second binding functional region targeting IgE forms a homodimer with the Fc region, and the first binding functional region targeting TSLP is connected to and / or fused to: the C-terminus of the Fc region, and / or the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the second binding functional region targeting IgE, forming a symmetrical bispecific antibody.

[0374] Asymmetric bispecific antibodies containing the Fc region

[0375] Implementation Scheme 209. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 208, wherein the bispecific antibody targeting TSLP and IgE is an asymmetric bispecific antibody.

[0376] Implementation Scheme 210. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 209, wherein the first binding functional region targeting TSLP and the second binding functional region targeting IgE are connected by an Fc region to form a heterodimer.

[0377] Implementation Scheme 211. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 210, wherein the first binding functional region targeting TSLP forms a homodimer with the Fc region, and the second binding functional region targeting IgE is connected to and / or fused to: the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the first binding functional region targeting TSLP, and / or the C-terminus of the Fc region to form an asymmetric bispecific antibody.

[0378] Implementation Scheme 212. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 211, wherein the second binding functional region targeting IgE forms a homodimer with the Fc region, and the first binding functional region targeting TSLP is connected to and / or fused to: the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the second binding functional region targeting IgE, and / or the C-terminus of the Fc region to form an asymmetric bispecific antibody.

[0379] Implementation Scheme 213. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 85 to 90, 106 to 108 and 124 to 126, wherein the second binding functional region targeting IgE forms a homodimer with the Fc region, and the first binding functional region of TSLP is linked to and / or fused to: the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the second binding functional region targeting IgE, and / or the C-terminus of the Fc region to form an asymmetric bispecific antibody.

[0380] Implementation Scheme 214. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 143 to 148, 164 to 166 and 182 to 184, wherein the second binding functional region targeting IgE forms a homodimer with the Fc region, and the first binding functional region of TSLP is linked to and / or fused to: the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the second binding functional region targeting IgE, and / or the C-terminus of the Fc region to form an asymmetric bispecific antibody.

[0381] Asymmetric bispecific antibodies are a class of bispecific antibodies that can simultaneously bind to two different antigens (or different epitopes of the same antigen), but whose molecular structure lacks symmetry. Their two antigen-binding arms (or functional domains) differ in molecular size, structural composition, or spatial arrangement, resulting in an asymmetric overall molecular conformation. This asymmetric structure may lead to "mismatch" problems (such as the formation of homodimers). This application utilizes any of the following techniques to address chain mismatch issues.

[0382] Implementation Scheme 215. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 214, wherein the asymmetric bispecific antibody can resolve chain mismatch by utilizing steric hindrance, represented by KiH technology.

[0383] For example, the bispecific antibody described in this invention can comprise two different heavy chains, each with its Fc region (especially the CH3 domain) engineered to obtain a heterodimer rather than a homodimer. For instance, the KiH technology employs the principle of steric hindrance and is commonly referred to as the "knobs-into-Holes" (KiH) technique. The general idea of ​​this technique is to introduce a sterically hindered amino acid side chain ("knob") at the interface of the CH3 domain of one heavy chain, while simultaneously creating a spatially accommodating "hole" or "hole" at the corresponding interface of the CH3 domain of the other heavy chain. The "knob" and "hole" are complementary. Typical examples of non-natural amino acids with large-volume side chains used to form the "knob" include, but are not limited to, arginine (R), tryptophan (W), tyrosine (Y), or phenylalanine (F). For example, threonine 366 (T366, according to EU designation) in the CH3 domain of the Fc region of human IgG1 can be mutated to tryptophan (T366W) to form an effective "groove". Examples of amino acids with small side chains used to form the "groove" include alanine (A), serine (S), threonine (T), and valine (V). This invention covers various combinations and positions of "groove" and "groove". For example, the "groove" mutation can be present on the first heavy chain, while the "groove" mutation is present on the second heavy chain, and vice versa. In one specific embodiment, KiH technology can be combined with other engineering modifications to further improve the stability and yield of heterodimers, such as introducing additional non-natural disulfide bonds to covalently link two different heavy chains. In one specific embodiment, the Fc region of the asymmetric bispecific antibody in this application is the Fc region disclosed in WO1996027011A1, CN117440969A, and Ridgway et al., Protein Eng. 9(7):617-621 (1996). The entire contents of the above documents are incorporated herein by reference.

