Anti-il-13 multispecific antibody constructs and uses thereof

Abstract

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

Description

ANTI-IL-13 MULTISPECIFIC ANTIBODY CONSTRUCTS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of, and priority to U.S. Provisional Application No.63 / 578,946, filed August 25, 2023, the content of which is incorporated herein by reference in its entirety. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The content of the electronic sequence listing (253272000140seqlist.xml; Size: 239,418 bytes; and Date of Creation: August 19, 2024) is herein incorporated by reference in its entirety. FIELD OF THE INVENTION

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

[0004] Many abnormal cells and tissues as well as many diseases display unique antigens that can be leveraged for immune cell-mediated clearance, including inflammatory diseases such as autoimmune disorders or asthma. These inflammatory diseases can each display one or more different target antigens or one or more different epitopes of the same target antigen. For example, some antigens are over-expressed, mutagenized, or selectively mutagenized in inflamed tissues. Therefore, antibodies targeting specific antigens present in diseases with systemic or localized inflammation can be used as therapeutics.

[0005] Interleukin (IL)-13 is a pleiotropic cytokine frequently associated with asthma and atopic dermatitis. IL-13 binds to a high-affinity heteromeric 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 engaging separate signaling cascades than IL-13Rα1. IL-13 is secreted predominantly by T helper type 2 cells (Th2 cells) and by type 2 innate lymphoid cells (ILC2). ILC2s produce IL-5 and IL-13 during allergic inflammation and bridge the innate and adaptive immune responses. ILC2 activity promotes T-helper 2 cell (Th2) response, and theconcurrent actions of ILC2 cells and Th2 cells also is 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 tralokinumab (AdbryTM; see, e.g., Brightling et al. Lancet Respir Med.2015, 3(9):692-701) and the mixed results of lebrikizumab (see, e.g., Hanania et al. Lancet Respir Med.2016, 4(10):781-796) for the treatment of severe asthma are demonstrative that other anti-IL-13 antibodies are needed for treating IL-13-associated diseases, in particular inflammatory diseases. In particular, the premature termination of the ACOUSTICS clinical trial for lebrikizumab due to adverse events in 73% of patients (see Szefler et al. Clin Transl Allergy 2022, 12(7):212176) is further indicative of a clear need for safer as well as more potent therapeutic options. BRIEF SUMMARY OF THE INVENTION

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

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

[0009] In some embodiments according to any of the multispecific constructs described above, the first antibody moiety comprises a heavy chain variable region (VH1) and a light chain variable region (VL1), wherein: the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66, or a variant thereof comprising up to 3 amino acid variations, (ii) a CDR-H2 comprising an 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 an 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 an amino acid sequence of SEQ ID NO:70, or a variant thereof comprising up to 3 amino acid variations, (ii) a CDR-L2 comprising an 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 an amino acid sequence of SEQ ID NO:72, or a variant thereof comprising up to 3 amino acid variations. In some embodiments,the VH1 comprises an 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 an 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, the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66, (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67, and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68, and the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70, (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71, and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO:65, and the VL1 comprises an amino acid sequence of SEQ ID NO:69.

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

[0011] In some embodiments according to any of the multispecific constructs described above, the first antibody moiety is an 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 according to any of the multispecific constructs described above, the first antibody moiety is a Fab (“anti-IL-13 Fab”). In some embodiments, the anti- IL-13 Fab comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO:124, and a second polypeptide comprising the amino acid sequence of SEQ ID NO:102 or 197.

[0013] In some embodiments according to any of the multispecific constructs described above, the first antibody moiety is a full-length antibody (“anti-IL-13 full-length antibody”). In some embodiments, the anti-IL-13 full-length antibody comprises an Fc domain derived from a human IgG (e.g., human IgG1, human IgG2, or human IgG4). In some embodiments, the Fc domain is derived from human IgG1, wherein: i) a first subunit and a second subunit of the Fc domain each comprises the amino acid sequence of any one of SEQ ID NOs:76-79; ii) a first subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:80, and a second subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:81; iii) a first subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:81, and a second subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:80; iv) a first subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:95, and a second subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:96; or v)a first subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:96, and a second subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:95. In some embodiments, the anti-IL-13 full-length 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: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.

[0014] In some embodiments according to any of the multispecific constructs described above, the second antigen is TSLP, wherein the second antibody moiety comprises a heavy chain variable region (VH2) and a light chain variable region (VL2), wherein: (a) the VH2 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:2; (ii) a CDR- H2 comprising an amino acid sequence of SEQ ID NO:3; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:4; and the VL2 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:6; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:7; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:8; (b) the VH2 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:12; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:13; and (iii) a CDR-H3comprising an amino acid sequence of SEQ ID NO:4; and the VL2 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:6; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:7; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:8; (c) the VH2 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22; and the VL2 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (ii) a CDR- L2 comprising an amino acid sequence of SEQ ID NO:25; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26; (d) the VH2 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:28; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:29; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:30; and the VL2 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:32; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:33; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:34; (e) the VH2 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:36; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:37; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:38; and the VL2 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:40; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:41; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:42; or (f) the VH2 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:44; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:45; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:46; and the VL2 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:48; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:49; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:50. In some embodiments, (a) the VH2 comprises an 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 an 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 an 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 an 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 an 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 an amino acid sequence of SEQ ID NO:15, or an amino acidsequence having at least about 80% sequence identity with SEQ ID NO:15; (d) the VH2 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 an 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 an 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 an 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 an 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 comprises an 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 an 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 comprises an amino acid sequence of SEQ ID NO:63, or an amino acid sequence having at least about 80% sequence identity withSEQ ID NO:63, and the VL2 comprises an 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 comprises an 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 comprises an 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 comprises an 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 an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 an 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 an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an amino acid sequence ofSEQ ID NO:64, or an amino acid sequence having at least about 80% sequence identity with SEQ ID NO:64, and the VL2 comprises an 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 comprises an 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 an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 an 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 an 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 an 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 comprises an 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 comprises an 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 according to any of the multispecific constructs described above, the second antibody moiety is selected from the group consisting of: a full-length antibody, a Fab, a Fab’, a F(ab’)2, an sdAb, and an scFv.

[0016] In some embodiments according to any of the multispecific constructs described above, the second antibody moiety is a full-length antibody. In some embodiments, the full- length antibody comprises an Fc domain derived from a human IgG (e.g., human IgG1, human IgG2, or human IgG4). In some embodiments, the Fc domain is derived from human IgG1, wherein: i) a first subunit and a second subunit of the Fc domain each comprises the amino acid sequence of any one of SEQ ID NOs:76-79; ii) a first subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:80, and a second subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:81; or iii) a first subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO: 81, and a 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 according to any of the multispecific constructs described above, the second antibody moiety is an scFv. In some embodiments, the second antibody moiety is an anti-TSLP scFv comprising the amino acid sequence of any one of SEQ ID NOs:106, 107, 218, 219, 226, 227, and 229.

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

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

[0020] In some embodiments according to any of the multispecific constructs described above, the multispecific constructs further comprise an Fc domain, wherein the Fc domain comprises a first subunit and a second subunit. In some embodiments, the Fc domain is derived from an 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 numbering). In someembodiments, 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 numbering). 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 numbering). In some embodiments, each subunit of the Fc domain comprises the amino acid sequence of SEQ ID NO:79. In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, (i) 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; (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.

[0021] In some embodiments according to any of the multispecific constructs described above, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; and wherein H1 and L1 form the anti-IL-13 antibody moiety, and H2 and L2 form the second antibody moiety. In some embodiments, the Fc domain is derived from human IgG1. In some embodiments, the L1-CL is derived from a human lambda light chain. In some embodiments, (a) the H1 comprises F170I, S183L, and V185L substitutions, and the L1 comprises an L135F substitution; (b) the H1 comprises F170V, S183I, and V185L substitutions, and the L1 comprises an L135F substitution; (c) the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions, and the L1 comprises E124C, L135F, and C214S substitutions; (d) the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions, and the L1 comprises E124C, L135F, and C214S substitutions; or (e) the H1 comprises F126C and C220S substitutions, and the L1 comprisesE124C and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, (a) the H1 comprises F170I, S183L, V185L, T366S, L368A, and Y407V substitutions, the L1 comprises an L135F substitution, and the H2 comprises a T366W substitution; (b) the H1 comprises F170I, S183L, V185L, and T366W substitutions, the L1 comprises an L135F substitution, and the H2 comprises T366S, L368A, and Y407V substitutions; (c) the H1 comprises F170V, S183I, V185L, T366S, L368A, and Y407V substitutions, the L1 comprises an L135F substitution, and the H2 comprises a T366W substitution; (d) the H1 comprises F170V, S183I, V185L, and T366W substitutions, the L1 comprises an L135F substitution, and the H2 comprises T366S, L368A, and Y407V substitutions; (e) the H1 comprises F126C, F170I, S183L, V185L, C220S, T366S, L368A, and Y407V substitutions, the L1 comprises E124C, L135F, and C214S substitutions, and the H2 comprises a T366W substitution; (f) the H1 comprises F126C, F170I, S183L, V185L, C220S, and T366W substitutions, the L1 comprises E124C, L135F, and C214S substitutions, and the H2 comprises T366S, L368A, and Y407V substitutions; (g) the H1 comprises F126C, F170V, S183I, V185L, C220S, T366S, L368A, and Y407V substitutions, the L1 comprises E124C, L135F, and C214S substitutions, and the H2 comprises a T366W substitution; (h) the H1 comprises F126C, F170V, S183I, V185L, C220S, and T366W substitutions, the L1 comprises E124C, L135F, and C214S substitutions, and the H2 comprises T366S, L368A, and Y407V substitutions; (i) the H1 comprises F126C, C220S, T366S, L368A, and Y407V substitutions, the L1 comprises E124C and C214S substitutions, and the H2 comprises a T366W substitution; or (j) the H1 comprises F126C, C220S, and T366W substitutions, the L1 comprises E124C and C214S substitutions, and the H2 comprises T366S, L368A, and Y407V substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, (a) the H1 comprises F170I, S183L, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, the L1 comprises an L135F substitution, and the H2 comprises L234A, L235A, T366W, M428L, and N434S substitutions; (b) the H1 comprises F170I, S183L, V185L, L234A, L235A, T366W, M428L, and N434S substitutions, the L1 comprises an L135F substitution, and the H2 comprises L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; (c) the H1 comprises F170V, S183I, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, the L1 comprises an L135F substitution, and the H2 comprises L234A, L235A, T366W, M428L, and N434S substitutions; (d) the H1 comprises F170V, S183I, V185L, L234A, L235A, T366W, M428L, and N434S substitutions, the L1 comprises an L135F substitution, and the H2 comprises L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; (e)the H1 comprises F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, the L1 comprises E124C, L135F, and C214S substitutions, and the H2 comprises L234A, L235A, T366W, M428L, and N434S substitutions; (f) the H1 comprises F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366W, M428L, and N434S substitutions, the L1 comprises E124C, L135F, and C214S substitutions, and the H2 comprises L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; (g) the H1 comprises F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, the L1 comprises E124C, L135F, and C214S substitutions, and the H2 comprises L234A, L235A, T366W, M428L, and N434S substitutions; (h) the H1 comprises F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366W, M428L, and N434S substitutions, the L1 comprises E124C, L135F, and C214S substitutions, and the H2 comprises L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; (i) the H1 comprises F126C, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, the L1 comprises E124C and C214S substitutions, and the H2 comprises L234A, L235A, T366W, M428L, and N434S substitutions; or (j) the H1 comprises F126C, C220S, L234A, L235A, T366W, M428L, and N434S substitutions, the L1 comprises E124C and C214S substitutions, and the H2 comprises L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, (a) the H1 comprises an amino acid sequence of SEQ ID NO:87, the L1 comprises an amino acid sequence of SEQ ID NO:173 or 202, and the H2 comprises an amino acid sequence of SEQ ID NO:85; (b) the H1 comprises an amino acid sequence of SEQ ID NO:88, the L1 comprises an amino acid sequence of SEQ ID NO:173 or 202, and the H2 comprises an amino acid sequence of SEQ ID NO:86; (c) the H1 comprises an amino acid sequence of SEQ ID NO:89, the L1 comprises an amino acid sequence of SEQ ID NO:173 or 202, and the H2 comprises an amino acid sequence of SEQ ID NO:85; (d) the H1 comprises an amino acid sequence of SEQ ID NO:90, the L1 comprises an amino acid sequence of SEQ ID NO:173 or 202, and the H2 comprises an amino acid sequence of SEQ ID NO:86; (e) the H1 comprises an amino acid sequence of SEQ ID NO:91, the L1 comprises an amino acid sequence of SEQ ID NO:174 or 203, and the H2 comprises an amino acid sequence of SEQ ID NO:85; (f) the H1 comprises an amino acid sequence of SEQ ID NO:92, the L1 comprises an amino acid sequence of SEQ ID NO:174 or 203, and the H2 comprises an amino acid sequence of SEQ ID NO:86; (g) the H1 comprises an amino acid sequence of SEQ ID NO:93, the L1 comprises an amino acid sequence of SEQ ID NO:174 or 203, and the H2 comprises anamino acid sequence of SEQ ID NO:85; (h) the H1 comprises an amino acid sequence of SEQ ID NO:94, the L1 comprises an amino acid sequence of SEQ ID NO:174 or 203, and the H2 comprises an amino acid sequence of SEQ ID NO:86; (i) the H1 comprises an amino acid sequence of SEQ ID NO:198, the L1 comprises an amino acid sequence of SEQ ID NO:204 or 205, and the H2 comprises an amino acid sequence of SEQ ID NO:85; or (j) the H1 comprises an amino acid sequence of SEQ ID NO:199, the L1 comprises an amino acid sequence of SEQ ID NO:204 or 205, and the H2 comprises an amino acid sequence of SEQ ID NO:86. In some embodiments, the L2-CL is derived from a human kappa light chain. In some embodiments, the second antigen is TSLP. In some embodiments, (a) the H1 comprises the amino acid sequence of SEQ ID NO:139, the L1 comprises the amino acid sequence of SEQ ID NO:122 or 207, the H2 comprises the amino acid sequence of SEQ ID NO:136, and the L2 comprises the amino acid sequence of SEQ ID NO:103; (b) the H1 comprises the amino acid sequence of SEQ ID NO:138, the L1 comprises the amino acid sequence of SEQ ID NO:122 or 207, the H2 comprises the amino acid sequence of SEQ ID NO:137, and the L2 comprises the amino acid sequence of SEQ ID NO:103; (c) the H1 comprises the amino acid sequence of SEQ ID NO:141, the L1 comprises the amino acid sequence of SEQ ID NO:122 or 207, the H2 comprises the amino acid sequence of SEQ ID NO:136, and the L2 comprises the amino acid sequence of SEQ ID NO:103; (d) the H1 comprises the amino acid sequence of SEQ ID NO:140, the L1 comprises the amino acid sequence of SEQ ID NO:122 or 207, the H2 comprises the amino acid sequence of SEQ ID NO:137, and the L2 comprises the amino acid sequence of SEQ ID NO:103; (e) the H1 comprises the amino acid sequence of SEQ ID NO:126, the L1 comprises the amino acid sequence of SEQ ID NO:120 or 208, the H2 comprises the amino acid sequence of SEQ ID NO:136, and the L2 comprises the amino acid sequence of SEQ ID NO:103; (f) the H1 comprises the amino acid sequence of SEQ ID NO:127, the L1 comprises the amino acid sequence of SEQ ID NO:120 or 208, the H2 comprises the amino acid sequence of SEQ ID NO:137, and the L2 comprises the amino acid sequence of SEQ ID NO:103; (g) the H1 comprises the amino acid sequence of SEQ ID NO:128, the L1 comprises the amino acid sequence of SEQ ID NO:120 or 208, the H2 comprises the amino acid sequence of SEQ ID NO:136, and the L2 comprises the amino acid sequence of SEQ ID NO:103; (h) the H1 comprises the amino acid sequence of SEQ ID NO:129, the L1 comprises the amino acid sequence of SEQ ID NO:120 or 208, the H2 comprises the amino acid sequence of SEQ ID NO:137, and the L2 comprises the amino acid sequence of SEQ ID NO:103; (i) the H1 comprises the amino acid sequence of SEQ ID NO:200, the L1 comprises the amino acid sequence of SEQ ID NO:121 or 206, the H2comprises the amino acid sequence of SEQ ID NO:136, and the L2 comprises the amino acid sequence of SEQ ID NO:103; or (j) the H1 comprises the amino acid sequence of SEQ ID NO:201, the L1 comprises the amino acid sequence of SEQ ID NO:121 or 206, the H2 comprises the amino acid sequence of SEQ ID NO:137, and the L2 comprises the amino acid sequence of SEQ ID NO:103. In some embodiments, the Fc domain is derived from human IgG1. In some embodiments, the L2-CL is derived from a human lambda light chain. In some embodiments, (a) the H2 comprises F170I, S183L, and V185L substitutions, and the L2 comprises an L135F substitution; (b) the H2 comprises F170V, S183I, and V185L substitutions, and the L2 comprises an L135F substitution; (c) the H2 comprises F126C, F170I, S183L, V185L, and C220S substitutions, and the L2 comprises E124C, L135F, and C214S substitutions; (d) the H2 comprises F126C, F170V, S183I, V185L, and C220S substitutions, and the L2 comprises E124C, L135F, and C214S substitutions; or (e) the H2 comprises F126C and C220S substitutions, and the L2 comprises E124C and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, (a) the H2 comprises F170I, S183L, V185L, T366S, L368A, and Y407V substitutions, the L2 comprises an L135F substitution, and the H1 comprises a T366W substitution; (b) the H2 comprises F170I, S183L, V185L, and T366W substitutions, the L2 comprises an L135F substitution, and the H1 comprises T366S, L368A, and Y407V substitutions; (c) the H2 comprises F170V, S183I, V185L, T366S, L368A, and Y407V substitutions, the L2 comprises an L135F substitution, and the H1 comprises a T366W substitution; (d) the H2 comprises F170V, S183I, V185L, and T366W substitutions, the L2 comprises an L135F substitution, and the H1 comprises T366S, L368A, and Y407V substitutions; (e) the H2 comprises F126C, F170I, S183L, V185L, C220S, T366S, L368A, and Y407V substitutions, the L2 comprises E124C, L135F, and C214S substitutions, and the H1 comprises a T366W substitution; (f) the H2 comprises F126C, F170I, S183L, V185L, C220S, and T366W substitutions, the L2 comprises E124C, L135F, and C214S substitutions, and the H1 comprises T366S, L368A, and Y407V substitutions; (g) the H2 comprises F126C, F170V, S183I, V185L, C220S, T366S, L368A, and Y407V substitutions, the L2 comprises E124C, L135F, and C214S substitutions, and the H1 comprises a T366W substitution; (h) the H2 comprises F126C, F170V, S183I, V185L, C220S, and T366W substitutions, the L2 comprises E124C, L135F, and C214S substitutions, and the H1 comprises T366S, L368A, and Y407V substitutions; (i) the H2 comprises F126C, C220S, T366S, L368A, and Y407V substitutions, the L2 comprises E124C and C214S substitutions, and the H1 comprises a T366W substitution; or (j) the H2 comprises F126C, C220S, and T366W substitutions, theL2 comprises E124C and C214S substitutions, and the H1 comprises T366S, L368A, and Y407V substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, (a) the H2 comprises F170I, S183L, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, the L2 comprises an L135F substitution, and the H1 comprises L234A, L235A, T366W, M428L, and N434S substitutions; (b) the H2 comprises F170I, S183L, V185L, L234A, L235A, T366W, M428L, and N434S substitutions, the L2 comprises an L135F substitution, and the H1 comprises L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; (c) the H2 comprises F170V, S183I, V185L, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, the L2 comprises an L135F substitution, and the H1 comprises L234A, L235A, T366W, M428L, and N434S substitutions; (d) the H2 comprises F170V, S183I, V185L, L234A, L235A, T366W, M428L, and N434S substitutions, the L2 comprises an L135F substitution, and the H1 comprises L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; (e) the H2 comprises F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, the L2 comprises E124C, L135F, and C214S substitutions, and the H1 comprises L234A, L235A, T366W, M428L, and N434S substitutions; (f) the H2 comprises F126C, F170I, S183L, V185L, C220S, L234A, L235A, T366W, M428L, and N434S substitutions, the L2 comprises E124C, L135F, and C214S substitutions, and the H1 comprises L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; (g) the H2 comprises F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, the L2 comprises E124C, L135F, and C214S substitutions, and the H1 comprises L234A, L235A, T366W, M428L, and N434S substitutions; (h) the H2 comprises F126C, F170V, S183I, V185L, C220S, L234A, L235A, T366W, M428L, and N434S substitutions, the L2 comprises E124C, L135F, and C214S substitutions, and the H1 comprises L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; (i) the H2 comprises F126C, C220S, L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions, the L2 comprises E124C and C214S substitutions, and the H1 comprises L234A, L235A, T366W, M428L, and N434S substitutions; or (j) the H2 comprises F126C, C220S, L234A, L235A, T366W, M428L, and N434S substitutions, the L2 comprises E124C and C214S substitutions, and the H1 comprises L234A, L235A, T366S, L368A, Y407V, M428L, and N434S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, (a) the H2 comprises an amino acid sequence of SEQ ID NO:87, the L2 comprises an amino acid sequence of SEQ ID NO:173 or 202, and the H1 comprises an amino acid sequence of SEQID NO:85; (b) the H2 comprises an amino acid sequence of SEQ ID NO:88, the L2 comprises an amino acid sequence of SEQ ID NO:173 or 202, and the H1 comprises an amino acid sequence of SEQ ID NO:86; (c) the H2 comprises an amino acid sequence of SEQ ID NO:89, the L2 comprises an amino acid sequence of SEQ ID NO:173 or 202, and the H1 comprises an amino acid sequence of SEQ ID NO:85; (d) the H2 comprises an amino acid sequence of SEQ ID NO:90, the L2 comprises an amino acid sequence of SEQ ID NO:173 or 202, and the H1 comprises an amino acid sequence of SEQ ID NO:86; (e) the H2 comprises an amino acid sequence of SEQ ID NO:91, the L2 comprises an amino acid sequence of SEQ ID NO:174 or 203, and the H1 comprises an amino acid sequence of SEQ ID NO:85; (f) the H2 comprises an amino acid sequence of SEQ ID NO:92, the L2 comprises an amino acid sequence of SEQ ID NO:174 or 203, and the H1 comprises an amino acid sequence of SEQ ID NO:86; (g) the H2 comprises an amino acid sequence of SEQ ID NO:93, the L2 comprises an amino acid sequence of SEQ ID NO:174 or 203, and the H1 comprises an amino acid sequence of SEQ ID NO:85; (h) the H2 comprises an amino acid sequence of SEQ ID NO:94, the L2 comprises an amino acid sequence of SEQ ID NO:174 or 203, and the H1 comprises an amino acid sequence of SEQ ID NO:86; (i) the H2 comprises an amino acid sequence of SEQ ID NO:198, the L2 comprises an amino acid sequence of SEQ ID NO:204 or 205, and the H1 comprises an amino acid sequence of SEQ ID NO:85; or (j) the H2 comprises an amino acid sequence of SEQ ID NO:199, the L2 comprises an amino acid sequence of SEQ ID NO:204 or 205, and the H1 comprises an amino acid sequence of SEQ ID NO:86. In some embodiments, the L1-CL is derived from a human kappa light chain. In some embodiments, the second antigen is TSLP.

