Anti-IL-25 antibodies and methods of their use.

Description

1 / 93 “ANTI-IL-25 ANTIBODIES AND METHODS OF USE” FIELD

[001] The present invention relates to antibodies and antibody fragments that bind to interleukin-25. The antibodies may be useful for the prevention and / or treatment of type 2 inflammatory diseases, autoimmune diseases or cancer. BACKGROUND

[002] The interleukin-17 (IL-17) family belongs to a group of cytokines that play a crucial role in inflammatory responses during autoimmune pathogenesis and in host defense against extracellular pathogens. IL-25 (also known as IL-17E) is produced not only by immune cells (e.g., T cells, dendritic cells, and macrophages) but also by other non-immune cells (e.g., fibroblasts, epithelial cells, and keratinocytes) and even some cancerous cells (such as melanoma, liver cancer, breast cancer, and cervical cancer) (Gowhari Shabgah, A., et al., Cancer Med. (2021) 10:51915202). The diversity of cellular sources suggests that IL-25 participates in many immune responses and cellular processes.

[003] IL-25 is distinctly different from other members of the IL17 family in terms of molecular structure and biological function. As an epithelial cell cytokine, IL-25, along with TSLP and IL-33, is responsible for the role of an “alarm” or barrier surface cytokine and alerts the immune system to extrinsic environmental threats (such as allergens, bacteria, viruses and helminths) and mobilizes host immune defense mechanisms (Ham, J. et al., Immune Netw. (2022) (1):e11, Borowczyk J. et al, Journal of Allergy and Clinical Immunology (2021) 148(1) 40-52). Recent studies suggest that epithelial cytokines also have a wide range of effector functions in numerous pathological conditions, including type 2 inflammatory diseases, allergic disorders, viral infections, chronic inflammatory disorders, autoimmune conditions, and cancer. Petition 870250103158, dated 11 / 11 / 2025, page 7 / 127 2 / 93

[004] IL-25 plays a dual role in regulating immune responses and in the pathogenesis of autoimmune diseases. As a pro-inflammatory cytokine, IL-25 exacerbates allergic inflammation by promoting the production of Th2 cytokines, including IL-4, IL-5, and IL-13, by Th2 cells. In addition, IL-25 can induce the proliferation and activation of innate immune cells, the production of other pro-inflammatory cytokines, and the recruitment of immune cells (Deng, C. et al., Front. Immunol (2021) 12:691559).

[005] On the other hand, IL-25 has been reported to play a role in autoimmune diseases as an anti-inflammatory cytokine and an inhibitor of innate and adaptive immunity (Saadoun, D. et al., Current pharmaceutical design (2011) 17:3781-3785. For example, the anti-inflammatory and immunosuppressive activities of IL-25 in rheumatoid arthritis are attributed to an IL-13-dependent downregulation of the Th17 cell response (Liu, D. et al., Sci Rep (2016) 6:36002).

[006] Furthermore, the expression of IL-25 and its receptor has been downregulated in several types of cancer compared to normal tissues. Therefore, it has been indicated that IL-25 may also play a secondary role in cancer progression or regression. The tumor-suppressive role of IL-25 is mainly attributed to the infiltration of eosinophils and B cells into the tumor microenvironment and the induction of apoptosis. In contrast, its tumor-supporting functions depend on the diversion of immune responses and the stimulation of EMT and cell growth (Gowhari Shabgah, A. et al., Cancer Med. (2021) 10: 5191- 5202).

[007] Although the IL-25 pathway is a recognized therapeutic target, only a single Phase I clinical trial evaluating the safety, tolerability, and pharmacokinetic characteristics of IL-25 has been identified to date. Consequently, there is an unmet need in the art for novel IL-25 antagonists, such as the anti-IL-25 antibodies described herein, for the treatment of diseases or disorders associated with IL-25 expression and / or signaling. Petition 870250103158, dated 11 / 11 / 2025, page 8 / 127 3 / 93 SUMMARY

[008] The present invention addresses the above need by providing antibodies and antibody fragments that bind to IL-25, including human IL-25. The antibodies and their antibody fragments are useful for the treatment of immune-mediated inflammatory diseases (IMIDs) (e.g., autoimmune diseases and inflammatory disorders) and cancer. Anti-IL-25 antibodies or their antibody fragments can be used alone (e.g., as monotherapy) or in combination with other immunotherapeutic agents. In an alternative embodiment, an antibody fragment of an IL-25 antibody described herein can be used as a component of a bispecific or multispecific antibody or fusion protein.

[009] In some embodiments, the anti-IL-25 antibody or antibody fragment thereof binds to the IL-25 cytokine (IL-17E) with high affinity and does not bind (i.e., binds specifically) to any other member of the IL-17 cytokine family.

[0010] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain region comprising CDR1: SEQ ID NO: 11, CDR2: SEQ ID NO: 12, and CDR3: SEQ ID NO: 13; and / or a variable light chain region comprising CDR1: SEQ ID NO: 14, CDR2: SEQ ID NO: 15, and CDR3: SEQ ID NO: 16

[0011] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain region comprising CDR1: SEQ ID NO: 17, CDR2: SEQ ID NO: 18, and CDR3: SEQ ID NO: 19; and / or a variable light chain region comprising CDR1: SEQ ID NO: 20, CDR2: SEQ ID NO: 21, and CDR3: SEQ ID NO: 22

[0012] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain region comprising CDR1: SEQ ID NO: 23, CDR2: SEQ ID NO: 24, and CDR3: SEQ ID NO: 25; and / or a variable light chain region comprising Petition 870250103158, dated 11 / 11 / 2025, page 9 / 127 4 / 93CDR1: SEQ ID NO: 26, CDR2: SEQ ID NO: 27, and CDR3: SEQ ID NO: 28

[0013] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain region comprising CDR1: SEQ ID NO: 29, CDR2: SEQ ID NO: 30, and CDR3: SEQ ID NO: 31; and / or a variable light chain region comprising CDR1: SEQ ID NO: 32, CDR2: SEQ ID NO: 33, and CDR3: SEQ ID NO: 34

[0014] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain region comprising CDR1: SEQ ID NO: 35, CDR2: SEQ ID NO: 36 and CDR3: SEQ ID NO: 37; and / or a variable light chain region comprising CDR1: SEQ ID NO: 38, CDR2: SEQ ID NO: 39 and CDR3: SEQ ID NO: 40

[0015] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain region comprising CDR1: SEQ ID NO:23 CDR2: SEQ ID NO: 49 and CDR3: SEQ ID NO: 25;and / or a variable light chain region comprising CDR1: SEQ ID NO: 50, CDR2: SEQ ID NO: 51 and CDR3: SEQ ID NO: 28;

[0016] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain region comprising CDR1: SEQ ID NO: 23, CDR2: SEQ ID NO: 52, and CDR3: SEQ ID NO: 25; and / or a variable light chain region comprising CDR1: SEQ ID NO: 50, CDR2: SEQ ID NO: 51, and CDR3: SEQ ID NO: 28

[0017] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain region with an amino acid sequence selected from the group consisting of the SEQ ID NOs: 1, 3, 5, 7 and 9.

[0018] In other embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable region of the light chain with an amino acid sequence selected from the group consisting of the SEQ ID NOs: 2, 4, 6, 8 and 10.

[0019] In other embodiments, the anti-IL-25 antibody or its fragment Petition 870250103158, dated 11 / 11 / 2025, page 10 / 127 5 / 93 of antibody comprises a variable heavy chain region with an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, 5, 7 and 9 and a variable light chain sequence selected from the group consisting of SEQ ID NOs: 2, 4, 6, 8 and 10.

[0020] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises a humanized heavy chain variable region with an amino acid sequence selected from the group consisting of SEQ IDs 44 and 47.

[0021] In other embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable humanized light chain region with an amino acid sequence selected from the group consisting of SEQ ID NOs: 45, 46 and 48.

[0022] In other embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain region with an amino acid sequence selected from the group consisting of SEQ ID NOs: 44 and 47 and a variable light chain sequence selected from the group consisting of SEQ ID NOs: 45, 46 and 48.

[0023] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain region sequence and a variable light chain region sequence, selected from the following combinations: (a) a variable heavy chain sequence comprising SEQ ID NO: 1 and a variable light chain sequence comprising SEQ ID NO: 2; (b) a variable heavy chain sequence comprising SEQ ID NO: 3 and a variable light chain sequence comprising SEQ ID NO: 4; (c) a variable heavy chain sequence comprising SEQ ID NO: 5 and a variable light chain sequence comprising SEQ ID NO: 6; Petition 870250103158, dated 11 / 11 / 2025, page 11 / 127 6 / 93 (d) a variable heavy chain sequence comprising SEQ ID NO: 7 and a variable light chain sequence comprising SEQ ID NO: 8; (e) a variable heavy chain sequence comprising SEQ ID NO: 9 and a variable light chain sequence comprising SEQ ID NO: 10; (f) a variable heavy chain sequence comprising SEQ ID NO: 44 and a variable light chain sequence comprising SEQ ID NO: 45; (g) a variable heavy chain sequence comprising SEQ ID NO: 44 and a variable light chain sequence comprising SEQ ID NO: 46 or (h) a variable heavy chain sequence comprising SEQ ID NO: 47 and a variable light chain sequence comprising SEQ ID NO: 48.

[0024] In some embodiments, the antibody is a human anti-IL-25 antibody.

[0025] In some embodiments, the antibody is a full-length antibody.

[0026] In some embodiments, the antibody is a full-length antibody comprising a constant region of human IgG1 selected from SEQ ID NO: 55 or SEQ ID NO: 56.

[0027] In some embodiments, the antibody fragment is selected from the group consisting of: Fab, Fab, F(ab)2, Fd, Fv, scFv and scFv-Fc fragments, a single-chain antibody, a minibody and a diabody.

[0028] In some embodiments, the antibody is a monoclonal antibody.

[0029] In some embodiments, the antibody is a human antibody (e.g., a fully human antibody).

[0030] In some embodiments, the antibody is a murine antibody. Petition 870250103158, dated 11 / 11 / 2025, p. 12 / 127 7 / 93

[0031] In some embodiments, the antibody is a chimeric antibody.

[0032] In some embodiments, the antibody is a bispecific antibody.

[0033] In some embodiments, the antibody is a humanized antibody.

[0034] The present invention also provides a pharmaceutical composition comprising the antibody or antibody fragment described herein and a pharmaceutically acceptable carrier.

[0035] Furthermore, the present invention provides methods for treating and / or preventing a type 2 inflammatory disease, autoimmune disease, allergic disorder, or cancer in a needy individual, the method comprising: administering to the individual the antibody or antibody-binding fragment as described herein.

[0036] The present invention also provides a polynucleotide composition comprising a first polynucleotide encoding a variable region of the heavy chain comprising the amino acid sequence presented in SEQ ID NOs: 1, 3, 5, 7, 9, 44 or 47; and a second polynucleotide encoding a variable region of the light chain comprising the amino acid sequence presented in SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46 or 48.

[0037] In addition, the present invention provides a vector composition comprising a first vector comprising a first polynucleotide as described herein (for example, a polynucleotide encoding the SEQ ID NOs: 1, 3, 5, 7, 9, 44 or 47); and a second vector comprising a second polynucleotide as described herein (for example, a polynucleotide encoding the SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46 or 48).

[0038] The present invention also provides a cell (for example, a CHO cell) comprising a polynucleotide composition described herein, or a vector composition described herein. Petition 870250103158, dated 11 / 11 / 2025, page 13 / 127 8 / 93

[0039] The present invention also provides methods for producing an anti-IL-25 antibody or antibody fragment thereof, as described herein, comprising cultivating a cell described herein expressing an anti-IL-25 antibody or antibody fragment thereof in a culture medium; and recovering the anti-IL-25 antibody or antibody fragment thereof from the medium. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] The preceding summary, as well as the following detailed description of the invention, will be better understood when read in conjunction with the accompanying figures. For the purpose of illustrating the invention, embodiments that are currently preferred are shown in the figures. It should be understood, however, that the invention is not limited to the precise arrangements, examples, and instrumentation shown.

[0041] Figures 1A - 1D provide the amino acid sequences of the VH and VL domains of anti-IL-25 antibodies and their respective CDR sequences. Sequence identifiers are provided and the CDRs determined by Kabat are underlined in the context of the variable domain sequence.

[0042] Figures 2A - B provide the amino acid sequence of human, mouse and cynomolgus monkey IL-25, and the amino acid sequences of the constant regions of human or mouse antibodies.

[0043] Figures 3A - 3C show the binding of anti-IL-25 antibodies to recombinant human, mouse, and cynomolgus IL-25 proteins. ELISA using goat anti-human IgG-HRP as detection demonstrates the binding of anti-IL-25 antibodies to recombinant human (3A) and mouse (3B) IL-25 proteins. ELISA using goat anti-human Kappa light chain HRP antibody as detection demonstrates the binding of anti-IL-25 antibodies to cynomolgus IL-25 proteins (3C).

[0044] Figure 4 demonstrates that anti-IL-25 antibodies inhibit human IL-25-induced NFkB signaling in HEK reporter cells. Petition 870250103158, 11 / 11 / 2025, p. 14 / 127 9 / 93 Blue IL-17.

[0045] Figure 5 shows that anti-IL-25 antibodies inhibit IL-25-induced CXCL-1 production in the HT29 human colon cancer cell line.

[0046] Figure 6 shows that anti-IL-25 antibodies inhibit IL-5 production induced by IL-25 in a human PBMC assay.

[0047] Figures 7A-7B show that anti-IL-25 antibodies reduce airway resistance in the OVA-induced asthma model. Airway hyperresponsiveness (AHR) of OVA-sensitized / challenged BALB / c mice to methacholine challenge. The AHR of each mouse is measured using the Buxo whole-body plethysmography (WBP) system on day 31. AHR is expressed as a percentage change from baseline pulmonary resistance level (Penh value). Dose-response data are presented as group means ± SEM (7A) and AUC of % of baseline Penh (7B). ** p < 0.01, *** p < 0.001 compared to OVA + Vehicle using repeated measurement / Bonferroni (7A) and ** p < 0.01, *** p < 0.001 compared to OVA + Vehicle using Anova / One-way Dunnett's (7B).

[0048] Figure 8 demonstrates that anti-IL-25 antibodies inhibit IL-5 production in the lung of the OVA-induced asthma model. ** p < 0.01, *** p < 0.001 compared to OVA + Vehicle using one-way Dunnett ANOVA.

[0049] Figures 9A - 9C show the binding of humanized anti-IL-25 antibodies to recombinant human IL-25 (9A), cynomolgus IL-25 (9B) and mouse IL-25 (9C) measured by ELISA.

[0050] Figure 10 demonstrates that humanized anti-IL-25 antibodies inhibit human IL-25-induced NFkB signaling in HEK-Blue IL-17 reporter cells.

[0051] Figure 11 shows that humanized anti-IL-25 antibodies inhibit IL-25-induced CXCL-1 production in the cancer cell line of Petition 870250103158, dated 11 / 11 / 2025, page 15 / 127 10 / 93 human colon HT29.

[0052] Figure 12 shows that humanized anti-IL-25 antibodies inhibit IL-5 production induced by IL-25 in a human PBMC assay. DETAILED DESCRIPTION

[0053] In order to make the invention more easily understood, certain technical and scientific terms are specifically defined below. Unless specifically defined elsewhere in this document, all other technical and scientific terms used herein have the meaning commonly understood by a person of ordinary skill in the art to which this invention pertains.

[0054] Throughout this invention, the following abbreviations will be used: mAb or Mab or MAb - Monoclonal antibody. CDR - Complementar determinant region in the immunoglobulin variable regions. HCDR - Complementar region of the heavy chain. LCDR - Complementar regions of the light chain. VH - Variable region of the immunoglobulin heavy chain. VL - Variable region of the immunoglobulin light chain. FR - Antibody structural region, variable regions of the immunoglobulin, excluding CDR regions.

[0055] As used herein, the term “interleukin-25” (used interchangeably with “IL-25”) refers to the native sequence polypeptide, isoforms, chimeric polypeptides, all homologs, fragments, and precursors of human IL-25. Amino acid sequences for human, cynomolgus, and murine IL-25 are provided in the NCBI Reference Sequences: NP_073626.1 (human) (SEQ ID NO: 41), XP_005560919.1 (cynomolgus monkey) (SEQ ID NO: 43), and NP_542767.1 (mouse) (SEQ ID NO: 42). IL-25 orthologs share -92% and -80% homology with the human protein in cynomolgus monkeys and mice, respectively. Petition 870250103158, dated 11 / 11 / 2025, p. 16 / 127 11 / 93 respectively.

[0056] As used herein, the term “IL-25 complex” refers to the IL-17RA / IL-17RB complex, also known as the IL-25 receptor.

[0057] As used herein, the term “IL-17RA” refers to the interleukin 17A receptor, also known as CDw217 (cluster of differentiation w217). The protein encoded by this gene (interleukin 17A receptor; IL-17RA) is a ubiquitous type I membrane glycoprotein that binds with low affinity to interleukin 17A.

[0058] As used herein, the term “IL-17RB” refers to the interleukin-17 receptor B. This receptor specifically binds to IL-17B and IL-17E (IL-25), but does not bind to IL-17A or IL-17C.

[0059] The term “antibody” here is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, and multispecific antibodies (e.g., bispecific antibodies).

[0060] An exemplary antibody, such as an IgG, comprises two heavy chains and two light chains. Each heavy chain is composed of a variable heavy chain region (abbreviated here as VH) and a constant heavy chain region. Each light chain is composed of a variable light chain region (abbreviated here as VL) and a constant light chain region. The VH and VL regions can be subdivided into regions of hypervariability, called complementarity-determining regions (CDRs), interspersed with more conserved regions, called structure regions (FRs). Each VH and VL is composed of three CDRs and four FRs, arranged from the amino terminal to the carboxy-terminal in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.

[0061] The hypervariable region generally encompasses amino acid residues of approximately 24-34 (LCDR1; “L” denotes light chain), 50-56 (LCDR2), and 89-97 (LCDR3) in the variable region of the light chain and approximately 31-35B (HCDR1; “H” denotes heavy chain), 50-65 (HCDR2), and 95-102 (HCDR3) Petition 870250103158, dated 11 / 11 / 2025, page 17 / 127 12 / 93 in the variable region of the heavy chain; Kabat et al., SEQUENCES OF PROTEINS OF IMMUNOLOGICAL INTEREST 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991) and / or those residues that form a hypervariable loop (e.g., residues 26-32 (LCDR1), 50-52 (LCDR2) and 91-96 (LCDR3) in the variable region of the light chain and 26-32 (HCDR1), 53-55 (HCDR2) and 96-101 (HCDR3) in the variable region of the heavy chain; Chothia and Lesk (1987) J. Mol. Biol. 196:901-917.

[0062] The term “monoclonal antibody,” as used herein, refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies that make up the population are identical and / or bind to the same epitope, except for possible variant antibodies, i.e., containing mutations that occur naturally or arise during the production of a monoclonal antibody preparation, such variants generally being present in minor quantities. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody in a monoclonal antibody preparation is directed against a single determinant on an antigen.Thus, the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and should not be interpreted as requiring the production of the antibody by any method. For example, the monoclonal antibodies to be used according to the present invention can be produced by a variety of techniques, including, but not limited to, the hybridoma method, recombinant DNA methods, phage display methods, and methods using transgenic animals containing all or part of the human immunoglobulin loci, such methods and other exemplary methods for producing monoclonal antibodies being described herein.

[0063] The term “chimeric” antibody refers to an antibody Petition 870250103158, dated 11 / 11 / 2025, page 18 / 127 13 / 93 recombinant in which a portion of the heavy and / or light chain is derived from a specific source or species, while the remainder of the heavy and / or light chain is derived from a different source or species.

[0064] A “human antibody” is an antibody that has an amino acid sequence corresponding to that of an antibody produced by a human being and / or has been made using any of the techniques for making human antibodies known to a person skilled in the art. This definition of a human antibody specifically excludes a humanized antibody comprising residues binding to non-human antigens. Human antibodies can be produced using various techniques known in the field, including methods described in 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 the antigen to a transgenic humanized animal that has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been deactivated, for example, immunized HuMab mice (see, for example, Nils Lonberg et al., 1994, Nature 368:856-859, WO 98 / 24884, WO 94 / 25585, WO 93 / 1227, WO 92 / 22645, WO 92 / 03918 and WO 01 / 09187 concerning HuMab mice), xenomice (see, for example, US Patents Nos. 6,075,181 and 6,150,584 concerning XENOMOUSE™ technology) or Trianni mice (see, for example, WO 2013 / 063391, WO 2017 / 035252 and WO 2017 / 136734).

