Anti-IL-13 multispecific antibody constructs and their use

Abstract

The present invention relates to multispecific constructs that specifically bind to IL-13 and a second target antigen (e.g., TSLP, IL-17A, IL-17F, TNF-α, and IFN-γ). Antibody constructs that specifically bind to IL-13 are also provided. Compositions, kits, methods of use (e.g., for the treatment of inflammatory diseases), and methods for producing them are also provided.

Description

Technical Field

[0001] (Cross-Reference to Related Application) This application claims the benefit of priority to U.S. Provisional Application No. 63 / 578,946 filed on August 25, 2023, the contents of which are incorporated herein by reference in their entirety.

[0002] (Reference to Electronic Sequence Listing) The contents of the electronic sequence listing (253272000140seqlist.xml, size: 239,418 bytes, and creation date: August 19, 2024) are incorporated herein by reference in their entirety.

[0003] (Field of the Invention) The present invention relates to multispecific constructs that specifically bind to IL-13 and a second target (e.g., TSLP). Further provided herein are isolated anti-IL-13 antibody constructs, pharmaceutical compositions comprising the multispecific constructs, methods of treating inflammatory diseases using the multispecific constructs, and kits comprising the multispecific constructs. Background Art

[0004] Many diseases, including many abnormal cells and tissues and inflammatory diseases such as autoimmune disorders or asthma, present unique antigens that can be exploited for immune cell-mediated clearance. Each of these inflammatory diseases can express one or more different target antigens or one or more different epitopes of the same target antigen. For example, some antigens are overexpressed, mutated, or selectively mutated in inflamed tissues. Accordingly, antibodies that target specific antigens present in diseases associated with systemic or local inflammation can be used as therapeutic agents.

[0005] Interleukin (IL)-13 is a pleiotropic cytokine often associated with asthma and atopic dermatitis. IL-13 binds to a high-affinity heteromer complex composed of interleukin-13 receptor-α1 (IL-13Rα1) and interleukin-4 receptor-α (IL-4Rα). IL-13 also binds to interleukin-13 receptor-α2 (IL-13Rα2), which has been identified as a decoy receptor involved in a different signaling cascade than IL-13Rα1. IL-13 is primarily secreted by T helper 2 cells (Th2 cells) and type 2 innate lymphoid cells (ILC2s). ILC2s produce IL-5 and IL-13 during allergic inflammation, bridging innate and adaptive immune responses. ILC2 activity promotes the T helper 2 cell (Th2) response, and the simultaneous action of ILC2 and Th2 cells is also associated with inflammatory diseases such as allergies and autoimmune disorders.

[0006] Recent results from clinical trials of anti-IL-13 antibodies, including the failures of tralokinumab (Adbry®, see, e.g., Brightling et al. Lancet Respir Med. 2015, 3(9):692-701) and the combined results of leburikizumab (see, e.g., Hanania et al. Lancet Respir Med. 2016, 4(10):781-796) in the treatment of severe asthma, demonstrate the need for other anti-IL-13 antibodies to treat IL-13-related diseases, particularly inflammatory diseases. In particular, the early termination of the ACOUSTICS clinical trial of leburikizumab due to adverse events in 73% of patients (Szefler et al. Clin Transl Allergy 2022, 12(7):212176) further highlights the clear need for safer and more potent treatment options. [Overview of the project]

[0007] The present invention provides multispecific constructs that specifically bind to IL-13 and a second target (e.g., TSLP), pharmaceutical compositions comprising such multispecific constructs, and methods for treating inflammatory diseases using these multispecific constructs. Isolated anti-IL-13 antibody constructs are also provided.

[0008] In one aspect of the present invention, a multispecific construct is provided comprising (1) a first antibody moiety that specifically binds to interleukin-13 (IL-13), and (2) a second antibody moiety that specifically binds to a second antigen. In some embodiments, the second antigen is a protein produced by immune cells. In some embodiments, the second antigen is thymic stromal lymphopoietin (TSLP).

[0009] In some embodiments following any of the above-described multispecific constructs, the first antibody moiety comprises a heavy chain variable region (VH1) and a light chain variable region (VL1), wherein VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, or a variant thereof containing up to three amino acid mutations, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, or a variant thereof containing up to three amino acid mutations, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, or a variant thereof containing up to three amino acid mutations, and VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, or a variant thereof containing up to three amino acid mutations, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, or a variant thereof containing up to three amino acid mutations, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, or a variant thereof containing up to three amino acid mutations. In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity with SEQ ID NO: 65, and VL1 includes the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity with SEQ ID NO: 69. In some embodiments, VH1 includes (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, and VL1 includes (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72. In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, and VL1 includes the amino acid sequence of SEQ ID NO: 69.

[0010] In some embodiments following any of the above-described multispecific constructs, the first antibody moiety is selected from the group consisting of full-length antibody, Fab, Fab', F(ab')2, sdAb, and scFv.

[0011] In some embodiments following any of the above multispecific constructs, the first antibody moiety is scFv ("anti-IL-13 scFv"). In some embodiments, anti-IL-13 scFv comprises the amino acid sequence of SEQ ID NO: 108.

[0012] In some embodiments following any of the above multispecific constructs, the first antibody moiety is Fab ("Anti-IL-13 Fab"). In some embodiments, Anti-IL-13 Fab comprises a first polypeptide having the amino acid sequence of SEQ ID NO: 124, and a second polypeptide having the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197.

[0013] In some embodiments following any of the above multispecific constructs, the first antibody portion is a full-length antibody ("anti-IL-13 full-length antibody"). In some embodiments, the anti-IL-13 full-length antibody includes an Fc domain derived from human IgG (e.g., human IgG1, human IgG2, or human IgG4). In some embodiments, the Fc domain is derived from human IgG1, and i) the first and second subunits of the Fc domain each contain one amino acid sequence from sequence numbers 76 to 79; ii) the first subunit of the Fc domain contains the amino acid sequence of sequence number 80 and the second subunit of the Fc domain contains the amino acid sequence of sequence number 81; iii) the first subunit of the Fc domain contains the amino acid sequence of sequence number 81 and the second subunit of the Fc domain contains the amino acid sequence of sequence number 80; iv) the first subunit of the Fc domain contains the amino acid sequence of sequence number 95 and the second subunit of the Fc domain contains the amino acid sequence of sequence number 96; or v) the first subunit of the Fc domain contains the amino acid sequence of sequence number 96 and the second subunit of the Fc domain contains the amino acid sequence of sequence number 95.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; ii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 101, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; iii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 123, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206; iv) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 209, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; v) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 210, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; vi ) each containing the amino acid sequence of SEQ ID NO: 211, and two light chains each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206; vii) each containing the amino acid sequence of SEQ ID NO: 212, and two light chains each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; viiii) each containing the amino acid sequence of SEQ ID NO: 213, and two light chains each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; ix) each containing the amino acid sequence of SEQ ID NO: 225, and two light chains each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; or x) a first heavy chain containing the amino acid sequence of SEQ ID NO: 130, a second heavy chain containing the amino acid sequence of SEQ ID NO: 131, and two light chains each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197.

[0014] In some embodiments following any of the above multispecific constructs, the second antigen is TSLP, and the second antibody portion comprises a heavy chain variable region (VH2) and a light chain variable region (VL2), where (a) VH2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 2, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 3, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 4, and VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7, and (iii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 8 (b) VH2 includes CDR-L3, or (i) VH2 includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 12, (ii) VH2 containing the amino acid sequence of SEQ ID NO: 13, and (iii) VH2 includes CDR-H3 containing the amino acid sequence of SEQ ID NO: 4, or (c) VH2 includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 6, (ii) VH2 containing the amino acid sequence of SEQ ID NO: 7, and (iii) VH2 containing CDR-L3 containing the amino acid sequence of SEQ ID NO: 8, -H2 and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, VL2 contains (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26, or (d) VH2 contains (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 28, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 29, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 30, VL2 contains (i) CDR containing the amino acid sequence of SEQ ID NO: 32 -L1 includes (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 33, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 34, or (e) VH2 includes (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 37, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 38, and VL2 includes (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 40, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 41, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 42,Alternatively, (f) VH2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 44, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 45, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 46, and VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 48, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 49, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 50. In some embodiments, (a) VH2 includes the amino acid sequence of SEQ ID NO: 1, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 1, and VL2 includes the amino acid sequence of SEQ ID NO: 5, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 5; (b) VH2 includes the amino acid sequence of SEQ ID NO: 9, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 9, and VL2 includes the amino acid sequence of SEQ ID NO: 10, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 10; (c) VH2 includes the amino acid sequence of SEQ ID NO: 11, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 11, and VL2 includes the amino acid sequence of SEQ ID NO: 15, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 15; (d) VH2 includes the amino acid sequence of SEQ ID NO: 19, or at least SEQ ID NO: 19 (e) VH2 contains an amino acid sequence with approximately 80% sequence identity, and VL2 contains the amino acid sequence of SEQ ID NO: 23, or an amino acid sequence with at least approximately 80% sequence identity with SEQ ID NO: 23, (f) VH2 contains the amino acid sequence of SEQ ID NO: 27, or an amino acid sequence with at least approximately 80% sequence identity with SEQ ID NO: 27, and VL2 contains the amino acid sequence of SEQ ID NO: 31, or an amino acid sequence with at least approximately 80% sequence identity with SEQ ID NO: 31, (g) VH2 contains the amino acid sequence of SEQ ID NO: 35, or an amino acid sequence with at least approximately 80% sequence identity with SEQ ID NO: 35, and VL2 contains the amino acid sequence of SEQ ID NO: 39, or an amino acid sequence with at least approximately 80% sequence identity with SEQ ID NO: 39, (g) VH2 contains the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least approximately 80% sequence identity with SEQ ID NO: 43, and VL2 contains the amino acid sequence of SEQ ID NO: 47,(i) VH2 contains an amino acid sequence that has at least approximately 80% sequence identity with SEQ ID NO: 47, or (h) VH2 contains the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence that has at least approximately 80% sequence identity with SEQ ID NO: 63, and VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence that has at least approximately 80% sequence identity with SEQ ID NO: 53, or (i) VH2 contains the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence that has at least approximately 80% sequence identity with SEQ ID NO: 63, and VL2 contains the amino acid sequence of SEQ ID NO: 54, or at least approximately (j)VH2 contains an amino acid sequence with 80% sequence identity, or VL2 contains an amino acid sequence with at least approximately 80% sequence identity to SEQ ID NO: 56, or an amino acid sequence with at least approximately 80% sequence identity to SEQ ID NO: 52, or an amino acid sequence with at least approximately 80% sequence identity to SEQ ID NO: 52, or (k)VH2 contains an amino acid sequence with at least approximately 80% sequence identity to SEQ ID NO: 55, or VL2 contains an amino acid sequence with at least approximately 80% sequence identity to SEQ ID NO: 51, or an amino acid sequence with at least approximately 80% sequence identity to SEQ ID NO: 51. (i)VH2 contains the amino acid sequence of SEQ ID NO 56, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO 56, and VL2 contains the amino acid sequence of SEQ ID NO 51, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO 51, (m)VH2 contains the amino acid sequence of SEQ ID NO 63, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO 63, and VL2 contains the amino acid sequence of SEQ ID NO 51, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO 51, or (n)VH2 (o)VH2 contains the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 64, and VL2 contains the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 51, or (o)VH2 contains the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 55, and VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 52, or (p)VH2 contains the amino acid sequence of SEQ ID NO: 58,(q)VH2 contains an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 58, and VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 52, or (r)VH2 contains the amino acid sequence of SEQ ID NO: 60, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 60, and VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 52, or (r)VH2 contains the amino acid sequence of SEQ ID NO: 64, or at least (s)VH2 contains an amino acid sequence with approximately 80% sequence identity, and VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence with at least approximately 80% sequence identity to SEQ ID NO: 52, or (s)VH2 contains the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence with at least approximately 80% sequence identity to SEQ ID NO: 55, and VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence with at least approximately 80% sequence identity to SEQ ID NO: 53, or (t)VH2 contains the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence with at least approximately 80% sequence identity to SEQ ID NO: 57. (u)VH2 contains an amino acid sequence, and VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 53, or (u)VH2 contains the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 58, and VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 53, or (v)VH2 contains the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 62, and VL2 is (w)VH2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 53, and VL2 contains the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 64, and VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 53, and (x)VH2 contains the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 55, and VL2 contains the amino acid sequence of SEQ ID NO: 54,(y) VH2 contains the amino acid sequence of SEQ ID NO: 54 or has at least approximately 80% sequence identity with SEQ ID NO: 61, and VL2 contains the amino acid sequence of SEQ ID NO: 54 or has at least approximately 80% sequence identity with SEQ ID NO: 54, or (z) VH2 contains the amino acid sequence of SEQ ID NO: 62 or has at least approximately 80% sequence identity with SEQ ID NO: 62, and VL2 contains the amino acid sequence of SEQ ID NO: 54 or has at least approximately 80% sequence identity with SEQ ID NO: 54, or (aa) VH2 contains the amino acid sequence of SEQ ID NO: 64 or has at least approximately 80% sequence identity with SEQ ID NO: 64, and VL2 contains the amino acid sequence of SEQ ID NO: 54 or has at least approximately 80% sequence identity with SEQ ID NO: 54, or (bb) VH2 contains the amino acid sequence of SEQ ID NO: 63 or has at least approximately 80% sequence identity with SEQ ID NO: 63 (cc)VH2 contains an amino acid sequence having the characteristic of being (sequence number 52), and VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 52; (cc)VH2 contains the amino acid sequence of SEQ ID NO: 188, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 188, and VL2 contains the amino acid sequence of SEQ ID NO: 189, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 189; (dd)VH2 contains the amino acid sequence of SEQ ID NO: 188, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 188, and VL2 contains the amino acid sequence of SEQ ID NO: 190, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 190; (ee)VH2 contains the amino acid sequence of SEQ ID NO: 228, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 228, and VL2 contains the amino acid sequence of SEQ ID NO: 190, or an amino acid sequence having at least approximately 80% sequence identity with SEQ ID NO: 190.

[0015] In some embodiments following any of the above multispecific constructs, the second antibody moiety is selected from the group consisting of full-length antibody, Fab, Fab', F(ab')2, sdAb, and scFv.

[0016] In some embodiments following any of the above multispecific constructs, the second antibody portion is a full-length antibody. In some embodiments, the full-length antibody includes an Fc domain derived from human IgG (e.g., human IgG1, human IgG2, or human IgG4). In some embodiments, the Fc domain is derived from human IgG1, and i) the first and second subunits of the Fc domain each contain one amino acid sequence from sequence numbers 76-79, ii) the first subunit of the Fc domain contains the amino acid sequence of sequence number 80 and the second subunit of the Fc domain contains the amino acid sequence of sequence number 81, or iii) the first subunit of the Fc domain contains the amino acid sequence of sequence number 81 and the second subunit of the Fc domain contains the amino acid sequence of sequence number 80. In some embodiments, the full-length antibody is a full-length anti-TSLP antibody comprising: i) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 104, and two light chains, each containing the amino acid sequence of SEQ ID NO: 103; ii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 105, and two light chains, each containing the amino acid sequence of SEQ ID NO: 103; or iii) a first heavy chain containing the amino acid sequence of SEQ ID NO: 136, a second heavy chain containing the amino acid sequence of SEQ ID NO: 137, and two light chains, each containing the amino acid sequence of SEQ ID NO: 103.

[0017] In some embodiments following any of the above multispecific constructs, the second antibody moiety is an scFv. In some embodiments, the second antibody moiety is an anti-TSLP scFv comprising any one amino acid sequence from SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 226, SEQ ID NO: 227, and SEQ ID NO: 229.

[0018] In some embodiments following any of the above multispecific constructs, the second antibody moiety is Fab. In some embodiments, the second antibody moiety is anti-TSLP Fab, which comprises a first polypeptide having the amino acid sequence of SEQ ID NO: 109 and a second polypeptide having the amino acid sequence of SEQ ID NO: 103.

[0019] In some embodiments following any of the above multispecific constructs, the first antibody moiety comprises a heavy chain (H1) and a light chain (L1), where H1 comprises VH1 and H1-CH1, and L1 comprises VL1 and L1-CL, and (i) H1 comprises substitutions at positions 170, 183, and 185 (EU numbering), L1 comprises a substitution at position 135 (EU numbering), and / or (ii) H1 comprises substitutions at positions 126 and 220 (EU numbering), and L1 comprises substitutions at positions 124 and 214 (EU numbering). In some embodiments, H1 comprises substitutions at F170, S183, and V185 (EU numbering), and L1 comprises a substitution at L135 (EU numbering). In some embodiments, the F170 substitution is F170I or F170V, the S183 substitution is S183L or S183I, and the V185 substitution is V185L. In some embodiments, the L135 substitution is L135F. In some embodiments, (a) H1 includes the F170I, S183L, and V185L substitutions (EU numbering) and L1 includes the L135F substitution (EU numbering), or (b) H1 includes the F170V, S183I, and V185L substitutions (EU numbering) and L1 includes the L135F substitution (EU numbering). In some embodiments, L1 is derived from the lambda light chain. In some embodiments, the lambda light chain includes the amino acid sequence of SEQ ID NO: 74 or SEQ ID NO: 75. In some embodiments, H1 includes substitutions at F126 and C220 (EU numbering), and L1 includes substitutions at E124 and C214 (EU numbering). In some embodiments, H1 includes substitutions at F126C and C220S (EU numbering), and L1 includes substitutions at E124C and C214S (EU numbering). In some embodiments, L1 is derived from a kappa light chain. In some embodiments, the kappa light chain contains the amino acid sequence of SEQ ID NO: 73. In some embodiments, H1 includes substitutions at F126 and C220 (EU numbering), and L1 includes substitutions at Q124 and C214 (EU numbering). In some embodiments, H1 includes substitutions at F126C and C220S (EU numbering), and L1 includes substitutions at Q124C and C214S (EU numbering).In some embodiments, (i) H1 includes substitutions for F126C, F170I, S183L, V185L, and C220S, and L1 includes substitutions for E124C, L135F, and C214S, or (ii) H1 includes substitutions for F126C, F170V, S183I, V185L, and C220S, and L1 includes substitutions for E124C, L135F, and C214S, or (i ii) H1 includes substitutions F126C, F170I, S183L, V185L, and C220S, and L1 includes substitutions Q124C, L135F, and C214S, or (iv) H1 includes substitutions F126C, F170V, S183I, V185L, and C220S, and L1 includes substitutions Q124C, L135F, and C214S, with the position following EU numbering.

[0020] In some embodiments following any of the above multispecific constructs, the multispecific construct further comprises an Fc domain, the Fc domain comprising a first subunit and a second subunit. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. In some embodiments, the Fc domain is derived from IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 77. In some embodiments, the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 78. In some embodiments, the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 79. In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 80 and the second subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 81; (ii) the first subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 81 and the second subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 80; (iii) the first subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 95 and the second subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 96; or (iv) the first subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 96 and the second subunit of the Fc domain includes the amino acid sequence of SEQ ID NO: 95.