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

[0023] In some embodiments according to any of the multispecific constructs described above, the first antibody moiety is an scFv (“anti-IL-13 scFv”), wherein the second antibody moiety 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 moiety to form a fusion polypeptide.

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

[0025] In some embodiments according to any of the multispecific constructs described above, the multispecific construct comprises two anti-IL-13 antibody moieties that are scFvs (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”), two second antibody moieties that are Fabs (“Fab1” and “Fab2”) specifically binding the 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 scFv1-optional linker-a 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-a 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 second target antigen is TSLP. In some embodiments, the first polypeptide and the fourth polypeptide each comprises the amino acid sequence of SEQ ID NO:103, and the second polypeptide and the third polypeptide each comprises the amino acid sequence of SEQ ID NO:110.

[0026] In some embodiments according to any of the multispecific constructs described above, the first antibody moiety is a full-length antibody (“anti-IL-13 full-length antibody”), wherein the second antibody moiety 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 according to any of the multispecific constructs described above, the multispecific construct comprises the first antibody moiety that is an anti-IL-13 full-length antibody, and two second antibody moieties that are scFvs (“scFv1” and “scFv2”) specifically binding the second target antigen; and wherein scFv1 is fused to the C-terminusof a 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 a second heavy chain of the anti-IL-13 full-length antibody to form a second fusion polypeptide. In some embodiments, the second target antigen is TSLP. In some embodiments, the anti-IL-13 full-length 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 comprises the amino acid sequence of SEQ ID NO:111. In some embodiments, the anti-IL-13 full-length 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, and wherein the first fusion polypeptide and the second fusion polypeptide each comprises the amino acid sequence of any one of SEQ ID NOs:220-223.

[0028] In some embodiments according to any of the multispecific constructs described above, the multispecific construct comprises two anti-IL-13 antibody moieties that are Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”), two second antibody moieties that are scFvs (“scFv1” and “scFv2”) that specifically bind 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-scFv1-optional linker-a first subunit of the Fc domain; iii) a third polypeptide comprising from N’ to C’: VH2-(H2-CH1)-optional linker-scFv2-optional linker-a 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 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 polypeptide and the fourth polypeptide each comprises the amino acid sequence of SEQ ID NO:102 or 197, and the second polypeptide and the third polypeptide each comprises the amino acid sequence of SEQ ID NO:112.

[0029] In some embodiments according to any of the multispecific constructs described above, the multispecific comprises two anti-IL-13 antibody moieties that are Fabs (“anti-IL- 13 Fab1” and “anti-IL-13 Fab2”), and a second antibody moiety that is 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 moiety; ii) a second polypeptide comprising from N’ to C’: a first heavy chain of the second antibody moiety-optional linker-VH1-(H1-CH1); iii) a third polypeptide comprising from N’ to C’: a second heavy chain of the second antibody moiety-optional linker-VH2-(H2-CH1); iv) afourth polypeptide comprising: a second light chain of the second antibody moiety; v) a fifth polypeptide comprising from N’ to C’: VL1-(L1-CL); and vi) a sixth polypeptide comprising from N’ to C’: VL2-(L2-CL); and wherein VL1-(L1-CL) and VH1-(H1-CH1) form anti-IL- 13 Fab1, and VL2-(L2-CL) and VH2-(H2-CH1) form anti-IL-13 Fab2. In some embodiments, the anti-IL-13 Fab1 comprises an H1 comprising the VH1-(H1-CH1), and an L1 comprising the VL1-(L1-CL); wherein the anti-IL-13 Fab2 comprises an H2 comprising the VH2-(H2-CH1), and an L2 comprising the VL2-(L2-CL); and wherein: (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C, L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C, L135F, and C214S substitutions; or (e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the second target antigen is TSLP (i.e., the second antibody moiety is an “anti-TSLP full-length antibody”). In some embodiments, the anti-TSLP full-length antibody comprises two 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.

[0030] In some embodiments according to any of the multispecific constructs described above, the multispecific construct comprises an anti-IL-13 antibody moiety that is a full- length antibody (“anti-IL-13 full-length antibody”), and two second antibody moieties that are Fabs (“Fab1” and “Fab2”) 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-optional linker-VH3-(H3-CH1); iii) a third polypeptide comprising from N’ to C’: a second heavy chain (H2) of the anti-IL-13 full- length antibody-optional linker-VH4-(H4-CH1); iv) a fourth polypeptide comprising: a second light chain (L2) of the anti-IL-13 full-length 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 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 comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135Fsubstitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C, L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C, L135F, and C214S substitutions; or (e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the anti-IL-13 full-length 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 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, the second target antigen is TSLP (i.e., the two second antibody moieties are “anti-TSLP Fab1” and “anti-TSLP Fab2”). In some embodiments, the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises 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 according to any of the multispecific constructs described above, the multispecific construct comprises two anti-IL-13 antibody moieties that are Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”), and the second antibody moiety that is a full- length antibody specifically binding to a second target antigen; wherein the multispecificconstruct 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-a first heavy chain of the second antibody moiety; iii) a third polypeptide comprising from N’ to C’: VH2- (H2-CH1)-optional linker-a second heavy chain of the second antibody moiety; iv) a fourth polypeptide comprising from N’ to C’: VL2-(L2-CL); v) a fifth polypeptide comprising: a first light chain of the second antibody moiety; and vi) a sixth polypeptide comprising: a second light chain of the second antibody moiety; and wherein VL1-(L1-CL) and VH1-(H1- CH1) form anti-IL-13 Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2. In some embodiments, the anti-IL-13 Fab1 comprises an H1 comprising the VH1-(H1-CH1), and an L1 comprising the VL1-(L1-CL); wherein the anti-IL-13 Fab2 comprises an H2 comprising the VH2-(H2-CH1), and an L2 comprising the VL2-(L2-CL); and wherein: (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C, L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C, L135F, and C214S substitutions; or (e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the second target antigen is TSLP (i.e., the second antibody moiety is an “anti-TSLP full-length antibody”). In some embodiments, the anti-TSLP full-length antibody comprises two 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.

[0032] In some embodiments according to any of the multispecific constructs described above, the multispecific construct comprises the first antibody moiety that is an anti-IL-13 full-length antibody, and two second antibody moieties that are Fabs (“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-a first heavy chain (H1) of the anti-IL-13 full-length antibody; iii) a third polypeptide comprising from N’ to C’: VH4-(H4-CH1)-optional linker-a second heavy chain (H2) of the anti-IL-13 full-length antibody; iv) a fourth polypeptide comprising from N’ to C’: VL4-(L4-CL); v) a fifth polypeptide comprising: a first light chain (L1) of the anti-IL-13 full-length antibody; and vi)a sixth polypeptide comprising: a second light chain (L2) of the anti-IL-13 full-length 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 comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C, L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C, L135F, and C214S substitutions; or (e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the anti-IL-13 full-length 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 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, the second target antigen is TSLP (i.e., the two second antibody moieties are “anti-TSLP Fab1” and “anti-TSLP Fab2”). In some embodiments, the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises 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] Also provided are pharmaceutical compositions comprising any of the multispecific constructs described herein, and optionally a pharmaceutically acceptable carrier.

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

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

[0036] Also provided are of producing any of the multispecific constructs described herein, comprising i) culturing a host cell comprising any of the isolated nucleic acids or the vectors described above, or any of the host cells described above under a condition suitable for the expression of the multispecific construct; and ii) obtaining the expressed multispecific construct.

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

[0038] In some embodiments according to any of the anti-IL-13 antibody constructs described above, (1) the VH comprises an 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 an 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, the VH comprises an amino acid sequence of SEQ ID NO:65, and the VL comprises an amino acid sequence of SEQ ID NO:69.

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

[0040] In some embodiments according to any of the anti-IL-13 antibody constructs described above, the anti-IL-13 antibody moiety is an 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 according to any of the anti-IL-13 antibody constructs described above, the anti-IL-13 antibody moiety is a Fab (“anti-IL-13 Fab”). In some embodiments, the anti-IL-13 Fab comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO:124, and a second polypeptide comprising the amino acid sequence of SEQ ID NO:102 or 197.

[0042] In some embodiments according to any of the anti-IL-13 antibody constructs described above, the anti-IL-13 antibody moiety is a full-length antibody (“anti-IL-13 full- length antibody”). In some embodiments, the anti-IL-13 full-length 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: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 comprisingthe 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 according to any of the anti-IL-13 antibody constructs described above, the isolated anti-IL-13 antibody construct is monospecific. In some embodiments, the isolated anti-IL-13 antibody construct is multispecific.

