Antibodies specifically recognizing thymic stromal lymphopoietin and uses thereof
By designing antibodies that specifically recognize human and cynomolgus monkey TSLP, the problem of poor effectiveness of existing antibodies in recognizing and neutralizing TSLP has been solved, achieving more effective treatment for diseases related to TSLP signaling.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- STAIDSON (BEIJING) BIOPHARMACEUTICALS CO LTD
- Filing Date
- 2022-01-27
- Publication Date
- 2026-07-14
AI Technical Summary
Existing antibodies are unable to effectively and specifically recognize and neutralize thymic stromal lymphopoietin (TSLP), resulting in poor efficacy in treating diseases related to TSLP signaling.
An antibody that can specifically recognize human and cynomolgus monkey TSLP was developed. By designing specific complementarity-determining regions (CDRs) of the heavy and light chain variable structural domains, the binding ability of the antibody to TSLP was improved.
It enhances the binding ability of antibodies to TSLP, providing a more effective treatment for diseases related to TSLP signaling, such as inflammatory diseases and autoimmune diseases.
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Figure CN115210258B_ABST
Abstract
Description
[0001] Submitting sequence lists as ASCII text files
[0002] The contents of the following submitted ASCII TEXT text file are incorporated herein by reference in their entirety: Sequence List in Computer-Readable Form (CRF) (Text name: 202102022277_SEQLIST.txt, Record date: 2021.02.02, Size: 72KB). Technical Field
[0003] This application relates to antibodies that specifically recognize thymic stromal lymphopoietin (TSLP), pharmaceutical compositions and kits containing the above-mentioned TSLP antibodies, methods of preparation and uses thereof, including methods for treating diseases related to TSLP signaling, such as inflammatory diseases. Background Technology
[0004] Full-length thymic stromal lymphopoietin (TSLP) was initially identified as a cytokine in the supernatant of mouse thymic stromal cells that induces the proliferation of pre-B cells (Friend, et al., Exp Hematol. 22(3):321, 1994). This mouse protein was later identified (Sims, et al., J Exp Med. 2000 Sep. 4; 192(5):671-80), and subsequently, in 2001, two independent teams identified human TSLP (Quentmeier, et al., Leukemia. 2001 August; 15(8):1286-92, Reche, et al., J Immunol. 2001 Jul. 1; 167(1):336-43).
[0005] Thymic stromal lymphopoietin (TSLP) is a cytokine that transmits signals via a heterodimeric receptor composed of the IL-7Rα subunit and TSLP-R. TSLP-R is a unique component that is homologous to the common cytokine receptor γ-chain (γc) (Pandey et al., Nat. Immunol. 2000, 1(1):59-64). TSLP is produced by epithelial cells on the barrier surface and activates dendritic cells expressing the TSLP receptor (TSLPR) to induce functional Th2 cells (Roan F et al., J Clin Invest 2019; 129:1441-51). In addition, TSLP is known to be associated with other diseases, including autoimmune diseases and cancer (Varricchi G et al., Front Immunol 2018; 9:1595). The TSLP receptor (TSLPR) complex consists of TSLPR and IL-7 receptor α (IL-7Rα) (Park LS, et al., J Exp Med 2000; 192:659–670). The combination of the TSLPR and IL-7R chains results in signal transduction with high affinity binding and activation of transcription activator 3 (STAT3) and STAT5 (Pandey A, et al., Nat Immunol 2000; 1:59–64). This broad pathophysiological profile encourages the use of TSLP and TSLPR-mediated signal transduction as therapeutic targets in type 2 cytokine-mediated allergic diseases. AMG157 is a fully human antibody against TSLP (used as a control in this example), developed by Amgen for the treatment of asthma and atopic dermatitis. This antibody is described in US Patent No. 7,982,016.
[0006] All publications, patents, patent applications, and disclosed information in published patent applications mentioned herein are incorporated herein by reference in their entirety.
[0007] Application Overview
[0008] On one hand, this application provides an isolated anti-TSLP antibody capable of specifically binding to human and / or cynomolgus monkey TSLP. In some embodiments, the isolated anti-TSLP antibody comprises: a heavy chain variable domain (V H ), the V HIt includes: a heavy chain complementarity determination region (HC-CDR)1, which contains SGYGWS (SEQ ID NO:1); HC-CDR2, which contains YX1SYYGSX2SYNPSLKS (SEQ ID NO:103), wherein X1 is I or F and X2 is I or T; and HC-CDR3, which contains TNLLYFX1X2 (SEQ ID NO:104), wherein X1 is D or E and X2 is S or Y; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR)1, which includes RASQX1X2SX3X4LA (SEQ ID NO:105), wherein X1 is G or S, X2 is V or I, X3 is N or S, and X4 is N or Y; LC-CDR2, which includes DX1SX2X3X4X5 (SEQ ID NO:106), wherein X1 is A or T, X2 is S or N, X3 is R or L, X4 is A or Q, and X5 is T or S; and LC-CDR3, which includes QQYSX1WPX2YX3 (SEQ ID NO:107), wherein X1 is D or N, X2 is Q or E, and X3 is T or S.
[0009] In some embodiments, an isolated anti-TSLP antibody is provided, which comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:1 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:7-9 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:16-18 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:25-28 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequences shown in SEQ ID NOs:39-41 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:50-53 or variants thereof, the variants comprising substitutions of up to about 3 amino acids.
[0010] In some embodiments, an isolated anti-TSLP antibody is provided, which comprises V H The V HV containing any of the amino acid sequences shown in SEQ ID NOs:65-72 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:84-90 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0011] In some embodiments, an isolated anti-TSLP antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:65. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:84. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:65. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:85. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iii)V H It contains V as shown in the amino acid sequence SEQ ID NO:66. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:84. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iv)V H It contains V as shown in the amino acid sequence SEQ ID NO:66. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:85. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (v)V H It contains V as shown in the amino acid sequence SEQ ID NO:67. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V LIt contains V as shown in the amino acid sequence SEQ ID NO:84. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (vi)V H It contains V as shown in the amino acid sequence SEQ ID NO:67. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:85. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (vii)V H It contains V as shown in the amino acid sequence SEQ ID NO:68. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:84. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (viii)V H It contains V as shown in the amino acid sequence SEQ ID NO:68. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:85. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (ix)V H It contains V as shown in the amino acid sequence SEQ ID NO:69. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:86. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (x)V H It contains V as shown in the amino acid sequence SEQ ID NO:70. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:87. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xi)V H It contains V as shown in the amino acid sequence SEQ ID NO:69. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V LIt contains V as shown in the amino acid sequence SEQ ID NO:88. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (xii)V H It contains V as shown in the amino acid sequence SEQ ID NO:71. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:89. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; or (xiii)V H It contains V as shown in the amino acid sequence SEQ ID NO:72. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:90. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0012] In some embodiments, an isolated anti-TSLP antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:7; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:25; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:50, or the V L (ii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V LContains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:25; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:51, or the V L (iii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:17, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:26; LC-CDR2, which contains the amino acid sequence SEQ ID NO:40; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:52, or the V L (iv) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:27; LC-CDR2, which contains the amino acid sequence SEQ ID NO:41; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:52, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (v)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:9; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The VL Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:28; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:52, or the V L Variants whose LC-CDRs contain substitutions of up to about 5 amino acids; or (vi)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:18, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:27; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:53, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0013] In some embodiments, any of the isolated anti-TSLP antibodies described above, the isolated anti-TSLP antibody comprises: V H It comprises any of the amino acid sequences shown in SEQ ID NOs:65-72 or variants thereof, said variants having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:65-72; and V L It comprises any of the amino acid sequences shown in SEQ ID NOs:84-90 or variants thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:84-90. In some embodiments, the isolated anti-TSLP antibody comprises: (i) V H It contains the amino acid sequence SEQ ID NO:65; and V L It contains the amino acid sequence SEQ ID NO:84; (ii)V H It contains the amino acid sequence SEQ ID NO:65; and V LIt contains the amino acid sequence SEQ ID NO:85; (iii)V H It contains the amino acid sequence SEQ ID NO:66; and V L It contains the amino acid sequence SEQ ID NO:84; (iv)V H It contains the amino acid sequence SEQ ID NO:66; and V L It contains the amino acid sequence SEQ ID NO:85; (v)V H It contains the amino acid sequence SEQ ID NO:67; and V L It contains the amino acid sequence SEQ ID NO:84; (vi)V H It contains the amino acid sequence SEQ ID NO:67; and V L It contains the amino acid sequence SEQ ID NO:85; (vii)V H It contains the amino acid sequence SEQ ID NO:68; and V L It contains the amino acid sequence SEQ ID NO:84; (viii)V H It contains the amino acid sequence SEQ ID NO:68; and V L It contains the amino acid sequence SEQ ID NO:85; (ix)V H It contains the amino acid sequence SEQ ID NO:69; and V L It contains the amino acid sequence SEQ ID NO:86; (x)V H It contains the amino acid sequence SEQ ID NO:70; and V L It contains the amino acid sequence SEQ ID NO:87; (xi)V H It contains the amino acid sequence SEQ ID NO:69; and V L It contains the amino acid sequence SEQ ID NO:88; (xii)V H It contains the amino acid sequence SEQ ID NO:71; and V L It contains the amino acid sequence SEQ ID NO:89; or (xiii)V H It contains the amino acid sequence SEQ ID NO:72; and V L It contains the amino acid sequence SEQ ID NO:90.