[0384] Implementation Scheme 216. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 215, wherein the asymmetric bispecific antibody can resolve chain mismatch by utilizing electrostatic interactions, represented by ART-Ig, BiMab, Biclonics or DEKK technology.

[0385] This technology utilizes electrostatic steering to ensure the preferential binding of two different heavy chains. Specifically, at the interface between two different CH3 domains, complementary electrostatic charges are introduced through amino acid mutations. This leverages the principle of "opposites attract, likes repel" to guide the formation of heterodimers while simultaneously inhibiting the assembly of homodimers. Specifically, the CH3 domain of the first polypeptide chain (e.g., the first Fc chain) is modified by introducing one or more positively charged amino acids (e.g., lysine K, arginine R) or negatively charged amino acids (e.g., aspartic acid D, glutamic acid E), thereby forming a local "charge cluster" at the interface. Correspondingly, at the complementary interface of the CH3 domain of the second polypeptide chain (e.g., the second Fc chain), one or more amino acids with opposite charges are introduced. The resulting electrostatic attraction greatly stabilizes the "positively charged" amino acid cluster. A heterodimer is formed by a "positively charged chain" and a "negatively charged chain". Conversely, two identical "positively charged chains" or two identical "negatively charged chains" become unstable due to electrostatic repulsion, thus significantly reducing the proportion of homodimers formed. For example, one CH3 chain may contain the mutant combination K392D and K409D (introducing a negative charge), while the other CH3 chain contains the complementary mutant combination D399K and E356K (introducing a positive charge). For example, the mutation of one CH3 chain is selected from K409D and K409E, and the mutation of the other CH3 chain is selected from D399K or D399R. In a specific embodiment, the Fc region of the asymmetric bispecific antibody in this application is WO2006106905A1, WO2007114325A1, WO2010129304A3. WO2013157953A1, Gunasekaran, Kannan et al. “Enhancing antibody Fcheterodimer formation through electrostatic steering effects: applications to bispecific molecules and monovalent IgG.” The Journal of biological chemistry vol.285,25(2010):19637-46 and De Nardis, Camilla etal. "A new approach for generating bispecific antibodies based on acommonlight chain format and the stable architecture of human The Fc region of immunoglobulin G1, as disclosed in The Journal of Biological Chemistry vol. 292, 35(2017): 14706-14717. The entire contents of the aforementioned literature are incorporated herein by reference.

[0386] Implementation Scheme 217. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 216, wherein the asymmetric bispecific antibody can resolve chain mismatch through in vitro recombination using techniques such as Duobody / cFAE (controlled Fab-arm exchange).

[0387] This method is "controlled Fab-arm exchange," with Genmab as an example. This method, represented by [the technology name], starts from two independent, homogeneous parental monoclonal antibodies and efficiently recombines functional bispecific antibodies through a precisely controlled chemical reaction process. It includes: (a) Independent production of parental antibodies: expressing and purifying two different parental monoclonal antibodies separately, such as a primary antibody targeting TSLP and a secondary antibody targeting IgE. (b) Introducing a key CH3 domain mutation: to achieve subsequent targeted exchange, a specific set of complementary amino acid mutations are introduced into the Fc region (specifically the CH3 domain) of the two parental antibodies. For example, an F405L mutation is introduced into the CH3 domain of one parental antibody, while a K409R mutation (according to EU designation) is introduced into the CH3 domain of the other parental antibody. (c) In vitro controlled exchange reaction: the two purified parental antibodies are mixed in an equimolar ratio. Subsequently, the disulfide bonds in the hinge region connecting the two heavy chains are selectively broken, while other disulfide bonds within the antibody molecule (such as the heavy-light chain inter-disulfide bond) remain intact. At this point, the antibody dissociates into a "half-antibody" (i.e., an HL unit consisting of one heavy chain and one light chain). (d) Recombination and Equilibrium: Subsequently, the reducing agent is removed or diluted, causing the disulfide bonds in the hinge region to re-oxidize and form. Due to the presence of complementary mutations in the CH3 domain (such as F405L / K409R), intermolecular recombination thermodynamically tends to form stable heterodimers. Ultimately, the reaction system reaches a dynamic equilibrium containing a high proportion (theoretically up to 50%) of structurally correct bispecific antibodies, along with the remaining two parental antibodies. In one specific embodiment, the Fc region of the asymmetric bispecific antibody described in this application is the Fc region disclosed in WO2008119353A1, Labrijn, AF et al., PNAS, 110(13), pp. 5145-5150 (2013), and AFLabrijn, et al., Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange, Proc. Natl. Acad. Sci. USA 110(13) 5145-5150. The entire contents of the above documents are incorporated herein by reference.

