Anti-il-13 multispecific antibody constructs and uses thereof

Abstract

The present invention relates to multispecific constructs that specifically bind IL-13 and a second target antigen (e.g., TSLP, IL-17A, IL-17F, TNF-a, and IFN-g). Antibody constructs that specifically bind IL-13 are also provided. Compositions, kits, methods of using (e.g., treating inflammatory diseases) and methods of making are also provided.

Description

Cross-references to related applications

[0001] This application claims the benefit and priority of U.S. Provisional Application No. 63 / 578,946, filed August 25, 2023, the contents of which are incorporated herein by reference in their entirety. Reference to the electronic sequence list

[0002] The contents of the electronic sequence list (253272000140seqlist.xml; size: 239,418 bytes; and creation date: August 19, 2024) are incorporated herein by reference in their entirety. Technical Field

[0003] This 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 multispecific constructs, methods for treating inflammatory diseases using multispecific constructs, and kits comprising multispecific constructs. Background Technology

[0004] Many abnormal cells and tissues, as well as many diseases, exhibit unique antigens that can be cleared by immune cells, including inflammatory diseases such as autoimmune disorders or asthma. These inflammatory diseases may each exhibit one or more different target antigens or one or more different epitopes of the same target antigen. For example, some antigens are overexpressed, mutagenized, or selectively mutagenized in inflamed tissues. Therefore, antibodies that target specific antigens present in diseases with systemic or local inflammation can be used as therapeutic agents.

[0005] Interleukin (IL)-13 is a pleiotropic cytokine commonly associated with asthma and atopic dermatitis. IL-13 binds to a high-affinity heteropolymeric 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), however, IL-13Rα2 has been identified as a decoy receptor, participating in a signaling cascade distinct from that of IL-13Rα1. IL-13 is primarily secreted by T helper 2 cells (Th2 cells) and type 2 innate lymphocytes (ILC2). ILC2 produces IL-5 and IL-13 during allergic inflammation and bridges innate and adaptive immune responses. ILC2 activity promotes T helper 2 cell (Th2) responses, and the simultaneous action of ILC2 cells 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 failure of trorocalumab for the treatment of severe asthma, according to Adbry)™ (See, for example, Brightling et al., Lancet Respir Med. 2015, 3(9):692-701) and the combined results of lerezomumab (see, for example, Hanania et al., Lancet Respir Med. 2016, 4(10):781-796) demonstrate the need for other anti-IL-13 antibodies to treat IL-13-related diseases, particularly inflammatory ones. In particular, the fact that 73% of patients prematurely terminated the lerezomab ACOUSTICS clinical trial due to adverse events (see Szefler et al., Clin Transl Allergy 2022, 12(7):212176) further underscores the clear need for safer and more effective treatment options. Summary of the Invention

[0007] This invention provides multispecific constructs that specifically bind to IL-13 and a second target (e.g., TSLP), pharmaceutical compositions comprising multispecific constructs, and methods of treating inflammatory diseases using multispecific constructs. Further, isolated anti-IL-13 antibody constructs are provided.

[0008] In one aspect of the invention, a multispecific construct is provided comprising: (1) a first antibody portion that specifically binds to interleukin-13 (IL-13), and (2) a second antibody portion 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 of any of the above-described multispecific constructs, the first antibody portion comprises a heavy chain variable region (VH1) and a light chain variable region (VL1), wherein VH1 comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof comprising up to 3 amino acid variations, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:67 or a variant thereof comprising up to 3 amino acid variations, and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:68 or a variant thereof comprising up to 3 amino acid variations, and VL1 comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:70 or a variant thereof comprising up to 3 amino acid variations, (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:71 or a variant thereof comprising up to 3 amino acid variations, and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:72 or a variant thereof comprising up to 3 amino acid variations. 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 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. In some embodiments, 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, and VL1 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. 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.

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

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

[0012] In some embodiments of any of the above-described multispecific constructs, the first antibody portion is Fab (“anti-IL-13 Fab”). In some embodiments, anti-IL-13 Fab comprises 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 197.

[0013] In some embodiments of any of the above-described 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 contains 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, wherein: i) the first and second subunits of the Fc domain each contain the amino acid sequence of any one of SEQ ID NO:76-79; ii) 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; iii) 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; iv) 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 v) the first subunit of the Fc domain contains the amino acid sequence of SEQ ID NO:96, and the second subunit of the Fc domain contains the amino acid sequence of SEQ ID NO:95.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 125 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197; ii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 101 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197; iii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 123 and two light chains each comprising the amino acid sequence of SEQ ID NO: 121 or 206; iv) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 209 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; v) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 210 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; vi) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 211 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197. Two light chains containing the amino acid sequence of SEQ ID NO: 121 or 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 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 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 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 197.

[0014] In some embodiments of any of the above-described multispecific constructs, the second antigen is TSLP, wherein the second antibody portion comprises a heavy chain variable region (VH2) and a light chain variable region (VL2), wherein: (a) the VH2 comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:2; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:3; and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:4; and the VL2 comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:6; (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:7; and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:8; (b) the VH2 comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:12; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:13; and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:8. The VL2 comprises (i) a CDR-L1 containing the amino acid sequence of SEQ ID NO: 6; (ii) a CDR-L2 containing the amino acid sequence of SEQ ID NO: 7; and (iii) a CDR-L3 containing the amino acid sequence of SEQ ID NO: 8; (c) the VH2 comprises (i) a CDR-L1 containing the amino acid sequence of SEQ ID NO: 20; (ii) a CDR-L2 containing the amino acid sequence of SEQ ID NO: 21; and (iii) a CDR-L3 containing the amino acid sequence of SEQ ID NO: 22; and the VL2 comprises (i) a CDR-L1 containing the amino acid sequence of SEQ ID NO: 24; (ii) a CDR-L2 containing the amino acid sequence of SEQ ID NO: 25; and (iii) a CDR-L3 containing the amino acid sequence of SEQ ID NO: 26; (d) the VH2 comprises (i) a CDR-L1 containing the amino acid sequence of SEQ ID NO: 28; (ii) a CDR-L3 containing the amino acid sequence of SEQ ID NO: 4; (ii) a CDR-L3 containing the amino acid sequence of SEQ ID NO: 6; (iii) a CDR-L3 containing the amino acid sequence of SEQ ID NO: 4; (iv) a CDR-L3 containing the amino acid sequence of SEQ ID NO: 6; (viii) a CDR-L3 containing the amino acid sequence of SEQ ID NO: 4; (viii ... (iii) 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 contains (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 contains (i) CDR-H1 containing the amino acid sequence of SEQ ID NO:36; and (ii) CDR-H2 containing the amino acid sequence of SEQ ID NO:37;(iii) CDR-H3 containing the amino acid sequence of SEQ ID NO:38; and the VL2 contains (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 VH2 contains (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 the VL2 contains (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) the VH2 comprises 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 comprises 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 comprises 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 comprises 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 comprises 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 comprises 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 comprises 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:10. NO:19 has an amino acid sequence with at least about 80% sequence identity, and the VL2 contains the amino acid sequence of SEQ ID NO:23 or an amino acid sequence with 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 with 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 with 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:39. NO:63 has an amino acid sequence with at least about 80% sequence identity, and the VL2 contains the amino acid sequence of SEQ ID NO:54 or an amino acid sequence with 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 with 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 with 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 with 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 with 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 with at least about 80% sequence identity with SEQ ID NO:56, and the VL2 contains SEQ ID NO:63 or an amino acid sequence with at least about 80% sequence identity with SEQ ID NO:56. The amino acid sequence of 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:64. NO:60 has an amino acid sequence with at least about 80% sequence identity, and the VL2 contains the amino acid sequence of SEQ ID NO:52 or an amino acid sequence with 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 with 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 with 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 with 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 with 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 with at least about 80% sequence identity with SEQ ID NO:57, and the VL2 contains SEQ ID NO:60. (u) The amino acid sequence of NO:53 or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO:53; and 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:62. (z) The VH2 contains the amino acid sequence of SEQ ID NO:61 or has at least about 80% sequence identity, and the VL2 contains the amino acid sequence of SEQ ID NO:54 or has 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 has 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 has at least about 80% sequence identity with SEQ ID NO:54; (b) The VH2 contains the amino acid sequence of SEQ ID NO:63 or has at least about 80% sequence identity with SEQ ID NO:63, and the VL2 contains the amino acid sequence of SEQ ID NO:64. The amino acid sequence of 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 VH2 contains 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 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.

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

[0016] In some embodiments of any of the multispecific constructs described above, the second antibody portion is a full-length antibody. In some embodiments, the full-length antibody comprises 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, wherein: i) the first and second subunits of the Fc domain each comprise the amino acid sequence of any one of SEQ ID NO:76-79; ii) the first subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:80, and the second subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:81; or iii) the first subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:81, and the second subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:80. In some embodiments, the full-length antibody is an anti-TSLP full-length antibody comprising: i) two heavy chains each comprising the amino acid sequence of SEQ ID NO:104 and two light chains each comprising the amino acid sequence of SEQ ID NO:103; ii) two heavy chains each comprising the amino acid sequence of SEQ ID NO:105 and two light chains each comprising the amino acid sequence of SEQ ID NO:103; or iii) a first heavy chain comprising the amino acid sequence of SEQ ID NO:136, a second heavy chain comprising the amino acid sequence of SEQ ID NO:137 and two light chains each comprising the amino acid sequence of SEQ ID NO:103.

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

[0018] In some embodiments of any of the above-described multispecific constructs, the second antibody portion is a Fab. In some embodiments, the second antibody portion is an anti-TSLP Fab, wherein the anti-TSLP Fab comprises 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.

[0019] In some embodiments of any of the above-described multispecific constructs, the first antibody portion comprises a heavy chain (H1) and a light chain (L1), wherein H1 comprises VH1 and H1-CH1, wherein L1 comprises VL1 and L1-CL, and wherein: (i) H1 contains substitutions at positions 170, 183, and 185 (EU number), and L1 contains a substitution at position 135 (EU number); and / or (ii) H1 contains substitutions at positions 126 and 220 (EU number), and L1 contains substitutions at positions 124 and 214 (EU number). In some embodiments, H1 contains substitutions at F170, S183, and V185 (EU number), and L1 contains a substitution at L135 (EU number). 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 contains F170I, S183L, and V185L substitutions (EU numbers), and L1 contains an L135F substitution (EU number); or (b) H1 contains F170V, S183I, and V185L substitutions (EU numbers), and L1 contains an L135F substitution (EU number). In some embodiments, L1 is derived from the λ light chain. In some embodiments, the λ light chain contains the amino acid sequence of SEQ ID NO: 74 or 75. In some embodiments, H1 contains substitutions at F126 and C220 (EU numbers), and L1 contains substitutions at E124 and C214 (EU numbers). In some embodiments, H1 contains F126C and C220S substitutions (EU numbers), and L1 contains E124C and C214S substitutions (EU numbers). In some embodiments, L1 is derived from the κ light chain. In some embodiments, the κ light chain comprises the amino acid sequence of SEQ ID NO:73. In some embodiments, H1 contains substitutions at F126 and C220 (EU number), and L1 contains substitutions at Q124 and C214 (EU number). In some embodiments, H1 contains F126C and C220S substitutions (EU number), and L1 contains Q124C and C214S substitutions (EU number).In some implementations, (i) H1 is substituted with F126C, F170I, S183L, V185L, and C220S, and L1 is substituted with E124C, L135F, and C214S; (ii) H1 is substituted with F126C, F170V, S183I, V185L, and C220S, and L1 is substituted with E124C, L135F, and C214S; (iii) H1 is substituted with F126C, F170I, S183L, V185L, and C220S, and L1 is substituted with Q124C, L135F, and C214S; or (iv) H1 includes F126C, F170V, S183I, V185L and C220S as substitutes, and L1 includes Q124C, L135F and C214S as substitutes; where the positions are according to EU designations.

[0020] In some embodiments of any of the multispecific constructs described above, the multispecific construct further comprises an Fc domain, wherein 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. In some embodiments, the Fc domain is derived from IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbers). In some embodiments, each subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:77. In some embodiments, the Fc domain comprises M428L and N434S substitutions (EU numbers). In some embodiments, each subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:78. In some embodiments, the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbers). In some embodiments, each subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:79. In some implementations, (i) the first subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number). In some embodiments, (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 first subunit of the Fc domain contains the amino acid sequence of SEQ ID NO:96, and the second subunit of the Fc domain contains the amino acid sequence of SEQ ID NO:95.

[0021] In some embodiments of any of the above-described multispecific constructs, the multispecific construct is a heterodimeric bispecific antibody comprising: i) a first light chain (L1) comprising VL1 and L1-CL; ii) a first heavy chain (H1) comprising VH1, H1-CH1, and a first subunit of an Fc domain; iii) a second heavy chain (H2) comprising VH2, H2-CH1, and a second subunit of an Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; and wherein 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 λ light chain. In some embodiments, (a) H1 contains F170I, S183L, and V185L substitutions, and L1 contains L135F substitution; (b) H1 contains F170V, S183I, and V185L substitutions, and L1 contains L135F substitution; (c) H1 contains F126C, F170I, S183L, V185L, and C220S substitutions, and L1 contains E124C, L135F, and C214S substitutions; (d) H1 contains F126C, F170V, S183I, V185L, and C220S substitutions, and L1 contains E124C, L135F, and C214S substitutions; or (e) H1 contains F126C and C220S substitutions, and L1 contains E124C and C214S substitutions; and wherein the amino acid positions are according to EU numbers. In some embodiments, (a) H1 comprises substitutions of F170I, S183L, V185L, T366S, L368A, and Y407V, L1 comprises substitutions of L135F, and H2 comprises substitutions of T366W; (b) H1 comprises substitutions of F170I, S183L, V185L, and T366W, L1 comprises substitutions of L135F, and H2 comprises substitutions of T366S, L368A, and Y407V; (c) H1 comprises substitutions of F170V, S183I, V185L, T366S, L368A, and Y407V, L1 comprises substitutions of L135F, and H2 comprises substitutions of T366W; (d) H1 contains F170V, S183I, V185L and T366W as substitutes, L1 contains L135F as substitutes, and H2 contains T366S, L368A and Y407V as substitutes; (e) H1 contains F126C, F170I, S183L, V185L, C220S, T366S, L368A and Y407V as substitutes, L1 contains E124C, L135F and C214S as substitutes, and H2 contains T366W as substitutes;(f) H1 ​​contains substitutions of F126C, F170I, S183L, V185L, C220S, and T366W; L1 contains substitutions of E124C, L135F, and C214S; and H2 contains substitutions of T366S, L368A, and Y407V; (g) H1 contains substitutions of F126C, F170V, S183I, V185L, C220S, T366S, L368A, and Y407V; L1 contains substitutions of E124C, L135F, and C214S; and H2 contains substitutions of T366W. (h) H1 contains substitutions of F126C, F170V, S183I, V185L, C220S, and T366W; L1 contains substitutions of E124C, L135F, and C214S; and H2 contains substitutions of T366S, L368A, and Y407V. (i) H1 contains substitutions of F126C, C220S, T366S, L368A, and Y407V; L1 contains substitutions of E124C and C214S; and H2 contains substitutions of T366W. Or (j) H1 contains F126C, C220S and T366W substitutions, L1 contains E124C and C214S substitutions, and H2 contains T366S, L368A and Y407V substitutions; and the amino acid positions are based on EU numbers. In some embodiments, (a) H1 comprises substitutions of F170I, S183L, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, L1 comprises a substitution of L135F, and H2 comprises substitutions of L234A, L235A, T366W, M428L, and N434S; (b) H1 comprises substitutions of F170I, S183L, V185L, L234A, L235A, T366W, M428L, and N434S, L1 comprises a substitution of L135F, and H2 comprises substitutions of L234A, L235A, T366S, L368A, Y407V, M428L, and N434S; (c) H1 includes F170V, S183I, V185L, L234A, L235A, T366S, L368A, Y407V, M428L and N434S as substitutes, L1 includes L135F as substitutes, and H2 includes L234A, L235A, T366W, M428L and N434S as substitutes; (d) H1 includes F170V, S183I, V185L, L234A, L235A, T366W, M428L and N434S as substitutes, L1 includes L135F as substitutes, and H2 includes L234A, L235A, T366S, L368A, Y407V, M428L and N434S as substitutes;(e) H1 comprises substitutions of F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S; L1 comprises substitutions of E124C, L135F, and C214S; and H2 comprises substitutions of L234A, L235A, T366W, M428L, and N434S; (f) H1 contains substitutions of F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366W, M428L, and N434S; L1 contains substitutions of E124C, L135F, and C214S; and H2 contains substitutions of L234A, L235A, T366S, L368A, Y407V, M428L, and N434S. (g) H1 includes substitutions of F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S; L1 includes substitutions of E124C, L135F, and C214S; and H2 includes substitutions of L234A, L235A, T366W, M428L, and N434S. (h) H1 includes substitutions of F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366W, M428L, and N434S; L1 includes substitutions of E124C, L135F, and C214S; and H2 includes substitutions of L234A, L235A, T366S, L368A, Y407V, M428L, and N434S; (i) H1 contains F126C, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; L1 contains E124C and C214S substitutions; and H2 contains L234A, L235A, T366W, M428L, and N434S substitutions; or (j) H1 contains F126C, C220S, L234A, L235A, T366W, M428L, and N434S substitutions; L1 contains E124C and C214S substitutions; and H2 contains L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; and the amino acid positions therein are according to EU numbers. 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 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 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 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 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 203, and H2 contains the amino acid sequence of SEQ ID NO: 85; (f) H1 ​​contains the amino acid sequence of SEQ ID NO: 92, L1 contains the amino acid sequence of SEQ ID NO: 174 or 203, and H2 contains the amino acid sequence of SEQ ID NO: 86. The amino acid sequence of SEQ ID NO:86; (g) H1 contains the amino acid sequence of SEQ ID NO:93, L1 contains the amino acid sequence of SEQ ID NO:174 or 203, and H2 contains the amino acid sequence of SEQ ID NO:85; (h) H1 contains the amino acid sequence of SEQ ID NO:94, L1 contains the amino acid sequence of SEQ ID NO:174 or 203, and H2 contains the amino acid sequence of SEQ ID NO:86; (i) H1 contains the amino acid sequence of SEQ ID NO:198, L1 contains the amino acid sequence of SEQ ID NO:204 or 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 205, and H2 contains the amino acid sequence of SEQ ID NO:86. In some embodiments, L2-CL is derived from the human κ light chain. In some embodiments, the second antigen is TSLP. In some embodiments, (a) H1 contains the amino acid sequence of SEQ ID NO:139, L1 contains the amino acid sequence of SEQ ID NO:122 or 207, H2 contains the amino acid sequence of SEQ ID NO:136, and 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 207, H2 contains the amino acid sequence of SEQ ID NO: 137, and L2 contains the amino acid sequence of SEQ ID NO: 103; (c) H1 contains the amino acid sequence of SEQ ID NO: 141, L1 contains the amino acid sequence of SEQ ID NO: 122 or 207, H2 contains the amino acid sequence of SEQ ID NO: 136, and L2 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 207, H2 contains the amino acid sequence of SEQ ID NO: 137, and 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 208, and H2 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 208, H2 contains the amino acid sequence of SEQ ID NO:137, and 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, and 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, and L2 contains the amino acid sequence of SEQ ID NO:103; (i) 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, and L2 contains the amino acid sequence of SEQ ID NO:103; The amino acid sequence of 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, and L2 contains the amino acid sequence of SEQ ID NO:103.Alternatively (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, and 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 λ light chain. In some embodiments, (a) H2 contains F170I, S183L, and V185L substitutions, and L2 contains L135F substitution; (b) H2 contains F170V, S183I, and V185L substitutions, and L2 contains L135F substitution; (c) H2 contains F126C, F170I, S183L, V185L, and C220S substitutions, and L2 contains E124C, L135F, and C214S substitutions; (d) H2 contains F126C, F170V, S183I, V185L, and C220S substitutions, and L2 contains E124C, L135F, and C214S substitutions; or (e) H2 contains F126C and C220S substitutions, and L2 contains E124C and C214S substitutions; and wherein the amino acid positions are according to EU numbers. In some embodiments, (a) H2 comprises substitutions of F170I, S183L, V185L, T366S, L368A, and Y407V, L2 comprises substitutions of L135F, and H1 comprises substitutions of T366W; (b) H2 comprises substitutions of F170I, S183L, V185L, and T366W, L2 comprises substitutions of L135F, and H1 comprises substitutions of T366S, L368A, and Y407V; (c) H2 comprises substitutions of F170V, S183I, V185L, T366S, L368A, and Y407V, L2 comprises substitutions of L135F, and H1 comprises substitutions of T366W; (d) H2 is replaced by F170V, S183I, V185L and T366W, L2 is replaced by L135F, and H1 is replaced by T366S, L368A and Y407V; (e) H2 is replaced by F126C, F170I, S183L, V185L, C220S, T366S, L368A and Y407V, L2 is replaced by E124C, L135F and C214S, and H1 is replaced by T366W; (f) H2 is replaced by F126C, F170I, S183L, V185L, C220S and T366W, L2 is replaced by E124C, L135F and C214S, and H1 is replaced by T366S, L368A and Y407V.(g) H2 contains substitutions of F126C, F170V, S183I, V185L, C220S, T366S, L368A, and Y407V; L2 contains substitutions of E124C, L135F, and C214S; and H1 contains substitutions of T366W. (h) H2 contains substitutions of F126C, F170V, S183I, V185L, C220S, and T366W; L2 contains substitutions of E124C, L135F, and C214S; and H1 contains substitutions of T366S, L368A, and Y407V. (i) H2 contains substitutions of F126C, C220S, T366S, L368A, and Y407V; L2 contains substitutions of E124C and C214S; and H1 contains substitutions of T366W. Or (j) H2 contains F126C, C220S and T366W substitutions, L2 contains E124C and C214S substitutions, and H1 contains T366S, L368A and Y407V substitutions; and the amino acid positions are based on EU numbers. In some embodiments, (a) H2 comprises substitutions of F170I, S183L, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, L2 comprises substitutions of L135F, and H1 comprises substitutions of L234A, L235A, T366W, M428L, and N434S; (b) H2 comprises substitutions of F170I, S183L, V185L, L234A, L235A, T366W, M428L, and N434S, L2 comprises substitutions of L135F, and H1 comprises substitutions of L234A, L235A, T366S, L368A, Y407V, M428L, and N434S; (c) H2 includes substitutions of F170V, S183I, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S; L2 includes substitutions of L135F; and H1 includes substitutions of L234A, L235A, T366W, M428L, and N434S. (d) H2 includes substitutions of F170V, S183I, V185L, L234A, L235A, T366W, M428L, and N434S; L2 includes substitutions of L135F; and H1 includes substitutions of L234A, L235A, T366S, L368A, Y407V, M428L, and N434S. (e) H2 includes F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L and N434S as substitutes; L2 includes E124C, L135F and C214S as substitutes; and H1 includes L234A, L235A, T366W, M428L and N434S as substitutes.(f) H2 is substituted with F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366W, M428L, and N434S; L2 is substituted with E124C, L135F, and C214S; and H1 is substituted with L234A, L235A, T366S, L368A, Y407V, M428L, and N434S; (g) H2 includes substitutions of F126C, F170V, S183I, 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. (h) H2 includes substitutions of F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366W, M428L, and N434S; L2 includes substitutions of E124C, L135F, and C214S; and H1 includes substitutions of L234A, L235A, T366S, L368A, Y407V, M428L, and N434S; (i) H2 contains F126C, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; L2 contains E124C and C214S substitutions; and H1 contains L234A, L235A, T366W, M428L, and N434S substitutions; or (j) H2 contains F126C, C220S, L234A, L235A, T366W, M428L, and N434S substitutions; L2 contains E124C and C214S substitutions; and H1 contains L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; and the amino acid positions therein are according to EU numbers. In some embodiments, (a) H2 contains the amino acid sequence of SEQ ID NO:87, L2 contains the amino acid sequence of SEQ ID NO:173 or 202, and H1 contains the amino acid sequence of SEQ ID NO:85; (b) H2 contains the amino acid sequence of SEQ ID NO:88, L2 contains the amino acid sequence of SEQ ID NO:173 or 202, and H1 contains the amino acid sequence of SEQ ID NO:86; (c) H2 contains the amino acid sequence of SEQ ID NO:89, L2 contains the amino acid sequence of SEQ ID NO:173 or 202, and H1 contains the amino acid sequence of SEQ ID NO:85.(d) H2 contains the amino acid sequence of SEQ ID NO:90, L2 contains the amino acid sequence of SEQ ID NO:173 or 202, and H1 contains 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 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 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 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 203, and H1 contains the amino acid sequence of SEQ ID NO:96. The amino acid sequence of SEQ ID NO:86; (i) the H2 contains the amino acid sequence of SEQ ID NO:198, the L2 contains the amino acid sequence of SEQ ID NO:204 or 205, and the H1 contains the amino acid sequence of SEQ ID NO:85; or (j) the H2 contains the amino acid sequence of SEQ ID NO:199, the L2 contains the amino acid sequence of SEQ ID NO:204 or 205, and the H1 contains the amino acid sequence of SEQ ID NO:86. In some embodiments, L1-CL is derived from the human κ light chain. In some embodiments, the second antigen is TSLP.