[0014] On one hand, this application provides an isolated anti-TSLP antibody capable of specifically binding to human and / or cynomolgus monkey TSLP, said isolated anti-TSLP antibody comprising: a heavy chain variable domain (V H ), the VH It includes: a heavy chain complementarity determination region (HC-CDR)1, which contains SYGIX1 (SEQ ID NO: 108), wherein X1 is N or S; HC-CDR2, which contains VIX1PLX2X3VX4X5YAEKFQG (SEQ ID NO: 109), wherein X1 is V or I, X2 is V or L, X3 is G or D, X4 is T or P, and X5 is I or N; and HC-CDR3, which contains GX1EYFYWYFDL (SEQ ID NO: 110), wherein X1 is Q or A; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR)1, which includes X1GX2X3SDIGGYX4RVS (SEQ ID NO:111), wherein X1 is S or T, X2 is S or T, X3 is S, T, I or N, and X4 is N or D; LC-CDR2, which includes X1X2X3KRX4S (SEQ ID NO:112), wherein X1 is D, G or E, X2 is V, F or I, X3 is S or N, and X4 is P or S; and LC-CDR3, which includes X1SYAX2X3X4X5FX6X7 (SEQ ID NO:113), wherein X1 is S or T, X2 is G or S, X3 is T or G, X4 is D or H, X5 is T or I, X6 is I, G, V or A, and X7 is L, I or F.
[0015] In some embodiments, an isolated anti-TSLP antibody is provided, which comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequences shown in SEQ ID NO:2-3 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; HC-CDR2, comprising the amino acid sequences shown in any of SEQ ID NOs:10-12 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and HC-CDR3, comprising the amino acid sequences shown in any of SEQ ID NOs:19-20 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:29-34 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequences shown in SEQ ID NOs:42-47 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-60 or variants thereof, the variants comprising substitutions of up to about 3 amino acids.
[0016] In some embodiments, an isolated anti-TSLP antibody is provided, which comprises V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:73-78 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:91-97 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0017] In some embodiments, an isolated anti-TSLP antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:73. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:91. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:74. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:91. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iii)V H It contains V as shown in the amino acid sequence SEQ ID NO:75. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:91. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iv)V H It contains V as shown in the amino acid sequence SEQ ID NO:73. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:92. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (v)V HIt contains V as shown in the amino acid sequence SEQ ID NO:73. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:93. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (vi)V H It contains V as shown in the amino acid sequence SEQ ID NO:73. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:94. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (vii)V H It contains V as shown in the amino acid sequence SEQ ID NO:76. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:95. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (viii)V H It contains V as shown in the amino acid sequence SEQ ID NO:77. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:96. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; or (ix)V H It contains V as shown in the amino acid sequence SEQ ID NO:78. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:97. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0018] In some embodiments, an isolated anti-TSLP antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V HVariants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:29; LC-CDR2, which contains the amino acid sequence SEQ ID NO:42; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:54, or the V L (ii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:30; LC-CDR2, which contains the amino acid sequence SEQ ID NO:43; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:55, or the V L (iii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:31; LC-CDR2, which contains the amino acid sequence SEQ ID NO:44; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:56, or the V L (iv) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:32; LC-CDR2, which contains the amino acid sequence SEQ ID NO:45; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:57, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (v)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:11; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:33; LC-CDR2, which contains the amino acid sequence SEQ ID NO:45; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:58, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (vi)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:31; LC-CDR2, which contains the amino acid sequence SEQ ID NO:46; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:59, or the V L Variants whose LC-CDRs contain substitutions of up to about 5 amino acids; or (vii)V HThe V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:20, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:34; LC-CDR2, which contains the amino acid sequence SEQ ID NO:47; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:60, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0019] In some embodiments, any of the isolated anti-TSLP antibodies described above, the isolated anti-TSLP antibody comprises: V H It comprises any of the amino acid sequences shown in SEQ ID NOs:73-78 or variants thereof, said variants having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:73-78; and V L It comprises any of the amino acid sequences shown in SEQ ID NOs:91-97 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:91-97. In some embodiments, the isolated anti-TSLP antibody comprises: (i) V H It contains the amino acid sequence SEQ ID NO:73; and V L It contains the amino acid sequence SEQ ID NO:91; (ii)V H It contains the amino acid sequence SEQ ID NO:74; and V L It contains the amino acid sequence SEQ ID NO:91; (iii)V H It contains the amino acid sequence SEQ ID NO:75; and V L It contains the amino acid sequence SEQ ID NO:91; (iv)V H It contains the amino acid sequence SEQ ID NO:73; and V L It contains the amino acid sequence SEQ ID NO:92; (v)VH It contains the amino acid sequence SEQ ID NO:73; and V L It contains the amino acid sequence SEQ ID NO:93; (vi)V H It contains the amino acid sequence SEQ ID NO:73; and V L It contains the amino acid sequence SEQ ID NO:94; (vii)V H It contains the amino acid sequence SEQ ID NO:76; and V L It contains the amino acid sequence SEQ ID NO:95; (viii)V H It contains the amino acid sequence SEQ ID NO:77; and V L It contains the amino acid sequence SEQ ID NO:96; or (ix)V H It contains the amino acid sequence SEQ ID NO:78; and V L It contains the amino acid sequence SEQ ID NO:97.