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

[0045] Also provided are pharmaceutical compositions comprising any of the isolated anti- IL-13 antibody constructs described above, and optionally a pharmaceutically acceptable carrier.

[0046] Also provided are isolated nucleic acids encoding any of any of the isolated anti-IL- 13 antibody constructs described above, vectors comprising such nucleic acids, and host cells comprising such nucleic acids or vectors.

[0047] Also provided are methods of treating an inflammatory disease in an individual, 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 human.

[0048] Also provided are methods of producing any of the isolated anti-IL-13 antibody constructs described above, comprising: i) culturing a host cell comprising any of the isolated nucleic acids or the vectors described above, or any of the host cells described above under a condition suitable for the expression of 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 present invention will become apparent from the subsequent detailed description and the appended claims. It is to be understood that one, some, or all of the properties of the various embodiments described herein may be combined to form other embodiments of the present invention.

[0050] The disclosures of all publications, patents, patent applications and published patent applications referred to herein are hereby incorporated herein by reference in their entirety.BRIEF DESCRIPTION OF THE DRAWINGS

[0051] FIG.1 shows the percent inhibition of TSLP signaling via the TSLP receptor complex expressed on the STAT5-HEK293 reporter cell when treated with exemplary anti- TSLP antibodies.

[0052] FIG.2 shows 51B2 and a US-FDA approved reference anti-TSLP Ab binding to overlapping but different epitopes on TSLP in an ELISA competition experiment. Ab, antibody; OD, optical density.

[0053] FIGs.3A-3B show 51B2 complete inhibition of TSLP-induced CCL17 secretion from PBMCs (FIG.3A) or isolated dendritic cells (FIG.3B) compared to a US-FDA approved reference anti-TSLP Ab.

[0054] FIG.4 shows the resulting IC50(nM) and IC90(nM) values for each generated humanized 51B2 antibody compared to the parental Ch51B2 antibody in human and cynomolgus monkey (“cyno”) TSLP inhibition assays using TSLP receptor complex- transfected HEK293 reporter cells. Humanized anti-TSLP antibodies bound by a box indicate the anti-TSLP antibodies selected for further analysis.

[0055] FIG.5A shows the percent inhibition of TSLP signaling via the TSLP receptor complex expressed on the STAT5-HEK293 reporter cell when treated with select humanized anti-TSLP antibodies (hz51B2 L2H2, hz51B2 L2H9, and hz51B2 L3H9). Ch51B2 parental chimeric antibody served as control.

[0056] FIG.5B shows equilibrium binding analysis of hz51B2 L3H9 binding to human TSLP in solutions.

[0057] FIGs.6A-6B show the anti-IL-13 antibody 73P1 enhanced neutralizing activity for cynomolgus monkey (“cyno”) IL-13 while maintaining the neutralizing activity for human IL-13 inhibition in the HEK-Blue 293 IL-13 reporter assay wherein secreted embryonic alkaline phosphatase (SEAP) is produced upon IL-13 signaling activation. FIG.6A shows Reference anti-IL-13 antibody #0 and anti-IL-13 antibody 73P1 neutralizing activity against human IL-13 using the IL-13 reporter assay across multiple concentrations and provides the IC50for both anti-IL-13 antibodies. FIG.6B shows Reference anti-IL-13 antibody #0 and anti-IL-13 antibody 73P1 neutralizing activity against cyno IL-13 using the IL-13 reporter assay across multiple concentrations and further provides the IC50for both anti-IL-13 antibodies. Conc., concentration; OD, optical density.

[0058] FIGs.7A-7B show the comparison of neutralizing activities of anti-IL-13 antibody 73P1 and two US-FDA or EMA approved anti-IL-13 antibodies, Reference anti-IL-13Antibody #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 assay, wherein secreted embryonic alkaline phosphatase (SEAP) is produced upon IL-13 signaling activation using wildtype (“WT”) IL-13 or IL-13 R110Q (a disease-associated variant of IL-13) as the stimuli. FIG. 7A shows the neutralizing activities of anti-IL-13 antibody 73P1 and Ref. anti-IL-13 Abs. #1 and #2 against wildtype human IL-13. FIG.7B shows the neutralizing activities of anti-IL-13 antibody 73P1 and Ref. anti-IL-13 Abs. #1 and #2 against the disease-associated human IL- 13 variant, R110Q, which displays increased IL-13 activity. IC50values are provided.

[0059] FIGs.8A-8D show schematic overviews of one set of exemplary bispecific anti- TSLP×IL-13 antibody constructs based on scFv fusions and insertions.

[0060] FIGs.9A-9B demonstrate the inhibitory activities from the TSLP×IL13 bispecific antibodies depicted in FIGs.8A-8D for TSLP and for IL-13. FIG.9A shows the percent inhibition of TSLP signaling through the TSLPR / IL-7Rα receptor complex expressed on the STAT5-HEK-293 reporter cell when treated with one of the bispecific antibodies. Luciferase production by the reporter cell acted as a readout for the TSLP binding activity. FIG.9B shows the percent inhibition of IL-13 signaling through the IL-13Rα1 / IL-4Rα receptor complex expressed on the HEK-293 reporter cell when treated with one of the bispecific antibodies. SEAP production and secretion by the reporter cell acted as a readout for the IL- 13 binding activity. IC90values for each antibody according to the antigen were calculated based on the antibody dose-dependent binding inhibition curve. Data were analyzed and presented using GraphPad. Ab, antibody; Conc., concentration.

[0061] FIG.10 shows the in vivo stabilities of the TSLP×IL-13 bispecific antibodies depicted in FIGs.8A-8D represented by in vivo antibody concentration after intravenous injection into C57Bl / 6 mice over time for both the anti-TSLP antigen binding moiety and the anti-IL-13 antigen binding moiety of each of the bispecific antibodies. Two animals were tested per antibody per dilution (n=2 / group).

[0062] FIGs.11A-11D show schematic overviews of one set of exemplary bispecific TSLP×IL-13 antibodies based on Fab fusions (Format PX128-I1 to PX128-I4, respectively).

[0063] FIGs.12A-12B demonstrate the inhibitory activities of the TSLP×IL-13 bispecific antibodies of Formats PX128-I1to PX128-I4 depicted in FIGs.11A-11D, and PX128-R2 depicted in FIG.13, for TSLP (FIG.12A) and for IL-13 (FIG.12B). FIG.12A shows the percent inhibition of TSLP signaling via the TSLP receptor complex expressed on the STAT5-HEK-293 reporter cell when treated with one of the bispecific antibodies. FIG.12B shows the percent inhibition of IL-13 signaling via the IL-13 receptor complex expressed onthe HEK-293 reporter cell when treated with one of the bispecific antibodies. Anti-IL-13 reference antibodies #2, #3, and #4 were included as positive controls. IC90values for each antibody according to the antigen were calculated based on the antibody dose-dependent binding inhibition curve. Data were analyzed and presented using GraphPad. Ab, antibody; Conc., concentration.

[0064] FIG.13 provides a schematic overview of a PX128-R2 heterodimeric bispecific antibody, wherein a first arm includes an anti-TSLP Fab fragment, and a second arm includes an anti-IL-13 Fab fragment. The Fc domain includes the knob-in-hole mutation. The CH1 and CL domains of the anti-IL-13 Fab fragment also include R2 mutations, which include mutations F126C and C220S in the heavy chain and mutations E124C and C214S in the light chain of the anti-IL-13 arm (all EU numbering).

[0065] FIG.14 provides a schematic overview of PX128-JT heterodimeric bispecific antibodies, wherein a first arm includes an anti-TSLP Fab fragment, and a second arm includes an anti-IL-13 Fab fragment. The Fc domain includes the knob-in-hole mutation. The CH1 and CL domains of the anti-IL-13 Fab fragment also include either the JT11 or the JT7 mutations. The JT11 mutations include F170V, S183I, and V185L in the HC and L135F in the LC of the anti-IL-13 arm (all EU numbering). The JT7 mutations include F170I, S183L, and V185L in the HC and L135F in the LC of the anti-IL-13 arm (all EU numbering).

[0066] FIG.15 provides a schematic overview of PX128-JT / R2 heterodimeric bispecific antibodies, wherein a first arm includes an anti-TSLP Fab fragment, and a second arm includes an anti-IL-13 Fab fragment. The Fc domain includes the knob-in-hole mutation. The heavy chain and light chain of the anti-IL-13 arm also include R2 mutations and either 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] FIG.16 shows the in vivo stabilities of PX128-JT7 and PX128-JT11 heterodimeric bispecific antibodies (depicted in FIG.14) represented by in vivo antibody concentration over time after intravenous injection into C57Bl / 6 mice for both the anti-TSLP antigen binding moiety and the anti-IL-13 antigen binding moiety. Two animals were tested per antibody per concentration (n=2 / group).

[0068] FIGs.17A-17B demonstrate the inhibitory activities of the heterodimeric bispecific antibodies depicted in FIGs.13-15 for TSLP (FIG.17A) and for IL-13 (FIG.17B). FIG. 17A shows the percent inhibition of TSLP signaling via the TSLP receptor complex expressed on the STAT5-HEK-293 reporter cell when treated with one of the heterodimeric bispecific antibodies. FIG.17B shows the percent inhibition of IL-13 signaling via the IL-13receptor complex expressed on the HEK-293-SEAP reporter cell when treated with one of the heterodimeric bispecific antibodies. IC90values for each antibody according to the antigen were calculated based on the antibody dose-dependent binding inhibition curve. Data were analyzed and presented using GraphPad. Ab, antibody; Conc., concentration.

[0069] FIGs.18A-18C show the level of CCL17 production in PBMCs treated with TSLP only (FIG.18A), IL-13 only (FIG.18B), or TSLP and IL-13 (FIG.18C), resulting from dose escalation of PX128-JT7 and PX128-JT11 heterodimeric bispecific antibodies depicted in FIG.14, as measured by ELISA assay. FIG.18A shows the CCL17 production due to treatment with 0.5 ng / ml TSLP alone. 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 of the cells with TSLP only (FIG.18A), IL-13 only (FIG.18B), or TSLP and IL-13 (FIG. 18C), and treatment with no antibody was included as a negative control.

[0070] FIG.19 shows the half-life in vivo stability of an exemplary PX128-JT11 heterodimeric bispecific antibody (depicted in FIG.14) represented by in vivo antibody concentration over time after intravenous bolus injection or subcutaneous injection into cynomolgus monkeys. Ref. TSLP×IL-13×HSA Ab. #4 was included as a control. Two animals were tested per antibody per concentration (n=2 / group). DETAILED DESCRIPTION OF THE INVENTION

[0071] The present invention provides a multispecific construct (such as a bispecific construct) comprising an anti-IL-13 antibody moiety that specifically binds to IL-13 and a second antibody moiety that specifically binds to a second target antigen (e.g., TSLP). In some embodiments, the multispecific construct comprises one anti-IL-13 antibody moiety. In some embodiments, the multispecific construct comprises two or more anti-IL-13 antibody moieties. In some embodiments, the multispecific construct comprises one antibody moiety specifically binding to a second target antigen or target epitope. In some embodiments, the multispecific construct comprises two or more antibody moieties specifically binding to one or more other target antigens or target epitopes. In some embodiments, the second antigen is a protein produced by an immune cell. In some embodiments, the second antigen is TSLP. The present invention in another aspect also provides novel anti-IL-13 antibody constructs.

[0072] After extensive investigation, inventors of the present application discovered that the multispecific constructs (e.g., anti-IL-13 multispecific constructs) described herein have several unexpected advantages compared to other multispecific proteins. First, the multispecific constructs described herein display stronger binding to IL-13 and improvedpotency compared to currently available anti-IL-13 antibodies or multispecific constructs thereof. Second, the multispecific constructs (e.g., anti-IL-13 multispecific constructs) have cross-reactivity to both human and cynomolgus monkey IL-13, which can facilitate extrapolation of the results of toxicity and efficacy studies from cynomolgus monkeys to human clinical studies. Third, certain multispecific constructs described herein were shown to be surprisingly stable in vivo, (e.g., both upon administration to mice and to cynomolgus monkeys) making them particularly suitable to be formulated in high concentrations. Fourth, the in vivo half-life of certain multispecific constructs described herein was shown to be much longer than other control multispecific antibodies (e.g., the half-life is at least about any of 1.5-fold, 2-fold, 4-fold, 5-fold, or more, of the half-life of a control multispecific antibody).

[0073] Also provided are pharmaceutical compositions and kits comprising any of the multispecific constructs or anti-IL-13 antibody constructs described herein, and methods of use thereof for treating inflammatory diseases, such as asthma, atopic dermatitis, or COPD. I. Definitions

[0074] As used herein, the term “treatment” refers to clinical intervention designed to alter the natural course of the individual or cell being treated during the course of clinical pathology. Desirable effects of treatment include decreasing the rate of disease progression, ameliorating or palliating the disease state, and remission or improved prognosis. For example, an individual is successfully “treated” if one or more symptoms associated with inflammatory diseases are mitigated or eliminated, including, but not limited to, reducing local or systemic inflammation, decreasing symptoms resulting from the disease, increasing the quality of life of those suffering from the disease, decreasing the dose of other medications required to treat the disease, etc.

[0075] As used herein, an “effective amount” refers to an amount of an agent or drug effective to treat a disease or disorder in a subject (such as an individual, e.g., a human). In the case of inflammatory disease, the effective amount of the agent may reduce the number of active immune cells; reduce the amount of pro-inflammatory cytokines; inhibit (i.e., slow to some extent and preferably stop) inflammatory immune cell activity locally and / or systemically; and / or relieve to some extent one or more of the symptoms associated with the inflammatory disease. As is understood in the clinical context, an effective amount of a drug, compound, or pharmaceutical composition may or may not be achieved in conjunction with another drug, compound, or pharmaceutical composition. Thus, an “effective amount” maybe considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable result may be or is achieved.

[0076] As used herein, an “individual” or a “subject” refers to a mammal, including, but not limited to, human, bovine, horse, feline, canine, rodent, or primate. In some embodiments, the individual is a human.

[0077] 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 as long as they exhibit the desired biological activity or function. As used herein, the terms “immunoglobulin” (Ig) and “antibody” are used interchangeably.

[0078] The term “full-length antibody” is used herein to refer to an antibody in its substantially intact form, not antibody fragments as defined below. The term particularly refers to an antibody with heavy chains that contain an Fc region. Full-length antibodies are usually heterotetrameric glycoproteins of about 150,000 Daltons, composed of two identical light (L) chains and two identical heavy (H) chains.

[0079] The term “constant domain” refers to the portion of an immunoglobulin molecule having a more conserved amino acid sequence relative to the other portion of the immunoglobulin, the variable domain, which contains the antigen binding site. The constant domain contains the CH1, CH2 and CH3 domains (collectively, CH) of the heavy chain and the CHL (or CL) domain of the light chain.

[0080] The “variable region” or “variable domain” of an antibody refers to the amino- terminal domains of the heavy or light chain of the antibody. The variable domain of the heavy chain may be referred to as “VH.” The variable domain of the light chain may be referred to as “VL.” These domains are generally the most variable parts of an antibody and contain the antigen-binding sites.

[0081] The term “variable” refers to the fact that certain portions of the variable domains differ extensively in sequence among antibodies and are used in the binding and specificity of each particular antibody for its particular antigen. However, the variability is not evenly distributed throughout the variable domains of antibodies. It is concentrated in three segments called hypervariable regions (HVRs, also referred to as CDRs) both in the light-chain and the heavy-chain variable domains. The more highly conserved portions of variable domains are called the framework regions (FR). The variable domains of native heavy and light chains each comprise four FRs, largely adopting a beta-sheet configuration, connected by threeHVRs, which form loops connecting, and in some cases forming part of, the beta-sheet structure. The HVRs in each chain are held together in close proximity by the FRs and, with the HVRs from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, National Institute of Health, Bethesda, Md. (1991)). The constant domains are not involved directly in the binding of an antibody to an antigen, but exhibit various effector functions, such as participation of the antibody in antibody-dependent cellular toxicity. The residues of the constant domains are described herein based on EU numbering.