[0021] In some embodiments following any of the above multispecific constructs, the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1, H1-CH1, and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1, and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL, where H1 and L1 form an anti-IL-13 antibody moiety and H2 and L2 form a second antibody moiety. In some embodiments, the Fc domain is derived from human IgG1. In some embodiments, L1-CL is derived from a human lambda light chain. In some embodiments, (a) H1 includes substitutions for F170I, S183L, and V185L, and L1 includes substitution for L135F; (b) H1 includes substitutions for F170V, S183I, and V185L, and L1 includes substitution for L135F; (c) H1 includes substitutions for F126C, F170I, S183L, V185L, and C220S, and L1 includes substitution for E124C. (d) H1 contains the L135F and C214S substitutions, and L1 contains the F126C, F170V, S183I, V185L and C220S substitutions, and L1 contains the E124C, L135F and C214S substitutions, or (e) H1 contains the F126C and C220S substitutions, and L1 contains the E124C and C214S substitutions, with amino acid positions following EU numbering. In some embodiments, (a) H1 includes substitutions for F170I, S183L, V185L, T366S, L368A, and Y407V, L1 includes substitution for L135F, and H2 includes substitution for T366W; (b) H1 includes substitutions for F170I, S183L, V185L, and T366W, L1 includes substitution for L135F, and H2 includes substitutions for T366S, L368A, and Y407V; (c) H1 includes substitutions for F170V, S183I, (d) H1 includes substitutions for V185L, T366S, L368A, and Y407V, L1 includes substitution for L135F, and H2 includes substitution for T366W, or (e) H1 includes substitutions for F170V, S183I, V185L, and T366W, L1 includes substitution for L135F, and H2 includes substitutions for T366S, L368A, and Y407V, or H1 includes substitutions for F126C, F170I, S183L, V185L, C220S, T366S, L368A,(f) H1 ​​includes substitution of F126C, F170I, S183L, V185L, C220S, and T366W, L1 includes substitution of E124C, L135F, and C214S, H2 includes substitution of T366S, L368A, and Y407V, (g) H1 includes substitution of F126C, F170V, S183I, V185L, C220S, T366S, L368A, and Y407V, L1 includes substitution of E124C, L135F, and C214S, H2 includes substitution of T366W, (h) H1 includes substitution of F12 (i) H1 contains the substitutions 6C, F170V, S183I, V185L, C220S, and T366W, L1 contains the substitutions E124C, L135F, and C214S, and H2 contains the substitutions T366S, L368A, and Y407V, or (j) H1 contains the substitutions F126C, C220S, T366S, L368A, and Y407V, L1 contains the substitutions E124C and C214S, and H2 contains the substitution T366W, or (j) H1 contains the substitutions F126C, C220S, and T366W, L1 contains the substitutions E124C and C214S, and H2 contains the substitutions T366S, L368A, and Y407V, with amino acid positions following EU numbering. In some embodiments, (a) H1 includes substitutions for F170I, S183L, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, L1 includes substitutions for L135F, and H2 includes substitutions for L234A, L235A, T366W, M428L, and N434S, or (b) H1 includes substitutions for F170I, S183L, V185L, L234A, L235A, T366W, M428L, and N434S, L1 includes substitutions for L135F, and H2 includes substitutions for L234 (c) H1 includes substitutions for A, L235A, T366S, L368A, Y407V, M428L, and N434S, L1 includes substitutions for F170V, S183I, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, L1 includes substitutions for L135F, H2 includes substitutions for L234A, L235A, T366W, M428L, and N434S, (d) H1 includes substitutions for F170V, S183I, V185L, L234A, L235A, T366W, M428L,(e) H1 includes substitutions for F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, (f) H1 ​​includes substitutions for F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, L1 includes substitutions for E124C, L135F, and C214S, H2 includes substitutions for L234A, L235A, T366W, M428L, and N434S, (f) H1 ​​includes substitutions for F12 (g) H1 includes substitutions for 6C, F170I, S183L, V185L, C220S, L234A, L235A, T366W, M428L, and N434S, and L1 includes substitutions for E124C, L135F, and C214S, and H2 includes substitutions for L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, or (g) H1 includes substitutions for F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, and L1 includes substitutions for E124C, L135 (h) H1 includes substitutions for F, and C214S, and H2 includes substitutions for L234A, L235A, T366W, M428L, and N434S, and L1 includes substitutions for E124C, L135F, and C214S, and H2 includes substitutions for L234A, L235A, T366W, M428L, and N434S, and (i) H1 includes substitutions for F126C, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, and (i) H1 includes substitutions for F126C, C220S, L234A, L235A, T36 (j) H1 includes the substitutions 6S, L368A, Y407V, M428L, and N434S, L1 includes the substitutions E124C and C214S, and H2 includes the substitutions L234A, L235A, T366W, M428L, and N434S, or (j) H1 includes the substitutions F126C, C220S, L234A, L235A, T366W, M428L, and N434S, L1 includes the substitutions E124C and C214S, and H2 includes the substitutions L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, with amino acid positions following EU numbering. In some embodiments,(a) H1 contains the amino acid sequence of SEQ ID NO: 87, L1 contains the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and H2 contains the amino acid sequence of SEQ ID NO: 85, (b) H1 contains the amino acid sequence of SEQ ID NO: 88, L1 contains the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and H2 contains the amino acid sequence of SEQ ID NO: 86, (c) H1 contains the amino acid sequence of SEQ ID NO: 89, L1 contains the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and H2 contains the amino acid sequence of SEQ ID NO: 85, (d) H1 contains the amino acid sequence of SEQ ID NO: 90, L1 contains the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and H2 contains the amino acid sequence of SEQ ID NO: 86, (e) H1 contains the amino acid sequence of SEQ ID NO: 91, L1 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and H2 contains the amino acid sequence of SEQ ID NO: 85, (f (g) H1 contains the amino acid sequence of SEQ ID NO: 92, L1 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and H2 contains the amino acid sequence of SEQ ID NO: 86; (h) H1 contains the amino acid sequence of SEQ ID NO: 93, L1 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and H2 contains the amino acid sequence of SEQ ID NO: 85; (i) H1 contains the amino acid sequence of SEQ ID NO: 198, L1 contains the amino acid sequence of SEQ ID NO: 204 or SEQ ID NO: 205, and H2 contains the amino acid sequence of SEQ ID NO: 85; or (j) H1 contains the amino acid sequence of SEQ ID NO: 199, L1 contains the amino acid sequence of SEQ ID NO: 204 or SEQ ID NO: 205, and H2 contains the amino acid sequence of SEQ ID NO: 86. In some embodiments, L2-CL is derived from the human kappa light chain. In some embodiments, the second antigen is TSLP. In some embodiments, (a) H1 comprises the amino acid sequence of SEQ ID NO: 139, L1 comprises the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, H2 comprises the amino acid sequence of SEQ ID NO: 136, L2 comprises the amino acid sequence of SEQ ID NO: 103, or (b) H1 comprises the amino acid sequence of SEQ ID NO: 138, L1 comprises the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, H2 comprises the amino acid sequence of SEQ ID NO: 137,(c) H1 contains the amino acid sequence of SEQ ID NO: 103, (d) H1 contains the amino acid sequence of SEQ ID NO: 140, L1 contains the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, H2 contains the amino acid sequence of SEQ ID NO: 136, L2 contains the amino acid sequence of SEQ ID NO: 103, (e) H1 contains the amino acid sequence of SEQ ID NO: 126, L1 contains the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, H2 contains the amino acid sequence of SEQ ID NO: 136, L2 contains the amino acid sequence of SEQ ID NO: 103, (f) H1 ​​contains the amino acid sequence of SEQ ID NO: 127, L1 contains the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, H2 contains the amino acid sequence of SEQ ID NO: 137, L2 contains the amino acid sequence of SEQ ID NO: 103 (g) H1 contains the amino acid sequence of SEQ ID NO: 128, L1 contains the amino acid sequence of SEQ ID NO: 120 or 208, H2 contains the amino acid sequence of SEQ ID NO: 136, L2 contains the amino acid sequence of SEQ ID NO: 103, (h) H1 contains the amino acid sequence of SEQ ID NO: 129, L1 contains the amino acid sequence of SEQ ID NO: 120 or 208, H2 contains the amino acid sequence of SEQ ID NO: 137, L2 contains the amino acid sequence of SEQ ID NO: 103, (i) H1 contains the amino acid sequence of SEQ ID NO: 200, L1 contains the amino acid sequence of SEQ ID NO: 121 or 206, H2 contains the amino acid sequence of SEQ ID NO: 136, L2 contains the amino acid sequence of SEQ ID NO: 103, or (j) H1 contains the amino acid sequence of SEQ ID NO: 201, L1 contains the amino acid sequence of SEQ ID NO: 121 or 206, H2 contains the amino acid sequence of SEQ ID NO: 137, L2 contains the amino acid sequence of SEQ ID NO: 103. In some embodiments, the Fc domain is derived from human IgG1. In some embodiments, L2-CL is derived from the human lambda light chain. In some embodiments, (a) H2 includes F170I, S183L, and V185L substitutions and L2 includes L135F substitution, (b) H2 includes F170V, S183I, and V185L substitutions and L2 includes L135F substitution, (c) H2 includes F126C, F170I, S183L, V185L,(d) H2 includes substitutions for F126C, F170V, S183I, V185L, and C220S, and L2 includes substitutions for E124C, L135F, and C214S, or (e) H2 includes substitutions for F126C and C220S, and L2 includes substitutions for E124C and C214S. Here, the amino acid positions follow EU numbering. In some embodiments, (a) H2 includes the substitutions F170I, S183L, V185L, T366S, L368A, and Y407V, L2 includes the substitution L135F, and H1 includes the substitution T366W; (b) H2 includes the substitutions F170I, S183L, V185L, and T366W, L2 includes the substitution L135F, and H1 includes the substitutions T366S, L368A, and Y407V; (c) H2 includes the substitutions F170V, S183I, V185L, T366S, L368A, and Y407V, and L2 includes the substitution L135F. (d) H1 includes T366W substitution, (d) H2 includes F170V, S183I, V185L, and T366W substitution, L2 includes L135F substitution, H1 includes T366S, L368A, and Y407V substitution, (e) H2 includes F126C, F170I, S183L, V185L, C220S, T366S, L368A, and Y407V substitution, L2 includes E124C, L135F, and C214S substitution, H1 includes T366W substitution, (f) H2 includes F126C, F170I, S183L, V185L, C220 (g) H2 includes substitutions of S and T366W, L2 includes substitutions of E124C, L135F, and C214S, and H1 includes substitutions of T366S, L368A, and Y407V, or (h) H2 includes substitutions of F126C, F170V, S183I, V185L, C220S, T366S, L368A, and Y407V, L2 includes substitutions of E124C, L135F, and C214S, and H1 includes substitutions of T366W, or (h) H2 includes substitutions of F126C, F170V, S183I, V185L, C220S, and T366W, and L2 includes substitutions of E124C (i) H2 includes substitutions of F126C, C220S, T366S, L368A, and Y407V, L2 includes substitutions of E124C and C214S, and H1 includes substitutions of T366W, or (j) H2 includes substitutions of F126C, C220S, and T366W, L2 includes substitutions of E124C and C214S, and H1 includes substitutions of T366S, L368A, and Y407V, where amino acid positions follow EU numbering. In some embodiments, (a) H2 includes substitutions of F170I, S183L, V185L, L234A,(b) H2 includes L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, L2 includes L135F substitution, H1 includes L234A, L235A, T366W, M428L, and N434S substitutions, (b) H2 includes F170I, S183L, V185L, L234A, L235A, T366W, M428L, and N434S substitutions, L2 includes L135F substitution, H1 includes L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, (c) H2 includes F170V, S183I, V185L (d) H2 includes L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, L2 includes L135F substitution, H1 includes L234A, L235A, T366W, M428L, and N434S substitutions, (d) H2 includes F170V, S183I, V185L, L234A, L235A, T366W, M428L, and N434S substitutions, L2 includes L135F substitution, H1 includes L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, (e) H2 includes F126C, F170I (f) H2 includes substitutions of S183L, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, L2 includes substitutions of E124C, L135F, and C214S, and H1 includes substitutions of L234A, L235A, T366W, M428L, and N434S, or (f) H2 includes substitutions of F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366W, M428L, and N434S, L2 includes substitutions of E124C, L135F, and C214S, and H1 includes substitutions of L234A, L2 (g) H2 includes substitutions of 35A, T366S, L368A, Y407V, M428L, and N434S, and L2 includes substitutions of E124C, L135F, and C214S, and H1 includes substitutions of L234A, L235A, T366W, M428L, and N434S, and (h) H2 includes substitutions of F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366W,(i) H2 includes substitutions for M428L and N434S, L2 includes substitutions for E124C, L135F and C214S, H1 includes substitutions for L234A, L235A, T366S, L368A, Y407V, M428L and N434S, or (i) H2 includes substitutions for F126C, C220S, L234A, L235A, T366S, L368A, Y407V, M428L and N434S, L2 includes substitutions for E124C and C21 (j) H1 includes 4S substitutions, with H1 including L234A, L235A, T366W, M428L, and N434S substitutions, or (j) H2 includes F126C, C220S, L234A, L235A, T366W, M428L, and N434S substitutions, with L2 including E124C and C214S substitutions, with H1 including L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions. In some embodiments, (a) H2 includes the amino acid sequence of SEQ ID NO: 87, L2 includes the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and H1 includes the amino acid sequence of SEQ ID NO: 85; (b) H2 includes the amino acid sequence of SEQ ID NO: 88, L2 includes the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and H1 includes the amino acid sequence of SEQ ID NO: 86; (c) H2 includes the amino acid sequence of SEQ ID NO: 89, L2 includes the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and H1 includes the amino acid sequence of SEQ ID NO: 85; (d) H2 includes the amino acid sequence of SEQ ID NO: 90, L2 includes the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and H1 includes the amino acid sequence of SEQ ID NO: 86 (e) H2 contains the amino acid sequence of SEQ ID NO: 91, L2 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and H1 contains the amino acid sequence of SEQ ID NO: 85, (f) H2 contains the amino acid sequence of SEQ ID NO: 92, L2 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and H1 contains the amino acid sequence of SEQ ID NO: 86, (g) H2 contains the amino acid sequence of SEQ ID NO: 93, L2 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and H1 contains the amino acid sequence of SEQ ID NO: 85, (h) H2 contains the amino acid sequence of SEQ ID NO: 94, L2 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and H1 contains the amino acid sequence of SEQ ID NO: 86,(i) H2 contains the amino acid sequence of SEQ ID NO: 198, L2 contains the amino acid sequence of SEQ ID NO: 204 or 205, and H1 contains the amino acid sequence of SEQ ID NO: 85, or (j) H2 contains the amino acid sequence of SEQ ID NO: 199, L2 contains the amino acid sequence of SEQ ID NO: 204 or 205, and H1 contains the amino acid sequence of SEQ ID NO: 86. In some embodiments, L1-CL is derived from the human kappa light chain. In some embodiments, the second antigen is TSLP.

[0022] In some embodiments following any of the above-described multispecific constructs, a first antibody moiety that specifically binds to IL-13 and a second antibody moiety that specifically binds to a second target antigen are fused to each other via a linker. In some embodiments, the linker comprises GG and one of the amino acid sequences from SEQ ID NOs. 98 to 99.

[0023] In some embodiments following any of the above-described multispecific constructs, the first antibody portion is scFv ("anti-IL-13 scFv"), the second antibody portion is a full-length antibody that specifically binds to a second target antigen, and the anti-IL-13 scFv is fused to one of the C-terminuses of the heavy chain of the second antibody portion to form a fusion polypeptide.

[0024] In some embodiments following any of the multispecific constructs described above, the multispecific construct comprises two anti-IL-13 antibody moieties ("anti-IL-13 scFv1" and "anti-IL-13 scFv2") which are scFv, the second antibody moiety being a full-length antibody that specifically binds to a second target antigen, anti-IL-13 scFv1 being fused to the C-terminus of the first heavy chain of the second antibody moiety to form a first fusion polypeptide, and anti-IL-13 scFv2 being fused to the C-terminus of the second heavy chain of the second antibody moiety to form a second fusion polypeptide. In some embodiments, the second target antigen is TSLP (i.e., the second antibody moiety is an "anti-TSLP full-length antibody"). In some embodiments, the anti-TSLP full-length antibody comprises two light chains, each containing the amino acid sequence of SEQ ID NO: 103, and two heavy chains, each containing the amino acid sequence of SEQ ID NO: 105, the first and second fusion polypeptides each containing the amino acid sequence of SEQ ID NO: 113.

[0025] In some embodiments following any of the above multispecific constructs, the multispecific construct comprises two anti-IL-13 antibody moieties that are scFv ("anti-IL-13 scFv1" and "anti-IL-13 scFv2"), two second antibody moieties that are Fab that specifically bind to a second target antigen ("Fab1" and "Fab2"), and an Fc domain, wherein the multispecific construct comprises: i) a first polypeptide comprising VL1-(L1-CL) from N' to C', ii) a second polypeptide comprising a first subunit of the Fc domain, VH1-(H1-CH1)-any linker-anti-IL-13 scFv1-any linker, and iii) VH2-(H2-CH1)-any linker-anti-IL-13 A third polypeptide comprising scFv2-an arbitrary linker-Fc domain second subunit, and iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C', where VL1-(L1-CL) and VH1-(H1-CH1) form Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form Fab2. In some embodiments, the second target antigen is TSLP. In some embodiments, the first and fourth polypeptides each comprise the amino acid sequence of SEQ ID NO: 103, and the second and third polypeptides each comprise the amino acid sequence of SEQ ID NO: 110.

[0026] In some embodiments following any of the above-described multispecific constructs, the first antibody portion is a full-length antibody ("anti-IL-13 full-length antibody"), and the second antibody portion is an scFv that specifically binds to a second target antigen, and the scFv is fused to one of the C-terminuses of the heavy chain of the anti-IL-13 full-length antibody to form a fusion polypeptide.

[0027] In some embodiments following any of the multispecific constructs described above, the multispecific construct comprises a first antibody moiety which is a full-length anti-IL-13 antibody, and two second antibody moieties ("scFv1" and "scFv2") which are scFvs that specifically bind to a second target antigen, wherein scFv1 is fused to the C-terminus of the first heavy chain of the full-length anti-IL-13 antibody to form a first fusion polypeptide, and scFv2 is fused to the C-terminus of the second heavy chain of the full-length anti-IL-13 antibody to form a second fusion polypeptide. In some embodiments, the second target antigen is TSLP. In some embodiments, the full-length anti-IL-13 antibody comprises two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, wherein the first and second fusion polypeptides each contain the amino acid sequence of SEQ ID NO: 111. In some embodiments, the full-length anti-IL-13 antibody comprises two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, and the first and second fusion polypeptides each contain one of the amino acid sequences from SEQ ID NO: 220 to SEQ ID NO: 223.

[0028] In some embodiments following any of the above multispecific constructs, the multispecific construct consists of two anti-IL-13 antibody moieties that are Fabs ("anti-IL-13 Fab1" and "anti-IL-13 Fab1"). Fab2) comprises two second antibody moieties ("scFv1" and "scFv2") which are scFv that specifically bind to a second target antigen, and an Fc domain, where the multispecific construct comprises i) a first polypeptide comprising VL1-(L1-CL) from N' to C', ii) a second polypeptide comprising a first subunit of VH1-(H1-CH1)-any linker-scFv1-any linker-Fc domain from N' to C', iii) a third polypeptide comprising a second subunit of VH2-(H2-CH1)-any linker-scFv2-any linker-Fc domain from N' to C', and iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C', where VH1-(H1-CH1) and VL1-(L1-CL) are anti-IL-13 Fab1 is formed, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2. In some embodiments, the second target antigen is TSLP. In some embodiments, the first polypeptide and the fourth polypeptide each contain the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, and the second polypeptide and the third polypeptide each contain the amino acid sequence of SEQ ID NO: 112.

[0029] In some embodiments following any of the above multispecific constructs, the multispecificity is achieved by two anti-IL-13 antibody moieties that are Fabs ("anti-IL-13 Fab1" and "anti-IL-13 Fab1"). The multispecific construct comprises a second antibody moiety, which is a full-length antibody specifically binding to a second target antigen, i) a first polypeptide comprising the first light chain of the second antibody moiety, ii) a second polypeptide comprising the first heavy chain of the second antibody moiety - an optional linker - VH1-(H1-CH1) from N' to C', iii) a third polypeptide comprising the second heavy chain of the second antibody moiety - an optional linker - VH2-(H2-CH1) from N' to C', iv) a fourth polypeptide comprising the second light chain of the second antibody moiety, v) a fifth polypeptide comprising VL1-(L1-CL) from N' to C', and vi) a sixth polypeptide comprising VL2-(L2-CL) from N' to C', wherein VL1-(L1-CL) and VH1-(H1-CH1) are anti-IL-13 Fab1 is formed, and VL2-(L2-CL) and VH2-(H2-CH1) form anti-IL-13 Fab2. In some embodiments, anti-IL-13 Fab1 includes H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL), and anti-IL-13 Fab2 contains H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL), and (a) H1 and H2 each contain substitutions of F170I, S183L, and V185L, and L1 and L2 each contain substitutions of L135F, or (b) H1 and H2 each contain substitutions of F170V, S183I, and V185L, and L1 and L2 each contain substitutions of L135F, or (c) H1 and H2 each contain substitutions of F126C, F170I, S183L, V185L, and C220 (d) H1 and H2 each contain S substitutions, with L1 and L2 each containing E124C, L135F, and C214S substitutions, and L1 and L2 each containing E124C, L135F, and C214S substitutions, or (e) H1 and H2 each contain F126C and C220S substitutions, with L1 and L2 each containing E124C and C214S substitutions, and amino acid positions conform to EU numbering.In some embodiments, the second target antigen is TSLP (i.e., the second antibody portion is a "full-length anti-TSLP antibody"). In some embodiments, the full-length anti-TSLP antibody comprises two heavy chains, each containing the amino acid sequence of SEQ ID NO: 105, and two light chains, each containing the amino acid sequence of SEQ ID NO: 103.

[0030] In some embodiments following any of the above multispecific constructs, the multispecific construct comprises an anti-IL-13 antibody moiety that is a full-length antibody ("anti-IL-13 full-length antibody") and two second antibody moieties ("Fab1" and "Fab2") that are Fabs that specifically bind to a second target antigen, wherein the multispecific construct comprises i) a first polypeptide comprising a first light chain (L1) of the anti-IL-13 full-length antibody, ii) a second polypeptide comprising a first heavy chain (H1) of the anti-IL-13 full-length antibody (optional linker) (H3-CH1) from N' to C', and iii) The polypeptide comprises: iv) a third polypeptide comprising the second heavy chain (H2) of the full-length anti-IL-13 antibody - an arbitrary linker - VH4-(H4-CH1); v) a fourth polypeptide comprising the second light chain (L2) of the full-length anti-IL-13 antibody; v) a fifth polypeptide comprising VL3-(L3-CL) from N' to C'; and vi) a sixth polypeptide comprising VL4-(L4-CL) from N' to C', wherein VH3-(H3-CH1) and VL3-(L3-CL) form Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form Fab2. In some embodiments, (a) H1 and H2 each include substitutions of F170I, S183L, and V185L, and L1 and L2 each include substitutions of L135F, (b) H1 and H2 each include substitutions of F170V, S183I, and V185L, and L1 and L2 each include substitutions of L135F, (c) H1 and H2 each include substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and L2 each (d) H1 and H2 each include the substitutions E124C, L135F, and C214S, and L1 and L2 each include the substitutions F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each include the substitutions E124C, L135F, and C214S, or (e) H1 and H2 each include the substitutions F126C and C220S, and L1 and L2 each include the substitutions E124C and C214S, with amino acid positions following EU numbering.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; ii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 209, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 210, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iv) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 211, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206; v) two light chains, each containing the amino acid sequence of SEQ ID NO: 212 The antibody comprises a heavy chain and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vi) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 213, and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; viiii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 101, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; or ix) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 123, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206. In some embodiments, the second target antigen is TSLP (i.e., the two second antibody portions are "anti-TSLP Fab1" and "anti-TSLP Fab2"). In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each comprise a first polypeptide containing the amino acid sequence of SEQ ID NO: 109 and a second polypeptide containing the amino acid sequence of SEQ ID NO: 103.

[0031] In some embodiments following any of the above multispecific constructs, the multispecific construct consists of two anti-IL-13 antibody moieties that are Fabs ("anti-IL-13 Fab1" and "anti-IL-13 Fab1"). Fab2) comprises a second antibody moiety which is a full-length antibody that specifically binds to a second target antigen, wherein the multispecific construct comprises i) a first polypeptide comprising VL1-(L1-CL) from N' to C', ii) a second polypeptide comprising VH1-(H1-CH1)-any linker-first heavy chain of the second antibody moiety from N' to C', iii) a third polypeptide comprising VH2-(H2-CH1)-any linker-second heavy chain of the second antibody moiety from N' to C', iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C', v) a fifth polypeptide comprising the first light chain of the second antibody moiety, and vi) a sixth polypeptide comprising the second light chain of the second antibody moiety, where VL1-(L1-CL) and VH1-(H1-CH1) are anti-IL-13 Fab1 is formed, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2. In some embodiments, anti-IL-13 Fab1 includes H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL), where anti-IL-13 Fab2 contains H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL), wherein (a) H1 and H2 each contain substitutions of F170I, S183L, and V185L, and L1 and L2 each contain substitutions of L135F, (b) H1 and H2 each contain substitutions of F170V, S183I, and V185L, and L1 and L2 each contain substitutions of L135F, (c) H1 and H2 each contain substitutions of F126C, F170I, S183L, V185L, and (d) H1 and H2 each contain the substitutions E124C, L135F, and C214S, and (e) H1 and H2 each contain the substitutions F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each contain the substitutions E124C, L135F, and C214S, with the amino acid positions following EU numbering.In some embodiments, the second target antigen is TSLP (i.e., the second antibody portion is a "full-length anti-TSLP antibody"). In some embodiments, the full-length anti-TSLP antibody comprises two heavy chains, each containing the amino acid sequence of SEQ ID NO: 105, and two light chains, each containing the amino acid sequence of SEQ ID NO: 103.

[0032] In some embodiments following any of the above multispecific constructs, the multispecific construct comprises a first antibody moiety which is a full-length anti-IL-13 antibody, and two second antibody moieties ("Fab1" and "Fab2") which are Fabs that specifically bind to a second target antigen, where the multispecific construct comprises: i) a first polypeptide comprising VL3-(L3-CL) from N' to C', ii) a second polypeptide comprising a first heavy chain (H1) of a full-length anti-IL-13 antibody, VH3-(H3-CH1)-any linker, and iii) N' to C The polypeptide comprises, iv) a third polypeptide containing the second heavy chain (H2) of the anti-IL-13 full-length antibody, VH4-(H4-CH1)-any linker-towards C', v) a fourth polypeptide containing VL4-(L4-CL) from N' to C', v) a fifth polypeptide containing the first light chain (L1) of the anti-IL-13 full-length antibody, and vi) a sixth polypeptide containing the second light chain (L2) of the anti-IL-13 full-length antibody, where VL3-(L3-CL) and VH3-(H3-CH1) form Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form Fab2. In some embodiments, (a) H1 and H2 each include substitutions of F170I, S183L, and V185L, and L1 and L2 each include substitutions of L135F, (b) H1 and H2 each include substitutions of F170V, S183I, and V185L, and L1 and L2 each include substitutions of L135F, (c) H1 and H2 each include substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and L2 each (d) H1 and H2 each include the substitutions E124C, L135F, and C214S, and L1 and L2 each include the substitutions F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each include the substitutions E124C, L135F, and C214S, or (e) H1 and H2 each include the substitutions F126C and C220S, and L1 and L2 each include the substitutions E124C and C214S, with amino acid positions following EU numbering.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; ii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 209, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 210, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iv) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 211, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206; v) two light chains, each containing the amino acid sequence of SEQ ID NO: 212 The antibody comprises a heavy chain and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vi) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 213, and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; viiii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 101, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; or ix) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 123, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206. In some embodiments, the second target antigen is TSLP (i.e., the two second antibody portions are "anti-TSLP Fab1" and "anti-TSLP Fab2"). In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each comprise a first polypeptide containing the amino acid sequence of SEQ ID NO: 109 and a second polypeptide containing the amino acid sequence of SEQ ID NO: 103.

[0033] Pharmaceutical compositions are also provided, comprising any of the multispecific constructs described herein and optionally a pharmaceutically acceptable carrier.

[0034] Also provided herein are isolated nucleic acids encoding any of the multispecific constructs described herein, vectors containing such nucleic acids, and host cells containing such nucleic acids or vectors.

[0035] Methods for treating inflammatory diseases in an individual are also provided, which include administering to the individual an effective amount of any of the multispecific constructs described herein or any of the pharmaceutical compositions described herein. In some embodiments, the inflammatory disease is asthma, atopic dermatitis, or chronic obstructive pulmonary disease (COPD). In some embodiments, the individual is a human.

[0036] A method for producing any of the multispecific constructs described herein is also provided, comprising: i) culturing a host cell containing any of the above-mentioned isolated nucleic acids or vectors, or any of the above-mentioned host cells, under conditions suitable for the expression of the multispecific construct; and ii) obtaining the expressed multispecific construct.

[0037] In another embodiment, the present invention provides an isolated antibody construct (anti-IL-13 antibody construct) comprising an antibody moiety that specifically binds to IL-13 ("anti-IL-13 antibody moiety"), the anti-IL-13 antibody moiety comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein (1) VH comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 68, and VL comprises (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 72.

[0038] In some embodiments according to any of the above anti-IL-13 antibody constructs, (1) VH comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity with SEQ ID NO: 65, and VL comprises the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity with SEQ ID NO: 69. In some embodiments, VH comprises the amino acid sequence of SEQ ID NO: 65, and VL comprises the amino acid sequence of SEQ ID NO: 69.

[0039] In some embodiments following any of the above anti-IL-13 antibody constructs, the anti-IL-13 antibody moiety is selected from the group consisting of full-length antibody, Fab, Fab', F(ab')2, diabody, and scFv.

[0040] In some embodiments following any of the above anti-IL-13 antibody constructs, the anti-IL-13 antibody portion is scFv ("anti-IL-13 scFv"). In some embodiments, anti-IL-13 scFv contains the amino acid sequence of SEQ ID NO: 108.

[0041] In some embodiments following any of the above anti-IL-13 antibody constructs, the anti-IL-13 antibody portion is Fab ("anti-IL-13 Fab"). In some embodiments, anti-IL-13 Fab comprises a first polypeptide having the amino acid sequence of SEQ ID NO: 124, and a second polypeptide having the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197.

[0042] In some embodiments following any of the above anti-IL-13 antibody constructs, the anti-IL-13 antibody portion is a full-length antibody ("anti-IL-13 full-length antibody"). In some embodiments, the anti-IL-13 full-length antibody is: i) two heavy chains each containing the amino acid sequence of SEQ ID NO: 125, and two light chains each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; ii) two heavy chains each containing the amino acid sequence of SEQ ID NO: 101, and two light chains each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; iii) two heavy chains each containing the amino acid sequence of SEQ ID NO: 123, and two light chains each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206; iv) two heavy chains each containing the amino acid sequence of SEQ ID NO: 209, and two light chains each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; v) two heavy chains each containing the amino acid sequence of SEQ ID NO: 210, and two light chains each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; i) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 211, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206; vii) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 212, and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; viii) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 213, and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; ix) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; x) A first heavy chain containing the amino acid sequence of SEQ ID NO: 130, a second heavy chain containing the amino acid sequence of SEQ ID NO: 131, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197.

[0043] In some embodiments following any of the above anti-IL-13 antibody constructs, the isolated anti-IL-13 antibody construct is monospecific. In some embodiments, the isolated anti-IL-13 antibody construct is multispecific.

[0044] In some embodiments following any of the above anti-IL-13 antibody constructs, the isolated anti-IL-13 antibody construct further comprises a second antibody moiety that specifically binds to a second antigen. In some embodiments, the anti-IL-13 antibody moiety and the second antibody moiety are fused to each other via a linker. In some embodiments, the linker comprises GG and one of the amino acid sequences from SEQ ID NOs. 98 to SEQ ID NOs. 99.

[0045] Pharmaceutical compositions are also provided, comprising one of the above-mentioned isolated anti-IL-13 antibody constructs and, optionally, a pharmaceutically acceptable carrier.

[0046] Isolated nucleic acids encoding any of the above-mentioned isolated anti-IL-13 antibody constructs, vectors containing such nucleic acids, and host cells containing such nucleic acids or vectors are also provided.

[0047] A method for treating an inflammatory disease in an individual is also provided, which comprises administering to the individual an effective amount of any of the above isolated anti-IL-13 antibody constructs or any of the above pharmaceutical compositions. In some embodiments, the inflammatory disease is asthma, atopic dermatitis, or COPD. In some embodiments, the individual is a human.

[0048] A method for producing any of the above-mentioned isolated anti-IL-13 antibody constructs is also provided, comprising: i) culturing a host cell containing any of the above-mentioned isolated nucleic acids or vectors, or any of the above-mentioned host cells, under conditions suitable for the expression of an anti-IL-13 antibody construct; and ii) obtaining the expressed anti-IL-13 antibody construct.

[0049] These and other aspects and advantages of the present invention will become apparent from the following detailed description and accompanying drawings. It should be understood that other embodiments of the present invention may be formed by combining one, some, or all of the characteristics of the various embodiments described herein.