[0020] On one hand, this application provides an isolated anti-TSLP antibody capable of specifically binding to human and / or cynomolgus monkey TSLP, said isolated anti-TSLP antibody comprising: a heavy chain variable domain (V H ), the V H It includes: a heavy chain complementarity determination region (HC-CDR)1 containing NYX1MT (SEQ ID NO: 114), where X1 is D or G; HC-CDR2 containing SITFASSYIYYADSVKG (SEQ ID NO: 13); and HC-CDR3 containing GGGAYX1GGSLDV (SEQ ID NO: 115), where X1 is H or Y; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR) 1, which includes RSSQSLLHX1X2X3YTYLH (SEQ ID NO: 116), wherein X1 is I or S, X2 is N or Y, and X3 is G or E; LC-CDR 2, which includes LVSX1RAS (SEQ ID NO: 117), wherein X1 is H or Y; and LC-CDR 3, which includes EQTLQTPX1X2 (SEQ ID NO: 118), wherein X1 is Y or F, and X2 is S or T.
[0021] In some embodiments, an isolated anti-TSLP antibody is provided, which comprises V H The V HContains: HC-CDR1, comprising the amino acid sequences shown in SEQ ID NO:4-5 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; HC-CDR2, comprising the amino acid sequences shown in any of SEQ ID NOs:13 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and HC-CDR3, comprising the amino acid sequences shown in any of SEQ ID NOs:21-22 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:35-37 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequences shown in SEQ ID NOs:48-49 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:61-63 or variants thereof, the variants comprising substitutions of up to about 3 amino acids.
[0022] In some embodiments, an isolated anti-TSLP antibody is provided, which comprises V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:79-81 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:98-100 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0023] In some embodiments, an isolated anti-TSLP antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:79. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:98. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:80. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:99.L Includes LC-CDR1, LC-CDR2 and LC-CDR3; or (iii)V H It contains V as shown in the amino acid sequence SEQ ID NO:81. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:100. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0024] In some embodiments, an isolated anti-TSLP antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:21, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:35; LC-CDR2, which contains the amino acid sequence SEQ ID NO:48; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:61, or the V L (ii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:22, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:36; LC-CDR2, which contains the amino acid sequence SEQ ID NO:48; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62, or the V L Variants whose LC-CDRs contain substitutions of up to about 5 amino acids; or (iii) V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:5; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:22, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:37; LC-CDR2, which contains the amino acid sequence SEQ ID NO:49; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:63, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0025] In some embodiments, any of the isolated anti-TSLP antibodies described above, the isolated anti-TSLP antibody comprises: V H It comprises any of the amino acid sequences shown in SEQ ID NOs:79-81 or variants thereof, said variants having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:79-81; and V L It comprises any of the amino acid sequences shown in SEQ ID NOs:98-100 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:98-100. In some embodiments, the isolated anti-TSLP antibody comprises: (i) V H It contains the amino acid sequence SEQ ID NO:79; and V L It contains the amino acid sequence SEQ ID NO:98; (ii)V H It contains the amino acid sequence SEQ ID NO:80; and V L It contains the amino acid sequence SEQ ID NO:99; or (iii)V H It contains the amino acid sequence SEQ ID NO:81; and V L It contains the amino acid sequence SEQ ID NO:100.
[0026] On one hand, this application provides an isolated anti-TSLP antibody capable of specifically binding to human and / or cynomolgus monkey TSLP, said isolated anti-TSLP antibody comprising: a heavy chain variable domain (VH ), the V H Includes: a heavy chain complementarity determination region (HC-CDR)1 containing SYAIS (SEQ ID NO: 6); HC-CDR2 containing MX1X2PLLGVTX3YAEKFQG (SEQ ID NO: 119), wherein X1 is L or I, X2 is V or I, and X3 is N or D; and HC-CDR3 containing GGX1NYLYWYFDL (SEQ ID NO: 120), wherein X1 is S or T; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR) 1, which contains TGTSSDIGGYNRX1S (SEQ ID NO:121), wherein X1 is V or I; LC-CDR 2, which contains X1VSKRPS (SEQ ID NO:122), wherein X1 is D or E; and LC-CDR 3, which contains SX1YAGTDTFVL (SEQ ID NO:123), wherein X1 is S or A.
[0027] In some embodiments, an isolated anti-TSLP antibody is provided, which comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:6 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:14-15 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:23-24 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and V L The V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in any of SEQ ID NOs:31 and 38 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NOs:42 and 45 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises the amino acid sequence shown in any of SEQ ID NOs:60 and 64 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids.
[0028] In some embodiments, an isolated anti-TSLP antibody is provided, which comprises V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:82-83 HIncludes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:101-102 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0029] In some embodiments, an isolated anti-TSLP antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:82. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:101. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; or (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:83. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:102. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0030] In some embodiments, an isolated anti-TSLP antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:6; HC-CDR2, which contains the amino acid sequence SEQ ID NO:14; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:23, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:38; LC-CDR2, which contains the amino acid sequence SEQ ID NO:42; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:60, or the V L Variants whose LC-CDRs contain substitutions of up to about 5 amino acids; or (ii) V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:6; HC-CDR2, which contains the amino acid sequence SEQ ID NO:15; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:24, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:31; LC-CDR2, which contains the amino acid sequence SEQ ID NO:45; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:64, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0031] In some embodiments, any of the isolated anti-TSLP antibodies described above, the isolated anti-TSLP antibody comprises: V H It comprises any of the amino acid sequences shown in SEQ ID NOs:82-83 or variants thereof, said variants having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:82-83; and V L It comprises any of the amino acid sequences shown in SEQ ID NOs:101-102 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:101-102. In some embodiments, the isolated anti-TSLP antibody comprises: (i) V H It contains the amino acid sequence SEQ ID NO:82; and V L It contains the amino acid sequence SEQ ID NO:101; or (ii) V H It contains the amino acid sequence SEQ ID NO:83; and V L It contains the amino acid sequence SEQ ID NO:102.
[0032] In some embodiments, an isolated anti-TSLP antibody is provided, having a Kd value of about 0.1 pM to about 1 nM that specifically binds to human TSLP.
[0033] In some embodiments, an isolated anti-TSLP antibody is provided that competitively binds specifically to TSLP, as described above. In some embodiments, an isolated anti-TSLP antibody is provided that specifically binds to the same epitope as described above.
[0034] In some embodiments, the isolated anti-TSLP antibody, as described above, comprises an Fc fragment. In some embodiments, the isolated anti-TSLP antibody is a full-length IgG antibody. In some embodiments, the isolated anti-TSLP antibody is a full-length IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the isolated anti-TSLP antibody is a chimeric, human, or humanized antibody. In some embodiments, the isolated anti-TSLP antibody is an antigen-binding fragment selected from Fab, Fab', F(ab')2, Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody, and linear antibody.
[0035] In some embodiments, an isolated nucleic acid molecule is provided, the nucleic acid molecule encoding any of the anti-TSLP antibodies described above. In some embodiments, a vector is provided, the vector comprising any of the nucleic acid molecules described above. In some embodiments, a host cell is provided, the host cell expressing any of the anti-TSLP antibodies described above, any of the nucleic acid molecules described above, or any of the vectors described above. In some embodiments, a method for preparing an anti-TSLP antibody is provided, comprising: a) culturing any of the host cells described above under conditions that enable efficient expression of anti-TSLP antibodies; and b) obtaining the expressed anti-TSLP antibody from the host cell. In some embodiments, a pharmaceutical composition is provided, comprising the isolated anti-TSLP antibody described above, a nucleic acid, a vector or isolated host cell, and a pharmaceutically acceptable vector.