[0022] In some embodiments of any of the above-described multispecific constructs, a first antibody portion specifically binding to IL-13 and a second antibody portion specifically binding to a second target antigen are fused together via a linker. In some embodiments, the linker comprises the amino acid sequence of either GG or SEQ ID NO:98-99.

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

[0024] In some embodiments of the multispecific construct described above, the multispecific construct comprises two anti-IL-13 antibody moieties (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”) as scFvs, and the second antibody moieties are full-length antibodies that specifically bind to a second target antigen; wherein anti-IL-13 scFv1 is fused to the C-terminus of the first heavy chain of the second antibody moieties 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 moieties to form a second fusion polypeptide. In some embodiments, the second target antigen is TSLP (i.e., the second antibody moieties are “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, and wherein the first fusion polypeptide and the second fusion polypeptide each contain the amino acid sequence of SEQ ID NO: 113.

[0025] In some embodiments of any of the above-described multispecific constructs, the multispecific construct comprises two anti-IL-13 antibody moieties as scFv (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”), two second antibody moieties as Fab (“Fab1” and “Fab2”) that specifically bind to a second target antigen, and an Fc domain; wherein the multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-anti-IL-13 iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-second subunit of the anti-IL-13scFv2-optional linker-Fc domain; and iv) a fourth polypeptide comprising, from N' to C': VL2-(L2-CL); wherein 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 of any of the above-described multispecific constructs, the first antibody portion is a full-length antibody (“anti-IL-13 full-length antibody”), wherein the second antibody portion is an scFv that specifically binds to the second target antigen, and wherein the scFv is fused to the C-terminus of one of the heavy chains of the anti-IL-13 full-length antibody to form a fusion polypeptide.

[0027] In some embodiments of the multispecific constructs described above, the multispecific construct comprises a first antibody portion as a full-length anti-IL-13 antibody and two second antibody portions as scFvs (“scFv1” and “scFv2”) that specifically bind to a second target antigen; and 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 comprising the amino acid sequence of SEQ ID NO: 125 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197, and wherein the first fusion polypeptide and the second fusion polypeptide each comprise 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 197, and wherein the first fusion polypeptide and the second fusion polypeptide each contain the amino acid sequence of any one of SEQ ID NO:220-223.

[0028] In some embodiments of any of the above-described multispecific constructs, the multispecific construct comprises two anti-IL-13 antibody portions as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab1”). The multispecific construct comprises: Fab2”), two second antibody moieties and an Fc domain of scFvs (“scFv1” and “scFv2”) that specifically bind to a second target antigen; wherein the multispecific construct comprises: i) a first polypeptide comprising, from N’ to C’: VL1-(L1-CL); ii) a second polypeptide comprising, from N’ to C’: VH1-(H1-CH1)-optional linker-scFv1-optional linker-first subunit of the Fc domain; iii) a third polypeptide comprising, from N’ to C’: VH2-(H2-CH1)-optional linker-scFv2-optional linker-second subunit of the Fc domain; and iv) a fourth polypeptide comprising, from N’ to C’: VL2-(L2-CL); and wherein VH1-(H1-CH1) and VL1-(L1-CL) form an anti-IL-13. Fab1, 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 and fourth peptides each comprise the amino acid sequence of SEQ ID NO:102 or 197, and the second and third peptides each comprise the amino acid sequence of SEQ ID NO:112.

[0029] In some embodiments of any of the above-described multispecific constructs, the multispecificity comprises two anti-IL-13 antibody moieties as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”) and a second antibody moieties as a full-length antibody that specifically binds to a second target antigen; wherein the multispecific construct comprises: i) a first polypeptide comprising: a first light chain of the second antibody moieties; ii) a second polypeptide comprising, from N' to C': a first heavy chain of the second antibody moieties - optionally a linker - VH1-(H1-CH1); iii) a third polypeptide comprising, from N' to C': a second heavy chain of the second antibody moieties - optionally a linker - VH2-(H2-C) H1); iv) a fourth polypeptide comprising: a second light chain of the second antibody portion; v) a fifth polypeptide comprising, from N' to C': VL1-(L1-CL); and vi) a sixth polypeptide comprising, from N' to C': VL2-(L2-CL); and wherein VL1-(L1-CL) and VH1-(H1-CH1) form anti-IL-13Fab1, and VL2-(L2-CL) and VH2-(H2-CH1) form anti-IL-13Fab2. In some embodiments, anti-IL-13 Fab1 comprises H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL); wherein anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL); and wherein: (a) H1 and H2 each contain F170I, S183L, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (b) H1 and H2 each contain F170V, S183I, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (c) H1 and H2 each contain F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each contain E124C, L135F, and C214S substitutions; (d) H1 and H2 each contain F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain E124C, L135F, and C214S substitutions; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C and C214S substitutions; wherein the amino acid positions are according to EU numbers. 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 of any of the above-described multispecific constructs, the multispecific construct comprises an anti-IL-13 antibody portion (“anti-IL-13 full-length antibody”) as a full-length antibody and two second antibody portions (“Fab1” and “Fab2”) as 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, from N' to C': a first heavy chain (H1) of the anti-IL-13 full-length antibody – optionally a linker – VH3-(H3-CH1); iii) a third polypeptide. The third polypeptide comprises, from N' to C': the second heavy chain (H2) of the full-length anti-IL-13 antibody - optional linker - VH4-(H4-CH1); iv) the fourth polypeptide comprises: the second light chain (L2) of the full-length anti-IL-13 antibody; v) the fifth polypeptide comprises, from N' to C': VL3-(L3-CL); and vi) the sixth polypeptide comprises, from N' to C': VL4-(L4-CL); and 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 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 L2 each contain substitutions of E124C, L135F, and C214S; (d) H1 and H2 each contain substitutions of F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each contain substitutions of E124C, L135F, and C214S; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C and C214S substitutions; and the amino acid positions are determined according to EU numbers.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 125 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197; ii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 209 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 210 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iv) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 211 and two light chains each comprising the amino acid sequence of SEQ ID NO: 121 or 206; v) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 212 and two light chains each comprising the amino acid sequence of SEQ ID NO: 120 or 208; vi) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 213 and two light chains each comprising the amino acid sequence of SEQ ID NO: 125 and 197 or 102 or 107 or 108 or 109 ... Two light chains comprising the amino acid sequence of SEQ ID NO: 120 or 208; vii) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 225 and two light chains comprising the amino acid sequence of SEQ ID NO: 102 or 197; viii) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 101 and two light chains comprising the amino acid sequence of SEQ ID NO: 102 or 197; or ix) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 123 and two light chains comprising the amino acid sequence of SEQ ID NO: 121 or 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 comprising the amino acid sequence of SEQ ID NO: 109 and a second polypeptide comprising the amino acid sequence of SEQ ID NO: 103.

[0031] In some embodiments of any of the above-described multispecific constructs, the multispecific construct comprises two anti-IL-13 antibody portions as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab1”). The multispecific construct comprises: Fab2” and a second antibody portion as a full-length antibody that specifically binds to a second target antigen; wherein the multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-first heavy chain of the second antibody portion; iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-second heavy chain of the second antibody portion; iv) a fourth polypeptide comprising, from N' to C': VL2-(L2-CL); v) a fifth polypeptide comprising: the first light chain of the second antibody portion; and vi) a sixth polypeptide comprising: the second light chain of the second antibody portion; and wherein VL1-(L1-CL) and VH1-(H1-CH1) form an anti-IL-13. Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form an anti-IL-13 Fab2. In some embodiments, the anti-IL-13 Fab1 comprises H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL); wherein the anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL); and wherein: (a) H1 and H2 each contain F170I, S183L, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (b) H1 and H2 each contain F170V, S183I, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (c) H1 and H2 each contain F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each contain E124C, L135F, and C214S substitutions; (d) H1 and H2 each contain F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain E124C, L135F, and C214S substitutions; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C and C214S substitutions; and wherein the amino acid positions are according to EU numbers. 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 of any of the above-described multispecific constructs, the multispecific construct comprises a first antibody portion as a full-length anti-IL-13 antibody and two second antibody portions as Fab (“Fab1” and “Fab2”) that specifically bind to a second target antigen; wherein the multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL3-(L3-CL); ii) a second polypeptide comprising, from N' to C': VH3-(H3-CH1)-optional linker-first heavy chain (H1) of the full-length anti-IL-13 antibody; iii) a third polypeptide comprising, from N' to C': VH3-(H3-CH1)-optional linker-first heavy chain (H1) of the full-length anti-IL-13 antibody; 'to C' comprises: VH4-(H4-CH1)-optional linker-second heavy chain (H2) of the full-length anti-IL-13 antibody; iv) a fourth polypeptide comprising from N' to C': VL4-(L4-CL); v) a fifth polypeptide comprising: the first light chain (L1) of the full-length anti-IL-13 antibody; and vi) a sixth polypeptide comprising: the second light chain (L2) of the full-length anti-IL-13 antibody; and 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 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 L2 each contain substitutions of E124C, L135F, and C214S; (d) H1 and H2 each contain substitutions of F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each contain substitutions of E124C, L135F, and C214S; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C and C214S substitutions; and the amino acid positions are determined according to EU numbers.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 125 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197; ii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 209 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 210 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iv) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 211 and two light chains each comprising the amino acid sequence of SEQ ID NO: 121 or 206; v) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 212 and two light chains each comprising the amino acid sequence of SEQ ID NO: 120 or 208; vi) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 213 and two light chains each comprising the amino acid sequence of SEQ ID NO: 125 and 197 or 102 or 107 or 108 or 109 ... Two light chains comprising the amino acid sequence of SEQ ID NO: 120 or 208; vii) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 225 and two light chains comprising the amino acid sequence of SEQ ID NO: 102 or 197; viii) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 101 and two light chains comprising the amino acid sequence of SEQ ID NO: 102 or 197; or ix) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 123 and two light chains comprising the amino acid sequence of SEQ ID NO: 121 or 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 comprising the amino acid sequence of SEQ ID NO: 109 and a second polypeptide comprising the amino acid sequence of SEQ ID NO: 103.

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

[0034] It also provides 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 an individual's inflammatory disease are also provided, including 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 person.

[0036] It also provides that generating any of the multispecific constructs described herein includes i) culturing a host cell containing any of the isolated nucleic acids or vectors described above, or any of the host cells described above, under conditions suitable for expressing the multispecific construct; and ii) obtaining the expressed multispecific construct.

[0037] In another aspect, the present invention provides an isolated antibody construct (anti-IL-13 antibody construct) comprising an antibody portion (“anti-IL-13 antibody portion”) that specifically binds to IL-13, wherein the anti-IL-13 antibody portion comprises a heavy chain variable region (VH) and a light chain variable region (VL), and 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 of any of the above-described 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 of any of the above-described anti-IL-13 antibody constructs, the anti-IL-13 antibody portion is selected from the group consisting of: full-length antibody, Fab, Fab', F(ab')2, biantibody, and scFv.

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

[0041] In some embodiments of any of the above-described anti-IL-13 antibody constructs, the anti-IL-13 antibody portion is Fab (“anti-IL-13 Fab”). In some embodiments, the anti-IL-13 Fab comprises 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 197.

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

[0043] In some embodiments of any of the above-described anti-IL-13 antibody constructs, the isolated anti-IL-13 antibody construct is single-specific. In some embodiments, the isolated anti-IL-13 antibody construct is multi-specific.

[0044] In some embodiments of any of the above-described anti-IL-13 antibody constructs, the isolated anti-IL-13 antibody construct further comprises a second antibody portion that specifically binds to a second antigen. In some embodiments, the anti-IL-13 antibody portion and the second antibody portion are fused together via a linker. In some embodiments, the linker comprises the amino acid sequence of either GG or SEQ ID NO:98-99.

[0045] Pharmaceutical compositions are also provided that comprise any of the isolated anti-IL-13 antibody constructs described above and optionally a pharmaceutically acceptable carrier.

[0046] It also provides isolated nucleic acids encoding any of the above-described isolated anti-IL-13 antibody constructs, vectors containing such nucleic acids, and host cells containing such nucleic acids or vectors.

[0047] Methods for treating an individual with an inflammatory disease are also provided, comprising administering to the individual an effective amount of any of the isolated anti-IL-13 antibody constructs described above or any of the pharmaceutical compositions described above. In some embodiments, the inflammatory disease is asthma, atopic dermatitis, or COPD. In some embodiments, the individual is a person.

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

[0049] These and other aspects and advantages of the invention will become apparent from the following detailed description and the appended claims. It should be understood that one, some, or all of the features of the various embodiments described herein can be combined to form other embodiments of the invention.

[0050] All publications, patents, patent applications, and published patent applications cited in this article are incorporated herein by reference in their entirety. Attached Figure Description

[0051] Figure 1 The percentage of TSLP signaling inhibition via the TSLP receptor complex expressed on STAT5-HEK293 reporter cells is shown when treated with an exemplary anti-TSLP antibody.

[0052] Figure 2 This shows that in a competitive ELISA assay, 51B2 and the US-FDA approved reference anti-TSLP Ab bind to overlapping but distinct epitopes on TSLP. Ab, antibody; OD, optical density.

[0053] Figures 3A to 3B It was shown that, compared to the US-FDA approved reference anti-TSLP Ab, 51B2 completely inhibited the PBMC ( Figure 3A ) or isolated dendritic cells ( Figure 3B TSLP-induced CCL17 secretion.

[0054] Figure 4 The IC50 values ​​of each generated humanized Ch51B2 antibody compared to the parental Ch51B2 antibody are shown in a TSLP inhibition assay performed on HEK293 reporter cells transfected with the TSLP receptor complex in humans and cynomolgus monkeys (“cyno”). 50 (nM) and IC 90 (nM) value. The humanized anti-TSLP antibody indicated by the box is the anti-TSLP antibody selected for further analysis.

[0055] Figure 5A The percentage of TSLP signaling inhibition via the TSLP receptor complex expressed on STAT5-HEK293 reporter cells is shown when treated with selected humanized anti-TSLP antibodies (hz51B2 L2H2, hz51B2 L2H9, and hz51B2 L3H9). The Ch51B2 parental chimeric antibody was used as a control.

[0056] Figure 5B The equilibrium binding analysis of hz51B2 L3H9 with human TSLP in solution is shown.

[0057] Figures 6A to 6B The study demonstrated that, in the HEK-Blue 293 IL-13 reporter gene assay, the anti-IL-13 antibody 73P1 enhanced the neutralizing activity against cynomolgus monkey (“cyno”) IL-13 while maintaining the neutralizing activity against human IL-13 inhibition, which produces secretory embryonic alkaline phosphatase (SEAP) upon activation of IL-13 signaling. Figure 6A The neutralizing activities of reference anti-IL-13 antibodies #0 and 73P1 against human IL-13 at multiple concentrations are shown using an IL-13 reporter gene assay, and the IC50 values ​​of the two anti-IL-13 antibodies are provided. 50 . Figure 6B The neutralizing activity of reference anti-IL-13 antibodies #0 and 73P1 against cyno IL-13 at multiple concentrations was shown using an IL-13 reporter gene assay, and the IC50 values ​​of the two anti-IL-13 antibodies were further provided. 50 Conc., concentration; OD, optical density.

[0058] Figures 7A to 7BThe study presents a comparison of the neutralizing activities of anti-IL-13 antibody 73P1 and two US-FDA or EMA-approved anti-IL-13 antibodies, as well as reference anti-IL-13 antibody #1 and reference anti-IL-13 antibody #2 (“Ref. Ab. #1” and “Ref. Ab. #2”) as positive controls, using the HEK-Blue 293 IL-13 reporter gene assay. Wild-type (“WT”) IL-13 or IL-13 R110Q (a disease-associated variant of IL-13) was used as a stimulus, and secretory embryonic alkaline phosphatase (SEAP) was produced following activation of IL-13 signaling. Figure 7A The neutralizing activity of anti-IL-13 antibodies 73P1 and Ref. anti-IL-13 Ab. #1 and #2 against wild-type human IL-13 was demonstrated. Figure 7B The neutralizing activity of anti-IL-13 antibodies 73P1 and Ref. anti-IL-13 Ab. #1 and #2 against the disease-associated human IL-13 variant R110Q was demonstrated, exhibiting increased IL-13 activity. IC50 was provided. 50 value.

[0059] Figures 8A to 8D A schematic overview of a set of exemplary bispecific anti-TSLP×IL-13 antibody constructs based on scFv fusion and insertion is shown.