[0082] As used herein, the term “CDR” or “complementarity determining region” is intended to mean the non-contiguous antigen combining sites found within the variable region of both heavy and light chain polypeptides. These particular regions have been described by Kabat et al., J. Biol. Chem.252:6609-6616 (1977); Kabat et al., U.S. 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 M.P. et al., Dev. Comp. Immunol., 27: 55-77 (2003); and Honegger and Plückthun, J. Mol. Biol., 309:657-670 (2001), where the definitions include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or grafted antibodies or variants thereof is intended to be within the scope of the term as defined and used herein. The amino acid residues which encompass the CDRs as defined by each of the above cited references are set forth below in Table A as a comparison. CDR prediction algorithms and interfaces are known in the art, including, for example, Abhinandan and Martin, Mol. Immunol., 45: 3832-3839 (2008); Ehrenmann F. et al., Nucleic Acids Res., 38: D301-D307 (2010); and Adolf-Bryfogle J. et al., Nucleic Acids Res., 43: D432-D438 (2015). The contents of the references cited in this paragraph are incorporated herein by reference in their entireties for use in the present application and for possible inclusion in one or more claims herein. The amino acid residues of the CDRs provided herein are described herein based on Kabat.Table A. CDR Definitions1Residue numbering follows the nomenclature of Kabat et al., supra 2Residue numbering follows the nomenclature of Chothia et al., supra 3Residue numbering follows the nomenclature of MacCallum et al., supra 4Residue numbering follows the nomenclature of Lefranc et al., supra 5Residue numbering follows the nomenclature of Honegger and Plückthun, supra

[0083] The “light chains” of antibodies (immunoglobulins) derived from any mammalian species can be assigned to one of two clearly distinct types, called kappa (“κ”) and lambda (“λ”), based on the amino acid sequences of their constant domains.

[0084] The term IgG “isotype” or “subclass” as used herein is meant any of the subclasses of immunoglobulins defined by the chemical and antigenic characteristics of their constant regions.

[0085] Depending on the amino acid sequences of the constant domains of their heavy chains, antibodies (immunoglobulins) can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called α, δ, ɛ, γ, and µ, respectively. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known and described generally in, for example, Abbas et al. Cellular and Mol. Immunology, 4thed. (W.B. Saunders, Co., 2000). An antibody may be part of a larger fusion molecule, formed by covalent or non-covalent association of the antibody with one or more other proteins or peptides.

[0086] “Antibody fragments” comprise a portion of an intact antibody, preferably comprising the antigen binding region thereof. 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 fragment, scFv); diabodies; linear antibodies; single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.

[0087] Papain digestion of antibodies 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 ability to crystallize readily. Pepsin treatment yields a F(ab’)2fragment that has two antigen-combining sites and is still capable of cross-linking antigen.

[0088] “Fv” is the minimum antibody fragment which contains a complete antigen-binding site. In one embodiment, a two-chain Fv species consists of a dimer of one heavy- and one light-chain variable domain in tight, non-covalent association. In a single-chain Fv (scFv) species, one heavy- and one light-chain variable domain can be covalently linked by a flexible peptide linker such that the light and heavy chains can associate in a “dimeric” structure analogous to that in a two-chain Fv species. It is in this configuration that the three HVRs of each variable domain interact to define an antigen-binding site on the surface of the VH-VL dimer. Collectively, the six HVRs confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three HVRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.

[0089] The Fab fragment has two polypeptide chains, containing the heavy- and light-chain variable domains (VH, VL), and also containing the constant domain of the light chain (CL) and the first constant domain (CH1) of the heavy chain. Fab’ fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH1 domain including one or more cysteines from the antibody hinge region. Fab’-SH is the designation herein for Fab’ in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab’)2antibody fragments originally were produced as pairs of Fab’ fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

[0090] “Single-chain Fv” or “scFv” antibody fragments comprise the VH and VL domains of antibody, wherein these domains are present in a single polypeptide chain. Generally, the scFv polypeptide further comprises a polypeptide linker between the VH and VL domains, which enables the scFv to form the desired structure for antigen binding. For a review of scFv, see, e.g., Pluckthün, The Pharmacology of Monoclonal Antibodies. Springer Berlin Heidelberg, 1994.269-315.

[0091] The “Fc” fragment comprises the carboxy-terminal portions of both heavy chains held together by di-sulfides. The effector functions of antibodies are determined by sequences in the Fc region, which is also the region recognized by Fc receptors (FcR) found on certain types of cells.

[0092] The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, e.g., the individual antibodies comprising the population are identical except for possible mutations, e.g., naturally occurring mutations, that may be present in minor amounts. Thus, the modifier “monoclonal” indicates the character of the antibody as not being a mixture of discrete antibodies. In some embodiments, such a monoclonal antibody typically includes an antibody comprising a polypeptide sequence that binds a target, wherein the target-binding polypeptide sequence was obtained by a process that includes the selection of a single target binding polypeptide sequence from a plurality of polypeptide sequences. For example, the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, or recombinant DNA clones. It should be understood that a selected target binding sequence can be further altered, for example, to improve affinity for the target, to humanize the target binding sequence, to improve its production in cell culture, to reduce its immunogenicity in vivo, to create a multispecific antibody, etc., and that an antibody comprising the altered target binding sequence is also a monoclonal antibody of this invention. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. In addition to their specificity, monoclonal antibody preparations are advantageous in that they are typically uncontaminated by other immunoglobulins.

[0093] The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the invention may be made by a variety of techniques, including, for example, the hybridoma method (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, 2nded.1988); Hammerling et al., Monoclonal Antibodies and T-Cell Hybridomas 563-681 (Elsevier, N.Y., 1981)), recombinant DNA methods (see, e.g., U.S. Pat. No.4,816,567), phage-display technologies (see, e.g., Clackson et al., Nature 352: 624-628 (1991); Marks et al., J. Mol. Biol.222: 581-597 (1992); Sidhu et al., J. Mol. Biol.338(2): 299-310 (2004); Lee et al., J. Mol. Biol.340(5): 1073-1093 (2004); Fellouse, Proc. Natl. Acad. Sci. USA 101(34): 12467- 12472 (2004); and Lee et al., J. Immunol. Methods 284(1-2): 119-132 (2004)), and technologies for producing human or human-like antibodies in animals that have parts or allof the human immunoglobulin loci or genes encoding human immunoglobulin sequences (see, e.g., WO 1998 / 24893; WO 1996 / 34096; WO 1996 / 33735; WO 1991 / 10741; Jakobovits et al., Proc. Natl. Acad. Sci. USA 90: 2551 (1993); Jakobovits et al., Nature 362: 255-258 (1993); Bruggemann et al., Year in Immunol.7:33 (1993); U.S. Pat. Nos.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)).

[0094] The monoclonal antibodies herein specifically include “chimeric” antibodies in which a portion of the heavy and / or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (see, e.g., U.S. Pat. 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 the antibody is derived from an antibody produced by, e.g., immunizing macaque monkeys with the antigen of interest.

[0095] “Humanized” forms of non-human (e.g., murine) antibodies are chimeric antibodies that contain minimal sequence derived from non-human immunoglobulin. In one embodiment, a humanized antibody is a human immunoglobulin (recipient antibody) in which residues from an HVR of the recipient are replaced by residues from an HVR of a non- human species (donor antibody) such as mouse, rat, rabbit, or nonhuman primate having the desired specificity, affinity, and / or capacity. In some instances, FR residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications may be made to further refine antibody performance. In general, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin, and all or substantially all of the FRs are those of a human immunoglobulin sequence. The humanized antibody optionally will also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of ahuman immunoglobulin. For further details, see, e.g., 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, e.g.,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. Pat. Nos.6,982,321 and 7,087,409.

[0096] A “human antibody” is one which possesses an amino acid sequence which corresponds to that of an antibody produced by a human and / or has been made using any of the techniques for making human antibodies as disclosed herein. This definition of a human antibody specifically excludes a humanized antibody comprising non-human antigen-binding residues. Human antibodies can be produced using various 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). Also available for the preparation of human monoclonal antibodies are methods 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 the antigen to a transgenic animal that has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled, e.g., immunized xenomice (see, e.g., U.S. Pat. Nos. 6,075,181 and 6,150,584 regarding XENOMOUSETMtechnology). See also, for example, Li et al., Proc. Natl. Acad. Sci. USA 103:3557-3562 (2006) regarding human antibodies generated via a human B-cell hybridoma technology.

[0097] The term “hypervariable region,” “HVR,” or “HV,” when used herein refers to the regions of an antibody variable domain which are hypervariable in sequence and / or form structurally defined loops. Generally, antibodies comprise six HVRs; three in the VH (H1, H2, H3), and three in the VL (L1, L2, L3). In native antibodies, H3 and L3 display the most diversity of the six HVRs, and H3 in particular is believed to play a unique role in conferring fine specificity to antibodies. See, e.g., Xu et al., Immunity 13:37-45 (2000); Johnson and Wu, in Methods in Molecular Biology 248:1-25 (Lo, ed., Human Press, Totowa, N.J., 2003). Indeed, naturally occurring camelid antibodies consisting of a heavy chain only are functional and stable in the absence of light chain. See, e.g., Hamers-Casterman et al., Nature 363:446- 448 (1993); Sheriff et al., Nature Struct. Biol.3:733-736 (1996). HVR is also referred to as “CDR” or “complementarity determining region”.

[0098] The structures and locations of immunoglobulin variable regions may be determined by reference to Kabat, E. A. et al., Sequences of Proteins of Immunological Interest.4thEdition. US Department of Health and Human Services.1987, and updates thereof, now available on the Internet (immuno.bme.nwu.edu).

[0099] “Framework” or “FR” residues are those variable domain residues other than the HVR residues as herein defined.

[0100] The term “covalently linked” as used herein, refers to a direct linkage through one or more chemical bonds or an indirect linkage through one or more linkers. Any suitable chemical bond can be used to create a direct linkage, including but not limited to, a covalent bond such as a peptide bond and a disulfide bond, or a non-covalent bond such as a hydrogen bond, a hydrophobic bond, an ionic bond, or a van der Waals bond.

[0101] “Covalent bond” as used herein refers to a stable bond between two atoms sharing one or more electrons. Examples of covalent bonds include, but are not limited to, peptide bonds and disulfide bonds. As used herein, “peptide bond” refers to a covalent bond formed between a carboxyl group of an amino acid and an amine group of an adjacent amino acid. A “disulfide bond” as used herein refers to a covalent bond formed between two sulfur atoms, such as a combination of a heavy chain fragment CH1 and a light chain fragment CL by one or more disulfide bonds. One or more disulfide bonds may be formed between the two fragments by linking the thiol groups in the two fragments. In some embodiments, one or more disulfide bonds can be formed between one or more cysteines of the heavy chain fragment and the light chain fragment, respectively. Disulfide bonds can be formed by oxidation of two thiol groups. In some embodiments, the covalent linkage is directly linked by a covalent bond. In some embodiments, the covalent linkage is directly linked by a peptide bond or a disulfide bond.

[0102] As used herein, the term “binds,” “specifically binds to,” or is “specific for” refers to measurable and reproducible interactions such as binding between a target and an antibody, which is determinative of the presence of the target in the presence of a heterogeneous population of molecules including biological molecules. For example, an antibody that binds to or specifically binds to a target (which can be an epitope) is an antibody that binds this target with greater affinity, avidity, more readily, and / or with greater duration than it binds to other targets. In one embodiment, the extent of binding of an antibody to an unrelated target is less than about 10% of the binding of the antibody to the target as measured, e.g., by a radioimmunoassay (RIA). In some embodiments, an antibody that specifically binds to a target has a dissociation constant (Kd) of ≤ 1μM, ≤ 100 nM, ≤ 10 nM, ≤ 1 nM, or ≤ 0.1 nM.In some embodiments, an antibody specifically binds to an epitope on a protein that is conserved among the protein from different species. In another embodiment, specific binding can include, but does not require, exclusive binding.

[0103] As used herein, “Percent (%) amino acid sequence identity” and “homology” with respect to a peptide, polypeptide, or antibody sequence are defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific peptide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or MEGALIGNTM(DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.

[0104] An amino acid substitution may include but is not limited to the replacement of one amino acid in a polypeptide with another amino acid. Exemplary substitutions are shown in Table B. Amino acid substitutions may be introduced into an antibody of interest and the products screened for a desired activity, e.g., retained / improved antigen binding, decreased immunogenicity, or improved ADCC or CDC. Table B. Exemplary amino acid substitutions.

[0105] Amino acids may be grouped according to common side-chain properties: (1) hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that influence chain orientation: Gly, Pro; and (6) aromatic: Trp, Tyr, Phe. Non-conservative substitutions will entail exchanging a member of one of these classes for another class.

[0106] The term “multispecific” as used in conjunction with an antibody or antigen binding protein refers to an antibody or antigen binding protein having polyepitopic specificity (i.e., is capable of specifically binding to two, three, or more, different epitopes on one biological molecule or is capable of specifically binding to epitopes on two, three, or more, different biological molecules). Unless otherwise indicated, the order in which the antigens bound by a multispecific antibody are listed in a multispecific antibody name is arbitrary.

[0107] The term “bispecific” as used in conjunction with an antibody or antigen binding protein refers to an antibody or antigen binding protein capable of specifically binding to two different epitopes on one biological molecule, or capable of specifically binding to epitopes on two different biological molecules. Unless otherwise indicated, the order in which the antigens bound by a bispecific antibody are listed in a bispecific antibody name is arbitrary.

[0108] The “knob-in-hole” strategy (see, e.g., PCT Intl. Publ. No. WO 2006 / 028936) has its plain and ordinary meaning as read in light of the specification and refers to a strategy that may be used to generate full-length bispecific antibodies. Briefly, selected amino acids forming the interface of the CH3 domains in human IgG can be mutated at positions affecting CH3 domain interactions to promote heterodimer formation. An amino acid with a small side chain (hole) is introduced into a heavy chain of an antibody specifically binding a first antigen and an amino acid with a large side chain (knob) is introduced into a heavy chain of an antibody specifically binding a second antigen. After co-expression of the two antibodies, a heterodimer is formed as a result of the preferential interaction of the heavy chain with a “hole” with the heavy chain with a “knob”.

[0109] The term “vector,” as used herein, refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. The term includes the vector as a self- replicating nucleic acid structure as well as the vector incorporated into the genome of a host cell into which it has been introduced. Certain 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.”

[0110] It is understood that embodiments of the invention described herein include “consisting of” and / or “consisting essentially of” embodiments.

[0111] Reference to “about” a value or parameter herein includes (and describes) variations that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X”.

[0112] The terms “about” and “approximately” mean within 20%, within 15%, within 10%, within 9%, within 8%, within 7%, within 6%, within 5%, within 4%, within 3%, within 2%, within 1%, or less of a given value or range.

[0113] As used herein, reference to “not” a value or parameter generally means and describes “other than” a value or parameter. For example, the method is not used to treat an inflammatory disease of type X means the method is used to treat inflammatory diseases of types other than X.

[0114] The term “about X-Y” used herein has the same meaning as “about X to about Y.”