[0065] The term “humanized antibody” refers to an antibody that has been designed to comprise one or more regions of human structure in the variable region, along with non-human (e.g., mouse, rat, or hamster) complementarity-determining regions (CDRs) of the heavy and / or light chain. In certain embodiments, a humanized antibody comprises sequences that are entirely human except for the CDR regions. Humanized antibodies are Petition 870250103158, dated 11 / 11 / 2025, page 19 / 127 14 / 93 antibodies are typically less immunogenic to humans compared to non-humanized antibodies and therefore offer therapeutic benefits in certain situations. Those skilled in the art will be aware of humanized antibodies and the appropriate techniques for their generation. See, for example, Hwang, WYK, et al., Methods 36:35, 2005; Queen et al., Proc. Natl. Acad. Sci. USA, 86:10029-10033, 1989; Jones et al., Nature, 321:522-25, 1986; Riechmann et al., Nature, 332:323-27, 1988; Verhoeyen et al., Science, 239:1534-36, 1988; Orlandi et al., Proc. Natl. Acad. Sci. USA, 86:3833-37, 1989; US Patents Nos. 5,225,539; 5,530,101; 5,585,089; 5,693,761; 5,693,762; 6,180,370; and Selick et al., WO 90 / 07861, each of which is incorporated herein by reference in its entirety.

[0066] The “class” of an antibody refers to the type of constant domain or constant region possessed by its heavy chain. There are five main classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these can be divided into subclasses (isotypes), for example, IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The constant domains of the heavy chain that correspond to the different classes of immunoglobulins are called α, δ, ε, γ, and μ, respectively.

[0067] The terms “antigen-binding domain” of an antibody (or simply “binding domain”) or similar terms refer to one or more fragments of an antibody that retain the ability to bind specifically to an antigen complex. Examples of binding fragments encompassed by the term “antigen-binding portion” of an antibody include (i) Fab fragments, monovalent fragments consisting of the VL, VH, CL, and CH domains; (ii) F(ab')2 fragments, bivalent fragments comprising two Fab fragments linked by a disulfide bridge in the hinge region; (iii) Fd fragments consisting of the VH and CH domains; (iv) Fv fragments consisting of the VL and VH domains of a single arm of an antibody; (v) dAb fragments Petition 870250103158, dated 11 / 11 / 2025, page 20 / 127 15 / 93 (Ward et al., (1989) Nature 341: 544-546), which consist of a VH domain; (vi) isolated complementarity-determining regions (CDRs) and (vii) combinations of two or more isolated CDRs that may optionally be joined by a synthetic ligand.

[0068] “Complementarity-determining region” or “CDR”, as the terms are used here, refers to short polypeptide sequences within the variable region of heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. There are three CDRs (designated CDR1, CDR2, and CDR3) in each VL and each VH.

[0069] As will be understood by those skilled in the art, the exact numbering and positioning of the CDRs may differ between different numbering systems. However, it should be understood that the invention of a variable heavy and / or variable light sequence includes the invention of the associated CDRs. Consequently, the invention of each variable heavy region is an invention of the vhCDRs (e.g., vhCDRI, vhCDR2, and vhCDR3) and the invention of each variable light region is an invention of the vICDRs (e.g., vICDRI, vlCDR2, and vlCDR3).

[0070] In certain embodiments, the CDRs of an antibody can be determined according to the IMGT numbering system, as described in Lefranc MP, (1999) The Immunologist 7: 132-136 and Lefranc MP et al, (1999) Nucleic Acids Res 27: 209-212, each of which is incorporated herein by reference in its entirety. Unless otherwise indicated herein, references to residue numbers in the variable domain of antibodies mean residue numbering by the Kabat numbering system.

[0071] In other modalities, the CDRs of an antibody can be determined according to MacCallum RM et al, (1996) J Mol Biol 262: 732-745, incorporated here by reference in its entirety. See also, for example, Martin A. Protein Sequence and Structure Analysis of Antibody Petition 870250103158, dated 11 / 11 / 2025, page 21 / 127 16 / 93 Variable Domains, in Antibody Engineering, Kontermann and Diibel, eds., Chapter 31, pp. 422-439, Springer-Verlag, Berlin (2001), incorporated herein by reference in its entirety. In other embodiments, the CDRs of an antibody can be determined according to the AbM numbering scheme, which refers to the AbM hypervariable regions, representing a compromise between Kabat CDRs and Chothia structural loops, and are used by the Oxford Molecular antibody modeling software AbM (Oxford Molecular Group, Inc.), incorporated herein by reference in its entirety.

[0072] “Structure” or “structure region” or “FR” refers to variable domain residuals other than hypervariable region (HVR) residuals. The FR of a variable domain generally consists of four FR domains: FR1, FR2, FR3, and FR4.

[0073] A “human consensus structure” is a structure that represents the amino acid residues most commonly found in a selection of human immunoglobulin VL or VH structure sequences. Generally, the selection of human immunoglobulin VL or VH sequences is from a variable domain sequence subgroup. Generally, the sequence subgroup is a subgroup as in Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, NIH Publication 913242, Bethesda Md. (1991), Vols. 1-3. In one embodiment, for the VL, the subgroup is the kappa I subgroup as in Kabat et al., supra. In one embodiment, for the VH, the subgroup is the III subgroup as in Kabat et al., supra.

[0074] The “hinge region” is generally defined as extending from 216-238 (EU numbering) or 226-251 (Kabat numbering) of human lgG1. The hinge can be divided into three distinct regions: the upper, the middle (e.g., the nucleus), and the lower.

[0075] The term “Fc region” here is used to define a C-terminal region of an immunoglobulin heavy chain containing at least Petition 870250103158, dated 11 / 11 / 2025, page 22 / 127 17 / 93 a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. In one embodiment, a human IgG heavy chain Fc region extends from Cys226, or Pro230, to the carboxyl terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. Unless otherwise specified herein, the numbering of amino acid residues in the Fc region or constant region is in accordance with the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Maryland. (1991).

[0076] A “blocking” antibody or an “antagonist” antibody is one that inhibits or reduces the biological activity of the antigen to which it binds. Certain blocking antibodies or antagonist antibodies substantially or completely inhibit the biological activity of the antigen.

[0077] An “antibody that binds to the same epitope” as a reference antibody refers to an antibody that contacts an overlapping set of amino acid residues of the antigen compared to the reference antibody or blocks the binding of the reference antibody to its antigen in a competition assay by 50% or more. The amino acid residues of an antibody that contact an antigen can be determined, for example, by determining the crystal structure of the antibody in complex with the antigen or by performing a hydrogen / deuterium exchange. In some embodiments, residues of an antibody that are within 5 Å of the antigen are considered to be in contact with the antigen.In some embodiments, an antibody that binds to the same epitope as a reference antibody blocks the binding of the reference antibody to its antigen in a competition assay by 50% or more and, conversely, the reference antibody blocks the binding of the antibody to its antigen in a competition assay by 50% or more.

[0078] The term “antibody fragment” refers to a molecule. Petition 870250103158, dated 11 / 11 / 2025, p. 23 / 127 18 / 93 different from an intact antibody which comprises a portion of an intact antibody that binds to the antigen to which the intact antibody binds. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab)2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv). Digestion of antibodies with papain produces two identical antigen-binding fragments, called “Fab” fragments, and a residual “Fc” fragment, a designation that reflects the ability to crystallize easily. The Fab fragment consists of an entire light chain (L) along with the variable region domain of the heavy chain (H) (VH) and the first constant domain of a heavy chain (CH1). Pepsin treatment of an antibody produces a single large F(ab)2 fragment that roughly corresponds to two disulfide-linked Fab fragments with divalent antigen-binding activity and is still capable of cross-linking the antigen.Fab fragments differ from Fab' fragments by having a few additional residues at the carboxylic terminus of the CH1 domain, including one or more cysteines from the hinge region of the antibody. Fab'-SH is the designation used here for Fab' in which the cysteine ​​residue(s) of the constant domains have a free thiol group. F(ab')2 antibody fragments were originally produced as pairs of Fab' fragments that have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

[0079] “Fv” consists of a dimer of a variable region heavy chain domain and a light chain domain in close, non-covalent association. From the folding of these two domains emanate six hypervariable loops (3 loops from each H and L chain) that contribute amino acid residues to antigen binding and confer antigen-binding specificity to the antibody.

[0080] “Single-chain Fv”, also abbreviated as “sFv” or “scFv”, are antibody fragments comprising antibody domains Petition 870250103158, dated 11 / 11 / 2025, page 24 / 127 19 / 93 VH and VL connected in a single polypeptide chain. Preferably, the sFv polypeptide further comprises a polypeptide linker between the VH and VL domains that allows sFv to form the desired structure for antigen binding. For a review of sFv, see Plückthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).

[0081] The term “isolated antibody,” when used to describe the various antibodies described herein, means an antibody that has been identified and separated and / or recovered from a cell or cell culture from which it was expressed. Contaminating components from its natural environment are materials that normally interfere with the diagnostic or therapeutic uses of the polypeptide and may include enzymes, hormones, and other protein or non-protein solutes. In some embodiments, an antibody is purified to a purity greater than 95% or 99%, as determined by, for example, electrophoretic approaches (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatographic approaches (e.g., ion exchange or reverse-phase HPLC). For a review of methods for assessing antibody purity, see, for example, Flatman et al., J. Chromatogr. B 848:79-87 (2007).In one embodiment, the antibody will be purified (1) to a degree sufficient to obtain at least 15 N-terminal or internal amino acid sequence residues by using a rotary cup sequencer, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver staining.

[0082] With respect to the binding of an antibody to a target molecule, the term “specific binding” or “binds specifically to” or is “specific for” a specific polypeptide or an epitope on a specific polypeptide target means a binding that is measurably different from a non-specific interaction. Specific binding can be measured, for example, by determining the binding of a molecule to Petition 870250103158, dated 11 / 11 / 2025, p. 25 / 127 20 / 93 comparison to the binding of a control molecule. For example, specific binding can be determined by competition with a control molecule that is similar to the target, for example, an unlabeled target excess. In this case, specific binding is indicated if the binding of the labeled target to a probe is competitively inhibited by the unlabeled target excess.The term “specific binding” or “binds specifically to” or is “specific to” a specific polypeptide or epitope on a specific polypeptide target, as used herein, may be exhibited, for example, by a molecule with a Kd for the target of 10⁴M or lower, alternatively 10⁵M or lower, alternatively 10⁶M or lower, alternatively 10⁷M or lower, alternatively 10⁸M or lower, alternatively 10⁹M or lower, alternatively 10¹⁰M or lower, alternatively 10¹¹M or lower, alternatively 10¹²M or lower, or a Kd in the range of 10⁴M to 10⁶M or 10⁶M to 10¹⁰M or 10⁷M to 10⁹M. As will be appreciated by the skilled craftsman, affinity and Kd values ​​are inversely related. A high affinity for an antigen is measured by a low KD value.In one embodiment, the term “specific binding” refers to binding in which a molecule binds to a specific polypeptide or epitope on a specific polypeptide without substantially binding to any other polypeptide or polypeptide epitope. As used herein, the terms “specific binding,” “binds specifically,” and “binds selectively” refer to the binding of the antibody to an epitope of interleukin-25.

[0083] The term “affinity,” as used herein, means the strength of the binding of an antibody to an epitope. The affinity of an antibody is given by the dissociation constant Kd, defined as [Ab]x[Ag] / [Ab-Ag], where [Ab-Ag] is the molar concentration of the antibody-antigen complex, [Ab] is the molar concentration of the unbound antibody, and [Ag] is the molar concentration of the unbound antigen. The affinity constant Ka is defined by 1 / Kd. Methods for determining the affinity of mAbs can be found in Petition 870250103158, dated 11 / 11 / 2025, p. 26 / 127 21 / 93 Harlow, et al., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1988), Coligan et al., eds., Current Protocols in Immunology, Greene Publishing Assoc, and Wiley Interscience, NY, (1992, 1993), and Muller, Meth. Enzymol. 92:589-601 (1983), whose references are fully incorporated herein by reference. A well-known standard method in the field for determining mAb affinity is the use of surface plasmon resonance (SPR) screening (such as by analysis with a BIAcore™ SPR analytical device).

[0084] An epitope is a technical term that indicates the site or sites of interaction between an antibody and its antigen(s). As described by (Janeway, C. Jr., P. Travers, et al. (2001). Immunobiology: The Immune System in Health and Disease. Part II, Sections 3-8. New York, Garland Publishing, Inc.): An antibody usually recognizes only a small region on the surface of a large molecule, such as a protein... [Certain epitopes] are likely composed of amino acids from different parts of the polypeptide chain [of the antigen] that have been joined together by protein folding. Antigenic determinants of this type are known as conformational or discontinuous epitopes because the recognized structure is composed of segments of the protein that are discontinuous in the amino acid sequence of the antigen, but are joined together in the three-dimensional structure. In contrast, an epitope composed of a single segment of the polypeptide chain is termed a continuous or linear epitope (Janeway, C. Jr.P. Travers, et al. (2001). Immunobiology: The Immune System in Health and Disease. Part II, Sections 3-8. New York, Garland Publishing, Inc.).

[0085] The term “KD”, as used herein, is intended to refer to the dissociation constant of a specific antibody-antigen interaction. It is calculated by the formula: Koff / Kon=KD.

[0086] The term “IC50”, as used herein, is intended to refer to the effective antibody concentration of the present invention required to Petition 870250103158, dated 11 / 11 / 2025, p. 27 / 127 22 / 93 inhibit a specific biological or biochemical function by 50%.

[0087] “EC5o with respect to an agent and a particular activity (e.g., binding to a cell, inhibition of enzymatic activity, activation or inhibition of an immune cell), refers to the efficient concentration of the agent that produces 50% of its maximum response or effect with respect to that activity. “ECioo with respect to an agent and a particular activity refers to the efficient concentration of the agent that produces its substantially maximum response with respect to that activity.

[0088] As used herein, the term “antibody-based immunotherapy” and “immunotherapy” are used to refer broadly to any form of therapy that relies on the targeting specificity of an anti-IL-25 antibody, bispecific molecule, multispecific molecule, binding agent, or fusion protein comprising an IL-25-specific binding agent, to mediate a direct or indirect effect on a cell characterized by aberrant IL-25 expression.The terms are intended to encompass treatment methods using bare antibodies, bispecific antibodies (including T cell engagement, NK cell engagement, and other immune cell / effector cell engagement formats), antibody-drug conjugates, cell therapies using T cells (CAR-T) or NK cells (CAR-NK) designed to comprise a chimeric antigen receptor specific for IL-25, and oncolytic viruses comprising an IL-25-specific binding agent, and gene therapies via administration of antigen-binding sequences of anti-IL-25 antibodies and expression of the corresponding antibody fragments in vivo.

[0089] As used herein, the term “group 2 innate lymphoid cell” (ILC2) refers to a type of immune cell that plays a crucial role in the early stages of immune responses against parasitic worms, allergens, and other environmental aggressors. ILC2s are part of the innate immune system, meaning they can respond rapidly to a Petition 870250103158, dated 11 / 11 / 2025, page 28 / 127 23 / 93 variety of stimuli without prior exposure or specific recognition of the pathogen. ILC2s are characterized by their ability to produce a variety of cytokines, including interleukin (IL)-5 and IL-13, which recruit and activate other immune cells, such as eosinophils, mast cells, and T helper 2 (Th2) cells, to promote a type 2 immune response. This type of response is important in combating parasitic infections, as well as in allergic reactions and tissue repair.

[0090] The term “type 2 inflammation,” also known as type 2 immune response, is a specific type of immune response that is activated in response to a variety of stimuli, including parasitic infections, allergens, and tissue damage. Type 2 inflammation is characterized by the activation of immune cells, such as group 2 innate lymphoid cells (ILC2), eosinophils, mast cells, and T helper 2 (Th2) cells, which produce cytokines such as interleukin (IL)-4, IL-5, and IL-13. The IL-25 / IL-25R axis I. IL-17 family of cytokines

[0091] The IL-17 family is a group of cytokines consisting of six members: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (also known as IL-25), and IL-17F. These cytokines are produced by various types of immune cells, including T cells, mast cells, and innate lymphoid cells, and play critical roles in innate and adaptive immune responses (McGeachy, MJ Immunity. April 16, 2019; 50(4): 892-906).

[0092] IL-17A and IL-17F are the best-studied members of the IL-17 family and are frequently co-expressed and have similar functions. They promote inflammation by inducing the expression of pro-inflammatory cytokines, chemokines, and adhesion molecules, and by stimulating the recruitment and activation of neutrophils and other immune cells.

[0093] IL-17B, IL-17C, and IL-17E have more specialized functions. IL-17B and IL-17C are involved in host defense against bacterial and fungal infections, while IL-17E is important in allergic responses. Petition 870250103158, dated 11 / 11 / 2025, page 29 / 127 24 / 93 and protection against parasitic infections.

[0094] IL-17 cytokines interact with various cell types, which express different heterodimeric receptor complexes, composed of five subunits homologous to IL-17-RA and IL-17RE, with IL-17RA common to all receptors. Each IL-17 receptor subunit is a protein containing a single transmembrane domain with several conserved motifs, such as extracellular fibronectin III-like motifs, transmembrane regions, and cytoplasmic SEF / IL-17R (SEFIR) domains (Zhang Q, J Biol Chem. 2013;288(51):36956-36965).

[0095] IL-17 family cytokines have been implicated in the pathogenesis of several inflammatory and autoimmune diseases, including psoriasis, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease, and are targets for therapeutic intervention in these conditions. II. IL-25 (IL-17E)

[0096] IL-25 has approximately 23% to 33% homology with other members of the IL-17 family and binds to specific IL-17 homologous receptors to transmit signals. The low sequence similarity of IL-25 with other family members suggests that it is highly unlikely that specific anti-IL-25 antibodies will bind to other members of the IL-17 family.

[0097] IL-25 is synthesized as a precursor molecule, which undergoes processing and cleavage to generate the mature and biologically active form of the cytokine. Cleavage of the IL-25 precursor is mediated by several proteases, including furin and other proprotein convertases (PCs), which cleave the precursor protein at specific sites to generate the mature cytokine. The exact sites and mechanisms of cleavage vary depending on the cell or tissue type in which it is produced. In particular, proteolytic cleavage of IL-25 at specific sites can enhance or inhibit its ability to activate downstream signaling pathways (Matsushita, K. et al. JCI Insight. February 27, 2020; 5(4): e131480). Petition 870250103158, dated 11 / 11 / 2025, page 30 / 127 25 / 93

[0098] IL-25 is secreted as a disulfide-linked homodimeric glycoprotein and is produced by a variety of cells, including epithelial cells, T cells, and innate lymphoid cells.

[0099] IL-25 interacts with and signals through the IL-25 receptor, which comprises heterodimeric subunits of the IL-17RB / IL-17RA receptor (Iwakura, et al., (2010), Immunity, 34:149). Through its receptor, IL-25 promotes and sustains the Th2-type immune response and induces the expansion of type 2 innate lymphoid cells (ILC2) and M2 macrophages.

[00100] Although IL-25 is widely produced by various cell types, the expression of its receptor is more limited. The IL-25 receptor is present in innate immune cells, such as invariant natural killer T cells (iNKTs), ILC2s, eosinophils, basophils, mast cells, and antigen-presenting cells (APCs). Cellular expression of IL-17RB and how IL-17RB expression changes in different disorders, particularly in inflammatory airway disorders and skin inflammation (Rickel EA, J Immunol. 2008;181 (6):4299-4310).

[00101] IL-25 interacts only with IL-17RB to allosterically facilitate the formation of the IL-17RB-IL-17RA 'end-to-end' interface, which is an essential receptor-receptor interaction required to initiate signal transduction.

[00102] Upon binding to its receptor complex, IL-25 triggers the recruitment and phosphorylation of ACT1, which serves as a critical adaptor protein for further signaling. IL-25 has been shown to activate several downstream signaling cascades, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), and Janus kinase / signal transducer and activator of transcription (JAK / STAT) in a cellular context-dependent manner (Borowczyk J et al., J Allergy Clin Immunol. Jul; 148(1):40-52 (2021), leading to the expression of several pro-inflammatory cytokines, chemokines, and other immune system-related genes (Amini P., et al. (2018). American Journal of Rhinology & Allergy, Petition 870250103158, dated 11 / 11 / 2025, page 31 / 127 26 / 93 32(2), 115-124.). III. Mechanism of action of IL-25 in pathogenesis

[00103] IL-25 can enhance a Th2-type immune response. Th2 cells are a subset of T cells that produce cytokines such as IL-4, IL-5, and IL-13, which are involved in allergic responses and defense against parasites. IL-25 can stimulate the differentiation of naive T cells into Th2 cells and increase the production of Th2 cytokines. This effect is important in regulating allergic responses and host defense against certain infections (Liu et al, J Immunol Res 2018).