[0060] Figures 9A to 9B It shows Figures 8A to 8D The inhibitory activity of the TSLP×IL13 bispecific antibody against TSLP and IL-13 is described in the paper. Figure 9A The percentage of TSLP signaling inhibition by the TSLPR / IL-7Rα receptor complex expressed on STAT5-HEK-293 reporter cells is shown when treated with one of the bispecific antibodies. The luciferase produced by the reporter cells serves as a readout for TSLP binding activity. Figure 9B The percentage of IL-13 signaling inhibition by the IL-13Rα1 / IL-4Rα receptor complex expressed on HEK-293 reporter cells is shown when treated with one of the bispecific antibodies. SEAP production and secretion by the reporter cells serve as readouts for IL-13 binding activity. IC50 values ​​for each antibody against the antigen were calculated based on antibody dose-dependent binding inhibition curves. 90 Values. Analyze and present data using GraphPad. Ab, antibody; Conc., concentration.

[0061] Figure 10 It shows Figures 8A to 8DThe in vivo stability of the TSLP×IL-13 bispecific antibodies described herein is represented by the change in in vivo antibody concentration over time after intravenous injection into C57Bl / 6 mice, targeting both the anti-TSLP antigen-binding moiety and the anti-IL-13 antigen-binding moiety of each of the bispecific antibodies. Two animals (n=2 / group) were tested for each antibody / dilution.

[0062] Figures 11A to 11D A schematic overview of a set of exemplary bispecific TSLP×IL-13 antibodies (in the forms PX128-I1 to PX128-I4, respectively) based on Fab fusions is shown.

[0063] Figures 12A to 12B It shows Figures 11A to 11D The forms depicted in the text are PX128-I1 to PX128-I4 and Figure 13 The PX128-R2 bispecific antibody against TSLP×IL-13 described in the text is a TSLP ( Figure 12A ) and IL-13 ( Figure 12B Inhibitory activity of ). Figure 12A The percentage of TSLP signaling inhibition via the TSLP receptor complex expressed on STAT5-HEK-293 reporter cells is shown when treated with one of the bispecific antibodies. Figure 12B The percentage of inhibition of IL-13 signaling via the IL-13 receptor complex expressed on HEK-293 reporter cells is shown when treated with one of the bispecific antibodies. Anti-IL-13 reference antibodies #2, #3, and #4 are included as positive controls. The IC50 value for each antibody against the antigen was calculated based on antibody dose-dependent binding inhibition curves. 90 Values. Analyze and present data using GraphPad. Ab, antibody; Conc., concentration.

[0064] Figure 13 A schematic overview of the PX128-R2 heterodimeric bispecific antibody is provided, wherein the first arm comprises an anti-TSLP Fab fragment and the second arm comprises an anti-IL-13 Fab fragment. The Fc domain includes a club-and-mortar mutation. The CH1 and CL domains of the anti-IL-13 Fab fragment also include 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 (both EU designations).

[0065] Figure 14A schematic overview of the PX128-JT heterodimeric bispecific antibody is provided, wherein the first arm includes an anti-TSLP Fab fragment and the second arm includes an anti-IL-13 Fab fragment. The Fc domain includes a club-and-mortar mutation. The CH1 and CL domains of the anti-IL-13 Fab fragment also include JT11 or JT7 mutations. JT11 mutations include F170V, S183I, and V185L in the HC region of the anti-IL-13 arm and L135F in the LC region (all EU numbers). JT7 mutations include F170I, S183L, and V185L in the HC region of the anti-IL-13 arm and L135F in the LC region (all EU numbers).

[0066] Figure 15 A schematic overview of the PX128-JT / R2 heterodimer bispecific antibody is provided, wherein the first arm includes an anti-TSLP Fab fragment and the second arm includes an anti-IL-13 Fab fragment. The Fc domain includes a club-and-mortise mutation. The heavy and light chains of the anti-IL-13 arm also include R2 mutations and JT11 or JT7 mutations (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).

[0067] Figure 16 The following are shown: PX128-JT7 and PX128-JT11 heterodimer bispecific antibodies (e.g.) Figure 14 The in vivo stability of the antibody (described) was represented by changes in in vivo antibody concentration over time after intravenous injection into C57Bl / 6 mice, targeting both the anti-TSLP antigen-binding moiety and the anti-IL-13 antigen-binding moiety. Each antibody at each concentration was tested in two animals (n=2 / group).

[0068] Figures 17A to 17B Showing Figures 13 to 15 The heterodimer bispecific antibody described in the paper targets TSLP ( Figure 17A ) and IL-13 ( Figure 17B Inhibitory activity of ). Figure 17A The percentage of TSLP signaling inhibition via the TSLP receptor complex expressed on STAT5-HEK-293 reporter cells is shown when treated with one of the heterodimeric bispecific antibodies. Figure 17B The percentage of IL-13 signaling via the IL-13 receptor complex expressed on HEK-293-SEAP reporter cells is shown when treated with one of the heterodimeric bispecific antibodies. The IC50 for each antibody based on the antigen was calculated based on antibody dose-dependent binding inhibition curves.90 Values. Analyze and present data using GraphPad. Ab, antibody; Conc., concentration.

[0069] Figures 18A to 18C The results, as measured by ELISA, are shown. Figure 14 The dose escalation of the PX128-JT7 and PX128-JT11 heterodimer bispecific antibodies described herein produces TSLP-only results. Figure 18A ), using only IL-13 ( Figure 18B ) or use TSLP and IL-13 ( Figure 18C The level of CCL17 in the processed PBMC is generated. Figure 18A The study demonstrates the production of CCL17 induced by treatment with only 0.5 ng / ml TSLP. References Ref. Anti-IL-13 Ab.#2, Ref. TSLP×IL-13 Ab.#3, Ref. TSLP×IL-13×HSA Ab.#4, and Ref. Anti-TSLP Ab.#5 were included as controls. Treatment with only TSLP (… Figure 18A ), using only IL-13 ( Figure 18B ) or use TSLP and IL-13 ( Figure 18C Cells were treated, including those not treated with antibodies as a negative control.

[0070] Figure 19 An exemplary PX128-JT11 heterodimer bispecific antibody (such as...) is shown. Figure 14 The in vivo half-life stability of the antibody (described) is represented by the change in in vivo antibody concentration over time after intravenous bolus or subcutaneous injection into cynomolgus monkeys. Ref. TSLP×IL-13×HSA Ab.#4 is included as a control. Two animals (n=2 / group) were tested for each antibody at each concentration. Detailed Implementation

[0071] This invention provides a multispecific construct (such as a bispecific construct) comprising an anti-IL-13 antibody portion that specifically binds to IL-13 and a second antibody portion that specifically binds to a second target antigen (e.g., TSLP). In some embodiments, the multispecific construct comprises one anti-IL-13 antibody portion. In some embodiments, the multispecific construct comprises two or more anti-IL-13 antibody portions. In some embodiments, the multispecific construct comprises one antibody portion that specifically binds to a second target antigen or target epitope. In some embodiments, the multispecific construct comprises two or more antibody portions 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. This invention also provides, in another aspect, a novel anti-IL-13 antibody construct.

[0072] Following extensive research, the inventors of this application have discovered several unexpected advantages of the multispecific constructs described herein (e.g., the anti-IL-13 multispecific construct) 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., the anti-IL-13 multispecific construct) show 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, some of the multispecific constructs described herein exhibit surprising in vivo stability (e.g., when administered simultaneously to mice and cynomolgus monkeys), making them particularly suitable for formulation at high concentrations. Fourth, some of the multispecific constructs described herein show in vivo half-lives that are significantly longer than those of other control multispecific antibodies (e.g., half-lives that are at least about 1.5, 2, 4, 5, or more times longer than the half-lives of control multispecific antibodies).

[0073] Pharmaceutical compositions and kits comprising either the multispecific constructs or anti-IL-13 antibody constructs described herein are also provided, as well as methods for using them to treat inflammatory diseases such as asthma, atopic dermatitis, or COPD.

[0074] I. Definition

[0075] As used herein, the term "treatment" refers to a clinical intervention designed to alter the natural processes of the treated individual or cells during a clinicopathological process. Desired therapeutic effects include reduced disease progression rates, improved or alleviated disease states, and remission or improved prognosis. For example, an individual is successfully "treated" if one or more symptoms associated with an inflammatory disease are reduced or eliminated, including but not limited to reduced local or systemic inflammation, reduced symptoms caused by the disease, improved quality of life for an individual with the disease, or reduced dosage of other medications required to treat the disease.

[0076] As used herein, “effective amount” refers to the amount of a drug or pharmacological agent that is effective in treating a disease or disorder of a subject (such as an individual, e.g., a person). In the case of an inflammatory disease, an effective amount of a drug may reduce the number of active immune cells; reduce the amount of pro-inflammatory cytokines; locally and / or systemically inhibit (i.e., to some extent slow down, and preferably terminate) the activity of inflammatory immune cells; and / or to some extent alleviate one or more symptoms associated with the inflammatory disease. As understood in a clinical context, an effective amount of a drug, compound, or pharmaceutical composition may or may not be achieved in combination with another drug, compound, or pharmaceutical composition. Therefore, an “effective amount” can be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be administered in an effective amount if the desired result is achieved or is achieved in combination with one or more other agents.

[0077] As used herein, "individual" or "subject" refers to a mammal, including but not limited to humans, cattle, horses, cats, dogs, rodents, or primates. In some implementations, the individual is a human.

[0078] The term “antibody” is used in the broadest sense and specifically covers monoclonal antibodies (including full-length monoclonal antibodies), multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, provided they exhibit the desired biological activity or function. As used herein, the terms “immunoglobulin” (Ig) and “antibody” are used interchangeably.

[0079] The term "full-length antibody" is used herein to refer to an antibody in its essentially complete form, rather than an antibody fragment as defined below. Specifically, it refers to antibodies with a heavy chain containing an Fc region. Full-length antibodies are typically heterotetrameric glycoproteins of approximately 150,000 Daltons, composed of two identical light (L) chains and two identical heavy (H) chains.

[0080] The term "constant domain" refers to a portion of an immunoglobulin molecule that has a more conserved amino acid sequence compared to other parts of the immunoglobulin, including the variable domain containing the antigen-binding site. The constant domain contains the C16 heavy chain. H 1. C H 2 and CH 3. The structural domains (collectively referred to as CH) and the C of the light chain H L (or CL) structural domain.

[0081] The "variable region" or "variable domain" of an antibody refers to the amino-terminal domain of either 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 typically the most variable parts of the antibody and contain antigen-binding sites.

[0082] The term "variable" refers to the fact that certain portions of a variable domain are widely sequence-differentiated between antibodies and are responsible for the binding and specificity of each particular antibody to its specific antigen. However, variability is not uniformly distributed throughout the entire variable domain of an antibody. It is concentrated in three segments called hypervariable regions (HVRs, also known as CDRs) in both the light chain and heavy chain variable domains. The more highly conserved portions of the variable domain are called frame regions (FRs). The native heavy and light chain variable domains each contain four FRs, predominantly in a β-sheet configuration, linked by three HVRs that form loops connecting the β-sheet structures and, in some cases, their portions. The HVRs in each chain are held tightly together by the FRs and, together with HVRs from the other chain, contribute to the formation of the antibody's antigen-binding site (see Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed., National Institute of Health, Bethesda, Md. (1991)). Constant domains do not directly participate in antibody-antigen binding but exhibit various effector functions, such as antibody involvement in antibody-dependent cytotoxicity. The residues of constant domains are described in this paper based on EU numbering.

[0083] As used herein, the term “CDR” or “complementarity-determining region” is intended to refer to a discontinuous antigen-binding site found within the variable region of heavy and light chain polypeptides. These specific regions have been described in the following literature: Kabat et al., J. Biol. Chem. 252:6609-6616 (1977); Kabat et al., US Dept. of Health and Human Services, “Sequences of proteins of immunological interest” (1991); Chothia et al., J. Mol. Biol. 196:901-917 (1987); Al-Lazikani B. et 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 MP et al., Dev. Comp. Immunol., 27: 55-77 (2003); and Honegger and Plückthun, J. Mol. Biol., 309:657-670 (2001), where, when compared with each other, the definitions include overlaps or subsets of amino acid residues. However, the application of either definition to refer to an antibody or a transplanted antibody or a variant thereof is intended to be within the scope of the terminology as defined and used herein. The amino acid residues covering the CDR defined in each of the references cited above are listed as a comparison 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 entire contents of the references cited in this paragraph are incorporated herein by reference for the purposes of this application and may be included in one or more of the claims herein. The amino acid residues of the CDRs provided herein are described based on Kabat.

[0084] Table A. CDR Definition

[0085]

[0086] 1 Residue numbering follows the nomenclature of Kabat et al., as above.

[0087] 2 Residue numbering follows the nomenclature of Chothia et al., as above.

[0088] 3 Residue numbering follows the nomenclature of MacCallum et al., as above.

[0089] 4 Residue numbering follows the nomenclature of Lefranc et al., as above.

[0090] 5 Residue numbering follows the Honegger and Plückthun nomenclature, as described above.

[0091] Based on the amino acid sequence of its constant structural domains, the "light chain" of antibodies (immunoglobulins) derived from any mammalian species can be designated as one of two completely different types (i.e., κ and λ).

[0092] As used herein, the term IgG “isotype” or “subclass” refers to any subclass of immunoglobulin defined by the chemical and antigenic characteristics of its constant region.

[0093] Antibodies (immunoglobulins) can be classified into different classes based on the amino acid sequence of their heavy chain constant domains. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these classes can be further subdivided into subclasses (isotypes), such as IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains corresponding to different classes of immunoglobulins are designated as α, δ, α, γ, and µ, respectively. The subunit structures and three-dimensional conformations of different classes of immunoglobulins are well-known and generally described, for example, in Abbas et al., Cellular and Mol. Immunology, 4th edition (WBSaunders, Co., 2000). Antibodies can be part of a larger fusion molecule formed by the covalent or non-covalent association of an antibody with one or more other proteins or peptides.

[0094] An "antibody fragment" comprises a portion of a complete 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 (such as single-chain variable fragments, scFv); biantibodies; linear antibodies; single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.

[0095] Antibody digestion with papain produces two identical antigen-binding fragments, called "Fab" fragments (each with a single antigen-binding site) and a residual "Fc" fragment (whose name reflects its tendency to crystallize). Pepsin treatment produces the F(ab')2 fragment, which has two antigen-binding sites and is still capable of cross-linking the antigen.

[0096] "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 a heavy-chain variable domain and a light-chain variable domain in tight non-covalent association. In a single-stranded Fv (scFv) species, a heavy-chain variable domain and a light-chain variable domain can be covalently linked by a flexible peptide linker, allowing the light and heavy chains to associate into a "dimer" structure similar to the dimer structure in the double-stranded Fv species. It is in this configuration that the three HVRs of each variable domain interact to define the antigen-binding site on the surface of the VH-VL dimer. The six HVRs collectively confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv containing only three HVRs specific to the antigen) has the ability to recognize and bind antigens, albeit with a lower affinity than the complete binding site.

[0097] The Fab fragment has two polypeptide chains containing a variable domain (VH) of the heavy chain and a variable domain (VL) of the light chain, and also contains a constant domain (CL) of the light chain and a first constant domain (C) of the heavy chain. H 1). The difference between the Fab' fragment and the Fab fragment lies in the heavy chain C containing one or more cysteine ​​residues from the antibody hinge region. H Several residues were added to the carboxyl terminus of the 1 domain. Fab'-SH is the name given in this paper to the Fab' whose constant domain contains cysteine ​​residues with free thiol groups. The F(ab')2 antibody fragment was initially generated as a Fab' fragment pair with a hinged cysteine ​​residue in between. Other chemical conjugations of antibody fragments are also known.

[0098] A "single-chain Fv" or "scFv" antibody fragment contains both the VH and VL domains of the antibody, which are contained within a single polypeptide chain. Typically, the scFv polypeptide also includes a polypeptide linker between the VH and VL domains, which allows the scFv to form the desired structure for antigen binding. For a review of scFvs, see, for example, Pluckthün, *The Pharmacology of Monoclonal Antibodies*. Springer Berlin, Heidelberg, 1994, pp. 269-315.

[0099] The “Fc” fragment contains the carboxyl-terminal portions of two heavy chains held together by disulfide bonds. The effector function of an antibody is determined by the sequence in the Fc region, which is also the region recognized by the Fc receptor (FcR) found on certain types of cells.

[0100] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous population of antibodies, for example, the individual antibodies constituting that population are identical except for the possibility of a small number of possible mutations (e.g., naturally occurring mutations). Therefore, the modifier "monoclonal" indicates that the antibody is not a mixture of discrete antibodies. In some embodiments, such monoclonal antibodies typically comprise an antibody containing a polypeptide sequence that binds to a target, wherein the target-binding polypeptide sequence is obtained by a method comprising selecting a single target-binding polypeptide sequence from a plurality of polypeptide sequences. For example, the selection process may be to select a unique clone from a pool of clones, such as hybridoma clones, phage clones, or recombinant DNA clones. It should be understood that the selected target-binding sequence can be further modified, for example, to improve affinity for the target, humanize the target-binding sequence, improve its production in cell cultures, reduce its immunogenicity in vivo, generate multispecific antibodies, etc., and antibodies containing modified target-binding sequences are also monoclonal antibodies of the present invention. In contrast to polyclonal antibody formulations, which typically comprise different antibodies against different determinants (epitopes), each monoclonal antibody in a monoclonal antibody formulation targets a single determinant on an antigen. In addition to their specificity, monoclonal antibody preparations have the advantage that they are generally not contaminated by other immunoglobulins.

[0101] The modifier “monoclonal” indicates that the antibody is derived from a substantially homologous group of antibodies and is not interpreted as requiring the antibody to be produced by any particular method. For example, the monoclonal antibodies used according to the present invention can be prepared by a variety of techniques, including, for example, hybridoma methods (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, 2nd edition 1988); Hammerling et al., Monoclonal Antibodies and T-Cell Hybridomas 563-681 (Elsevier, NY, 1981)), recombinant DNA methods (see, for example, U.S. Patent No. 4,816,567), phage display techniques (see, for example, 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 101(34): 12467-12472 (2004); and Lee et al., J. Immunol. Methods 284(1-2): 119-132 (2004)), and techniques for generating human or human-like antibodies in animals having a portion or all of the human immunoglobulin loci or genes encoding human immunoglobulin sequences (see, for example, WO 1998 / 24893; WO 1996 / 34096; WO 1996 / 33735; WO1991 / 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 Immunol.7:33 (1993); U.S. Patents 5,545,807, 5,545,806, 5,569,825, 5,625,126, 5,633,425 and 5,661,016; Marks et al., Bio / Technology 10: 779-783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368: 812-813 (1994); Fishwild et al., Nature Biotechnol. 14: 845-851 (1996); Neuberger, Nature Biotechnol. 14: 826 (1996); and Lonberg and Huszar, Intern. Rev. Immunol. 13: 65-93 (1995)). .

[0102] The monoclonal antibodies described herein specifically comprise “chimeric” sequences in which a portion of the heavy and / or light chain is identical or homologous to a corresponding sequence in an antibody derived from a specific species or belonging to a specific antibody species or subclass, while the remainder of the chain is identical or homologous to a corresponding sequence in an antibody derived from another species or belonging to another antibody species or subclass, as well as fragments of such antibodies, provided 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, wherein the antigen-binding region of an antibody is derived from antibodies produced by, for example, immunizing a macaque with the antigen of interest.

[0103] Humanized forms of nonhuman (e.g., mouse) antibodies are chimeric antibodies containing minimal sequences derived from nonhuman immunoglobulins. In one embodiment, the humanized antibody is a human immunoglobulin (recipient antibody) in which residues in the recipient's HVR are replaced by residues in the HVR of a nonhuman species (donor antibody) such as a mouse, rat, rabbit, or nonhuman primate having the desired specificity, affinity, and / or ability. In some cases, FR residues of the human immunoglobulin are replaced by corresponding nonhuman residues. Furthermore, the humanized antibody may contain residues not found in either the recipient or donor antibody. These modifications can be made to further improve antibody performance. Generally, the humanized antibody will contain at least one, and typically two, variable domains, wherein all or substantially all of the hypervariable loops correspond to those of the nonhuman immunoglobulin, and all or substantially all of the FRs are those of the human immunoglobulin sequence. The humanized antibody will also optionally contain at least a portion of the immunoglobulin constant region (Fc), typically at least a portion of the constant region of the human immunoglobulin. For further details, see, for example, Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992). See also, for example, Vaswani and Hamilton, Ann. Allergy, Asthma & Immunol. 1:105-115 (1998); Harris, Biochem. Soc. Transactions 23:1035-1038 (1995); Hurle and Gross, Curr. Op. Biotech. 5:428-433 (1994); and U.S. Patent Nos. 6,982,321 and 7,087,409.