[0388] Implementation Scheme 218. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 217, wherein the asymmetric bispecific antibody can resolve chain mismatches by utilizing domain exchange technology, such as CrossMab technology.

[0389] This technology uses genetic engineering to exchange a pair of homologous domains between the heavy and light chains of a Fab arm, thereby disrupting their pairing ability with non-corresponding chains and forcing them to bind correctly and specifically. This invention covers various embodiments of the CrossMab technology, including but not limited to: CrossMab (CH1-CL): On a Fab arm (e.g., the Fab arm targeting target B), the CH1 domain of the heavy chain is swapped with the constant (CL) domain of the light chain. Thus, the heavy chain structure of this arm becomes VH-CL-Hinge..., while its paired light chain structure becomes VL-CH1. Since the VH-CL fragment can only stably pair with the VL-CH1 fragment, it can effectively prevent mismatch with another unmodified normal light chain (VL-CL). CrossMab (VH-VL): The variable (VH) domain of the heavy chain and the variable (VL) domain of the light chain can be exchanged on a Fab arm. Thus, the heavy chain structure of the arm becomes VL-CH1-Hinge…, while its paired light chain structure becomes VH-CL. Similarly, this non-natural arrangement of domains ensures the uniqueness of the pairing. In one specific embodiment, this application uses the methods from WO2009080251A1 and Schaefer et al., PNAS108(27):11187-11192, 2011 to resolve chain mismatches. The entire contents of the aforementioned documents are incorporated herein by reference.

[0390] Implementation Scheme 219. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 218, wherein the asymmetric bispecific antibody can resolve chain mismatch by introducing a non-natural disulfide bond.

[0391] This technique involves site-directed mutagenesis, introducing a cysteine ​​(Cys) residue at the interface between two strands. In the oxidative environment of cellular expression, these two spatially adjacent cysteine ​​residues form a covalent disulfide bond, effectively "locking" the two correct strands together and physically preventing strand mismatch. In one specific embodiment, this application uses the methods disclosed in WO2009089004A1, WO2019196522A1, and Wranik, B. Je et al., J. Biol. Chem. 287, pp. 43331-43339 (2012) to introduce non-natural disulfide bonds to resolve strand mismatch. The entire contents of the aforementioned documents are incorporated herein by reference.

[0392] Implementation Scheme 220. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 219, wherein the asymmetric bispecific antibody can resolve chain mismatch by introducing a complementary domain.

[0393] This technology involves introducing or constructing novel complementary structural domains with a natural tendency for heterodimerization, or systematically modifying existing interfaces to create entirely new, orthogonal pairing specificity. This includes, but is not limited to, the following techniques:

[0394] (a)SEED platform (strand exchanged engineered domain)

[0395] This technology addresses heavy chain mismatch by constructing chimeric CH3 domains. Specifically, alternating β-sheet segments in the CH3 domains of human IgG and IgA are interchanged, resulting in two complementary but self-unpaired CH3 chains. For example, one chain could have the structure IgG-IgA-IgG..., and the other IgA-IgG-IgA.... This structural complementarity strongly drives the formation of heterodimers while inhibiting homodimerization. See, for example, WO2007110205A2 and Davis et al., Protein Engineering, Design and Selection 23(4):195–202, 2010.

[0396] (b)Azymetric TM technology

[0397] This technology modifies the CH3 domain of the heavy chain, driving heterodimerization through a unique and complementary combination of amino acid mutations. Unlike the classic "mortar and pestle" technique, these mutant combinations are screened through extensive protein structure and sequence analysis and computational modeling, aiming to maximize heterodimer yield and stability. This technique was developed by Zymeworks and is described in detail in, for example, WO2012058768A1.