[00104] IL-25 can also stimulate innate lymphoid cells (ILC2s). ILCs are a group of immune cells that play a role in defense against pathogens and tissue repair. ILC2s are a subset of ILCs that produce Th2 cytokines and are involved in allergic responses. IL-25 can stimulate the activation and proliferation of ILC2s, leading to the production of Th2 cytokines and the initiation of immune responses (Wu. J. Front Immunol. 2022; 13: 986118).

[00105] IL-25 can also promote the accumulation of inducible co-stimulatory molecules (ICOs) and T1 / ST2 in nucleocytes. Nuocytes are a recently discovered subset of innate immune cells that produce Th2 cytokines and play a role in allergy and host defense. IL-25 can promote the accumulation of ICOS and T1 / ST2, which are molecules expressed on the surface of nucleocytes and involved in their activation and function (C. Wang, et al. PLoS One, vol. 11, no. 9).

[00106] IL-25 can also stimulate the differentiation of naive T cells into Th2 cells, leading to the production of Th2 cytokines such as IL-4, IL-5, and IL-13.

[00107] In addition, IL-25 increases the production of chemokines and promotes eosinophil recruitment and inflammation. Chemokines regulate the migration and activation of immune cells. IL-25 can increase the production of chemokines that promote eosinophil recruitment, Petition 870250103158, dated 11 / 11 / 2025, page 32 / 127 27 / 93 involved in defense against parasites and allergic responses. This recruitment can lead to inflammation and tissue damage (J. Beale, et al Sci Trans Med, v6, no. 256, (2014).

[00108] IL-25 can also promote airway remodeling, which refers to structural changes in the airways that occur in response to chronic inflammation. This can include increased mucus secretion, extracellular collagen deposition, smooth muscle cell proliferation, and angiogenesis (formation of new blood vessels). These changes can lead to airway obstruction and impaired breathing (M. Suzukawa, et al., J Immunol. 2012 Oct 1; 189(7)). IV. Therapeutic management of diseases and disorders related to IL-25 a. Type 2 inflammatory disorders

[00109] Diseases of the respiratory system, such as asthma and allergies, are characterized by type 2 inflammation. IL-25, a type 2 cytokine produced by Th2 cells, induces the production of IL-4, IL-5, and IL-13, leading to inflammation of the respiratory tract.

[00110] Asthma is a heterogeneous inflammatory disease characterized by airflow obstruction, wheezing, eosinophilia, and airway neutrophilia. Asthma can be broadly divided into two categories: eosinophilic (Th2) and non-eosinophilic (non-Th2), but multiple phenotypes are recognized, with variable underlying biology.

[00111] Elevated plasma levels of IL-25 are associated with the allergic asthma phenotype (Tang W., et al. Int Arch Allergy Immunol; 163: 510 (2014)), and sputum IL-25 concentration correlates with disease severity. Sputum IL-25 also increases in patients with atopic asthma compared to patients with non-atopic asthma (Paplinska-Goryca M. et al. Postepy Dermatol Alergol; 35: 462-469 (2018)). The relationship between IL-25 and neutrophilic airway inflammation suggests a pleiotropic role of IL-25 in the immune response in asthma. Furthermore, an allele Petition 870250103158, dated 11 / 11 / 2025, page 33 / 127 A rare 28 / 93 polymorphism of a component of the IL-25 receptor, IL-17RB, is associated with a reduced incidence of asthma (Jung JS, et al. Association of IL-17RB gene polymorphism with asthma. Chest 135: 1173-1180 (2009).

[00112] In animal models of asthma, overexpression or administration of recombinant IL-25 triggers allergic responses characterized by Th2 cytokine expression, eosinophilia, and mucus hypersecretion (US 6,159,193). The effects of IL-25 blockade may be due to the reduction of Th2 cytokines in allergic responses and the inhibition of the expression of critical chemokines that promote an exacerbated inflammatory response (Petersen BC et al., Future Med Chem;4:833-6 (2012)). Administration of anti-IL-25 antibodies has been shown to significantly reduce airway hyperreactivity, Th2-associated cytokine levels, IgE levels, and goblet cell hyperplasia (Fort MM, et al., Immunity;15:985-95 (2001), Rickel EA, et al., J Immunol;181:4299-310 (2008), Ballantyne, SJ et al., Journal of Allergy and Clinical Immunology:120 (6): 1324-1331 (2007)).Furthermore, IL-25 knockout mice showed reduced lung pathology in an asthma model (Ballantyne, SJ, et al., Borowczyk J et al., J Allergy Clin Immunol. Jul;148(1):40-52 (2021)). These data indicate that targeting IL-25 or IL-17RB+ immune cells may be a promising strategy for treating allergic inflammation, as demonstrated in a preclinical study with ABM125, an anti-IL-25 monoclonal antibody (Lee, J., et al. Biochemical and biophysical research communications, 495(1), 1391-1397)).

[00113] Psoriasis is an autoimmune disease that causes skin inflammation, characterized by epidermal hyperplasia, increased angiogenesis, and dermal inflammation. Although the exact cause of psoriasis is unknown, studies suggest that an imbalance of Th1 / Th2 cells and the involvement of Th17 cells may contribute to the disease.IL-25, a cytokine produced by keratinocytes, has been found to promote skin inflammation by recruiting neutrophils and activating macrophages. IL-25 is highly expressed in... Petition 870250103158, dated 11 / 11 / 2025, p. 34 / 127 29 / 93 skin lesions in patients with psoriasis and promotes the proliferation of IL-17RB+ keratinocytes, exacerbating the disease. Keratinocytes can be activated by IL-25 through the activation of the STAT3 transcription factor, leading to the expression of IL-17RB (Xu M, et al., Inflammation. Immunity (2018) 48(4):787-98)). Blocking IL-17RA, a co-receptor of IL-17A, IL-17F, and IL-25, has demonstrated high efficacy in the treatment of psoriasis, suggesting that blocking IL-25 may be a promising strategy to combat skin inflammation. b. Autoimmune Diseases

[00114] Studies have suggested that IL-25 may have both pro-inflammatory and anti-inflammatory effects, depending on the specific disease context and the cells involved. In some autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS), IL-25 has been found to have a protective effect as both an anti-inflammatory cytokine and an inhibitor of innate and adaptive immunity. In some diseases, such as Inflammatory Bowel Disease (IBD) and Systemic Lupus Erythematosus (SLE), IL-25 has a dual role, both pro-inflammatory and anti-inflammatory, in regulating immune responses during disease development. (Deng, D., et al. Front Immunol. 2021; 12: 691559).

[00115] However, in other autoimmune diseases, such as Sjögren's Syndrome (SS), studies have indicated that IL-25 plays a pathogenic role during the development of SS. Studies have shown that IL-17A plays a key role in the pathogenesis of Sjögren's syndrome, promoting the activity of Th17 cells. Recently, it has been observed that IL-25 is significantly increased in the SG and peripheral blood of patients with SS and promotes the activation of inflammatory ILC2s. Blocking IL-25 using a neutralizing antibody improves salivary flow rate and SG tissue damage in mice with experimental SS, accompanied by decreased ILC2 infiltration. Upregulation of TRAF6 in CD3+ T cells and ILC2s in SGs of Petition 870250103158, dated 11 / 11 / 2025, page 35 / 127 30 / 93 patients with pSS suggests that IL-25 signals are functional through the coordinated activation of ERK1 / 2 and related transcription factors (Guggino G, Arthritis Rheumatol (2018) 70(8):1265-75).

[00116] Overall, the impact of IL-25 on autoimmune diseases is complex and context-dependent, and more research is needed to fully understand its role in these diseases and explore its potential as a therapeutic target. Blocking IL-25 may be a promising strategy to combat autoimmune diseases such as Sjögren's syndrome. c. Cancer

[00117] IL-25 has been shown to have potential anticancer effects by modulating immune responses and inhibiting tumor growth (Shabgah.A, et al Cancer Med. 2021 Aug; 10(15): 5191-5202).

[00118] IL-25 can stimulate the activity of immune cells, such as natural killer (NK) cells, dendritic cells, and CD8+ T cells, which can directly kill cancerous cells. It can also promote the production of other cytokines that enhance the activity of immune cells, such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) (Sfanos, KS, et al. (2014). Clinical cancer research, 20(12), 3254-3265).

[00119] In addition to its immune-boosting effects, IL-25 has been found to have direct antitumor effects in several types of cancer. For example, IL-25 has been shown to induce apoptosis (programmed cell death) in prostate cancer cells and inhibit the growth of colon cancer cells by blocking cell cycle progression (Zhang, J., et al. (2019). Oncology Letters, 18(5), 5179-5186).

[00120] Furthermore, IL-25 has been found to increase the effectiveness of chemotherapy and radiotherapy in preclinical cancer models. Treatment with IL-25 has been shown to sensitize cancer cells to chemotherapy, increasing their susceptibility to cell death, and enhances the effects of radiotherapy by stimulating immune responses and reducing tumor blood vessel density (Bao, H et al. (2017). Petition 870250103158, dated 11 / 11 / 2025, page 36 / 127 31 / 93 Scientific reports, 7(1), 1-11).

[00121] Taken together, these results suggest that IL-25 has promising potential as an anticancer agent, alone or in combination with other treatments. However, more research is needed to fully understand the mechanisms underlying its antitumor effects and to explore its potential as a therapeutic agent in clinical settings. Anti-IL-25 antibodies

[00122] The anti-IL-25 antibodies of the invention (e.g., IL25Ab1, IL25Ab2, IL25Ab3, IL25Ab4, IL25Ab5, IL25Ab6, IL25Ab7, IL25Ab8, IL25Ab9, IL25Ab10, and IL25Ab11) bind (e.g., bind specifically) to human IL-25. These antibodies and their fragments can be useful in disrupting the IL-25 / IL-25R binding interaction. These antibodies and their fragments are characterized by unique sets of CDR sequences, specificity for IL-25, and are useful in the treatment of type 2 inflammatory diseases, autoimmune diseases, or cancer as monotherapy or in combination with other agents. More specifically, the invention relates to antibodies and fragments thereof that bind to human IL-25 and their use to modulate IL-25-mediated activity of cells located in an inflammatory disease microenvironment or in a tumor microenvironment.

[00123] In one embodiment, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain (VH) region with a set of CDRs (HCDR1, HCDR2, and HCDR3) described in Table 1. For example, the anti-IL-25 antibody or its antibody fragment may comprise a set of CDRs corresponding to the CDRs in one or more of the anti-IL-25 antibodies described in Table 1 (e.g., the HCDRs of the IL25Ab1 antibody).

[00124] In another embodiment, the anti-IL-25 antibody or fragment thereof comprises a variable light chain (VL) region with a set of Petition 870250103158, dated 11 / 11 / 2025, page 37 / 127 32 / 93 CDRs (LCDR1, LCDR2, and LCDR3), as described in Table 2. For example, the anti-IL-25 antibody or its antibody fragment may comprise a set of CDRs corresponding to the CDRs in one or more of the anti-IL-25 antibodies described in Table 2 (for example, the LCDRs of the IL25Ab1 antibody).

[00125] In an alternative embodiment, the anti-IL-25 antibody or its antibody fragment comprises a VH with a set of CDRs (HCDR1, HCDR2 and HCDR3) as described in Table 1, and a VL with a set of CDRs (LCDR1, LCDR2 and LCDR3) as described in Table 2. Table 1: CDR Sequences of Murine Variable Heavy Chain (VH) Domains Anti-IL-25 Ab CDR1 CDR2 CDR3 IL25Ab1 SEQ ID NO: 11 SEQ ID NO: 12 SEQ ID NO: 13 IL25Ab2 SEQ ID NO: 17 SEQ ID NO: 18 SEQ ID NO: 19 IL25Ab3 SEQ ID NO: 23 SEQ ID NO: 24 SEQ ID NO: 25 IL25Ab4 SEQ ID NO: 29 SEQ ID NO: 30 SEQ ID NO: 31 IL25Ab5 SEQ ID NO: 35 SEQ ID NO: 36 SEQ ID NO: 37 Table 2: CDR Sequences of Murine Variable Light Chain (VL) Domains Anti-IL-25 Ab CDR1 CDR2 CDR3 IL25Ab1 SEQ ID NO: 14 SEQ ID NO: 15 SEQ ID NO: 16 IL25Ab2 SEQ ID NO: 20 SEQ ID NO: 21 SEQ ID NO: 22 IL25Ab3 SEQ ID NO: 26 SEQ ID NO: 27 SEQ ID NO: 28 IL25Ab4 SEQ ID NO: 32 SEQ ID NO: 33 SEQ ID NO: 34 IL25Ab5 SEQ ID NO: 38 SEQ ID NO: 39 SEQ ID NO: 40

[00126] In one embodiment, the anti-IL-25 antibody or its antibody fragment comprises a humanized heavy chain variable region (HV) with a set of CDRs (HCDR1, HCDR2 and HCDR3) described in Petition 870250103158, dated 11 / 11 / 2025, page 38 / 127 33 / 93 Table 3. For example, the anti-IL-25 antibody or its antibody fragment may comprise a set of CDRs corresponding to the CDRs in one or more of the anti-IL-25 antibodies described in Table 1 (e.g., the HCDRs of the IL25Ab6 antibody).

[00127] In another embodiment, the anti-IL-25 antibody or fragment thereof comprises a humanized variable light chain (VL) region with a set of CDRs (LCDR1, LCDR2, and LCDR3), as described in Table 4. For example, the anti-IL-25 antibody or its antibody fragment may comprise a set of CDRs corresponding to the CDRs in one or more of the anti-IL-25 antibodies described in Table 2 (e.g., the LCDRs of the IL25Ab6 antibody).

[00128] In an alternative embodiment, the anti-IL-25 antibody or its antibody fragment comprises a VH with a set of CDRs (HCDR1, HCDR2 and HCDR3) as described in Table 3, and a VL with a set of CDRs (LCDR1, LCDR2 and LCDR3) as described in Table 4. Table 3: Humanized (VH) variable heavy chain domain CDR sequences Anti-IL-25 Ab CDR1 CDR2 CDR3 IL25Ab6 / IL25Ab7 / IL25Ab9 / IL25Ab10 SEQ ID NO: 23 SEQ ID NO: 49 SEQ ID NO: 25 IL25Ab8 / IL25Ab11 SEQ ID NO: 23 SEQ ID NO: 52 SEQ ID NO: 25 Table 4: CDR Sequences of Variable Domains of Humanized Light Chain (VL) Anti-IL-25 Ab CDR1 CDR2 CDR3 IL25Ab6 / IL25Ab7 / IL25Ab8 / IL25Ab9 / IL25Ab10 / IL25Ab11 SEQ ID NO: 50 SEQ ID NO: 51 SEQ ID NO: 28

[00129] In one embodiment, the anti-IL-25 antibody or its fragment of Petition 870250103158, dated 11 / 11 / 2025, page 39 / 127 34 / 93 antibody comprises a VH with a set of complementarity-determining regions (HCDR1, HCDR2 and HCDR3) selected from the group consisting of: (i) HCDR1: SEQ ID NO: 11, HCDR2: SEQ ID NO: 12, HCDR3: SEQ ID NO: 13; (ii) HCDR1: SEQ ID NO: 17, HCDR2: SEQ ID NO: 18, HCDR3: SEQ ID NO: 19; (iii) HCDR1: SEQ ID NO: 23, HCDR2: SEQ ID NO: 24, HCDR3: SEQ ID NO: 25; (iv) HCDR1: SEQ ID NO: 29, HCDR2: SEQ ID NO: 30, HCDR3: SEQ ID NO: 31; (v) HCDR1: SEQ ID NO: 35, HCDR2: SEQ ID NO: 36, HCDR3: SEQ ID NO: 37; (vi) HCDR1: SEQ ID NO: 23, HCDR2: SEQ ID NO: 49, HCDR3: SEQ ID NO: 25 and (vii) HCDR1: SEQ ID NO: 23 HCDR2: SEQ ID NO: 52, HCDR3: SEQ ID NO: 25

[00130] In another embodiment, the anti-IL-25 antibody or its antibody fragment comprises a VL with a set of complementarity-determining regions (LCDR1, LCDR2 and LCDR3) selected from the group consisting of: (i) LCDR1: SEQ ID NO: 14, LCDR2: SEQ ID NO: 15, LCDR3: SEQ ID NO: 16; (ii) LCDR1: SEQ ID NO: 20, LCDR2: SEQ ID NO: 21, LCDR3: SEQ ID NO: 22; (iii) LCDR1: SEQ ID NO: 26, LCDR2: SEQ ID NO: 27, LCDR3: SEQ ID NO: 28; (iv) LCDR1: SEQ ID NO: 32, LCDR2: SEQ ID NO: 33, LCDR3: SEQ ID NO: 34; (v) LCDR1: SEQ ID NO: 38, LCDR2: SEQ ID NO: 39, LCDR3: SEQ Petition 870250103158, dated 11 / 11 / 2025, page 40 / 127 35 / 93 ID NO: 40; and (vi) LCDR1: SEQ ID NO: 50, LCDR2: SEQ ID NO: 51, LCDR3: SEQ ID NO: 28

[00131] In another embodiment, the anti-IL-25 antibody or its antibody fragment comprises: (a) a VH having a set of complementarity-determining regions (HCDR1, HCDR2 and HCDR3) selected from the group consisting of: (i) HCDR1: SEQ ID NO: 11, HCDR2: SEQ ID NO: 12, HCDR3: SEQ ID NO:13; (ii) HCDR1: SEQ ID NO: 17, HCDR2: SEQ ID NO: 18, HCDR3: SEQ ID NO:19; (iii) HCDR1: SEQ ID NO: 23, HCDR2: SEQ ID NO: 24, HCDR3: SEQ ID NO: 25; (iv) HCDR1: SEQ ID NO: 29, HCDR2: SEQ ID NO: 30, HCDR3: SEQ ID NO: 31; (v) HCDR1: SEQ ID NO: 35, HCDR2: SEQ ID NO: 36, HCDR3: SEQ ID NO: 37; (vi) HCDR1: SEQ ID NO: 23, HCDR2: SEQ ID NO: 49, HCDR3: SEQ ID NO: 25 and (vii) HCDR1: SEQ ID NO: 23 HCDR2: SEQ ID NO: 52, HCDR3: SEQ ID NO: 25 (b) a VL having a set of complementarity-determining regions (LCDR1, LCDR2 and LCDR3) selected from the group consisting of: (i) LCDR1: SEQ ID NO: 14, LCDR2: SEQ ID NO: 15, LCDR3: SEQ ID NO: 16; (ii) LCDR1: SEQ ID NO: 20, LCDR2: SEQ ID NO: 21, LCDR3: SEQ ID NO: 22; (iii) LCDR1: SEQ ID NO: 26, LCDR2: SEQ ID NO: 27, LCDR3: SEQ Petition 870250103158, dated 11 / 11 / 2025, page 41 / 127 36 / 93 ID NO: 28; (iv) LCDR1: SEQ ID NO: 32, LCDR2: SEQ ID NO: 33, LCDR3: SEQ ID NO: 34; (v) LCDR1: SEQ ID NO: 38, LCDR2: SEQ ID NO: 39, LCDR3: SEQ ID NO: 40; (vi) LCDR1: SEQ ID NO: 50, LCDR2: SEQ ID NO: 51, LCDR3: SEQ ID NO: 28.