[0104] "Human antibody" refers to an antibody having an amino acid sequence corresponding to that of an antibody produced by humans and / or prepared using any technique for preparing human antibodies as disclosed herein. This definition of human antibody specifically excludes humanized antibodies containing 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 also used for preparing human monoclonal antibodies are described in Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, 77 (1985); Boerner et al., J. Immunol. 147(1):86-95 (1991). See also van Dijk and van de Winkel, Curr. Opin. Pharmacol. 5: 368-74 (2001). Human antibodies can be prepared by administering an antigen to a transgenic animal that has been modified to produce such antibodies in response to antigen challenge, but whose endogenous loci have been disabled, for example, in immunized xenogeneic mice (see, for example, U.S. Patent Nos. 6,075,181 and 6,150,584, concerning XENOMOUSE). ™ (Technology). For information on human antibodies generated via human B-cell hybridoma technology, see, for example, Li et al., Proc. Natl. Acad. Sci. USA 103:3557-3562 (2006).

[0105] The terms “hypervariant region,” “HVR,” or “HV,” as used herein, refer to regions within the variable domains of an antibody that exhibit sequence hypervariability and / or form structurally defined loops. Typically, antibodies contain six HVRs: three in the VH domain (H1, H2, H3) and three in the VL domain (L1, L2, L3). In native antibodies, H3 and L3 exhibit the greatest diversity among the six HVRs, and H3, in particular, is considered to play a unique role in conferring fine specificity to antibodies. See, for example, Xu et al., Immunity 13:37–45 (2000); Johnson and Wu, Methods in Molecular Biology 248:1–25 (Lo ed., HumanPress, Totowa, NJ, 2003). Indeed, naturally occurring camel antibodies consisting solely 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); Sheriff et al., Nature Struct. Biol. 3:733-736 (1996). HVR is also known as “CDR” or “complementary determinant region”.

[0106] The structure and location of the immunoglobulin variable region can be determined by referring to Kabat, E.A. et al., Sequences of Proteins of Immunological Interest. 4th ed. US Department of Health and Human Services. 1987 and its updates (now available on the Internet (immuno.bme.nwu.edu)).

[0107] "Frame" or "FR" residues are those variable domain residues other than HVR residues as defined herein.

[0108] As used herein, the term "covalent link" refers to a direct link through one or more chemical bonds or an indirect link through one or more junctions. Direct links can be generated using any suitable chemical bond, including but not limited to covalent bonds such as peptide and disulfide bonds, or non-covalent bonds such as hydrogen bonds, hydrophobic bonds, ionic bonds, or van der Waals bonds.

[0109] As used herein, a "covalent bond" is 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, a "peptide bond" is a covalent bond formed between the carboxyl group of an amino acid and the amino group of an adjacent amino acid. As used herein, a "disulfide bond" is a covalent bond formed between two sulfur atoms, such as in a heavy chain segment C. H 1 and the light chain segment CL are linked by a combination of one or more disulfide bonds. One or more disulfide bonds can be formed between the two segments by connecting thiol groups in the two segments. In some embodiments, one or more disulfide bonds may be formed between one or more cysteine ​​residues of the heavy chain segment and the light chain segment, respectively. Disulfide bonds can be formed by the oxidation of two thiol groups. In some embodiments, the covalent bonds are directly linked by covalent bonds. In some embodiments, the covalent bonds are directly linked by peptide bonds or disulfide bonds.

[0110] As used herein, the terms “binding,” “specifically binding,” or “specific to” refer to a measurable and reproducible interaction, such as the binding between a target and an antibody, which determines the presence of the target in the presence of a heterogeneous molecular population comprising 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 with greater affinity, cohesion, ease of binding, and / or longer duration of binding compared to its binding to other targets. In one embodiment, the degree to which the antibody binds to an unrelated target is less than about 10% of the antibody-target binding, as measured, for example, by radioimmunoassay (RIA). In some embodiments, antibodies that specifically bind to a target have a dissociation constant (Ki) of ≤ 1 μM, ≤ 100 nM, ≤ 10 nM, ≤ 1 nM, or ≤ 0.1 nM. d In some embodiments, the antibody specifically binds to an epitope on a protein that is conserved across proteins from different species. In another embodiment, specific binding may include, but is not required to be, exclusive binding.

[0111] As used herein, the “percentage of amino acid sequence identity (%)” relative to a peptide, polypeptide, or antibody sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical to amino acid residues in a specific peptide or polypeptide sequence, after alignment and cleavage to achieve the maximum percentage of sequence identity, if necessary, and without considering any conserved substitutions as part of the sequence identity. Alignments performed for the purpose of determining the percentage of amino acid sequence identity can be performed in a variety of ways within the scope of the art, such as using publicly available computer software such as BLAST, BLAST-2, ALIGN, or MEGALIGN. ™(DNASTAR) software. Those skilled in the art can determine the appropriate parameters for measuring alignment, including any algorithms required to achieve maximum alignment across the full length of the sequences to be compared.

[0112] Amino acid substitutions may include, but are not limited to, the replacement of one amino acid in a peptide with another. Exemplary substitutions are shown in Table B. Amino acid substitutions can be introduced into antibodies of interest, and the desired activity of the product can be screened, such as preserved / improved antigen binding, reduced immunogenicity, or improved ADCC or CDC.

[0113] Table B. Exemplary Amino Acid Substitutions .

[0114]

[0115] Amino acids can be grouped according to common side chain characteristics: (1) hydrophobic: leucine, Met, Ala, Val, Leu, Ile; (2) neutral-hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues affecting chain orientation: Gly, Pro; and (6) aromatic: Trp, Tyr, Phe. Non-conservative substitutions will require swapping members from one category to another.

[0116] The term "multispecific" used in conjunction with antibodies or antigen-binding proteins refers to antibodies or antigen-binding proteins that have multi-epitope specificity (i.e., the ability to specifically bind to two, three, or more different epitopes on a single biomolecule, or the ability to specifically bind to epitopes on two, three, or more different biomolecules). Unless otherwise specified, the order in which the antigens bound to a multispecific antibody are listed in its name is arbitrary.

[0117] The term "bispecific" 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 a single biomolecule, or specifically bind to epitopes on two different biomolecules. Unless otherwise specified, the order in which the antigens bound to a bispecific antibody are listed in its name is arbitrary.

[0118] The "mortar and pestle" strategy (see, for example, PCT International Publication No. WO 2006 / 028936) has its simple and general meaning as understood in the specification, and refers to a strategy that can be used to generate full-length bispecific antibodies. In short, it involves the formation of C in human IgG. H The selection of amino acids at the junction of the three domains can affect C. HMutations at the sites of the three domain interactions promote heterodimer formation. Amino acids with small side chains (potassium) are introduced into the heavy chain of an antibody that specifically binds to the first antigen, while amino acids with large side chains (grossroots) are introduced into the heavy chain of an antibody that specifically binds to the second antigen. After co-expression of the two antibodies, heterodimers form due to the preferential interaction between the "potassium" and "grossroots" heavy chains.

[0119] As used herein, the term "vector" refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. This term includes vectors that function as self-replicating nucleic acid structures, as well as vectors that are integrated into the genome of the host cell to which they are introduced. Some vectors are capable of directing the expression of nucleic acids to which they are operatively linked. Such vectors are referred to herein as "expression vectors."

[0120] It should be understood that the embodiments of the present invention described herein include embodiments that are "composed of" and / or "substantially composed of".

[0121] The use of "about" in this article to refer to a value or parameter includes (and describes) variations relating to that value or parameter itself. For example, a description of "about X" includes a description of "X".

[0122] The terms “about” and “approximately” mean within 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less of a given value or range.

[0123] As used herein, references to "not" values ​​or parameters generally mean and describe values ​​or parameters that are "other than" or "not otherwise". For example, "This method is not used to treat type X inflammatory diseases" means that this method is used to treat inflammatory diseases other than type X.

[0124] The term “about XY” as used in this article has the same meaning as “about X to about Y”.

[0125] As used herein and in the appended claims, the singular forms “a / an,” “or,” and “the / said” include plural references unless the context clearly indicates otherwise.

[0126] II. Multispecific anti-IL-13 antibody construct

[0127] In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising: i) a first antibody portion that specifically binds to interleukin-13 (IL-13; "anti-IL-13 antibody portion", such as any of the anti-IL-13 antibody portions described herein), and ii) a second antibody portion that specifically binds to a second target antigen. In some embodiments, the second target antigen is IL-13 (e.g., an epitope that is the same as or different from the epitope bound to the first antibody portion). 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, such as 1 or 2) anti-IL-13 antibody portions (e.g., scFv, Fab, or full-length antibody). In some embodiments, the multispecific construct comprises first and second anti-IL-13 antibody portions (e.g., first and second anti-IL-13 Fab, or first and second anti-IL-13 scFv), a third antibody portion (e.g., Fab, scFv) optionally specifically binding to a third target antigen, and a fourth antibody portion optionally specifically binding to a fourth target antigen. In some embodiments, the multispecific construct comprises: a first anti-IL-13 antibody portion, a second antibody portion specifically binding to a second target antigen, and a third antibody portion specifically binding to a third target antigen. In some embodiments, the first and second anti-IL-13 antibody portions have the same amino acid sequence. In some embodiments, the first and second anti-IL-13 antibody portions have different amino acid sequences. In some embodiments, the first and second anti-IL-13 antibody portions bind to the same IL-13 epitope. In some embodiments, the first and second anti-IL-13 antibody portions bind to different IL-13 epitopes. In some embodiments, the third and fourth antibody portions have the same amino acid sequence. In some embodiments, the third and fourth antibody moieties have different amino acid sequences. In some embodiments, the third and fourth antibody moieties bind to the same target epitope. In some embodiments, the third and fourth antibody moieties bind to different target epitopes.

[0128] In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising: i) a first antibody component for specifically binding IL-13, and ii) a second antibody component for specifically binding a second target antigen. In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising: i) a first antibody component for specifically binding IL-13, and ii) a second antibody component for specifically binding TSLP. In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising: i) a first antibody component for specifically binding IL-13, and ii) a second antibody portion (such as any of the second antibody portions described herein) for specifically binding a second target antigen. In some embodiments, a multispecific construct or isolated anti-IL-13 antibody construct is provided, comprising: i) a first antibody component for specifically binding IL-13, and ii) a second antibody portion (such as any of the anti-TSLP portions described herein) for specifically binding TSLP. The anti-IL-13 antibody moiety described herein may possess one or more of the following advantageous properties, including, for example: 1) high binding affinity for 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; 4) inhibiting IL-13 signaling through the IL-13Rα1 / IL-4Rα complex. The anti-TSLP antibody moiety described herein may possess one or more of the following advantageous properties, including, for example: 1) high binding affinity for TSLP; 2) blocking TSLP / TSLPR interaction; 3) inhibiting TSLP signaling through the TSLPR / IL-7Rα complex.

[0129] In some embodiments, the multispecific constructs described herein have an increased (e.g., an increase of at least about 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more times) in vivo half-life compared to a single anti-IL-13 antibody moiety (e.g., Fab, scFv, full-length antibody). In some embodiments, the multispecific constructs described herein have an increased (e.g., an increase of at least about 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more times) in vivo half-life compared to a single second antibody moiety that specifically recognizes a second antigen (e.g., TSLP).

[0130] In some embodiments, a multispecific construct is provided comprising: a first antibody portion as an anti-IL-13 scFv (e.g., any anti-IL-13 scFv described herein) and a second antibody portion as a full-length antibody that specifically binds to a second target antigen (e.g., TSLP), wherein the anti-IL-13 scFv is fused to the C-terminus of one of the heavy chains of the second antibody portion to form a fusion polypeptide. In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody portions as scFvs (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”, for example, either of the anti-IL-13 scFvs described herein) and a second antibody portion as 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 portion 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 portion 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, such as human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU numbers). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU numbers). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU numbers), and the second subunit of the Fc domain contains T366W substitutions (EU numbers); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU numbers), and the first subunit of the Fc domain contains T366W substitutions (EU numbers).

[0131] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as scFv (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”, for example, any of the anti-IL-13 scFvs described herein), two second antibody moieties as 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, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-anti-IL-13 scFv1-optional linker-first subunit of the Fc domain; iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-anti-IL-13 scFv2 - optional linker - second subunit of the Fc domain; and iv) a fourth polypeptide comprising, from N' to C': VL2-(L2-CL); and wherein 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, such as human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU number). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU number). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU number). In some implementations, (i) the first subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number).

[0132] In some embodiments, a multispecific construct is provided comprising: a first antibody portion as an anti-IL-13 full-length antibody (e.g., any of the anti-IL-13 full-length antibodies described herein) and a second antibody portion as an scFv that specifically binds to a second target antigen (e.g., TSLP), wherein the scFv portion is fused to the C-terminus of one of the heavy chains of the anti-IL-13 full-length antibody to form a fusion polypeptide. In some embodiments, a multispecific construct is provided comprising: a first antibody portion as an anti-IL-13 full-length antibody (e.g., any of the anti-IL-13 full-length antibodies described herein) and two second antibody portions as 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 anti-IL-13 full-length antibody to form a first fusion polypeptide, and scFv2 is fused to the C-terminus of the second heavy chain of the anti-IL-13 full-length 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, such as human IgG1. In some embodiments, each subunit of the Fc domain contains L234A and L235A substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number).

[0133] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, for example, the anti-IL-13 antibody moieties described herein). The multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-scFv1-optional linker-Fc domain first subunit; iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-scFv2-optional linker-Fc domain second subunit; and iv) a fourth polypeptide comprising, from N' to C': VL2-(L2-CL); and wherein VH1-(H1-CH1) and VL1-(L1-CL) form an anti-IL-13 antibody. Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 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, such as human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU number). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU number). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU number). In some implementations, (i) the first subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number).

[0134] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, for example, the anti-IL-13 antibody moieties described herein). The multispecific construct comprises: i) a first polypeptide comprising: a first light chain of the second antibody portion; ii) a second polypeptide comprising, from N' to C': a first heavy chain of the second antibody portion - optionally a linker - VH1-(H1-CH1); iii) a third polypeptide comprising, from N' to C': a second heavy chain of the second antibody portion - optionally a linker - VH2-(H2-CH1); iv) a fourth polypeptide comprising: a second light chain of the second antibody portion; v) a fifth polypeptide comprising, from N' to C': VL1-(L1-CL); and vi) a sixth polypeptide comprising, from N' to C': VL2-(L2-CL); and wherein VL1-(L1-CL) and VH1-(H1-CH1) form an anti-IL-13. Fab1, and VL2-(L2-CL) and VH2-(H2-CH1) form an anti-IL-13 Fab2. In some embodiments, the anti-IL-13 Fab1 comprises H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL); wherein the anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL); wherein: (a) H1 and H2 each contain F170I, S183L and V185L substitutions, and L1 and L2 each contain L135F substitutions; (b) H1 and H2 each contain F170V, S183I and V185L substitutions, and L1 and L2 each contain L135F substitutions; (c) H1 and H2 each contain F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each contain F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; wherein the amino acid positions are according to EU numbers. In some embodiments, the full-length antibody contains an Fc domain, wherein the Fc domain contains 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, such as human IgG1. In some embodiments, each subunit of the Fc domain contains L234A and L235A substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number). In some implementations, the light chain of the full-length antibody is derived from the κ light chain.

[0135] In some embodiments, a multispecific construct is provided comprising: a first anti-IL-13 antibody portion as a full-length antibody (“anti-IL-13 full-length antibody”; for example, any of the anti-IL-13 full-length antibodies described herein) and two second antibody portions as Fab (“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 the anti-IL-13 full-length antibody; ii) a second polypeptide comprising, from N' to C': a first heavy chain (H1) of the anti-IL-13 full-length antibody - optionally a linker - VH3 - ( iii) a third polypeptide comprising, from N' to C': the second heavy chain (H2) of the full-length anti-IL-13 antibody - optionally a linker - VH4-(H4-CH1); iv) a fourth polypeptide comprising: the second light chain (L2) of the full-length anti-IL-13 antibody; v) a fifth polypeptide comprising, from N' to C': VL3-(L3-CL); and vi) a sixth polypeptide comprising, from N' to C': VL4-(L4-CL); and 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 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 L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; (d) H1 and H2 each contain substitutions of F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; and the amino acid positions therein are according to EU numbers. In some embodiments, the full-length anti-IL-13 antibody contains an Fc domain, wherein the Fc domain contains 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, such as human IgG1. In some embodiments, each subunit of the Fc domain contains L234A and L235A substitutions (EU numbers).In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU designations). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU designations). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU designations), and the second subunit of the Fc domain contains T366W substitutions (EU designations); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU designations), and the first subunit of the Fc domain contains T366W substitutions (EU designations). In some embodiments, L3-CL and L4-CL are derived from the κ light chain.

[0136] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, for example, the anti-IL-13 antibody moieties described herein). The multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-first heavy chain of the second antibody portion; iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-second heavy chain of the second antibody portion; iv) a fourth polypeptide comprising, from N' to C': VL2-(L2-CL); v) a fifth polypeptide comprising, the first light chain of the second antibody portion; and vi) a sixth polypeptide comprising, the second light chain of the second antibody portion; and wherein VL1-(L1-CL) and VH1-(H1-CH1) form an anti-IL-13. Fab1, 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); wherein anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL); wherein: (a) H1 and H2 each contain F170I, S183L and V185L substitutions, and L1 and L2 each contain L135F substitutions; (b) H1 and H2 each contain F170V, S183I, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (c) H1 and H2 each contain F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each contain F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; and the amino acid positions therein are according to EU numbers. In some embodiments, the full-length antibody contains an Fc domain, wherein the Fc domain contains 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, such as human IgG1. In some embodiments, each subunit of the Fc domain contains L234A and L235A substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number). In some implementations, the light chain of the full-length antibody is derived from the κ light chain.

[0137] In some embodiments, a multispecific construct is provided comprising: a first antibody portion as a full-length IL-13 antibody (e.g., any of the full-length anti-IL-13 antibodies described herein) and two second antibody portions as Fab (“Fab1” and “Fab2”) that specifically bind a second target antigen (e.g., TSLP); wherein the multispecific construct comprises: i) a first polypeptide comprising, from N’ to C’: VL3-(L3-CL); ii) a second polypeptide comprising, from N’ to C’: VH3-(H3-CH1)-optional linker-first heavy chain (H1) of the full-length anti-IL-13 antibody; iii) a third antibody portion; and iv) a second antibody portion. The peptide, the third polypeptide comprising from N' to C': VH4-(H4-CH1)-optional linker-second heavy chain (H2) of the full-length anti-IL-13 antibody; iv) the fourth polypeptide comprising from N' to C': VL4-(L4-CL); v) the fifth polypeptide comprising from N' to C': the first light chain (L1) of the full-length anti-IL-13 antibody; and vi) the sixth polypeptide comprising from N' to C': the second light chain (L2) of the full-length anti-IL-13 antibody; and 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 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 L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; (d) H1 and H2 each contain substitutions of F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; wherein the amino acid positions are according to EU numbers. In some embodiments, the full-length IL-13 antibody contains an Fc domain, wherein the Fc domain contains 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, such as human IgG1. In some embodiments, each subunit of the Fc domain contains L234A and L235A substitutions (EU numbers).In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU designations). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU designations). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU designations), and the second subunit of the Fc domain contains T366W substitutions (EU designations); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU designations), and the first subunit of the Fc domain contains T366W substitutions (EU designations). In some embodiments, L3-CL and L4-CL are derived from the κ light chain.

[0138] In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety 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 contains substitutions at positions 170, 183, and 185 (EU number), and L1 contains a substitution at position 135 (EU number); and / or (ii) H1 contains substitutions at positions 126 and 220 (EU number), and L1 contains substitutions at positions 124 and 214 (EU number). In some embodiments, H1 contains substitutions at positions F170, S183, and V185 (EU number), and L1 contains a substitution at position L135 (EU number). In some embodiments, H1 contains substitutions F170I, S183L, and V185L (EU number), and L1 contains a substitution L135F (EU number). In some embodiments, H1 contains substitutions F170V, S183I, and V185L (EU number), and L1 contains a substitution L135F (EU number). In some embodiments, L1 is derived from the λ light chain (e.g., a λ light chain containing the amino acid sequence of SEQ ID NO: 74 or 75). In some embodiments, H1 contains substitutions at positions F126 and C220 (EU number), and L1 contains substitutions at positions E124 and C214 (EU number). In some embodiments, H1 contains F126C and C220S substitutions (EU number), and L1 contains E124C and C214S substitutions (EU number). In some embodiments, L2 is derived from the κ light chain. In some embodiments, L1 is derived from the κ light chain (e.g., a κ light chain containing the amino acid sequence of SEQ ID NO: 73). In some embodiments, H1 contains substitutions at positions F126 and C220 (EU number), and L1 contains substitutions at positions Q124 and C214 (EU number). In some embodiments, H1 contains F126C and C220S substitutions (EU designations), and L1 contains Q124C and C214S substitutions (EU designations). In some embodiments, L2 is derived from the λ 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, wherein the positions are based on EU numbers. 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; wherein the positions are based on EU numbers. In some implementations, (i) H1 is substituted with F126C, F170I, S183L, V185L, and C220S, and L1 is substituted with E124C, L135F, and C214S; (ii) H1 is substituted with F126C, F170V, S183I, V185L, and C220S, and L1 is substituted with E124C, L135F, and C214S; (iii) H1 is substituted with F126C, F170I, S183L, V185L, and C220S, and L1 is substituted with Q124C, L135F, and C214S; or (iv) H1 contains substitutions of F126C, F170V, S183I, V185L, and C220S, and L1 contains substitutions of Q124C, L135F, and C214S; and the positions therein are according to EU designations. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain contains substitutions of L234A and L235A (EU designations). In some embodiments, each subunit of the Fc domain contains substitutions of M428L and N434S (EU designations). In some embodiments, each subunit of the Fc domain contains substitutions of M252Y, S254T, and T256E (EU designations). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain contains T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain contains T366W substitution (EU numbering). In some embodiments, the mutations described herein in H1 and L1 may alternatively occur in H2 and L2.