[0398] c)WuXiBody TM technology

[0399] This technology introduces the constant structural domain (TCR) of the α / β chain of the T cell receptor into the heavy chain and light chain, respectively, promoting the correct pairing of the light and heavy chains. This platform technology can be found in WO2019057122A1.

[0400] (d) Orthogonal Fab Interface

[0401] This technology involves deep modification of one of the Fab interfaces. By introducing a set of complementary mutations, the modified VH' binds only with high affinity to the modified VL', while losing its binding ability to the native VL or VH. This makes the pairing relationship of this Fab arm "orthogonal," meaning it does not interfere with the other native Fab arm in the antibody, thus ensuring the correct assembly of the light and heavy chains. For details, see Lewis et al., Nature Biotechnology 32:191-198, 2014 and WO2014150973A1. The entire contents of the above references are incorporated herein by reference.

[0402] Implementation Scheme 221. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 220, wherein the asymmetric bispecific antibody uses a common light chain to directly link the heavy chain and light chain (TcBsIgG, OAscFab-IgG, LUZ-Y, etc.) to solve chain mismatch.

[0403] Functional modification or silencing of the Fc area

[0404] Implementation Scheme 222. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 221, wherein the modification of the Fc region achieves effects such as prolonging the antibody half-life, enhancing or weakening the Fc region-mediated immune effect, for example, by prolonging the half-life through mutations in the Fc region such as M428L / N434S; M252Y / S254T / T256E; T250Q / M428L; N434A; for example, by prolonging the half-life through mutations in the Fc region such as S239D / I332E; S239D / I332E / A330L; G236A; F243L / R292P / Y300L / V305I / P396L; K326W / E33 3S; S267E / H268F / S324T mutations or removal of core fucose linked to Fc can enhance Fc-mediated immune effects; for example, L234A / L235A, L234A / L235A / P329G, L234F / L235E / P331S mutations in the Fc region of IgG1, H268Q / V309L / A330S / P331S, E233P / L234V / L235A mutations in the Fc region of IgG2, and L235E or F234A / L235A; N297A, N297Q or N297G mutations in the Fc region of IgG4 can weaken Fc-mediated immune effects.

[0405] Implementation Scheme 223. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 222, wherein the Fc region of the bispecific antibody described in this application is, for example, the Fc region described in Liu et al., 2024, *Chinese Journal of Clinical Medicine* 31(1):143-153, and Abdeldaim et al., 2023, *Pharmaceutics* 15(10):2402. The entire contents of the above references are incorporated herein by reference.

[0406] Antibody fragment linkers without Fc region

[0407] Implementation Scheme 224. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 223, wherein the heavy chain variable region and / or light chain variable region of the first binding functional region targeting TSLP and / or the second binding functional region targeting IgE in the bispecific antibody are "camelized" to obtain a single-domain antibody containing only VH or VL and maintaining stability and function.

[0408] The "camelization" modification involves altering the hydrophobic interaction interface between the VH and VL. In a conventional VH / VL, this interface consists of a set of hydrophobic amino acids. In "camelization," these hydrophobic amino acids are mutated to more hydrophilic amino acids commonly found at their corresponding positions in the native VHH, eliminating their tendency to aggregate in aqueous solutions. This typically involves site-directed mutagenesis of the VH's Framework Region 2 (FR2). For example, typical human VH sites such as Val37, Gly44, Leu45, and Trp47 are mutated to those common in camel VHHs, such as Phe / Tyr37, Glu44, Arg45, and Gly47. Furthermore, the length or sequence of the CDR3 loop may be modified to better cover the original VH / VL interface, further enhancing stability. For details on the "camelization" transformation, please refer to Davies et al., 1995, Biotechnology (NY) 13(5):475-479; Pang et al., 2022, Mycotoxin Res. 38(1):51-60; Bélanger [References:] et al., 2025, Protein Sci. 34(5):e70114; PCT application WO 94 / 04678, etc. The entire contents of the above references are incorporated herein by reference.

[0409] Implementation Scheme 225. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 224, wherein the CDR regions of the heavy chain variable region and / or light chain variable region of the first binding functional region targeting TSLP and / or the second binding functional region targeting IgE are transplanted to a stable single-domain antibody framework (sdAbframeworks) using CDR transplantation technology to obtain a single-domain antibody.