[00132] In one embodiment, the antibody or antibody fragment thereof comprises a combination of a VH and a VL having a set of complementarity-determining regions (CDR1, CDR2 and CDR3) selected from the group consisting of: (i) VH: CDR1: SEQ ID NO: 11, CDR2: SEQ ID NO: 12, CDR3: SEQ ID NO: 13, VL: CDR1: SEQ ID NO: 14, CDR2: SEQ ID NO: 15, CDR3: SEQ ID NO: 16; (ii) VH: CDR1: SEQ ID NO: 17, CDR2: SEQ ID NO: 18, CDR3: SEQ ID NO: 19, VL: CDR1: SEQ ID NO: 20, CDR2: SEQ ID NO: 21, CDR3: SEQ ID NO: 22; (iii) VH: CDR1: SEQ ID NO: 23, CDR2: SEQ ID NO: 24, CDR3: SEQ ID NO: 25, VL: CDR1: SEQ ID NO: 26, CDR2: SEQ ID NO: 27, CDR3: SEQ ID NO: 28; (iv) VH: CDR1: SEQ ID NO: 29, CDR2: SEQ ID NO: 30, CDR3: SEQ ID NO: 31, VL: CDR1: SEQ ID NO: 32, CDR2: SEQ ID NO: 33, CDR3: SEQ ID NO: 34; (v) VH: CDR1: SEQ ID NO: 35, CDR2: SEQ ID NO: 36, CDR3: SEQ ID NO: 37, VL: CDR1: SEQ ID NO: 38, CDR2: SEQ ID NO: 39, CDR3: SEQ ID NO: 40; (vi) VH: CDR1: SEQ ID NO: 23, CDR2: SEQ ID NO: 49, CDR3: SEQ ID NO: 25, VL: CDR1: SEQ ID NO: 50, CDR2: SEQ ID NO: 51, CDR3: SEQ ID NO: 28; and (vii) VH: CDR1: SEQ ID NO: 23, CDR2: SEQ ID NO: 52, CDR3: SEQ Petition 870250103158, dated 11 / 11 / 2025, page 42 / 127 37 / 93 ID NO: 25, VL: CDR1: SEQ ID NO: 50, CDR2: SEQ ID NO:51, CDR3: SEQ ID NO: 28

[00133] In one embodiment, the anti-IL-25 antibody or its antibody fragment comprises a variable heavy chain sequence selected from the group consisting of: SEQ ID NOs: 1, 3, 5, 7, 9, 44 and 47; and / or a variable light chain sequence selected from the group consisting of: SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46 and 48.

[00134] In one embodiment, the anti-IL-25 antibody or its antibody fragment comprises a pair of variable heavy chain and variable light chain sequences, selected from the following combinations: a variable heavy chain sequence comprising SEQ ID NO: 1 and a variable light chain sequence comprising SEQ ID NO: 2; a variable heavy chain sequence comprising SEQ ID NO: 3 and a variable light chain sequence comprising SEQ ID NO: 4; a variable heavy chain sequence comprising SEQ ID NO: 5 and a variable light chain sequence comprising SEQ ID NO: 6; and a variable heavy chain sequence comprising SEQ ID NO: 7 a variable light chain sequence comprising SEQ ID NO: 8; a variable heavy chain sequence comprising SEQ ID NO: 9 a variable light chain sequence comprising SEQ ID NO: 10;a variable heavy chain sequence comprising SEQ ID NO: 44 and a variable light chain sequence comprising SEQ ID NO: 45; a variable heavy chain sequence comprising SEQ ID NO: 44 and a variable light chain sequence comprising SEQ ID NO: 46; and a variable heavy chain sequence comprising SEQ ID NO: 47 and a variable light chain sequence comprising SEQ ID NO: 48. A person skilled in the art will further understand that the variable light and variable heavy chains may be selected independently, or mixed and combined, to prepare an anti-IL-25 antibody or fragment thereof comprising a combination of variable heavy chains; Petition 870250103158, dated 11 / 11 / 2025, page 43 / 127 38 / 93 and a variable light chain that is distinct from the pairs identified above.

[00135] In one embodiment, the anti-IL-25 antibody or its antibody fragment comprises a pair of variable heavy chain and variable light chain sequences, selected from the following combinations: a variable heavy chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 1 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 2; a variable heavy chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 3 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 4; a variable heavy chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 5 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 6; a variable heavy chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 7 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 8;a variable heavy chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 9 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 10; a variable heavy chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 44 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 45; a variable heavy chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 44 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 46;and a variable heavy chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 47 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 48. Those skilled in the art will further understand that the variable light and variable heavy chains can be selected independently, or mixed and combined, to prepare an anti-IL-25 antibody or antibody fragment comprising a combination of variable heavy chain and variable light chain that is distinct from the pairs identified above. Petition 870250103158, dated 11 / 11 / 2025, page 44 / 127 39 / 93

[00136] In some embodiments, the anti-IL-25 antibody or its antibody fragment comprises one or more conservative amino acid substitutions. A person skilled in the art will recognize that a conservative amino acid substitution is a substitution of one amino acid for another amino acid that has similar structural or chemical properties, such as, for example, a similar side chain. Exemplary conservative substitutions are described in the art, for example, in Watson et al., Molecular Biology of the Gene, The Benjamin / Cummings Publication Company, 4th Ed. (1987).

[00137] “Conservative modifications” refer to amino acid modifications that do not significantly affect or alter the binding characteristics of the antibody containing the amino acid sequences. Conservative modifications include amino acid substitutions, additions, and deletions. Conservative substitutions are those in which the amino acid is replaced by an amino acid residue with a similar side chain.Families of amino acid residues with similar side chains are well defined and include amino acids with acidic side chains (e.g., aspartic acid, glutamic acid), basic side chains (e.g., lysine, arginine, histidine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), uncharged polar side chains (e.g., glycine, asparagine, glutamine, cysteine, serine, threonine, tyrosine, tryptophan), aromatic side chains (e.g., phenylalanine, tryptophan, histidine, tyrosine), aliphatic side chains (e.g., glycine, alanine, valine, leucine, isoleucine, serine, threonine), amide (e.g., asparagine, glutamine), beta-branched side chains (e.g., threonine, valine, isoleucine) and sulfur-containing side chains (cysteine, methionine).Furthermore, any native residue in the polypeptide can also be replaced by alanine, as previously described for alanine scavenging mutagenesis (MacLennan et al. (1998) Acta Physiol Sc and Suppl 643: 55-67;). Petition 870250103158, dated 11 / 11 / 2025, p. 45 / 127 40 / 93 Sasaki et al. (1998) Adv Biophys 35: 1-24). Amino acid substitutions in the antibodies of the invention can be made by known methods, for example, by PCR mutagenesis (US Patent No. 4,683,195).

[00138] In some embodiments, the antibody or fragment thereof comprises a variable heavy chain sequence comprising an amino acid sequence with at least about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity with the amino acid sequence established in SEQ ID NOs: 1, 3, 5, 7, 9, 44, or 47. In other embodiments, the antibody or fragment thereof retains the binding and / or functional activity of an antibody or fragment thereof comprising the variable heavy chain sequence of SEQ ID NOs: 1, 3, 5, 7, 9, 44, or 47. In other embodiments, the antibody or fragment thereof comprises the variable heavy chain sequence of SEQ ID NOs: 1, 3, 5, 7, 9, 44, or 47 and has one or more conservative amino acid substitutions, for example, 1, 2, 3, 4, 5, 1-2, 1-3, 1-4 or 1-5 conservative amino acid substitutions in the variable sequence of the heavy chain.In other embodiments, one or more conservative amino acid substitutions fall within one or more structural regions in the SEQ ID NOS: 1, 3, 5, 7 or 9, 44 or 47 (based on the Kabat numbering system).

[00139] In specific embodiments, the antibody or fragment thereof comprises a variable heavy chain sequence with at least about 95%, about 96%, about 97%, about 98% or about 99% sequence identity with the sequence of the variable heavy chain region of the antibody or fragment thereof established in SEQ ID NOs: 1, 3, 5, 7, 9, 44 or 47, comprises one or more conservative amino acid substitutions in a structural region and retains the binding and / or functional activity of an antibody or fragment thereof comprising a variable heavy chain sequence as established in SEQ ID NOs: 1, 3, 5, 7, 9, 44 or 47 and a variable light chain sequence as Petition 870250103158, dated 11 / 11 / 2025, p. 46 / 127 41 / 93 established in SEQ ID Nos: 2, 4, 6, 8, 10, 45, 46 or 48.

[00140] In some embodiments, the antibody or a fragment thereof comprises a variable light chain sequence comprising an amino acid sequence with at least about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity with the amino acid sequence established in SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46, or 48.

[00141] In other embodiments, the antibody or fragment thereof retains the binding and / or functional activity of an antibody or fragment thereof comprising the variable light chain sequence of SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46 or 48.

[00142] In other embodiments, the antibody or fragment thereof comprises the variable light chain sequence of SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46 or 48 and has one or more conservative amino acid substitutions, for example, 1, 2, 3, 4, 5, 1-2, 1-3, 1-4 or 1-5 conservative amino acid substitutions in the variable light chain sequence. In other embodiments, one or more conservative amino acid substitutions fall within one or more structure regions in SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46 or 48 (based on the Kabat numbering system).

[00143] In specific embodiments, the antibody or fragment thereof comprises a variable light chain sequence with at least about 95%, about 96%, about 97%, about 98%, or about 99% sequence identity with the variable region sequence of the light chain of the antibody or fragment thereof established in SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46, or 48.

[00144] In some embodiments, the anti-IL25 antibody comprises one or more conservative amino acid substitutions in a structural region and retains the binding and / or functional activity of an antibody or fragment thereof comprising a variable heavy chain sequence, Petition 870250103158, dated 11 / 11 / 2025, page 47 / 127 42 / 93 as set forth in SEQ ID Nos: 1, 3, 5, 7, 9, 44 or 47 and a variable light chain sequence as set forth in SEQ ID Nos: 2, 4, 6, 8, 10, 45, 46 or 48.

[00145] In some embodiments, the anti-IL-25 antibody is a monoclonal antibody. In some embodiments, the anti-IL-25 antibody is a human antibody or antigen-binding portions thereof. In other embodiments, the anti-IL-25 antibody is a murine antibody or a chimeric antibody. In some embodiments, the anti-IL-25 antibody is a humanized antibody. In some embodiments, the anti-IL-25 antibody is a fully human antibody. In an alternative embodiment, an antibody fragment comprising the antigen-binding portion of one or more of the described anti-IL-25 antibodies may be incorporated into a bi- or multispecific antibody or into a fusion protein.

[00146] In one embodiment, the anti-IL-25 antibody or its antibody fragment comprises all six murine CDR regions of IL25Ab1, IL25Ab2, IL25Ab3, IL25Ab4, or IL25Ab5 antibodies formatted as a chimeric or humanized antibody. In other embodiments, the anti-IL-25 antibody or its antibody fragment comprises all six CDR regions of one of the described murine antibodies.

[00147] In some embodiments, the anti-IL-25 antibody is a humanized antibody (e.g., IL25Ab6, IL25Ab7, IL25Ab8, IL25Ab9, IL25Ab10, or IL25Ab11) comprising the VH / VL CDR regions set forth in Tables 3 and 4.

[00148] In some embodiments, the antibody is a full-length antibody. In other embodiments, the antibody is an antibody fragment including, for example, an antibody fragment selected from the group consisting of: Fab, Fab', F(ab)2, Fv, domain antibodies (dAbs) and complementarity-determining region (CDR) fragments, single-chain antibodies (scFv), chimeric antibodies, diabodies, triabodies, tetrabodies, miniantibodies and polypeptides containing at Petition 870250103158, dated 11 / 11 / 2025, page 48 / 127 43 / 93 minus a portion of an immunoglobulin that is sufficient to confer specific IL-25 binding to the polypeptide.

[00149] In some embodiments, a variable region domain of an anti-IL-25 antibody described herein may be covalently linked at a C-terminal amino acid to at least one other antibody domain or a fragment thereof. Thus, for example, a VH domain that is present in the variable region domain may be linked to an immunoglobulin CH1 domain, or a fragment thereof. Similarly, a VL domain may be linked to a CK domain or a fragment thereof. Thus, for example, the antibody may be a Fab fragment in which the antigen-binding domain contains associated VH and VL domains, covalently linked at their C-terminus to a CH1 and CK domain, respectively. The CH1 domain may be extended with more amino acids, for example, to provide a hinge region or a portion of a hinge region domain, as found in a Fab fragment, or to provide more domains, such as the CH2 and CH3 domains of the antibody.

[00150] In some embodiments, a variable region domain of an anti-IL-25 antibody described herein may be covalently linked at a C-terminal amino acid to a constant region of the antibody. For example, a VL domain may be linked to the mouse Kappa constant region (SEQ ID NO: 54) or the human Kappa constant region (SEQ ID NO: 57). Similarly, a VH domain may be linked to the mouse IgG1 constant region (SEQ ID NO: 53), the human IgG1 constant region (SEQ ID NO: 55), or another antibody constant region, such as human IgG4 or IgG2. Constant regions may contain certain mutations to modulate the properties of a derived antibody. For example, a triple YTE mutation may be introduced into the human IgG1 constant region (SEQ ID NO: 56) to extend the antibody half-life. Fc mutations that modulate the effector functions of the antibody may also be introduced. Petition 870250103158, dated 11 / 11 / 2025, p. 49 / 127 44 / 93

[00151] Thus, in one embodiment, the antibody fragment comprises at least one CDR as described herein. The antibody fragment may comprise at least two, three, four, five, or six CDRs as described herein. The antibody fragment may further comprise at least one variable region domain of an antibody described herein. The variable region domain may be of any size or amino acid composition and will generally comprise at least one CDR sequence responsible for binding to human IL-25, for example, CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and / or CDR-L3 as described herein, and which is adjacent to or in structure with one or more structure sequences.

[00152] In a further aspect, the anti-IL-25 antibody or antibody fragment thereof exhibits one or more of the following properties: (a) is specific to human IL-25 and has the ability to block IL-25 from binding to its receptor; (b) inhibits, interferes with, or modulates the interaction of IL-25 with IL-25 receptor signal transduction; (c) inhibits IL-25-induced intracellular NF-kB activation; (d) inhibits human IL-25-induced IL-5 production in human PBMCs; (e) inhibits human IL-25-induced CXCL-1 production in a human colon cancer cell line; (f) binds to mouse and cynomolgus IL-25; (g) reduces IL-5 production in the lung of the OVA-induced asthma model; and (h) improves airway resistance in the OVA-induced asthma model.

[00153] In one embodiment, anti-IL-25 antibodies or antibody fragments thereof can reduce, inhibit, interfere with, and / or modulate at least one of the biological responses related to IL-25 and, as such, are useful for Petition 870250103158, dated 11 / 11 / 2025, p. 50 / 127 45 / 93 improve the effects of diseases or disorders related to IL-25. Such antibodies and their antibody fragments can be used, for example, to reduce, inhibit, interfere with and / or modulate IL-25 signaling, IL-25 activation of epithelial cells and type 2 lymphocytes, IL-25 activation of tumor cells, or induce the production of pro-inflammatory cytokines.

[00154] The described antibodies (e.g., IL25Ab1, IL25Ab2, IL25Ab3, IL25Ab4, IL25Ab5, IL25Ab6, IL25Ab7, IL25Ab8, IL25Ab9, IL25Ab10, and IL25Ab11) bind (e.g., bind specifically) to human IL25. Amino acid sequences of closely related human IL-17 family members (IL-17A (Q16552), IL-17B (Q9UHF5), IL-17C (Q9P0M4), IL-17D (Q8TAD2), and IL-17F (Q96PD4)) were retrieved from UniProt. Human IL-25 exhibits low homology with its phylogenetically close relatives. IL-25 shows very low sequence similarity with other family members, ranging from 23.2% to 32.7%. Based on low homology, it is unlikely that anti-IL25 antibodies will bind to members of the IL17 family.

[00155] Antibodies typically bind specifically to their cognate antigen with high affinity, reflected by a dissociation constant (KD) of 10⁻⁷ to 10⁻¹¹M or less. Any KD greater than about 10⁻⁶M is generally considered indicative of nonspecific binding. As used herein, an antibody that binds specifically to an antigen refers to an antibody that binds to the antigen and substantially identical antigens with high affinity, meaning having a KD of 10⁻⁷M or less, preferably 10⁻⁸M or less, even more preferably 5 x 10⁻⁹M or less, and preferably between 10⁻⁸M and 10⁻¹⁰M or less, but does not bind with high affinity to an unrelated antigen. The antibodies described bind to human IL₂5 with high affinity, with a KD determined by BLI <1.0E⁻¹².

[00156] The term cross-reaction, as used herein, refers to the ability of the specific anti-human IL-25 antibody described herein to cross-react. Petition 870250103158, dated 11 / 11 / 2025, page 51 / 127 46 / 93 bind to IL25 from a different species. For example, an antibody described herein may also bind to IL25 from another species (e.g., cynomolgus monkey or mouse IL25). As used herein, cross-reactivity can be measured by detecting specific reactivity with purified antigen in binding assays (e.g., SPR, ELISA) or functional binding or interaction with cells that physiologically express IL25. Methods for determining cross-reactivity include standard binding assays, as described herein, for example, by BIACORE® surface plasmon resonance (SPR) analysis using a BIACORE® 2000 SPR instrument (Biacore AB, Uppsala, Sweden), biolayer interferometry (BLI), or flow cytometry techniques.

[00157] The described human IL2-5 antibodies, IL25Ab1 to IL25Ab11, all bind to cynomolgus monkey IL-25 with remarkable affinity. IL25Ab1 to IL25Ab11 bind to cynomolgus and mouse IL-25 in ELISA assays with affinities comparable to the binding affinity to human IL-25.

[00158] In certain embodiments, an antibody provided herein is a chimeric antibody. Certain chimeric antibodies are described, for example, in U.S. Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. U.S., 81:6851-6855 (1984)). In one example, a chimeric antibody comprises a non-human variable region (e.g., a variable region derived from a mouse, rat, hamster, rabbit, or non-human primate such as a monkey) and a human constant region. In another example, a chimeric antibody is a “class-switched” antibody in which the class or subclass has been altered from that of the original antibody. Chimeric antibodies include antibody fragments themselves.

[00159] Antibodies can be prepared as chimeric antibodies or antibody fragments with murine variable regions and human constant regions. Human antibody constant regions can be Petition 870250103158, dated 11 / 11 / 2025, page 52 / 127 47 / 93 of reported allotypes, reviewed in Jefferis et al., Human immunoglobulin allotypes: possible implications for immunogenicity. MAbs 1, 332-338 (2009). In one embodiment, the constant region of the human heavy chain uses a consensus human IgG1 constant region sequence (SEQ ID NO: 55) while the constant region of the light chain uses a consensus human kappa constant region sequence (SEQ ID NO: 57). Human IgG1 may be chosen because it is one of the most common subtypes for chimeric antibody generation and may provide effector function. The human kappa constant region may be used because most parental murine antibodies are of the mouse kappa light chain.

[00160] In certain embodiments, a chimeric antibody is a humanized antibody. Typically, a non-human antibody is humanized to reduce immunogenicity to humans while maintaining the specificity and affinity of the parent non-human antibody. Generally, a humanized antibody comprises one or more variable domains in which HVRs, for example, CDRs (or portions thereof) are derived from a non-human antibody, and FRs (or portions thereof) are derived from human antibody sequences. A humanized antibody will optionally also comprise at least a portion of a human constant region. In some embodiments, some FR residues in a humanized antibody are replaced by corresponding residues from a non-human antibody (e.g., the antibody from which the HVR residues are derived), for example, to restore and / or improve the antibody's binding specificity or affinity.In some embodiments, certain CDR residues in a humanized antibody (e.g., residues 1, 2, 3, 4, or 5) can be mutated to enhance the antibody's growth capability.

[00161] Humanized antibodies and methods for producing them are reviewed, for example, in Almagro and Fransson, Front. Biosci. 13:1619-1633 (2008), and are further described, for example, in Riechmann et al., Petition 870250103158, dated 11 / 11 / 2025, page 53 / 127 48 / 93 Nature 332:323-329 (1988); Queen et al., Proc. Nat'l Acad. Sci. EUA 86:10029-10033 (1989); US Patent Nos. 5,821,337, 7,527,791, 6,982,321 and 7,087,409; Kashmiri et al., Methods 36:25-34 (2005) (describing the specificity-determining region (SDR) graft); Padlan, Mol. Immunol. 28:489-498 (1991) (describing “resurfacing”); DallAcqua et al., Methods 36:43-60 (2005) (describing “FR shuffling”); and Osbourn et al., Methods 36:61-68 (2005) and Klimka et al., Br. J. Cancer, 83:252-260 (2000) (describing the guided selection approach for FR shuffling).

[00162] Human structure regions that can be used for humanization include, but are not limited to, structure regions selected using the “best fit” method (see, for example, Sims et al. J. Immunol. 151:2296 (1993)); structure regions derived from the consensus sequence of human antibodies from a particular subgroup of variable light or heavy chain regions (see, for example, Carter et al. Proc. Natl. Acad. Sci. USA, 89:4285 (1992); and Presta et al. J. Immunol., 151:2623 (1993)); mature human structural regions (somatically mutated) or human germline structural regions (see, for example, Almagro and Fransson, Front. Biosci. 13:1619-1633 (2008)) and structural regions derived from RF screening libraries (see, for example, Baca et al., J. Biol. Chem. 272:10678-10684 (1997) and Rosok et al., J. Biol. Chem. 271:22611-22618 (1996)).