[0050] All publications, patents, patent applications, and published applications referred to herein are incorporated herein in their entirety by reference. [Brief explanation of the drawing]

[0051] [Figure 1] This shows the percentage of inhibition of TSLP signaling via the TSLP receptor complex expressed on STAT5-HEK293 reporter cells after treatment with an exemplary anti-TSLP antibody. [Figure 2] In ELISA competitive experiments, 51B2 and the US FDA-approved reference anti-TSLP antibody were shown to bind to overlapping but different epitopes on TSLP. Ab, antibody; OD, optical density. [Figure 3A] Compared to a US FDA-approved reference anti-TSLP antibody, 51B2 completely inhibits TSLP-induced CCL17 secretion from PBMCs (Figure 3A) or isolated dendritic cells (Figure 3B). [Figure 3B] Compared to a US FDA-approved reference anti-TSLP antibody, 51B2 completely inhibits TSLP-induced CCL17 secretion from PBMCs (Figure 3A) or isolated dendritic cells (Figure 3B). [Figure 4] The IC50(nM) and IC90(nM) values ​​obtained for each humanized 51B2 antibody produced, compared to the parental Ch51B2 antibody, are shown in human and cynomolgus monkey ("cyno") TSLP inhibition assays using HEK293 reporter cells transfected with the TSLP receptor complex. Humanized anti-TSLP antibodies enclosed in boxes are those selected for further analysis. [Figure 5A] This shows the percentage of inhibition of TSLP signaling via the TSLP receptor complex expressed on STAT5-HEK293 reporter cells after treatment with selected humanized anti-TSLP antibodies (hz51B2 L2H2, hz51B2 L2H9, and hz51B2 L3H9). Ch51B2 parental chimeric antibody was used as a control. [Figure 5B] This shows the equilibrium binding analysis of hz51B2 L3H9 binding to human TSLP in solution. [Figure 6A] This shows that anti-IL-13 antibody 73P1 enhanced the neutralizing activity of cynomolgus monkey ("cyno") IL-13 while maintaining its neutralizing activity against human IL-13 in the HEK-Blue 293 IL-13 reporter assay, in which secreted embryonic alkaline phosphatase (SEAP) is produced upon activation of IL-13 signaling. Figure 6A shows the neutralizing activity of reference anti-IL-13 antibody #0 and anti-IL-13 antibody 73P1 against human IL-13 using IL-13 reporter assays at multiple concentrations, and provides the IC50 for both anti-IL-13 antibodies. Figure 6B shows the neutralizing activity of reference anti-IL-13 antibody #0 and anti-IL-13 antibody 73P1 against cynomolgus monkey IL-13 using IL-13 reporter assays at multiple concentrations, and further provides the IC50 for both anti-IL-13 antibodies. Conc., concentration; OD, optical density. [Figure 6B] This shows that anti-IL-13 antibody 73P1 enhanced the neutralizing activity of cynomolgus monkey ("cyno") IL-13 while maintaining its neutralizing activity against human IL-13 in the HEK-Blue 293 IL-13 reporter assay, in which secreted embryonic alkaline phosphatase (SEAP) is produced upon activation of IL-13 signaling. Figure 6A shows the neutralizing activity of reference anti-IL-13 antibody #0 and anti-IL-13 antibody 73P1 against human IL-13 using IL-13 reporter assays at multiple concentrations, and provides the IC50 for both anti-IL-13 antibodies. Figure 6B shows the neutralizing activity of reference anti-IL-13 antibody #0 and anti-IL-13 antibody 73P1 against cynomolgus monkey IL-13 using IL-13 reporter assays at multiple concentrations, and further provides the IC50 for both anti-IL-13 antibodies. Conc., concentration; OD, optical density. [Figure 7A]This study compares the neutralizing activity of anti-IL-13 antibody 73P1 with two US FDA or EMA-approved anti-IL-13 antibodies, reference anti-IL-13 antibody #1 and reference anti-IL-13 antibody #2 ("Ref.Ab.#1" and "Ref.Ab.#2"), as positive controls. This was done using the HEK-Blue 293 IL-13 reporter assay, in which secreted embryonic alkaline phosphatase (SEAP) is produced upon activation of IL-13 signaling using wild-type ("WT") IL-13 or IL-13 R110Q (a disease-associated variant of IL-13) as a stimulus. Figure 7A shows the neutralizing activity of anti-IL-13 antibody 73P1, as well as reference anti-IL-13 antibodies #1 and #2, against wild-type human IL-13. Figure 7B shows the neutralizing activity of anti-IL-13 antibody 73P1, as well as reference anti-IL-13 antibodies #1 and #2, against the disease-associated human IL-13 variant R110Q, which exhibits increased IL-13 activity. IC50 values ​​are provided. [Figure 7B] This study compares the neutralizing activity of anti-IL-13 antibody 73P1 with two US FDA or EMA-approved anti-IL-13 antibodies, reference anti-IL-13 antibody #1 and reference anti-IL-13 antibody #2 ("Ref.Ab.#1" and "Ref.Ab.#2"), as positive controls. This was done using the HEK-Blue 293 IL-13 reporter assay, in which secreted embryonic alkaline phosphatase (SEAP) is produced upon activation of IL-13 signaling using wild-type ("WT") IL-13 or IL-13 R110Q (a disease-associated variant of IL-13) as a stimulus. Figure 7A shows the neutralizing activity of anti-IL-13 antibody 73P1, as well as reference anti-IL-13 antibodies #1 and #2, against wild-type human IL-13. Figure 7B shows the neutralizing activity of anti-IL-13 antibody 73P1, as well as reference anti-IL-13 antibodies #1 and #2, against the disease-associated human IL-13 variant R110Q, which exhibits increased IL-13 activity. IC50 values ​​are provided. [Figure 8A] A schematic diagram of one set of exemplary bispecific anti-TSLP × IL-13 antibody constructs based on scFv fusion and insertion is shown. [Figure 8B] A schematic diagram of one set of exemplary bispecific anti-TSLP × IL-13 antibody constructs based on scFv fusion and insertion is shown. [Figure 8C] A schematic diagram of one set of exemplary bispecific anti-TSLP × IL-13 antibody constructs based on scFv fusion and insertion is shown. [Figure 8D] A schematic diagram of one set of exemplary bispecific anti-TSLP × IL-13 antibody constructs based on scFv fusion and insertion is shown. [Figure 9A] Figures 8A to 8D demonstrate the inhibitory activity against TSLP and IL-13 from the TSLP × IL-13 bispecific antibodies. Figure 9A shows the percentage of inhibition of TSLP signaling via the TSLPR / IL-7Rα receptor complex expressed on STAT5-HEK-293 reporter cells after treatment with one of the bispecific antibodies. Luciferase production by reporter cells functioned as a readout for TSLP binding activity. Figure 9B shows the percentage of inhibition of IL-13 signaling via the IL-13Rα1 / IL-4Rα receptor complex expressed on HEK-293 reporter cells after treatment with one of the bispecific antibodies. SEAP production and secretion by reporter cells functioned as a readout for IL-13 binding activity. The IC90 values ​​of each antibody, depending on the antigen, were calculated based on antibody dose-dependent binding inhibition curves. The data were analyzed and presented using GraphPad. Ab, antibody; Conc., concentration. [Figure 9B]Figures 8A to 8D demonstrate the inhibitory activity against TSLP and IL-13 from the TSLP × IL-13 bispecific antibodies. Figure 9A shows the percentage of inhibition of TSLP signaling via the TSLPR / IL-7Rα receptor complex expressed on STAT5-HEK-293 reporter cells after treatment with one of the bispecific antibodies. Luciferase production by reporter cells functioned as a readout for TSLP binding activity. Figure 9B shows the percentage of inhibition of IL-13 signaling via the IL-13Rα1 / IL-4Rα receptor complex expressed on HEK-293 reporter cells after treatment with one of the bispecific antibodies. SEAP production and secretion by reporter cells functioned as a readout for IL-13 binding activity. The IC90 values ​​of each antibody, depending on the antigen, were calculated based on antibody dose-dependent binding inhibition curves. The data were analyzed and presented using GraphPad. Ab, antibody; Conc., concentration. [Figure 10] Figures 8A to 8D show the in vivo stability of the TSLP × IL-13 bispecific antibodies, which is represented by the time course of in vivo antibody concentrations of both the anti-TSLP antigen binding moiety and the anti-IL-13 antigen binding moiety of the bispecific antibody after intravenous injection into C57Bl / 6 mice. Two animals were tested for each antibody at each dilution (n=2 / group). [Figure 11A] A schematic diagram of an exemplary set of bispecific TSLP × IL-13 antibodies based on Fab fusion is shown (formats PX128-I1 to PX128-I4, respectively). [Figure 11B] A schematic diagram of an exemplary set of bispecific TSLP × IL-13 antibodies based on Fab fusion is shown (formats PX128-I1 to PX128-I4, respectively). [Figure 11C] A schematic diagram of an exemplary set of bispecific TSLP × IL-13 antibodies based on Fab fusion is shown (formats PX128-I1 to PX128-I4, respectively). [Figure 11D] A schematic diagram of an exemplary set of bispecific TSLP × IL-13 antibodies based on Fab fusion is shown (formats PX128-I1 to PX128-I4, respectively). [Figure 12A] Figures 11A–11D, format PX128-I1–PX128-I4, and Figure 13, format PX128-R2, demonstrate the inhibitory activity of TSLP (Figure 12A) and IL-13 (Figure 12B) of TSLP × IL-13 bispecific antibodies. Figure 12A shows the percentage inhibition of TSLP signaling via the TSLP receptor complex expressed on STAT5-HEK-293 reporter cells after treatment with one of the bispecific antibodies. Figure 12B shows the percentage inhibition of IL-13 signaling via the IL-13 receptor complex expressed on HEK-293 reporter cells after treatment with one of the bispecific antibodies. Anti-IL-13 reference antibodies #2, #3, and #4 were included as positive controls. The IC90 values ​​for each antibody, depending on the antigen, were calculated based on antibody dose-dependent binding inhibition curves. Data were analyzed and presented using GraphPad. Ab, antibody; Conc., concentration. [Figure 12B] Figures 11A–11D, format PX128-I1–PX128-I4, and Figure 13, format PX128-R2, demonstrate the inhibitory activity of TSLP (Figure 12A) and IL-13 (Figure 12B) of TSLP × IL-13 bispecific antibodies. Figure 12A shows the percentage inhibition of TSLP signaling via the TSLP receptor complex expressed on STAT5-HEK-293 reporter cells after treatment with one of the bispecific antibodies. Figure 12B shows the percentage inhibition of IL-13 signaling via the IL-13 receptor complex expressed on HEK-293 reporter cells after treatment with one of the bispecific antibodies. Anti-IL-13 reference antibodies #2, #3, and #4 were included as positive controls. The IC90 values ​​for each antibody, depending on the antigen, were calculated based on antibody dose-dependent binding inhibition curves. Data were analyzed and presented using GraphPad. Ab, antibody; Conc., concentration. [Figure 13]A schematic diagram of a PX128-R2 heterodimer bispecific antibody is provided, in which the first arm contains an anti-TSLP Fab fragment and the second arm contains an anti-IL-13 Fab fragment. The Fc domain contains a knob-in-hole mutation. The CH1 and CL domains of the anti-IL-13 Fab fragment also contain R2 mutations, including mutations F126C and C220S in the heavy chain of the anti-IL-13 arm, and mutations E124C and C214S in the light chain (all EU numbered). [Figure 14] A schematic diagram of the PX128-JT heterodimer bispecific antibody is provided, in which the first arm contains an anti-TSLP Fab fragment and the second arm contains an anti-IL-13 Fab fragment. The Fc domain contains a knob-in-hole mutation. The CH1 and CL domains of the anti-IL-13 Fab fragment also contain either a JT11 or JT7 mutation. The JT11 mutations include F170V, S183I, and V185L in the HC of the anti-IL-13 arm, and L135F in the LC (all EU numbered). The JT7 mutations include F170I, S183L, and V185L in the HC of the anti-IL-13 arm, and L135F in the LC (all EU numbered). [Figure 15] A schematic diagram of a PX128-JT / R2 heterodimer bispecific antibody is provided, in which the first arm contains an anti-TSLP Fab fragment and the second arm contains an anti-IL-13 Fab fragment. The Fc domain contains a knob-in-hole mutation. The heavy and light chains of the anti-IL-13 arm also contain either an R2 mutation and either a JT11 or JT7 mutation (HC:JT11 / R2-HC:F126C, F170V, S183I, V185L, and C220S, or JT7 / R2-HC:F126C, F170I, S183L, V185L, and C220S, LC:E124C, L135F, and C214S). [Figure 16] The in vivo stability of the PX128-JT7 and PX128-JT11 heterodimer bispecific antibodies (shown in Figure 14) is demonstrated, represented by the time-course in vivo antibody concentrations of both the anti-TSLP antigen-binding and anti-IL-13 antigen-binding moieties after intravenous injection into C57Bl / 6 mice. Two animals were tested for each antibody concentration (n=2 / group). [Figure 17A] Figures 13–15 demonstrate the inhibitory activity of heterodimeric bispecific antibodies against TSLP (Figure 17A) and IL-13 (Figure 17B). Figure 17A shows the percentage of inhibition of TSLP signaling via the TSLP receptor complex expressed on STAT5-HEK-293 reporter cells after treatment with one of the heterodimeric bispecific antibodies. Figure 17B shows the percentage of inhibition of IL-13 signaling via the IL-13 receptor complex expressed on HEK-293-SEAP reporter cells after treatment with one of the heterodimeric bispecific antibodies. The IC90 values ​​for each antibody, depending on the antigen, were calculated based on antibody dose-dependent binding inhibition curves. The data were analyzed and presented using GraphPad. Ab: Antibody; Conc.: Concentration. [Figure 17B] Figures 13–15 demonstrate the inhibitory activity of heterodimeric bispecific antibodies against TSLP (Figure 17A) and IL-13 (Figure 17B). Figure 17A shows the percentage of inhibition of TSLP signaling via the TSLP receptor complex expressed on STAT5-HEK-293 reporter cells after treatment with one of the heterodimeric bispecific antibodies. Figure 17B shows the percentage of inhibition of IL-13 signaling via the IL-13 receptor complex expressed on HEK-293-SEAP reporter cells after treatment with one of the heterodimeric bispecific antibodies. The IC90 values ​​for each antibody, depending on the antigen, were calculated based on antibody dose-dependent binding inhibition curves. The data were analyzed and presented using GraphPad. Ab: Antibody; Conc.: Concentration. [Figure 18A]Figure 14 shows the levels of CCL17 production in PBMCs treated with TSLP alone (Figure 18A), IL-13 alone (Figure 18B), or TSLP and IL-13 (Figure 18C), obtained by dose escalation of PX128-JT7 and PX128-JT11 heterodimer bispecific antibodies, as measured by ELISA assay. Figure 18A shows CCL17 production after treatment with 0.5 ng / mL of TSLP alone. Reference anti-IL-13 antibody #2, reference TSLP × IL-13 antibody #3, reference TSLP × IL-13 × HSA antibody #4, and reference anti-TSLP antibody #5 were included as controls. Negative controls were included for cells treated with TSLP alone (Figure 18A), IL-13 alone (Figure 18B), or TSLP and IL-13 (Figure 18C), as well as for cells treated without antibody. [Figure 18B] Figure 14 shows the levels of CCL17 production in PBMCs treated with TSLP alone (Figure 18A), IL-13 alone (Figure 18B), or TSLP and IL-13 (Figure 18C), obtained by dose escalation of PX128-JT7 and PX128-JT11 heterodimer bispecific antibodies, as measured by ELISA assay. Figure 18A shows CCL17 production after treatment with 0.5 ng / mL of TSLP alone. Reference anti-IL-13 antibody #2, reference TSLP × IL-13 antibody #3, reference TSLP × IL-13 × HSA antibody #4, and reference anti-TSLP antibody #5 were included as controls. Negative controls were included for cells treated with TSLP alone (Figure 18A), IL-13 alone (Figure 18B), or TSLP and IL-13 (Figure 18C), as well as for cells treated without antibody. [Figure 18C]Figure 14 shows the levels of CCL17 production in PBMCs treated with TSLP alone (Figure 18A), IL-13 alone (Figure 18B), or TSLP and IL-13 (Figure 18C), obtained by dose escalation of PX128-JT7 and PX128-JT11 heterodimer bispecific antibodies, as measured by ELISA assay. Figure 18A shows CCL17 production after treatment with 0.5 ng / mL of TSLP alone. Reference anti-IL-13 antibody #2, reference TSLP × IL-13 antibody #3, reference TSLP × IL-13 × HSA antibody #4, and reference anti-TSLP antibody #5 were included as controls. Negative controls were included for cells treated with TSLP alone (Figure 18A), IL-13 alone (Figure 18B), or TSLP and IL-13 (Figure 18C), as well as for cells treated without antibody. [Figure 19] The half-life in vivo stability of an exemplary PX128-JT11 heterodimer bispecific antibody (shown in Figure 14) is shown, represented by the in vivo antibody concentration over time after intravenous bolus or subcutaneous injection into cynomolgus monkeys. A reference TSLP×IL-13×HSA antibody #4 was included as a control. Two animals were tested for each antibody concentration (n=2 / group). Detailed description of the invention

[0052] The present invention provides a multispecific construct (such as a bispecific construct) comprising an anti-IL-13 antibody moiety that specifically binds to IL-13, and a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP). In some embodiments, the multispecific construct comprises one anti-IL-13 antibody moiety. In some embodiments, the multispecific construct comprises two or more anti-IL-13 antibody moieties. In some embodiments, the multispecific construct comprises one antibody moiety that specifically binds to a second target antigen or target epitope. In some embodiments, the multispecific construct comprises two or more antibody moieties that specifically bind to one or more other target antigens or target epitopes. In some embodiments, the second antigen is a protein produced by immune cells. In some embodiments, the second antigen is TSLP. In another embodiment, the present invention also provides novel anti-IL-13 antibody constructs.

[0053] Following extensive research, the inventors of this application have found that the multispecific constructs described herein (e.g., anti-IL-13 multispecific constructs) possess several unexpected advantages compared to other multispecific proteins. First, the multispecific constructs described herein exhibit stronger binding to IL-13 and improved potency compared to currently available anti-IL-13 antibodies or their multispecific constructs. Second, the multispecific constructs (e.g., anti-IL-13 multispecific constructs) exhibit cross-reactivity with both human and cynomolgus monkey IL-13, which facilitates the extrapolation of toxicity and efficacy studies from cynomolgus monkeys to human clinical studies. Third, certain multispecific constructs described herein have been shown to be remarkably stable in vivo (e.g., when administered to both mice and cynomolgus monkeys), making them particularly suitable for formulation at high concentrations. Fourth, the in vivo half-lives of certain multispecific constructs described herein have been shown to be significantly longer than those of other control multispecific antibodies (for example, the half-lives are at least about 1.5 times, 2 times, 4 times, 5 times, or more than, the half-lives of control multispecific antibodies).

[0054] Pharmaceutical compositions and kits comprising either the multispecific construct or the anti-IL-13 antibody construct described herein are also provided, as well as methods of use thereof for treating inflammatory diseases such as asthma, atopic dermatitis, or COPD.

[0055] I. Definition As used herein, the term “treatment” refers to a clinical intervention designed to alter the natural course of an individual or cell being treated in the course of clinicopathology. Desired effects of treatment include a decrease in the rate of disease progression, improvement or mitigation of the disease state, and remission or improved prognosis. For example, if one or more symptoms associated with an inflammatory disease are alleviated or eliminated, the individual is successfully “treated,” which includes, but is not limited to, reducing local or systemic inflammation, decreasing symptoms resulting from the disease, increasing the quality of life of the affected individual, or reducing the dosage of other drugs required to treat the disease.

[0056] As used herein, “effective dose” refers to the amount of an agent or drug that is effective in treating a disease or disorder in a subject (an individual, e.g., a human). In the case of inflammatory diseases, an effective dose of an agent may reduce the number of active immune cells, reduce the amount of pro-inflammatory cytokines, inhibit (i.e., slow, preferably stop) inflammatory immune cell activity locally and / or systemically, and / or alleviate to some extent one or more of the symptoms associated with the inflammatory disease. As understood in clinical contexts, an effective dose of a drug, compound, or pharmaceutical composition may or may not be achieved in combination with another drug, compound, or pharmaceutical composition. Thus, “effective dose” may be considered in a situation in which one or more therapeutic agents are administered, and a single agent may be considered to be given in an effective dose if, in combination with one or more other agents, the desired outcome can or would be achieved.

[0057] As used herein, “individual” or “subject” refers to mammals, including but not limited to humans, cattle, horses, cats, dogs, rodents, or primates. In some embodiments, the individual is a human.

[0058] The term "antibody" is used broadly and specifically includes monoclonal antibodies (including full-length monoclonal antibodies), multispecific antibodies (e.g., bispecific antibodies), and antibody fragments insofar as they exhibit the desired biological activity. As used herein, the terms "immunoglobulin" (Ig) and "antibody" are interchangeable.

[0059] The term "full-length antibody" is used herein to refer to an antibody in its substantially intact form, rather than an antibody fragment as defined below. This term specifically refers to an antibody having a heavy chain containing an Fc region. A full-length antibody is typically a heterotetrameric glycoprotein with approximately 150,000 daltons, composed of two identical light (L) chains and two identical heavy (H) chains.

[0060] The term "constant domain" refers to the portion of the immunoglobulin molecule that contains the antigen-binding site and has a more conserved amino acid sequence compared to the variable domain. The constant domain is the C of the heavy chain. H 1, C H 2, and C H 3 domains (collectively, CH) and the light chain C H It contains an L (or CL) domain.

[0061] The "variable region" or "variable domain" of an antibody refers to the amino-terminal domain of the heavy or light chain. The variable domain of the heavy chain may be referred to as "VH," and the variable domain of the light chain may be referred to as "VL." These domains are generally the most variable parts of the antibody and contain the antigen-binding site.

[0062] The term "variable" refers to the fact that certain portions of the variable domain have widely different sequences across antibodies, and these differences are used in the binding and specificity of each particular antibody to a particular antigen. However, variability is not evenly distributed throughout the entire variable domain of an antibody. It is concentrated in three segments called hypervariable regions (also known as HVRs or CDRs) in both the light and heavy chain variable domains. The more highly conserved portions of the variable domain are called framework regions (FRs). The variable domains of the naive heavy and light chains each contain four FRs, most of which take the form of a beta-sheet structure, connected by three HVRs, forming loops that connect the beta-sheet structures, and in some cases forming parts of the beta-sheet structures. The HVRs in each chain are held together in close proximity by the FR regions and, using HVRs from other chains, contribute to the formation of the antibody's antigen-binding site (see Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, National Institute of Health, Bethesda, Md. (1991)). The constant domain does not directly participate in antibody binding to antigens, but exhibits various effector functions, such as the involvement of antibodies in antibody-dependent cytotoxicity. The residues of the constant domain are described herein based on EU numbering.

[0063] As used herein, the terms “CDR” or “complementarity-determining region” are intended to mean discontinuous antigen-binding sites found within the variable regions of both heavy and light chain polypeptides. These specific regions have been described in Kabat et al., J. Biol. al., J.Mol.Biol.,273:927-948(1997), MacCallum et al.,J.Mol.Biol.262:732-745(1996), Abhinandan and Martin,Mol.Immunol.,45:3832-3839(2008), Lefranc MPet The definitions are described in al., Dev. Comp. Immunol., 27:55-77 (2003), and Honegger and Pluckthun, J. Mol. Biol., 309:657-670 (2001), and include overlaps or subsets of amino acid residues when compared to one another. Nevertheless, the application of any definition to refer to a CDR of an antibody or grafted antibody or its variant is intended to be within the scope of the terms defined and used herein. For comparison, the amino acid residues encompassing a CDR as defined by each of the above cited references are shown in Table A below. CDR prediction algorithms and interfaces are known in the art, including, for example, Abhinandan and Martin, Mol.Immunol., 45:3832-3839 (2008), Ehrenmann F. et al., Nucleic Acids Res., 38:D301-D307 (2010), and Adolf-Bryfogle J. et al., Nucleic Acids Res., 43:D432-D438 (2015).The contents of the references cited in this paragraph are each incorporated herein by reference in their entireties for use in the present application and to allow for inclusion in one or more claims of the present specification. Amino acid residues of the CDRs provided herein are described herein based on Kabat.

[0064]

Table 1

[0065] The "light chain" of an antibody (immunoglobulin) derived from any mammalian species can be assigned to one of two clearly distinct types, namely kappa (κ) and lambda (λ), based on the amino acid sequence of their constant domains.

[0066] As used herein, the term IgG "isotype" or "subclass" means any of the subclasses of immunoglobulins defined by the chemical and antigenic characteristics of their constant regions.

[0067] Depending on the amino acid sequence of the constant domains of their heavy chains, antibodies (immunoglobulins) can be assigned to different "classes." There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, some of which can be further classified into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains corresponding to different classes of immunoglobulins are called α, δ, ε, γ, and μ, respectively. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known, and generally, see, for example, Abbas et al., Cellular and Mol. Immunology, 4. th This is described in ed. (WBSaunders, Co., 2000). The antibody may be part of a larger fusion molecule formed by covalent or noncovalent bonding between the antibody and one or more other proteins or peptides.

[0068] An "antibody fragment" comprises a portion of an intact antibody, preferably including its antigen-binding region. In some embodiments, the antibody fragment described herein is an antigen-binding fragment. Examples of antibody fragments or antigen-binding fragments include Fab, Fab', F(ab')2, and Fv fragments (single-chain variable fragments, scFv, etc.), diabodies; linear antibodies; single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.

[0069] Papain digestion of antibodies produces two identical antigen-binding fragments called "Fab" fragments, each with a single antigen-binding site, while the remaining "Fc" fragment, whose name reflects its ability to easily crystallize, is also produced. Pepsin treatment yields an F(ab')2 fragment, which has two antigen-binding sites and can still crosslink antigens.

[0070] "Fv" is the smallest antibody fragment containing a complete antigen-binding site. In one embodiment, a double-stranded Fv species consists of a dimer of one heavy-chain variable domain and one light-chain variable domain that are rigidly non-covalently associated. In a single-stranded Fv (scFv) species, the one heavy-chain and one light-chain variable domain can be covalently linked by a flexible peptide linker so that the light and heavy chains can associate in a "dimer" structure similar to that in a double-stranded Fv species. In this configuration, the three HVRs in each variable domain interact to define the antigen-binding site on the surface of the VH-VL dimer. Collectively, the six HVRs confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv containing only three antigen-specific HVRs) has the ability to recognize and bind to an antigen, albeit with lower affinity than a complete binding site.