[0139] In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 contains substitutions at positions 170, 183, and 185 (EU number), and L1 contains a substitution at position 135 (EU number). In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 comprises F170I, S183L, and V185L substitutions (EU number), and L1 comprises L135F substitution (EU number). In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 comprises F170V, S183I, and V185L substitutions (EU number), and L1 comprises L135F substitution (EU number).In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain contains L234A and L235A substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number). In some embodiments, (a) H1 comprises substitutions of F170I, S183L, V185L, T366S, L368A, and Y407V, L1 comprises substitutions of L135F, and H2 comprises substitutions of T366W; (b) H1 comprises substitutions of F170I, S183L, V185L, and T366W, L1 comprises substitutions of L135F, and H2 comprises substitutions of T366S, L368A, and Y407V; (c) H1 comprises substitutions of F170V, S183I, V185L, T366S, L368A, and Y407V, L1 comprises substitutions of L135F, and H2 comprises substitutions of T366W; or (d) H1 contains F170V, S183I, V185L, and T366W substitutions, L1 contains L135F substitutions, and H2 contains T366S, L368A, and Y407V substitutions; and the amino acid positions therein are according to EU numbers. In some embodiments, L1 is derived from the λ light chain, and L2 is derived from the κ light chain.

[0140] In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 contains substitutions at positions 126 and 220 (EU number), and L1 contains substitutions at positions 124 and 214 (EU number). In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 comprises F126C and C220S substitutions (EU number), and L1 comprises E124C and C214S substitutions (EU number). In some implementations, L2 is derived from the κ light chain.In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 comprises F126C and C220S substitutions (EU number), and L1 comprises Q124C and C214S substitutions (EU number). In some embodiments, L2 is derived from the λ light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain contains L234A and L235A substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number).In some embodiments, (a) H1 comprises substitutions of F126C, C220S, T366S, L368A, and Y407V, L1 comprises substitutions of E124C and C214S, and H2 comprises substitutions of T366W; (b) H1 comprises substitutions of F126C, C220S, and T366W, L1 comprises substitutions of E124C and C214S, and H2 comprises substitutions of T366S, L368A, and Y407V; (c) H1 comprises substitutions of F126C, C220S, T366S, L368A, and Y407V, L1 comprises substitutions of Q124C and C214S, and H2 comprises substitutions of T366W; or (d) H1 contains F126C, C220S and T366W substitutions, L1 contains Q124C and C214S substitutions, and H2 contains T366S, L368A and Y407V substitutions; and the amino acid positions are based on EU numbers.

[0141] In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an Fc domain; and iv) a second light chain (L1-CL) comprising VH1 and H1-CH1, and a second subunit of an Fc domain; and iv) a second light chain (L1-CL) comprising VH1 and H1-CH1, and a first ... 2) The second light chain comprises VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 contains substitutions at positions 126, 170, 183, 185, and 220 (EU number), and L1 contains substitutions at positions 124, 135, and 214 (EU number). In some embodiments, L1 is derived from the λ light chain. In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an Fc domain; and iv) a second light chain (L2). The second light chain comprises VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 comprises F126C, F170I, S183L, V185L and C220S substitutions (EU number), and L1 comprises E124C, L135F and C214S substitutions (EU number).In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an Fc domain; and iv) a second light chain (L2). The second light chain comprises VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU number), and L1 comprises E124C, L135F, and C214S substitutions (EU number). In some embodiments, L2 is derived from the κ light chain. In some embodiments, L1 is derived from the κ light chain. In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an Fc domain; and iv) a second light chain (L2). The second light chain comprises VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 comprises F126C, F170I, S183L, V185L and C220S substitutions (EU number), and L1 comprises Q124C, L135F and C214S substitutions (EU number).In some embodiments, a multispecific construct is provided, wherein the multispecific construct is a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an Fc domain; and iv) a second light chain (L2). The second light chain comprises VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); and wherein H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU number), and L1 comprises Q124C, L135F, and C214S substitutions (EU number). In some embodiments, L2 is derived from the λ light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU number). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU number). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU numbers). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU numbers), and the second subunit of the Fc domain contains T366W substitutions (EU numbers); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU numbers), and the first subunit of the Fc domain contains T366W substitutions (EU numbers).In some embodiments, (a) H1 comprises substitutions of F126C, F170I, S183L, V185L, C220S, T366S, L368A, and Y407V, L1 comprises substitutions of E124C (or Q124C), L135F, and C214S, and H2 comprises substitutions of T366W; (b) H1 comprises substitutions of F126C, F170I, S183L, V185L, C220S, and T366W, L1 comprises substitutions of E124C (or Q124C), L135F, and C214S, and H2 comprises substitutions of T366S, L368A, and Y407V; (c) H1 contains F126C, F170V, S183I, V185L, C220S, T366S, L368A, and Y407V substitutions; L1 contains E124C (or Q124C), L135F, and C214S substitutions; and H2 contains T366W substitutions; or (d) H1 contains F126C, F170V, S183I, V185L, C220S, and T366W substitutions; L1 contains E124C (or Q124C), L135F, and C214S substitutions; and H2 contains T366S, L368A, and Y407V substitutions; and the amino acid positions therein are according to EU designations.

[0142] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein H2 contains substitutions at positions 170, 183, and 185 (EU number), and L2 contains a substitution at position 135 (EU number). In some embodiments, H2 contains substitutions at positions F170, S183, and V185 (EU number), and L2 contains a substitution at position L135 (EU number). In some embodiments, H2 contains substitutions at F170I, S183L, and V185L (EU number), and L2 contains a substitution at L135F (EU number). In some embodiments, L2 is derived from the λ light chain. In some embodiments, L2 is derived from the κ light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain contains substitutions at L234A and L235A (EU number). In some embodiments, each subunit of the Fc domain contains substitutions at M428L and N434S (EU number). In some embodiments, each subunit of the Fc domain contains substitutions at M252Y, S254T, and T256E (EU number). In some implementations, (i) the first subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number).

[0143] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein H2 contains substitutions at positions 170, 183, and 185 (EU number), and L2 contains a substitution at position 135 (EU number). In some embodiments, H2 contains substitutions at positions F170, S183, and V185 (EU number), and L2 contains a substitution at position L135 (EU number). In some embodiments, H2 contains substitutions at F170V, S183I, and V185L (EU number), and L2 contains a substitution at L135F (EU number). In some embodiments, L2 is derived from the λ light chain. In some embodiments, L2 is derived from the κ light chain. In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain contains substitutions at L234A and L235A (EU number). In some embodiments, each subunit of the Fc domain contains substitutions at M428L and N434S (EU number). In some embodiments, each subunit of the Fc domain contains substitutions at M252Y, S254T, and T256E (EU number). In some implementations, (i) the first subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number).

[0144] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein H2 contains substitutions at positions 126 and 220 (EU number), and L2 contains substitutions at positions 124 and 214 (EU number). In some embodiments, L2 is derived from the λ light chain. In some embodiments, H2 contains substitutions at positions F126 and C220 (EU number), and L2 contains substitutions at positions E124 and C214 (EU number). In some embodiments, H2 contains F126C and C220S substitutions (EU number), and L2 contains E124C and C214S substitutions (EU number). In some embodiments, L2 is derived from the κ light chain. In some embodiments, H2 contains substitutions at positions F126 and C220 (EU number), and L2 contains substitutions at positions Q124 and C214 (EU number). In some embodiments, H2 contains F126C and C220S substitutions (EU number), and L2 contains Q124C and C214S substitutions (EU number). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain contains L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain contains T366W substitutions (EU numbering); or (ii) the second subunit of the Fc domain contains T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain contains T366W substitutions (EU numbering).

[0145] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an Fc domain; and iv) a... The second light chain (L2) comprises VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein H2 contains substitutions at positions 126, 170, 183, 185, and 220 (EU number), and L2 contains substitutions at positions 124, 135, and 214 (EU number). In some embodiments, L2 is derived from the λ light chain. In some embodiments, H2 contains substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L2 contains substitutions at positions E124, L135, and C214 (EU number). In some embodiments, H2 comprises substitutions of F126C, F170I, S183L, V185L, and C220S (EU number), and L2 comprises substitutions of E124C, L135F, and C214S (EU number). In some embodiments, L2 is derived from the κ light chain. In some embodiments, H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L2 comprises substitutions at positions Q124, L135, and C214 (EU number). In some embodiments, H2 comprises substitutions of F126C, F170I, S183L, V185L, and C220S (EU number), and L2 comprises substitutions of Q124C, L135F, and C214S (EU number). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain contains L234A and L235A substitutions (EU designations). In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU designations). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU designations).In some implementations, (i) the first subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number).

[0146] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an Fc domain; and iv) a... The second light chain (L2) comprises VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein H2 contains substitutions at positions 126, 170, 183, 185, and 220 (EU number), and L2 contains substitutions at positions 124, 135, and 214 (EU number). In some embodiments, L2 is derived from the λ light chain. In some embodiments, H2 contains substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L2 contains substitutions at positions E124, L135, and C214 (EU number). In some embodiments, H2 comprises substitutions of F126C, F170V, S183I, V185L, and C220S (EU number), and L2 comprises substitutions of E124C, L135F, and C214S (EU number). In some embodiments, L2 is derived from the κ light chain. In some embodiments, H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L2 comprises substitutions at positions Q124, L135, and C214 (EU number). In some embodiments, H2 comprises substitutions of F126C, F170V, S183I, V185L, and C220S (EU number), and L2 comprises substitutions of Q124C, L135F, and C214S (EU number). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain contains L234A and L235A substitutions (EU designations). In some embodiments, each subunit of the Fc domain contains M428L and N434S substitutions (EU designations). In some embodiments, each subunit of the Fc domain contains M252Y, S254T, and T256E substitutions (EU designations).In some implementations, (i) the first subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number).

[0147] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody portions of an scFv (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”, for example, either of the anti-IL-13 scFvs described herein) and a second antibody portion as 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 a first heavy chain of the second antibody portion to form a first fusion polypeptide, and anti-IL-13 scFv2 is fused to the C-terminus of a second heavy chain of the second antibody portion to form a second fusion polypeptide; and wherein anti-IL-13 scFv1 and anti-IL-13 scFv2 each comprise: (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:68; (iv) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:68. 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 comprise: VH comprising the amino acid sequence of SEQ ID NO:65 and VL comprising the amino acid sequence of SEQ ID NO:69.

[0148] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as scFv (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”, for example, any of the anti-IL-13 scFvs described herein), two second antibody moieties as 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, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-anti-IL-13 scFv1-optional linker-first subunit of the Fc domain; iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-anti-IL-13 scFv2 - optional linker - second subunit of Fc domain; and iv) a fourth polypeptide comprising from N' to C': VL2-(L2-CL); wherein VL1-(L1-CL) and VH1-(H1-CH1) form Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form Fab2; and wherein 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) comprising SEQ ID NO:66; CDR-L3 is the amino acid sequence of 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.

[0149] In some embodiments, a multispecific construct is provided comprising: a first antibody portion as an anti-IL-13 full-length antibody (e.g., any of the anti-IL-13 full-length antibodies described herein) and two second antibody portions as 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 anti-IL-13 full-length antibody to form a first fusion polypeptide, and scFv2 is fused to the C-terminus of the second heavy chain of the anti-IL-13 full-length antibody to form a second fusion polypeptide; and wherein the anti-IL-13 full-length antibody comprises: (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:70; (v) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:66; (vi) 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, the full-length anti-IL-13 antibody comprises: VH comprising the amino acid sequence of SEQ ID NO:65 and VL comprising the amino acid sequence of SEQ ID NO:69. In some embodiments, the full-length anti-IL-13 antibody comprises two heavy chains each comprising the amino acid sequence of SEQ ID NO:125 and two light chains each comprising the amino acid sequence of SEQ ID NO:102 or 197. In some embodiments, the full-length anti-IL-13 antibody comprises two heavy chains each comprising the amino acid sequence of SEQ ID NO:225 and two light chains each comprising the amino acid sequence of SEQ ID NO:102 or 197.

[0150] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, for example, the anti-IL-13 antibody moieties described herein). The multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-scFv1-optional linker-first subunit of the Fc domain; iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-scFv2-optional linker-second subunit of the Fc domain; and iv) a fourth polypeptide comprising, from N' to C': VL2-(L2-CL); wherein VH1-(H1-CH1) and VL1-(L1-CL) form an anti-IL-13 antibody. Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2; wherein 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. In some embodiments, anti-IL-13 Fab1 and anti-IL-13 Fab2 each comprise: VH comprising the amino acid sequence of SEQ ID NO:65 and VL comprising the amino acid sequence of SEQ ID NO:69.

[0151] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, for example, the anti-IL-13 antibody moieties described herein). The multispecific construct comprises: i) a first polypeptide comprising: a first light chain of the second antibody portion; ii) a second polypeptide comprising, from N' to C': a first heavy chain of the second antibody portion - optionally a linker - VH1-(H1-CH1); iii) a third polypeptide comprising, from N' to C': a second heavy chain of the second antibody portion - optionally a linker - VH2-(H2-CH1); iv) a fourth polypeptide comprising: a second light chain of the second antibody portion; v) a fifth polypeptide comprising, from N' to C': VL1-(L1-CL); and vi) a sixth polypeptide comprising, from N' to C': VL2-(L2-CL); wherein VL1-(L1-CL) and VH1-(H1-CH1) form an anti-IL-13. Fab1, and VL2-(L2-CL) and VH2-(H2-CH1) form anti-IL-13 Fab2; wherein 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. In some embodiments, anti-IL-13 Fab1 and anti-IL-13 Fab2 each comprise: VH comprising the amino acid sequence of SEQ ID NO:65 and VL comprising 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); wherein anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL); and wherein: (a) H1 and H2 each contain F170I, S183L, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (b) H1 and H2 each contain F170V, S183I, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (c) H1 and H2 each contain F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each contain F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; wherein the amino acid positions are according to EU numbers. In some embodiments, the light chain of the full-length antibody is derived from the κ light chain.

[0152] In some embodiments, a multispecific construct is provided comprising: a first antibody portion as a full-length anti-IL-13 antibody (e.g., any of the full-length anti-IL-13 antibodies described herein) and two second antibody portions as Fab (“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 the full-length anti-IL-13 antibody; ii) a second polypeptide comprising, from N' to C': a first heavy chain (H1) of the full-length anti-IL-13 antibody - optionally a linker -VH3-(H3-CH1); iii) a third polypeptide, which comprises: The third polypeptide from N' to C' comprises: the second heavy chain (H2) of the full-length anti-IL-13 antibody - optional linker - VH4-(H4-CH1); iv) the fourth polypeptide comprising: the second light chain (L2) of the full-length anti-IL-13 antibody; v) the fifth polypeptide from N' to C' comprising: VL3-(L3-CL); and vi) the sixth polypeptide from N' to C' comprising: VL4-(L4-CL); wherein VL3-(L3-CL) and VH3-(H3-CH1) form Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form Fab2; and wherein the full-length anti-IL-13 antibody comprises: (i) comprising SEQ (ii) CDR-H1 containing the amino acid sequence of SEQ ID NO:66; (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, (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 L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; (d) H1 and H2 each contain substitutions of F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; and the amino acid positions are based on EU numbers. In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 125 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197; ii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 209 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 210 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iv) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 211 and two light chains each comprising the amino acid sequence of SEQ ID NO: 121 or 206; v) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 212 and two light chains each comprising the amino acid sequence of SEQ ID NO: 120 or 208; vi) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 213 and two light chains each comprising the amino acid sequence of SEQ ID NO: 120 or 197. Two light chains comprising the amino acid sequence of SEQ ID NO: 120 or 208; vii) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 225 and two light chains comprising the amino acid sequence of SEQ ID NO: 102 or 197; viii) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 101 and two light chains comprising the amino acid sequence of SEQ ID NO: 102 or 197; or ix) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 123 and two light chains comprising the amino acid sequence of SEQ ID NO: 121 or 206. In some embodiments, L3-CL and L4-CL are derived from the κ light chain.

[0153] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, for example, the anti-IL-13 antibody moieties described herein). The multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-first heavy chain of the second antibody portion; iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-second heavy chain of the second antibody portion; iv) a fourth polypeptide comprising, from N' to C': VL2-(L2-CL); v) a fifth polypeptide comprising, the first light chain of the second antibody portion; and vi) a sixth polypeptide comprising, the second light chain of the second antibody portion; wherein VL1-(L1-CL) and VH1-(H1-CH1) form an anti-IL-13. Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2; wherein 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. In some embodiments, anti-IL-13 Fab1 and anti-IL-13 Fab2 each comprise: VH comprising the amino acid sequence of SEQ ID NO:65 and VL comprising 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); wherein anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL); wherein: (a) H1 and H2 each contain F170I, S183L, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (b) H1 and H2 each contain F170V, S183I, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (c) H1 and H2 each contain F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each contain F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; wherein the amino acid positions are according to EU numbers. In some embodiments, the light chain of the full-length antibody is derived from the κ light chain.

[0154] In some embodiments, a multispecific construct is provided comprising: a first antibody portion as a full-length anti-IL-13 antibody (e.g., any of the full-length anti-IL-13 antibodies described herein) and two second antibody portions as Fab (“Fab1” and “Fab2”) that specifically bind a second target antigen (e.g., TSLP); wherein the multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL3-(L3-CL); ii) a second polypeptide comprising, from N' to C': VH3-(H3-CH1)-optional linker-first heavy chain (H1) of the full-length anti-IL-13 antibody; iii) a third polypeptide comprising, from N' to C': VH3-(H3-CH1)-optional linker-first heavy chain (H1) of the full-length anti-IL-13 antibody; and ...iv) a second antibody portion comprising, from N' to C': VH3-(H3-CH1)-optional linker-first heavy chain (H1) of the full-length anti-IL-13 antibody; and iv) a third antibody portion comprising, from N' to C': VH3-(H3-CH1)-option linker-first heavy chain (H1) of the full-length anti-IL-13 antibody; and iv) a second antibody portion comprising, from N' to C': VH3-(H3-CH1)-option linker-first heavy chain (H1) of the full-length anti-IL-13 antibody; and iv) a third antibody portion comprising, from N' to C': VH3-(H3-CH1)-option linker-first heavy chain (H1) of the full-length anti-IL-13 antibody; and iv) a second antibody portion comprising, from N' to C': VH3-(H3 C' comprises: VH4-(H4-CH1)-optional linker-second heavy chain (H2) of the full-length anti-IL-13 antibody; iv) a fourth polypeptide comprising, from N' to C': VL4-(L4-CL); v) a fifth polypeptide comprising, from N' to C': a first light chain (L1) of the full-length anti-IL-13 antibody; and vi) a sixth polypeptide comprising, from N' to C': a second light chain (L2) of the full-length anti-IL-13 antibody; wherein VL3-(L3-CL) and VH3-(H3-CH1) form Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form Fab2; and wherein the full-length anti-IL-13 antibody comprises: (i) comprising SEQ 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, the full-length anti-IL-13 antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 65 and VL comprising the amino acid sequence of SEQ ID NO: 69.In some embodiments, (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 L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; (d) H1 and H2 each contain substitutions of F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; and the amino acid positions are based on EU numbers. In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 125 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197; ii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 209 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 210 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iv) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 211 and two light chains each comprising the amino acid sequence of SEQ ID NO: 121 or 206; v) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 212 and two light chains each comprising the amino acid sequence of SEQ ID NO: 120 or 208; vi) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 213 and two light chains each comprising the amino acid sequence of SEQ ID NO: 125 and 197 or 102 or 107 or 108 or 109 ... Two light chains comprising the amino acid sequence of SEQ ID NO: 120 or 208; vii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 225 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197; viii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 101 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197; or ix) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 123 and two light chains each comprising the amino acid sequence of SEQ ID NO: 121 or 206. In some embodiments, L3-CL and L4-CL are derived from the κ light chain.