[00163] For human or humanized antibodies, such as the IgG1 antibody, amino acid substitutions have been introduced in the Fc region to modulate antibody interactions with Fcy, FcRn, or complement receptors, resulting in modulated antibody effector functions and / or antibody half-life (see, for example, Damelang, T., et al. Impact of structural modifications of IgG antibodies on effector functions. Front Immunol 14: 1304365 (2023)). Among the Fc mutations that prolong antibody half-life are YTE (M252Y, S254T, and T256E in EU numbering) and LS. Petition 870250103158, dated 11 / 11 / 2025, p. 54 / 127 49 / 93 (M428L and N434S) are two examples used in the literature. IL-25 Antibody Production Methods

[00164] An anti-IL-25 antibody or antibody fragment thereof may be made by any method known in the art. For example, a recipient may be immunized with soluble recombinant human IL-25 protein, or a fragment or peptide conjugated to a carrier protein thereof. Any suitable method of immunization may be used. Such methods may include adjuvants, other immunostimulants, repeated booster immunizations, and the use of one or more routes of immunization.

[00165] Any suitable source of human IL-25 can be used as an immunogen for the generation of anti-IL-25 antibodies of the compositions and methods described herein. Different forms of the IL-25 antigen can be used to generate antibody sufficient to generate biological activity. Thus, the triggering IL-25 antigen can be a single epitope, multiple epitopes, or the entire protein alone or in combination with one or more immunogenicity-enhancing agents. In some respects, the triggering antigen is either a full-length isolated soluble protein, or a soluble protein comprising less than the full-length sequence (e.g., immunizing with a peptide comprising a specific IL-25 moiety or epitopes). As used herein, the term “moiety” refers to the minimum number of amino acids or nucleic acids, as appropriate, to constitute an immunogenic epitope of the antigen of interest.Any genetic vectors suitable for transforming the cells of interest may be employed, including but not limited to adenoviral vectors, plasmids, and nonviral vectors such as cationic lipids.

[00166] It is desirable to prepare monoclonal antibodies (mAbs) from various mammalian hosts, such as mice, rodents, primates, humans, etc. A description of the techniques for preparing such antibodies is provided. Petition 870250103158, dated 11 / 11 / 2025, page 55 / 127 50 / 93 monoclonal antibodies can be found in, for example, Sties et al. (eds.) BASIC AND CLINICAL IMMUNOLOGY (4th ed.) Lance Medical Publication, Los Altos, CA, and references cited therein; Harlow and Lane (1988) ANTIBODIES: A LABORATORY MANUAL CSH Press; Goding (1986) MONOCLONAL ANTIBODIES: PRINCIPLES AND PRACTICE (2nd ed.) Academic Press, New York, NY. Typically, spleen cells from an animal immunized with a desired antigen are immortalized, usually by fusion with a myeloma cell. See Kohler and Milstein (196) Eur. J. Immunol. 6:511-519. Alternative immortalization methods include transformation with Epstein-Barr virus, oncogene or retrovirus, or other methods known in the art. See, for example, Doyle et al. (eds. 1994 and periodic supplements) CELL AND TISSUE CULTURE: LABORATORY PROCEDURES, John Wiley and Sons, New York, NY.Colonies originating from immortalized single cells are screened for antibody production with the desired specificity and affinity for the antigen, and the yield of monoclonal antibodies produced by such cells can be increased by various techniques, including injection into the peritoneal cavity of a vertebrate host. Alternatively, DNA sequences encoding a monoclonal antibody or an antigen-binding fragment thereof can be isolated by screening a human B-cell DNA library according to, for example, the general protocol described by Huse et al., (1989) Science 246: 1275-1281. Thus, antibodies can be obtained by a variety of techniques familiar to researchers skilled in the art.

[00167] Other suitable techniques involve selecting antibody libraries from phages, yeasts, viruses, or similar vectors. See, for example, Huse et al., supra; and Ward et al., (1989) Nature 341:544-546. The polypeptides and antibodies described herein may be used with or without modification, including chimeric or humanized antibodies. Frequently, the polypeptides and antibodies will be labeled by the covalent or non-covalent attachment of a signaling substance. Petition 870250103158, dated 11 / 11 / 2025, page 56 / 127 51 / 93 detectable. A wide variety of labels and conjugation techniques are known and widely reported in the scientific and patent literature. Suitable markers include radionuclides, enzymes, substrates, cofactors, inhibitors, fluorescent fractions, chemiluminescent fractions, magnetic particles, and the like. Patents teaching the use of such labels include U.S. Patents Nos. 3,817,837; 3,850,752; 3,996,345; 4,277,437; 4,275,149; and 4,366,241. In addition, recombinant immunoglobulins can be produced, see Cabilly U.S. Patent No. 4,816,567; and Queen et al. (1989) Proc. Nat'l Acad. Sci. USA 86: 10029-10023; or performed in transgenic mice, see Nils Lonberg et al., (1994), Nature 368:856-859; and Mendez et al. (1997) Nature Genetics 15: 146-156; TRANSGENIC ANIMALS AND METHODS OF USE (WO 2012 / 62118), Medarex, Trianni, Abgenix, Ablexis, OminiAb, Harbour and other technologies.

[00168] In some embodiments, the ability of the produced antibody to bind to IL-25 can be assessed using standard binding assays such as surface plasmon resonance (SPR), Octet (BLI), ELISA, Western blot, immunofluorescence, flow cytometry analysis, chemotaxis assays, and cell migration assays. In some respects, the produced antibody can also be evaluated for its ability to inhibit IL-25, block IL-25 receptor signal transduction, and inhibit the subsequent effects of the IL-25-mediated inflammatory microenvironment, including inhibition of IL-25-induced NFkB signaling, IL-5 production, and / or CXCL1 production.

[00169] Antibody compositions prepared from cells can be purified using, for example, hydroxyapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being a typical purification technique. The suitability of protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc domains present in the antibody. Protein A can be used to purify antibodies based on heavy chains. Petition 870250103158, dated 11 / 11 / 2025, page 57 / 127 52 / 93 human γ1, γ2, or γ4 (see, for example, Lindmark et al., 1983 J. Immunol. Meth. 62:1-13). G protein is recommended for all mouse isotypes and for human γ3 (see, for example, Guss et al., 1986 EMBO J. 5:1567-1575). A matrix to which an affinity ligand is attached is usually agarose, but other matrices are available. Mechanically stable matrices, such as controlled-pore glass or poly(styrenedivinyl)benzene, allow faster flow rates and shorter processing times than can be obtained with agarose. When the antibody comprises a CH3 domain, Bakerbond ABX™ resin (JT Baker, Phillipsburg, NJ) is useful for purification.Other techniques for protein purification, such as fractionation on an ion-exchange column, ethanol precipitation, reverse-phase HPLC, silica chromatography, SEPHAROSE™ heparin chromatography on anionic or cationic exchange resin (such as a polyaspartic acid column), focused chromatography, SDS-PAGE, and ammonium sulfate precipitation are also available, depending on the antibody to be recovered.

[00170] After any preliminary purification step, the mixture comprising the antibody of interest and contaminants may be subjected to low pH hydrophobic interaction chromatography using an elution buffer at a pH between about 2.5-4.5, typically performed at low salt concentrations (e.g., about 0-0.25 M salt).

[00171] Also included are nucleic acids that hybridize under low, moderate, and high stringency conditions, as defined herein, to all or a portion (e.g., the portion encoding the variable region) of the nucleotide sequence represented by isolated polynucleotide sequence(s) encoding an antibody or antibody fragment of the present invention. The hybridizing portion of the hybridizing nucleic acid typically has at least 15 (e.g., 20, 25, 30, or 50) nucleotides in length. The hybridizing portion of the nucleic acid is at least 80%, for example, at least 90%, at least Petition 870250103158, dated 11 / 11 / 2025, p. 58 / 127 53 / 93 95%, at least 98%, or at least 99% identical to the sequence of a portion or all of a nucleic acid encoding an anti-IL-25 polypeptide (e.g., a variable region of the heavy chain or light chain) or its complement. Hybridizing nucleic acids of the type described herein can be used, for example, as a cloning probe, a primer, e.g., a PCR primer, or a diagnostic probe. Polynucleotides, Vectors and Cells

[00172] Other embodiments include isolated polynucleotides comprising a sequence encoding an anti-IL-25 antibody or antibody fragment thereof, vectors and cells comprising the polynucleotides, and recombinant techniques for antibody production. Isolated polynucleotides may encode any desired form of the anti-IL-25 antibody, including, for example, full-length monoclonal antibodies, Fab, Fab, F(ab)2 and Fv fragments, diabodies, linear antibodies, single-chain antibody molecules, mini-antibodies, and multispecific antibodies formed from antibody fragments.

[00173] Some embodiments include isolated polynucleotides comprising sequences encoding the variable region of the heavy chain of an antibody or antibody fragment having the amino acid sequence of SEQ ID NOs: 1, 3, 5, 7, 9, 44 and 47. Some embodiments include isolated polynucleotides comprising sequences encoding the variable region of the light chain of an antibody or antibody fragment having the amino acid sequence of SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46 and 48.

[00174] In one embodiment, the isolated polynucleotide sequence(s) encode(s) an antibody or antibody fragment having a variable heavy chain region and a variable light chain region comprising the amino acid sequences of: (a) a variable heavy chain sequence comprising SEQ ID NO: 1 and a variable light chain sequence comprising SEQ ID Petition 870250103158, dated 11 / 11 / 2025, page 59 / 127 54 / 93 NO: 2; (b) a variable heavy chain sequence comprising SEQ ID NO: 3 and a variable light chain sequence comprising SEQ ID NO: 4; (c) a variable heavy chain sequence comprising SEQ ID NO: 5 and a variable light chain sequence comprising SEQ ID NO: 6; (d) a variable heavy chain sequence comprising SEQ ID NO: 7 and a variable light chain sequence comprising SEQ ID NO: 8; (e) a variable heavy chain sequence comprising SEQ ID NO: 9 and a variable light chain sequence comprising SEQ ID NO: 10; (f) a variable heavy chain sequence comprising SEQ ID NO: 44 and a variable light chain sequence comprising SEQ ID NO: 45; (g) a variable heavy chain sequence comprising SEQ ID NO: 44 and a variable light chain sequence comprising SEQ ID NO: 46; or (h) a variable heavy chain sequence comprising SEQ ID NO: 47 and a variable light chain sequence comprising SEQ ID NO: 48.

[00175] In another embodiment, the isolated polynucleotide sequence(s) encode(s) an antibody or antibody fragment having a variable light chain region and a variable heavy chain region comprising the amino acid sequences of: (a) a variable heavy chain sequence that is 90%, 95% or 99% identical to SEQ ID NO: 1 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 2; (b) a variable heavy chain sequence that is 90%, 95% or 99% identical to SEQ ID NO: 3 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 4; Petition 870250103158, dated 11 / 11 / 2025, page 60 / 127 55 / 93 (c) a variable heavy chain sequence that is 90%, 95% or 99% identical to SEQ ID NO: 5 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 6; (d) a variable heavy chain sequence that is 90%, 95% or 99% identical to SEQ ID NO: 7 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 8; (e) a variable heavy chain sequence that is 90%, 95% or 99% identical to SEQ ID NO: 9 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 10; (f) a variable heavy chain sequence that is 90%, 95% or 99% identical to SEQ ID NO: 44 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 45; (g) a variable heavy chain sequence that is 90%, 95% or 99% identical to SEQ ID NO: 44 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 46; or (h) a variable heavy chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 47 and a variable light chain sequence that is 90%, 95%, or 99% identical to SEQ ID NO: 48.

[00176] The polynucleotide(s) comprising a sequence encoding an anti-IL-25 antibody or antibody fragment thereof may be fused to one or more regulatory or control sequences, as known in the art, and may be contained in suitable expression vectors or cells, as known in the art. Each of the polynucleotide molecules encoding the variable domains of the heavy or light chain may be independently fused to a polynucleotide sequence encoding a constant domain, such as a human constant domain, allowing the production of intact antibodies. Alternatively, polynucleotides, or portions thereof, may be fused, providing a template for the production of a single-chain antibody.

[00177] For recombinant production, a polynucleotide that codes for Petition 870250103158, dated 11 / 11 / 2025, page 61 / 127 56 / 93 An antibody or antibody fragment is inserted into a replicable vector for cloning (DNA amplification) or for expression. Many vectors suitable for expressing recombinant antibody are available. Vector components generally include, but are not limited to, one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence.

[00178] The anti-IL-25 antibody or its antibody fragment can also be produced as fusion polypeptides, in which the antibody or its fragment is fused with a heterologous polypeptide, such as a signal sequence or another polypeptide having a specific cleavage site at the amino terminus of the mature protein or polypeptide. The heterologous signal sequence selected is typically one that is recognized and processed (i.e., cleaved by a signal peptidase) by the cell. For prokaryotic cells that do not recognize and process the anti-IL-25 antibody signal sequence, the signal sequence can be replaced with a prokaryotic signal sequence. The signal sequence can be, for example, alkaline phosphatase, penicillinase, lipoprotein, thermostable enterotoxin II leaders, and the like.For yeast secretion, the native signal sequence can be replaced, for example, by a leader sequence obtained from yeast invertase factor alpha (including Saccharomyces and Kluyveromyces factor α leaders), acid phosphatase, C. albicans glucoamylase, or the signal described in WO 90 / 13646. In mammalian cells, mammalian signal sequences, as well as viral secretory leaders, for example, the herpes simplex gD signal, can be used. The DNA of this precursor region is framelinked to the DNA encoding the anti-IL-25 antibody.

[00179] Expression and cloning vectors contain a nucleic acid sequence that allows the vector to replicate in one or more selected cells. Generally, in cloning vectors, this sequence allows Petition 870250103158, dated 11 / 11 / 2025, page 62 / 127 57 / 93 that the vector replicates independently of the host's chromosomal DNA and includes origins of replication or autonomous replication sequences. These sequences are well known for a variety of bacteria, yeasts, and viruses. The pBR322 plasmid origin of replication is suitable for most Gram-negative bacteria, the 2-υ plasmid origin is suitable for yeasts, and several viral origins (SV40, polyoma, adenovirus, VSV, and BPV) are useful for cloning vectors into mammalian cells. Generally, the origin of the replication component is not necessary for mammalian expression vectors (the SV40 origin can usually be used simply because it contains the initial promoter).

[00180] Expression and cloning vectors may contain a gene encoding a selectable marker to facilitate expression identification. Typical selectable marker genes encode proteins that confer resistance to antibiotics or other toxins, for example, ampicillin, neomycin, methotrexate, or tetracycline, or alternatively, are auxotrophic complement deficiencies, or, in other alternatives, provide specific nutrients that are not present in complex media, for example, the gene encoding D-alanine racemase for bacilli. Non-therapeutic uses

[00181] The anti-IL-25 antibody or antibody fragment described herein are useful as affinity purification agents. In this process, antibodies are immobilized on a solid phase, such as a protein A resin, using methods well known in the art. The immobilized antibody is placed in contact with a sample containing the IL-25 protein (or fragment thereof) to be purified, and then the support is washed with a suitable solvent that will remove substantially all material in the sample except the IL-25 protein, which is bound to the immobilized antibody. Finally, the support is washed with another suitable solvent that will release the IL-25 protein from the antibody.

[00182] An anti-IL-25 antibody or a fragment of it also Petition 870250103158, dated 11 / 11 / 2025, page 63 / 127 58 / 93 is useful in diagnostic assays for detecting and / or quantifying the IL-25 protein, for example, by detecting IL-25 expression in specific cells, tissues, or serum. Anti-IL-25 antibodies can be used for diagnosis, for example, to monitor the development or progression of a disease as part of a clinical trial procedure to, for example, determine the effectiveness of a particular treatment and / or prevention regimen. Detection can be facilitated by coupling the anti-IL-25 antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, radioactive materials, positron-emitting metals using various positron emission tomography techniques, and non-radioactive paramagnetic metal ions. See, for example, U.S. Patent No. 4,741.900 for metal ions that can be conjugated to antibodies for use as diagnostics according to the present invention.

[00183] Anti-IL-25 antibody or antibody fragments thereof can be used in methods to diagnose an IL-25-associated disorder (e.g., a disorder characterized by abnormal IL-25 expression) or to determine whether an individual has an increased risk of developing an IL-25-associated disorder. Such methods include placing a biological sample from an individual in contact with an anti-IL-25 antibody or antibody fragment thereof and detecting the antibody's binding to IL-25. By "biological sample" is meant any biological sample obtained from an individual, cell line, tissue culture, or other source of cells that potentially express IL-25. Methods for obtaining biopsies of mammalian tissues and body fluids are well known in the art.

[00184] In some embodiments, the method may further comprise comparing the IL-25 level in a patient sample with a control sample (e.g., an individual who does not have an IL-25-associated disorder) to determine if the patient has an associated disorder. Petition 870250103158, dated 11 / 11 / 2025, p. 64 / 127 59 / 93 for IL-25 or is at risk of developing an IL-25-associated disorder.

[00185] It will be advantageous in some modalities, for example, for diagnostic purposes, to label the antibody with a detectable fraction. Several detectable markers are available, including radioisotopes, fluorescent markers, enzymatic substrate markers, and the like. The marker can be indirectly conjugated with the antibody using several known techniques. For example, the antibody can be conjugated with biotin, and any of the three broad categories of markers mentioned above can be conjugated with avidin, or vice versa. Biotin binds selectively to avidin, and therefore the marker can be conjugated with the antibody in this indirect way. Alternatively, to achieve indirect conjugation of the marker with the antibody, the antibody can be conjugated with a small hapten (such as digoxin), and one of the different types of markers mentioned above is conjugated with an anti-hapten antibody (e.g., antidigoxin antibody).Thus, indirect conjugation of the marker with the antibody can be achieved.

[00186] Examples of radioisotope markers include 35S, 14C, 125I, 3H, and 131I. The antibody can be labeled with the radioisotope using the techniques described in, for example, Current Protocols in Immunology, Volumes 1 and 2, 1991, Coligen et al., Ed. Wiley-Interscience, New York, NY, Pubs. Radioactivity can be measured, for example, by scintillation counting.

[00187] Exemplary fluorescent markers include markers derived from rare earth chelates (europium chelates) or fluorescein and its derivatives, rhodamine and its derivatives, dansil, lissamine, phycoerythrin, and Texas red are available. Fluorescent markers can be conjugated to antibodies using known techniques, such as those described in Current Protocols in Immunology, for example. Fluorescence can be quantified using a fluorometer.

[00188] There are several well-characterized enzyme-substrate markers Petition 870250103158, dated 11 / 11 / 2025, page 65 / 127 60 / 93 known in the art (see, for example, U.S. Patent No. 4,275,149). The enzyme generally catalyzes a chemical change in the chromogenic substrate that can be measured using various techniques. For example, the change may be a color change in a substrate that can be measured spectrophotometrically. Alternatively, the enzyme may alter the fluorescence or chemiluminescence of the substrate. Techniques for quantifying a change in fluorescence are described above. The chemiluminescent substrate becomes electronically excited by a chemical reaction and may then emit light that can be measured using a chemiluminometer, for example, or donate energy to a fluorescent acceptor.

[00189] Examples of enzymatic markers include luciferases such as firefly luciferase and bacterial luciferase (U.S. Patent No. 4,737,456), luciferin, 2,3-dihydrophthalazinediones, malate dehydrogenase, urease, peroxidase such as horseradish peroxidase (HRPO), alkaline phosphatase, β-galactosidase, glucoamylase, lysozyme, saccharide oxidases (such as glucose oxidase, galactose oxidase and glucose-6-phosphate dehydrogenase), heterocyclic oxidases (such as uricase and xanthine oxidase), lactoperoxidase, microperoxidase and the like. Techniques for conjugating enzymes to antibodies are described, for example, in O'Sullivan et al., 1981, Methods for the Preparation of Enzyme-Antibody Conjugates for use in Enzyme Immunoassay, in Methods in Enzym. (J. Langone & H. Van Vunakis, eds.), Academic press, NY, 73: 147-166.

[00190] Examples of enzyme-substrate combinations include, for example: Horseradish peroxidase (HRPO) with hydrogen peroxidase as a substrate, wherein the hydrogen peroxidase oxidizes a dye precursor, such as orthophenylenediamine (OPD) or 3,3,5,5-tetramethylbenzidine hydrochloride (TMB); alkaline phosphatase (AP) with para-nitrophenyl phosphate as a chromogenic substrate; and β-D-galactosidase (β-D-Gal) with a chromogenic substrate, such as p-nitrophenyl-δ-galactosidase or the fluorogenic substrate 4-methylumbelliferyl-δ-galactosidase. Petition 870250103158, dated 11 / 11 / 2025, page 66 / 127 61 / 93

[00191] In another embodiment, the anti-IL-25 antibody or antibody fragment thereof is used without labeling and detected with a labeled antibody that binds to the anti-IL-25 antibody or antibody fragment thereof.