[0071] The Fab fragment contains heavy chain and light chain variable domains (VH, VL), as well as a constant domain (CL) of the light chain and a first constant domain (C) of the heavy chain. H 1) It has two polypeptide chains, which also contain. The Fab' fragment is a heavy chain C containing one or more cysteines from the antibody hinge region. H It differs from the Fab fragment by having several residues added to the carboxyl terminus of one domain. Fab'-SH is the heretical designation for Fab' having a free thiol group on the cysteine ​​residue of the constant domain. The F(ab')2 antibody fragment was originally produced as a pair with Fab' fragments having a hinged cysteine ​​between them. Other chemical couplings of antibody fragments are also known.

[0072] A "single-stranded Fv" or "scFv" antibody fragment contains the VH and VL domains of the antibody, and these domains are present within a single polypeptide chain. Generally, scFv polypeptides further include a polypeptide linker between the VH and VL domains, which allows the scFv to form a desired structure for antigen binding. For an overview of scFv, see, for example, Pluckthun, The Pharmacology of Monoclonal Antibodies. Springer Berlin Heidelberg, 1994. 269-315.

[0073] The "Fc" fragment contains the carboxyl terminal portions of both heavy chains, held together by a disulfide. The effector function of the antibody is determined by the sequence of the Fc region, which is also the region recognized by the Fc receptor (FcR) found on cells of certain species.

[0074] As used herein, the term “monoclonal antibody” refers to an antibody obtained from a substantially homogeneous population of antibodies, where, for example, the individual antibodies constituting the population are identical except for any possible mutations that may be present in trace amounts, such as spontaneously occurring mutations. Thus, the modifier “monoclonal” indicates a characteristic of the antibody that it is not a mixture of distinct antibodies. In some embodiments, such a monoclonal antibody typically comprises an antibody containing a target-binding polypeptide sequence, and the target-binding polypeptide sequence is obtained by a process comprising the selection of a single target-binding polypeptide sequence from a plurality of polypeptide sequences. For example, the selection process may be the selection of a unique clone from a plurality of clones, such as a hybridoma clone, a phage clone, or a pool of recombinant DNA clones. It should be understood that the selected target-binding sequence may be further modified, for example, to improve affinity for a target, to humanize the target-binding sequence, to improve its production in cell culture, to reduce its immunogenicity in vivo, to produce a multispecific antibody, and that an antibody containing a modified target-binding sequence is also a monoclonal antibody of the present invention. In contrast to polyclonal antibody preparations, which typically contain different antibodies against different determinants (epitopes), each monoclonal antibody in a monoclonal antibody preparation is against a single determinant on an antigen. In addition to their specificity, monoclonal antibody preparations have the advantage of being typically free from contamination by other immunoglobulins.

[0075] The modifier "monoclonal" indicates the characteristic of antibodies obtained from a substantially homogeneous population of antibodies and should not be interpreted as requiring antibody production by any particular method. For example, monoclonal antibodies used in accordance with the present invention are, for example, produced by hybridoma (e.g., Kohler and Milstein, Nature 256:495-97 (1975), Hongo et al., Hybridoma 14(3):253-260 (1995), Harlow et al., Antibodies: A Laboratory Manual, (Cold Spring Harbor Laboratory Press, 2 nd(ed. 1988), Hammerling et al., Monoclonal Antibodies and T-Cell Hybridomas 563-681 (Elsevier, NY, 1981), Recombinant DNA method (see, e.g., U.S. Patent No. 4,816,567), Phage display technology (e.g., Clackson et al., Nature 352:624-628 (1991), Marks et al., J.Mol.Biol.222:581-597 (1992), Sidhu et al., J.Mol.Biol.338(2):299-310 (2004), Lee et al., J.Mol.Biol.340(5):1073-1093 (2004), Fellouse, Proc. Natl. Acad. Sci. USA See 101(34):12467-12472(2004) and Lee et al., J.Immunol.Methods 284(1-2):119-132(2004), as well as techniques for producing human or human-like antibodies in animals having some or all of the human immunoglobulin locus or genes encoding human immunoglobulin sequences (e.g., International Publication No. 1998 / 24893, International Publication No. 1996 / 34096, International Publication No. 1996 / 33735, International Publication No. 1991 / 10741, Jakobovits et al., Proc.Natl.Acad.Sci.USA 90:2551(1993), Jakobovits et al., Nature 362:255-258(1993), Bruggemann et al., Year in Selected from Immunol. 7:33 (1993), U.S. Patent Nos. 5,545,807, 5,545,806, 5,569,825, 5,625,126, 5,633,425, and 5,661,016, and Marks et al., Bio / Technology 10:779-783 (1992), Lonberg et al., Nature 368:856-859 (1994), Morrison, Nature 368:812-813 (1994), and Fishwild et al., Nature Biotechnol.It can be prepared by various techniques, including (see 14:845-851 (1996), Neuberger, Nature Biotechnol. 14:826 (1996), and Lonberg and Huszar, Intern. Rev. Immunol. 13:65-93 (1995)).

[0076] The term "monoclonal antibody" as used herein specifically includes "chimeric" antibodies in which a portion of the heavy chain and / or light chain is identical or homologous to a corresponding sequence of an antibody derived from a particular species or belonging to a particular antibody class or subclass, while the rest of the chain is identical or homologous to a corresponding sequence of an antibody derived from another species or belonging to another antibody class or subclass, and also includes fragments of such antibodies insofar as they exhibit the desired biological activity (see, for example, U.S. Patent No. 4,816,567 and Morrison et al., Proc. Natl. Acad. Sci. USA 81:6851-6855 (1984)). Chimeric antibodies include PRIMATIZED® antibodies in which the antigen-binding region of the antibody is derived, for example, from an antibody produced by immunizing macaque monkeys with the antigen of interest.

[0077] The "humanized" form of a non-human (e.g., mouse) antibody is a chimeric antibody containing a minimal sequence derived from a non-human immunoglobulin. In one embodiment, the humanized antibody is a human immunoglobulin (recipient antibody) in which residues derived from the recipient's HVR are replaced by residues derived from the HVR of a non-human species (donor antibody) (e.g., mouse, rat, rabbit, or non-human primate) having the desired specificity, affinity, and / or capabilities. In some examples, FR residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, the humanized antibody may contain residues not found in either the recipient antibody or the donor antibody. These modifications may be made to further improve the performance of the antibody. Generally, the humanized antibody will contain substantially all of at least one, typically two, variable domains, in which all or substantially all hypervariable loops correspond to the hypervariable loops of the non-human immunoglobulin, and all or substantially all FRs are FRs of the human immunoglobulin sequence. Humanized antibodies also optionally include the constant region (Fc) of immunoglobulins, typically at least a portion of the Fc of human immunoglobulins. For further details, see, for example, Jones et al., Nature 321:522-525 (1986), Riechmann et al., Nature 332:323-329 (1988), and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992). See, for example, Vaswani and Hamilton, Ann. Allergy, Asthma & Immunol. 1:105-115 (1998), Harris, Biochem. Soc. Transactions 23:1035-1038 (1995), Hurle and Gross, Curr. Op. Biotech. 5:428-433 (1994), and U.S. Patent Nos. 6,982,321 and 7,087,409.

[0078] A “human antibody” is defined as one having an amino acid sequence corresponding to the amino acid sequence of an antibody produced by a human, and / or one prepared using any of the techniques for producing human antibodies disclosed herein. Specifically, this definition of a human antibody excludes humanized antibodies that contain non-human antigen-binding residues. Human antibodies can be produced using a variety of techniques known in the art, including phage display libraries. (Hoogenboom and Winter, J.Mol.Biol.227:381(1991), Marks et al., J.Mol.Biol.222:581(1991)). Methods described in Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, 77(1985), and Boerner et al., J.Immunol.147(1):86-95(1991) are also available for the preparation of human monoclonal antibodies. Furthermore, the method described in van Dijk and van de Winkel, Curr. Opin. Pharmacol. 5:368-74 (2001) can be used. Human antibodies can be prepared by administering an antigen to transgenic animals, such as immunized xenomouses, which are modified to produce such antibodies in response to antigen challenge but whose endogenous gene locus is deactivated (see, for example, U.S. Patents 6,075,181 and 6,150,584 relating to XENOMOUSE® technology). Also, see, for example, Li, et al., Proc. Natl. Acad. Sci. USA 103:3557-3562 (2006) (referring to human antibodies produced via human B-cell hybridoma technology).

[0079] As used herein, the terms “hypervariable region,” “HVR,” or “HV” refer to regions of antibody variable domains that are hypervariable in sequence and / or form structurally defined loops. Generally, antibodies contain six HVRs: three VH(H1, H2, H3) and three VL(L1, L2, L3). In natural antibodies, H3 and L3 exhibit the highest diversity among the six HVRs, and H3 in particular is thought to play a unique role in conferring superior specificity to antibodies. See, for example, Xu et al., Immunity 13:37-45 (2000) and Johnson and Wu, in Methods in Molecular Biology 248:1-25 (Lo, ed., Human Press, Totowa, NJ, 2003). In fact, naturally occurring camel antibodies consisting only of heavy chains are functional and stable in the absence of light chains. See, for example, Hamers-Casterman et al., Nature 363:446-448 (1993) and Sheriff et al., Nature Struct. Biol. 3:733-736 (1996). HVR is also called "CDR" or "complementarity-determining region".

[0080] The structure and location of immunoglobulin variable regions can be determined by referring to Kabat, EA et al., Sequences of Proteins of Immunological Interest, 4th Edition, US Department of Health and Human Services, 1987, and its latest edition (currently available online at immuno.bme.nwu.edu).

[0081] A “framework” or “FR” residue is a variable domain residue other than an HVR residue as defined herein.

[0082] As used herein, the term “covalent” refers to a direct bond via one or more chemical bonds, or an indirect bond via one or more linkers. Direct bonds can be made using any suitable chemical bond, including, but not limited to, covalent bonds such as peptide bonds and disulfide bonds, or non-covalent bonds such as hydrogen bonds, hydrophobic bonds, ionic bonds, or van der Waals bonds.

[0083] As used herein, “covalent bond” refers to a stable bond between two atoms that share one or more electrons. Examples of covalent bonds include, but are not limited to, peptide bonds and disulfide bonds. As used herein, “peptide bond” refers to a covalent bond formed between the carboxyl group of an amino acid and the amine group of an adjacent amino acid. As used herein, “disulfide bond” refers to a heavy chain fragment C bonded by one or more disulfide bonds. H This refers to a covalent bond formed between two sulfur atoms, such as a combination of 1 and the light chain fragment CL. One or more disulfide bonds can be formed between two fragments by linking thiol groups in the two fragments. In some embodiments, one or more disulfide bonds can be formed between one or more cysteine ​​groups of the heavy chain fragment and the light chain fragment, respectively. Disulfide bonds can be formed by the oxidation of two thiol groups. In some embodiments, covalent bonds are directly linked by covalent bonds. In some embodiments, covalent bonds are directly linked by peptide bonds or disulfide bonds.

[0084] As used herein, the terms “binding,” “specifically binding,” or “specific to” refer to measurable and reproducible interactions, such as binding between a target and an antibody, that determine the presence of the target in the presence of a heterogeneous population of molecules, including biomolecules. For example, an antibody that binds to or specifically binds to a target (which may be an epitope) is an antibody that binds to this target more readily, with higher affinity, binding strength, and / or for a longer duration than an antibody that binds to other targets. In one embodiment, the degree of antibody binding to an unrelated target is less than about 10% of the antibody binding to the target, as measured, for example, by radioimmunoassay (RIA). In some embodiments, an antibody that specifically binds to a target has a dissociation constant (K) of ≤1 μM, ≤100 nM, ≤10 nM, ≤1 nM, or ≤0.1 nM. d ) has. In some embodiments, the antibody specifically binds to an epitope on a protein that is conserved between proteins from different species. In other embodiments, specific binding may include, but is not required, exclusive binding.

[0085] As used herein, “amino acid sequence identity percentage (%)” and “homology” for a peptide, polypeptide, or antibody sequence are defined as the percentage of amino acid residues in a candidate sequence that are identical to amino acid residues in a particular peptide or polypeptide sequence after the sequences have been aligned and gaps introduced as necessary, without considering any conservative substitutions as part of the sequence identity, to achieve the maximum sequence identity percentage. Alignment for the purpose of determining amino acid sequence identity percentage can be achieved by various methods within the scope of the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or MEGALIGN® (DNASTAR) software. A person skilled in the art can determine appropriate parameters for measuring the alignment, including any algorithm necessary to achieve the maximum alignment over the entire length of the sequences being compared.

[0086] Amino acid substitutions may include, but are not limited to, the replacement of one amino acid in a polypeptide with another. Exemplary substitutions are shown in Table B. Amino acid substitutions can be introduced into antibodies of interest, and the products can be screened for desired activity of ADCC or CDC, for example, maintained / improved antigen binding, reduced immunogenicity, or improved ADCC or CDC activity.

[0087] [Table 2]

[0088] Amino acids can be classified according to their common side-chain properties: (1) Hydrophobic: norleucine, Met, Ala, Val, Leu, Ile; (2) Neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) Acidic: Asp, Glu; (4) Basic: His, Lys, Arg; (5) Residues that affect chain orientation: Gly, Pro; (6) Aromatic: Trp, Tyr, Phe. Non-conservative substitutions involve exchanging a member of one of these classes for a member of another class.

[0089] The term "multispecificity," as used in conjunction with antibodies or antigen-binding proteins, refers to antibodies or antigen-binding proteins that possess polyepitope specificity (i.e., they can specifically bind to two, three, or more different epitopes on one biomolecule, or to two, three, or more different epitopes on two, three, or more different biomolecules). Unless otherwise indicated, the order in which the antigens bound by a multispecific antibody are listed in the multispecific antibody name is arbitrary.

[0090] The term "bispecificity," used in conjunction with antibodies or antigen-binding proteins, refers to an antibody or antigen-binding protein that can specifically bind to two different epitopes on one biomolecule, or to two different epitopes on two different biomolecules. Unless otherwise specified, the order in which the antigens bound by a bispecific antibody are listed in the bispecific antibody name is arbitrary.

[0091] The “knob-in-hole” strategy (see, for example, International Publication No. 2006 / 028936) has its plain, ordinary meaning when read in light of this specification and refers to a strategy that may be used to produce full-length bispecific antibodies. In short, C in human IgG H Selected amino acids that form the interface of the three domains are used to promote heterodimer formation. H Mutations can be induced at positions that affect the three-domain interaction. An amino acid with a small side chain (hole) is introduced into the heavy chain of the antibody that specifically binds to the first antigen, and an amino acid with a large side chain (knob) is introduced into the heavy chain of the antibody that specifically binds to the second antigen. After co-expression of the two antibodies, a heterodimer is formed as a result of the preferential interaction between the heavy chain with the "hole" and the heavy chain with the "knob".

[0092] As used herein, the term “vector” means a nucleic acid molecule capable of propagating another ligated nucleic acid. This term includes vectors as self-replicating nucleic acid structures, and vectors incorporated into the genome of a host cell into which they are introduced. Certain vectors can be directed to the expression of nucleic acids into which they are manipulably ligated. Such vectors are referred to herein as “expression vectors.”

[0093] Embodiments of the present invention described herein are understood to include embodiments that "consist" and / or "consisting essentially of".

[0094] In this specification, references to values ​​or parameters “approximately” include (and shall be described) variations relating to the value or parameter itself. For example, a statement referring to “approximately X” includes a statement of “X.”

[0095] The terms "approximately" and "about" refer to a percentage of a given value or range that is within 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less than 20% of that value or range.

[0096] Where used herein, references to a value or parameter "not" generally mean and describe something "other than" a value or parameter. For example, "The method is not used to treat inflammatory diseases of type X" means that the method is used to treat inflammatory diseases of types other than X.

[0097] As used herein, the term "approximately X to Y" has the same meaning as "approximately X to approximately Y".

[0098] As used herein and in the appended claims, unless otherwise explicitly indicated by the context, the singular forms "a," "an," and "the" include plural referents.

[0099] II. Multispecific anti-IL-13 antibody construct In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising i) a first antibody moiety that specifically binds to interleukin-13 (IL-13, "anti-IL-13 antibody moiety," e.g., any of the anti-IL-13 antibody moieties described herein), and ii) a second antibody moiety that specifically binds to a second target antigen. In some embodiments, the second target antigen is IL-13 (e.g., the same epitope or a different epitope as that to which the first antibody moiety binds). In some embodiments, the second target antigen is not IL-13. In some embodiments, the second target antigen is TSLP. In some embodiments, the multispecific construct or isolated anti-IL-13 antibody construct described herein comprises one or more (e.g., 1, 2, 3, 4, 5, or more, e.g., 1 or 2) anti-IL-13 antibody moieties (e.g., scFv, Fab, or full-length antibody). In some embodiments, the multispecific construct includes a first anti-IL-13 antibody moiety and a second anti-IL-13 antibody moiety (e.g., a first anti-IL-13 Fab and a second anti-IL-13 Fab, or a first anti-IL-13 scFv and a second anti-IL-13 scFv), an optional third antibody moiety that specifically binds to a third target antigen (e.g., Fab, scFv), and an optional fourth antibody moiety that specifically binds to a fourth target antigen. In some embodiments, the multispecific construct includes a first anti-IL-13 antibody moiety, a second antibody moiety that specifically binds to a second target antigen, and a third antibody moiety that specifically binds to a third target antigen. In some embodiments, the first anti-IL-13 antibody moiety and the second anti-IL-13 antibody moiety have the same amino acid sequence. In some embodiments, the first anti-IL-13 antibody moiety and the second anti-IL-13 antibody moiety have different amino acid sequences. In some embodiments, the first anti-IL-13 antibody moiety and the second anti-IL-13 antibody moiety bind to the same IL-13 epitope. In some embodiments, the first anti-IL-13 antibody moiety and the second anti-IL-13 antibody moiety bind to different IL-13 epitopes. In some embodiments, the third antibody moiety and the fourth antibody moiety have the same amino acid sequence.In some embodiments, the third antibody moiety and the fourth antibody moiety have different amino acid sequences. In some embodiments, the third antibody moiety and the fourth antibody moiety bind to the same target epitope. In some embodiments, the third antibody moiety and the fourth antibody moiety bind to different target epitopes.

[0100] In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising i) a first antibody means for specifically binding to IL-13, and ii) a second antibody means for specifically binding to a second target antigen. In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising i) a first antibody means for specifically binding to IL-13, and ii) a second antibody means for specifically binding to TSLP. In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising i) a first antibody means for specifically binding to IL-13, and ii) a second antibody means for specifically binding to a second target antigen (such as any of the second antibody moieties described herein). In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising i) a first antibody means for specifically binding to IL-13, and ii) a second antibody moiety for specifically binding to TSLP (such as any of the anti-TSLP moieties described herein). In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising i) a first antibody moiety that specifically binds to IL-13 (e.g., one of the anti-IL-13 antibody moieties described herein), and ii) a second antibody means for specifically binding to TSLP. The anti-IL-13 antibody moieties described herein may have one or more advantageous properties, for example, 1) high binding affinity to IL-13, 2) binding to the IL-13 / IL-13Rα1 complex, 3) blocking the recruitment of IL-4Rα to IL-13Rα1 to prevent the formation of the IL-13Rα1 / IL-4Rα complex, and 4) inhibition of IL-13 signaling via the IL-13Rα1 / IL-4Rα complex. The anti-TSLP antibody moieties described herein may have one or more advantageous properties, including, for example, 1) high binding affinity to TSLP, 2) blockade of TSLP / TSLPR interaction, and 3) inhibition of TSLP signaling via the TSLPR / IL-7Rα complex.

[0101] In some embodiments, the multispecific constructs described herein exhibit an increased in vivo half-life compared to the anti-IL-13 antibody moiety (e.g., Fab, scFv, full-length antibody) alone (e.g., an increase of at least about 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10 times, or more). In some embodiments, the multispecific constructs described herein exhibit an increased in vivo half-life compared to the second antibody moiety that specifically recognizes a second antigen (e.g., TSLP) alone (e.g., an increase of at least about 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10 times, or more).

[0102] In some embodiments, a multispecific construct is provided comprising a first antibody moiety which is an anti-IL-13 scFv (e.g., any of the anti-IL-13 scFvs described herein) and a second antibody moiety which is a full-length antibody that specifically binds to a second target antigen (e.g., TSLP), wherein the anti-IL-13 scFv is fused to one of the C-terminuses of the heavy chain of the second antibody moiety to form a fusion polypeptide. In some embodiments, a multispecific construct is provided comprising two anti-IL-13 antibody moieties that are scFv ("anti-IL-13 scFv1" and "anti-IL-13 scFv2", e.g., any of the anti-IL-13 scFv described herein), and a second antibody moiety that is a full-length antibody that specifically binds to a second target antigen (e.g., TSLP), wherein anti-IL-13 scFv1 is fused to the C-terminus of the first heavy chain of the second antibody moiety to form a first fusion polypeptide, and anti-IL-13 scFv2 is fused to the C-terminus of the second heavy chain of the second antibody moiety to form a second fusion polypeptide. In some embodiments, the Fc domain of the full-length antibody comprises a first subunit and a second subunit. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes the M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes the M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (iv)(a) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (b) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0103] In some embodiments, a multispecific construct is provided comprising two anti-IL-13 antibody moieties that are scFv ("anti-IL-13 scFv1" and "anti-IL-13 scFv2", e.g., any of the anti-IL-13 scFv described herein), two second antibody moieties that are Fab ("Fab1" and "Fab2") that specifically bind to a second target antigen (e.g., TSLP), and an Fc domain, wherein the multispecific construct comprises i) a first polypeptide comprising VL1-(L1-CL) from N' to C', ii) a second polypeptide comprising a first subunit of the Fc domain of VH1-(H1-CH1)-any linker-anti-IL-13 scFv1-any linker-Fc domain from N' to C', and iii) VH2-(H2-CH1)-any linker-anti-IL-13 scFv2-optional linker-a third polypeptide comprising a second subunit of the Fc domain, and iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C', where VL1-(L1-CL) and VH1-(H1-CH1) form Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form Fab2. In some embodiments, the Fc domain comprises a first subunit and a second subunit. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0104] In some embodiments, a multispecific construct is provided comprising a first antibody moiety which is a full-length anti-IL-13 antibody (e.g., any of the full-length anti-IL-13 antibodies described herein), and a second antibody moiety which is an scFv that specifically binds to a second target antigen (e.g., TSLP), wherein the scFv moiety is fused to one C-terminus of the heavy chain of the full-length anti-IL-13 antibody to form a fusion polypeptide. In some embodiments, a multispecific construct is provided comprising a first antibody moiety which is a full-length anti-IL-13 antibody (e.g., any of the full-length anti-IL-13 antibodies described herein), and two second antibody moieties ("scFv1" and "scFv2") which are scFv that specifically bind to a second target antigen (e.g., TSLP), wherein scFv1 is fused to the C-terminus of the first heavy chain of the full-length anti-IL-13 antibody to form a first fusion polypeptide, and scFv2 is fused to the C-terminus of the second heavy chain of the full-length anti-IL-13 antibody to form a second fusion polypeptide. In some embodiments, the Fc domain of the full-length anti-IL-13 antibody is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0105] In some embodiments, the Fab consists of two anti-IL-13 antibody moieties ("anti-IL-13 Fab1" and "anti-IL-13 Fab2", for example, the anti-IL-13 described herein). A multispecific construct is provided comprising: one of Fabs; two second antibody moieties ("scFv1" and "scFv2") which are scFvs that specifically bind to a second target antigen (e.g., TSLP); and an Fc domain, wherein the multispecific construct comprises: i) a first polypeptide comprising VL1-(L1-CL) from N' to C'; ii) a second polypeptide comprising a first subunit of VH1-(H1-CH1)-any linker-scFv1-any linker-Fc domain from N' to C'; iii) a third polypeptide comprising a second subunit of VH2-(H2-CH1)-any linker-scFv2-any linker-Fc domain from N' to C'; and iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C', wherein VH1-(H1-CH1) and VL1-(L1-CL) are anti-IL-13 Fab1 is formed, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2. In some embodiments, the Fc domain includes a first subunit and a second subunit. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0106] In some embodiments, the Fab consists of two anti-IL-13 antibody moieties ("anti-IL-13 Fab1" and "anti-IL-13 Fab2", for example, the anti-IL-13 described herein). A multispecific construct is provided comprising one of the following: a first antibody moiety (Fab) and a second antibody moiety which is a full-length antibody that specifically binds to a second target antigen (e.g., TSLP), wherein the multispecific construct comprises: i) a first polypeptide comprising a first light chain of the second antibody moiety; ii) a second polypeptide comprising, from N' to C', the first heavy chain of the second antibody moiety - an optional linker - VH1-(H1-CH1); iii) a third polypeptide comprising, from N' to C', the second heavy chain of the second antibody moiety - an optional linker - VH2-(H2-CH1); iv) a fourth polypeptide comprising a second light chain of the second antibody moiety; v) a fifth polypeptide comprising, from N' to C', VL1-(L1-CL); and vi) a sixth polypeptide comprising, from N' to C', VL1-(L1-CL) and VH1-(H1-CH1) are anti-IL-13 Fab1 is formed, and VL2-(L2-CL) and VH2-(H2-CH1) form anti-IL-13 Fab2.In some embodiments, anti-IL-13 Fab1 comprises H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL), where anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL), where (a) H1 and H2 each include substitutions of F170I, S183L, and V185L, and L1 and L2 each include substitutions of L135F, (b) H1 and H2 each include substitutions of F170V, S183I, and V185L, and L1 and L2 each include substitutions of L135F, or (c) H1 and H2 each include substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and L2 (d) H1 and H2 each contain the E124C (or Q124C), L135F, and C214S substitutions, and L1 and L2 each contain the F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C), L135F, and C214S substitutions, or (e) H1 and H2 each contain the F126C and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C) and C214S substitutions, with the amino acid positions following EU numbering. In some embodiments, the full-length antibody includes an Fc domain, and the Fc domain includes a first subunit and a second subunit. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0107] In some embodiments, the light chain of the full-length antibody is derived from the kappa light chain.