[0410] The aforementioned "single-domain antibody" can be obtained by immunizing camelids (such as alpacas and llamas) with, for example, TSLP or IgE (or fragments thereof). Alternatively, phage display technology can be used to screen for sdAbs that specifically bind to TSLP or IgE from natural (from immunized animals), semi-synthetic, or fully synthetic sdAb libraries; see WO2017198212 for details. Alternatively, yeast display technology can be used to screen sdAb gene libraries to obtain sdAbs with high affinity for the target antigen TSLP or IgE; see US6423538 for details.

[0411] Implementation Scheme 226. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 225, wherein the heavy chain variable regions of the first binding functional region targeting TSLP and the second binding functional region targeting IgE are linked by a linker.

[0412] Implementation Scheme 227. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 226, wherein the heavy chain variable region and / or light chain variable region of the first binding functional region targeting TSLP and the heavy chain variable region and / or light chain variable region of the second binding functional region targeting IgE are connected by a linker.

[0413] Implementation Scheme 228. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 227, wherein the single-domain antibody is linked by a linker.

[0414] Implementation Scheme 229. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 85 to 90, 106 to 108 and 124 to 126, wherein the heavy chain variable regions of the first binding functional region targeting TSLP and the second binding functional region targeting IgE are linked by a linker; and

[0415] The heavy chain variable regions of the first binding functional region targeting TSLP and the heavy chain variable regions and light chain variable regions of the second binding functional region targeting IgE are connected by connectors.

[0416] Implementation Scheme 230. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 143 to 148, 164 to 166, and 182 to 184, wherein the heavy chain variable regions of the first binding functional region targeting TSLP and the second binding functional region targeting IgE are linked by a linker; and

[0417] The heavy chain variable regions of the first binding functional region targeting TSLP and the heavy chain variable regions and light chain variable regions of the second binding functional region targeting IgE are connected by connectors.

[0418] Implementation Scheme 231. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 230, wherein the linker is a linking peptide.

[0419] Implementation Scheme 232. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 231, wherein the linker peptide is a flexible linker peptide, such as a glycine- and serine-rich peptide, such as (G4S)n (where n = 1-5, preferably n = 3), for example, flexible linker peptides such as KESGSVSSEQLAQFRSLD, EGKSSGSGSESKST, GSAGSAAGSGEF, (GGGGA)2GGGGS, (Gly)6, (Gly)8, etc. Such linker peptides provide sufficient space and degrees of freedom for the linked domains to fold independently and function.

[0420] Implementation Scheme 233. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 232, wherein the linker peptide is a rigid or semi-rigid linker peptide, such as containing proline or an α-helical structure, for example (EAAAK)n, ASTKGP, (XP)n, where X represents any amino acid and P represents proline, preferably alanine, lysine or glutamic acid.

[0421] Implementation Scheme 234. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 233, wherein the linker peptide can be a cleavable linker peptide, such as Val-Cit, Phe-Lys, matrix metalloproteinase (MMP) substrates, etc.

[0422] Implementation Scheme 235. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 234, wherein the linker is a non-peptide linker, such as polyethylene glycol (PEG).

[0423] Implementation Scheme 236. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 235, wherein the linker may be Protein Engineering, 9(3), 299-305, 1996, CN101198698B, Chen et al. Adv Drug Deliv Rev Linking peptides or chemically synthesized linkers disclosed in 65(10):1357-1369,2014.

[0424] The linker can be used to link any of the above antigen-binding fragments (such as single-domain antibodies, scFv, etc.) to the same or different antigen-binding fragments, or to any feasible position similar to IgG antibodies, or to homologous or heterologous Fc region fragments, or to human serum albumin, or to other functional fragments.

[0425] Implementation Scheme 237. A bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 236, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, the two heavy chain variable regions being connected by a linker with the sequence SEQ ID NO:231; and

[0426] The second binding functional region targeting IgE includes one or more heavy chain variable regions, which are connected by connectors, and / or includes one or more light chain variable regions, which are connected by connectors, and / or the heavy chain variable regions are connected to the light chain variable regions by connectors; and

[0427] The first binding functional region of the TSLP and the second binding functional region of the targeted IgE are connected by a connector.