[00192] The antibodies and antibody fragments described herein may be employed in any known assay method, such as competitive binding assays, direct and indirect sandwich assays, and immunoprecipitation assays. See, for example, Zola, Monoclonal Antibodies: A Manual of Techniques, pp. 147-158 (CRC Press, Inc. 1987).

[00193] Anti-IL-25 antibody or antibody fragments thereof can be used to inhibit ligand binding to the IL-25 receptor. Such methods comprise administering an anti-IL-25 antibody to a cell (e.g., a mammalian cell) or cellular environment, whereby IL-25 receptor-mediated signaling is inhibited. These methods can be performed in vitro or in vivo. By “cellular environment” is meant the tissue, medium, or extracellular matrix surrounding a cell. Compositions and Treatment Methods

[00194] The invention also provides compositions including, for example, pharmaceutical compositions comprising an anti-IL-25 antibody or antibody fragment thereof. Such compositions have numerous therapeutic uses for the treatment, prevention or improvement of diseases or disorders (for example, diseases or disorders involving biological activity mediated by the IL-25 / IL-25 receptor signaling axis), such as an immune-mediated inflammatory disorder or an autoimmune disease.

[00195] An anti-IL-25 antibody or antibody fragment thereof described herein is useful in the treatment of various diseases or disorders, including type 2 inflammatory diseases, autoimmune diseases, or cancer. In particular, the antibodies described are useful for the treatment of immune-mediated inflammatory airway disorders.

[00196] Methods for treating a disorder associated with IL-25 Petition 870250103158, dated 11 / 11 / 2025, page 67 / 127 62 / 93 comprise administering a therapeutically effective amount of an anti-IL-25 antibody or antibody fragment thereof to an individual in need thereof. The present invention also provides methods for the treatment or prevention of Type 2 inflammatory disease, comprising administering a composition or formulation comprising an anti-IL-25 antibody or antibody fragment thereof, and optionally other immune-based therapy, to an individual in need thereof. The described anti-IL-25 antibodies may be administered as adjunctive therapy or in combination with other cytokine inhibitors.

[00197] The antibodies described are also useful in methods of prevention or treatment of airway hyperresponsiveness (AHR) or airway inflammation, including, but not limited to, allergic asthma, non-allergic asthma, severe refractory asthma, asthma exacerbations, virus-induced asthma, virus-induced asthma exacerbations, steroid-resistant asthma, steroid-sensitive asthma, eosinophilic asthma, non-eosinophilic asthma, and related disorders. Furthermore, the term includes virus-induced asthma exacerbations.

[00198] The antibodies described are also useful in methods of prevention or treatment of chronic obstructive pulmonary disease (COPD) in a patient who needs them, by administering an anti-IL-25 antibody or an antigen-binding fragment of the same, as described herein.

[00199] The antibodies described are also useful in methods of prevention or treatment of inflammatory bowel disease (IBD). In this context, IBD refers to a group of disorders affecting the large intestine or the mucous layer of the colon and includes ulcerative colitis, Crohn's disease, collagenous colitis, lymphocytic colitis, ischemic colitis, bypass colitis, Behçet's syndrome, infectious colitis, indeterminate colitis, and other related conditions characterized by inflammation.

[00200] The antibodies described are also useful in methods of Petition 870250103158, dated 11 / 11 / 2025, page 68 / 127 63 / 93 Prevention or treatment of atopic dermatitis (AD), including, but not limited to, inflammatory skin conditions marked by intense itching and dry, scaly eczematous lesions. AD can result from epidermal barrier dysfunction, allergies to certain foods, pollen, mold, dust mites, animal exposure to radiation, and / or asthma. The methods described here can be used to treat various degrees of AD, including mild, moderate, moderately severe, and severe forms.

[00201] The antibodies described are also useful in methods of prevention or treatment of various diseases and disorders, such as Eosinophilic Granulomatosis with Polyangiitis or EGPA (also known as Churg-Strauss Syndrome), allergy, allergic rhinitis, allergic airway inflammation, food hypersensitivity, urticaria (including chronic idiopathic urticaria), eosinophilic pneumonia, eosinophilic esophagitis, hypereosinophilic syndrome, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, rheumatoid arthritis, vasculitis, uveitis, cancer, and graft-versus-host disease.

[00202] The antibodies described are also useful in cancer treatment methods, alone (e.g., as monotherapies) or in combination with other immunotherapeutic agents and / or chemotherapy.

[00203] Antibodies can be administered alone or in combination with other compositions useful for treating an immune-mediated inflammatory disorder or an autoimmune disease. In some embodiments, compositions including, for example, pharmaceutical compositions comprising anti-IL-25 antibody may further comprise a therapeutic agent, conjugated or unconjugated to the binding agent.

[00204] In some respects, a composition is provided, for example, a pharmaceutical composition comprising one or more antibodies described herein. Pharmaceutical compositions may be formulated with pharmaceutically acceptable vehicles or diluents, as well as any Petition 870250103158, dated 11 / 11 / 2025, page 69 / 127 64 / 93 other known adjuvants and excipients, according to conventional techniques, such as those described in Remington: The Science and Practice of Pharmacy, 19th Edition, Gennaro, Ed., Mack Publishing Co., Easton, Pa., 1995

[00205] Typically, compositions for administration by injection are sterile isotonic aqueous buffer solutions. When necessary, the pharmaceutical product may also include a solubilizing agent and a local anesthetic, such as lidocaine, to relieve pain at the injection site. Generally, the ingredients are supplied separately or mixed in unit dosage form, for example, as a dry lyophilized powder or concentrate without water in a tightly closed container, such as an ampoule or sachet, indicating the amount of active agent. When the pharmaceutical product is administered by infusion, it may be dispensed with an infusion bottle containing sterile pharmaceutical-grade water or saline solution. When the pharmaceutical product is administered by injection, an ampoule of sterile water for injection or saline solution may be supplied so that the ingredients can be mixed before administration.

[00206] As used herein, “pharmaceutically acceptable carrier” includes any and all solvents, dispersing media, coatings, antibacterial and antifungal agents, isotonic agents and absorption retardants and the like that are physiologically compatible. Preferably, the carrier is suitable for intravenous, intramuscular, subcutaneous, parenteral, spinal or epidermal administration (e.g., by injection or infusion). Depending on the route of administration, the active compound, i.e., antibody, bispecific and multispecific molecule, may be coated with a material to protect the compound from the action of acids and other natural conditions that may inactivate it.

[00207] A composition can be administered by a variety of methods known in the art. How will it be appreciated by a person Petition 870250103158, dated 11 / 11 / 2025, pp. 70 / 127 65 / 93 skilled in the art, the route and / or mode of administration will vary depending on the desired results. Active compounds can be prepared with carriers that will protect the compound against rapid release, such as a controlled-release formulation, including implants, transdermal patches, and microencapsulated delivery systems. Biodegradable and biocompatible polymers such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid can be used. The methods for preparing such formulations are generally known to those skilled in the art. See, for example, Sustained and Controlled Release Drug Delivery Systems, J.R. Robinson, ed., Marcel Dekker, Inc., New York, 1978.

[00208] The dosage levels of the active ingredients in pharmaceutical compositions may be varied in order to obtain an amount of the active ingredient that is effective in achieving the desired therapeutic response for a given individual, composition and route of administration, without being toxic to the individual. The dosage level selected will depend on a variety of pharmacokinetic factors, including the activity of the specific compositions employed, the route of administration, the time of administration, the excretion rate of the specific compound employed, the duration of treatment, other medications, compounds and / or materials used in combination with the specific compositions employed, the age, sex, weight, condition, general health and previous medical history of the patient treated and similar factors well known in the medical arts.

[00209] The pharmaceutical compositions described herein may be administered in effective amounts.An “effective amount” refers to the amount that achieves a desired reaction or effect, alone or in conjunction with additional doses. In the case of treatment of a specific disease or condition, the desired reaction preferably refers to the inhibition of the disease course. This includes slowing the progression of the disease and, in particular, halting or reversing it. Petition 870250103158, dated 11 / 11 / 2025, page 71 / 127 66 / 93 disease progression.

[00210] In some respects, the compositions described herein are administered to patients, for example, in vivo, to treat or prevent a variety of disorders, such as those described herein. Preferred patients include human patients with disorders that can be corrected or improved by the administration of agents that modulate a biological activity of the IL-25 / IL-25 receptor signaling axis.

[00211] In some respects, conventional viral and nonviral gene transfer methods can be used to introduce nucleic acids encoding antibodies or their derivatives, as described herein, into mammalian cells or target tissues. Such methods can be used to deliver antibody-encoding nucleic acids to cells in vitro. In some embodiments, antibody-encoding nucleic acids or their derivatives are delivered for gene therapy uses in vivo or ex vivo. In other embodiments, gene delivery techniques are used to study antibody activity in cell or animal models. Nonviral vector delivery systems include DNA plasmids, naked nucleic acid, and nucleic acid complexed with a delivery vehicle such as a liposome. Viral vector delivery systems include DNA and RNA viruses, which have episomal or integrated genomes after delivery to the cell.These methods are well known in the field.

[00212] Nonviral administration methods of engineered polypeptide-encoding nucleic acids of the invention include lipofection, microinjection, biolistics, virosomes, liposomes, immunoliposomes, polycation or lipid:nucleic acid conjugates, nude DNA, artificial virions, and agent-enhanced DNA uptake. Lipofection methods and lipofection reagents are well known in the art (e.g., Transfectam™ and Lipofectin™). Cationic and neutral lipids suitable for efficient lipofection of polynucleotide receptor recognition include those of Felgner, WO 91 / 17424, WO 91 / 16024. Administration Petition 870250103158, dated 11 / 11 / 2025, p. 72 / 127 67 / 93 can be performed in cells (ex vivo administration) or in target tissues (in vivo administration). The preparation of lipid:nucleic acid complexes, including targeted liposomes, such as immunolipid complexes, is well known to a specialist in the field.

[00213] The use of RNA- or DNA-based viral systems for the delivery of nucleic acids encoding the antibodies described herein leverages highly evolved processes to target a virus to specific cells in the body and traffic the viral load to the nucleus. Viral vectors can be administered directly to patients (in vivo) or can be used to treat cells in vitro and the modified cells are administered to patients (ex vivo). Conventional viral systems for the delivery of polypeptides of the invention may include retroviral, lentiviral, adenoviral, adeno-associated, and herpes simplex virus vectors for gene transfer. Viral vectors are currently the most efficient and versatile method of gene transfer into target cells and tissues.Integration into the host genome is possible with gene transfer methods from retroviruses, lentiviruses, and adeno-associated viruses, generally resulting in long-term expression of the inserted transgene. Furthermore, high transduction efficiencies have been observed in many different target cell and tissue types.

[00214] All patents and publications identified are expressly incorporated herein by reference for the purpose of describing and disclosing, for example, the methodologies described in such publications that may be used in connection with the invention. These publications are provided only for inventions prior to the filing date of this application. Nothing in this respect should be construed as an admission that the inventors do not have the right to anticipate such invention by virtue of prior invention or for any other reason. All statements as to the date or representation as to the content of these documents are based on information available to the applicants and Petition 870250103158, dated 11 / 11 / 2025, p. 73 / 127 68 / 93 does not constitute any admission as to the accuracy of the dates or content of these documents.

[00215] To the extent not already indicated, it will be understood by persons skilled in the art that any of the various modalities described and illustrated herein may be further modified to incorporate features shown in any of the other modalities described herein.

[00216] The broad scope of this invention is best understood with reference to the following examples, which are not intended to limit disclosures to specific embodiments. The specific embodiments described herein are offered only as examples, and the invention should be limited by the terms of the appended claims, together with the full scope of the equivalents to which such claims are entitled. ILLUSTRATION OF THE SUBJECT TECHNOLOGY AS CLAUSES

[00217] Several examples of aspects are described as numbered clauses (1, 2, 3, etc.) for convenience. These are provided as examples and do not limit the subject matter of technology. The reference number identifications are provided below only as examples and for illustrative purposes, and the clauses are not limited by these identifications.

[00218] Clause 1: an anti-IL-25 antibody comprising: (a) a variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 23 (HCDR1); the amino acid sequence of SEQ ID NO: 49 (HCDR2); and the amino acid sequence of SEQ ID NO: 25 (HCDR3); and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 50 (LCDR1); the amino acid sequence of SEQ ID NO: 51 (LCDR2); and the amino acid sequence of SEQ ID NO: 28 (LCDR3); (b) a variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 23 (HCDR1); the amino acid sequence of SEQ ID NO: 52 (HCDR2); and the amino acid sequence of SEQ ID NO: 25 (HCDR3); and a variable region of the light chain Petition 870250103158, dated 11 / 11 / 2025, page 74 / 127 69 / 93 comprising the amino acid sequence of SEQ ID NO: 50 (LCDR1); the amino acid sequence of SEQ ID NO: 51 (LCDR2); and the amino acid sequence of SEQ ID NO: 28 (LCDR3); (c) a variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 11 (HCDR1); the amino acid sequence of SEQ ID NO: 12 (HCDR2); and the amino acid sequence of SEQ ID NO: 13 (HCDR3); and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 14 (LCDR1); the amino acid sequence of SEQ ID NO: 15 (LCDR2); and the amino acid sequence of SEQ ID NO: 16 (LCDR3); (d) a variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 17 (HCDR1); the amino acid sequence of SEQ ID NO: 18 (HCDR2); and the amino acid sequence of SEQ ID NO: 19 (HCDR3); and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 20 (LCDR1); the amino acid sequence of SEQ ID NO: 21 (LCDR2);and the amino acid sequence of SEQ ID NO: 22 (LCDR3); (e) a variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 23 (HCDR1); the amino acid sequence of SEQ ID NO: 24 (HCDR2); and the amino acid sequence of SEQ ID NO: 25 (HCDR3); and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 26 (LCDR1); the amino acid sequence of SEQ ID NO: 27 (LCDR2); and the amino acid sequence of SEQ ID NO: 28 (LCDR3); (f) a variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 29 (HCDR1); the amino acid sequence of SEQ ID NO: 30 (HCDR2); and the amino acid sequence of SEQ ID NO: 31 (HCDR3); and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 32 (LCDR1); the amino acid sequence of SEQ ID NO: 33 (LCDR2); and the amino acid sequence of SEQ ID NO: 34 (LCDR3);or (g) a variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 35 (HCDR1); the amino acid sequence of; Petition 870250103158, dated 11 / 11 / 2025, p. 75 / 127 70 / 93 SEQ ID NO: 36 (HCDR2); and the amino acid sequence of SEQ ID NO: 37 (HCDR3); and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 38 (LCDR1); the amino acid sequence of SEQ ID NO: 39 (LCDR2); and the amino acid sequence of SEQ ID NO: 40 (LCDR3).

[00219] Clause 2: the anti-IL-25 antibody or an antigen-binding fragment thereof from clause 1, wherein the antibody or antigen-binding fragment thereof comprises a variable region of the heavy chain comprising the amino acid sequence of any of the SEQ ID NOs: 1, 3, 5, 7, 9, 44 or 47; and a variable region of the light chain comprising the amino acid sequence of any of the SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46 or 48.

[00220] Clause 3: the anti-IL-25 antibody of clause 1, wherein the antibody comprises: (a) a variable region heavy chain sequence of SEQ ID NO: 44 and a variable region light chain sequence of SEQ ID NO: 45; (b) a variable region heavy chain sequence of SEQ ID NO: 44 and a variable region light chain sequence of SEQ ID NO: 46; (c) a variable region heavy chain sequence of SEQ ID NO: 47 and a variable region light chain sequence of SEQ ID NO: 48; (d) a variable region heavy chain sequence of SEQ ID NO: 1 and a variable region light chain sequence of SEQ ID NO: 2; (e) a variable region heavy chain sequence of SEQ ID NO: 3 and a variable region light chain sequence of SEQ ID NO: 4; (f) a variable region heavy chain sequence with SEQ ID NO: 5 and a variable region light chain sequence with SEQ ID NO: 6;(g) a variable region heavy chain sequence with SEQ ID NO: 7 and a variable region light chain sequence with SEQ ID NO: 8; or (h) a variable region heavy chain sequence with SEQ ID NO: 9 and a variable region light chain sequence with SEQ ID NO: 10.;

[00221] Clause 4: the anti-IL-25 antibody of clause 1, wherein the Petition 870250103158, dated 11 / 11 / 2025, pp. 76 / 127 71 / 93 antibody is an anti-human anti-IL-25 antibody.

[00222] Clause 5: the anti-IL-25 antibody of clause 1, wherein the antibody is a full-length antibody comprising a constant region of human IgG1 selected from SEQ ID NO: 55 or SEQ ID NO: 56.

[00223] Clause 6: the anti-IL-25 antibody of clause 1, wherein the antibody is an antibody fragment.

[00224] Clause 7: the anti-IL-25 antibody of clause 4, wherein the antibody fragment is selected from the group consisting of: fragment Fab, Fab, F(ab)2, Fd, Fv, scFv and scFv-Fc, a single-chain antibody, a minibody and a diabody.

[00225] Clause 8: the anti-IL-25 antibody from clause 1, where the antibody is a monoclonal antibody.

[00226] Clause 9: the anti-IL-25 antibody from clause 1, where the antibody is a human antibody.

[00227] Clause 10: the anti-IL-25 antibody from clause 1, where the antibody is a murine antibody.

[00228] Clause 11: the anti-IL-25 antibody of clause 1, where the antibody is a chimeric antibody.

[00229] Clause 12: the anti-IL-25 antibody of clause 1, where the antibody is a bispecific or multispecific antibody.

[00230] Clause 13: the anti-IL-25 antibody of clause 1, where the antibody is a humanized antibody.

[00231] Clause 14: a pharmaceutical composition comprising the antibody of clause 1 and a pharmaceutically acceptable carrier.

[00232] Clause 15: a method of treating and / or preventing a type 2 inflammatory disease, autoimmune disease, allergic disorder or cancer in an individual who needs it, the method comprising: administering to the individual the antibody of clause 1.

[00233] Clause 16: a polynucleotide composition Petition 870250103158, dated 11 / 11 / 2025, page 77 / 127 72 / 93 comprising: a) a first polynucleotide encoding a variable region of the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 1, 3, 5, 7, 9, 44 or 47; and b) a second polynucleotide encoding a variable region of the light chain comprising the amino acid sequence set forth in SEQ ID NO: 2, 4, 6, 8, 10, 45, 46 or 48.

[00234] Clause 17: A vector composition comprising: a) a first vector comprising the first polynucleotide of clause 16; and b) a second vector comprising the second polynucleotide of clause 16.

[00235] Clause 18: a cell comprising the polynucleotide composition according to clause 16, or a vector composition according to clause 17.

[00236] Clause 19: a method for producing an anti-IL25 antibody according to clause 1, the method comprising cultivating the cell of clause 18 in a culture medium; and recovering the anti-IL-25 antibody from the medium. EXAMPLES General Methods

[00237] Methods for protein purification are described, including immunoprecipitation, chromatography, and electrophoresis. See, for example, Coligan et al. (2000) Current Protocols in Protein Science, Vol. 1, John Wiley and Sons, Inc., New York. Chemical analyses, chemical modifications, post-translational modifications, production of fusion proteins, and protein glycosylation are described. See, for example, Coligan et al. (2000) Current Protocols in Protein Science, Vol. 2, John Wiley and Sons, Inc., New York; Ausubel et al. (2001) Current Protocols in Molecular Biology, Vol. 3, John Wiley and Sons, Inc., NY, NY, pp. 16,0.5-16,22,17; Sigma-Aldrich, Co. (2001) Products for Life Science Research, St. Louis, Mo.; pp. 45-89; Amersham Pharmacia Biotech (2001) BioDirectory, Piscataway, NJ, pp. Petition 870250103158, dated 11 / 11 / 2025, page 78 / 127 73 / 93 384-391. The production, purification, and fragmentation of polyclonal and monoclonal antibodies are described. Coligan et al. (2001) Current Protocols in Immunology, Vol. 1, John Wiley and Sons, Inc., New York; Harlow and Lane (1999) Using Antibodies, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Harlow and Lane, supra.