[0036] In some embodiments, a method of treating a desired individual disease or condition is provided, comprising administering to the individual an effective amount of any of the anti-TSLP antibodies or pharmaceutical compositions described herein. In some embodiments, the use of the anti-TSLP antibodies or pharmaceutical compositions described herein in treating a disease or condition is provided. In some embodiments, the use of any of the anti-TSLP antibodies described herein in preparing a pharmaceutical composition for treating a desired individual disease or condition is provided. In some embodiments, the use of the anti-TSLP antibodies or pharmaceutical compositions described herein in manufacturing a medicament for treating a disease or condition is provided. In some embodiments, the disease or condition is TSLP-related, including inflammatory or autoimmune diseases or conditions. In some embodiments, the disease or condition is selected from the group consisting of asthma, chronic obstructive pulmonary disease, allergic rhinitis, allergic sinusitis, allergic conjunctivitis, eosinophilic esophagitis, and atopic dermatitis.
[0037] It also provides pharmaceutical compositions, kits, and manufactured products containing any of the anti-TSLP antibodies described above. Attached Figure Description
[0038] Figure 1A-1F The results shown are the binding affinity of an exemplary anti-TSLP antibody to human TSLP, analyzed by ELISA.
[0039] Figures 2A-2F The results shown are the binding affinity of an exemplary anti-TSLP antibody to cynomolgus monkey TSLP, analyzed by ELISA.
[0040] Figure 3A The results shown are the affinity Kd between the detected anti-TSLP antibodies TSLP-0107 or TSLP-0202 and human TSLP. Figure 3B The results shown represent the affinity Kd between the detected anti-TSLP antibodies TSLP-0107 or TSLP-0202 and cynomolgus monkey TSLP.
[0041] Figure 4 The results shown are the cross-reactivity results of an exemplary anti-TSLP antibody with its homolog IL-7 analyzed by ELISA.
[0042] Figure 5A The results show that the rabbit anti-TSLP polyclonal antibody can bind to human short TSLP. Figure 5B The results show that the rabbit anti-TSLP polyclonal antibody can bind to the full-length human TSLP. Figure 5C The results show that the anti-TSLP antibody TSLP-01 cannot bind to human short TSLP. Figure 5D The results show that the anti-TSLP antibody TSLP-01 cannot bind to the full-length human TSLP.
[0043] Figure 6 The results shown are from the detection of an exemplary anti-TSLP antibody inhibiting TARC release in human PBMCs.
[0044] Figures 7A-7D The results shown are pharmacokinetic analysis results of rats after subcutaneous injection of different antibodies or exemplary anti-TSLP antibodies at 30 mg / kg or 10 mg / kg, as measured by ELISA. Figure 7A The pharmacokinetic results are shown for rats after subcutaneous injection of 30 mg / kg of anti-TSLP antibody TSLP-0107 or AMG157. Figure 7B The pharmacokinetic results are shown for rats after subcutaneous injection of 10 mg / kg of anti-TSLP antibody TSLP-0107 or AMG157. Figure 7C The pharmacokinetic results are shown for rats after subcutaneous injection of 30 mg / kg of anti-TSLP antibody TSLP-0202 or AMG157. Figure 7A The pharmacokinetic results are shown for rats after subcutaneous injection of 10 mg / kg of anti-TSLP antibody TSLP-0202 or AMG157.
[0045] Detailed description of this application
[0046] This application provides an isolated anti-TSLP antibody that specifically binds to human and / or cynomolgus monkey TSLP. Through a combination of scFv phage library screening, affinity maturation, and appropriately designed biochemical and biological experiments, this invention has identified a highly efficient antibody molecule capable of binding to human and / or cynomolgus monkey TSLP and inhibiting the interaction of human and / or cynomolgus monkey TSLP with its receptor. The results presented herein demonstrate, in various biological experiments, that the antibody provided in this application exhibits high affinity for human and / or cynomolgus monkey TSLP compared to the known anti-TSLP antibody AMG157 (Amgen), and surprisingly, is even more effective than AMG157.
[0047] The anti-TSLP antibodies provided in this application include, for example, full-length anti-TSLP antibodies, anti-TSLP single-chain antibodies (scFvs), anti-TSLP Fc fusion proteins, multispecific (e.g., bispecific) anti-TSLP antibodies, anti-TSLP immunoconjugates, and the like.
[0048] It also provides nucleic acids encoding anti-TSLP antibodies, compositions containing anti-TSLP antibodies, and methods for preparing and using the anti-TSLP antibodies described in this application.
[0049] definition
[0050] As described herein, “treatment” or “treating” is a method of obtaining a beneficial or desired outcome, including clinical outcomes. For the purposes of this application, the beneficial or desired clinical outcomes include, but are not limited to, one or more of the following: relief of one or more symptoms caused by a disease, reduction of disease severity, stabilization of the disease (e.g., prevention or delay of disease exacerbation), prevention or delay of disease spread (e.g., metastasis), prevention or delay of disease recurrence, delay or slowing of disease progression, improvement of disease status, relief of the disease (partial or complete), reduction of the dosage of one or more other medications required to treat the disease, delay of disease progression, improvement or enhancement of quality of life, weight gain, and / or prolonged survival. Additionally, “treatment” also includes a reduction in disease pathological outcomes (e.g., tumor volume in the case of cancer). The methods of this application consider any one or more aspects of these treatments.
[0051] The term "antibody" includes both full-length antibodies and their antigen-binding fragments. A full-length antibody consists of two heavy chains and two light chains. Variable regions in both the light and heavy chains are responsible for antigen binding. The variable regions in both chains typically include three hypervariable loops, referred to as complementarity-determining regions (CDRs) (light chain (LC) CDRs include LC-CDR1, LC-CDR2, and LC-CDR3; heavy chain (HC) CDRs include HC-CDR1, HC-CDR2, and HC-CDR3). The CDR boundaries of the antibodies or antigen-binding fragments disclosed herein can be defined or identified according to the Kabat, Chothia, or Al-Lazikani conventions (Al-Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991). Three CDR regions of the heavy or light chain are inserted between flanking segments called framework regions (FRs), which are more conserved than the CDR regions and form a scaffold supporting the hypervariable loop. The constant regions of the heavy and light chains do not participate in antigen binding but exhibit a variety of effector functions. Antibodies are classified or typed based on the amino acid sequence of their heavy chain constant regions. The five major classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, characterized by having α, δ, ε, γ, and μ-type heavy chains, respectively. Several major antibody classes are subclassed, such as IgG1 (γ1 heavy chain), IgG2 (γ2 heavy chain), IgG3 (γ3 heavy chain), IgG4 (γ4 heavy chain), IgA1 (α1 heavy chain n), or IgA2 (α2 heavy chain).
[0052] As described herein, the term "antigen-binding fragment" includes antibody fragments, including, for example, double-chain antibodies (diabody), Fab, Fab', F(ab')2, Fv fragments, disulfide-stabilized Fv fragments (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized double-chain antibodies (ds double-chain antibodies), single-chain Fv (scFv), scFv dimers (divalent double-chain antibodies), multispecific antibodies composed of antibody fragments containing one or more CDRs, single-domain antibodies, nanobodies, domain antibodies, divalent domain antibodies, or any other antibody fragment capable of binding to an antigen but not containing a complete antibody structure. Antigen-binding fragments also include fusion proteins comprising antibody fragments as described above. Antigen-binding fragments also include fusion proteins comprising antibody fragments as described above. Antigen-binding fragments are capable of binding the same antigen to a parent antibody or a parent antibody fragment (such as a parental scFv). In some embodiments, the antigen-binding fragment may include one or more CDRs from a specific human antibody, which are transplanted into the frame region from one or more different human antibodies.