[0108] In some embodiments, a multispecific construct is provided comprising a first anti-IL-13 antibody moiety which is a full-length antibody ("full-length anti-IL-13 antibody," e.g., any of the full-length anti-IL-13 antibodies described herein), and two second antibody moieties which are Fabs that specifically bind to a second target antigen (e.g., TSLP), wherein the multispecific construct comprises i) a first polypeptide comprising a first light chain (L1) of the full-length anti-IL-13 antibody, and ii) a second polypeptide comprising a first heavy chain (H1) of the full-length anti-IL-13 antibody, arranged from N' to C', an optional linker, VH3, and VH3-(H3-CH1). iii) a third polypeptide comprising the second heavy chain (H2) of the full-length anti-IL-13 antibody - an arbitrary linker - VH4-(H4-CH1) from N' to C', iv) a fourth polypeptide comprising the second light chain (L2) of the full-length anti-IL-13 antibody, v) a fifth polypeptide comprising VL3-(L3-CL) from N' to C', and vi) a sixth polypeptide comprising VL4-(L4-CL) from N' to C', wherein VL3-(L3-CL) and VH3-(H3-CH1) form Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form Fab2. In some embodiments, (a) H1 and H2 each include substitutions of F170I, S183L, and V185L, and L1 and L2 each include substitutions of L135F; (b) H1 and H2 each include substitutions of F170V, S183I, and V185L, and L1 and L2 each include substitutions of L135F; (c) H1 and H2 each include substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and L2 each include substitutions of E124C (or Q124 (c) containing the substitutions of L135F and C214S, (d) H1 and H2 each containing the substitutions of F126C, F170V, S183I, V185L and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C), L135F and C214S, or (e) H1 and H2 each containing the substitutions of F126C and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C) and C214S, with amino acid positions following EU numbering.In some embodiments, the anti-IL-13 full-length antibody includes an Fc domain, the Fc domain comprising a first subunit and a second subunit. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering). In some embodiments, L3-CL and L4-CL are derived from kappa light chains.

[0109] In some embodiments, the Fab consists of two anti-IL-13 antibody moieties ("anti-IL-13 Fab1" and "anti-IL-13 Fab2", for example, the anti-IL-13 described herein). A multispecific construct is provided comprising one of the following: Fab, and a second antibody moiety which is a full-length antibody that specifically binds to a second target antigen (e.g., TSLP), wherein the multispecific construct comprises: i) a first polypeptide comprising VL1-(L1-CL) from N' to C'; ii) a second polypeptide comprising VH1-(H1-CH1)-any linker-first heavy chain of the second antibody moiety from N' to C'; iii) a third polypeptide comprising VH2-(H2-CH1)-any linker-second heavy chain of the second antibody moiety from N' to C'; iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C'; v) a fifth polypeptide comprising the first light chain of the second antibody moiety; and vi) a sixth polypeptide comprising the second light chain of the second antibody moiety, wherein VL1-(L1-CL) and VH1-(H1-CH1) are anti-IL-13 Fab1 is formed, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2.In some embodiments, anti-IL-13 Fab1 comprises H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL), where anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL), where (a) H1 and H2 each contain substitutions of F170I, S183L, and V185L, and L1 and L2 each contain substitutions of L135F, (b) H1 and H2 each contain substitutions of F170V, S183I, and V185L, and L1 and L2 each contain substitutions of L135F, (c) H1 and H2 each contain substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and (d) L2 each contains the E124C (or Q124C), L135F, and C214S substitutions, or (e) H1 and H2 each contain the F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C), L135F, and C214S substitutions, or (e) H1 and H2 each contain the F126C and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C) and C214S substitutions, with the amino acid positions following EU numbering. In some embodiments, the full-length antibody includes an Fc domain, where the Fc domain includes a first subunit and a second subunit. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain contains the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain contains the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain contains the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain contains the T366W substitution (EU numbering). In some embodiments, the light chain of the full-length antibody is derived from the kappa light chain.

[0110] In some embodiments, a multispecific construct is provided comprising a first antibody moiety which is a full-length anti-IL-13 antibody (e.g., any of the full-length anti-IL-13 antibodies described herein), and two second antibody moieties ("Fab1" and "Fab2") which are Fabs that specifically bind to a second target antigen (e.g., TSLP), wherein the multispecific construct comprises: i) a first polypeptide comprising VL3-(L3-CL) from N' to C', ii) a second polypeptide comprising the first heavy chain (H1) of a VH3-(H3-CH1)-any linker-full-length anti-IL-13 antibody from N' to C', and iii) N' to C iv) A third polypeptide comprising VH4-(H4-CH1)-any linker-second heavy chain (H2) of the full-length anti-IL-13 antibody, moving from N' to C'; v) A fifth polypeptide comprising VL4-(L4-CL) moving from N' to C'; and vi) A sixth polypeptide comprising the second light chain (L2) of the full-length anti-IL-13 antibody, moving from N' to C', where VL3-(L3-CL) and VH3-(H3-CH1) form Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form Fab2. In some embodiments, (a) H1 and H2 each include substitutions of F170I, S183L, and V185L, and L1 and L2 each include substitutions of L135F; (b) H1 and H2 each include substitutions of F170V, S183I, and V185L, and L1 and L2 each include substitutions of L135F; (c) H1 and H2 each include substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and L2 each include substitutions of E124C (or Q124 (c) containing the substitutions of L135F and C214S, (d) H1 and H2 each containing the substitutions of F126C, F170V, S183I, V185L and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C), L135F and C214S, or (e) H1 and H2 each containing the substitutions of F126C and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C) and C214S, with amino acid positions following EU numbering.In some embodiments, the IL-13 full-length antibody includes an Fc domain, which comprises a first subunit and a second subunit. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering). In some embodiments, L3-CL and L4-CL are derived from kappa light chains.

[0111] In some embodiments, a multispecific construct is provided, which is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP). In some embodiments, (i) H1 includes substitutions at positions 170, 183, and 185 (EU numbering), and L1 includes substitution at position 135 (EU numbering), and / or (ii) H1 includes substitutions at positions 126 and 220 (EU numbering), and L1 includes substitutions at positions 124 and 214 (EU numbering). In some embodiments, H1 includes substitutions at positions F170, S183, and V185 (EU numbering), and L1 includes substitution at position L135 (EU numbering). In some embodiments, H1 includes substitutions at F170I, S183L, and V185L (EU numbering), and L1 includes substitution at L135F (EU numbering). In some embodiments, H1 includes substitutions at F170V, S183I, and V185L (EU numbering), and L1 includes substitution at L135F (EU numbering). In some embodiments, L1 is derived from a lambda light chain (e.g., a lambda light chain containing the amino acid sequence of SEQ ID NO: 74 or SEQ ID NO: 75). In some embodiments, H1 includes substitutions at positions F126 and C220 (EU numbering), and L1 includes substitutions at positions E124 and C214 (EU numbering). In some embodiments, H1 includes F126C and C220S substitutions (EU numbering), and L1 includes E124C and C214S substitutions (EU numbering). In some embodiments, L2 is derived from a kappa light chain. In some embodiments, L1 is derived from a kappa light chain (e.g., a kappa light chain containing the amino acid sequence of SEQ ID NO: 73).In some embodiments, H1 includes substitutions at positions F126 and C220 (EU numbering), and L1 includes substitutions at positions Q124 and C214 (EU numbering). In some embodiments, H1 includes substitutions F126C and C220S (EU numbering), and L1 includes substitutions Q124C and C214S (EU numbering). In some embodiments, L2 is derived from the lambda light chain. In some embodiments, H1 includes substitutions at positions 126, 170, 183, 185, and 220, and L1 includes substitutions at positions 124, 135, and 214, with positions according to EU numbering. In some embodiments, (i) H1 includes substitutions at positions F126, F170, S183, V185, and C220, and L1 includes substitutions at positions E124, L135, and C214, or (ii) H1 includes substitutions at positions F126, F170, S183, V185, and C220, and L1 includes substitutions at positions Q124, L135, and C214, where the positions are assigned by EU numbering. In some embodiments, (i) H1 includes substitutions for F126C, F170I, S183L, V185L, and C220S, and L1 includes substitutions for E124C, L135F, and C214S, or (ii) H1 includes substitutions for F126C, F170V, S183I, V185L, and C220S, and L1 includes substitutions for E124C, L135F, and C214S, or (i ii) H1 includes the substitutions F126C, F170I, S183L, V185L, and C220S, and L1 includes the substitutions Q124C, L135F, and C214S, or (iv) H1 includes the substitutions F126C, F170V, S183I, V185L, and C220S, and L1 includes the substitutions Q124C, L135F, and C214S, with the position determined by EU numbering. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain includes the substitutions L234A and L235A (EU numbering). In some embodiments, each subunit of the Fc domain includes the substitutions M428L and N434S (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain contains the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain contains the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain contains the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain contains the T366W substitution (EU numbering). In some embodiments, the mutations in H1 and L1 described herein may instead be on H2 and L2.

[0112] In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1, and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), wherein H1 includes substitutions at positions 170, 183, and 185 (EU numbering), and L1 includes a substitution at position 135 (EU numbering). In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1, and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), and H1 comprises F170I, S183L, and V185L substitutions (EU numbering), and L1 comprises L135F substitution (EU numbering).In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP). Furthermore, wherein H1 comprises F170V, S183I, and V185L substitutions (EU numbering), and L1 comprises L135F substitution (EU numbering). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).In some embodiments, (a) H1 includes substitutions for F170I, S183L, V185L, T366S, L368A, and Y407V, L1 includes substitutions for L135F, and H2 includes substitutions for T366W, (b) H1 includes substitutions for F170I, S183L, V185L, and T366W, L1 includes substitutions for L135F, and H2 includes substitutions for T366S, L368A, and Y407V, (c) (d) H1 includes the substitutions F170V, S183I, V185L, T366S, L368A, and Y407V, L1 includes the substitution L135F, and H2 includes the substitution T366W, or (d) H1 includes the substitutions F170V, S183I, V185L, and T366W, L1 includes the substitution L135F, and H2 includes the substitutions T366S, L368A, and Y407V, with the amino acid positions following EU numbering. In some embodiments, L1 is derived from the lambda light chain and L2 is derived from the kappa light chain. In some embodiments, L2 is derived from the lambda light chain and L1 is derived from the kappa light chain.

[0113] In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, where H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP). H1 includes substitutions at positions 126 and 220 (EU numbering), and L1 includes substitutions at positions 124 and 214 (EU numbering). In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), wherein H1 comprises F126C and C220S substitutions (EU numbering) and L1 comprises E124C and C214S substitutions (EU numbering). In some embodiments, L2 is derived from a kappa light chain.In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), wherein H1 comprises the F126C and C220S substitution (EU numbering), and L1 comprises the Q124C and C214S substitution (EU numbering). In some embodiments, L2 is derived from the lambda light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).In some embodiments, (a) H1 includes substitutions of F126C, C220S, T366S, L368A, and Y407V, L1 includes substitutions of E124C and C214S, and H2 includes substitutions of T366W, (b) H1 includes substitutions of F126C, C220S, and T366W, L1 includes substitutions of E124C and C214S, and H2 includes substitutions of T366S, L368A, and Y407V, (c) (d) H1 contains the substitutions F126C, C220S, T366S, L368A, and Y407V, L1 contains the substitutions Q124C and C214S, and H2 contains the substitution T366W, or (d) H1 contains the substitutions F126C, C220S, and T366W, L1 contains the substitutions Q124C and C214S, and H2 contains the substitutions T366S, L368A, and Y407V, with amino acid positions following EU numbering.

[0114] In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. This is a bispecific antibody, where H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), with H1 including substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and L1 including substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, L1 is derived from a lambda light chain. In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer double comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. A specific antibody, where H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), with H1 comprising F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and L1 comprising E124C, L135F, and C214S substitutions (EU numbering).In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. Herein, H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), wherein H1 includes the F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and L1 includes the E124C, L135F, and C214S substitutions (EU numbering). In some embodiments, L2 is derived from a kappa light chain. In some embodiments, L1 is derived from a kappa light chain. In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. Herein, H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), wherein H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and L1 comprises Q124C, L135F, and C214S substitutions (EU numbering).In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. Herein, H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), wherein H1 includes F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and L1 includes Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, L2 is derived from a lambda light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes the M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).In some embodiments, (a) H1 includes substitutions of F126C, F170I, S183L, V185L, C220S, T366S, L368A, and Y407V, L1 includes substitutions of E124C (or Q124C), L135F, and C214S, and H2 includes substitutions of T366W, (b) H1 includes substitutions of F126C, F170I, S183L, V185L, C220S, and T366W, L1 includes substitutions of E124C (or Q124C), L135F, and C214S, and H2 includes substitutions of T366S, L368A, and Y407V, (c) (d) H1 includes the substitutions F126C, F170V, S183I, V185L, C220S, T366S, L368A, and Y407V, L1 includes the substitutions E124C (or Q124C), L135F, and C214S, and H2 includes the substitution T366W, or (d) H1 includes the substitutions F126C, F170V, S183I, V185L, C220S, and T366W, L1 includes the substitutions E124C (or Q124C), L135F, and C214S, and H2 includes the substitutions T366S, L368A, and Y407V, with amino acid positions following EU numbering.

[0115] In some embodiments, a multispecific construct is provided comprising a heterodimeric bispecific antibody, the heterodimeric bispecific antibody comprising i) a first light chain (L1) comprising VL1 and L1-CL, ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain, iii) a second heavy chain (H2) comprising VH2, H2-CH1 and a second subunit of the Fc domain, and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), wherein H2 includes substitutions at positions 170, 183, and 185 (EU numbering), and L2 includes a substitution at position 135 (EU numbering). In some embodiments, H2 includes substitutions at the positions of F170, S183, and V185 (EU numbering), and L2 includes substitution at the position of L135 (EU numbering). In some embodiments, H2 includes substitutions of F170I, S183L, and V185L (EU numbering), and L2 includes substitutions of L135F (EU numbering). In some embodiments, L2 is derived from the lambda light chain. In some embodiments, L2 is derived from the kappa light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain includes substitutions of L234A and L235A (EU numbering). In some embodiments, each subunit of the Fc domain includes substitutions of M428L and N434S (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0116] In some embodiments, a multispecific construct is provided comprising a heterodimeric bispecific antibody, the heterodimeric bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), wherein H2 comprises substitutions at positions 170, 183, and 185 (EU numbering), and L2 comprises a substitution at position 135 (EU numbering). In some embodiments, H2 includes substitutions at the positions of F170, S183, and V185 (EU numbering), and L2 includes substitution at the position of L135 (EU numbering). In some embodiments, H2 includes substitutions of F170V, S183I, and V185L (EU numbering), and L2 includes substitutions of L135F (EU numbering). In some embodiments, L2 is derived from the lambda light chain. In some embodiments, L2 is derived from the kappa light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain includes substitutions of L234A and L235A (EU numbering). In some embodiments, each subunit of the Fc domain includes substitutions of M428L and N434S (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0117] In some embodiments, the heterodimer bispecific antibody comprises i) a first light chain (L1) containing VL1 and L1-CL, ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain, iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain, and iv) a second light chain (L2) containing VL2 and L2-CL, where H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), with H2 including substitutions at positions 126 and 220 (EU numbering) and L2 including substitutions at positions 124 and 214 (EU numbering). In some embodiments, L2 is derived from a lambda light chain. In some embodiments, H2 includes substitutions at the F126 and C220 (EU numbering) positions, and L2 includes substitutions at the E124 and C214 (EU numbering) positions. In some embodiments, H2 includes F126C and C220S substitutions (EU numbering), and L2 includes E124C and C214S substitutions (EU numbering). In some embodiments, L2 is derived from the kappa light chain. In some embodiments, H2 includes substitutions at the F126 and C220 (EU numbering) positions, and L2 includes substitutions at the Q124 and C214 (EU numbering) positions. In some embodiments, H2 includes F126C and C220S substitutions (EU numbering), and L2 includes Q124C and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0118] In some embodiments, the heterodimer bispecific antibody comprises i) a first light chain (L1) containing VL1 and L1-CL, ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain, iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain, and iv) a second light chain (L2) containing VL2 and L2-CL, where H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), with H2 including substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and L2 including substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, L2 is derived from the lambda light chain. In some embodiments, H2 includes substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and L2 includes substitutions at positions E124, L135, and C214 (EU numbering). In some embodiments, H2 includes substitutions at F126C, F170I, S183L, V185L, and C220S (EU numbering), and L2 includes substitutions at E124C, L135F, and C214S (EU numbering). In some embodiments, L2 is derived from the kappa light chain. In some embodiments, H2 includes substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and L2 includes substitutions at positions Q124, L135, and C214 (EU numbering). In some embodiments, H2 includes the substitutions F126C, F170I, S183L, V185L, and C220S (EU numbering), and L2 includes the substitutions Q124C, L135F, and C214S (EU numbering). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain includes the substitutions L234A and L235A (EU numbering). In some embodiments, each subunit of the Fc domain includes the substitutions M428L and N434S (EU numbering).In some embodiments, each subunit of the Fc domain includes the M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0119] In some embodiments, the heterodimer bispecific antibody comprises i) a first light chain (L1) containing VL1 and L1-CL, ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain, iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain, and iv) a second light chain (L2) containing VL2 and L2-CL, where H1 and H2 and L2 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), wherein H2 includes substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and L2 includes substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, L2 is derived from a lambda light chain. In some embodiments, H2 includes substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and L2 includes substitutions at positions E124, L135, and C214 (EU numbering). In some embodiments, H2 includes substitutions (EU numbering) for F126C, F170V, S183I, V185L, and C220S, and L2 includes substitutions (EU numbering) for E124C, L135F, and C214S. In some embodiments, L2 is derived from the kappa light chain. In some embodiments, H2 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L2 includes substitutions at the positions of Q124, L135, and C214 (EU numbering). In some embodiments, H2 includes substitutions (EU numbering) for F126C, F170V, S183I, V185L, and C220S, and L2 includes substitutions (EU numbering) for Q124C, L135F, and C214S. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering).In some embodiments, each subunit of the Fc domain includes the M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain includes the M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0120] In some embodiments, a multispecific construct is provided comprising two anti-IL-13 antibody moieties that are scFv ("anti-IL-13 scFv1" and "anti-IL-13 scFv2", e.g., either of the anti-IL-13 scFv described herein), and a second antibody moiety that is a full-length antibody that specifically binds to a second target antigen (e.g., TSLP), wherein anti-IL-13 scFv1 is fused to the C-terminus of the first heavy chain of the second antibody moiety to form a first fusion polypeptide, and anti-IL-13 scFv2 is fused to the C-terminus of the second heavy chain of the second antibody moiety to form a second fusion polypeptide, and anti-IL-13 scFv1 and anti-IL-13 Each scFv2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72. In some embodiments, anti-IL-13 scFv1 and anti-IL-13 scFv2 each comprise VH containing the amino acid sequence of SEQ ID NO: 65 and VL containing the amino acid sequence of SEQ ID NO: 69.

[0121] In some embodiments, a multispecific construct is provided comprising two anti-IL-13 antibody moieties that are scFv ("anti-IL-13 scFv1" and "anti-IL-13 scFv2", e.g., any of the anti-IL-13 scFv described herein), two second antibody moieties that are Fab ("Fab1" and "Fab2") that specifically bind to a second target antigen (e.g., TSLP), and an Fc domain, wherein the multispecific construct comprises: i) a first polypeptide comprising VL1-(L1-CL) from N' to C', ii) a second polypeptide comprising a first subunit of the Fc domain of VH1-(H1-CH1)-any linker-anti-IL-13 scFv1-any linker-Fc domain from N' to C', and iii) VH2-(H2-CH1)-any linker-anti-IL-13 A third polypeptide comprising scFv2-any linker-Fc domain second subunit, and iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C', where VL1-(L1-CL) and VH1-(H1-CH1) form Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form Fab2, and anti-IL-13 scFv1 and anti-IL-13 scFv2 each comprise (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 72. In some embodiments, anti-IL-13 scFv1 and anti-IL-13 scFv2 each include VH containing the amino acid sequence of SEQ ID NO: 65 and VL containing the amino acid sequence of SEQ ID NO: 69.

[0122] In some embodiments, a multispecific construct is provided comprising a first antibody moiety which is a full-length anti-IL-13 antibody (e.g., any of the full-length anti-IL-13 antibodies described herein), and two second antibody moieties which are scFvs ("scFv1" and "scFv2") that specifically bind to a second target antigen (e.g., TSLP), wherein scFv1 is fused to the C-terminus of the first heavy chain of the full-length anti-IL-13 antibody to form a first fusion polypeptide, and scFv2 is fused to the C-terminus of the full-length anti-IL-13 antibody A second heavy chain is fused to the C-terminus to form a second fusion polypeptide, and the full-length anti-IL-13 antibody comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72. In some embodiments, the full-length anti-IL-13 antibody comprises VH containing the amino acid sequence of SEQ ID NO: 65, and VL containing the amino acid sequence of SEQ ID NO: 69. In some embodiments, the full-length anti-IL-13 antibody comprises two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197. In some embodiments, the full-length anti-IL-13 antibody comprises two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197.

[0123] In some embodiments, the Fab consists of two anti-IL-13 antibody moieties ("anti-IL-13 Fab1" and "anti-IL-13 Fab2", for example, the anti-IL-13 antibody moieties described herein). A multispecific construct is provided comprising: one of Fabs; two second antibody moieties ("scFv1" and "scFv2") which are scFvs that specifically bind to a second target antigen (e.g., TSLP); and an Fc domain, wherein the multispecific construct comprises: i) a first polypeptide comprising VL1-(L1-CL) from N' to C'; ii) a second polypeptide comprising a first subunit of VH1-(H1-CH1)-any linker-scFv1-any linker-Fc domain from N' to C'; iii) a third polypeptide comprising a second subunit of VH2-(H2-CH1)-any linker-scFv2-any linker-Fc domain from N' to C'; and iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C', where VH1-(H1-CH1) and VL1-(L1-CL) are anti-IL-13 Fab1 is formed, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2, and anti-IL-13 Fab1 and anti-IL-13 Fab2 each include (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, and (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72. In some embodiments, anti-IL-13 Fab1 and anti-IL-13 Fab2 each include VH containing the amino acid sequence of SEQ ID NO: 65, and VL containing the amino acid sequence of SEQ ID NO: 69.

[0124] In some embodiments, the Fab consists of two anti-IL-13 antibody moieties ("anti-IL-13 Fab1" and "anti-IL-13 Fab2", for example, the anti-IL-13 described herein). A multispecific construct is provided comprising one of the following: a first antibody moiety (Fab), and a second antibody moiety which is a full-length antibody that specifically binds to a second target antigen (e.g., TSLP), wherein the multispecific construct comprises: i) a first polypeptide comprising a first light chain of the second antibody moiety; ii) a second polypeptide comprising a first heavy chain of the second antibody moiety - an optional linker - VH1-(H1-CH1) from N' to C'; iii) a third polypeptide comprising a second heavy chain of the second antibody moiety - an optional linker - VH2-(H2-CH1) from N' to C'; iv) a fourth polypeptide comprising a second light chain of the second antibody moiety; v) a fifth polypeptide comprising VL1-(L1-CL) from N' to C'; and vi) a sixth polypeptide comprising VL2-(L2-CL) from N' to C', wherein VL1-(L1-CL) and VH1-(H1-CH1) are anti-IL-13 Fab1 is formed, and VL2-(L2-CL) and VH2-(H2-CH1) form anti-IL-13 Fab2, and anti-IL-13 Fab1 and anti-IL-13 Fab2 each include (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72. In some embodiments, anti-IL-13 Fab1 and anti-IL-13 Fab2 each include VH containing the amino acid sequence of SEQ ID NO: 65, and VL containing the amino acid sequence of SEQ ID NO: 69.In some embodiments, anti-IL-13 Fab1 comprises H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL), where anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL), where (a) H1 and H2 each contain substitutions of F170I, S183L, and V185L, and L1 and L2 each contain substitutions of L135F, (b) H1 and H2 each contain substitutions of F170V, S183I, and V185L, and L1 and L2 each contain substitutions of L135F, (c) H1 and H2 each contain substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 (d) H1 and H2 each contain the E124C (or Q124C), L135F, and C214S substitutions, and L1 and L2 each contain the F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C), L135F, and C214S substitutions, or (e) H1 and H2 each contain the F126C and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C) and C214S substitutions, with the amino acid positions following EU numbering. In some embodiments, the light chain of the full-length antibody is derived from the kappa light chain.

[0125] In some embodiments, a multispecific construct is provided comprising a first antibody moiety which is a full-length anti-IL-13 antibody (e.g., any of the full-length anti-IL-13 antibodies described herein), and two second antibody moieties which are Fabs ("Fab1" and "Fab2") that specifically bind to a second target antigen (e.g., TSLP), wherein the multispecific construct comprises: i) a first polypeptide comprising a first light chain (L1) of a full-length anti-IL-13 antibody; ii) a second polypeptide comprising a first heavy chain (H1) of a full-length anti-IL-13 antibody - an optional linker - VH3-(H3-CH1) from N' to C'; iii) a third polypeptide comprising a second heavy chain (H2) of a full-length anti-IL-13 antibody - an optional linker - VH4-(H4-CH1) from N' to C'; and iv) a second light chain (L The anti-IL-13 full-length antibody comprises (i) a fourth polypeptide containing the amino acid sequence of SEQ ID NO: 6, (ii) a fifth polypeptide containing VL3-(L3-CL) from N' to C', and (vi) a sixth polypeptide containing VL4-(L4-CL) from N' to C', where VL3-(L3-CL) and VH3-(H3-CH1) form Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form Fab2, and (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 60, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72. In some embodiments, the full-length anti-IL-13 antibody comprises VH, which contains the amino acid sequence of SEQ ID NO: 65, and VL, which contains the amino acid sequence of SEQ ID NO: 69.In some embodiments, (a) H1 and H2 each include substitutions of F170I, S183L, and V185L, and L1 and L2 each include substitutions of L135F; (b) H1 and H2 each include substitutions of F170V, S183I, and V185L, and L1 and L2 each include substitutions of L135F; (c) H1 and H2 each include substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and L2 each include substitutions of E124C (or Q124 (c) containing the substitutions of L135F and C214S, (d) H1 and H2 each containing the substitutions of F126C, F170V, S183I, V185L and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C), L135F and C214S, or (e) H1 and H2 each containing the substitutions of F126C and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C) and C214S, with amino acid positions following EU numbering.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; ii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 209, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 210, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iv) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 211, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206; v) two light chains, each containing the amino acid sequence of SEQ ID NO: 212 The configuration includes a heavy chain and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vi) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 213, and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; viiii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 101, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; or ix) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 123, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206. In some embodiments, L3-CL and L4-CL are derived from kappa light chains.