[0115] As used herein and in the appended claims, the singular forms “a,” “or,” and “the” include plural referents unless the context clearly dictates otherwise. II. Multispecific Anti-IL-13 Antibody Constructs

[0116] In some embodiments, there is provided a a multispecific construct or an isolated anti- IL-13 antibody construct comprising: i) a first antibody moiety that specifically binds to interleukin-13 (IL-13; “anti-IL-13 antibody moiety”, e.g., any of the anti-IL-13 antibody moieties described herein), and ii) a second antibody moiety that specifically binds to a second target antigen. In some embodiments, the second target antigen is IL-13 (e.g., same epitope or different epitope from that bound by the first antibody moiety). 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 moieties (e.g., scFv, Fab, or full-length antibody). In some embodiments, the multispecific construct comprises a first and a second anti-IL-13 antibody moiety (e.g., a first and a second anti-IL-13 Fab, or a first and a second anti-IL-13 scFv), optionally a third antibody moiety (e.g., Fab, scFv) specifically binding to a third target antigen, and optionally a fourth antibody moiety specifically binding to a fourth target antigen. In some embodiments, the multispecific construct comprises: a first anti-IL-13 antibody moiety, a second antibody moiety specifically binding to a second target antigen, and a third antibody moiety specifically binding to a third target antigen. In some embodiments, the first anti-IL-13 antibody moiety and the second anti-IL-13 antibody moiety have the same amino acid sequence. In some embodiments, the first anti-IL-13 antibodymoiety and the second anti-IL-13 antibody moiety have different amino acid sequences. In some embodiments, the first anti-IL-13 antibody moiety and the second anti-IL-13 antibody moiety bind to the same IL-13 epitope. In some embodiments, the first anti-IL-13 antibody moiety and the second anti-IL-13 antibody moiety bind to different IL-13 epitopes. In some embodiments, the third antibody moiety and the fourth antibody moiety have the same amino acid sequence. In some embodiments, the third antibody moiety and the fourth antibody moiety have different amino acid sequences. In some embodiments, the third antibody moiety and the fourth antibody moiety bind to the same target epitope. In some embodiments, the third antibody moiety and the fourth antibody moiety bind to different target epitopes.

[0117] In some embodiments, there is provided a multispecific construct or an isolated anti- IL-13 antibody construct comprising: i) a first antibody means for specifically binding to IL- 13, and ii) a second antibody means for specifically binding to a second target antigen. In some embodiments, there is provided a multispecific construct or an isolated anti-IL-13 antibody construct comprising: i) a first antibody means for specifically binding to IL-13, and ii) a second antibody means for specifically binding to TSLP. In some embodiments, there is provided a multispecific construct or an isolated anti-IL-13 antibody construct comprising: i) a first antibody means for specifically binding to IL-13, and ii) a second antibody moiety that specifically binds to a second target antigen (such as any of the second antibody moieties described herein). In some embodiments, there is provided a multispecific construct or an isolated anti-IL-13 antibody construct comprising: i) a first antibody means for specifically binding to IL-13, and ii) a second antibody moiety that specifically binds to TSLP (such as any of the anti-TSLP moeities described herein). In some embodiments, there is provided a multispecific construct or an isolated anti-IL-13 antibody construct comprising: i) a first antibody moiety that specifically binds to IL-13 (such as any of the anti-IL-13 antibody moieties described herein), and ii) a second antibody means for specifically binding to TSLP. The anti-IL-13 antibody moieties described herein can have one or more of the following advantageous properties, including, for example, 1) high binding affinity to IL-13; 2) binding to IL-13 / IL-13Rα1 complex; 3) blocking recruitment of IL-4Rα to IL-13Rα1 to prevent formation of the IL-13Rα1 / IL-4Rα complex; and 4) inhibiting IL-13 signaling through the IL-13Rα1 / IL-4Rα complex. The anti-TSLP antibody moieties described herein can have one or more of the following advantageous properties, including, for example, 1) high binding affinity to TSLP; 2) blocking TSLP / TSLPR interaction; and 3) inhibiting TSLP signaling through the TSLPR / IL-7Rα complex.

[0118] In some embodiments, the multispecific constructs described herein have an increased (e.g., increasing at least about any of 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more times) in vivo half- life compared to the anti-IL-13 antibody moiety (e.g., Fab, scFv, full-length antibody) alone. In some embodiments, the multispecific constructs described herein have an increased (e.g., increasing at least about any of 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more times) in vivo half-life compared to the second antibody moiety specifically recognizing the second antigen (e.g., TSLP) alone.

[0119] In some embodiments, there is provided a multispecific construct comprising: a first antibody moiety that is an anti-IL-13 scFv (e.g., any of the anti-IL-13 scFvs described herein) and a second antibody moiety that is a full-length antibody that specifically binds to a second target antigen (e.g., TSLP), wherein the anti-IL-13 scFv is fused to the C-terminus of one of the heavy chains of the second antibody moiety to form a fusion polypeptide. In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are scFvs (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”, e.g., any of the anti-IL- 13 scFvs described herein), and a second antibody moiety that is a full-length antibody specifically binding 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 moiety 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 moiety to form a second fusion polypeptide. In some embodiments, the Fc domain of the full-length antibody comprises a first subunit and a second subunit. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0120] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are scFvs (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”, e.g., any of the anti-IL-13 scFvs described herein), two second antibody moieties that are Fabs(“Fab1” and “Fab2”) specifically binding 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-a 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-a 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 an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0121] In some embodiments, there is provided a multispecific construct comprising: a first antibody moiety that is an anti-IL-13 full-length antibody (e.g., any of the anti-IL-13 full- length antibodies described herein), and a second antibody moiety that is an scFv that specifically binds to a second target antigen (e.g., TSLP), wherein the scFv moiety 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, there is provided a multispecific construct comprising: a first antibody moiety that is an anti-IL-13 full-length antibody (e.g., any of the anti-IL-13 full-length antibodies described herein), and two second antibody moieties that are scFvs (“scFv1” and “scFv2”) specifically binding to a second target antigen (e.g., TSLP), wherein scFv1 is fused to the C-terminus of a 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 a 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 anti-IL-13 full-length antibody is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235Asubstitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0122] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, e.g., any of the anti-IL-13 Fabs described herein), two second antibody moieties that are scFvs (“scFv1” and “scFv2”) specifically binding 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-scFv1-optional linker-a first subunit of the Fc domain; iii) a third polypeptide comprising from N’ to C’: VH2-(H2-CH1)-optional linker-scFv2-optional linker-a 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 anti-IL-13 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 an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0123] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, e.g., any of the anti-IL-13 Fabs described herein), and a second antibody moiety that is a full- length antibody specifically binding to a second target antigen (e.g., TSLP), wherein themultispecific construct comprises: i) a first polypeptide comprising: a first light chain of the second antibody moiety; ii) a second polypeptide comprising from N’ to C’: a first heavy chain of the second antibody moiety-optional linker-VH1-(H1-CH1); iii) a third polypeptide comprising from N’ to C’: a second heavy chain of the second antibody moiety-optional linker-VH2-(H2-CH1); iv) a fourth polypeptide comprising: a second light chain of the second antibody moiety; v) a fifth polypeptide comprising from N’ to C’: VL1-(L1-CL); and vi) a sixth polypeptide comprising from N’ to C’: VL2-(L2-CL); and wherein VL1-(L1-CL) and VH1-(H1-CH1) form anti-IL-13 Fab1, and VL2-(L2-CL) and VH2-(H2-CH1) form anti- IL-13 Fab2. In some embodiments, the anti-IL-13 Fab1 comprises an H1 comprising the VH1-(H1-CH1), and an L1 comprising the VL1-(L1-CL); wherein the anti-IL-13 Fab2 comprises an H2 comprising the VH2-(H2-CH1), and an L2 comprising the VL2-(L2-CL); wherein: (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or (e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the full-length antibody 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 an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).In some embodiments, the light chain of the full-length antibody is derived from a kappa light chain.

[0124] In some embodiments, there is provided a multispecific construct comprising: a first anti-IL-13 antibody moiety that is a full-length antibody (“anti-IL-13 full-length antibody”; e.g., any of the anti-IL-13 full-length antibodies described herein), and two second antibody moieties that are Fabs (“Fab1” and “Fab2”) specifically binding 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- optional linker-VH3-(H3-CH1); iii) a third polypeptide comprising from N’ to C’: a second heavy chain (H2) of the anti-IL-13 full-length antibody-optional linker-VH4-(H4-CH1); iv) a fourth polypeptide comprising: a second light chain (L2) of the anti-IL-13 full-length 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 comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or (e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the anti-IL-13 full-length antibody 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 an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), andthe first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, L3-CL and L4-CL are derived from a kappa light chain.

[0125] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, e.g., any of the anti-IL-13 Fabs described herein), and a second antibody moiety that is a full- length antibody specifically binding to a second target antigen (e.g., 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-a first heavy chain of the second antibody moiety; iii) a third polypeptide comprising from N’ to C’: VH2-(H2-CH1)-optional linker-a second heavy chain of the second antibody moiety; iv) a fourth polypeptide comprising from N’ to C’: VL2-(L2-CL); v) a fifth polypeptide comprising: a first light chain of the second antibody moiety; and vi) a sixth polypeptide comprising: a second light chain of the second antibody moiety; and wherein VL1-(L1-CL) and VH1-(H1-CH1) form anti-IL-13 Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti- IL-13 Fab2. In some embodiments, the anti-IL-13 Fab1 comprises an H1 comprising the VH1-(H1-CH1), and an L1 comprising the VL1-(L1-CL); wherein the anti-IL-13 Fab2 comprises an H2 comprising the VH2-(H2-CH1), and an L2 comprising the VL2-(L2-CL); wherein: (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or (e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the full-length antibody 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 an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domaincomprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, the light chain of the full-length antibody is derived from a kappa light chain.

[0126] In some embodiments, there is provided a multispecific construct comprising: a first antibody moiety that is an IL-13 full-length antibody (e.g., any of the anti-IL-13 full-length antibodies described herein), and two second antibody moieties that are Fabs (“Fab1” and “Fab2”) specifically binding to 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-a first heavy chain (H1) of the anti-IL-13 full-length antibody; iii) a third polypeptide comprising from N’ to C’: VH4-(H4-CH1)-optional linker-a second heavy chain (H2) of the anti-IL-13 full-length 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 anti-IL-13 full-length antibody; and vi) a sixth polypeptide comprising from N’ to C’: a second light chain (L2) of the anti-IL-13 full-length 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 comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or (e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the IL-13 full-length antibody 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 an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256Esubstitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).In some embodiments, L3-CL and L4-CL are derived from a kappa light chain.

[0127] In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding to a second target antigen (e.g., TSLP). In some embodiments, (i) the H1 comprises substitutions at positions 170, 183, and 185 (EU numbering), and the L1 comprises a substitution at position 135 (EU numbering); and / or (ii) the H1 comprises substitutions at positions 126 and 220 (EU numbering), and the L1 comprises substitutions at positions 124 and 214 (EU numbering). In some embodiments, the H1 comprises substitutions at positions F170, S183, and V185 (EU numbering), and the L1 comprises a substitution at position L135 (EU numbering). In some embodiments, the H1 comprises F170I, S183L, and V185L substitutions (EU numbering), and the L1 comprises an L135F substitution (EU numbering). In some embodiments, the H1 comprises F170V, S183I, and V185L substitutions (EU numbering), and the L1 comprises an L135F substitution (EU numbering). In some embodiments, the L1 is derived from a lambda light chain (e.g., a lambda light chain comprising the amino acid sequence of SEQ ID NO:74 or 75). In some embodiments, the H1 comprises substitutions at positions F126 and C220 (EU numbering), and the L1 comprises substitutions at positions E124 and C214 (EU numbering). In some embodiments, the H1 comprises F126C and C220S substitutions (EU numbering), and the L1 comprises E124C and C214S substitutions (EU numbering). In some embodiments, L2 is derived from a kappa light chain. In some embodiments, the L1 is derived from a kappa light chain (e.g., a kappa light chain comprising the amino acid sequence of SEQ ID NO:73). In some embodiments, the H1 comprises substitutions at positions F126 and C220 (EU numbering), and the L1 comprises substitutions at positions Q124 and C214 (EU numbering). In some embodiments, the H1 comprises F126C and C220S substitutions (EU numbering),and the L1 comprises Q124C and C214S substitutions (EU numbering). In some embodiments, L2 is derived from a lambda light chain. In some embodiments, the H1 comprises substitutions at 126, 170, 183, 185, and 220 positions, and the L1 comprises substitutions at 124, 135, and 214 positions, wherein the position is according to EU numbering. In some embodiments, (i) the H1 comprises substitutions at F126, F170, S183, V185, and C220 positions, and the L1 comprises substitutions at E124, L135, and C214 positions; or (ii) the H1 comprises substitutions at F126, F170, S183, V185, and C220 positions, and the L1 comprises substitutions at Q124, L135, and C214 positions; wherein the position is according to EU numbering. In some embodiments, (i) the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions, and the L1 comprises E124C, L135F, and C214S substitutions; (ii) the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions, and the L1 comprises E124C, L135F, and C214S substitutions; (iii) the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions, and the L1 comprises Q124C, L135F, and C214S substitutions; or (iv) the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions, and the L1 comprises Q124C, L135F, and C214S substitutions; and wherein the position is according to EU numbering. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, the mutations in H1 and L1 described herein can be on H2 and L2 instead.

[0128] In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibodymoiety specifically binding to a second target antigen (e.g., TSLP); and wherein the H1 comprises substitutions at positions 170, 183, and 185 (EU numbering), and the L1 comprises a substitution at position 135 (EU numbering). In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti- IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding to a second target antigen (e.g., TSLP); and wherein the H1 comprises F170I, S183L, and V185L substitutions (EU numbering), and the L1 comprises an L135F substitution (EU numbering). In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding to a second target antigen (e.g., TSLP); and wherein the H1 comprises F170V, S183I, and V185L substitutions (EU numbering), and the L1 comprises an L135F substitution (EU numbering). In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, (a) the H1 comprises F170I, S183L, V185L, T366S, L368A, and Y407V substitutions, the L1 comprises an L135F substitution, and the H2 comprises a T366W substitution; (b) the H1 comprises F170I,S183L, V185L, and T366W substitutions, the L1 comprises an L135F substitution, and the H2 comprises T366S, L368A, and Y407V substitutions; (c) the H1 comprises F170V, S183I, V185L, T366S, L368A, and Y407V substitutions, the L1 comprises an L135F substitution, and the H2 comprises a T366W substitution; or (d) the H1 comprises F170V, S183I, V185L, and T366W substitutions, the L1 comprises an L135F substitution, and the H2 comprises T366S, L368A, and Y407V substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, L1 is derived from a lambda light chain, and L2 is derived from a kappa light chain. In some embodiments, L2 is derived from a lambda light chain, and L1 is derived from a kappa light chain.

[0129] In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding to a second target antigen (e.g., TSLP); and wherein the H1 comprises substitutions at positions 126 and 220 (EU numbering), and the L1 comprises substitutions at positions 124 and 214 (EU numbering). In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding a second target antigen (e.g., TSLP); and wherein the H1 comprises F126C and C220S substitutions (EU numbering), and the L1 comprises E124C and C214S substitutions (EU numbering). In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding a second target antigen (e.g., TSLP); and wherein the H1 comprises F126C and C220S substitutions (EU numbering), and the L1 comprises Q124C and C214S substitutions (EU numbering). In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, (a) the H1 comprises F126C, C220S, T366S, L368A, and Y407V substitutions, the L1 comprises E124C and C214S substitutions, and the H2 comprises a T366W substitution; (b) the H1 comprises F126C, C220S, and T366W substitutions, the L1 comprises E124C and C214S substitutions, and the H2 comprises T366S, L368A, and Y407V substitutions; (c) the H1 comprises F126C, C220S, T366S, L368A, and Y407V substitutions, the L1 comprises Q124C and C214S substitutions, and the H2 comprises a T366W substitution; or (d) the H1 comprises F126C, C220S, and T366W substitutions, the L1 comprises Q124C and C214S substitutions, and the H2 comprises T366S, L368A, and Y407V substitutions; and wherein the amino acid position is according to EU numbering.