[0155] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) comprising SEQ ID NO:66; 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; and wherein VL1 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; and wherein H1 comprises substitutions (EU numbers) at positions 170, 183 and 185, and L1 comprises substitutions (EU numbers) at position 135. In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) 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% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69. 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, H1 comprises substitutions at positions F170, S183, and V185 (EU number), and L1 comprises substitutions at position L135 (EU number). In some embodiments, H1 comprises F170I, S183L, and V185L substitutions (EU designation), and L1 comprises L135F substitutions (EU designation). In some embodiments, L1 is derived from the λ light chain. In some embodiments, L1 is derived from the κ light chain.In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU number); (ii) M428L and N434S substitutions (EU number); and / or (iii) M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain comprises T366W substitution (EU number); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain comprises T366W substitution (EU number). In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO:138 or 139, or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:138 or 139, and L1 comprises the amino acid sequence of SEQ ID NO:122 or 207, or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:122 or 207. In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO:138 or 139, and L1 comprises the amino acid sequence of SEQ ID NO:122 or 207.

[0156] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) comprising SEQ ID NO:66; 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; and wherein VL1 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; and wherein H1 comprises substitutions (EU numbers) at positions 170, 183 and 185, and L1 comprises substitutions (EU numbers) at position 135. In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) 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% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69. 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, H1 comprises substitutions at positions F170, S183, and V185 (EU number), and L1 comprises substitutions at position L135 (EU number). In some embodiments, H1 comprises F170V, S183I, and V185L substitutions (EU designation), and L1 comprises L135F substitutions (EU designation). In some embodiments, L1 is derived from the λ light chain. In some embodiments, L1 is derived from the κ light chain.In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU number); (ii) M428L and N434S substitutions (EU number); and / or (iii) M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain comprises T366W substitution (EU number); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain comprises T366W substitution (EU number). In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO:140 or 141, or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:140 or 141, and L1 comprises the amino acid sequence of SEQ ID NO:122 or 207, or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:122 or 207. In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO:140 or 141, and L1 comprises the amino acid sequence of SEQ ID NO:122 or 207.

[0157] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) comprising SEQ ID NO:66; (iii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:67; and wherein VL1 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; and wherein H1 comprises substitutions at positions 126 and 220 (EU number), and L1 comprises substitutions at positions 124 and 214 (EU number). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) 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% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69. 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 λ light chain. In some embodiments, H1 contains substitutions at positions F126 and C220 (EU number), and L1 contains substitutions at positions E124 and C214 (EU number). In some embodiments, H1 contains F126C and C220S substitutions (EU designation), and L1 contains E124C and C214S substitutions (EU designation). In some embodiments, L1 is derived from the κ light chain.In some embodiments, H1 contains substitutions at positions F126 and C220 (EU number), and L1 contains substitutions at positions Q124 and C214 (EU number). In some embodiments, H1 contains F126C and C220S substitutions (EU number), and L1 contains Q124C and C214S substitutions (EU number). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain contains: (i) L234A and L235A substitutions (EU number); (ii) M428L and N434S substitutions (EU number); and / or (iii) M252Y, S254T, and T256E substitutions (EU number). In some implementations, (i) the first subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number). In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO:200 or 201, or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:200 or 201, and L1 comprises the amino acid sequence of SEQ ID NO:121 or 206, or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:121 or 206. In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO:200 or 201, and L1 comprises the amino acid sequence of SEQ ID NO:121 or 206.

[0158] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) comprising SEQ ID NO:66; 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; and wherein VL1 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; and wherein H1 comprises substitutions at positions 126, 170, 183, 185 and 220 (EU number), and L1 comprises substitutions at positions 124, 135 and 214 (EU number). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) 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% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69. 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 λ light chain. In some embodiments, H1 contains substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L1 contains substitutions at positions E124, L135, and C214 (EU number).In some embodiments, H1 comprises substitutions of F126C, F170I, S183L, V185L, and C220S (EU number), and L1 comprises substitutions of E124C, L135F, and C214S (EU number). In some embodiments, L1 is derived from the κ light chain. In some embodiments, H1 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L1 comprises substitutions at positions Q124, L135, and C214 (EU number). In some embodiments, H1 comprises substitutions of F126C, F170I, S183L, V185L, and C220S (EU number), and L1 comprises substitutions of Q124C, L135F, and C214S (EU number). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain includes: (i) L234A and L235A substitutions (EU numbers); (ii) M428L and N434S substitutions (EU numbers); and / or (iii) M252Y, S254T, and T256E substitutions (EU numbers). In some embodiments, (i) the first subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the second subunit of the Fc domain includes T366W substitutions (EU numbers); or (ii) the second subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the first subunit of the Fc domain includes T366W substitutions (EU numbers). In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO: 126 or 127, or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO: 126 or 127, and L1 comprises the amino acid sequence of SEQ ID NO: 120 or 208, or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO: 120 or 208. In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO: 126 or 127, and L1 comprises the amino acid sequence of SEQ ID NO: 120 or 208.

[0159] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) comprising SEQ ID NO:66; 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; and wherein VL1 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; and wherein H1 comprises substitutions at positions 234, 235, 428, 434, 126, 170, 183, 185 and 220 (EU number), and L1 comprises substitutions at positions 124, 135 and 214 (EU number). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) 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% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69. 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 λ light chain. In some embodiments, H1 contains substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L1 contains substitutions at positions E124, L135, and C214 (EU number).In some embodiments, H1 comprises substitutions of F126C, F170V, S183I, V185L, and C220S (EU number), and L1 comprises substitutions of E124C, L135F, and C214S (EU number). In some embodiments, L1 is derived from the κ light chain. In some embodiments, H1 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L1 comprises substitutions at positions Q124, L135, and C214 (EU number). In some embodiments, H1 comprises substitutions of F126C, F170V, S183I, V185L, and C220S (EU number), and L1 comprises substitutions of Q124C, L135F, and C214S (EU number). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain includes: (i) L234A and L235A substitutions (EU numbers); (ii) M428L and N434S substitutions (EU numbers); and / or (iii) M252Y, S254T, and T256E substitutions (EU numbers). In some embodiments, (i) the first subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the second subunit of the Fc domain includes T366W substitutions (EU numbers); or (ii) the second subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the first subunit of the Fc domain includes T366W substitutions (EU numbers). In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO:128 or 129, or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:128 or 129, and L1 comprises the amino acid sequence of SEQ ID NO:120 or 208, or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:120 or 208. In some embodiments, H1 comprises the amino acid sequence of SEQ ID NO:128 or 129, and L1 comprises the amino acid sequence of SEQ ID NO:120 or 208.

[0160] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) comprising SEQ ID NO:66; 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; and wherein VL1 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; and wherein H2 comprises substitutions (EU numbers) at positions 170, 183 and 185, and L2 comprises substitutions (EU numbers) at position 135. In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) 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% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69. 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 positions F170, S183, and V185 (EU number), and L2 comprises a substitution at position L135 (EU number). In some embodiments, H2 comprises F170I, S183L, and V185L substitutions (EU designations), and L2 comprises L135F substitutions (EU designation). In some embodiments, L2 is derived from the λ light chain. In some embodiments, L2 is derived from the κ light chain.In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU number); (ii) M428L and N434S substitutions (EU number); and / or (iii) M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain comprises T366W substitution (EU number); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain comprises T366W substitution (EU number).

[0161] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) comprising SEQ ID NO:66; 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; and wherein VL1 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; and wherein H2 comprises substitutions (EU numbers) at positions 170, 183 and 185, and L2 comprises substitutions (EU numbers) at position 135. In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) 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% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69. 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 positions F170, S183, and V185 (EU number), and L2 comprises a substitution at position L135 (EU number). In some embodiments, H2 comprises F170V, S183I, and V185L substitutions (EU designation), and L2 comprises L135F substitutions (EU designation). In some embodiments, L2 is derived from the λ light chain. In some embodiments, L2 is derived from the κ light chain.In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU number); (ii) M428L and N434S substitutions (EU number); and / or (iii) M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain comprises T366W substitution (EU number); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain comprises T366W substitution (EU number).

[0162] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) comprising SEQ ID NO:66; (iii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:67; and wherein VL1 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; and wherein H2 comprises substitutions at positions 126 and 220 (EU number), and L2 comprises substitutions at positions 124 and 214 (EU number). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) 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% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69. 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 λ light chain. In some embodiments, H2 contains substitutions at positions F126 and C220 (EU number), and L2 contains substitutions at positions E124 and C214 (EU number). In some embodiments, H2 contains F126C and C220S substitutions (EU designation), and L2 contains E124C and C214S substitutions (EU designation). In some embodiments, L2 is derived from the κ light chain.In some embodiments, H2 contains substitutions at positions F126 and C220 (EU number), and L2 contains substitutions at positions Q124 and C214 (EU number). In some embodiments, H2 contains F126C and C220S substitutions (EU number), and L2 contains Q124C and C214S substitutions (EU number). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain contains: (i) L234A and L235A substitutions (EU number); (ii) M428L and N434S substitutions (EU number); and / or (iii) M252Y, S254T, and T256E substitutions (EU number). In some implementations, (i) the first subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the second subunit of the Fc domain contains T366W substitution (EU number); or (ii) the second subunit of the Fc domain contains T366S, L368A and Y407V substitutions (EU number), and the first subunit of the Fc domain contains T366W substitution (EU number).

[0163] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) comprising SEQ ID NO:66; 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; and wherein VL1 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; and wherein H2 comprises substitutions at positions 126, 170, 183, 185 and 220 (EU number), and L2 comprises substitutions at positions 124, 135 and 214 (EU number). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) 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% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69. 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 λ light chain. In some embodiments, H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L2 comprises substitutions at positions E124, L135, and C214 (EU number).In some embodiments, H2 comprises substitutions of F126C, F170I, S183L, V185L, and C220S (EU number), and L2 comprises substitutions of E124C, L135F, and C214S (EU number). In some embodiments, L2 is derived from the κ light chain. In some embodiments, H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L2 comprises substitutions at positions Q124, L135, and C214 (EU number). In some embodiments, H2 comprises substitutions of F126C, F170I, S183L, V185L, and C220S (EU number), and L2 comprises substitutions of Q124C, L135F, and C214S (EU number). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain includes: (i) L234A and L235A substitutions (EU numbers); (ii) M428L and N434S substitutions (EU numbers); and / or (iii) M252Y, S254T, and T256E substitutions (EU numbers). In some embodiments, (i) the first subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the second subunit of the Fc domain includes T366W substitutions (EU numbers); or (ii) the second subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the first subunit of the Fc domain includes T366W substitutions (EU numbers).

[0164] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety described herein), and H2 and L2 form a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP); wherein VH1 comprises (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) comprising SEQ ID NO:66; 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; and wherein VL1 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; and wherein H2 comprises substitutions at positions 126, 170, 183, 185 and 220 (EU number), and L2 comprises substitutions at positions 124, 135 and 214 (EU number). In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) 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% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69. 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 λ light chain. In some embodiments, H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L2 comprises substitutions at positions E124, L135, and C214 (EU number).In some embodiments, H2 comprises substitutions of F126C, F170V, S183I, V185L, and C220S (EU number), and L2 comprises substitutions of E124C, L135F, and C214S (EU number). In some embodiments, L2 is derived from the κ light chain. In some embodiments, H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L2 comprises substitutions at positions Q124, L135, and C214 (EU number). In some embodiments, H2 comprises substitutions of F126C, F170V, S183I, V185L, and C220S (EU number), and L2 comprises substitutions of Q124C, L135F, and C214S (EU number). In some embodiments, the Fc domain is derived from IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, such as human IgG1. In some embodiments, each subunit of the Fc domain includes: (i) L234A and L235A substitutions (EU numbers); (ii) M428L and N434S substitutions (EU numbers); and / or (iii) M252Y, S254T, and T256E substitutions (EU numbers). In some embodiments, (i) the first subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the second subunit of the Fc domain includes T366W substitutions (EU numbers); or (ii) the second subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the first subunit of the Fc domain includes T366W substitutions (EU numbers).

[0165] In some embodiments, a multispecific construct is provided comprising: two first antibody portions (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”) as anti-IL-13 scFv and a second antibody portion (“anti-TSLP full-length antibody”) as a full-length antibody specifically binding 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; wherein anti-IL-13 scFv1 and anti-IL-13 scFv2 each comprise: (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:68; (iv) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:68. 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 wherein the full-length anti-TSLP antibody comprises: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:21; (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:22; (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO:24; (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:25; and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:26. In some embodiments, anti-IL-13 scFv1 and anti-IL-13 scFv2 each comprise a VH comprising the amino acid sequence of SEQ ID NO:65 and a VL comprising the amino acid sequence of SEQ ID NO:69.In some embodiments, the full-length anti-TSLP antibody comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:53; (b) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:54; (c) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:189; (d) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH comprising the amino acid sequence of SEQ ID NO:228 and a VL comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, anti-IL-13 scFv1 and anti-IL-13 scFv2 each comprise the amino acid sequence of SEQ ID NO:108. In some embodiments, the full-length anti-TSLP antibody comprises: i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 104 and a light chain comprising the amino acid sequence of SEQ ID NO: 103; or ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 105 and a light chain comprising the amino acid sequence of SEQ ID NO: 103. In some embodiments, the linker comprises the amino acid sequence of either GG or SEQ ID NO: 98-99. In some embodiments, the full-length anti-TSLP antibody comprises two light chains each comprising the amino acid sequence of SEQ ID NO: 103 and two heavy chains each comprising the amino acid sequence of SEQ ID NO: 105, and the first fusion polypeptide and the second fusion polypeptide each comprise the amino acid sequence of SEQ ID NO: 113.

[0166] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as scFv (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”), two second antibody moieties as Fabs that specifically bind TSLP (“anti-TSLP Fab1” and “anti-TSLP Fab2”), and an Fc domain; wherein the multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-anti-IL-13 scFv1-optional linker-first subunit of the Fc domain; iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-anti-IL-13 scFv2 - optional linker - second subunit of Fc domain; and iv) a fourth polypeptide comprising, from N' to C': VL2-(L2-CL); wherein VL1-(L1-CL) and VH1-(H1-CH1) form anti-TSLP Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-TSLP Fab2; wherein 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) comprising SEQ ID CDR-L3 comprising the amino acid sequence of SEQ ID NO:72; and wherein anti-TSLP Fab1 and anti-TSLP Fab2 each comprise: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:21; (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:22; (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO:24; (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:25; and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:26. In some embodiments, anti-IL-13 scFv1 and anti-IL-13 scFv2 each comprise VH comprising the amino acid sequence of SEQ ID NO:65 and VL comprising the amino acid sequence of SEQ ID NO:69.In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each comprise: (a) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:53; (b) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:54; (c) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:189; (d) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH comprising the amino acid sequence of SEQ ID NO:228 and a VL comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, anti-IL-13 scFv1 and anti-IL-13 scFv2 each comprise 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 either GG or SEQ ID NO:98-99. 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.

[0167] In some embodiments, a multispecific construct is provided comprising: a first antibody portion as a full-length anti-IL-13 antibody and two second antibody portions (“anti-TSLP scFv1” and “anti-TSLP scFv2”) as scFvs that specifically bind TSLP; wherein anti-TSLP scFv1 is fused 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 is fused 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; wherein the full-length anti-IL-13 antibody comprises: (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:70; (v) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:66; 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; wherein anti-TSLP scFv1 and anti-TSLP scFv2 each comprise: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:21; (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:22; (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO:24; (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:25; and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:26. In some embodiments, the full-length anti-IL-13 antibody comprises VH comprising the amino acid sequence of SEQ ID NO:65 and VL comprising the amino acid sequence of SEQ ID NO:69.In some embodiments, anti-TSLP scFv1 and anti-TSLP scFv2 each comprise: (a) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:53; (b) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:54; (c) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:189; (d) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH comprising the amino acid sequence of SEQ ID NO:228 and a VL comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, the full-length anti-IL-13 antibody comprises two heavy chains each comprising the amino acid sequence of SEQ ID NO:125 and two light chains each comprising the amino acid sequence of SEQ ID NO:102 or 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 197. In some embodiments, anti-TSLP scFv1 and anti-TSLP scFv2 each comprise the amino acid sequence of any one of SEQ ID NO: 106, 107, 218, 219, 226, 227, and 229. In some embodiments, the linker comprises the amino acid sequence of any one of GG and SEQ ID NO: 98-99. 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 197, wherein the first fusion polypeptide and the second fusion polypeptide each comprise 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 197, and wherein the first fusion polypeptide and the second fusion polypeptide each contain the amino acid sequence of any one of SEQ ID NO:220-223.

[0168] 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”) as scFvs that specifically bind to TSLP, and an Fc domain; wherein the multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-anti-TSLP scFv1-optional linker-first subunit of the Fc domain; iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-anti-TSLP scFv2-optional linker-second subunit of the Fc domain; and iv) a fourth polypeptide comprising, from N' to C': VL2-(L2-CL); wherein 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; wherein 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) comprising SEQ ID CDR-L3 comprising the amino acid sequence of SEQ ID NO:72; and wherein anti-TSLP scFv1 and anti-TSLP scFv2 each comprise: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:21; (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:22; (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO:24; (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:25; and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:26. In some embodiments, anti-IL-13Fab1 and anti-IL-13Fab2 each comprise VH comprising the amino acid sequence of SEQ ID NO:65 and VL comprising the amino acid sequence of SEQ ID NO:69.In some embodiments, anti-TSLP scFv1 and anti-TSLP scFv2 each comprise: (a) a VH comprising the amino acid sequence of SEQ ID NO: 63 and a VL comprising the amino acid sequence of SEQ ID NO: 53; (b) a VH comprising the amino acid sequence of SEQ ID NO: 63 and a VL comprising the amino acid sequence of SEQ ID NO: 54; (c) a VH comprising the amino acid sequence of SEQ ID NO: 188 and a VL comprising the amino acid sequence of SEQ ID NO: 189; (d) a VH comprising the amino acid sequence of SEQ ID NO: 188 and a VL comprising the amino acid sequence of SEQ ID NO: 190; or (e) a VH comprising the amino acid sequence of SEQ ID NO: 228 and a VL comprising 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 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 197. In some embodiments, anti-TSLP scFv1 and anti-TSLP scFv2 each comprise an amino acid sequence from any of SEQ ID NO: 106, 107, 218, 219, 226, 227, and 229. In some embodiments, the linker comprises an amino acid sequence independently selected from any of GG and SEQ ID NO: 98-99. In some embodiments, the first and fourth peptides each comprise an amino acid sequence from SEQ ID NO: 102 or 197, and the second and third peptides each comprise an amino acid sequence from SEQ ID NO: 112.

[0169] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab1”). The multispecific construct comprises: Fab2” and a second antibody portion (“anti-TSLP full-length antibody”) as a full-length antibody specifically binding to TSLP; wherein the multispecific construct comprises: i) a first polypeptide comprising: a first light chain of the anti-TSLP full-length antibody; ii) a second polypeptide comprising, from N' to C': a first heavy chain of the anti-TSLP full-length antibody – optionally a linker – VH1-(H1-CH1); iii) a third polypeptide comprising, from N' to C': a second heavy chain of the anti-TSLP full-length antibody – optionally a linker – VH2-(H2-CH1); iv) a fourth polypeptide comprising: a second light chain of the anti-TSLP full-length antibody; v) a fifth polypeptide comprising, from N' to C': VL1-(L1-CL); and vi) a sixth polypeptide comprising, from N' to C': VL2-(L2-CL); wherein VL1-(L1-CL) and VH1-(H1-CH1) form an anti-IL-13. Fab1, and VL2-(L2-CL) and VH2-(H2-CH1) form anti-IL-13 Fab2; wherein 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 wherein the full-length anti-TSLP antibody comprises: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:21; (iii) comprising the amino acid sequence of SEQ ID NO:20; and (iv) 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 wherein the full-length anti-TSLP antibody comprises: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:21; and (iii) CDR-L2 comprising the amino acid sequence of SEQ ID NO:20; and (iv) CDR-L2 comprising the amino acid sequence of SEQ ID NO:20; and (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:21; and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:72; and (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO:20; and (iv) CDR-L2 comprising the amino acid sequence of SEQ ID NO:20; and ( 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 contain 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-TSLP antibody comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:53; (b) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:54; (c) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:189; (d) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH comprising the amino acid sequence of SEQ ID NO:228 and a VL comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, anti-IL-13 Fab1 comprises H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL); wherein anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL); and wherein: (a) H1 and H2 each contain F170I, S183L, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (b) H1 and H2 each contain F170V, S183I, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (c) H1 and H2 each contain F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each contain F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; wherein the amino acid positions are according to EU numbers. In some embodiments, the light chain of the full-length anti-TSLP antibody is derived from the κ light chain. In some embodiments, the full-length anti-TSLP antibody comprises i) two heavy chains each comprising the amino acid sequence of SEQ ID NO:104 and a light chain comprising the amino acid sequence of SEQ ID NO:103; or ii) a heavy chain comprising the amino acid sequence of SEQ ID NO:105 and a light chain comprising the amino acid sequence of SEQ ID NO:103. In some embodiments, the linker comprises an amino acid sequence independently selected from either GG or SEQ ID NO:98-99.