[0053] As described herein, the term "epitope" refers to a specific atom or amino acid group on an antigen that an antibody or antibody portion binds to. If two antibodies or antibody portions exhibit competitive binding to an antigen, they may bind to the same epitope on the antigen.
[0054] As described herein, when the first antibody inhibits the binding of the second antibody to the TSLP target by at least 50% (e.g., at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%) at an equimolar concentration, the first antibody “competitively” binds to the TSLP target with the second antibody, and vice versa. PCT Publication WO 03 / 48731 describes a high-throughput antibody “epitope classification” method based on cross-competition.
[0055] As described herein, the terms "specifically bind," "specifically recognize," or "specific to" refer to measurable and reproducible interactions, such as antibody binding to a target that confirms the presence of that target in a heterogeneous group of molecules, including biomolecules. For example, an antibody's ability to specifically recognize a target (which may be an epitope) means that the antibody binds to that target with higher affinity, stronger binding, and / or more persistent binding compared to binding to other targets. In some embodiments, an antibody that specifically recognizes an antigen reacts with one or more antigenic determinants of the antigen with a binding affinity at least 10 times greater than its binding affinity to other targets.
[0056] As described herein, an “isolated” anti-TSLP antibody is an anti-TSLP antibody that (1) is not related to naturally occurring proteins, (2) does not contain other proteins of the same origin, (3) is expressed by cells of a different species, or (4) does not exist in nature.
[0057] As described herein, the term “isolated nucleic acid” refers to a nucleic acid or combination thereof of genomic, cDNA, or synthetic origin. Depending on its origin, the “isolated nucleic acid” (1) is not related to all or part of the polynucleotides in “isolated nucleic acids” found in nature, (2) can be operatively linked to polynucleotides not naturally associated with it, or (3) does not exist in nature as part of a longer sequence.
[0058] As described in this article, the term "CDR" or "complementarity-determining region" refers to a discontinuous antigen-binding site found within the variable domains of heavy and light chain polypeptides. In the literature Kabat et al., J. Biol. Chem. 252: 6609-6616 (1977); Kabat et al., USDept. 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. al., J. Mol. Biol., 273: 927-948 (1997); MacCallum et al., J. Mol. Biol. 262: 732-745 (1996); Abhinandan and Martin, Mol. Immunol., 45: 3832-3839 (2008); Lefranc MPet These specific regions have been described in al., Dev. Comp. Immunol., 27:55-77 (2003); and Honegger and Plückthun, J. Mol. Biol., 309:657-670 (2001), where these definitions include overlaps or subsets of amino acid residues when compared with each other. However, any definition used to indicate a CDR of an antibody or transplanted antibody or its variants is included within the scope of the terminology defined and used herein. Table 1 lists the positions of the amino acid residues included in the CDRs defined by the aforementioned references for comparison. Algorithms and interfaces for CDR prediction are known in the art, including, for example, those described in Abhinandan and Martin, Mol. Immunol., 45:3832-3839 (2008); Ehrenmann F. et al., Nucleic Acids Res., 38:D301-D307 (2010); and Adolf-Bryfogle J. et al., Nucleic Acids Res., 43:D432-D438 (2015). The entire contents of the references cited in this paragraph are incorporated herein by reference for the purposes of this application and one or more claims that may be included herein.
[0059] Table 1: CDR Definition
[0060]
[0061] 1 The amino acid residue numbering follows the nomenclature method described in Kabat et al. above.
[0062] 2 The amino acid residue numbering follows the nomenclature method described in Chothia et al. above.
[0063] 3 The amino acid residue numbering follows the nomenclature method described in MacCallum et al. above.
[0064] 4 The amino acid residue numbering follows the nomenclature method described in Lefranc et al. above.
[0065] 5 The amino acid residue numbering follows the nomenclature method described in Honegger and Plückthun.
[0066] The term "chimeric antibody" refers to an antibody whose heavy chain and / or light chain portion is identical or homologous to the corresponding sequence in an antibody from a particular species or belonging to a particular antibody species or subclass, while the remaining portion of this chain is identical or homologous to the corresponding sequence in an antibody from another genus or belonging to another antibody species or subclass, as well as fragments of such antibodies, provided they possess the biological activity described in this application (see US Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)).
[0067] "Fv" is the smallest antibody fragment containing a complete antigen recognition and binding site. This fragment is a dimer formed by a heavy chain variable domain and a light chain variable domain tightly and non-covalently linked. The folding of these two domains derives six hypervariable rings (three in the light chain and three in the heavy chain), which provide the antibody with amino acid residues for binding to the antigen and confer the antibody's specificity for antigen binding. However, even a single variable domain (or half of the Fv fragment, containing only three antigen-specific CDRs) can recognize and bind to antigens, although its affinity is lower than that of the complete binding site.
[0068] "Single-chain Fv", also abbreviated as "sFv" or "scFv", is a type of Fv containing V molecules linked together to form a single polypeptide chain. H and V L Antibody fragments of antibody domains. In some embodiments, the scFv polypeptide further includes V H and V LThe linker polypeptide between the domains allows scFv to form an ideal structure for antigen binding. For an overview of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).
[0069] The term "diabodies" refers to antibodies that are formed in V... H and V L Small antibody fragments are prepared by constructing scFv fragments (see above) using short linkers (e.g., 5–10 residues) between domains. This allows the variable domains to pair between chains rather than within chains, resulting in a bivalent fragment, i.e., a fragment with two antigen-binding sites. Bispecific double-chain antibodies are heterodimers of two “crossed” scFv fragments, where the V0 of the two antibodies... H and V L The domains are located on different polypeptide chains. Double-chain antibodies are fully described in EP 404,097; WO 93 / 11161; Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).
[0070] The “humanized” form of non-human (e.g., rodent) antibodies is a chimeric antibody, which includes a minimal sequence derived from the non-human antibody. In most cases, humanized antibodies are human immunoglobulins (receptor antibodies), where the hypervariable region (HVR) residues of the receptor antibody are replaced by hypervariable region residues from non-human species such as mice, rats, rabbits, or non-human primates (donor antibodies) that possess desirable antibody specificity, affinity, and performance. In some cases, residues in the human immunoglobulin framework region (FR) are replaced by corresponding non-human residues. Additionally, humanized antibodies may include residues not present in either the receptor or donor antibody. These modifications can further improve antibody performance. Typically, humanized antibodies substantially contain at least one, usually two, variable domains, where all or substantially all of the hypervariable loops correspond to the hypervariable loops of a non-human immunoglobulin, and all or substantially all of the framework regions are human immunoglobulin sequences. Humanized antibodies optionally also include at least a portion of the immunoglobulin constant region (Fc), typically the constant region of a human immunoglobulin. For details, please refer to 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).
[0071] The "percentage of amino acid sequence identity (%)" or "homology" of the peptide and antibody sequences identified in this paper is defined as the percentage of identical amino acid residues in a candidate sequence compared to a peptide sequence, assuming that conserved substitutions are part of sequence identity. The percentage of amino acid sequence identity can be determined using various alignment methods within the scope of the art, such as publicly available computer software like BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. Those skilled in the art can determine suitable parameters for measuring alignment, including any algorithm required to maximize alignment across the full length of the compared sequences. However, for the purposes of this paper, the percentage of amino acid sequence identity values were generated using the sequence alignment computer program MUSCLE (Edgar, RC, Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, RC, BMC Bioinformatics 5(1):113, 2004).