[00238] The hybridoma or cell culture supernatant containing an anti-IL-25 antibody was purified using a HiTrap G protein column (GE, cat. No. 17040401) according to the manufacturer's protocol. Briefly, the column was equilibrated with DPBS (Gibco, cat. No. 14190136) for 5 CV and the supernatant was loaded using a syringe / infusion pump (Legato 200, KDS) at room temperature and a residence time of 3 minutes. The column was washed with 5 CV of DPBS and elution was performed with 4 CV of pH 2.8 elution buffer (Fisher Scientific, cat. No. PI21004), neutralized with 1M Tris-HCl, pH 8.5 (Fisher Scientific, cat. No. 50-843-270) and analyzed by A280 (DropSense96, Trinean). The purified material was then buffer-exchanged in DPBS using 30 kDa MWCO centrifugal filters (EMD Millipore, cat. No. UFC803024). The final pool was analyzed by A280 and stored at 2-8°C or -20°C.

[00239] Standard methods in molecular biology are described. See, for example, Maniatis et al. (1982) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Sambrook and Russell (2001) Molecular Cloning, 3rd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Wu (1993) Recombinant DNA, Vol. 217, Academic Press, San Diego, California. Standard methods also appear in Ausbel et al. (2001) Current Protocols in Molecular Biology, Vols. 1-4, John Wiley and Sons, Inc. New York, NY, which describes cloning in bacterial cells and DNA mutagenesis (Vol. 1), cloning in mammalian and yeast cells (Vol. 2), glycoconjugates and protein expression (Vol. 3), and bioinformatics (Vol. 4).

[00240] The sequences for the variable regions of the heavy and light chains Petition 870250103158, dated 11 / 11 / 2025, page 79 / 127 74 / 93 hybridoma clones were determined as described below. Total RNA was extracted from 1-2 x10⁶ hybridoma cells using the Qiagen RNeasy Plus Mini kit (Germantown, MD, USA). cDNA was generated by performing 5' RACE reactions using the Takara SMARTer RACE 5' / 3' kit (Mountainview, CA, USA). PCR was performed using the NEB Q5 High-Fidelity DNA Polymerase (Ipswich, MA, USA) to amplify the variable regions of the heavy and light chains using the Takara Universal Primer Mix in combination with gene-specific primers for the appropriate mouse immunoglobulin 3' constant region. The amplified variable regions for the heavy and light chains were run on 2% agarose gels, the appropriate bands were excised and then purified on gel using the Qiagen Mini Elute Gel Extraction Kit.The purified PCR products were cloned using the Invitrogen Zero Blunt PCR Cloning Kit (Carlsbad, CA, USA), transformed into Takara Stellar Competent E. coli cells, and seeded onto LB Agar plates + 50 µg / ml kanamycin. Direct sequencing of the Sanger colony was performed using GeneWiz (South Plainfield, NJ, USA). The resulting nucleotide sequences were analyzed using IMGT V-QUEST to identify productive rearrangements and analyze translated protein sequences. CDR determination was based on Kabat numbering.

[00241] Selected VH or VL chains were amplified by PCR and cloned into a pcDNA3.4-based expression vector harboring the constant region of human IgG1 (Uniprot P01857 or its allotype) or human Kappa light chain (UniProt P01834). Paired plasmids expressing heavy and light chains were transfected into Expi293 cells (Thermo Fisher Scientific) following the vendor's Expi293 expression system protocol. Five days after transfection, culture supernatants were collected by centrifugation. Chimeric antibodies were purified by one-step affinity purification using a protein A column and buffer exchanged to PBS pH 7.2 or 20 mM Petition 870250103158, dated 11 / 11 / 2025, page 80 / 127 75 / 93 histidine pH 5.5.

[00242] Methods for flow cytometry, including fluorescence-activated cell sorting detection systems (FACS®), are available. See Owens et al. (1994) Principles of Flow Cytometry for Clinical Laboratory Practice, John Wiley and Sons, Hoboken, NJ; Givan (2001) Flow Cytometry, 2nd ed.; Wiley-Liss, Hoboken, NJ; Shapiro (2003) Practical Flow Cytometry, John Wiley and Sons, Hoboken, NJ. Suitable fluorescent reagents for modifying nucleic acids, including nucleic acid primers and probes, polypeptides, and antibodies, for use, for example, as diagnostic reagents, are available. Molecular Probes (2003) Catalogue, Molecular Probes, Inc., Eugene, Oreg.; SigmaAldrich (2003) Catalogue, St. Louis, Mo.

[00243] Standard techniques for characterizing ligand / receptor interactions are available. See, for example, Coligan et al. (2001) Current Protocols in Immunology, Vol. 4, John Wiley, Inc., New York. Standard methods for functional characterization of antibodies appropriate for characterizing antibodies with specific mechanisms of action are also well known to those skilled in the art.

[00244] Two specific antibodies for internal IL-25, referred to herein as IL-25-PC2 and IL-25-PC4, were prepared. IL-25-PC2 was prepared based on publicly available information published in WO 2016 / 049000 A2 (VH, SEQ ID NO: 114; and VL, SEQ ID NO: 122) and IL-25PC4 was prepared based on publicly available information published in WO 2020 / 102935 A1 (VH, SEQ ID NO: 12; and VL, SEQ ID NO: 13). Both antibodies were used to establish the binding and functional assays used to evaluate and characterize the specific anti-IL-25 antibodies described herein.

[00245] Software packages and databases are available to determine, for example, antigenic fragments, leader sequences, protein folding, functional domains, CDR annotation, sites of Petition 870250103158, dated 11 / 11 / 2025, page 81 / 127 76 / 93 glycosylation and sequence alignments. EXAMPLE 1: Generation of anti-IL-25 antibodies

[00246] Anti-IL-25 antibodies were generated by immunizing wild-type or transgenic / humanized mice.

[00247] Immunization. Mice were immunized with recombinant human IL-25 protein intraperitoneally, subcutaneously, in the paw pad, or at the base of the tail. The immune response was monitored by retro-orbital bleeding. Plasma was screened by ELISA (as described below), and mice with sufficient anti-human IL-25 titers were used for fusions. Mice were stimulated intraperitoneally, intravenously, in the paw pad, or at the base of the tail with recombinant human IL-25 protein before sacrifice and removal of the spleen and lymph nodes.

[00248] Selection of Balb / c Mice Producing Anti-IL-25 Antibodies. To select Balb / c mice that produce antibodies that bind to IL-25, sera from immunized mice were screened by ELISA for IL-25 binding. Briefly, an ELISA plate coated with recombinant human IL-25 protein was incubated with serum dilutions from immunized mice for one hour at room temperature, the plate was washed, and specific antibody binding was detected with HRP-labeled anti-mouse IgG antibody. The plate was read using an ELISA reader (Biotek). The hybridoma supernatants were tested for specific anti-IL-25 binding by ELISA, as described above.

[00249] Generation of antibody-producing hybridomas for IL-25. To generate antibody-producing hybridomas of the invention, splenocytes and lymph node cells were isolated from an immunized mouse fused to an appropriate immortalized cell line, such as a mouse myeloma cell line. The resulting hybridomas were screened for the production of antibodies specific to antigens. For example, single-cell suspensions of splenocytes and lymph node cells of Petition 870250103158, dated 11 / 11 / 2025, page 82 / 127 77 / 93 immunized mice were fused to an equal number of Sp2 / 0 non-secreting mouse IgG myeloma cells (ATCC, CRL 1581) by electrofusion. The cells were placed in 96-well flat-bottom tissue culture plates, followed by 2 weeks of incubation in screening medium (HAT medium) and then transferred to hybridoma culture medium. Approximately 10–14 days after cell plating, individual well supernatants were screened by ELISA as described above. Antibody-secreting hybridomas were transferred to 24-well plates, screened again, and if still positive for anti-IL-25, the positive hybridomas were subcloned by limiting dilution or sorting using a single-cell sorter. Stable subclones were then cultured in vitro to generate small amounts of antibodies to be used for purification and characterization. EXAMPLE 2: Binding of specific anti-IL-25 antibodies

[00250] In this study, the ability of five described anti-IL-25 antibodies (IL25Ab1 to Ab5) to bind to human and mouse IL-25 was evaluated using ELISA. Briefly, recombinant human IL-25 protein (Acro, catalog number: IL5-H4221, batch number: 40120CNF1-UT) or recombinant mouse IL-25 protein (Sino Biological Inc, catalog number: 50138-M07H, batch number: LC15AP0607) was directly coated onto ELISA plates, respectively. Recombinant antibodies were then added to the plates, followed by detection using goat anti-human IgG-HRP (Jackson ImmunoResearch, catalog number: 109-035-098, batch number: 157400). After adding the ABTS substrate (Moss Inc., catalog no.: ABTS-1000, lot no.: 03086202), the ELISA plates were read using an ELISA plate reader (Bioteck).

[00251] Figure 3A shows that the five described anti-IL-25 antibodies bound to recombinant human IL-25 protein in a dose-dependent manner, with EC50 values ​​ranging from 0.010 nM to 0.034 nM. The Petition 870250103158, dated 11 / 11 / 2025, page 83 / 127 78 / 93 positive control antibodies IL-25-PC2 (a recombinant antibody made by NovaRock, batch no.: P09282021JLF) and IL-25-PC4 (a recombinant antibody made by NovaRock, batch no.: A10032022JLF) had EC50 values ​​of 0.026 nM and 0.028 nM, respectively. The human IgG1 isotype control (InVivoMab, catalog no.: BE0297, batch no.: 760620M1) showed no binding.

[00252] Figure 3B shows that the five described anti-IL-25 antibodies also bound to recombinant mouse IL-25 protein in a dose-dependent manner, with EC50 values ​​ranging from 0.012 nM to 0.035 nM. The positive control antibodies IL-25-PC2 and IL-25-PC4 showed EC50 values ​​of 0.022 nM and 0.021 nM, respectively.

[00253] In another study, the ability of five described anti-IL-25 antibodies (IL25Ab1 to Ab5) to bind to cynomolgus IL-25 was evaluated using ELISA. Briefly, recombinant human IL-25 protein (Acro, catalog number: IL5-H4221, batch number: 401-20CNF1-UT) or recombinant cynomolgus IL-25 protein (Sino Biological Inc, catalog number: custom order, batch number: MB17MA2715) was directly coated onto ELISA plates, respectively. Recombinant antibodies were then added to the plates, followed by detection using goat anti-human kappa light chain HRP antibody (Novus, catalog no.: NBP1-75064, batch no.: 68-188-010920). After adding the ABTS substrate (Moss Inc., catalog no.: ABTS-1000, lot no.: 03086202), the ELISA plates were read using an ELISA plate reader (Bioteck).

[00254] Figure 3C shows that the five described anti-IL-25 antibodies also bound to recombinant cynomolgus IL-25 protein in a dose-dependent manner, with similar binding activity when compared to the positive control antibodies IL-25-PC2 and IL-25-PC4. Table 5: EC50 binding of IL-25 antibodies to IL-25 proteins Goat anti-human IgG-HRP antibody Petition 870250103158, dated 11 / 11 / 2025, page 84 / 127 79 / 93 Human IL-25 ELISA EC50 detection, nM; Mouse IL-25 ELISA EC50, nM; IL25Ab1 0.020 0.015; IL25Ab2 0.017 0.012; IL25Ab3 0.022 0.013; IL25Ab4 0.034 0.026; IL25Ab5 0.010 0.035; IL25-PC2 0.026 0.022; IL25-PC4 0.028 0.021 EXAMPLE 3: Binding kinetics of specific anti-IL-25 antibodies

[00255] The binding kinetics of the described anti-IL-25 antibodies to recombinant human IL-25 were determined using Sartorius Octet® Bio-Layer Interferometry (BLI) systems. The assay uses anti-IL-25 monoclonal antibodies as a ligand and recombinant human IL-25 protein as an analyte.

[00256] In summary, the assays were performed by first capturing 5 pg / ml of anti-IL-25 antibodies using Fc Octet anti-human biosensors. The biosensors captured with mAb were then submerged in wells containing serially diluted human IL-25 for 4 to 6 minutes, followed by a dissociation time of 10 to 15 minutes. Binding sensorgrams were collected and analyzed using Octet Data Analysis software.

[00257] Table 6 summarizes the KD values ​​for the anti-IL25 antibodies described in this study. The data suggest that these antibodies have a strong binding affinity to recombinant human IL-25 and exhibit rapid activation and slow deactivation kinetic characteristics. Table 6: Binding kinetics of anti-IL-25 antibody Antibody ka (1 / Ms) kd (1 / s) KD (M) IL25Ab1 1.25E+06 <1.0E-07 <1.0E-12 Petition 870250103158, dated 11 / 11 / 2025, page 85 / 127 80 / 93 IL25Ab2 1.36E+06 <1.0E-07 <1.0E-12 IL25Ab3 8.75E+05 <1.0E-07 <1.0E-12 IL25Ab4 1.20E+06 <1.0E-07 <1.0E-12 IL25Ab5 2.48E+06 <1.0E-07 <1.0E-12 IL25-PC2 7.80E+05 <1.0E-07 <1.0E-12 EXAMPLE 4: Blocking IL-25-induced NF-kB signaling

[00258] IL-25 interacts and signals via an IL-25 receptor comprising the heterodimeric subunits IL-17RA and IL-17RB. The activated heterodimeric receptor recruits the adaptor Act1, leading to the ubiquitination of TNF receptor-associated factor 6 (TRAF6). This, in turn, triggers a signaling cascade resulting in the activation of NF-κB and AP-1.

[00259] A HEK-293 reporter cell line was used to study the blocking activity of anti-IL-25 antibodies. HEK-Blue™ IL-17 cells (InvivoGen, San Diego, CA) were generated by stable transfection of human genes encoding the heterodimeric receptor IL-17RA / IL-17RC and the adaptor molecule Act1 into the HEK293 human embryonic kidney cell line. These cells also express a secreted embryonic alkaline phosphatase (SEAP) reporter gene that is inducible by NF-κB and AP-1.

[00260] In this study, HEK-Blue™ IL-17 cells were treated with recombinant human IL-25 at 5 ng / ml together with serially diluted IL-25 antibodies. After overnight incubation, the NF-κB response was determined using QUANTI-Blue™ solution, a SEAP detection reagent, by reading the optical density (OD) at 655 nm.

[00261] As shown in Figure 4 and summarized in Table 7, the five described anti-IL-25 antibodies effectively blocked IL-25-induced NF-κB signaling in a dose-dependent manner, with IC50 values ​​ranging from 0.049 nM to 0.073 nM. The positive control antibodies IL-25PC2 and IL-25PC4 showed IC50 values ​​of 0.062 nM and 0.456 nM, respectively. Petition 870250103158, dated 11 / 11 / 2025, page 86 / 127 81 / 93 respectively. The human IgG1 isotype control showed no blocking activity. Table 7. Inhibitory activity of IL-25 antibodies in the NFkB signaling assay. IC50, nM IL25Ab1 0.052 IL25Ab2 0.068 IL25Ab3 0.049 IL25Ab4 0.073 IL25Ab5 0.061 IL25-PC2 0.062 IL25-PC4 0.456 EXAMPLE 5: Blocking IL-25-induced CXCL1 production

[00262] Interleukin-17 (IL-17) expression is significantly elevated in the peripheral blood of patients with inflammatory bowel disease (IBD), indicating that IL-17 may play a crucial role in the physiological and pathological processes of the disease. Because the HT-29 intestinal epithelial cell line has normal colonic epithelial structures and functions, it has been the most commonly used cell line in the laboratory to study the immunological mechanisms of the intestinal mucosa.

[00263] To determine whether the described anti-IL-25 antibodies can block the production of the inflammatory cytokine CXCL1 induced by human IL-25, HT-29 cells were seeded in assay plates. Subsequently, a combination of serially diluted anti-IL-25 antibody and hIL-25 was added to their respective wells, and the cells were incubated for 72 hours at 37°C. The supernatants were then collected for CXCL1 ELISA, using the Human CXCL1 ELISA Ready-SET-Go kit (R&System D #DY275).The results, presented in Figure 5 and Table 8, demonstrate that five described anti-IL-25 antibodies effectively blocked IL-25-stimulated CXCL1 production, reducing it. Petition 870250103158, dated 11 / 11 / 2025, page 87 / 127 82 / 93 potentially recruiting immune cells and preventing the development of inflammation.

[00264] IC50 values ​​ranged from 0.067 nM to 0.089 nM. The positive control antibodies IL-25-PC2 and IL-25-PC4 showed IC50 values ​​of 0.066 nM and 0.877 nM, respectively. The human IgG1 isotype control showed no blocking activity. Table 8. IL-25 Antibody Activity in Blocking CXCL1 Production IC50, nM IL25Ab1 0.071 IL25Ab2 0.089 IL25Ab3 0.067 IL25Ab4 0.076 IL25Ab5 0.077 IL25-PC2 0.066 IL25-PC4 0.877 EXAMPLE 6: Blocking IL-5 production induced by IL-25

[00265] IL-25 has been implicated as a type 2 cytokine produced by Th2 cells, which was able to induce the expression of the IL-4, IL-5, and IL-13 genes. The induction of these cytokines resulted in Th2-like responses, marked by increased serum levels of IgE, IgG, and IgA, blood eosinophilia, and pathological changes in the lungs and digestive tract, which included eosinophilic infiltrates, increased mucus production, and hyperplasia / hypertrophy of epithelial cells.

[00266] To better characterize the biological functions of IL25 antibodies and evaluate their potential in the treatment of inflammatory diseases, human PBMCs were used in this assay. When treating human PBMCs with 30 U / ml of recombinant hIL-2 and 2 ng / ml of recombinant hIL-25 for 6 days, a significant amount of IL-5 was produced. However, if the cells were co-treated with IL-25 blocking antibodies, the IL-5 level was greatly reduced, suggesting that an IL-25 antibody may suppress the type II response. Petition 870250103158, dated 11 / 11 / 2025, p. 88 / 127 83 / 93 2.

[00267] As shown in Figure 6 and summarized in Table 9, all five IL-25 antibodies described effectively blocked IL-25-induced IL5 production in a dose-dependent manner, with IC50 values ​​ranging from 0.12 nM to 0.26 nM. The positive control antibodies IL-25-PC2 and IL-25-PC4 showed IC50 values ​​of 0.26 nM and 12.99 nM, respectively. The human IgG1 isotype control showed no blocking activity. Table 9. IL-25 Antibody Activity in Blocking IL-5 Production IC50, nM IL25Ab1 0.12 IL25Ab2 0.14 IL25Ab3 0.16 IL25Ab4 0.15 IL25Ab5 0.26 IL25-PC2 0.26 IL25-PC4 12.99 EXAMPLE 7: In vivo efficacy of the specific anti-IL-25 antibody in the OVA-induced asthma model

[00268] The OVA-induced asthma model was used to study the in vivo efficacy of specific anti-IL-25 antibodies. Male BALB / c mice aged six to seven weeks were divided into 6 groups (10 mice in each group): (1) control group; (2) OVA + vehicle group; (3-6) OVA + anti-IL-25 antibody group. Mice in the OVA group were sensitized by intraperitoneal injection of an aluminum hydroxide-containing OVA solution on days 1 and 14, and challenged by aerosolization of a 1% OVA solution for 30 minutes using the BUXCO aerosol dosing system on days 28, 29, and 31. Anti-IL-25 antibodies were injected subcutaneously at 10 mg / kg on days 14, 17, 20, 23, 26, 29, and 31. All antibodies tested were made in mouse IgG1 format. Petition 870250103158, dated 11 / 11 / 2025, page 89 / 127 84 / 93 On day 31, pulmonary resistance in response to a variety of aerosolized methacholine was measured by whole-body plethysmography (WBP, Buxco BFE0100 WBP). On day 32, mice were anesthetized and BALF was obtained by lung lavage with PBS containing 1% FBS.

[00269] Airway hyperresponsiveness is a characteristic of asthma. In Figure 7, mice in the OVA + Vehicle group showed significantly increased airway resistance to methacholine compared to the control group. Treatment with IL25Ab3 significantly reduced airway resistance. IL25Ab4, IL25Ab5, and IL25PC4 showed a slight reduction in airway resistance. However, this reduction did not reach statistical significance. Airway resistance was represented as methacholine dose-response data presented as a percentage change from baseline pulmonary resistance level (Penh value) (Figure 7A) and AUC of % of baseline Penh (Figure 7B).