[0126] In some embodiments, the Fab consists of two anti-IL-13 antibody moieties ("anti-IL-13 Fab1" and "anti-IL-13 Fab2", for example, the anti-IL-13 antibody moieties described herein). A multispecific construct is provided comprising either Fab, and a second antibody moiety which is a full-length antibody that specifically binds to a second target antigen (e.g., TSLP), wherein the multispecific construct comprises: i) a first polypeptide comprising VL1-(L1-CL) from N' to C'; ii) a second polypeptide comprising VH1-(H1-CH1)-any linker-first heavy chain of the second antibody moiety from N' to C'; iii) a third polypeptide comprising VH2-(H2-CH1)-any linker-second heavy chain of the second antibody moiety from N' to C'; iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C'; v) a fifth polypeptide comprising the first light chain of the second antibody moiety; and vi) a sixth polypeptide comprising the second light chain of the second antibody moiety, wherein VL1-(L1-CL) and VH1-(H1-CH1) are anti-IL-13 Fab1 is formed, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2, where anti-IL-13 Fab1 and anti-IL-13 Fab2 each include (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, and (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72. In some embodiments, anti-IL-13 Fab1 and anti-IL-13 Fab2 each include VH containing the amino acid sequence of SEQ ID NO: 65, and VL containing the amino acid sequence of SEQ ID NO: 69.In some embodiments, anti-IL-13 Fab1 comprises H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL), where anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL), where (a) H1 and H2 each contain substitutions of F170I, S183L, and V185L, and L1 and L2 each contain substitutions of L135F, (b) H1 and H2 each contain substitutions of F170V, S183I, and V185L, and L1 and L2 each contain substitutions of L135F, (c) H1 and H2 each contain substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and (d) L2 each contains the E124C (or Q124C), L135F, and C214S substitutions, or (e) H1 and H2 each contain the F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C), L135F, and C214S substitutions, or (f) H1 ​​and H2 each contain the F126C and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C) and C214S substitutions, with the amino acid positions following EU numbering. In some embodiments, the light chain of the full-length antibody is derived from the kappa light chain.

[0127] In some embodiments, a multispecific construct is provided comprising a first antibody moiety which is a full-length anti-IL-13 antibody (e.g., any of the full-length anti-IL-13 antibodies described herein), and two second antibody moieties ("Fab1" and "Fab2") which are Fabs that specifically bind to a second target antigen (e.g., TSLP), wherein the multispecific construct comprises: i) a first polypeptide comprising VL3-(L3-CL) from N' to C', ii) a second polypeptide comprising a first heavy chain (H1) of a VH3-(H3-CH1)-any linker-full-length anti-IL-13 antibody from N' to C', iii) a third polypeptide comprising a second heavy chain (H2) of a VH4-(H4-CH1)-any linker-full-length anti-IL-13 antibody from N' to C', and iv) a polyspecific construct comprising VL4-(L4-CL) from N' to C' The fourth polypeptide comprises v) a fifth polypeptide containing the first light chain (L1) of the full-length anti-IL-13 antibody from N' to C', and vi) a sixth polypeptide containing the second light chain (L2) of the full-length anti-IL-13 antibody from N' to C', where VL3-(L3-CL) and VH3-(H3-CH1) form Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form Fab2, and the full-length anti-IL-13 antibody comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, and (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72. In some embodiments, the full-length anti-IL-13 antibody comprises VH, which contains the amino acid sequence of SEQ ID NO: 65, and VL, which contains the amino acid sequence of SEQ ID NO: 69.In some embodiments, (a) H1 and H2 each include substitutions of F170I, S183L, and V185L, and L1 and L2 each include substitutions of L135F; (b) H1 and H2 each include substitutions of F170V, S183I, and V185L, and L1 and L2 each include substitutions of L135F; (c) H1 and H2 each include substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and L2 each include substitutions of E124C (or Q124 (c) containing the substitutions of L135F and C214S, (d) H1 and H2 each containing the substitutions of F126C, F170V, S183I, V185L and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C), L135F and C214S, or (e) H1 and H2 each containing the substitutions of F126C and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C) and C214S, with amino acid positions following EU numbering.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; ii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 209, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 210, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iv) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 211, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206; v) two light chains, each containing the amino acid sequence of SEQ ID NO: 212 The configuration includes a heavy chain and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vi) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 213, and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; viiii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 101, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; or ix) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 123, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206. In some embodiments, L3-CL and L4-CL are derived from kappa light chains.

[0128] In some embodiments, the heterodimer bispecific antibody comprises: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL, where H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second target antigen (e.g., TSL). A second antibody moiety specifically binds to P), and VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68; VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72; H1 includes substitutions at positions 170, 183, and 185 (EU numbering); and L1 includes a substitution at position 135 (EU numbering). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity with SEQ ID NO: 65 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 includes the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity with SEQ ID NO: 69 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, and VL1 includes the amino acid sequence of SEQ ID NO: 69. In some embodiments, H1 includes substitutions at the positions of F170, S183, and V185 (EU numbering), and L1 includes a substitution at the position of L135 (EU numbering). In some embodiments, H1 includes substitutions F170I, S183L, and V185L (EU numbering), and L1 includes substitutions L135F (EU numbering). In some embodiments, L1 is derived from the lambda light chain.In some embodiments, L1 is derived from the kappa light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering). In some embodiments, H1 includes the amino acid sequence of SEQ ID NO: 138 or SEQ ID NO: 139, or a variant thereof having at least about 80% (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO: 138 or SEQ ID NO: 139, and L1 includes the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, or a variant thereof having at least about 80% (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO: 122 or SEQ ID NO: 207.

[0129] In some embodiments, the heterodimer bispecific antibody comprises: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL, where H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 specifically bind to a second target antigen (e.g., TSLP). The antibody moiety is formed by two such moieties, where VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, and where VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, and where H1 includes substitutions at positions 170, 183, and 185 (EU numbering), and L1 includes a substitution at position 135 (EU numbering). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 includes the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, and VL1 includes the amino acid sequence of SEQ ID NO: 69. In some embodiments, H1 includes substitutions at the positions of F170, S183, and V185 (EU numbering), and L1 includes a substitution at the position of L135 (EU numbering). In some embodiments, H1 includes substitutions for F170V, S183I, and V185L (EU numbering), and L1 includes substitutions for L135F (EU numbering).In some embodiments, L1 is derived from a lambda light chain. In some embodiments, L1 is derived from a kappa light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering). In some embodiments, H1 includes the amino acid sequence of SEQ ID NO: 140 or SEQ ID NO: 141, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to SEQ ID NO: 140 or SEQ ID NO: 141, and L1 includes the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to SEQ ID NO: 122 or SEQ ID NO: 207. In some embodiments, H1 includes the amino acid sequence of SEQ ID NO: 140 or SEQ ID NO: 141, and L1 includes the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207.

[0130] In some embodiments, the heterodimer bispecific antibody comprises: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL, where H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 are specific to a second target antigen (e.g., TSLP). A second antibody moiety is formed that binds to, where VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, and where VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, with H1 containing substitutions at positions 126 and 220 (EU numbering), and L1 containing substitutions at positions 124 and 214 (EU numbering). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 comprises the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, and VL1 comprises the amino acid sequence of SEQ ID NO: 69. In some embodiments, L1 is derived from the lambda light chain. In some embodiments, H1 includes substitutions at positions F126 and C220 (EU numbering), and L1 includes substitutions at positions E124 and C214 (EU numbering).In some embodiments, H1 includes F126C and C220S substitutions (EU numbering), and L1 includes E124C and C214S substitutions (EU numbering). In some embodiments, L1 is derived from the kappa light chain. In some embodiments, H1 includes substitutions at the positions of F126 and C220 (EU numbering), and L1 includes substitutions at the positions of Q124 and C214 (EU numbering). In some embodiments, H1 includes F126C and C220S substitutions (EU numbering), and L1 includes Q124C and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain includes T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain includes T366W substitution (EU numbering). In some embodiments, H1 includes the amino acid sequence of SEQ ID NO: 200 or SEQ ID NO: 201, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to SEQ ID NO: 200 or SEQ ID NO: 201, and L1 includes the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to SEQ ID NO: 121 or SEQ ID NO: 206.In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO: 200 or SEQ ID NO: 201, and L1 comprises the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206.

[0131] In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. Herein, H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), where VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68. Furthermore, VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, where H1 includes substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and L1 includes substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 comprises the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, and VL1 comprises the amino acid sequence of SEQ ID NO: 69. In some embodiments, L1 is derived from the lambda light chain. In some embodiments, H1 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L1 includes substitutions at the positions of E124, L135, and C214 (EU numbering). In some embodiments, H1 includes substitutions at the positions of F126C, F170I, S183L, V185L, and C220S (EU numbering), and L1 includes substitutions at the positions of E124C, L135F, and C214S (EU numbering). In some embodiments, L1 is derived from the kappa light chain. In some embodiments, H1 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L1 includes substitutions at the positions of Q124, L135, and C214 (EU numbering). In some embodiments, H1 includes substitutions for F126C, F170I, S183L, V185L, and C220S (EU numbering), and L1 includes substitutions for Q124C, L135F, and C214S (EU numbering).In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering). In some embodiments, H1 includes the amino acid sequence of SEQ ID NO: 126 or SEQ ID NO: 127, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to SEQ ID NO: 126 or SEQ ID NO: 127, and L1 includes the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to SEQ ID NO: 120 or SEQ ID NO: 208. In some embodiments, H1 includes the amino acid sequence of SEQ ID NO: 126 or SEQ ID NO: 127, and L1 includes the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208.

[0132] In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. Herein, H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), where VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68. Furthermore, VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, H1 includes substitutions at positions 234, 235, 428, 434, 126, 170, 183, 185, and 220 (EU numbering), and L1 includes substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 comprises the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, and VL1 comprises the amino acid sequence of SEQ ID NO: 69. In some embodiments, L1 is derived from the lambda light chain. In some embodiments, H1 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L1 includes substitutions at the positions of E124, L135, and C214 (EU numbering). In some embodiments, H1 includes substitutions at the positions of F126C, F170V, S183I, V185L, and C220S (EU numbering), and L1 includes substitutions at the positions of E124C, L135F, and C214S (EU numbering). In some embodiments, L1 is derived from the kappa light chain. In some embodiments, H1 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L1 includes substitutions at the positions of Q124, L135, and C214 (EU numbering). In some embodiments, H1 includes substitutions for F126C, F170V, S183I, V185L, and C220S (EU numbering), and L1 includes substitutions for Q124C, L135F, and C214S (EU numbering).In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering). In some embodiments, H1 includes the amino acid sequence of SEQ ID NO: 128 or SEQ ID NO: 129, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to SEQ ID NO: 128 or SEQ ID NO: 129, and L1 includes the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to SEQ ID NO: 120 or SEQ ID NO: 208. In some embodiments, H1 includes the amino acid sequence of SEQ ID NO: 128 or SEQ ID NO: 129, and L1 includes the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208.

[0133] In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. Herein, H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), where VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68. Furthermore, VL1 includes (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, where H2 includes substitutions at positions 170, 183, and 185 (EU numbering), and L2 includes a substitution at position 135 (EU numbering). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 includes the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, and VL1 comprises the amino acid sequence of SEQ ID NO: 69. In some embodiments, H2 comprises substitutions at the F170, S183, and V185 (EU numbering) positions, and L2 comprises a substitution at the L135 (EU numbering) position. In some embodiments, H2 comprises the F170I, S183L, and V185L substitutions (EU numbering), and L2 comprises the L135F substitution (EU numbering). In some embodiments, L2 is derived from the lambda light chain. In some embodiments, L2 is derived from the kappa light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0134] In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. Here, H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), where VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68. Furthermore, VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, wherein H2 includes substitutions at positions 170, 183, and 185 (EU numbering), and L2 includes a substitution at position 135 (EU numbering). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 includes the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, and VL1 includes the amino acid sequence of SEQ ID NO: 69. In some embodiments, H2 includes substitutions at positions F170, S183, and V185 (EU numbering), and L2 includes a substitution at position L135 (EU numbering). In some embodiments, H2 includes F170V, S183I, and V185L substitutions (EU numbering), and L2 includes L135F substitution (EU numbering). In some embodiments, L2 is derived from the lambda light chain. In some embodiments, L2 is derived from the kappa light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0135] In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. Here, H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), where VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68. Furthermore, VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, wherein H2 includes substitutions at positions 126 and 220 (EU numbering), and L2 includes substitutions at positions 124 and 214 (EU numbering). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 comprises the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, and VL1 comprises the amino acid sequence of SEQ ID NO: 69. In some embodiments, L2 is derived from the lambda light chain. In some embodiments, H2 includes substitutions at positions F126 and C220 (EU numbering), and L2 includes substitutions at positions E124 and C214 (EU numbering). In some embodiments, H2 includes F126C and C220S substitutions (EU numbering), and L2 includes E124C and C214S substitutions (EU numbering). In some embodiments, L2 is derived from the kappa light chain. In some embodiments, H2 includes substitutions at the positions of F126 and C220 (EU numbering), and L2 includes substitutions at the positions of Q124 and C214 (EU numbering). In some embodiments, H2 includes F126C and C220S substitutions (EU numbering), and L2 includes Q124C and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1.In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain includes T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain includes T366W substitution (EU numbering).

[0136] In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. Here, H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), where VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68. Furthermore, VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, wherein H2 includes substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and L2 includes substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 comprises the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, and VL1 comprises the amino acid sequence of SEQ ID NO: 69. In some embodiments, L2 is derived from the lambda light chain. In some embodiments, H2 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L2 includes substitutions at the positions of E124, L135, and C214 (EU numbering). In some embodiments, H2 includes substitutions at the positions of F126C, F170I, S183L, V185L, and C220S (EU numbering), and L2 includes substitutions at the positions of E124C, L135F, and C214S (EU numbering). In some embodiments, L2 is derived from the kappa light chain. In some embodiments, H2 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L2 includes substitutions at the positions of Q124, L135, and C214 (EU numbering). In some embodiments, H2 includes substitutions (EU numbering) for F126C, F170I, S183L, V185L, and C220S, and L2 includes substitutions (EU numbering) for Q124C, L135F, and C214S.In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0137] In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) containing VL1 and L1-CL; ii) a first heavy chain (H1) containing VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) containing VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) containing VL2 and L2-CL. Here, H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP), where VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68. Furthermore, VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, wherein H2 includes substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and L2 includes substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 comprises the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO: 65, and VL1 comprises the amino acid sequence of SEQ ID NO: 69. In some embodiments, L2 is derived from the lambda light chain. In some embodiments, H2 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L2 includes substitutions at the positions of E124, L135, and C214 (EU numbering). In some embodiments, H2 includes substitutions at the positions of F126C, F170V, S183I, V185L, and C220S (EU numbering), and L2 includes substitutions at the positions of E124C, L135F, and C214S (EU numbering). In some embodiments, L2 is derived from the kappa light chain. In some embodiments, H2 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L2 includes substitutions at the positions of Q124, L135, and C214 (EU numbering). In some embodiments, H2 includes substitutions for F126C, F170V, S183I, V185L, and C220S (EU numbering), and L2 includes substitutions for Q124C, L135F, and C214S (EU numbering).In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering).

[0138] In some embodiments, a multispecific construct is provided comprising two first antibody moieties ("anti-IL-13 scFv1" and "anti-IL-13 scFv2") which are anti-IL-13 scFv, and a second antibody moiety ("anti-TSLP full-length antibody") which is a full-length antibody that specifically binds to TSLP, wherein anti-IL-13 scFv1 is fused to the C-terminus of the first heavy chain of the anti-TSLP full-length antibody via an optional linker to form a first fusion polypeptide, and anti-IL-13 scFv2 is fused to the C-terminus of the second heavy chain of the anti-TSLP full-length antibody via an optional linker to form a second fusion polypeptide, and anti-IL-13 scFv1 and anti-IL-13 Each scFv2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72. The full-length anti-TSLP antibody comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26. In some embodiments, anti-IL-13 scFv1 and anti-IL-13 scFv2 each include a VH containing the amino acid sequence of SEQ ID NO: 65 and a VL containing the amino acid sequence of SEQ ID NO: 69. In some embodiments, the full-length anti-TSLP antibody includes (a) a VH containing the amino acid sequence of SEQ ID NO: 63 and a VL containing the amino acid sequence of SEQ ID NO: 53, (b) a VH containing the amino acid sequence of SEQ ID NO: 63 and a VL containing the amino acid sequence of SEQ ID NO: 54, (c) a VH containing the amino acid sequence of SEQ ID NO: 188 and a VL containing the amino acid sequence of SEQ ID NO: 189, (d) a VH containing the amino acid sequence of SEQ ID NO: 188 and a VL containing the amino acid sequence of SEQ ID NO: 190, or (e) a VH containing the amino acid sequence of SEQ ID NO: 228 and a VL containing the amino acid sequence of SEQ ID NO: 190.In some embodiments, anti-IL-13 scFv1 and anti-IL-13 scFv2 each contain the amino acid sequence of SEQ ID NO: 108. In some embodiments, the full-length anti-TSLP antibody contains i) a heavy chain containing the amino acid sequence of SEQ ID NO: 104 and a light chain containing the amino acid sequence of SEQ ID NO: 103, or ii) a heavy chain containing the amino acid sequence of SEQ ID NO: 105 and a light chain containing the amino acid sequence of SEQ ID NO: 103. In some embodiments, the linker contains GG and one of the amino acid sequences from SEQ ID NO: 98 to SEQ ID NO: 99. In some embodiments, the full-length anti-TSLP antibody contains two light chains, each containing the amino acid sequence of SEQ ID NO: 103, and two heavy chains, each containing the amino acid sequence of SEQ ID NO: 105, and the first and second fusion polypeptides each contain the amino acid sequence of SEQ ID NO: 113.

[0139] In some embodiments, a multispecific construct is provided comprising two anti-IL-13 antibody moieties that are scFv ("anti-IL-13 scFv1" and "anti-IL-13 scFv2"), two second antibody moieties that are Fab that specifically bind to TSLP ("anti-TSLP Fab1" and "anti-TSLP Fab2"), and an Fc domain, wherein the multispecific construct comprises: i) a first polypeptide comprising VL1-(L1-CL) from N' to C', ii) a second polypeptide comprising a first subunit of the anti-IL-13 scFv1-any linker-Fc domain from N' to C', and iii) VH2-(H2-CH1)-any linker-anti-IL-13 A third polypeptide comprising scFv2-any linker-Fc domain second subunit, and iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C', where VL1-(L1-CL) and VH1-(H1-CH1) form anti-TSLP Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-TSLP Fab2, where anti-IL-13 scFv1 and anti-IL-13 scFv2 each comprise (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 72, thus forming anti-TSLP Fab1 and anti-TSLP Each Fab2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26.In some embodiments, anti-IL-13 scFv1 and anti-IL-13 scFv2 each include a VH containing the amino acid sequence of SEQ ID NO: 65 and a VL containing the amino acid sequence of SEQ ID NO: 69. In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each include (a) a VH containing the amino acid sequence of SEQ ID NO: 63 and a VL containing the amino acid sequence of SEQ ID NO: 53, (b) a VH containing the amino acid sequence of SEQ ID NO: 63 and a VL containing the amino acid sequence of SEQ ID NO: 54, (c) a VH containing the amino acid sequence of SEQ ID NO: 188 and a VL containing the amino acid sequence of SEQ ID NO: 189, (d) a VH containing the amino acid sequence of SEQ ID NO: 188 and a VL containing the amino acid sequence of SEQ ID NO: 190, or (e) a VH containing the amino acid sequence of SEQ ID NO: 228 and a VL containing the amino acid sequence of SEQ ID NO: 190. In some embodiments, anti-IL-13 scFv1 and anti-IL-13 scFv2 each include the amino acid sequence of SEQ ID NO: 108. In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each comprise a first polypeptide containing the amino acid sequence of SEQ ID NO: 109 and a second polypeptide containing the amino acid sequence of SEQ ID NO: 103. In some embodiments, the linker comprises an amino acid sequence independently selected from GG and any one of SEQ ID NOs: 98 to 99. In some embodiments, the first polypeptide and the fourth polypeptide each comprise the amino acid sequence of SEQ ID NO: 103, and the second polypeptide and the third polypeptide each comprise the amino acid sequence of SEQ ID NO: 110.

[0140] In some embodiments, a multispecific construct is provided comprising a first antibody moiety which is a full-length anti-IL-13 antibody, and two second antibody moieties ("anti-TSLP scFv1" and "anti-TSLP scFv2") which are scFvs that specifically bind to TSLP, wherein anti-TSLP scFv1 fuses to the C-terminus of the first heavy chain of the full-length anti-IL-13 antibody via an optional linker to form a first fusion polypeptide, and anti-TSLP scFv2 fuses to the C-terminus of the second heavy chain of the full-length anti-IL-13 antibody via an optional linker to form a second fusion polypeptide, the full-length anti-IL-13 antibody comprising (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, and herein, anti-TSLP scFv1 and anti-TSLP Each of the scFv2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26. In some embodiments, the full-length anti-IL-13 antibody comprises VH containing the amino acid sequence of SEQ ID NO: 65, and VL containing the amino acid sequence of SEQ ID NO: 69. In some embodiments, anti-TSLP scFv1 and anti-TSLP scFv2 each comprise (a) VH containing the amino acid sequence of SEQ ID NO: 63 and VL containing the amino acid sequence of SEQ ID NO: 53, (b) VH containing the amino acid sequence of SEQ ID NO: 63 and VL containing the amino acid sequence of SEQ ID NO: 54, (c) VH containing the amino acid sequence of SEQ ID NO: 188 and VL containing the amino acid sequence of SEQ ID NO: 189, (d) VH containing the amino acid sequence of SEQ ID NO: 188 and VL containing the amino acid sequence of SEQ ID NO: 190, or (e) VH containing the amino acid sequence of SEQ ID NO: 228 and VL containing the amino acid sequence of SEQ ID NO: 190. In some embodiments, the full-length anti-IL-13 antibody comprises two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197. In some embodiments, anti-TSLP scFv1 and anti-TSLP scFv2 each contain one of the amino acid sequences of SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 226, SEQ ID NO: 227, and SEQ ID NO: 229. In some embodiments, the linker contains GG and one of the amino acid sequences of SEQ ID NOs. 98 to 99. In some embodiments, the full-length anti-IL-13 antibody contains two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, where the first and second fusion polypeptides each contain the amino acid sequence of SEQ ID NO: 111. In some embodiments, the full-length anti-IL-13 antibody contains two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, where the first and second fusion polypeptides each contain one of the amino acid sequences of SEQ ID NOs. 220 to 223.

[0141] In some embodiments, a multispecific construct is provided comprising two anti-IL-13 Fabs ("anti-IL-13 Fab1" and "anti-IL-13 Fab2"), two second antibody moieties ("anti-TSLP scFv1" and "anti-TSLP scFv2") which are scFvs that specifically bind to TSLP, and an Fc domain, wherein the multispecific construct comprises: i) a first polypeptide comprising VL1-(L1-CL) from N' to C', ii) a second polypeptide comprising a first subunit of the Fc domain, VH1-(H1-CH1)-optional linker-anti-TSLP scFv1-optional linker-Fc domain, and iii) VH2-(H2-CH1)-optional linker-anti-TSLP A third polypeptide comprising scFv2-any linker-Fc domain second subunit, and iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C', where VH1-(H1-CH1) and VL1-(L1-CL) form anti-IL-13 Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2, where anti-IL-13 Fab1 and anti-IL-13 Fab2 each comprise (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 72, and where, anti-TSLP scFv1 and anti-TSLP scFv2 each include (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26.In some embodiments, anti-IL-13 Fab1 and anti-IL-13 Fab2 each include a VH containing the amino acid sequence of SEQ ID NO: 65 and a VL containing the amino acid sequence of SEQ ID NO: 69. In some embodiments, anti-TSLP scFv1 and anti-TSLP scFv2 each include (a) a first polypeptide containing the amino acid sequence of SEQ ID NO: 63 and a second polypeptide containing the amino acid sequence of SEQ ID NO: 53, (b) a VH containing the amino acid sequence of SEQ ID NO: 63 and a VL containing the amino acid sequence of SEQ ID NO: 54, (c) a VH containing the amino acid sequence of SEQ ID NO: 188 and a VL containing the amino acid sequence of SEQ ID NO: 189, (d) a VH containing the amino acid sequence of SEQ ID NO: 188 and a VL containing the amino acid sequence of SEQ ID NO: 190, or (e) a VH containing the amino acid sequence of SEQ ID NO: 228 and a VL containing the amino acid sequence of SEQ ID NO: 190. In some embodiments, anti-IL-13 Fab1 and anti-IL-13 Fab2 each comprise a first polypeptide containing the amino acid sequence of SEQ ID NO: 124 and a second polypeptide containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197. In some embodiments, anti-TSLP scFv1 and anti-TSLP scFv2 each comprise one of the amino acid sequences of SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 226, SEQ ID NO: 227, and SEQ ID NO: 229. In some embodiments, the linker comprises an amino acid sequence independently selected from GG and one of SEQ ID NOs. 98 to 99. In some embodiments, the first polypeptide and the fourth polypeptide each comprise the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, and the second polypeptide and the third polypeptide each comprise the amino acid sequence of SEQ ID NO: 112.