[0072] The term "Fc receptor" or "FcR" is used to describe receptors that bind to the Fc region of antibodies. In some embodiments, the FcR described in this application is an FcR that binds to IgG antibodies (a type of γ receptor), including receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternative splicing forms of these receptors. FcγRII receptors include FcγRIIA ("activating receptor") and FcγRIIB ("inhibiting receptor"), which have similar amino acid sequences and differ primarily in their cytoplasmic domains. The cytoplasmic domain of the activating receptor FcγRIIA contains an immunoreceptor tyrosine activation motif (ITAM). The cytoplasmic domain of the inhibitory receptor FcγRIIB contains an immunoreceptor tyrosine inhibitory motif (ITIM) (see M.in.). Annu.Rev.Immunol.15:203-234 (1997)). The term also includes allotypes, such as FcγRIIIA allotypes: FcγRIIIA-Phe158, FcγRIIIA-Val158, FcγRIIA-R131 and / or FcγRIIA-H131. FcRs are described in Ravetch and Kinet, Annu.Rev.Immunol 9:457-92 (1991) and Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J.Lab.Clin.Med.126:330-41 (1995). In this application, the term FcR covers other types of FcRs, including those to be identified in the future. The term FcR also includes the neonatal receptor FcRn, which is responsible for transferring maternal IgGs to the newborn (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)).
[0073] The term "FcRn" refers to the neonatal Fc receptor (FcRn). FcRn is structurally similar to the major histocompatibility complex (MHC), consisting of an α-chain non-covalently bound to β2-microglobulin. The various functions of the neonatal Fc receptor FcRn are described in Ghetie and Ward (2000) Annu. Rev. Immunol. 18, 739-766. FcRn plays an important role in the passive transport of immunoglobulin IgGs from the mother to the newborn and in regulating serum IgG levels. As a rescue receptor, FcRn can bind and transport endocytotic IgG in its intact form both intracellularly and intercellularly, protecting it from the default degradation pathway.
[0074] The "CH1 domain" of the human IgG Fc region typically extends from amino acid 118 to amino acid 215 (EU numbering system).
[0075] The "hinge region" is typically defined as extending from Glu at position 216 to Pro at position 230 of human IgG1 (Burton, Molec. Immunol. 22:161-206 (1985)). By placing the first and last cysteine residues that form the inter-heavy chain disulfide bond at the same positions as IgG1, it is possible to align the hinge regions of other IgG isotypes with the IgG1 sequence.
[0076] The "CH2 domain" of the human IgG Fc region typically extends from amino acid 231 to amino acid 340. The unique feature of the CH2 domain is that it does not pair tightly with another region; instead, two N-terminal branched sugar chains are inserted between the two CH2 domains of the intact native IgG molecule. It is speculated that the sugars may act as a substitute for domain-to-domain pairing, helping to maintain the stability of the CH2 domain. (Burton, Molec Immunol. 22:161-206 (1985)).
[0077] The “CH3” domain includes the extension from the C-terminal residue to the CH2 domain within the Fc region (from amino acid 341 to the C-terminus of the antibody sequence, typically amino acid 446 or 447 of IgG).
[0078] "Functional Fc fragments" possess the "effective functions" inherent in the natural Fc region sequence. Exemplary "effective functions" include C1q binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; and downregulation of cell surface receptors (such as B cell receptors; BCR). These effector functions typically require the Fc region to bind to a binding domain (such as the antibody variable region) and can be evaluated using a variety of experimental methods known in the art.
[0079] Antibodies with IgG Fc variants exhibiting "altered" FcR binding affinity or ADCC activity show enhanced or weakened FcR binding activity (such as FcγR or FcRn) and / or ADCC activity compared to the parent peptide or peptides containing the native Fc sequence. Fc variants exhibiting "enhanced binding" to FcRs have higher binding affinity (e.g., lower apparent Kd or IC50) to at least one FcR compared to the parent peptide or peptides containing the native IgG Fc sequence. 50(Value). In some embodiments, the binding affinity is enhanced by 3 times compared to the parent peptide, for example, 5, 10, 25, 50, 60, 100, 150, 200, or even up to 500 times, or the binding affinity is increased by 25% to 1000%. Fc variants exhibit “reduced binding” to FcRs, having a lower affinity for at least one FcR compared to the parent peptide (e.g., higher apparent Kd or IC). 50 (Value). Compared with the parent peptide, its binding ability is reduced by 40% or more.
[0080] Antibody-dependent cell-mediated cytotoxicity (ADCC) is a form of cytotoxicity in which secreted Ig binds to Fc receptors (FcRs) present on certain cytotoxic cells, such as natural killer (NK) cells, neutrophils, and macrophages. This allows these cytotoxic effector cells to specifically bind to target cells carrying antigens and subsequently kill the target cells using cytotoxins. Antibodies "arm" the cytotoxic cells and are essential for this killing. Among the main cell types mediating ADCC, NK cells express only FcγRIII, while monocytes express FcγRI, FcγRII, and FcγRIII. The expression of FcRs on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991). The ADCC activity of target molecules can be assessed by in vitro ADCC experiments, described in U.S. Patent Nos. 5,500,362 or 5,821,337. Effector cells suitable for such experiments include peripheral blood mononuclear cells (PBMCs) and natural killer cells (NK cells). Alternatively, or additionally, the ADCC activity of the target molecule can also be assessed in vivo, as described, for example, in animal models disclosed in Clynes et al. PNAS (USA) 95:652-656 (1998).
[0081] Peptides containing Fc region variants exhibit "enhanced ADCC activity" or are more effective at mediating ADCC effects in the presence of human effector cells compared to peptides containing wild-type IgG Fc or parental peptides. These peptides, when experimentally present in substantially the same quantity as those containing wild-type IgG Fc (or parental peptides), mediate ADCC more effectively both in vitro and in vivo. Such variants are typically identified using any in vitro ADCC assay known in the art, such as experiments or methods for identifying ADCC activity, for example in animal models. In some embodiments, such variants mediate ADCC with a 5 to 100-fold, for example, 25 to 50-fold, efficiency improvement compared to wild-type Fc (or parental peptide).
[0082] "Complement-dependent cytotoxicity" or "CDC" refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (C1q) to an antibody (a subclass with a suitable structure) that binds to a homologous antigen. To assess complement activation, CDC assays can be performed, as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996). Peptide variants with altered Fc region amino acid sequences and increased or decreased C1q binding capacity are described in U.S. Patent Nos. 6,194,551B1 and WO99 / 51642. The contents of these patent publications are expressly incorporated herein by reference. See also Idusogie et al. J. Immunol. 164:4178-4184 (2000).
[0083] Unless otherwise stated, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate forms of each other and encode the same amino acid sequence. Nucleotide sequences encoding proteins or RNA may also include introns; for example, nucleotide sequences encoding proteins may contain introns in certain forms.
[0084] The term "operationally ligated" refers to a functional link between a regulatory sequence and a heterologous nucleotide sequence, thereby enabling the latter to be expressed. For example, the first and second nucleotide sequences are operably ligated when they are in a functional relationship. Similarly, if a promoter affects the transcription or expression of a coding sequence, the promoter and coding sequence are operably ligated. Typically, operably ligated DNA sequences are contiguous, and, if necessary, two protein-coding regions can be ligated within the same reading frame.