[0428] Implementation Scheme 238. Use of the bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 237 in the preparation of a medicament for treating allergic diseases or autoimmune inflammatory diseases associated with TSLP or IgE.

[0429] Preferably, the allergic diseases or autoimmune inflammatory diseases include atopic dermatitis, allergic asthma, allergic rhinitis, eosinophilic esophagitis, chronic spontaneous urticaria, acute urticaria, allergic conjunctivitis, rheumatoid arthritis, and systemic lupus erythematosus, etc.

[0430] Implementation Scheme 239. A method for treating an allergic disease or autoimmune inflammatory disease associated with TSLP or IgE, comprising administering to a subject in need a bispecific antibody targeting TSLP and IgE according to any one of Implementation Schemes 1 to 237.

[0431] Preferably, the allergic diseases or autoimmune inflammatory diseases include atopic dermatitis, allergic asthma, allergic rhinitis, eosinophilic esophagitis, chronic spontaneous urticaria, acute urticaria, allergic conjunctivitis, rheumatoid arthritis, and systemic lupus erythematosus, etc.

[0432] Implementation Scheme 240. Bispecific antibody therapy targeting TSLP and IgE according to any one of Implementation Schemes 1 to 237 and TSLP Or its use in treating IgE-related allergic diseases or autoimmune inflammatory diseases.

[0433] Preferably, the allergic diseases or autoimmune inflammatory diseases include atopic dermatitis, allergic asthma, allergic rhinitis, eosinophilic esophagitis, chronic spontaneous urticaria, acute urticaria, allergic conjunctivitis, rheumatoid arthritis, and systemic lupus erythematosus, etc.

[0434] Example

[0435] The following detailed embodiments further illustrate some preferred implementations and aspects of the present invention. These embodiments should not be construed as limiting the scope of the invention.

[0436] Example 1: Expression and purification of TSLP×IgEκλ ​​bispecific antibody

[0437] Plasmids encoding the corresponding antibody fragments were mixed at a ratio of κ light chain:λ light chain:heavy chain 1:heavy chain 2 = 1:1:1:1, and then mixed with 3 mg / mL PEI. This mixture was then co-transfected into CHO-S cells and cultured in 500 mL CD CHO AGT medium (Gibco#12490-001) at 37°C and 5% CO2 at 150 rpm. On days 2, 4, and 6 after transient transfection, 4% CHO Feed C+ (Gibco#A25031-05) was added. When cell viability dropped to approximately 85%, the fermentation broth was harvested, filtered, and purified by Protein A affinity chromatography. The concentrated broth was transferred to PBS, and absorbance (Nanodrop) was measured. Protein concentration was calculated using the theoretical extinction coefficient.

[0438] The TSLP×IgEκλ ​​bispecific antibody was further purified using Capto S ImpAct ion exchange chromatography via gradient elution. Figure 1 The elution peaks were combined, and the monomer content shown by SEC-HPLC was higher than 95% (Table 1). Mass spectrometry analysis of F(ab)2 molecular weight revealed no mismatches in the TSLP×IgEκλ001 purified sample. Figure 2In the TSLP×IgEκλ002 purified sample, the light chain mismatch ratio was approximately 5.9%, and no TSLP homodimers or IgE homodimers were detected. Figure 3 ).

[0439] Table 1. Purity of TSLP×IgEκλ ​​bispecific antibody (SEC-HPLC)

[0440] All disclosures and patents mentioned in this application are incorporated herein by reference. Various modifications and variations of the methods and compositions described herein will be apparent to those skilled in the art without departing from the scope and spirit of the invention. While the invention has been described through specific preferred embodiments, it should be understood that the claimed invention should not be unduly limited to these specific embodiments. In fact, various variations of the described modes of carrying out the invention that will be apparent to those skilled in the art are intended to be included within the scope of the appended claims. sequence list

Claims

1. A bispecific antibody targeting TSLP and IgE, comprising: (a) Targeting the first binding functional region of TSLP; and (b) Targeting the second binding functional region of IgE.