[00270] Interleukin-5 (IL-5) plays a central pathogenic role in the differentiation, recruitment, survival, and degranulation of eosinophils. The powerful actions of IL-5 in inducing, maintaining, and amplifying eosinophilic inflammation, such as asthma, have been reported. In Figure 8, a significant increase in IL-5 in bronchoalveolar lavage fluid (BALF) in the OVA-induced asthma model when comparing OVA + vehicle mice with control mice. Treatments with IL25Ab3, IL25Ab5, and IL25-PC4 significantly reduced IL-5 production in BALF. Treatment with IL25Ab4 decreased IL-5 production (not significantly). EXAMPLE 8: Humanization of anti-IL-25Ab3

[00271] Murine anti-IL-25Ab3 was humanized using the CDR grafting approach. The variable regions of the murine Ab3 heavy chain and light chain were derived from the mouse germlines IGHV118*01 and IGKV10-94*01, respectively. The variable region of the heavy chain was used to search the germline database of Petition 870250103158, dated 11 / 11 / 2025, pp. 90 / 127 85 / 93 human antibodies, and the human germline sequence with the highest similarity, human IGHV1-2*02, was selected as a template for heavy chain CDR grafting. Similarly, human IGKV1-33*01 was selected as a template for light chain CDR grafting. During gridding, structural templates of the antibodies were generated, and selected reverse mutations were introduced to maintain proper antibody folding. A total of 5 heavy chain variants and 4 light chain variants were designed and cloned into expression constructs. 20 pairs of humanization variants of heavy chain and light chain were made as human Fab and IgG1 antibodies. Fab fragments of the humanization variants were used to measure binding affinity in the BLI instrument, and human IgG1 antibodies were used for binding ELISA as well as functional assays.Table 10 shows that the 3 main selected humanized Fabs have similar binding affinity to the murine parental Fab. Table 10: Binding affinity of humanized IL-25 antibody Fabs to IL-25 proteins KD (M) kon(1 / Ms) kdis(1 / s) Fab IL25Ab6 1.86E-09 1.34E+05 2.49E-04 IL25Ab7 Fab 1.80E-09 1.61E+05 2.90E-04 IL25Ab8 Fab 1.78E-09 1.41E+05 2.51 E-04 IL25Ab3 Fab 1.89E-09 1.50E+05 2.85E-04 EXAMPLE 9: Binding of humanized anti-IL-25 antibodies to recombinant human, mouse, and cynomolgus IL-25 proteins

[00272] In this study, the ability of three humanized anti-IL-25 antibodies generated in hlgG1 (IL25Ab6 to Ab8) and hlgG1 YTE (IL25Ab9 to Ab11) formats to bind to human, mouse, and cynomolgus IL-25 was evaluated using ELISA. Briefly, recombinant human IL-25 protein (Acro, catalog number: IL5-H4221, number of Petition 870250103158, dated 11 / 11 / 2025, p. 91 / 127 86 / 93 batch: 401-20CNF1-UT), recombinant mouse IL-25 protein (Sino Biological Inc, catalog number: 50138-M07H, batch number: LC15AP0607) or recombinant cynomolgus IL-25 protein (Sino Biological Inc, catalog number: custom order, batch number: MB17MA2715) were directly coated onto ELISA plates, respectively. Recombinant antibodies were then added to the plates, followed by detection using goat anti-human kappa light chain HRP antibody (Novus, catalog no.: NBP1-75064, batch no.: 68-188010920). After adding the ABTS substrate (Moss Inc., catalog no.: ABTS1000, lot no.: 03086202), the ELISA plates were read using an ELISA plate reader (Bioteck).

[00273] Figure 9A shows that all humanized anti-IL-25 antibodies bound to human IL-25 protein in a dose-dependent manner, with EC50 values ​​ranging from 0.302 nM to 0.404 nM. The murine-derived anti-IL-25 specific antibody (IL25Ab3), the IL-25-PC2 and IL-25-PC4 positive control antibodies showed EC50 values ​​of 0.506 nM, 0.334 nM, and 0.585 nM, respectively. The human IgG1 isotype control showed no binding.

[00274] Figure 9B shows that all humanized anti-IL-25 antibodies bound to cynomolgus IL-25 protein in a dose-dependent manner, with EC50 values ​​ranging from 0.222 nM to 0.295 nM. The murine-derived anti-IL-25 specific antibody (IL25Ab3), the IL-25-PC2 and IL-25-PC4 positive control antibodies, showed EC50 values ​​of 0.364 nM, 0.365 nM, and 0.408 nM, respectively. The human IgG1 isotype control showed no binding.

[00275] Figure 9C shows that all humanized anti-IL-25 antibodies bound to mouse IL-25 protein in a dose-dependent manner, with EC50 values ​​ranging from 0.232 nM to 0.332 nM. The murine-derived anti-IL-25 specific antibody (IL25Ab3), the positive control antibodies IL-25-PC2 and IL-25-PC4, showed EC50 values ​​of Petition 870250103158, dated 11 / 11 / 2025, p. 92 / 127 87 / 93 0.390 nM, 0.420 nM, and 0.407 nM, respectively. The human IgG1 isotype control showed no binding. These results are summarized in Table 11. Table 11: EC50 of IL-25 antibody binding to IL-25 proteins EC50 from Human IL-25 ELISA, nM EC50 from Cynomolgus IL-25 ELISA, nM EC50 from Mouse IL-25 ELISA, nM IL25Ab3 0.506 0.364 0.390 IL25Ab6 0.302 0.241 0.242 IL25Ab7 0.327 0.245 0.243 IL25Ab8 0.404 0.295 0.332 IL25Ab9 0.312 0.222 0.232 IL25Ab10 0.364 0.266 0.284 IL25Ab11 0.318 0.239 0.258 IL25-PC2 0.334 0.365 0.420 IL25-PC4 0.585 0.408 0.407 EXAMPLE 10: Blocking IL-25-induced NF-kB signaling

[00276] In this study, we examined the blocking activity of humanized anti-IL-25 antibodies using HEK-Blue™ IL-17 cells (InvivoGen, San Diego, CA), as described in Example 4. In summary, reporter cells were treated with recombinant human IL-25 at 5 ng / ml along with serially diluted IL-25 antibodies. After overnight incubation, the NF-κB response was determined using QUANTI-Blue™ solution, a SEAP detection reagent, and reading the optical density (OD) at 655 nm.

[00277] As shown in Figure 10 and summarized in Table 12, all humanized anti-IL-25 antibodies effectively blocked IL-25-induced NF-κB signaling in a dose-dependent manner, with IC50 values ​​ranging from 0.037 nM to 0.052 nM. The origin of the specific anti-IL-25 antibody (IL25Ab3) in mice, the control antibodies Petition 870250103158, dated 11 / 11 / 2025, page 93 / 127 88 / 93 positive IL-25-PC2 and IL-25-PC4 showed IC50 values ​​of 0.037 nM, 0.030 nM, and 0.513 nM, respectively. The human IgG1 isotype control showed no blocking activity. Table 12. Inhibitory activity of IL-25 antibodies in the NFkB signaling assay. IC50, nM IL25Ab3 0.037 IL25Ab6 0.048 IL25Ab7 0.042 IL25Ab8 0.041 IL25Ab9 0.043 IL25Ab10 0.052 IL25Ab11 0.037 IL25-PC2 0.030 IL25-PC4 0.513 EXAMPLE 11: Blocking IL-25-induced CXCL1 production

[00278] To determine whether humanized anti-IL-25 antibodies can block the production of the inflammatory cytokine CXCL1 induced by human IL-25, HT-29 cells endogenously expressing the IL17 receptor were used as described in Example 5. In summary, HT29 cells were stimulated with hIL-25 in a combination of serially diluted anti-IL25 antibodies for 72 hours at 37°C. Supernatants were then collected for CXCL1 level measurement using the Human CXCL1 ELISA Ready-SET-Go kit (R&System D #DY275). The results, presented in Figure 11 and Table 13, demonstrate that the humanized anti-IL-25 antibodies maintained strong blocking activity against IL-25-induced CXCL1 production, potentially reducing immune cell recruitment and preventing the development of inflammation.

[00279] The IC50 values ​​of the humanized antibodies (IL25Ab6-Ab11) ranged from 0.183 nM to 0.225 nM. The origin of the specific anti-IL25 antibody. [Illegible text: 870250103158, 11 / 11 / 2025, p. 94 / 127] In mice using the 89 / 93 antibody (IL25Ab3), the positive control antibodies IL-25-PC2 and IL-25-PC4 showed IC50 values ​​of 0.144 nM, 0.148 nM, and 1.84 nM, respectively. The human IgG1 isotype control showed no blocking activity. Table 13. IL-25 Antibody Activity in Blocking CXCL1 Production IC50, nM IL25Ab3 0.144 IL25Ab6 0.225 IL25Ab7 0.183 IL25Ab8 0.199 IL25Ab9 0.225 IL25Ab10 0.198 IL25Ab11 0.187 IL25-PC2 0.148 IL25-PC4 1.84 EXAMPLE 12: Blocking IL-5 production induced by IL-25

[00280] To better characterize the biological functions of humanized IL-25 antibodies and evaluate their potential in the treatment of inflammatory diseases, a human PBMC assay was performed as described in Example 6. In summary, IL-25 induced a significant amount of IL-5 production by human PBMCs in the presence of 30 U / ml of recombinant hIL-2. The blocking activity of the humanized anti-IL-25 antibodies was determined to indicate their type 2 inflammatory response suppression activity.

[00281] As shown in Figure 12 and summarized in Table 14, all humanized antibodies against IL-25 effectively blocked IL-25-induced IL-5 production in a dose-dependent manner, with IC50 values ​​ranging from 0.381 nM to 1.43 nM. The anti-IL-25 specific antibody (IL25Ab3) originating from mice, the positive control antibodies IL-25-PC2 and IL-25-PC4 showed IC50 values ​​of 0.302 nM, Petition 870250103158, dated 11 / 11 / 2025, pp. 95 / 127 90 / 93 0.394 nM and 7.15 nM, respectively. The human IgG1 isotype control showed no blocking activity. Table 14. IL-25 Antibody Activity in Blocking IL-5 Production IC50, nM IL25Ab3 0.302 IL25Ab6 0.381 IL25Ab7 0.850 IL25Ab8 1.04 IL25Ab9 0.435 IL25Ab10 1.43 IL25Ab11 0.953 IL25-PC2 0.394 IL25-PC4 7.15

[00282] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth, used in the specification and claims, should be understood as modified in all cases by the term “about”. Consequently, unless otherwise indicated, the numerical parameters set forth in the specification and appended claims are approximations that may vary depending on the desired properties sought to be obtained by the present invention. At a minimum, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be interpreted in light of the reported number of significant digits and applying common rounding techniques.

[00283] Although the ranges and numerical parameters that define the broad scope of the invention are approximations, the numerical values ​​presented in the specific examples are reported to the greatest extent possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in its Petition 870250103158, dated 11 / 11 / 2025, pp. 96 / 127 91 / 93 respective test measurements.

[00284] The terms “a”, “an”, “the” and similar referents used in the context of the invention description (especially in the context of the following claims) are to be interpreted to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by the context. The quotation of value ranges presented herein serves only as a shorthand method for individually referring to each separate value within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein may be performed in any suitable order, unless otherwise indicated or clearly contradicted by the context. The use of any and all examples or exemplary language (e.g., “such as”) provided herein is for the sole purpose of further clarifying the invention and does not represent a limitation to the scope of the otherwise claimed invention.No language in the specification should be interpreted as indicating any unclaimed element essential to the practice of the invention.

[00285] Alternative groupings of elements or embodiments of the invention described herein shall not be construed as limitations. Each member of the group may be referenced and claimed individually or in any combination with other members of the group or other elements found herein. It is foreseen that one or more members of a group may be included or excluded from a group for reasons of convenience and / or patentability. When such inclusion or exclusion occurs, the specification is considered to contain the group as modified, thus fulfilling the written description of all Markush groups used in the appended claims.

[00286] Certain embodiments of this invention are described herein, including the best known method of carrying out the invention by the inventors. Naturally, variations on these described embodiments will become Petition 870250103158, dated 11 / 11 / 2025, pp. 97 / 127 92 / 93 apparent to persons skilled in the art after reading the preceding description. The inventor expects that skilled craftsmen will employ such variations as appropriate, and the inventors intend that the invention be practiced in a manner different from that specifically described herein. Consequently, this invention includes all modifications and equivalents of the subject matter set forth in the appended claims, as permitted by applicable law. Furthermore, any combination of the elements described above in all possible variations is encompassed by the invention, unless otherwise indicated herein or clearly contradicted by the context.

[00287] The specific embodiments described herein may be further limited in the claims by using the language “consisting of” or “essentially consisting of”. When used in the claims, whether as filed or added by amendment, the transitional term “consisting of” excludes any element, step or ingredient not specified in the claims. The transitional term “essentially consisting of” limits the scope of a claim to the materials or steps specified and those that do not materially affect the basic and novel features. The embodiments of the invention thus claimed are inherently or expressly described and enabled herein.

[00288] It should be understood that the embodiments of the invention described herein are illustrative of the principles of the present invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, but not limitation, alternative configurations of the present invention may be used in accordance with the teachings contained herein. Consequently, the present invention is not limited to what is precisely shown and described.

[00289] Although the present invention has been described and illustrated herein by reference to various specific materials, procedures and examples, Petition 870250103158, dated 11 / 11 / 2025, pp. 98 / 127 93 / 93 It is understood that the invention is not limited to the particular combinations of materials and procedures selected for this purpose. Numerous variations of such details may be implied, as will be appreciated by those skilled in the art. The specification and examples are intended to be considered merely exemplary, with the true scope and spirit of the invention being indicated by the following claims. All references, patents and patent applications mentioned in this application are incorporated herein by reference in their entirety. Petition 870250103158, dated 11 / 11 / 2025, pp. 99 / 127

Claims

1 / 5 CLAIMS 1. Anti-IL-25 antibody characterized in that it comprises: (a) a variable heavy chain region comprising the amino acid sequence SEQ ID NO: 23 (HCDR1); the amino acid sequence SEQ ID NO: 49 (HCDR2); and the amino acid sequence SEQ ID NO: 25 (HCDR3); and a variable light chain region comprising the amino acid sequence SEQ ID NO: 50 (LCDR1); the amino acid sequence SEQ ID NO: 51 (LCDR2); and the amino acid sequence SEQ ID NO: 28 (LCDR3); (b) a variable heavy chain region comprising the amino acid sequence SEQ ID NO: 23 (HCDR1); the amino acid sequence SEQ ID NO: 52 (HCDR2); and the amino acid sequence SEQ ID NO: 25 (HCDR3); and a variable light chain region comprising the amino acid sequence with SEQ ID NO: 50 (LCDR1); the amino acid sequence with SEQ ID NO: 51 (LCDR2); and the amino acid sequence with SEQ ID NO: 28 (LCDR3);(c) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 11 (HCDR1); the amino acid sequence of SEQ ID NO: 12 (HCDR2); and the amino acid sequence of SEQ ID NO: 13 (HCDR3); and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 14 (LCDR1); the amino acid sequence of SEQ ID NO: 15 (LCDR2); and the amino acid sequence of SEQ ID NO: 16 (LCDR3); (d) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 17 (HCDR1); the amino acid sequence of SEQ ID NO: 18 (HCDR2); and the amino acid sequence of SEQ ID NO: 19 (HCDR3); and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 20 (LCDR1); the amino acid sequence of SEQ ID NO: 21 (LCDR2); and the sequence of Petition 870250103158, dated 11 / 11 / 2025, page 100 / 127 2 / 5 amino acids of SEQ ID NO: 22 (LCDR3);(e) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 23 (HCDR1); the amino acid sequence of SEQ ID NO: 24 (HCDR2); and the amino acid sequence of SEQ ID NO: 25 (HCDR3); and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 26 (LCDR1); the amino acid sequence of SEQ ID NO: 27 (LCDR2); and the amino acid sequence of SEQ ID NO: 28 (LCDR3); (f) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 29 (HCDR1); the amino acid sequence of SEQ ID NO: 30 (HCDR2); and the amino acid sequence of SEQ ID NO: 31 (HCDR3); and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 32 (LCDR1); the amino acid sequence of SEQ ID NO: 33 (LCDR2); and the amino acid sequence of SEQ ID NO: 34 (LCDR3); or (g) a variable heavy chain region comprising the amino acid sequence of SEQ ID NO: 35 (HCDR1);the amino acid sequence of SEQ ID NO: 36 (HCDR2); and the amino acid sequence of SEQ ID NO: 37 (HCDR3); and a variable light chain region comprising the amino acid sequence of SEQ ID NO: 38 (LCDR1); the amino acid sequence of SEQ ID NO: 39 (LCDR2); and the amino acid sequence of SEQ ID NO: 40 (LCDR3).

2. Anti-IL-25 antibody or an antigen-binding fragment thereof, according to claim 1, characterized in that the antibody or its antigen-binding fragment comprises a variable heavy chain region comprising the amino acid sequence of any of the SEQ ID NOs: 1, 3, 5, 7, 9, 44 or 47; and a variable light chain region comprising the amino acid sequence of any of the SEQ ID NOs: 2, 4, 6, 8, 10, 45, 46 or 48.

3. Anti-IL-25 antibody according to claim 1, characterized in that it comprises: Petition 870250103158, dated 11 / 11 / 2025, page 101 / 127 3 / 5 (a) a sequence of the variable region of the heavy chain of SEQ ID NO: 44 and a sequence of the variable region of the light chain of SEQ ID NO: 45; (b) a sequence of the variable region of the heavy chain of SEQ ID NO: 44 and a sequence of the variable region of the light chain of SEQ ID NO: 46; (c) a sequence of the variable region of the heavy chain of SEQ ID NO: 47 and a sequence of the variable region of the light chain of SEQ ID NO: 48; (d) a sequence of the variable region of the heavy chain of SEQ ID NO: 1 and a sequence of the variable region of the light chain of SEQ ID NO: 2; (e) a sequence from the variable region of the heavy chain of SEQ ID NO: 3 and a sequence from the variable region of the light chain of SEQ ID NO: 4; (f) a sequence from the variable region of the heavy chain of SEQ ID NO: 5 and a sequence from the variable region of the light chain of SEQ ID NO: 6;(g) a sequence from the variable region of the heavy chain of SEQ ID NO: 7 and a sequence from the variable region of the light chain of SEQ ID NO: 8; or (h) a sequence from the variable region of the heavy chain of SEQ ID NO: 9 and a sequence from the variable region of the light chain of SEQ ID NO: 10.; 4. Anti-IL-25 antibody, according to claim 1, characterized in that the antibody is a human anti-IL-25 antibody.

5. Anti-IL-25 antibody, according to claim 1, characterized in that the antibody is a full-length antibody comprising a constant region of human IgG1 selected from SEQ ID NO: 55 or SEQ ID NO:

56. Petition 870250103158, dated 11 / 11 / 2025, pp. 102 / 127 4 / 5 6. Anti-IL-25 antibody, according to claim 1, characterized in that the antibody is an antibody fragment.

7. Anti-IL-25 antibody, according to claim 4, characterized in that the antibody fragment is selected from the group consisting of: Fab, Fab, F(ab)2, Fd, Fv, scFv and scFvFc fragments, a single-chain antibody, a minibody, and a diabody.

8. Anti-IL-25 antibody, according to claim 1, characterized in that the antibody is a monoclonal antibody.

9. Anti-IL-25 antibody, according to claim 1, characterized in that the antibody is a human antibody.

10. Anti-IL-25 antibody, according to claim 1, characterized in that the antibody is a murine antibody.

11. Anti-IL-25 antibody, according to claim 1, characterized in that the antibody is a chimeric antibody.

12. Anti-IL-25 antibody, according to claim 1, characterized in that the antibody is a bispecific or multispecific antibody.

13. Anti-IL-25 antibody, according to claim 1, characterized in that the antibody is a humanized antibody.

14. Pharmaceutical composition characterized in that it comprises the antibody as defined in claim 1 and a pharmaceutically acceptable carrier.

15. A method for treating and / or preventing a Type 2 inflammatory disease, autoimmune disease, allergic disorder, or cancer in an individual in need thereof, characterized in that it comprises: administering to the individual the antibody as defined in claim 1.

16. Polynucleotide composition characterized in that it comprises: a) a first polynucleotide encoding a variable heavy chain region comprising the amino acid sequence shown in SEQ ID NO: 1, 3, 5, 7, 9, 44 or 47; and b) a second polynucleotide encoding a variable light chain region comprising the amino acid sequence shown in SEQ ID NO: 2, 4, 6, 8, 10, 45, 46 or 48.

17. Vector composition characterized in that it comprises: a) a first vector comprising the first polynucleotide, as defined in claim 16; and b) a second vector comprising the second polynucleotide, as defined in claim 16.

18. A cell characterized in that it comprises a polynucleotide composition as defined in claim 16, or a vector composition as defined in claim 17.

19. Method for producing an anti-IL-25 antibody according to claim 1, characterized in that the method comprises culturing the cell as defined in claim 18 in a culture medium; and recovering the anti-IL-25 antibody from the media. Petition 870250103158, dated 11 / 11 / 2025, pp. 104 / 127

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