[0130] In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding a second target antigen (e.g., TSLP); and wherein the H1 comprises substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and the L1 comprises substitutions at positions 124, 135, and 214 (EU numbering). In someembodiments, the L1 is derived from a lambda light chain. In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding a second target antigen (e.g., TSLP); and wherein the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and the L1 comprises E124C, L135F, and C214S substitutions (EU numbering). In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding a second target antigen (e.g., TSLP); and wherein the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and the L1 comprises E124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti- IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding a second target antigen (e.g., TSLP); and wherein the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and the L1 comprises Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, there is provided a multispecific construct, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form an anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form a second antibody moiety specifically binding a second target antigen (e.g., TSLP); and wherein the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and the L1 comprises Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, (a) the H1 comprises F126C, F170I, S183L, V185L, C220S, T366S, L368A, and Y407V substitutions, the L1 comprises E124C (or Q124C), L135F, and C214S substitutions, and the H2 comprises a T366W substitution; (b) the H1 comprises F126C, F170I, S183L, V185L, C220S, and T366W substitutions, the L1 comprises E124C (or Q124C), L135F, and C214S substitutions, and the H2 comprises T366S, L368A, and Y407V substitutions; (c) the H1 comprises F126C, F170V, S183I, V185L, C220S, T366S, L368A, and Y407V substitutions, the L1 comprises E124C (or Q124C), L135F, and C214S substitutions, and the H2 comprises a T366W substitution; or (d) the H1 comprises F126C, F170V, S183I, V185L, C220S, and T366W substitutions, the L1 comprises E124C (or Q124C), L135F, and C214S substitutions, and the H2 comprises T366S, L368A, and Y407V substitutions; and wherein the amino acid position is according to EU numbering.

[0131] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically bindinga second target antigen (e.g., TSLP); wherein the H2 comprises substitutions at positions 170, 183, and 185 (EU numbering), and the L2 comprises a substitution at position 135 (EU numbering). In some embodiments, the H2 comprises substitutions at positions F170, S183, and V185 (EU numbering), and the L2 comprises a substitution at position L135 (EU numbering). In some embodiments, the H2 comprises F170I, S183L, and V185L substitutions (EU numbering), and the L2 comprises an L135F substitution (EU numbering). In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0132] In some embodiments, there is provided a multispecific construct comprising a heterodimeric bispecific antibody comprisingi) 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the H2 comprises substitutions at positions 170, 183, and 185 (EU numbering), and the L2 comprises a substitution at position 135 (EU numbering). In some embodiments, the H2 comprises substitutions at positions F170, S183, and V185 (EU numbering), and the L2 comprises a substitution at position L135 (EU numbering). In some embodiments, the H2 comprises F170V, S183I, and V185L substitutions (EU numbering), and the L2 comprises an L135F substitution (EU numbering). In some embodiments, the L2 is derived from a lambda light chain. In some embodiments,the L2 is derived from a kappa light chain. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0133] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the H2 comprises substitutions at positions 126 and 220 (EU numbering), and the L2 comprises substitutions at positions 124 and 214 (EU numbering). In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the H2 comprises substitutions at positions F126 and C220 (EU numbering), and the L2 comprises substitutions at positions E124 and C214 (EU numbering). In some embodiments, the H2 comprises F126C and C220S substitutions (EU numbering), and the L2 comprises E124C and C214S substitutions (EU numbering). In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, the H2 comprises substitutions at positions F126 and C220 (EU numbering), and the L2 comprises substitutions at positions Q124 and C214 (EU numbering). In some embodiments, the H2 comprises F126C and C220S substitutions (EU numbering), and the L2 comprises Q124C and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domaincomprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0134] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the H2 comprises substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and the L2 comprises substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L2 comprises substitutions at positions E124, L135, and C214 (EU numbering). In some embodiments, the H2 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and the L2 comprises E124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, the H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L2 comprises substitutions at positions Q124, L135, and C214 (EU numbering). In some embodiments, the H2 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and the L2 comprises Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunitof the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0135] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the H2 comprises substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and the L2 comprises substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L2 comprises substitutions at positions E124, L135, and C214 (EU numbering). In some embodiments, the H2 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and the L2 comprises E124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, the H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L2 comprises substitutions at positions Q124, L135, and C214 (EU numbering). In some embodiments, the H2 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and the L2 comprises Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises L234A and L235A substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M428L and N434S substitutions (EU numbering). In some embodiments, each subunit of the Fc domain comprises M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0136] In some embodiments, there is provided a multispecific construct comprising: two anti-IL13 antibody moieties that are scFvs (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”, e.g.,any of the anti-IL-13 scFvs described herein), and a second antibody moiety that is a full- length antibody specifically binding 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 moiety 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 moiety to form a second fusion polypeptide; and wherein the anti-IL-13 scFv1 and the anti-IL-13 scFv2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72. In some embodiments, the anti-IL-13 scFv1 and the anti-IL-13 scFv2 each comprises: a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69.

[0137] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are scFvs (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”, e.g., any of the anti-IL-13 scFvs described herein), two second antibody moieties that are Fabs (“Fab1” and “Fab2”) specifically binding 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-a 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-a second subunit of the 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 the anti-IL-13 scFv1 and the anti- IL-13 scFv2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR- H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72. In some embodiments, the anti-IL-13 scFv1 and the anti-IL-13 scFv2 each comprises: a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69.

[0138] In some embodiments, there is provided a multispecific construct comprising: a first antibody moiety that is an anti-IL-13 full-length antibody (e.g., any of the anti-IL-13 full-length antibodies described herein), and two second antibody moieties that are scFvs (“scFv1” and “scFv2”) specifically binding to a second target antigen (e.g., TSLP); wherein scFv1 is fused to the C-terminus of a 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 a 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 an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR- L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72. In some embodiments, the anti-IL-13 full-length antibody comprises: a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-IL-13 full-length 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 anti-IL-13 full-length 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.

[0139] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, e.g., any of the anti-IL-13 Fabs described herein), two second antibody moieties that are scFvs (“scFv1” and “scFv2”) specifically binding 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-scFv1-optional linker-a first subunit of the Fc domain; iii) a third polypeptide comprising from N’ to C’: VH2-(H2-CH1)-optional linker-scFv2-optional linker-a 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; and wherein the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72. Insome embodiments, the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises: a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69.

[0140] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, e.g., any of the anti-IL-13 Fabs described herein), and a second antibody moiety that is a full- length antibody specifically binding to a second target antigen (e.g., TSLP); wherein the multispecific construct comprises: i) a first polypeptide comprising: a first light chain of the second antibody moiety; ii) a second polypeptide comprising from N’ to C’: a first heavy chain of the second antibody moiety-optional linker-VH1-(H1-CH1); iii) a third polypeptide comprising from N’ to C’: a second heavy chain of the second antibody moiety-optional linker-VH2-(H2-CH1); iv) a fourth polypeptide comprising: a second light chain of the second antibody moiety; v) a fifth polypeptide comprising from N’ to C’: VL1-(L1-CL); and vi) a sixth polypeptide comprising from N’ to C’: VL2-(L2-CL); wherein VL1-(L1-CL) and VH1-(H1-CH1) form anti-IL-13 Fab1, and VL2-(L2-CL) and VH2-(H2-CH1) form anti-IL- 13 Fab2; and wherein the anti-IL-13 Fab1 and the anti- IL-13 Fab2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72. In some embodiments, the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises: 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 anti-IL-13 Fab1 comprises an H1 comprising the VH1- (H1-CH1), and an L1 comprising the VL1-(L1-CL); wherein the anti-IL-13 Fab2 comprises an H2 comprising the VH2-(H2-CH1), and an L2 comprising the VL2-(L2-CL); and wherein: (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (orQ124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the light chain of the full-length antibody is derived from a kappa light chain.

[0141] In some embodiments, there is provided a multispecific construct comprising: a first antibody moiety that is an anti-IL-13 full-length antibody (e.g., any of the anti-IL-13 full- length antibodies described herein), and two second antibody moieties that are Fabs (“Fab1” and “Fab2”) specifically binding 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-optional linker-VH3-(H3-CH1); iii) a third polypeptide comprising from N’ to C’: a second heavy chain (H2) of the anti-IL-13 full- length antibody-optional linker-VH4-(H4-CH1); iv) a fourth polypeptide comprising: a second light chain (L2) of the anti-IL-13 full-length 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 Fab1, and VH4-(H4- CH1) and VL4-(L4-CL) form Fab2; and wherein the anti-IL-13 full-length antibody comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR- H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72. In some embodiments, the anti-IL-13 full-length antibody comprises: 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, (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the anti-IL-13 full-length antibody comprises: i) two heavy chains each comprising the amino acid sequence of SEQ ID NO:125, and two lightchains 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 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 a kappa light chain.

[0142] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”, e.g., any of the anti-IL-13 Fabs described herein), and a second antibody moiety that is a full- length antibody specifically binding to a second target antigen (e.g., 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-a first heavy chain of the second antibody moiety; iii) a third polypeptide comprising from N’ to C’: VH2-(H2-CH1)-optional linker-a second heavy chain of the second antibody moiety; iv) a fourth polypeptide comprising from N’ to C’: VL2-(L2-CL); v) a fifth polypeptide comprising: a first light chain of the second antibody moiety; and vi) a sixth polypeptide comprising: a second light chain of the second antibody moiety; wherein VL1-(L1-CL) and VH1-(H1-CH1) form anti-IL-13 Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL- 13 Fab2; and wherein the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ IDNO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72. In some embodiments, the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises: 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 anti-IL-13 Fab1 comprises an H1 comprising the VH1- (H1-CH1), and an L1 comprising the VL1-(L1-CL); wherein the anti-IL-13 Fab2 comprises an H2 comprising the VH2-(H2-CH1), and an L2 comprising the VL2-(L2-CL); wherein: (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the light chain of the full-length antibody is derived from a kappa light chain.

[0143] In some embodiments, there is provided a multispecific construct comprising: a first antibody moiety that is an anti-IL-13 full-length antibody (e.g., any of the anti-IL-13 full- length antibodies described herein), and two second antibody moieties that are Fabs (“Fab1” and “Fab2”) specifically binding to 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-a first heavy chain (H1) of the anti-IL-13 full-length antibody; iii) a third polypeptide comprising from N’ to C’: VH4-(H4-CH1)-optional linker-a second heavy chain (H2) of the anti-IL-13 full-length 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 anti-IL-13 full-length antibody; and vi) a sixth polypeptide comprising from N’ to C’: a second light chain (L2) of the anti-IL-13 full-length antibody; wherein VL3-(L3-CL) and VH3-(H3-CH1) form Fab1 and VH4-(H4-CH1) and VL4-(L4-CL) form Fab2; and wherein the anti-IL-13 full-length antibody comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR- H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising anamino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72. In some embodiments, the anti-IL-13 full-length antibody comprises: 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, (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the anti-IL-13 full-length 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 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 a kappa light chain.

[0144] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the H1 comprises substitutions at positions 170, 183, and 185 (EU numbering), and the L1 comprises a substitution at position 135 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the H1 comprises substitutions at positions F170, S183, and V185 (EU numbering), and the L1 comprises a substitution at position L135 (EU numbering). In some embodiments, the H1 comprises F170I, S183L, and V185L substitutions (EU numbering), and the L1 comprises an L135F substitution (EU numbering). In some embodiments, the L1 is derived from a lambda light chain. In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fcdomain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:138 or 139, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:122 or 207. In some embodiments, the H1 comprises the amino acid sequence of SEQ ID NO:138 or 139, and the L1 comprises the amino acid sequence of SEQ ID NO:122 or 207.

[0145] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the H1 comprises substitutions at positions 170, 183, and 185 (EU numbering), and the L1 comprises a substitution at position 135 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the H1 comprises substitutions at positions F170, S183, and V185 (EU numbering), and the L1 comprises a substitution at position L135 (EU numbering). In some embodiments, the H1 comprisesF170V, S183I, and V185L substitutions (EU numbering), and the L1 comprises an L135F substitution (EU numbering). In some embodiments, the L1 is derived from a lambda light chain. In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:140 or 141, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:122 or 207. In some embodiments, the H1 comprises the amino acid sequence of SEQ ID NO:140 or 141, and the L1 comprises the amino acid sequence of SEQ ID NO:122 or 207.

[0146] In some embodiments, there is provided a multispecific construct comprising a heterodimeric bispecific antibody comprisingi) 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the H1 comprises substitutions at positions 126 and 220 (EU numbering), and the L1 comprisessubstitutions at positions 124 and 214 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the L1 is derived from a lambda light chain. In some embodiments, the H1 comprises substitutions at positions F126 and C220 (EU numbering), and the L1 comprises substitutions at positions E124 and C214 (EU numbering). In some embodiments, the H1 comprises F126C and C220S substitutions (EU numbering), and the L1 comprises E124C and C214S substitutions (EU numbering). In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, the H1 comprises substitutions at positions F126 and C220 (EU numbering), and the L1 comprises substitutions at positions Q124 and C214 (EU numbering). In some embodiments, the H1 comprises F126C and C220S substitutions (EU numbering), and the L1 comprises Q124C and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:200 or 201, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:121 or 206. In some embodiments, the H1 comprises the amino acid sequence of SEQ ID NO:200 or 201, and the L1 comprises the amino acid sequence of SEQ ID NO:121 or 206.

[0147] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the H1 comprises substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and the L1 comprises substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the L1 is derived from a lambda light chain. In some embodiments, the H1 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L1 comprises substitutions at positions E124, L135, and C214 (EU numbering). In some embodiments, the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and the L1 comprises E124C, L135F, and C214S substitutions (EU numbering. In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, the H1 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L1 comprises substitutions at positions Q124, L135, and C214 (EU numbering). In some embodiments, the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and the L1 comprises Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In someembodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:126 or 127, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:120 or 208. In some embodiments, the H1 comprises the amino acid sequence of SEQ ID NO:126 or 127, and the L1 comprises the amino acid sequence of SEQ ID NO:120 or 208.

[0148] In some embodiments, there is provided a multispecific construct comprising a heterodimeric bispecific antibody comprisingi) 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the H1 comprises substitutions at positions 234, 235, 428, 434, 126, 170, 183, 185, and 220 (EU numbering), and the L1 comprises substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:65, and the VL1 comprises the amino acid sequence of SEQ ID NO:69, or a variant thereof having atleast about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the L1 is derived from a lambda light chain. In some embodiments, the H1 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L1 comprises substitutions at positions E124, L135, and C214 (EU numbering). In some embodiments, the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and the L1 comprises E124C, L135F, and C214S substitutions (EU numbering. In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, the H1 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L1 comprises substitutions at positions Q124, L135, and C214 (EU numbering). In some embodiments, the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and the L1 comprises Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:128 or 129, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:120 or 208. In some embodiments, the H1 comprises the amino acid sequence of SEQ ID NO:128 or 129, and the L1 comprises the amino acid sequence of SEQ ID NO:120 or 208.

[0149] In some embodiments, there is provided a multispecific construct 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 subunitof the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the H2 comprises substitutions at positions 170, 183, and 185 (EU numbering), and the L2 comprises substitutions at position 135 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, VH1 comprises the amino acid sequence of SEQ ID NO:65, and the VL1 comprises the amino acid sequence of SEQ ID NO:69. In some embodiments, the H2 comprises substitutions at positions F170, S183, and V185 (EU numbering), and the L2 comprises a substitution at position L135 (EU numbering). In some embodiments, the H2 comprises F170I, S183L, and V185L substitutions (EU numbering), and the L2 comprises an L135F substitution (EU numbering). In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0150] In some embodiments, there is provided a multispecific construct comprising a heterodimeric bispecific antibody comprising: i) a first light chain (L1) comprising VL1 andL1-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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the H2 comprises substitutions at positions 170, 183, and 185 (EU numbering), and the L2 comprises a substitution at position 135 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the H2 comprises substitutions at positions F170, S183, and V185 (EU numbering), and the L2 comprises a substitution at position L135 (EU numbering). In some embodiments, the H2 comprises F170V, S183I, and V185L substitutions (EU numbering), and the L2 comprises an L135F substitution (EU numbering). In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0151] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the H2 comprises substitutions at positions 126 and 220 (EU numbering), and the L2 comprises substitutions at positions 124 and 214 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the H2 comprises substitutions at positions F126 and C220 (EU numbering), and the L2 comprises substitutions at positions E124 and C214 (EU numbering). In some embodiments, the H2 comprises F126C and C220S substitutions (EU numbering), and the L2 comprises E124C and C214S substitutions (EU numbering). In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, the H2 comprises substitutions at positions F126 and C220 (EU numbering), and the L2 comprises substitutions at positions Q124 and C214 (EU numbering). In some embodiments, the H2 comprises F126C and C220S substitutions (EU numbering), and the L2 comprises Q124C and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EUnumbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0152] In some embodiments, there is provided a multispecific construct comprising a heterodimeric bispecific antibody comprisingi) 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the H2 comprises substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and the L2 comprises substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L2 comprises substitutions at positions E124, L135, and C214 (EU numbering). In some embodiments, the H2 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and the L2 comprises E124C, L135F, and C214S substitutions (EU numbering. In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, theH2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L2 comprises substitutions at positions Q124, L135, and C214 (EU numbering). In some embodiments, the H2 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and the L2 comprises Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0153] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding a second target antigen (e.g., TSLP); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the H2 comprises substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and the L2 comprises substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQID NO:69. In some embodiments, 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. In some embodiments, the L2 is derived from a lambda light chain. In some embodiments, the H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L2 comprises substitutions at positions E124, L135, and C214 (EU numbering). In some embodiments, the H2 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and the L2 comprises E124C, L135F, and C214S substitutions (EU numbering. In some embodiments, the L2 is derived from a kappa light chain. In some embodiments, the H2 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L2 comprises substitutions at positions Q124, L135, and C214 (EU numbering). In some embodiments, the H2 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and the L2 comprises Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering).