2. The bispecific antibody targeting TSLP and IgE according to claim 1, wherein the first binding functional region targeting TSLP includes a heavy chain variable region (VH) and / or a light chain variable region (VL). The heavy chain variable region includes heavy chain complementarity-determining regions (HCDRs) 1, HCDR 2, and HCDR 3; and / or the light chain variable region includes light chain complementarity-determining regions (HCDRs). complementarity-determining region, LCDR)1, LCDR2 and LCDR3; and The second binding functional region targeting IgE includes a heavy chain variable region (VH) and / or a light chain variable region (VL); wherein the heavy chain variable region contains a heavy chain complementarity determining region. The complementarity-determining region (HCDR)1, HCDR2, and HCDR3; and / or the light chain variable region includes the light chain complementarity-determining region (LCDR)1, LCDR2, and LCDR3.

3. The bispecific antibody targeting TSLP and IgE according to claim 1 or 2, wherein the first binding functional region targeting TSLP comprises one or more heavy chain variable regions and / or one or more light chain variable regions, for example, one, two, three, four or five heavy chain variable regions and / or one, two, three, four or five light chain variable regions; and The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four or five heavy chain variable regions and / or one, two, three, four or five light chain variable regions.

4. The bispecific antibody targeting TSLP and IgE according to any one of claims 1 to 3, wherein one or more heavy chain variable regions of the first binding functional region targeting TSLP are linked by a linker; and / or One or more light chain variable regions of the first binding functional region of the targeted TSLP are connected by connectors; and / or The heavy chain variable region and the light chain variable region of the first binding functional region of the targeted TSLP are connected by a connector; and / or One or more heavy chain variable regions of the second binding functional region targeting IgE are connected by connectors; and / or One or more light chain variable regions of the second binding functional region targeting IgE are connected by connectors; and / or The heavy chain variable region and the light chain variable region of the second binding functional region targeting IgE are connected by a connector; and / or The first binding functional region of the target TSLP and the second binding functional region of the target IgE are connected by a connector.

5. The bispecific antibody targeting TSLP and IgE according to any one of claims 1 to 4, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:1; the first binding functional region targeting TSLP comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:5; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:9; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:13; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:17; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:21; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of sequence VH of SEQ ID NO:25; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of sequence VH with sequence SEQ ID NO:26; or The first binding functional region targeting TSLP includes two heavy chain variable regions, wherein the HCDR1, HCDR2, and HCDR3 of the first heavy chain variable region are the HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:25, and the HCDR1, HCDR2, and HCDR3 of the second heavy chain variable region are the HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:26; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:39; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:43; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:47; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:51; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:55; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:59; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:63; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:67; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:71; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:75; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:79; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:83; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:87; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:91; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:95; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:96; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:97; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:98; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:119; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:120; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:123; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:124; or The first binding functional region targeting TSLP includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:198; the first binding functional region targeting TSLP includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:

202.

6. The bispecific antibody targeting TSLP and IgE according to any one of claims 1-5, wherein the second binding functional region targeting IgE comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:206; the second binding functional region targeting IgE comprises a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with the sequence SEQ ID NO:210; or The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:218; or The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with sequence SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL with sequence SEQ ID NO:

226.

7. The bispecific antibody targeting TSLP and IgE according to any one of claims 1 to 6, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are the HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:25; and The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four, or five, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable regions are independently selected from the HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:206, SEQ ID NO:214, and SEQ ID NO:222; and / or the LCDR1, LCDR2, and LCDR3 of the light chain variable regions are independently selected from the LCDR1, LCDR2, and LCDR3 of VL shown in SEQ ID NO:210, SEQ ID NO:218, and SEQ ID NO:226; Preferably, the second binding functional region targeting IgE includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are the HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are the LCDR1, LCDR2, and LCDR3 of VL shown in SEQ ID NO:210; or The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH as shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL as shown in SEQ ID NO:218; or The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL shown in SEQ ID NO:

226.