[0085] "Homology" refers to the sequence similarity or identity between two polypeptides or two nucleic acid molecules. If the same position in two compared sequences is the same base or amino acid monomer subunit, for example, if both DNA molecules have adenine at the same position, then the two DNA molecules are homologous at that position. The percentage of homology between two sequences is a function calculated by multiplying the number of matching or homologous positions in the two sequences to the total number of positions, and then multiplying by 100. For example, if 6 out of 10 positions in two sequences are matching or homologous, then the two sequences are 60% homologous. For instance, the DNA sequences ATTGCC and TATGGC have 50% homology. Generally, when comparing two sequences, the goal is to obtain the maximum homology.
[0086] The “effective amount” of the anti-TSLP antibody or composition disclosed herein refers to an amount sufficient to achieve a specific purpose. The “effective amount” can be determined empirically and by known methods associated with said purpose.
[0087] The term "therapeutic effective amount" refers to the amount of the anti-TSLP antibody or composition disclosed herein that is effective in "treating" an individual's disease or condition. In the case of cancer, the therapeutically effective amount of the anti-TSLP antibody or composition disclosed herein can reduce the number of cancer cells; reduce tumor size and weight; inhibit (i.e., slowly and preferably stop) cancer cell infiltration into surrounding organs; inhibit (i.e., slowly and preferably stop) tumor metastasis; inhibit tumor growth to a certain extent; and / or alleviate one or more symptoms associated with cancer to a certain extent. Within the range of preventing growth and / or killing existing cancer cells, the anti-TSLP antibody or composition disclosed herein may be cytotoxic and / or cytosolic. In some embodiments, the therapeutically effective amount is an amount that inhibits growth. In some embodiments, the therapeutically effective amount is an amount that prolongs patient survival. In some embodiments, the therapeutically effective amount is an amount that improves patient progression-free survival.
[0088] As used herein, "pharmaceuticalally acceptable" or "pharmacologically compatible" means a material that has no biological activity or other undesirable properties, such as the ability to be incorporated into a pharmaceutical composition given to a patient without causing significant adverse biological reactions, or that does not interact harmfully with any other components contained in the composition. Pharmaceutically acceptable carriers or excipients preferably meet the required standards for toxicological and manufacturing testing and / or are included in the inactive ingredient guidance prepared by the U.S. Food and Drug Administration.
[0089] The embodiments of this application described herein should be understood to include embodiments that are “composed of” and / or “substantially composed of”.
[0090] In this article, “about” is used to refer to a numerical value or parameter, including (and descriptions) variations for that value or parameter itself. For example, a description involving “about X” includes a description of “X”.
[0091] As used in this article, mentioning "not" a value or parameter usually means and describes something other than a certain value or parameter. For example, "This method cannot be used to treat type X cancer" means that this method is generally used to treat other types of cancer besides type X.
[0092] Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” used herein and in the claims include plural objects.
[0093] Anti-TSLP antibody
[0094] On one hand, this application provides anti-TSLP antibodies that specifically bind to human and / or cynomolgus monkey TSLP. The anti-TSLP antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules comprising heavy chain and / or light chain CDRs as described herein. On the other hand, this application provides isolated antibodies that bind to TSLP. Anticipated anti-TSLP antibodies include, for example, full-length anti-TSLP antibodies (such as full-length IgG1 or IgG4), anti-TSLP single-chain antibodies, anti-TSLP Fc fusion proteins, multispecific (such as bispecific) anti-TSLP antibodies, anti-TSLP immunoconjugates, and the like. In some embodiments, the anti-TSLP antibody is a full-length antibody (such as full-length IgG1 or IgG4) or its antigen-binding fragment that specifically binds to TSLP. In some embodiments, the anti-TSLP antibody is Fab, Fab', F(ab')2, Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody, or linear antibody. In some embodiments, an antibody that specifically binds to TSLP means that the antibody's affinity for TSLP is at least 10 times greater than its affinity for binding to non-target antibodies (including, for example, 10, 10). 2 10 3 10 4 10 5 10 6 , or 10 7 (Multiple times). In some embodiments, non-target refers to an antigen that is not a TSLP. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence-activated cell sorting (FACS) analysis, or radioimmunoprecipitation (RIA). Kd value can be determined by methods known in the art, such as surface plasmon resonance (SPR) technology or biolayer interference (BLI) technology.
[0095] While this document discusses anti-TSLP antibodies containing human sequences (e.g., human heavy and light chain variable domains containing human CDR sequences), non-human anti-TSLP antibodies are also considered. In some embodiments, non-human anti-TSLP antibodies comprise the human CDR sequence and non-human frame region sequence of the anti-TSLP antibodies described herein. In some embodiments, the non-human frame region sequence comprises any sequence used to generate heavy and / or light chain variable domains using one or more human CDR sequences as described herein, including, for example, mammals such as mice, rats, rabbits, pigs, cattle (e.g., bulls, buffalo), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., apes, macaques), etc. In some embodiments, non-human anti-TSLP antibodies comprise anti-TSLP antibodies generated by transplanting one or more human CDR sequences as described herein into a non-human frame region (e.g., a mouse or chicken frame region sequence).
[0096] An exemplary natural human TSLP has a complete amino acid sequence comprising or consisting of the amino acid sequence shown in SEQ ID NO: 128. An exemplary modified human TSLP has an amino acid sequence comprising or consisting of the amino acid sequence shown in SEQ ID NO: 129.
[0097] In some embodiments, the anti-TSLP antibody described herein specifically recognizes epitopes in human TSLP. In some embodiments, the anti-TSLP antibody cross-reacts with TSLP from species other than humans. In some embodiments, the anti-TSLP antibody is completely specific to human TSLP and does not cross-react with TSLP from other non-human species.
[0098] In some embodiments, the anti-TSLP antibody cross-reacts with at least one allelic variant of the TSLP protein (or a fragment thereof). In some embodiments, the allelic variant has up to 30 amino acid substitutions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) compared to the naturally occurring TSLP protein (or a fragment thereof) (e.g., conserved substitutions). In some embodiments, the anti-TSLP antibody does not cross-react with any allelic variant of the TSLP protein (or a fragment thereof).
[0099] In some embodiments, the anti-TSLP antibody cross-reacts with at least one interspecies variant of the TSLP protein. In some embodiments, for example, the TSLP protein (or a fragment thereof) is human TSLP, and the interspecies variant of the TSLP protein (or a fragment thereof) is a variant found in cynomolgus monkeys. In some embodiments, the anti-TSLP antibody does not cross-react with any interspecies variant of the TSLP protein.
[0100] In some embodiments, any anti-TSLP antibody as described herein includes an antibody heavy chain constant region and an antibody light chain constant region. In some embodiments, the anti-TSLP antibody includes an IgG1 type heavy chain constant region. In some embodiments, the anti-TSLP antibody includes an IgG2 type heavy chain constant region. In some embodiments, the anti-TSLP antibody includes an IgG3 type heavy chain constant region. In some embodiments, the anti-TSLP antibody includes an IgG4 type heavy chain constant region. In some embodiments, the heavy chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:124. In some embodiments, the heavy chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:125. In some embodiments, the anti-TSLP antibody includes a λ light chain constant region. In some embodiments, the anti-TSLP antibody includes a κ light chain constant region. In some embodiments, the light chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:126. In some embodiments, the anti-TSLP antibody includes a λ light chain constant region. In some embodiments, the light chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:127. In some embodiments, the anti-TSLP antibody comprises an antibody heavy chain variable domain and an antibody light chain variable domain.