[0154] In some embodiments, there is provided a multispecific construct comprising: two first antibody moieties that are anti-IL-13 scFvs (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”), and a second antibody moiety that is a full-length antibody specifically binding to TSLP (“anti-TSLP full-length antibody”), wherein anti-IL-13 scFv1 is fused to the C-terminus of a 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 a second heavy chain of the anti-TSLP full-length antibody via an optional linker to form a second fusion polypeptide; wherein the anti-IL-13 scFv1 and the anti-IL-13 scFv2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) aCDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the anti-TSLP full-length antibody comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; (iii) a CDR- H3 comprising an amino acid sequence of SEQ ID NO:22; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26. In some embodiments, the anti-IL-13 scFv1 and the anti-IL-13 scFv2 each comprises a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-TSLP full-length antibody comprises: (a) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:53; (b) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:54; (c) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:189; (d) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:190; or (e) a VH comprising an amino acid sequence of SEQ ID NO:228, and a VL comprising an amino acid sequence of SEQ ID NO:190. In some embodiments, the anti-IL- 13 scFv1 and the anti-IL-13 scFv2 each comprises the amino acid sequence of SEQ ID NO:108. In some embodiments, the anti-TSLP full-length 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 an amino acid sequence of any one of GG and SEQ ID NOs:98-99. In some embodiments, the anti-TSLP full-length 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 comprises the amino acid sequence of SEQ ID NO:113.

[0155] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are scFvs (“anti-IL-13 scFv1” and “anti-IL-13 scFv2”), two second antibody moieties that are Fabs that specifically binds to 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-afirst 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-a second subunit of the 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 the anti-IL-13 scFv1 and the anti-IL-13 scFv2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22; (iv) a CDR- L1 comprising an amino acid sequence of SEQ ID NO:24; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26. In some embodiments, the anti-IL-13 scFv1 and the anti-IL-13 scFv2 each comprises a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises: (a) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:53; (b) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:54; (c) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:189; (d) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:190; or (e) a VH comprising an amino acid sequence of SEQ ID NO:228, and a VL comprising an amino acid sequence of SEQ ID NO:190. In some embodiments, the anti-IL-13 scFv1 and the anti-IL-13 scFv2 each comprises the amino acid sequence of SEQ ID NO:108. In some embodiments, the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises 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 any one of GG and SEQ ID NOs:98-99. In some embodiments, the first polypeptide and the fourth polypeptide each comprises the amino acid sequence of SEQ ID NO:103, and thesecond polypeptide and the third polypeptide each comprises the amino acid sequence of SEQ ID NO:110.

[0156] In some embodiments, there is provided a multispecific construct comprising: a first antibody moiety that is an anti-IL-13 full-length antibody, and two second antibody moieties that are scFvs specifically binding to TSLP (“anti-TSLP scFv1” and “anti-TSLP scFv2”); wherein anti-TSLP scFv1 is fused to the C-terminus of a first heavy chain of the anti-IL-13 full-length antibody via an optional linker to form a first fusion polypeptide, and anti-TSLP scFv2 is fused to the C-terminus of a second heavy chain of the anti-IL-13 full-length antibody via an optional linker to form a second fusion polypeptide; wherein the anti-IL-13 full-length antibody comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR- H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the anti-TSLP scFv1 and the anti-TSLP scFv2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (v) a CDR- L2 comprising an amino acid sequence of SEQ ID NO:25; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26. In some embodiments, anti-IL-13 full-length antibody comprises a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-TSLP scFv1 and the anti-TSLP scFv2 each comprises: (a) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:53; (b) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:54; (c) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:189; (d) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:190; or (e) a VH comprising an amino acid sequence of SEQ ID NO:228, and a VL comprising an amino acid sequence of SEQ ID NO:190. In some embodiments, the anti-IL-13 full-length 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 anti-IL-13 full-length antibody comprises two heavy chains each comprising the amino acidsequence of SEQ ID NO:225, and two light chains each comprising the amino acid sequence of SEQ ID NO:102 or 197. In some embodiments, the anti-TSLP scFv1 and the anti-TSLP scFv2 each comprises the amino acid sequence of any one of SEQ ID NOs:106, 107, 218, 219, 226, 227, and 229. In some embodiments, the linker comprises an amino acid sequence of any one of GG and SEQ ID NOs:98-99. In some embodiments, the anti-IL-13 full-length 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, wherein the first fusion polypeptide and the second fusion polypeptide each comprises the amino acid sequence of SEQ ID NO:111. In some embodiments, the anti-IL-13 full- length 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, and wherein the first fusion polypeptide and the second fusion polypeptide each comprises the amino acid sequence of any one of SEQ ID NOs:220-223.

[0157] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”), two second antibody moieties that are scFvs specifically binding to TSLP (“anti-TSLP scFv1” and “anti-TSLP scFv2”), 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 the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR- L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the anti-TSLP scFv1 and the anti-TSLP scFv2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26. Insome embodiments, the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-TSLP scFv1 and the anti-TSLP scFv2 each comprises: (a) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:53; (b) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:54; (c) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:189; (d) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:190; or (e) a VH comprising an amino acid sequence of SEQ ID NO:228, and a VL comprising an amino acid sequence of SEQ ID NO:190. In some embodiments, the anti-IL- 13 Fab1 and the anti-IL-13 Fab2 each comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO:124, and a second polypeptide comprising the amino acid sequence of SEQ ID NO:102 or 197. In some embodiments, the anti-TSLP scFv1 and the anti-TSLP scFv2 each comprises the amino acid sequence of any one of SEQ ID NOs:106, 107, 218, 219, 226, 227, and 229. In some embodiments, the linker comprises an amino acid sequence independently selected from any one of GG and SEQ ID NOs:98-99. In some embodiments, the first polypeptide and the fourth polypeptide each comprises the amino acid sequence of SEQ ID NO:102 or 197, and the second polypeptide and the third polypeptide each comprises the amino acid sequence of SEQ ID NO:112.

[0158] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”), and a second antibody moiety that is a full-length antibody specifically binding to TSLP (“anti- TSLP full-length antibody”); 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-optional linker-VH1-(H1-CH1); iii) a third polypeptide comprising from N’ to C’: a second heavy chain of the anti-TSLP full-length antibody-optional 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 anti-IL-13 Fab1, and VL2-(L2-CL) and VH2-(H2-CH1) form anti-IL-13 Fab2; wherein the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the anti-TSLP full-length antibody comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26. In some embodiments, the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-TSLP full-length antibody comprises: (a) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:53; (b) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:54; (c) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:189; (d) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:190; or (e) a VH comprising an amino acid sequence of SEQ ID NO:228, and a VL comprising an amino acid sequence of SEQ ID NO:190. In some embodiments, the anti-IL-13 Fab1 comprises an H1 comprising the VH1- (H1-CH1), and an L1 comprising the VL1-(L1-CL); wherein the anti-IL-13 Fab2 comprises an H2 comprising the VH2-(H2-CH1), and an L2 comprising the VL2-(L2-CL); and wherein: (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the light chains of the anti-TSLP full-length antibody are derived from kappa light chain. In some embodiments, the anti-TSLP full-length 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 any one of GG and SEQ ID NOs:98-99.

[0159] In some embodiments, there is provided a multispecific construct comprising: an anti- IL-13 antibody moiety that is a full-length antibody (“anti-IL-13 full-length antibody”), and two second antibody moieties that are Fabs specifically binding to TSLP (“anti-TSLP Fab1” and “anti-TSLP Fab2”); 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-optional linker-VH3-(H3-CH1); iii) a third polypeptide comprising from N’ to C’: a second heavy chain (H2) of the anti-IL-13 full-length antibody-optional linker-VH4-(H4- CH1); iv) a fourth polypeptide comprising: a second light chain (L2) of the anti-IL-13 full- length 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 anti-TSLP Fab1, and VH4-(H4-CH1) and VL4-(L4-CL) form anti-TSLP Fab2; wherein the anti-IL-13 full length antibody comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26. In some embodiments, the anti-IL-13 full length antibody comprises a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises: (a) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:53; (b) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:54; (c) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acidsequence of SEQ ID NO:189; (d) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:190; or (e) a VH comprising an amino acid sequence of SEQ ID NO:228, and a VL comprising an amino acid sequence of SEQ ID NO:190. In some embodiments, (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the anti-IL-13 full-length 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 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 a kappa light chain. In some embodiments, the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO:109, and a second polypeptide comprising the amino acid sequenceof SEQ ID NO:103. In some embodiments, the linker comprises an amino acid sequence independently selected from any one of GG and SEQ ID NOs:98-99.

[0160] In some embodiments, there is provided a multispecific construct comprising: two anti-IL-13 antibody moieties that are Fabs (“anti-IL-13 Fab1” and “anti-IL-13 Fab2”), and a second antibody moiety that is a full-length antibody specifically binding to TSLP (“anti- TSLP full-length antibody”); 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-a first heavy chain of the anti-TSLP full- length antibody; iii) a third polypeptide comprising from N’ to C’: VH2-(H2-CH1)-optional linker-a 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: a first light chain of the anti-TSLP full-length antibody; and vi) a sixth polypeptide comprising: a second light chain of the anti-TSLP full-length antibody; wherein VL1-(L1-CL) and VH1-(H1-CH1) form anti-IL-13 Fab1, and VH2-(H2-CH1) and VL2-(L2-CL) form anti-IL-13 Fab2; wherein the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the anti-TSLP full-length antibody comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26. In some embodiments, the anti-IL-13 Fab1 and the anti-IL-13 Fab2 each comprises a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-TSLP full-length antibody comprises: (a) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:53; (b) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:54; (c) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:189; (d) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:190; or (e) a VH comprising an aminoacid sequence of SEQ ID NO:228, and a VL comprising an amino acid sequence of SEQ ID NO:190. In some embodiments, the anti-IL-13 Fab1 comprises an H1 comprising the VH1- (H1-CH1), and an L1 comprising the VL1-(L1-CL); wherein the anti-IL-13 Fab2 comprises an H2 comprising the VH2-(H2-CH1), and an L2 comprising the VL2-(L2-CL); and wherein: (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the light chains of the anti-TSLP full-length antibody are derived from a kappa light chain. In some embodiments, the anti-TSLP full-length 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 any one of GG and SEQ ID NOs:98-99.

[0161] In some embodiments, there is provided a multispecific construct comprising: a first antibody moiety that is an anti-IL-13 full-length antibody, and two second antibody moieties that are Fabs specifically binding to TSLP (“anti-TSLP Fab1” and “anti-TSLP Fab2”); 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-a first heavy chain (H1) of the anti-IL-13 full-length antibody; iii) a third polypeptide comprising from N’ to C’: VH4-(H4-CH1)-optional linker-a second heavy chain (H2) of the anti-IL-13 full-length 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 anti-IL-13 full-length antibody; and vi) a sixth polypeptide comprising from N’ to C’: a second light chain (L2) of the anti-IL-13 full-length 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 anti-IL-13 full-length antibody comprises: (i) a CDR-H1 comprisingan amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; and wherein the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises: (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22; (iv) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (v) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (vi) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26. In some embodiments, the anti-IL-13 full-length antibody comprises a VH comprising an amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises: (a) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:53; (b) a VH comprising an amino acid sequence of SEQ ID NO:63, and a VL comprising an amino acid sequence of SEQ ID NO:54; (c) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:189; (d) a VH comprising an amino acid sequence of SEQ ID NO:188, and a VL comprising an amino acid sequence of SEQ ID NO:190; or (e) a VH comprising an amino acid sequence of SEQ ID NO:228, and a VL comprising an amino acid sequence of SEQ ID NO:190. In some embodiments, (a) H1 and H2 each comprises F170I, S183L, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (b) H1 and H2 each comprises F170V, S183I, and V185L substitutions, and L1 and L2 each comprises an L135F substitution; (c) H1 and H2 each comprises F126C, F170I, S183L, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; (d) H1 and H2 each comprises F126C, F170V, S183I, V185L, and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C), L135F, and C214S substitutions; or e) H1 and H2 each comprises F126C and C220S substitutions, and L1 and L2 each comprises E124C (or Q124C) and C214S substitutions; and wherein the amino acid position is according to EU numbering. In some embodiments, the anti-IL-13 full-length 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 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 a kappa light chain. In some embodiments, the anti-TSLP Fab1 and the anti-TSLP Fab2 each comprises 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 any one of GG and SEQ ID NOs:98-99.

[0162] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety (e.g., any of the anti-IL-13 antibody moieties described herein), and H2 and L2 form the second antibody moiety specifically binding to TSLP (“anti-TSLP antibody moiety”); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; wherein the anti-TSLP antibody moiety comprises: a VH2 comprising (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ IDNO:21; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22, and a VL2 comprising (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26; and wherein the H1 comprises substitutions at positions 170, 183, and 185 (EU numbering), and the L1 comprises a substitution at position 135 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the anti-TSLP antibody moiety comprises: (a) a VH2 comprising the amino acid sequence of SEQ ID NO:63, and a VL2 comprising the amino acid sequence of SEQ ID NO:53; (b) a VH2 comprising the amino acid sequence of SEQ ID NO:63, and a VL2 comprising the amino acid sequence of SEQ ID NO:54; (c) a VH2 comprising the amino acid sequence of SEQ ID NO:188, and a VL2 comprising the amino acid sequence of SEQ ID NO:189; (d) a VH2 comprising the amino acid sequence of SEQ ID NO:188, and a VL2 comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH2 comprising the amino acid sequence of SEQ ID NO:228, and a VL2 comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, the H1 comprises substitutions at positions F170, S183, and V185 (EU numbering), and the L1 comprises a substitution at position L135 (EU numbering). In some embodiments, the H1 comprises F170I, S183L, and V185L substitutions (EU numbering), and the L1 comprises an L135F substitution (EU numbering). In some embodiments, the L1 is derived from a lambda light chain. In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, the anti-IL-13 antibody moiety 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to the amino acid sequence of SEQ ID NO:102 or 197. In some embodiments, the anti-TSLP antibody moiety comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO:109, or avariant thereof having at least about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, (i) the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:139, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:122 or 207, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:136, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103; or (ii) the H1 comprises the amino acid sequence of SEQ ID NO:138, or a variant thereof having at least about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:138, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:122 or 207, the H2 comprises the amino acid sequence of SEQ ID NO:137, or a variant thereof having at least about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:137, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103. In some embodiments, (i)the H1 comprises the amino acid sequence of SEQ ID NO:139, the L1 comprises the amino acid sequence of SEQ ID NO:122 or 207, the H2 comprises the amino acid sequence of SEQ ID NO:136, and the L2 comprises the amino acid sequence of SEQ ID NO:103; or (ii) the H1 comprises the amino acid sequence of SEQ ID NO:138, the L1 comprises the amino acid sequence of SEQ ID NO:122 or 207, the H2 comprises the amino acid sequence of SEQ ID NO:137, and the L2 comprises the amino acid sequence of SEQ ID NO:103.