[0170] In some embodiments, a multispecific construct is provided comprising: an anti-IL-13 antibody portion as a full-length antibody (“anti-IL-13 full-length antibody”) and two second antibody portions (“anti-TSLP Fab1” and “anti-TSLP Fab1”) as Fabs that specifically bind to TSLP. Fab2”); 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, from N' to C': a first heavy chain (H1) of a full-length anti-IL-13 antibody - optionally a linker - VH3-(H3-CH1); iii) a third polypeptide comprising, from N' to C': a second heavy chain (H2) of a full-length anti-IL-13 antibody - optionally a linker - VH4-(H4-CH1); iv) a fourth polypeptide comprising: a second light chain (L2) of a full-length anti-IL-13 antibody; v) a fifth polypeptide comprising, from N' to C': VL3-(L3-CL); and vi) a sixth polypeptide comprising, from N' to C': VL4-(L4-CL); wherein VL3-(L3-CL) and VH3-(H3-CH1) form an anti-TSLP antibody. Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form anti-TSLP Fab2; wherein the full-length anti-IL-13 antibody 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; (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 wherein anti-TSLP Fab1 and anti-TSLP Fab2 each comprise: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:21; (iii) comprising the amino acid sequence of SEQ ID NO:20; 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 comprise: (a) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:53; (b) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:54; (c) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:189; (d) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH comprising the amino acid sequence of SEQ ID NO:228 and a VL comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, (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 L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; (d) H1 and H2 each contain substitutions of F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; and the amino acid positions are based on EU numbers.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 125 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197; ii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 209 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 210 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iv) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 211 and two light chains each comprising the amino acid sequence of SEQ ID NO: 121 or 206; v) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 212 and two light chains each comprising the amino acid sequence of SEQ ID NO: 120 or 208; vi) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 213 and two light chains each comprising the amino acid sequence of SEQ ID NO: 125 or 197. Two light chains comprising the amino acid sequence of SEQ ID NO: 120 or 208; vii) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 225 and two light chains comprising the amino acid sequence of SEQ ID NO: 102 or 197; viii) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 101 and two light chains comprising the amino acid sequence of SEQ ID NO: 102 or 197; or ix) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 123 and two light chains comprising the amino acid sequence of SEQ ID NO: 121 or 206. In some embodiments, L3-CL and L4-CL are derived from the κ light chain. In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each comprise a first polypeptide comprising the amino acid sequence of SEQ ID NO: 109 and a second polypeptide comprising the amino acid sequence of SEQ ID NO: 103. In some embodiments, the linker comprises an amino acid sequence independently selected from either GG or SEQ ID NO: 98-99.

[0171] In some embodiments, a multispecific construct is provided comprising: two anti-IL-13 antibody moieties as Fab (“anti-IL-13 Fab1” and “anti-IL-13 Fab1”). The multispecific construct comprises: Fab2” and a second antibody portion (“anti-TSLP full-length antibody”) as a full-length antibody specifically binding to TSLP; wherein the multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL1-(L1-CL); ii) a second polypeptide comprising, from N' to C': VH1-(H1-CH1)-optional linker-first heavy chain of the anti-TSLP full-length antibody; iii) a third polypeptide comprising, from N' to C': VH2-(H2-CH1)-optional linker-second heavy chain of the anti-TSLP full-length antibody; iv) a fourth polypeptide comprising, from N' to C': VL2-(L2-CL); v) a fifth polypeptide comprising: first light chain of the anti-TSLP full-length antibody; and vi) a sixth polypeptide comprising: second light chain of the anti-TSLP full-length antibody; wherein VL1-(L1-CL) and VH1-(H1-CH1) form an anti-IL-13. Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2; wherein 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 wherein the full-length anti-TSLP antibody comprises: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:21; and (iii) comprising the amino acid sequence of SEQ ID NO:20; 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 contain 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-TSLP antibody comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:53; (b) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:54; (c) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:189; (d) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH comprising the amino acid sequence of SEQ ID NO:228 and a VL comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, anti-IL-13 Fab1 comprises H1 containing VH1-(H1-CH1) and L1 containing VL1-(L1-CL); wherein anti-IL-13 Fab2 comprises H2 containing VH2-(H2-CH1) and L2 containing VL2-(L2-CL); and wherein: (a) H1 and H2 each contain F170I, S183L, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (b) H1 and H2 each contain F170V, S183I, and V185L substitutions, and L1 and L2 each contain L135F substitutions; (c) H1 and H2 each contain F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each contain F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each contain E124C (or Q124C), L135F, and C214S substitutions; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; wherein the amino acid positions are according to EU numbers. In some embodiments, the light chain of the full-length anti-TSLP antibody is derived from the κ light chain. In some embodiments, the full-length anti-TSLP antibody comprises i) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 104 and two light chains each comprising the amino acid sequence of SEQ ID NO: 103; or ii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 105 and two light chains each comprising the amino acid sequence of SEQ ID NO: 103. In some embodiments, the linker comprises an amino acid sequence independently selected from either GG or SEQ ID NO: 98-99.

[0172] In some embodiments, a multispecific construct is provided comprising: a first antibody portion as a full-length anti-IL-13 antibody and two second antibody portions (“anti-TSLP Fab1” and “anti-TSLP Fab2”) as Fabs that specifically bind to TSLP; wherein the multispecific construct comprises: i) a first polypeptide comprising, from N' to C': VL3-(L3-CL); ii) a second polypeptide comprising, from N' to C': VH3-(H3-CH1)-optional linker-first heavy chain (H1) of the full-length anti-IL-13 antibody; iii) a third polypeptide comprising, from N' to C': VH4-(H4-CH1)-optional linker-first heavy chain (H1) of the full-length anti-IL-13 antibody. The antibody's second heavy chain (H2); iv) a fourth polypeptide comprising, from N' to C': VL4-(L4-CL); v) a fifth polypeptide comprising, from N' to C': the first light chain (L1) of the full-length anti-IL-13 antibody; and vi) a sixth polypeptide comprising, from N' to C': the second light chain (L2) of the full-length anti-IL-13 antibody; wherein VL3-(L3-CL) and VH3-(H3-CH1) form anti-TSLP. Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form anti-TSLP Fab2; wherein the full-length anti-IL-13 antibody 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; (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 wherein anti-TSLP Fab1 and anti-TSLP Fab2 each comprise: (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:21; (iii) comprising the amino acid sequence of SEQ ID NO:20; 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 comprise: (a) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:53; (b) a VH comprising the amino acid sequence of SEQ ID NO:63 and a VL comprising the amino acid sequence of SEQ ID NO:54; (c) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:189; (d) a VH comprising the amino acid sequence of SEQ ID NO:188 and a VL comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH comprising the amino acid sequence of SEQ ID NO:228 and a VL comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, (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 L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; (d) H1 and H2 each contain substitutions of F126C, F170V, S183I, V185L, and C220S, and L1 and L2 each contain substitutions of E124C (or Q124C), L135F, and C214S; or (e) H1 and H2 each contain F126C and C220S substitutions, and L1 and L2 each contain E124C (or Q124C) and C214S substitutions; and the amino acid positions are based on EU numbers.In some embodiments, the full-length anti-IL-13 antibody comprises: i) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 125 and two light chains each comprising the amino acid sequence of SEQ ID NO: 102 or 197; ii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 209 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iii) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 210 and two light chains each comprising the amino acid sequence of SEQ ID NO: 122 or 207; iv) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 211 and two light chains each comprising the amino acid sequence of SEQ ID NO: 121 or 206; v) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 212 and two light chains each comprising the amino acid sequence of SEQ ID NO: 120 or 208; vi) two heavy chains each comprising the amino acid sequence of SEQ ID NO: 213 and two light chains each comprising the amino acid sequence of SEQ ID NO: 125 or 197. Two light chains comprising the amino acid sequence of SEQ ID NO: 120 or 208; vii) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 225 and two light chains comprising the amino acid sequence of SEQ ID NO: 102 or 197; viii) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 101 and two light chains comprising the amino acid sequence of SEQ ID NO: 102 or 197; or ix) each comprising two heavy chains comprising the amino acid sequence of SEQ ID NO: 123 and two light chains comprising the amino acid sequence of SEQ ID NO: 121 or 206. In some embodiments, L3-CL and L4-CL are derived from the κ light chain. In some embodiments, anti-TSLP Fab1 and anti-TSLP Fab2 each comprise a first polypeptide comprising the amino acid sequence of SEQ ID NO: 109 and a second polypeptide comprising the amino acid sequence of SEQ ID NO: 103. In some embodiments, the linker comprises an amino acid sequence independently selected from either GG or SEQ ID NO: 98-99.

[0173] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 moiety 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) comprising SEQ ID NO:66; The CDR-H2 comprising the amino acid sequence of SEQ ID NO: 67; (iii) the CDR-H3 comprising the amino acid sequence of SEQ ID NO: 68; and wherein VL1 comprises (i) the CDR-L1 comprising the amino acid sequence of SEQ ID NO: 70; (ii) the CDR-L2 comprising the amino acid sequence of SEQ ID NO: 71; and (iii) the CDR-L3 comprising the amino acid sequence of SEQ ID NO: 72; wherein the anti-TSLP antibody portion comprises: VH2 comprising (i) the CDR-H1 comprising the amino acid sequence of SEQ ID NO: 20; (ii) the CDR-H2 comprising the amino acid sequence of SEQ ID NO: 21; and (iii) the CDR-H3 comprising the amino acid sequence of SEQ ID NO: 22, and VL2 comprising (i) the CDR-L1 comprising the amino acid sequence of SEQ ID NO: 24; (ii) the CDR-L2 comprising the amino acid sequence of SEQ ID NO: 25; and (iii) the CDR-L3 comprising the amino acid sequence of SEQ ID NO: 67; CDR-L3 of the amino acid sequence of NO:26; wherein H1 contains substitutions at positions 170, 183, and 185 (EU number), and L1 contains a substitution at position 135 (EU number). In some embodiments, VH1 contains the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:65, and VL1 contains the amino acid sequence of SEQ ID NO:69 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69.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, the anti-TSLP antibody portion comprises: (a) VH2 comprising the amino acid sequence of SEQ ID NO:63 and VL2 comprising the amino acid sequence of SEQ ID NO:53; (b) VH2 comprising the amino acid sequence of SEQ ID NO:63 and VL2 comprising the amino acid sequence of SEQ ID NO:54; (c) VH2 comprising the amino acid sequence of SEQ ID NO:188 and VL2 comprising the amino acid sequence of SEQ ID NO:189; (d) VH2 comprising the amino acid sequence of SEQ ID NO:188 and VL2 comprising the amino acid sequence of SEQ ID NO:190; or (e) VH2 comprising the amino acid sequence of SEQ ID NO:228 and VL2 comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, H1 contains substitutions at positions F170, S183, and V185 (EU designation), and L1 contains substitutions at position L135 (EU designation). In some embodiments, H1 contains substitutions at F170I, S183L, and V185L (EU designation), and L1 contains substitutions at L135F (EU designation). In some embodiments, L1 is derived from the λ light chain. In some embodiments, L1 is derived from the κ light chain. In some embodiments, the anti-IL-13 antibody portion comprises: a first polypeptide comprising the amino acid sequence of SEQ ID NO:124 or a variant thereof having at least about 80% (such as 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 197 or a variant thereof having at least about 80% (such as 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 197. In some embodiments, the anti-TSLP antibody portion comprises: a first polypeptide comprising the amino acid sequence of SEQ ID NO:109 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:109, and a second polypeptide comprising the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as 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, such as human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU number); (ii) M428L and N434S substitutions (EU number); and / or (iii) M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain comprises T366W substitution (EU number); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain comprises T366W substitution (EU number).In some embodiments, (i) H1 comprises the amino acid sequence of SEQ ID NO:139 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:139; L1 comprises the amino acid sequence of SEQ ID NO:122 or 207 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:122 or 207; H2 comprises the amino acid sequence of SEQ ID NO:136 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:136; and L2 comprises the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:139; and L2 comprises the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:139. NO:103 has a variant having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity; or (ii) H1 contains the amino acid sequence of SEQ ID NO:138 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:138, L1 contains the amino acid sequence of SEQ ID NO:122 or 207 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:122 or 207, H2 contains the amino acid sequence of SEQ ID NO:137 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:137, and H2 contains the amino acid sequence of SEQ ID NO:137 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:138. NO:137 has a variant with at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity, and L2 contains the amino acid sequence of SEQ ID NO:103 or a variant thereof with at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:103.In some embodiments, (i) H1 contains the amino acid sequence of SEQ ID NO:139, L1 contains the amino acid sequence of SEQ ID NO:122 or 207, H2 contains the amino acid sequence of SEQ ID NO:136, and L2 contains the amino acid sequence of SEQ ID NO:103; or (ii) H1 contains the amino acid sequence of SEQ ID NO:138, L1 contains the amino acid sequence of SEQ ID NO:122 or 207, H2 contains the amino acid sequence of SEQ ID NO:137, and L2 contains the amino acid sequence of SEQ ID NO:103.

[0174] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 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) comprising SEQ ID NO:67. The CDR-H3 of the amino acid sequence of SEQ ID NO: 68; and wherein VL1 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; wherein the anti-TSLP antibody portion comprises: VH2 comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 21; and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 22, and VL2 comprising (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 24; (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 25; and (iii) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 68; CDR-L3 of the amino acid sequence of NO:26; wherein H1 contains substitutions at positions 170, 183, and 185 (EU number), and L1 contains a substitution at position 135 (EU number). In some embodiments, VH1 contains the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:65, and VL1 contains the amino acid sequence of SEQ ID NO:69 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69.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, the anti-TSLP antibody portion comprises: (a) VH2 comprising the amino acid sequence of SEQ ID NO:63 and VL2 comprising the amino acid sequence of SEQ ID NO:53; (b) VH2 comprising the amino acid sequence of SEQ ID NO:63 and VL2 comprising the amino acid sequence of SEQ ID NO:54; (c) VH2 comprising the amino acid sequence of SEQ ID NO:188 and VL2 comprising the amino acid sequence of SEQ ID NO:189; (d) VH2 comprising the amino acid sequence of SEQ ID NO:188 and VL2 comprising the amino acid sequence of SEQ ID NO:190; or (e) VH2 comprising the amino acid sequence of SEQ ID NO:228 and VL2 comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, H1 contains substitutions at positions F170, S183, and V185 (EU designation), and L1 contains substitutions at position L135 (EU designation). In some embodiments, H1 contains substitutions at F170V, S183I, and V185L (EU designation), and L1 contains substitutions at L135F (EU designation). In some embodiments, L1 is derived from the λ light chain. In some embodiments, L1 is derived from the κ light chain. In some embodiments, the anti-IL-13 antibody portion comprises: a first polypeptide comprising the amino acid sequence of SEQ ID NO:124 or a variant thereof having at least about 80% (such as 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 197 or a variant thereof having at least about 80% (such as 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 197. In some embodiments, the anti-TSLP antibody portion comprises: a first polypeptide comprising the amino acid sequence of SEQ ID NO:109 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:109, and a second polypeptide comprising the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as 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, such as human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU number); (ii) M428L and N434S substitutions (EU number); and / or (iii) M252Y, S254T, and T256E substitutions (EU number). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the second subunit of the Fc domain comprises T366W substitution (EU number); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU number), and the first subunit of the Fc domain comprises T366W substitution (EU number).In some embodiments, (i) H1 comprises the amino acid sequence of SEQ ID NO:141 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:141; L1 comprises the amino acid sequence of SEQ ID NO:122 or 207 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:122 or 207; H2 comprises the amino acid sequence of SEQ ID NO:136 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:136; and L2 comprises the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:141; and L2 comprises the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:141. NO:103 has a variant having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity; or (ii) H1 contains the amino acid sequence of SEQ ID NO:140 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:140, L1 contains the amino acid sequence of SEQ ID NO:122 or 207 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:122 or 207, H2 contains the amino acid sequence of SEQ ID NO:137 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:140, and H2 contains the amino acid sequence of SEQ ID NO:137 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:140. NO:137 has a variant with at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity, and L2 contains the amino acid sequence of SEQ ID NO:103 or a variant thereof with at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:103.In some embodiments, (i) H1 contains the amino acid sequence of SEQ ID NO:141, L1 contains the amino acid sequence of SEQ ID NO:122 or 207, H2 contains the amino acid sequence of SEQ ID NO:136, and L2 contains the amino acid sequence of SEQ ID NO:103; or (ii) H1 contains the amino acid sequence of SEQ ID NO:140, L1 contains the amino acid sequence of SEQ ID NO:122 or 207, H2 contains the amino acid sequence of SEQ ID NO:137, and L2 contains the amino acid sequence of SEQ ID NO:103.

[0175] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 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) comprising SEQ ID NO:67. The CDR-H3 of the amino acid sequence of SEQ ID NO: 68; and wherein VL1 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; wherein the anti-TSLP antibody portion comprises: VH2 comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 21; and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 22, and VL2 comprising (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 24; (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 25; and (iii) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 68; CDR-L3 of the amino acid sequence of NO:26; wherein H1 contains substitutions at positions 126 and 220 (EU number), and L1 contains substitutions at positions 124 and 214 (EU number). In some embodiments, VH1 contains the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:65, and VL1 contains the amino acid sequence of SEQ ID NO:69 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:69.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, the anti-TSLP antibody portion comprises: (a) VH2 comprising the amino acid sequence of SEQ ID NO:63 and VL2 comprising the amino acid sequence of SEQ ID NO:53; (b) VH2 comprising the amino acid sequence of SEQ ID NO:63 and VL2 comprising the amino acid sequence of SEQ ID NO:54; (c) VH2 comprising the amino acid sequence of SEQ ID NO:188 and VL2 comprising the amino acid sequence of SEQ ID NO:189; (d) VH2 comprising the amino acid sequence of SEQ ID NO:188 and VL2 comprising the amino acid sequence of SEQ ID NO:190; or (e) VH2 comprising the amino acid sequence of SEQ ID NO:228 and VL2 comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, L1 is derived from the λ light chain. In some embodiments, H1 contains substitutions at positions F126 and C220 (EU number), and L1 contains substitutions at positions E124 and C214 (EU number). In some embodiments, H1 contains F126C and C220S substitutions (EU number), and L1 contains E124C and C214S substitutions (EU number). In some embodiments, L1 is derived from the κ light chain. In some embodiments, H1 contains substitutions at positions F126 and C220 (EU number), and L1 contains substitutions at positions Q124 and C214 (EU number). In some embodiments, H1 contains F126C and C220S substitutions (EU number), and L1 contains Q124C and C214S substitutions (EU number). In some embodiments, the anti-IL-13 antibody portion comprises: a first polypeptide comprising the amino acid sequence of SEQ ID NO:124 or a variant thereof having at least about 80% (such as 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 197 or a variant thereof having at least about 80% (such as 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 197.In some embodiments, the anti-TSLP antibody portion comprises: a first polypeptide comprising the amino acid sequence of SEQ ID NO:109 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:109; and a second polypeptide comprising the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as 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, such as human IgG1. In some embodiments, each subunit of the Fc domain includes: (i) L234A and L235A substitutions (EU numbers); (ii) M428L and N434S substitutions (EU numbers); and / or (iii) M252Y, S254T, and T256E substitutions (EU numbers). In some embodiments, (i) the first subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the second subunit of the Fc domain includes T366W substitution (EU number); or (ii) the second subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the first subunit of the Fc domain includes T366W substitution (EU number).In some embodiments, (i) H1 comprises the amino acid sequence of SEQ ID NO:200 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:200; L1 comprises the amino acid sequence of SEQ ID NO:121 or 206 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:121 or 206; H2 comprises the amino acid sequence of SEQ ID NO:136 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:136; and L2 comprises the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:103. NO:103 has a variant having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity; or (ii) H1 contains the amino acid sequence of SEQ ID NO:201 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:201, L1 contains the amino acid sequence of SEQ ID NO:121 or 206 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:121 or 206, H2 contains the amino acid sequence of SEQ ID NO:137 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:137, and H2 contains the amino acid sequence of SEQ ID NO:137 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:137. NO:137 has a variant having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity, and L2 contains the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:103.In some embodiments, (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, and L2 contains the amino acid sequence of SEQ ID NO:103; or (ii) 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, and L2 contains the amino acid sequence of SEQ ID NO:103.