[0142] In some embodiments, the Fab consists of two anti-IL-13 antibody portions ("anti-IL-13 Fab1" and "anti-IL-13 Fab1"). A multispecific construct is provided comprising Fab2) and a second antibody moiety ("anti-TSLP full-length antibody") which is a full-length antibody that specifically binds to TSLP, the multispecific construct comprising i) a first polypeptide comprising a first light chain of the anti-TSLP full-length antibody, ii) a second polypeptide comprising a first heavy chain of the anti-TSLP full-length antibody - an optional linker - VH1-(H1-CH1) from N' to C', iii) a third polypeptide comprising a second heavy chain of the anti-TSLP full-length antibody - an optional linker - VH2-(H2-CH1) from N' to C', iv) a fourth polypeptide comprising a second light chain of the anti-TSLP full-length antibody, v) a fifth polypeptide comprising VL1-(L1-CL) from N' to C', and vi) a sixth polypeptide comprising VL2-(L2-CL) from N' to C', wherein VL1-(L1-CL) and VH1-(H1-CH1) are anti-IL-13 Fab1 is formed, and VL2-(L2-CL) and VH2-(H2-CH1) form anti-IL-13 Fab2. Here, anti-IL-13 Fab1 and anti-IL-13 Fab2 each include (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72. Here, the full-length anti-TSLP antibody includes (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26.In some embodiments, anti-IL-13 Fab1 and anti-IL-13 Fab2 each include VH containing the amino acid sequence of SEQ ID NO: 65 and VL containing the amino acid sequence of SEQ ID NO: 69, and in some embodiments, the full-length anti-TSLP antibody includes (a) VH containing the amino acid sequence of SEQ ID NO: 63 and VL containing the amino acid sequence of SEQ ID NO: 53, (b) VH containing the amino acid sequence of SEQ ID NO: 63 and VL containing the amino acid sequence of SEQ ID NO: 54, (c) VH containing the amino acid sequence of SEQ ID NO: 188 and VL containing the amino acid sequence of SEQ ID NO: 189, (d) VH containing the amino acid sequence of SEQ ID NO: 188 and VL containing the amino acid sequence of SEQ ID NO: 190, or (e) VH containing the amino acid sequence of SEQ ID NO: 228 and VL containing the amino acid sequence of SEQ ID NO: 190. In some embodiments, anti-IL-13 Fab1 includes H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL), where anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL), wherein (a) H1 and H2 each contain substitutions of F170I, S183L, and V185L, and L1 and L2 each contain substitutions of L135F, (b) H1 and H2 each contain substitutions of F170V, S183I, and V185L, and L1 and L2 each contain substitutions of L135F, (c) H1 and H2 each contain substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 (d) H1 and H2 each contain the E124C (or Q124C), L135F, and C214S substitutions, and L1 and L2 each contain the F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C), L135F, and C214S substitutions, or (e) H1 and H2 each contain the F126C and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C) and C214S substitutions, with the amino acid positions following EU numbering. In some embodiments, the light chain of the full-length anti-TSLP antibody is derived from the kappa light chain.In some embodiments, the full-length anti-TSLP antibody comprises i) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 104, and a light chain containing the amino acid sequence of SEQ ID NO: 103, or ii) a heavy chain containing the amino acid sequence of SEQ ID NO: 105, and a light chain containing the amino acid sequence of SEQ ID NO: 103. In some embodiments, the linker comprises an amino acid sequence independently selected from GG and any one of SEQ ID NOs. 98 to 99.

[0143] In some embodiments, the antibody consists of a full-length antibody portion ("anti-IL-13 full-length antibody") and two second antibody portions ("anti-TSLP Fab1" and "anti-TSLP Fab1") which are Fabs that specifically bind to TSLP. A multispecific construct is provided comprising "Fab2"), where the multispecific construct comprises: i) a first polypeptide comprising the first light chain (L1) of the full-length anti-IL-13 antibody; ii) a second polypeptide comprising the first heavy chain (H1) of the full-length anti-IL-13 antibody - an optional linker - VH3-(H3-CH1) from N' to C'; iii) a third polypeptide comprising the second heavy chain (H2) of the full-length anti-IL-13 antibody - an optional linker - VH4-(H4-CH1) from N' to C'; iv) a fourth polypeptide comprising the second light chain (L2) of the full-length anti-IL-13 antibody; v) a fifth polypeptide comprising VL3-(L3-CL) from N' to C'; and vi) a sixth polypeptide comprising VL4-(L4-CL) from N' to C', where VL3-(L3-CL) and VH3-(H3-CH1) are anti-TSLP Fab1 is formed, and VH4-(H4-CH1) and VL4-(L4-CL) form anti-TSLP Fab2, and the full-length anti-IL-13 antibody comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, and herein, anti-TSLP Fab1 and anti-TSLP Each Fab2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26. In some embodiments, the full-length anti-IL-13 antibody comprises VH containing the amino acid sequence of SEQ ID NO: 65, and VL containing the amino acid sequence of SEQ ID NO: 69.In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each include (a) a VH containing the amino acid sequence of SEQ ID NO: 63 and a VL containing the amino acid sequence of SEQ ID NO: 53, (b) a VH containing the amino acid sequence of SEQ ID NO: 63 and a VL containing the amino acid sequence of SEQ ID NO: 54, (c) a VH containing the amino acid sequence of SEQ ID NO: 188 and a VL containing the amino acid sequence of SEQ ID NO: 189, (d) a VH containing the amino acid sequence of SEQ ID NO: 188 and a VL containing the amino acid sequence of SEQ ID NO: 190, or (e) a VH containing the amino acid sequence of SEQ ID NO: 228 and a VL containing the amino acid sequence of SEQ ID NO: 190. In some embodiments, (a) H1 and H2 each include substitutions of F170I, S183L, and V185L, and L1 and L2 each include substitutions of L135F; (b) H1 and H2 each include substitutions of F170V, S183I, and V185L, and L1 and L2 each include substitutions of L135F; (c) H1 and H2 each include substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and L2 each include substitutions of E124C (or Q124 (c) containing the substitutions of L135F and C214S, (d) H1 and H2 each containing the substitutions of F126C, F170V, S183I, V185L and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C), L135F and C214S, or (e) H1 and H2 each containing the substitutions of F126C and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C) and C214S, with amino acid positions following EU numbering.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; ii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 209, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 210, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iv) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 211, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206; v) two light chains, each containing the amino acid sequence of SEQ ID NO: 212 The configuration includes a heavy chain and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vi) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 213, and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; viiii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 101, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; or ix) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 123, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206. In some embodiments, L3-CL and L4-CL are derived from kappa light chains. In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each comprise a first polypeptide containing the amino acid sequence of SEQ ID NO: 109 and a second polypeptide containing the amino acid sequence of SEQ ID NO: 103. In some embodiments, the linker comprises an amino acid sequence independently selected from GG and any one of SEQ ID NOs: 98 to 99.

[0144] In some embodiments, there are two Fabs, which are anti-IL-13 antibody portions ("anti-IL-13 Fab1" and "anti-IL-13 Fab1"). A multispecific construct is provided comprising "Fab2"), and a second antibody moiety ("anti-TSLP full-length antibody") which is a full-length antibody that specifically binds to TSLP, wherein the multispecific construct comprises i) a first polypeptide comprising VL1-(L1-CL) from N' to C', ii) a second polypeptide comprising VH1-(H1-CH1)-any linker-first heavy chain of the anti-TSLP full-length antibody from N' to C', iii) a third polypeptide comprising VH2-(H2-CH1)-any linker-second heavy chain of the anti-TSLP full-length antibody from N' to C', iv) a fourth polypeptide comprising VL2-(L2-CL) from N' to C', v) a fifth polypeptide comprising a first light chain of the anti-TSLP full-length antibody, and vi) a sixth polypeptide comprising a second light chain of the anti-TSLP full-length antibody, wherein VL1-(L1-CL) and VH1-(H1-CH1) are anti-IL-13 Fab1 is formed, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2. Here, anti-IL-13 Fab1 and anti-IL-13 Fab2 each include (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, and here, the full-length anti-TSLP antibody includes (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, or (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26.In some embodiments, anti-IL-13 Fab1 and anti-IL-13 Fab2 each include VH containing the amino acid sequence of SEQ ID NO: 65 and VL containing the amino acid sequence of SEQ ID NO: 69, and in some embodiments, the full-length anti-TSLP antibody includes (a) VH containing the amino acid sequence of SEQ ID NO: 63 and VL containing the amino acid sequence of SEQ ID NO: 53, (b) VH containing the amino acid sequence of SEQ ID NO: 63 and VL containing the amino acid sequence of SEQ ID NO: 54, (c) VH containing the amino acid sequence of SEQ ID NO: 188 and VL containing the amino acid sequence of SEQ ID NO: 189, (d) VH containing the amino acid sequence of SEQ ID NO: 188 and VL containing the amino acid sequence of SEQ ID NO: 190, or (e) VH containing the amino acid sequence of SEQ ID NO: 228 and VL containing the amino acid sequence of SEQ ID NO: 190. In some embodiments, anti-IL-13 Fab1 includes H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL), where anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL), wherein (a) H1 and H2 each contain substitutions of F170I, S183L, and V185L, and L1 and L2 each contain substitutions of L135F, (b) H1 and H2 each contain substitutions of F170V, S183I, and V185L, and L1 and L2 each contain substitutions of L135F, (c) H1 and H2 each contain substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 (d) H1 and H2 each contain the E124C (or Q124C), L135F, and C214S substitutions, and L1 and L2 each contain the F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C), L135F, and C214S substitutions, or (e) H1 and H2 each contain the F126C and C220S substitutions, and L1 and L2 each contain the E124C (or Q124C) and C214S substitutions, with the amino acid positions following EU numbering. In some embodiments, the light chain of the full-length anti-TSLP antibody is derived from the kappa light chain.In some embodiments, the full-length anti-TSLP antibody comprises i) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 104, and two light chains, each containing the amino acid sequence of SEQ ID NO: 103, or ii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 105, and two light chains, each containing the amino acid sequence of SEQ ID NO: 103. In some embodiments, the linker comprises an amino acid sequence independently selected from GG and any one of SEQ ID NOs. 98 to 99.

[0145] In some embodiments, a multispecific construct is provided comprising a first antibody moiety which is a full-length anti-IL-13 antibody, and two second antibody moieties ("anti-TSLP Fab1" and "anti-TSLP Fab2") which are Fabs that specifically bind to TSLP, wherein the multispecific construct comprises: i) a first polypeptide comprising VL3-(L3-CL) from N' to C', ii) a second polypeptide comprising the first heavy chain (H1) of a VH3-(H3-CH1)-any linker-anti-IL-13 full-length antibody from N' to C', and iii) a second heavy chain (H1) of a VH4-(H4-CH1)-any linker-anti-IL-13 full-length antibody from N' to C'. The polypeptide comprises a third polypeptide containing chain (H2), iv) a fourth polypeptide containing VL4-(L4-CL) from N' to C', v) a fifth polypeptide containing the first light chain (L1) of the full-length anti-IL-13 antibody from the N-terminus to the C-terminus, and vi) a sixth polypeptide containing the second light chain (L2) of the full-length anti-IL-13 antibody from the N-terminus to the C-terminus, where VL3-(L3-CL) and VH3-(H3-CH1) are anti-TSLP Fab1 is formed, and VH4-(H4-CH1) and VL4-(L4-CL) form anti-TSLP Fab2, where the full-length anti-IL-13 antibody comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, and where anti-TSLP Fab1 and anti-TSLP Each Fab2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, (iv) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (v) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (vi) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26. In some embodiments, the full-length anti-IL-13 antibody comprises VH containing the amino acid sequence of SEQ ID NO: 65, and VL containing the amino acid sequence of SEQ ID NO: 69.In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each include (a) a VH containing the amino acid sequence of SEQ ID NO: 63 and a VL containing the amino acid sequence of SEQ ID NO: 53, (b) a VH containing the amino acid sequence of SEQ ID NO: 63 and a VL containing the amino acid sequence of SEQ ID NO: 54, (c) a VH containing the amino acid sequence of SEQ ID NO: 188 and a VL containing the amino acid sequence of SEQ ID NO: 189, (d) a VH containing the amino acid sequence of SEQ ID NO: 188 and a VL containing the amino acid sequence of SEQ ID NO: 190, or (e) a VH containing the amino acid sequence of SEQ ID NO: 228 and a VL containing the amino acid sequence of SEQ ID NO: 190. In some embodiments, (a) H1 and H2 each include substitutions of F170I, S183L, and V185L, and L1 and L2 each include substitutions of L135F; (b) H1 and H2 each include substitutions of F170V, S183I, and V185L, and L1 and L2 each include substitutions of L135F; (c) H1 and H2 each include substitutions of F126C, F170I, S183L, V185L, and C220S, and L1 and L2 each include substitutions of E124C (or Q124 (c) containing the substitutions of L135F and C214S, (d) H1 and H2 each containing the substitutions of F126C, F170V, S183I, V185L and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C), L135F and C214S, or (e) H1 and H2 each containing the substitutions of F126C and C220S, and L1 and L2 each containing the substitutions of E124C (or Q124C) and C214S, with amino acid positions following EU numbering.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; ii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 209, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 210, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207; iv) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 211, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206; v) two light chains, each containing the amino acid sequence of SEQ ID NO: 212 The configuration includes a heavy chain and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vi) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 213, and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208; vii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; viiii) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 101, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197; or ix) two heavy chains, each containing the amino acid sequence of SEQ ID NO: 123, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206. In some embodiments, L3-CL and L4-CL are derived from kappa light chains. In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each comprise a first polypeptide containing the amino acid sequence of SEQ ID NO: 109 and a second polypeptide containing the amino acid sequence of SEQ ID NO: 103. In some embodiments, the linker comprises an amino acid sequence independently selected from GG and any one of SEQ ID NOs: 98 to 99.

[0146] In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety that specifically binds to TSLP ("anti-TSLP antibody moiety"), wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 68. Furthermore, VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, or the anti-TSLP antibody portion comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, and VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26, further, where H1 includes substitutions at positions 170, 183, and 185 (EU numbering), and L1 includes a substitution at position 135 (EU numbering). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 includes the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, and VL1 includes the amino acid sequence of SEQ ID NO: 69. In some embodiments, the anti-TSLP antibody moiety includes (a) VH2 containing the amino acid sequence of SEQ ID NO: 63 and VL2 containing the amino acid sequence of SEQ ID NO: 53, (b) VH2 containing the amino acid sequence of SEQ ID NO: 63 and VL2 containing the amino acid sequence of SEQ ID NO: 54, (c) VH2 containing the amino acid sequence of SEQ ID NO: 188 and VL2 containing the amino acid sequence of SEQ ID NO: 189, (d) VH2 containing the amino acid sequence of SEQ ID NO: 188 and VL2 containing the amino acid sequence of SEQ ID NO: 190, or (e) VH2 containing the amino acid sequence of SEQ ID NO: 228 and VL2 containing the amino acid sequence of SEQ ID NO: 190. In some embodiments, H1 includes substitutions at the positions of F170, S183, and V185 (EU numbering), and L1 includes a substitution at the position of L135 (EU numbering).In some embodiments, H1 includes F170I, S183L, and V185L substitutions (EU numbering), and L1 includes L135F substitution (EU numbering). In some embodiments, L1 is derived from a lambda light chain. In some embodiments, L1 is derived from a kappa light chain. In some embodiments, the anti-IL-13 antibody moiety includes a first polypeptide comprising the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO: 124, and a second polypeptide comprising the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, or a variant thereof having at least about 80% (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197. In some embodiments, the anti-TSLP antibody moiety comprises a first polypeptide containing the amino acid sequence of SEQ ID NO: 109, or a variant thereof having at least about 80% (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO: 109, and a second polypeptide containing the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO: 103. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering). In some embodiments, (i) H1 includes the amino acid sequence of SEQ ID NO: 139, or a variant thereof having at least about 80% sequence identity with SEQ ID NO: 139 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). L1 includes the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, or a variant thereof having at least approximately 80% (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO: 122 or SEQ ID NO: 207, and H2 includes the amino acid sequence of SEQ ID NO: 136, or a variant thereof having at least approximately 80% (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO: 136. L2 contains the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least approximately 80% sequence identity with SEQ ID NO: 103 (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), or (ii) H1 contains the amino acid sequence of SEQ ID NO: 138, or a variant thereof having at least approximately 80% sequence identity with SEQ ID NO: 138 (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and L1 is sequence number H2 includes the amino acid sequence of sequence number 122 or sequence number 207, or a variant thereof having at least approximately 80% (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with sequence number 122 or sequence number 207, and H2 includes the amino acid sequence of sequence number 137, or a variant thereof having at least approximately 80% (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with sequence number 137, L2 includes the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% sequence identity with SEQ ID NO: 103 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, (i) H1 includes the amino acid sequence of SEQ ID NO: 139, L1 includes the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, H2 includes the amino acid sequence of SEQ ID NO: 136, and L2 includes the amino acid sequence of SEQ ID NO: 103, or (ii) H1 includes the amino acid sequence of SEQ ID NO: 138, L1 includes the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, H2 includes the amino acid sequence of SEQ ID NO: 137, and L2 includes the amino acid sequence of SEQ ID NO: 103.

[0147] In some embodiments, a multispecific construct is provided, where the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety, and H2 and L2 form a second antibody moiety ("anti-TSLP antibody moiety") that specifically binds to TSLP, where VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 68. Furthermore, VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, where the anti-TSLP antibody moiety ("anti-TSLP antibody moiety") comprises (i) VH2, which is a first polypeptide comprising CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, and VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26, further, where H1 includes substitutions at positions 170, 183, and 185 (EU numbering), and L1 includes a substitution at position 135 (EU numbering). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 includes the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, and VL1 includes the amino acid sequence of SEQ ID NO: 69. In some embodiments, the anti-TSLP antibody portion includes (a) VH2 containing the amino acid sequence of SEQ ID NO: 63 and VL2 containing the amino acid sequence of SEQ ID NO: 53, (b) VH2 containing the amino acid sequence of SEQ ID NO: 63 and VL2 containing the amino acid sequence of SEQ ID NO: 54, (c) VH2 containing the amino acid sequence of SEQ ID NO: 188 and VL2 containing the amino acid sequence of SEQ ID NO: 189, (d) VH2 containing the amino acid sequence of SEQ ID NO: 188 and VL2 containing the amino acid sequence of SEQ ID NO: 190, or (e) VH2 containing the amino acid sequence of SEQ ID NO: 228 and VL2 containing the amino acid sequence of SEQ ID NO: 190.In some embodiments, H1 includes substitutions at the positions of F170, S183, and V185 (EU numbering), and L1 includes substitution at the position of L135 (EU numbering). In some embodiments, H1 includes substitutions (EU numbering) of F170V, S183I, and V185L, and L1 includes substitutions (EU numbering) of L135F. In some embodiments, L1 is derived from a lambda light chain. In some embodiments, L1 is derived from a kappa light chain. In some embodiments, the anti-IL-13 antibody moiety comprises a first polypeptide containing the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to SEQ ID NO: 124, and a second polypeptide containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197. In some embodiments, the anti-TSLP antibody moiety comprises a first polypeptide containing the amino acid sequence of SEQ ID NO: 109, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 109 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and a second polypeptide containing the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 103 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering).In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering). In some embodiments, (i) H1 includes the amino acid sequence of SEQ ID NO: 141, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 141 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). L1 includes the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, or a variant thereof having at least approximately 80% (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 122 or SEQ ID NO: 207, and H2 includes the amino acid sequence of SEQ ID NO: 136, or a variant thereof having at least approximately 80% (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 136, and, L2 includes the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least approximately 80% sequence identity with SEQ ID NO: 103 (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). Alternatively, in some embodiments, (ii) H1 includes the amino acid sequence of SEQ ID NO: 140, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 140 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more); L1 includes the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 122 or SEQ ID NO: 207 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more); H2 includes the amino acid sequence of SEQ ID NO: 137, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 137 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more); and L2 includes the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 103 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, (i) H1 includes the amino acid sequence of SEQ ID NO: 141, L1 includes the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, H2 includes the amino acid sequence of SEQ ID NO: 136, and L2 includes the amino acid sequence of SEQ ID NO: 103, or (ii) H1 includes the amino acid sequence of SEQ ID NO: 140, L1 includes the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, H2 includes the amino acid sequence of SEQ ID NO: 137, and L2 includes the amino acid sequence of SEQ ID NO: 103. In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety, and H2 and L2 form a second antibody moiety ("anti-TSLP antibody moiety") that specifically binds to TSLP, wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 68. Furthermore, VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, where the anti-TSLP antibody moiety ("anti-TSLP antibody moiety") comprises (i) VH2, a first polypeptide comprising CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, and VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26, further, where H1 includes substitutions at positions 126 and 220 (EU numbering), and L1 includes substitutions at positions 124 and 214 (EU numbering). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 includes the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, and VL1 includes the amino acid sequence of SEQ ID NO: 69. In some embodiments, the anti-TSLP antibody moiety includes (a) VH2 containing the amino acid sequence of SEQ ID NO: 63 and VL2 containing the amino acid sequence of SEQ ID NO: 53, (b) VH2 containing the amino acid sequence of SEQ ID NO: 63 and VL2 containing the amino acid sequence of SEQ ID NO: 54, (c) VH2 containing the amino acid sequence of SEQ ID NO: 188 and VL2 containing the amino acid sequence of SEQ ID NO: 189, (d) VH2 containing the amino acid sequence of SEQ ID NO: 188 and VL2 containing the amino acid sequence of SEQ ID NO: 190, or (e) VH2 containing the amino acid sequence of SEQ ID NO: 228 and VL2 containing the amino acid sequence of SEQ ID NO: 190. In some embodiments, L1 is derived from the lambda light chain.In some embodiments, H1 includes substitutions at the positions of F126 and C220 (EU numbering), and L1 includes substitutions at the positions of E124 and C214 (EU numbering). In some embodiments, H1 includes substitutions at the positions of F126C and C220S (EU numbering), and L1 includes substitutions at the positions of E124C and C214S (EU numbering). In some embodiments, L1 is derived from the kappa light chain. In some embodiments, H1 includes substitutions at the positions of F126 and C220 (EU numbering), and L1 includes substitutions at the positions of Q124 and C214 (EU numbering). In some embodiments, H1 includes substitutions at the positions of F126C and C220S (EU numbering), and L1 includes substitutions at the positions of Q124C and C214S (EU numbering). In some embodiments, the anti-IL-13 antibody moiety comprises a first polypeptide containing the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to SEQ ID NO: 124, and a second polypeptide containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, or a variant thereof having at least about 80% sequence identity (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) to the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197. In some embodiments, the anti-TSLP antibody moiety comprises a first polypeptide containing the amino acid sequence of SEQ ID NO: 109, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 109 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and a second polypeptide containing the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 103 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1.In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain includes T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain includes T366W substitution (EU numbering). In some embodiments, (i) H1 includes the amino acid sequence of SEQ ID NO: 200, or a variant thereof having at least about 80% sequence identity with respect to SEQ ID NO: 200 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). L1 includes the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206, or a variant thereof having at least approximately 80% (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 121 or SEQ ID NO: 206, and H2 includes the amino acid sequence of SEQ ID NO: 136, or a variant thereof having at least approximately 80% (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 136, and, L2 includes the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least approximately 80% sequence identity with SEQ ID NO: 103 (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). Alternatively, in some embodiments, (ii) H1 includes the amino acid sequence of SEQ ID NO: 201, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 201 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more); L1 includes the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 121 or SEQ ID NO: 206 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more); H2 includes the amino acid sequence of SEQ ID NO: 137, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 137 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more); and L2 includes the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 103 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, (i) H1 includes the amino acid sequence of SEQ ID NO: 200, L1 includes the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206, H2 includes the amino acid sequence of SEQ ID NO: 136, and L2 includes the amino acid sequence of SEQ ID NO: 103, or (ii) H1 includes the amino acid sequence of SEQ ID NO: 201, L1 includes the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206, H2 includes the amino acid sequence of SEQ ID NO: 137, and L2 includes the amino acid sequence of SEQ ID NO: 103. In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a heterodimer bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1 and H1-CH1 and a first subunit of the Fc domain; iii) a second heavy chain (H2) comprising VH2, H2-CH1 and a second subunit of the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL, wherein H1 and L1 form an anti-IL-13 antibody moiety, and H2 and L2 form a second antibody moiety ("anti-TSLP antibody moiety") that specifically binds to TSLP, wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 68. Furthermore, here, VL1 includes (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, where the anti-TSLP antibody moiety ("anti-TSLP antibody moiety") includes (i) VH2, which is a first polypeptide containing CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, and ( iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, VL2 containing (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26, H1 containing substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and L1 containing substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 65 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and VL1 includes the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 69 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, VH1 includes the amino acid sequence of SEQ ID NO: 65, and VL1 includes the amino acid sequence of SEQ ID NO: 69. In some embodiments, the anti-TSLP antibody moiety includes (a) VH2 containing the amino acid sequence of SEQ ID NO: 63 and VL2 containing the amino acid sequence of SEQ ID NO: 53, (b) VH2 containing the amino acid sequence of SEQ ID NO: 63 and VL2 containing the amino acid sequence of SEQ ID NO: 54, (c) VH2 containing the amino acid sequence of SEQ ID NO: 188 and VL2 containing the amino acid sequence of SEQ ID NO: 189, (d) VH2 containing the amino acid sequence of SEQ ID NO: 188 and VL2 containing the amino acid sequence of SEQ ID NO: 190, or (e) VH2 containing the amino acid sequence of SEQ ID NO: 228 and VL2 containing the amino acid sequence of SEQ ID NO: 190. In some embodiments, L1 is derived from the lambda light chain.In some embodiments, H1 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L1 includes substitutions at the positions of E124, L135, and C214 (EU numbering). In some embodiments, H1 includes substitutions (EU numbering) of F126C, F170I, S183L, V185L, and C220S, and L1 includes substitutions (EU numbering) of E124C, L135F, and C214S. In some embodiments, L1 is derived from the kappa light chain. In some embodiments, H1 includes substitutions at the positions of F126, F170, S183, V185, and C220 (EU numbering), and L1 includes substitutions at the positions of Q124, L135, and C214 (EU numbering). In some embodiments, H1 includes F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and L1 includes Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the anti-IL-13 antibody moiety includes a first polypeptide comprising the amino acid sequence of SEQ ID NO: 124, or a variant thereof having at least about 80% (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO: 124, and a second polypeptide comprising the amino acids of SEQ ID NO: 102 or SEQ ID NO: 197, or a variant thereof having at least about 80% (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197. In some embodiments, the anti-TSLP antibody moiety comprises a first polypeptide containing the amino acid sequence of SEQ ID NO: 109, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 109 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more), and a second polypeptide containing the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 103 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more).In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, for example, human IgG1. In some embodiments, each subunit of the Fc domain includes (i) L234A and L235A substitutions (EU numbering), (ii) M428L and N434S substitutions (EU numbering), and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (ii) the second subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the first subunit of the Fc domain includes the T366W substitution (EU numbering). In some embodiments, (i) H1 includes the amino acid sequence of SEQ ID NO: 126, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 126 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). L1 includes the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, or a variant thereof having at least approximately 80% (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 120 or SEQ ID NO: 208, and H2 includes the amino acid sequence of SEQ ID NO: 136, or a variant thereof having at least approximately 80% (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO: 136, and, L2 includes the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least approximately 80% sequence identity with SEQ ID NO: 103 (for example, at least approximately 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). Alternatively, in some embodiments, (ii) H1 includes the amino acid sequence of SEQ ID NO: 127, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 127 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more); L1 includes the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 120 or SEQ ID NO: 208 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more); H2 includes the amino acid sequence of SEQ ID NO: 137, or a variant thereof having at least about 80% sequence identity to SEQ ID NO: 137 (e.g., at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more); and L2 includes the amino acid sequence of SEQ ID NO: 103, or a variant thereof having at least about 80% sequence identity with respect to SEQ ID NO: 103 (for example, at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more). In some embodiments, (i) H1 includes the amino acid sequence of SEQ ID NO: 126, L1 includes the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, H2 includes the amino acid sequence of SEQ ID NO: 136, and L2 includes the amino acid sequence of SEQ ID NO: 103, or (ii) H1 includes the amino acid sequence of SEQ ID NO: 127, L1 includes the amino a...