[0163] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety, and H2 and L2 form the second antibody moiety specifically binding to TSLP (“anti-TSLP antibody moiety”); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; wherein the anti-TSLP antibody moiety comprises: a VH2 comprising (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22, and a VL2 comprising (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26; and wherein the H1 comprises substitutions at positions 170, 183, and 185 (EU numbering), and the L1 comprises a substitution at position 135 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the anti-TSLP antibody moiety comprises: (a) a VH2 comprising the amino acid sequence of SEQ ID NO:63, and aVL2 comprising the amino acid sequence of SEQ ID NO:53; (b) a VH2 comprising the amino acid sequence of SEQ ID NO:63, and a VL2 comprising the amino acid sequence of SEQ ID NO:54; (c) a VH2 comprising the amino acid sequence of SEQ ID NO:188, and a VL2 comprising the amino acid sequence of SEQ ID NO:189; (d) a VH2 comprising the amino acid sequence of SEQ ID NO:188, and a VL2 comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH2 comprising the amino acid sequence of SEQ ID NO:228, and a VL2 comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, the H1 comprises substitutions at positions F170, S183, and V185 (EU numbering), and the L1 comprises a substitution at position L135 (EU numbering). In some embodiments, the H1 comprises F170V, S183I, and V185L substitutions (EU numbering), and the L1 comprises an L135F substitution (EU numbering). In some embodiments, the L1 is derived from a lambda light chain. In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, the anti-IL-13 antibody moiety 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to the amino acid sequence of SEQ ID NO:102 or 197. In some embodiments, the anti-TSLP antibody moiety 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, (i) the H1 comprises the aminoacid sequence of SEQ ID NO:141, or a variant thereof having at least about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:141, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:122 or 207, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:136, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103; or (ii) the H1 comprises the amino acid sequence of SEQ ID NO:140, or a variant thereof having at least about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:140, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:122 or 207, the H2 comprises the amino acid sequence of SEQ ID NO:137, or a variant thereof having at least about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:137, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103. In some embodiments, (i) the H1 comprises the amino acid sequence of SEQ ID NO:141, the L1 comprises the amino acid sequence of SEQ ID NO:122 or 207, the H2 comprises the amino acid sequence of SEQ ID NO:136, and the L2 comprises the amino acid sequence of SEQ ID NO:103; or (ii) the H1 comprises the amino acid sequence of SEQ ID NO:140, the L1 comprises the amino acid sequence of SEQ ID NO:122 or 207, the H2 comprises the amino acid sequence of SEQ ID NO:137, and the L2 comprises the amino acid sequence of SEQ ID NO:103.

[0164] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety, and H2 and L2 form the second antibody moiety specifically binding to TSLP (“anti-TSLP antibody moiety”); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprisingan amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; wherein the anti-TSLP antibody moiety comprises: a VH2 comprising (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22, and a VL2 comprising (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26; and wherein the H1 comprises substitutions at positions 126 and 220 (EU numbering), and the L1 comprises substitutions at positions 124 and 214 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the anti-TSLP antibody moiety comprises: (a) a VH2 comprising the amino acid sequence of SEQ ID NO:63, and a VL2 comprising the amino acid sequence of SEQ ID NO:53; (b) a VH2 comprising the amino acid sequence of SEQ ID NO:63, and a VL2 comprising the amino acid sequence of SEQ ID NO:54; (c) a VH2 comprising the amino acid sequence of SEQ ID NO:188, and a VL2 comprising the amino acid sequence of SEQ ID NO:189; (d) a VH2 comprising the amino acid sequence of SEQ ID NO:188, and a VL2 comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH2 comprising the amino acid sequence of SEQ ID NO:228, and a VL2 comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, the L1 is derived from a lambda light chain. In some embodiments, the H1 comprises substitutions at positions F126 and C220 (EU numbering), and the L1 comprises substitutions at positions E124 and C214 (EU numbering). In some embodiments, the H1 comprises F126C and C220S substitutions (EU numbering), and the L1 comprises E124C and C214S substitutions (EU numbering). In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, the H1 comprises substitutions at positions F126 and C220 (EU numbering), and the L1 comprises substitutions at positions Q124 and C214(EU numbering). In some embodiments, the H1 comprises F126C and C220S substitutions (EU numbering), and the L1 comprises Q124C and C214S substitutions (EU numbering). In some embodiments, the anti-IL-13 antibody moiety 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to the amino acid sequence of SEQ ID NO:102 or 197. In some embodiments, the anti-TSLP antibody moiety 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, (i) the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:200, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:121 or 206, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:136, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103; or (ii) the H1 comprises theamino acid sequence of SEQ ID NO:201, or a variant thereof having at least about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:201, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:121 or 206, the H2 comprises the amino acid sequence of SEQ ID NO:137, or a variant thereof having at least about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:137, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103. In some embodiments, (i) the H1 comprises the amino acid sequence of SEQ ID NO:200, the L1 comprises the amino acid sequence of SEQ ID NO:121 or 206, the H2 comprises the amino acid sequence of SEQ ID NO:136, and the L2 comprises the amino acid sequence of SEQ ID NO:103; or (ii) the H1 comprises the amino acid sequence of SEQ ID NO:201, the L1 comprises the amino acid sequence of SEQ ID NO:121 or 206, the H2 comprises the amino acid sequence of SEQ ID NO:137, and the L2 comprises the amino acid sequence of SEQ ID NO:103.

[0165] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety, and H2 and L2 form the second antibody moiety specifically binding to TSLP (“anti-TSLP antibody moiety”); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; wherein the anti-TSLP antibody moiety comprises: a VH2 comprising (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22, and a VL2 comprising (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26; and wherein the H1comprises substitutions at positions 126, 170, 183, 185, and 220 (EU numbering); and the L1 comprises substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, 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. In some embodiments, the anti-TSLP antibody moiety comprises: (a) a VH2 comprising the amino acid sequence of SEQ ID NO:63, and a VL2 comprising the amino acid sequence of SEQ ID NO:53; (b) a VH2 comprising the amino acid sequence of SEQ ID NO:63, and a VL2 comprising the amino acid sequence of SEQ ID NO:54; (c) a VH2 comprising the amino acid sequence of SEQ ID NO:188, and a VL2 comprising the amino acid sequence of SEQ ID NO:189; (d) a VH2 comprising the amino acid sequence of SEQ ID NO:188, and a VL2 comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH2 comprising the amino acid sequence of SEQ ID NO:228, and a VL2 comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, the L1 is derived from a lambda light chain. In some embodiments, the H1 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L1 comprises substitutions at positions E124, L135, and C214 (EU numbering). In some embodiments, the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and the L1 comprises E124C, L135F, and C214S substitutions (EU numbering. In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, the H1 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L1 comprises substitutions at positions Q124, L135, and C214 (EU numbering). In some embodiments, the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions (EU numbering), and the L1 comprises Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the anti-IL-13 antibody moiety 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to the amino acid of SEQ ID NO:102 or 197. Insome embodiments, the anti-TSLP antibody moiety 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments, each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, (i) the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:126, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:120 or 208, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:136, and the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103; or (ii) the H1 comprises the amino acid sequence of SEQ ID NO:127, or a variant thereof having at least about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:127, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:120 or 208, the H2 comprises the amino acid sequence of SEQ ID NO:137, or a variant thereof having at least about 80% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:137, and the L2 comprises the amino acid sequence of SEQ ID NO:103, or a variant thereof having at least about 80% (suchas at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103. In some embodiments, (i) the H1 comprises the amino acid sequence of SEQ ID NO:126, the L1 comprises the amino acid sequence of SEQ ID NO:120 or 208, the H2 comprises the amino acid sequence of SEQ ID NO:136, and the L2 comprises the amino acid sequence of SEQ ID NO:103; or (ii) the H1 comprises the amino acid sequence of SEQ ID NO:127, the L1 comprises the amino acid sequence of SEQ ID NO:120 or 208, the H2 comprises the amino acid sequence of SEQ ID NO:137, and the L2 comprises the amino acid sequence of SEQ ID NO:103.

[0166] In some embodiments, there is provided a multispecific construct 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; wherein H1 and L1 form the anti-IL-13 antibody moiety, and H2 and L2 form the second antibody moiety specifically binding to TSLP (“anti-TSLP antibody moiety”); wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67; (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68; and wherein the VL1 comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72; wherein the anti-TSLP antibody moiety comprises: a VH2 comprising (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:20; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:21; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:22, and a VL2 comprising (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:24; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:25; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:26; and wherein the H1 comprises substitutions at positions 126, 170, 183, 185, and 220 (EU numbering), and the L1 comprises substitutions at positions 124, 135, and 214 (EU numbering). In some embodiments, the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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% (such as at least about any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:69. In some embodiments, the VH1 comprises the amino acid sequence of SEQ IDNO:65, and the VL1 comprises an amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-TSLP antibody moiety comprises: (a) a VH2 comprising the amino acid sequence of SEQ ID NO:63, and a VL2 comprising the amino acid sequence of SEQ ID NO:53; (b) a VH2 comprising the amino acid sequence of SEQ ID NO:63, and a VL2 comprising the amino acid sequence of SEQ ID NO:54; (c) a VH2 comprising the amino acid sequence of SEQ ID NO:188, and a VL2 comprising the amino acid sequence of SEQ ID NO:189; (d) a VH2 comprising the amino acid sequence of SEQ ID NO:188, and a VL2 comprising the amino acid sequence of SEQ ID NO:190; or (e) a VH2 comprising the amino acid sequence of SEQ ID NO:228, and a VL2 comprising the amino acid sequence of SEQ ID NO:190. In some embodiments, the L1 is derived from a lambda light chain. In some embodiments, the H1 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L1 comprises substitutions at positions E124, L135, and C214 (EU numbering). In some embodiments, the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and the L1 comprises E124C, L135F, and C214S substitutions (EU numbering. In some embodiments, the L1 is derived from a kappa light chain. In some embodiments, the H1 comprises substitutions at positions F126, F170, S183, V185, and C220 (EU numbering), and the L1 comprises substitutions at positions Q124, L135, and C214 (EU numbering). In some embodiments, the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions (EU numbering), and the L1 comprises Q124C, L135F, and C214S substitutions (EU numbering). In some embodiments, the anti-IL-13 antibody moiety 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to the amino acid sequence of SEQ ID NO:102 or 197. In some embodiments, the anti-TSLP antibody moiety 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:103. In some embodiments, the Fc domain is derived from an IgG selected from the group consisting of IgG1, IgG2, IgG3, and IgG4, e.g., human IgG1. In some embodiments,each subunit of the Fc domain comprises: (i) L234A and L235A substitutions (EU numbering); (ii) M428L and N434S substitutions (EU numbering; and / or (iii) M252Y, S254T, and T256E substitutions (EU numbering). In some embodiments, (i) the first subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the second subunit of the Fc domain comprises a T366W substitution (EU numbering); or (ii) the second subunit of the Fc domain comprises T366S, L368A, and Y407V substitutions (EU numbering), and the first subunit of the Fc domain comprises a T366W substitution (EU numbering). In some embodiments, (i) the 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 any of 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more) sequence identity to SEQ ID NO:128, the...

Claims

CLAIMS What is claimed is:

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

2. The multispecific construct of claim 1, wherein the first antibody moiety comprises a heavy chain variable region (VH1) and a light chain variable region (VL1), wherein the VH1 comprises (i) a CDR-H1 comprising an amino acid sequence of SEQ ID NO:66, or a variant thereof comprising up to 3 amino acid variations, (ii) a CDR-H2 comprising an 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 an 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 an amino acid sequence of SEQ ID NO:70, or a variant thereof comprising up to 3 amino acid variations, (ii) a CDR-L2 comprising an 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 an amino acid sequence of SEQ ID NO:72, or a variant thereof comprising up to 3 amino acid variations.

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

72.

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

69.

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

7. The multispecific construct of claim 6, wherein the first antibody moiety is an scFv (anti-IL-13 scFv).

8. The multispecific construct of claim 6, wherein the first antibody moiety is a Fab (anti-IL-13 Fab).

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

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

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

50.

12. The multispecific construct of claim 11, wherein: (a) the VH2 comprises an 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 an 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 an 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 VL2comprises an 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 an 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 an 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 an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 an 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 an 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 an 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 an 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 comprises an 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 an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 an 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 VL2comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 comprises an 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 an 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 an 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 an 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 comprises an 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 comprises an 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 of any one of claims 1-12, wherein the second antibody moiety is selected from the group consisting of: a full-length antibody, a Fab, a Fab’, a F(ab’)2, an sdAb, and an scFv.

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

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

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

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

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

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

20. The multispecific construct of 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) wherein the L135 substitution is L135F.

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

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

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

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

25. The multispecific construct of any one of claims 18-21, wherein the L1 is derived from a kappa light chain.

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

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

28. The multispecific construct of any one of claims 18-27, wherein (i) the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions, and the L1 comprises E124C, L135F, and C214S substitutions; (ii) the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions, and the L1 comprises E124C, L135F, and C214S substitutions; (iii) the H1 comprises F126C, F170I, S183L, V185L, and C220S substitutions, and the L1 comprises Q124C, L135F, and C214S substitutions; or (iv) the H1 comprises F126C, F170V, S183I, V185L, and C220S substitutions, and the L1 comprises Q124C, L135F, and C214S substitutions; and wherein the position is according to EU numbering.

29. The multispecific construct of any one of claims 1-8, 10-13, and 15-28, 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 of claim 29, wherein the Fc domain is derived from IgG1.

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

32. The multispecific construct of claim 31, wherein: (i) 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; (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 of any one of claims 1-5, 10-12, and 18-32, 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, 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 the Fc domain; and iv) a second light chain (L2) comprising VL2 and L2-CL; and wherein H1 and L1 form the anti-IL-13 antibody moiety, and H2 and L2 form the second antibody moiety.

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

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

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

86.

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

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

103.

39. An isolated antibody construct (anti-IL-13 antibody construct) comprising an antibody moiety that specifically binds interleukin-13 (IL-13) (anti-IL-13 antibody moiety), wherein the 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 an amino acid sequence of SEQ ID NO:66, or a variant thereof comprising up to 3 amino acids variations; (ii) a CDR-H2 comprising an amino acid sequence of SEQ ID NO:67, or a variant thereof comprising up to 3 amino acids variations; and (iii) a CDR-H3 comprising an amino acid sequence of SEQ ID NO:68, or a variant thereof comprising up to 3 amino acids variations; and the VL comprises (i) a CDR-L1 comprising an amino acid sequence of SEQ ID NO:70, or a variant thereof comprising up to 3 amino acids variations; (ii) a CDR-L2 comprising an amino acid sequence of SEQ ID NO:71, or a variant thereof comprising up to3 amino acids variations; and (iii) a CDR-L3 comprising an amino acid sequence of SEQ ID NO:72, or a variant thereof comprising up to 3 amino acids variations.

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

72.

41. The isolated anti-IL-13 antibody construct of claim 39 or 40, wherein the VH comprises an 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 an 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 of claim 41, wherein the VH comprises an amino acid sequence of SEQ ID NO:65, and the VL comprises an amino acid sequence of SEQ ID NO:

69.

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

44. The isolated anti-IL-13 antibody construct of claim 43, wherein the anti-IL-13 antibody moiety is an scFv (anti-IL-13 scFv).

45. The isolated anti-IL-13 antibody construct of 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 of claim 43, wherein the anti-IL-13 antibody moiety is a Fab (anti-IL-13 Fab).

47. The isolated anti-IL-13 antibody construct of claim 46, wherein the anti-IL-13 Fab comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO:124, and a second polypeptide comprising the amino acid sequence of SEQ ID NO:102 or 197.

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

49. The isolated anti-IL-13 antibody construct of claim 48, wherein the anti-IL-13 full- length 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: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.

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

51. The isolated anti-IL-13 antibody construct of claim 50, wherein the isolated anti-IL- 13 antibody construct further comprises a second antibody moiety that specifically binds to a second antigen.

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

53. An isolated nucleic acid or a vector encoding one or more polypeptides of the multispecific construct of any one of claims 1-38 or the isolated anti-IL-13 antibody construct of any one of claims 39-51.

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

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

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

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

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