8. The bispecific antibody targeting TSLP and IgE according to any one of claims 1 to 7, wherein the first binding functional region targeting TSLP comprises a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are the HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:26; and The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four, or five, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable regions are independently selected from the HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:206, SEQ ID NO:214, and SEQ ID NO:222; and / or the LCDR1, LCDR2, and LCDR3 of the light chain variable regions are independently selected from the LCDR1, LCDR2, and LCDR3 of VL shown in SEQ ID NO:210, SEQ ID NO:218, and SEQ ID NO:226; Preferably, the second binding functional region targeting IgE includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are the HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are the LCDR1, LCDR2, and LCDR3 of VL shown in SEQ ID NO:210; or The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH as shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL as shown in SEQ ID NO:218; or The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL shown in SEQ ID NO:

226.

9. The bispecific antibody targeting TSLP and IgE according to any one of claims 1 to 8, wherein the first binding functional region targeting TSLP comprises two heavy chain variable regions, wherein the HCDR1, HCDR2, and HCDR3 of the first heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:25, and the HCDR1, HCDR2, and HCDR3 of the second heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH with the sequence SEQ ID NO:26; and The second binding functional region targeting IgE includes one or more heavy chain variable regions and / or one or more light chain variable regions, such as one, two, three, four, or five, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable regions are independently selected from the HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:206, SEQ ID NO:214, and SEQ ID NO:222; and / or the LCDR1, LCDR2, and LCDR3 of the light chain variable regions are independently selected from the LCDR1, LCDR2, and LCDR3 of VL shown in SEQ ID NO:210, SEQ ID NO:218, and SEQ ID NO:226; Preferably, the second binding functional region targeting IgE includes a heavy chain variable region, wherein the HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are the HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:206; the second binding functional region targeting IgE includes a light chain variable region, wherein the LCDR1, LCDR2, and LCDR3 of the light chain variable region are the LCDR1, LCDR2, and LCDR3 of VL shown in SEQ ID NO:210; or The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH as shown in SEQ ID NO:214; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL as shown in SEQ ID NO:218; or The second binding functional region targeting IgE includes a heavy chain variable region, wherein HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are HCDR1, HCDR2, and HCDR3 of VH shown in SEQ ID NO:222; the second binding functional region targeting IgE includes a light chain variable region, wherein LCDR1, LCDR2, and LCDR3 of the light chain variable region are LCDR1, LCDR2, and LCDR3 of VL shown in SEQ ID NO:

226.

10. The bispecific antibody targeting TSLP and IgE according to any one of claims 1 to 9, wherein the bispecific antibody targeting TSLP and IgE is selected from symmetrical bispecific antibodies containing an Fc region, asymmetrical bispecific antibodies containing an Fc region, and antibody fragment conjugates without an Fc region. Preferably, the first binding functional region targeting TSLP forms a homodimer with the Fc region, and the second binding functional region targeting IgE is linked to and / or fused to: the C-terminus of the Fc region, and / or the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the first binding functional region targeting TSLP, forming a symmetrical bispecific antibody; or The second binding functional region targeting IgE forms a homodimer with the Fc region, and the first binding functional region targeting TSLP is linked to and / or fused to: the C-terminus of the Fc region, and / or the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the second binding functional region targeting IgE, forming a symmetrical bispecific antibody; or The first binding functional region targeting TSLP and the second binding functional region targeting IgE are connected through the Fc region to form a heterodimer; or The first binding functional region targeting TSLP forms a homodimer with the Fc region, and the second binding functional region targeting IgE is linked to and / or fused to: the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the first binding functional region targeting TSLP, and / or the C-terminus of the Fc region, forming an asymmetric bispecific antibody; or The second binding functional region targeting IgE forms a homodimer with the Fc region, and the first binding functional region targeting TSLP is linked to and / or fused to: the N-terminus of the heavy chain and / or the N-terminus and / or the C-terminus of the light chain of the second binding functional region targeting IgE, and / or the C-terminus of the Fc region, forming an asymmetric bispecific antibody; or The bispecific antibody targeting TSLP and IgE, wherein the first binding functional region targeting TSLP and the second binding functional region targeting IgE are linked by a linker; and the heavy chain variable region and / or light chain variable region of the second binding functional region targeting IgE are linked by a linker; or The first binding functional region targeting TSLP and the second binding functional region targeting IgE are connected by connectors, and the heavy chain variable region and / or light chain variable region of the first binding functional region targeting TSLP are connected by connectors, and the heavy chain variable region and / or light chain variable region of the second binding functional region targeting IgE are connected by connectors.

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