[0176] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 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) comprising SEQ ID NO:67. The CDR-H3 of the amino acid sequence of SEQ ID NO: 68; and wherein VL1 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; wherein the anti-TSLP antibody portion comprises: VH2 comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 21; and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 22, and VL2 comprising (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 24; (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 25; and (iii) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 68; CDR-L3 of the amino acid sequence of NO:26; wherein H1 contains substitutions at positions 126, 170, 183, 185, and 220 (EU number); and L1 contains substitutions at positions 124, 135, and 214 (EU number). In some embodiments, VH1 contains the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO:65, and VL1 contains the amino acid sequence of SEQ ID NO:69 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO:69.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, the anti-TSLP antibody portion comprises: (a) VH2 comprising the amino acid sequence of SEQ ID NO:63 and VL2 comprising the amino acid sequence of SEQ ID NO:53; (b) VH2 comprising the amino acid sequence of SEQ ID NO:63 and VL2 comprising the amino acid sequence of SEQ ID NO:54; (c) VH2 comprising the amino acid sequence of SEQ ID NO:188 and VL2 comprising the amino acid sequence of SEQ ID NO:189; (d) VH2 comprising the amino acid sequence of SEQ ID NO:188 and VL2 comprising the amino acid sequence of SEQ ID NO:190; or (e) VH2 comprising the amino acid sequence of SEQ ID NO:228 and VL2 comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, L1 is derived from the λ light chain. In some embodiments, H1 contains substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L1 contains substitutions at positions E124, L135, and C214 (EU number). In some embodiments, H1 contains substitutions at F126C, F170I, S183L, V185L, and C220S (EU number), and L1 contains substitutions at E124C, L135F, and C214S (EU number). In some embodiments, L1 is derived from the κ light chain. In some embodiments, H1 contains substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L1 contains substitutions at positions Q124, L135, and C214 (EU number). In some embodiments, H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbers), and L1 comprises Q124C, L135F, and C214S substitutions (EU numbers). In some embodiments, the anti-IL-13 antibody portion comprises: a first polypeptide comprising the amino acid sequence of SEQ ID NO:124 or a variant thereof having at least about 80% (such as 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 197 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:102 or 197.In some embodiments, the anti-TSLP antibody portion comprises: a first polypeptide comprising the amino acid sequence of SEQ ID NO:109 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:109; and a second polypeptide comprising the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as 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, such as human IgG1. In some embodiments, each subunit of the Fc domain includes: (i) L234A and L235A substitutions (EU numbers); (ii) M428L and N434S substitutions (EU numbers); and / or (iii) M252Y, S254T, and T256E substitutions (EU numbers). In some embodiments, (i) the first subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the second subunit of the Fc domain includes T366W substitutions (EU numbers); or (ii) the second subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the first subunit of the Fc domain includes T366W substitutions (EU numbers).In some embodiments, (i) H1 comprises the amino acid sequence of SEQ ID NO:126 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:126; L1 comprises the amino acid sequence of SEQ ID NO:120 or 208 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:120 or 208; H2 comprises the amino acid sequence of SEQ ID NO:136 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:136; and L2 comprises the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:126; and L2 comprises the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:126. NO:103 has a variant with at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity; or (ii) H1 contains the amino acid sequence of SEQ ID NO:127 or a variant thereof with at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:127, L1 contains the amino acid sequence of SEQ ID NO:120 or 208 or a variant thereof with at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:120 or 208, H2 contains the amino acid sequence of SEQ ID NO:137 or a variant thereof with at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:127, and ... 80% (such as at least 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:127, and H2 contains the amino acid sequence of SEQ ID NO:137 or a variant thereof with at least 80% (such as at least 85%, 90%, 95%, 96%, 97%, 98 NO:137 has a variant having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity, and L2 contains the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:103.In some embodiments, (i) H1 contains the amino acid sequence of SEQ ID NO:126, L1 contains the amino acid sequence of SEQ ID NO:120 or 208, H2 contains the amino acid sequence of SEQ ID NO:136, and L2 contains the amino acid sequence of SEQ ID NO:103; or (ii) H1 contains the amino acid sequence of SEQ ID NO:127, L1 contains the amino acid sequence of SEQ ID NO:120 or 208, H2 contains the amino acid sequence of SEQ ID NO:137, and L2 contains the amino acid sequence of SEQ ID NO:103.

[0177] In some embodiments, a multispecific construct is provided comprising a 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 an Fc domain; iii) a second heavy chain (H2) comprising VH2 and H2-CH1, and a second subunit of an 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 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) comprising SEQ ID NO:67. The CDR-H3 of the amino acid sequence of SEQ ID NO: 68; and wherein VL1 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; wherein the anti-TSLP antibody portion comprises: VH2 comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 20; (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 21; and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 22, and VL2 comprising (i) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 24; (ii) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 25; and (iii) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 68; CDR-L3 of the amino acid sequence of SEQ ID NO:26; wherein H1 contains substitutions at positions 126, 170, 183, 185, and 220 (EU number), and L1 contains substitutions at positions 124, 135, and 214 (EU number). In some embodiments, VH1 contains the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO:65, and VL1 contains the amino acid sequence of SEQ ID NO:69 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity with SEQ ID NO:69.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, the anti-TSLP antibody portion comprises: (a) VH2 comprising the amino acid sequence of SEQ ID NO:63 and VL2 comprising the amino acid sequence of SEQ ID NO:53; (b) VH2 comprising the amino acid sequence of SEQ ID NO:63 and VL2 comprising the amino acid sequence of SEQ ID NO:54; (c) VH2 comprising the amino acid sequence of SEQ ID NO:188 and VL2 comprising the amino acid sequence of SEQ ID NO:189; (d) VH2 comprising the amino acid sequence of SEQ ID NO:188 and VL2 comprising the amino acid sequence of SEQ ID NO:190; or (e) VH2 comprising the amino acid sequence of SEQ ID NO:228 and VL2 comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, L1 is derived from the λ light chain. In some embodiments, H1 contains substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L1 contains substitutions at positions E124, L135, and C214 (EU number). In some embodiments, H1 contains substitutions at F126C, F170V, S183I, V185L, and C220S (EU number), and L1 contains substitutions at E124C, L135F, and C214S (EU number). In some embodiments, L1 is derived from the κ light chain. In some embodiments, H1 contains substitutions at positions F126, F170, S183, V185, and C220 (EU number), and L1 contains substitutions at positions Q124, L135, and C214 (EU number). In some embodiments, H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbers), and L1 comprises Q124C, L135F, and C214S substitutions (EU numbers). In some embodiments, the anti-IL-13 antibody portion comprises: a first polypeptide comprising the amino acid sequence of SEQ ID NO:124 or a variant thereof having at least about 80% (such as 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 197 or a variant thereof having at least about 80% (such as 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 197.In some embodiments, the anti-TSLP antibody portion comprises: a first polypeptide comprising the amino acid sequence of SEQ ID NO:109 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:109; and a second polypeptide comprising the amino acid sequence of SEQ ID NO:103 or a variant thereof having at least about 80% (such as 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, such as human IgG1. In some embodiments, each subunit of the Fc domain includes: (i) L234A and L235A substitutions (EU numbers); (ii) M428L and N434S substitutions (EU numbers); and / or (iii) M252Y, S254T, and T256E substitutions (EU numbers). In some embodiments, (i) the first subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the second subunit of the Fc domain includes T366W substitutions (EU numbers); or (ii) the second subunit of the Fc domain includes T366S, L368A, and Y407V substitutions (EU numbers), and the first subunit of the Fc domain includes T366W substitutions (EU numbers).In some embodiments, (i) H1 comprises the amino acid sequence of SEQ ID NO:128 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:128; L1 comprises the amino acid sequence of SEQ ID NO:120 or 208 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:120 or 208; H2 comprises the amino acid sequence of SEQ ID NO:136 or a variant thereof having at least about 80% (such as at least about 85%, 90%, 95%, 96%, 97%, 98%, 99% or more) sequence identity with SEQ ID NO:136; and L2 comprises the amino acid sequence of SEQ ID NO:103 or a variant thereof having ...

Claims

1. A multispecific construct, the multispecific construct comprising: (1) The first antibody portion, which specifically binds to interleukin-13 (IL-13), and (2) The second antibody portion specifically binds to the 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), wherein the VH1 comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof comprising up to 3 amino acid variations, (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:67 or a variant thereof comprising up to 3 amino acid variations, and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:68 or a variant thereof comprising up to 3 amino acid variations, and the VL1 comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:70 or a variant thereof comprising up to 3 amino acid variations, (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:71 or a variant thereof comprising up to 3 amino acid variations, and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:72 or a variant thereof comprising up to 3 amino acid variations.

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

72.

4. The multispecific construct according to claim 2 or 3, wherein the 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 the 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 the VH1 comprises the amino acid sequence of SEQ ID NO:65, and the VL1 comprises the amino acid sequence of SEQ ID NO:

69.

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

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

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

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

10. The multispecific construct according to any one of claims 1 to 9, wherein the second antigen is thymic stromal lymphopoietin (TSLP).

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

50.

12. The multispecific construct according to claim 11, wherein: (a) The VH2 comprises 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 comprises 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 comprises 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 comprises 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 comprises 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 comprises 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 comprises 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 comprises 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 comprises 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 comprises 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 comprises 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 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; or (ee) The VH2 contains 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 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.

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

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

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

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

17. The multispecific construct of claim 16, wherein the second antibody portion is anti-TSLP Fab, and wherein the anti-TSLP Fab comprises 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.

18. The multispecific construct according to any one of claims 1 to 5, 8, and 10 to 17, wherein the first antibody moiety comprises a heavy chain (H1) and a light chain (L1), wherein the H1 comprises VH1 and H1-CH1, wherein the L1 comprises VL1 and L1-CL, and wherein: (i) The H1 includes the substitution at positions 170, 183, and 185 (EU number), and the L1 includes the substitution at position 135 (EU number); and / or (ii) The H1 is contained in the substitution at positions 126 and 220 (EU number), and the L1 is contained in the substitution at positions 124 and 214 (EU number).

19. The multispecific construct of claim 18, wherein H1 comprises substitutions at positions F170, S183, and V185 (EU number), and L1 comprises substitutions at position L135 (EU number).

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

21. The multispecific construct according to claim 20, wherein: (a) H1 contains F170I, S183L and V185L substitutions (EU designations), and L1 contains L135F substitutions (EU designation); or (b) H1 contains F170V, S183I and V185L substitutions (EU designation), and L1 contains L135F substitutions (EU designation).

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

23. The multispecific construct of claim 22, wherein H1 comprises substitutions at positions F126 and C220 (EU number), and L1 comprises substitutions at positions E124 and C214 (EU number).

24. The multispecific construct of claim 23, wherein H1 comprises F126C and C220S substitutions (EU number), and L1 comprises E124C and C214S substitutions (EU number).

25. The multispecific construct according to any one of claims 18 to 21, wherein the L1 is derived from the κ light chain.

26. The multispecific construct of claim 25, wherein H1 comprises substitutions at positions F126 and C220 (EU number), and L1 comprises substitutions at positions Q124 and C214 (EU number).

27. The multispecific construct of claim 26, wherein H1 comprises F126C and C220S substitutions (EU number), and L1 comprises Q124C and C214S substitutions (EU number).

28. The multispecific construct according to any one of claims 18 to 27, wherein (i) H1 is substituted with F126C, F170I, S183L, V185L and C220S, and L1 is substituted with E124C, L135F and C214S; (ii) H1 is substituted with F126C, F170V, S183I, V185L and C220S, and L1 is substituted with E124C, L135F and C214S; (iii) H1 is substituted with F126C, F170I, S183L, V185L and C220S, and L1 is substituted with Q124C, L135F and C214S; or (iv) H1 is substituted with F126C, F170V, S183I, V185L, and C220S, and L1 is substituted with Q124C, L135F, and C214S; and The location is based on the EU number.

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, wherein the Fc domain comprises a first subunit and a second subunit.

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

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

32. The multispecific construct according to claim 31, wherein: (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 comprises the amino acid sequence of SEQ ID NO:81, and the second subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:80; (iii) The first subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:95, and the second subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:96; or (iv) 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 multispecific construct according to any one of claims 1 to 5, 10 to 12, and 18 to 32, wherein the multispecific construct is a heterodimeric bispecific antibody, the heterodimeric bispecific antibody comprising: i) A first light chain (L1), the first light chain comprising VL1 and L1-CL; ii) The first heavy chain (H1) comprises VH1, H1-CH1 and the 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; and H1 and L1 form the anti-IL-13 antibody portion, and H2 and L2 form the second antibody portion.

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

35. The multispecific construct according to claim 33 or 34, wherein: (a) H1 is substituted with F170I, S183L and V185L, and L1 is substituted with L135F; (b) H1 comprises F170V, S183I and V185L substitutions, and L1 comprises L135F substitutions; (c) H1 is substituted with F126C, F170I, S183L, V185L and C220S, and L1 is substituted with E124C, L135F and C214S. (d) H1 is substituted with F126C, F170V, S183I, V185L and C220S, and L1 is substituted with E124C, L135F and C214S; (e) H1 contains F126C and C220S substitutions, and L1 contains E124C and C214S substitutions; (f) H1 ​​is substituted with F170I, S183L, V185L, T366S, L368A and Y407V, L1 is substituted with L135F and H2 is substituted with T366W. (g) H1 is substituted with F170I, S183L, V185L and T366W, L1 is substituted with L135F, and H2 is substituted with T366S, L368A and Y407V. (h) H1 is substituted with F170V, S183I, V185L, T366S, L368A and Y407V, L1 is substituted with L135F and H2 is substituted with T366W. (i) H1 is substituted with F170V, S183I, V185L and T366W, L1 is substituted with L135F, and H2 is substituted with T366S, L368A and Y407V. (j) H1 is substituted with F126C, F170I, S183L, V185L, C220S, T366S, L368A and Y407V, L1 is substituted with E124C, L135F and C214S, and H2 is substituted with T366W. (k) H1 is substituted with F126C, F170I, S183L, V185L, C220S and T366W, L1 is substituted with E124C, L135F and C214S, and H2 is substituted with T366S, L368A and Y407V. (l) H1 is substituted with F126C, F170V, S183I, V185L, C220S, T366S, L368A and Y407V, L1 is substituted with E124C, L135F and C214S, and H2 is substituted with T366W. (m) H1 is substituted with F126C, F170V, S183I, V185L, C220S and T366W, L1 is substituted with E124C, L135F and C214S, and H2 is substituted with T366S, L368A and Y407V. (n) H1 is substituted with F126C, C220S, T366S, L368A and Y407V, L1 is substituted with E124C and C214S, and H2 is substituted with T366W. (o) H1 is substituted with F126C, C220S and T366W, L1 is substituted with E124C and C214S, and H2 is substituted with T366S, L368A and Y407V. (p) H1 is substituted with F170I, S183L, V185L, L234A, L235A, T366S, L368A, Y407V, M428L and N434S, L1 is substituted with L135F, and H2 is substituted with L234A, L235A, T366W, M428L and N434S; (q) H1 is substituted with F170I, S183L, V185L, L234A, L235A, T366W, M428L and N434S, L1 is substituted with L135F, and H2 is substituted with L234A, L235A, T366S, L368A, Y407V, M428L and N434S; (r) H1 is substituted with F170V, S183I, V185L, L234A, L235A, T366S, L368A, Y407V, M428L and N434S, L1 is substituted with L135F, and H2 is substituted with L234A, L235A, T366W, M428L and N434S; (s) H1 is substituted with F170V, S183I, V185L, L234A, L235A, T366W, M428L and N434S, L1 is substituted with L135F, and H2 is substituted with L234A, L235A, T366S, L368A, Y407V, M428L and N434S; (t) H1 is substituted with F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L and N434S, L1 is substituted with E124C, L135F and C214S, and H2 is substituted with L234A, L235A, T366W, M428L and N434S; (u) H1 is substituted with F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366W, M428L and N434S, L1 is substituted with E124C, L135F and C214S, and H2 is substituted with L234A, L235A, T366S, L368A, Y407V, M428L and N434S; (v) H1 is substituted with F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L and N434S, L1 is substituted with E124C, L135F and C214S, and H2 is substituted with L234A, L235A, T366W, M428L and N434S; (w) H1 is substituted with F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366W, M428L and N434S, L1 is substituted with E124C, L135F and C214S, and H2 is substituted with L234A, L235A, T366S, L368A, Y407V, M428L and N434S; (x) H1 is substituted with F126C, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S, L1 is substituted with E124C and C214S, and H2 is substituted with L234A, L235A, T366W, M428L, and N434S; or (y) H1 is substituted with F126C, C220S, L234A, L235A, T366W, M428L, and N434S; L1 is substituted with E124C and C214S; and H2 is substituted with L234A, L235A, T366S, L368A, Y407V, M428L, and N434S. The amino acid positions are based on EU designations.

36. The multispecific construct according to claim 35, wherein: (a) H1 contains the amino acid sequence of SEQ ID NO:87, L1 contains the amino acid sequence of SEQ ID NO:173 or 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 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 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 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 203, and H2 contains the amino acid sequence of SEQ ID NO:85; (f) H1 ​​contains the amino acid sequence of SEQ ID NO:92, L1 contains the amino acid sequence of SEQ ID NO:174 or 203, and H2 contains the amino acid sequence of SEQ ID NO:86; (g) H1 contains the amino acid sequence of SEQ ID NO:93, L1 contains the amino acid sequence of SEQ ID NO:174 or 203, and H2 contains the amino acid sequence of SEQ ID NO:85; (h) H1 contains the amino acid sequence of SEQ ID NO:94, L1 contains the amino acid sequence of SEQ ID NO:174 or 203, and H2 contains the amino acid sequence of SEQ ID NO:86; (i) H1 contains the amino acid sequence of SEQ ID NO:198, L1 contains the amino acid sequence of SEQ ID NO:204 or 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 205, and H2 contains 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 human κ light chain.

38. The multispecific construct of claim 37, wherein the second antigen is TSLP, and wherein: (a) H1 contains the amino acid sequence of SEQ ID NO:139, L1 contains the amino acid sequence of SEQ ID NO:122 or 207, H2 contains the amino acid sequence of SEQ ID NO:136, and 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 207, H2 contains the amino acid sequence of SEQ ID NO:137, and L2 contains the amino acid sequence of SEQ ID NO:

103. (c) H1 contains the amino acid sequence of SEQ ID NO:141, L1 contains the amino acid sequence of SEQ ID NO:122 or 207, H2 contains the amino acid sequence of SEQ ID NO:136, and L2 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 207, H2 contains the amino acid sequence of SEQ ID NO:137, and 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 208, H2 contains the amino acid sequence of SEQ ID NO:136, and 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 208, H2 contains the amino acid sequence of SEQ ID NO:137, and 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, and 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, and 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, and 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, and L2 contains the amino acid sequence of SEQ ID NO:

103.

39. An isolated antibody construct (anti-IL-13 antibody construct), said isolated antibody construct comprising an antibody moiety (anti-IL-13 antibody moiety) specifically binding to interleukin-13 (IL-13), wherein said anti-IL-13 antibody moiety comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein: The VH comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof comprising up to 3 amino acid variations; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:67 or a variant thereof comprising up to 3 amino acid variations; and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:68 or a variant thereof comprising up to 3 amino acid variations; and the VL comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:70 or a variant thereof comprising up to 3 amino acid variations; (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:71 or a variant thereof comprising up to 3 amino acid variations; and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:72 or a variant thereof comprising up to 3 amino acid variations.

40. The isolated anti-IL-13 antibody construct according to claim 39, wherein the 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 the 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.

41. The isolated anti-IL-13 antibody construct according to claim 39 or 40, wherein the 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 the 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 the VH comprises the amino acid sequence of SEQ ID NO:65, and the 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: full-length antibody, Fab, Fab', F(ab')2, biantibody 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 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 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 isolated anti-IL-13 antibody construct according to claim 48, wherein 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 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 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 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 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 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 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 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 208. ix) Each of the following two heavy chains contains the amino acid sequence of SEQ ID NO:225 and each of the following two light chains contains the amino acid sequence of SEQ ID NO:102 or 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 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, wherein the isolated anti-IL-13 antibody construct further comprises a second antibody portion 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, said isolated nucleic acid or vector encoding one or more polypeptides of 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.

54. A host cell comprising the isolated nucleic acid or vector according to claim 53.

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

56. The method according to claim 55, (i) The inflammatory disease mentioned above is asthma, atopic dermatitis, or chronic obstructive pulmonary disease (COPD); and / or (ii) The individual mentioned therein is a person.

57. A method for generating a multispecific construct or an anti-IL-13 antibody construct, the method comprising: i) Culture host cells containing the isolated nucleic acid or vector according to claim 53 or the host cells according to claim 54 under conditions suitable for expressing the multispecific construct or the anti-IL-13 antibody construct; and ii) Obtain the expressed multispecific construct or anti-IL-13 antibody construct.

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