Claims

1. A multispecific construct, (1) A first antibody moiety that specifically binds to interleukin-13 (IL-13), and (2) A multispecific construct comprising a second antibody moiety that specifically binds to a second antigen.

2. The multispecific construct according to claim 1, wherein the first antibody portion comprises a heavy chain variable region (VH1) and a light chain variable region (VL1), and the VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, or a variant thereof containing up to three amino acid mutations, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, or a variant thereof containing up to three amino acid mutations, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, or a variant thereof containing up to three amino acid mutations, and the VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, or a variant thereof containing up to three amino acid mutations, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, or a variant thereof containing up to three amino acid mutations, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 72, or a variant thereof containing up to three amino acid mutations.

3. The multispecific construct according to claim 2, wherein VH1 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, and VL1 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO:

72.

4. The multispecific construct according to claim 2 or 3, wherein VH1 comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity with SEQ ID NO: 65, and VL1 comprises the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity with SEQ ID NO:

69.

5. The multispecific construct according to claim 4, wherein VH1 comprises the amino acid sequence of SEQ ID NO: 65 and VL1 comprises the amino acid sequence of SEQ ID NO:

69.

6. The first antibody portion is a full-length antibody, Fab, Fab', F(ab') ２ A multi-specific construct according to any one of claims 1 to 5, selected from the group consisting of sdAb and scFv.

7. The multispecific construct according to claim 6, wherein the first antibody portion is scFv (anti-IL-13 scFv).

8. The multispecific construct according to claim 6, wherein the first antibody portion is Fab (anti-IL-13 Fab).

9. The multispecific construct according to claim 6, wherein the first antibody portion is a full-length antibody (anti-IL-13 full-length antibody).

10. The multispecific construct according to any one of claims 1 to 9, wherein the second antigen is thymic interstitial lymphocyte necrosis factor (TSLP).

11. The second antibody portion includes a heavy chain variable region (VH2) and a light chain variable region (VL2), (a) The VH2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 2, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 3, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 4, and the VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8, (b) The VH2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 12, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 13, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 4, and the VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 6, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 7, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 8, (c) The VH2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 20, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 21, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 22, and the VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 24, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 25, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 26, (d) The VH2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 28, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 29, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 30, and the VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 32, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 33, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 34, (e) The VH2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 37, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 38, and the VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 40, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 41, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO: 42, or (f) The multispecific construct according to claim 10, wherein VH2 comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 44, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 45, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 46, and VL2 comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 48, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 49, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO:

50.

12. (a) The VH2 contains the amino acid sequence of SEQ ID NO: 1, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 1, and the VL2 contains the amino acid sequence of SEQ ID NO: 5, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 5, (b) The VH2 contains the amino acid sequence of SEQ ID NO: 9, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 9, and the VL2 contains the amino acid sequence of SEQ ID NO: 10, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 10, (c) The VH2 contains the amino acid sequence of SEQ ID NO: 11, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 11, and the VL2 contains the amino acid sequence of SEQ ID NO: 15, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 15, (d) The VH2 contains the amino acid sequence of SEQ ID NO: 19, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 19, and the VL2 contains the amino acid sequence of SEQ ID NO: 23, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 23, (e) The VH2 contains the amino acid sequence of SEQ ID NO: 27, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 27, and the VL2 contains the amino acid sequence of SEQ ID NO: 31, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 31, (f) The VH2 contains the amino acid sequence of SEQ ID NO: 35, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 35, and the VL2 contains the amino acid sequence of SEQ ID NO: 39, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 39, (g) The VH2 contains the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 43, and the VL2 contains the amino acid sequence of SEQ ID NO: 47, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 47, (h) The VH2 contains the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 63, and the VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 53, (i) The VH2 contains the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 63, and the VL2 contains the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 54, (j) The VH2 contains the amino acid sequence of SEQ ID NO: 56, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 56, and the VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 52, (k) The VH2 contains the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 55, and the VL2 contains the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 51, (l) The VH2 contains the amino acid sequence of SEQ ID NO: 56, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 56, and the VL2 contains the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 51, (m) The VH2 contains the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 63, and the VL2 contains the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 51, (n) The VH2 contains the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 64, and the VL2 contains the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 51, (o) The VH2 contains the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 55, and the VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 52, (p) The VH2 contains the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 58, and the VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 52, (q) The VH2 contains the amino acid sequence of SEQ ID NO: 60, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 60, and the VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 52, (r) The VH2 contains the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 64, and the VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 52, (s) The VH2 contains the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 55, and the VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 53, (t) The VH2 contains the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 57, and the VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 53, (u) The VH2 contains the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 58, and the VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 53, (v) The VH2 contains the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 62, and the VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 53, (w) The VH2 contains the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 64, and the VL2 contains the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 53, (x) The VH2 contains the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 55, and the VL2 contains the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 54, (y) The VH2 contains the amino acid sequence of SEQ ID NO: 61, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 61, and the VL2 contains the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 54, (z) The VH2 contains the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 62, and the VL2 contains the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 54, (aa) The VH2 contains the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 64, and the VL2 contains the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 54, (bb) The VH2 contains the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 63, and the VL2 contains the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 52, (cc) The VH2 contains the amino acid sequence of SEQ ID NO: 188, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 188, and the VL2 contains the amino acid sequence of SEQ ID NO: 189, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 189, (dd) The VH2 contains the amino acid sequence of SEQ ID NO: 188, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 188, and the VL2 contains the amino acid sequence of SEQ ID NO: 190, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 190, or (ee) The multispecific construct according to claim 11, wherein VH2 comprises the amino acid sequence of SEQ ID NO: 228, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 228, and VL2 comprises the amino acid sequence of SEQ ID NO: 190, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO:

190.

13. The second antibody portion is full-length antibody, Fab, Fab', F(ab') ２ A multi-specific construct according to any one of claims 1 to 12, selected from the group consisting of sdAb and scFv.

14. The multispecific construct according to claim 13, wherein the second antibody portion is a full-length antibody.

15. The multispecific construct according to claim 13, wherein the second antibody portion is scFv.

16. The multispecific construct according to claim 13, wherein the second antibody portion is Fab.

17. The multispecific construct according to claim 16, wherein the second antibody portion is an anti-TSLP Fab, and the anti-TSLP Fab comprises a first polypeptide having the amino acid sequence of SEQ ID NO: 109 and a second polypeptide having the amino acid sequence of SEQ ID NO:

103.

18. The first antibody portion comprises a heavy chain (H1) and a light chain (L1), where H1 comprises VH1 and H1-CH1, and L1 comprises VL1 and L1-CL. (i) The H1 includes substitutions at positions 170, 183, and 185 (EU numbering), and the L1 includes substitutions at position 135 (EU numbering), and / or (ii) The multiple specificity structure according to any one of claims 1 to 5, 8, and 10 to 17, wherein H1 includes substitutions at positions 126 and 220 (EU numbering) and L1 includes substitutions at positions 124 and 214 (EU numbering).

19. The multiple specificity structure according to claim 18, wherein H1 includes substitution at positions F170, S183, and V185 (EU numbering), and L1 includes substitution at position L135 (EU numbering).

20. (i) The substitution of F170 is F170I or F170V, the substitution of S183 is S183L or S183I, the substitution of V185 is V185L, and / or (ii) The multispecific construct according to claim 19, wherein the L135 substitution is L135F.

21. (a) The H1 includes the substitutions F170I, S183L, and V185L (EU numbering), and the L1 includes the substitution L135F (EU numbering), or (b) The multispecific construct according to claim 20, wherein H1 comprises F170V, S183I, and V185L substitutions (EU numbering), and L1 comprises L135F substitutions (EU numbering).

22. The multispecific construct according to any one of claims 18 to 21, wherein L1 is derived from a lambda light chain.

23. The multiple specificity structure according to claim 22, wherein H1 includes substitution at positions F126 and C220 (EU numbering), and L1 includes substitution at positions E124 and C214 (EU numbering).

24. The multispecific construct according to claim 23, wherein H1 includes F126C and C220S substitution (EU numbering) and L1 includes E124C and C214S substitution (EU numbering).

25. The multiple specificity construct according to any one of claims 18 to 21, wherein L1 is derived from a kappa light chain.

26. The multiple specificity structure according to claim 25, wherein H1 includes substitution at positions F126 and C220 (EU numbering), and L1 includes substitution at positions Q124 and C214 (EU numbering).

27. The multi-specific construct according to claim 26, wherein H1 includes F126C and C220S substitution (EU numbering) and L1 includes Q124C and C214S substitution (EU numbering).

28. (i) The above H1 includes substitutions for F126C, F170I, S183L, V185L, and C220S, and the above L1 includes substitutions for E124C, L135F, and C214S, (ii) The above H1 includes substitutions for F126C, F170V, S183I, V185L, and C220S, and the above L1 includes substitutions for E124C, L135F, and C214S, (iii) The above H1 includes substitutions for F126C, F170I, S183L, V185L, and C220S, and the above L1 includes substitutions for Q124C, L135F, and C214S, or (iv) The above H1 includes substitutions for F126C, F170V, S183I, V185L, and C220S, and the above L1 includes substitutions for Q124C, L135F, and C214S, The multiple specific structure according to any one of claims 18 to 27, wherein the aforementioned position conforms to EU numbering.

29. The multispecific construct according to any one of claims 1 to 8, 10 to 13, and 15 to 28, wherein the multispecific construct further comprises an Fc domain, the Fc domain comprising a first subunit and a second subunit.

30. The multispecific construct according to claim 29, wherein the Fc domain is derived from IgG1.

31. (i) Each subunit of the Fc domain includes L234A and L235A substitutions (EU numbering), (ii) Each subunit of the Fc domain includes M428L and N434S substitutions (EU numbering), (iii) Each subunit of the Fc domain includes M252Y, S254T, and T256E substitutions (EU numbering), and / or (iv) (a) The first subunit of the Fc domain includes the T366S, L368A, and Y407V substitution (EU numbering), and the second subunit of the Fc domain includes the T366W substitution (EU numbering), or (b) The multispecific construct according to claim 29 or 30, wherein the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises T366W substitution (EU numbering).

32. (i) The first subunit of the Fc domain contains the amino acid sequence of SEQ ID NO: 80, and the second subunit of the Fc domain contains the amino acid sequence of SEQ ID NO: 81, (ii) The first subunit of the Fc domain contains the amino acid sequence of SEQ ID NO: 81, and the second subunit of the Fc domain contains the amino acid sequence of SEQ ID NO: 80, (iii) The first subunit of the Fc domain contains the amino acid sequence of SEQ ID NO: 95, and the second subunit of the Fc domain contains the amino acid sequence of SEQ ID NO: 96, or (iv) The multispecific construct according to claim 31, wherein the first subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO: 96, and the second subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:

95.

33. The aforementioned multi-specific construct is i) A first light chain (L1) including VL1 and L1-CL, ii) A first heavy chain (H1) comprising VH1, H1-CH1, and a first subunit of the Fc domain, iii) VH2, H2-CH1, and a second heavy chain (H2) including a second subunit of the Fc domain, and iv) A heterodimer bispecific antibody containing a second light chain (L2) including VL2 and L2-CL, A multispecific construct according to any one of claims 1 to 5, 10 to 12, and 18 to 32, wherein H1 and L1 form an anti-IL-13 antibody moiety, and H2 and L2 form the second antibody moiety.

34. (i) The Fc domain is derived from human IgG1 and / or, (ii) The multispecific construct according to claim 33, wherein the L1-CL is derived from a human lambda light chain.

35. (a) The above H1 includes substitutions for F170I, S183L, and V185L, and the above L1 includes substitutions for L135F, (b) The above H1 includes substitutions for F170V, S183I, and V185L, and the above L1 includes substitutions for L135F, (c) The above H1 includes substitutions for F126C, F170I, S183L, V185L, and C220S, and the above L1 includes substitutions for E124C, L135F, and C214S, (d) The above H1 includes substitutions for F126C, F170V, S183I, V185L, and C220S, and the above L1 includes substitutions for E124C, L135F, and C214S, (e) The above H1 includes substitutions of F126C and C220S, and the above L1 includes substitutions of E124C and C214S, (f) The above H1 includes substitutions for F170I, S183L, V185L, T366S, L368A, and Y407V, the above L1 includes substitutions for L135F, and the above H2 includes substitutions for T366W, (g) The above H1 includes substitutions for F170I, S183L, V185L, and T366W, the above L1 includes substitutions for L135F, and the above H2 includes substitutions for T366S, L368A, and Y407V, (h) The above H1 includes substitutions for F170V, S183I, V185L, T366S, L368A, and Y407V, the above L1 includes substitutions for L135F, and the above H2 includes substitutions for T366W, (i) The above H1 includes substitutions for F170V, S183I, V185L, and T366W, the above L1 includes substitutions for L135F, and the above H2 includes substitutions for T366S, L368A, and Y407V, (j) The above H1 includes substitutions for F126C, F170I, S183L, V185L, C220S, T366S, L368A, and Y407V, the above L1 includes substitutions for E124C, L135F, and C214S, and the above H2 includes substitutions for T366W, (k) The above H1 includes substitutions for F126C, F170I, S183L, V185L, C220S, and T366W, the above L1 includes substitutions for E124C, L135F, and C214S, and the above H2 includes substitutions for T366S, L368A, and Y407V, (l) The above H1 includes substitutions for F126C, F170V, S183I, V185L, C220S, T366S, L368A, and Y407V, the above L1 includes substitutions for E124C, L135F, and C214S, and the above H2 includes substitutions for T366W, (m) The above H1 includes substitutions for F126C, F170V, S183I, V185L, C220S, and T366W, the above L1 includes substitutions for E124C, L135F, and C214S, and the above H2 includes substitutions for T366S, L368A, and Y407V, (n) The above H1 includes substitutions for F126C, C220S, T366S, L368A, and Y407V, the above L1 includes substitutions for E124C and C214S, and the above H2 includes substitutions for T366W, (o) The above H1 includes substitutions for F126C, C220S, and T366W, the above L1 includes substitutions for E124C and C214S, and the above H2 includes substitutions for T366S, L368A, and Y407V, (p) The above H1 includes substitutions for F170I, S183L, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, the above L1 includes substitutions for L135F, and the above H2 includes substitutions for L234A, L235A, T366W, M428L, and N434S, (q) The above H1 includes substitutions for F170I, S183L, V185L, L234A, L235A, T366W, M428L, and N434S, the above L1 includes substitutions for L135F, and the above H2 includes substitutions for L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, (r) The above H1 includes substitutions for F170V, S183I, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, the above L1 includes substitutions for L135F, and the above H2 includes substitutions for L234A, L235A, T366W, M428L, and N434S, (s) The above H1 includes substitutions for F170V, S183I, V185L, L234A, L235A, T366W, M428L, and N434S, the above L1 includes substitutions for L135F, and the above H2 includes substitutions for L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, (t) The above H1 includes substitutions for F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, the above L1 includes substitutions for E124C, L135F, and C214S, and the above H2 includes substitutions for L234A, L235A, T366W, M428L, and N434S, (u) The above H1 includes substitutions for F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366W, M428L, and N434S, the above L1 includes substitutions for E124C, L135F, and C214S, and the above H2 includes substitutions for L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, (v) The above H1 includes substitutions for F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, the above L1 includes substitutions for E124C, L135F, and C214S, and the above H2 includes substitutions for L234A, L235A, T366W, M428L, and N434S, (w) The above H1 includes substitutions for F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366W, M428L, and N434S, the above L1 includes substitutions for E124C, L135F, and C214S, and the above H2 includes substitutions for L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, (x) The above H1 includes substitutions for F126C, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, the above L1 includes substitutions for E124C and C214S, and the above H2 includes substitutions for L234A, L235A, T366W, M428L, and N434S, or (y) The above H1 includes substitutions for F126C, C220S, L234A, L235A, T366W, M428L, and N434S, the above L1 includes substitutions for E124C and C214S, and the above H2 includes substitutions for L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, The multispecific construct according to claim 33 or 34, wherein the amino acid positions conform to EU numbering.

36. (a) The H1 contains the amino acid sequence of SEQ ID NO: 87, the L1 contains the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and the H2 contains the amino acid sequence of SEQ ID NO: 85, (b) The H1 contains the amino acid sequence of SEQ ID NO: 88, the L1 contains the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and the H2 contains the amino acid sequence of SEQ ID NO: 86, (c) The H1 contains the amino acid sequence of SEQ ID NO: 89, the L1 contains the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and the H2 contains the amino acid sequence of SEQ ID NO: 85, (d) The H1 contains the amino acid sequence of SEQ ID NO: 90, the L1 contains the amino acid sequence of SEQ ID NO: 173 or SEQ ID NO: 202, and the H2 contains the amino acid sequence of SEQ ID NO: 86, (e) The H1 contains the amino acid sequence of SEQ ID NO: 91, the L1 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and the H2 contains the amino acid sequence of SEQ ID NO: 85, (f) The H1 contains the amino acid sequence of SEQ ID NO: 92, the L1 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and the H2 contains the amino acid sequence of SEQ ID NO: 86, (g) The H1 contains the amino acid sequence of SEQ ID NO: 93, the L1 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and the H2 contains the amino acid sequence of SEQ ID NO: 85, (h) The above H1 contains the amino acid sequence of SEQ ID NO: 94, the above L1 contains the amino acid sequence of SEQ ID NO: 174 or SEQ ID NO: 203, and the above H2 contains the amino acid sequence of SEQ ID NO: 86, (i) The H1 contains the amino acid sequence of SEQ ID NO: 198, the L1 contains the amino acid sequence of SEQ ID NO: 204 or SEQ ID NO: 205, and the H2 contains the amino acid sequence of SEQ ID NO: 85, or (j) The multispecific construct according to claim 35, wherein H1 comprises the amino acid sequence of SEQ ID NO: 199, L1 comprises the amino acid sequence of SEQ ID NO: 204 or SEQ ID NO: 205, and H2 comprises the amino acid sequence of SEQ ID NO:

86.

37. The multispecific construct according to any one of claims 33 to 36, wherein the L2-CL is derived from a human kappa light chain.

38. The second antigen is TSLP, (a) H1 contains the amino acid sequence of SEQ ID NO: 139, L1 contains the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, H2 contains the amino acid sequence of SEQ ID NO: 136, L2 contains the amino acid sequence of SEQ ID NO: 103, (b) H1 contains the amino acid sequence of SEQ ID NO: 138, L1 contains the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, H2 contains the amino acid sequence of SEQ ID NO: 137, L2 contains the amino acid sequence of SEQ ID NO: 103, (c) The H1 contains the amino acid sequence of SEQ ID NO: 141, the L1 contains the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, the H2 contains the amino acid sequence of SEQ ID NO: 136, and the L2 contains the amino acid sequence of SEQ ID NO: 103, (d) The H1 contains the amino acid sequence of SEQ ID NO: 140, the L1 contains the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, the H2 contains the amino acid sequence of SEQ ID NO: 137, and the L2 contains the amino acid sequence of SEQ ID NO: 103, (e) The H1 contains the amino acid sequence of SEQ ID NO: 126, the L1 contains the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, the H2 contains the amino acid sequence of SEQ ID NO: 136, and the L2 contains the amino acid sequence of SEQ ID NO: 103, (f) The H1 contains the amino acid sequence of SEQ ID NO: 127, the L1 contains the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, the H2 contains the amino acid sequence of SEQ ID NO: 137, and the L2 contains the amino acid sequence of SEQ ID NO: 103, (g) The H1 contains the amino acid sequence of SEQ ID NO: 128, the L1 contains the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, the H2 contains the amino acid sequence of SEQ ID NO: 136, and the L2 contains the amino acid sequence of SEQ ID NO: 103, (h) The above H1 contains the amino acid sequence of SEQ ID NO: 129, the above L1 contains the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, the above H2 contains the amino acid sequence of SEQ ID NO: 137, and the above L2 contains the amino acid sequence of SEQ ID NO: 103, (i) H1 contains the amino acid sequence of SEQ ID NO: 200, L1 contains the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206, H2 contains the amino acid sequence of SEQ ID NO: 136, L2 contains the amino acid sequence of SEQ ID NO: 103, or (j) The multispecific construct according to claim 37, wherein H1 comprises the amino acid sequence of SEQ ID NO: 201, L1 comprises the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206, H2 comprises the amino acid sequence of SEQ ID NO: 137, and L2 comprises the amino acid sequence of SEQ ID NO:

103.

39. An isolated antibody construct (anti-IL-13 antibody construct) comprising an antibody moiety (anti-IL-13 antibody moiety) that specifically binds to interleukin-13 (IL-13), wherein the anti-IL-13 antibody moiety comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the VH comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 66 or a variant thereof containing up to three amino acid mutations, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 67 or a variant thereof containing up to three amino acid mutations, and (iii) sequence An isolated anti-IL-13 antibody construct comprising CDR-H3 comprising the amino acid sequence of number 68 or a variant thereof containing up to three amino acid mutations, wherein VL comprises (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof containing up to three amino acid mutations, (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 71 or a variant thereof containing up to three amino acid mutations, and (iii) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 72 or a variant thereof containing up to three amino acid mutations.

40. The isolated anti-IL-13 antibody construct according to claim 39, wherein VH comprises (i) CDR-H1 containing the amino acid sequence of SEQ ID NO: 66, (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO: 67, and (iii) CDR-H3 containing the amino acid sequence of SEQ ID NO: 68, and VL comprises (i) CDR-L1 containing the amino acid sequence of SEQ ID NO: 70, (ii) CDR-L2 containing the amino acid sequence of SEQ ID NO: 71, and (iii) CDR-L3 containing the amino acid sequence of SEQ ID NO:

72.

41. The isolated anti-IL-13 antibody construct according to claim 39 or 40, wherein VH comprises the amino acid sequence of SEQ ID NO: 65, or a variant thereof having at least about 80% sequence identity with SEQ ID NO: 65, and VL comprises the amino acid sequence of SEQ ID NO: 69, or a variant thereof having at least about 80% sequence identity with SEQ ID NO:

69.

42. The isolated anti-IL-13 antibody construct according to claim 41, wherein VH comprises the amino acid sequence of SEQ ID NO: 65 and VL comprises the amino acid sequence of SEQ ID NO:

69.

43. The isolated anti-IL-13 antibody construct according to any one of claims 39 to 42, wherein the anti-IL-13 antibody portion is selected from the group consisting of a full-length antibody, Fab, Fab', F(ab')2, a diabody, and scFv.

44. The isolated anti-IL-13 antibody construct according to claim 43, wherein the anti-IL-13 antibody portion is scFv (anti-IL-13 scFv).

45. The isolated anti-IL-13 antibody construct according to claim 44, wherein the anti-IL-13 scFv comprises the amino acid sequence of SEQ ID NO:

108.

46. The isolated anti-IL-13 antibody construct according to claim 43, wherein the anti-IL-13 antibody portion is Fab (anti-IL-13 Fab).

47. The isolated anti-IL-13 antibody construct according to claim 46, wherein the anti-IL-13 Fab comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO: 124 and a second polypeptide comprising the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO:

197.

48. The isolated anti-IL-13 antibody construct according to claim 43, wherein the anti-IL-13 antibody portion is a full-length antibody (full-length anti-IL-13 antibody).

49. The aforementioned full-length anti-IL-13 antibody, i) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 125, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, ii) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 101, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, iii) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 123, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206, iv) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 209, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, v) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 210, and two light chains, each containing the amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 207, vi) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 211, and two light chains, each containing the amino acid sequence of SEQ ID NO: 121 or SEQ ID NO: 206, vii) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 212, and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, viiii) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 213, and two light chains, each containing the amino acid sequence of SEQ ID NO: 120 or SEQ ID NO: 208, ix) Two heavy chains, each containing the amino acid sequence of SEQ ID NO: 225, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO: 197, or x) The isolated anti-IL-13 antibody construct according to claim 48, comprising a first heavy chain containing the amino acid sequence of SEQ ID NO: 130, a second heavy chain containing the amino acid sequence of SEQ ID NO: 131, and two light chains, each containing the amino acid sequence of SEQ ID NO: 102 or SEQ ID NO:

197.

50. The isolated anti-IL-13 antibody construct according to any one of claims 39 to 49, wherein the isolated anti-IL-13 antibody construct is multispecific.

51. The isolated anti-IL-13 antibody construct according to claim 50, further comprising a second antibody moiety that specifically binds to a second antigen.

52. A pharmaceutical composition comprising (i) a multispecific construct according to any one of claims 1 to 38, or an isolated anti-IL-13 antibody construct according to any one of claims 39 to 51, and (ii) a pharmaceutically acceptable carrier.

53. An isolated nucleic acid or vector encoding one or more polypeptides from the multispecific constructs described in any one of claims 1 to 38 or the isolated anti-IL-13 antibody constructs described in any one of claims 39 to 51.

54. A host cell comprising the isolated nucleic acid or vector described in claim 53.

55. A method for treating an inflammatory disease in an individual, comprising administering to the individual an effective amount of the pharmaceutical composition according to claim 52.

56. (i) The inflammatory disease is asthma, atopic dermatitis, or chronic obstructive pulmonary disease (COPD), and / or (ii) The method according to claim 55, wherein the individual is a human.

57. A method for producing a multispecific construct or an anti-IL-13 antibody construct, i) Culturing a host cell containing the isolated nucleic acid or vector described in claim 53, or the host cell described in claim 54, under conditions suitable for the expression of the multispecific construct or the anti-IL-13 antibody construct, ii) A method comprising obtaining the expressed multispecific construct or the expressed anti-IL-13 antibody construct.

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