[0101] In some embodiments, the anti-TSLP antibody comprises V H The V H The HC-CDR1 comprises SGYGWS (SEQ ID NO:1); HC-CDR2 comprises YX1SYYGSX2SYNPSLKS (SEQ ID NO:103), wherein X1 is I or F and X2 is I or T; and HC-CDR3 comprises TNLLYFX1X2 (SEQ ID NO:104), wherein X1 is D or E and X2 is S or Y; and a light chain variable structural domain (V L ), the V LIt includes: a light chain complementarity determination region (LC-CDR)1, which includes RASQX1X2SX3X4LA (SEQ ID NO:105), wherein X1 is G or S, X2 is V or I, X3 is N or S, and X4 is N or Y; LC-CDR2, which includes DX1SX2X3X4X5 (SEQ ID NO:106), wherein X1 is A or T, X2 is S or N, X3 is R or L, X4 is A or Q, and X5 is T or S; and LC-CDR3, which includes QQYSX1WPX2YX3 (SEQ ID NO:107), wherein X1 is D or N, X2 is Q or E, and X3 is T or S.
[0102] In some embodiments, the anti-TSLP antibody comprises V H The V H It comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:1 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); HC-CDR2, which comprises the amino acid sequence shown in any of SEQ ID NOs:7-9 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and HC-CDR3, which comprises the amino acid sequence shown in any of SEQ ID NOs:16-18 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).
[0103] In some embodiments, the anti-TSLP antibody comprises V H The V H It comprises: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:1; HC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:7-9; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:16-18.
[0104] In some embodiments, the anti-TSLP antibody comprises V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:25-28 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:39-41 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:50-53 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
[0105] In some embodiments, the anti-TSLP antibody comprises V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:25-28; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:39-41; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:50-53.
[0106] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:1 or a variant thereof, said variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:7-9 or a variant thereof, said variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:16-18 or a variant thereof, said variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:25-28 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:39-41 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:50-53 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
[0107] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:1; HC-CDR2, which contains the amino acid sequences shown in any of SEQ ID NOs:7-9; and HC-CDR3, which contains the amino acid sequences shown in any of SEQ ID NOs:16-18; and V L The V LIt comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:25-28; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:39-41; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:50-53.
[0108] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:7; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:25; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:50, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0109] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:7; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:25, LC-CDR2, which contains the amino acid sequence SEQ ID NO:39, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:50.
[0110] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:25; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:51, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0111] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:25; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:51.
[0112] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:17, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:26; LC-CDR2, which contains the amino acid sequence SEQ ID NO:40; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:52, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0113] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:17; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:26; LC-CDR2, which contains the amino acid sequence SEQ ID NO:40; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:52.
[0114] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:27; LC-CDR2, which contains the amino acid sequence SEQ ID NO:41; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:52, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0115] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:27; LC-CDR2, which contains the amino acid sequence SEQ ID NO:41; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:52.
[0116] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:9; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:28; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:52, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0117] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:9; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:16; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:28; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:52.
[0118] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:18, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:27; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:53, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0119] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:18; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:27; LC-CDR2, which contains the amino acid sequence SEQ ID NO:39; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:53.
[0120] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence shown in SEQ ID NOs:1, 7-9, 16-18 or variants thereof, said variants containing substitutions of up to about 5 amino acids; and V L The V L Contains the amino acid sequence shown in SEQ ID NOs:25-28, 39-41, 50-53 or variants thereof, said variants containing substitutions of up to about 5 amino acids. In some embodiments, the anti-TSLP antibody contains V H The V H Contains the amino acid sequences shown in SEQ ID NOs:1, 7-9, 16-18; and V L The V L It contains the amino acid sequences shown in SEQ ID NOs:25-28, 39-41, and 50-53.
[0121] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:1, 7, and 16, or containing V with up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:25, 39, and 50, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:1, 7, and 16; and V L The V L It contains amino acid sequences SEQ ID NOs:25, 39 and 50.
[0122] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:1, 8, and 16, or containing V with up to 5 amino acid substitutions. H Variant; and VL The V L Containing amino acid sequences SEQ ID NOs:25, 39, and 51, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:1, 8, and 16; and V L The V L It contains amino acid sequences SEQ ID NOs:25, 39 and 51.
[0123] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:1, 8, and 17, or containing V with up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:26, 40, and 52, or V containing up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:1, 8, and 17; and V L The V L It contains amino acid sequences SEQ ID NOs:26, 40 and 52.
[0124] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:1, 8, and 16, or containing V with up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:27, 41, and 52, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:1, 8, and 16; and V L The V L It contains amino acid sequences SEQ ID NOs:27, 41 and 52.
[0125] In some embodiments, the anti-TSLP antibody comprises V H The VH Containing amino acid sequences SEQ ID NOs:1, 9, and 16, or V containing up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:28, 39, and 52, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:1, 9, and 16; and V L The V L It contains amino acid sequences SEQ ID NOs:28, 39 and 52.
[0126] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:1, 8, and 18, or containing V with up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:27, 39, and 53, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:1, 8, and 18; and V L The V L It contains amino acid sequences SEQ ID NOs:27, 39 and 53.
[0127] In some embodiments, the anti-TSLP antibody comprises V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:65-72 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:84-90 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0128] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains V as shown in SEQ ID NO:65, an amino acid sequenceH It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in the amino acid sequence SEQ ID NO:66 H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:67 of the amino acid sequence H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:68, an amino acid sequence H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in the amino acid sequence SEQ ID NO:69 H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:70 H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:71 H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:72, an amino acid sequence H It contains one, two, or three HC-CDRs.
[0129] In some embodiments, the anti-TSLP antibody comprises V L The V L Contains V as shown in SEQ ID NO:84, an amino acid sequence L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody comprises V as shown in SEQ ID NO:85 of the amino acid sequence. L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains VL The V L Contains V as shown in SEQ ID NO:86 of the amino acid sequence L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains V L The V L Contains V as shown in SEQ ID NO:87, an amino acid sequence L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains V L The V L Contains V as shown in SEQ ID NO:88, an amino acid sequence L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains V L The V L Contains V as shown in SEQ ID NO:89 of the amino acid sequence L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains V L The V L Contains V as shown in SEQ ID NO:90 L It may contain one, two, or three LC-CDRs.
[0130] In some embodiments, the anti-TSLP antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:65. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:84. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:65. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:85. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:66. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and VL It contains V as shown in the amino acid sequence SEQ ID NO:84. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:66. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:85. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:67. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:84. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:67. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:85. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:68. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:84. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:68. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:85. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V.H It contains V as shown in the amino acid sequence SEQ ID NO:69. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:86. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:70. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:87. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:69. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:88. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:71. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:89. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:72. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:90. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0131] In some embodiments, the anti-TSLP antibody comprises V H The V HContains any of the amino acid sequences shown in SEQ ID NOs:65-72 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:65-72, and V L The V L The antibody comprises any of the amino acid sequences shown in SEQ ID NOs:84-90 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:84-90. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:65-72, and V L The V L It contains any of the amino acid sequences shown in SEQ ID NOs:84-90.
[0132] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:65 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:65, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:84 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:84. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:65, and V L The V L It contains the amino acid sequence SEQ ID NO:84.
[0133] In some embodiments, the anti-TSLP antibody comprises V H The V HContains the amino acid sequence SEQ ID NO:65 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:65, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:85 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:85. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:65, and V L The V L It contains the amino acid sequence SEQ ID NO:85.
[0134] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:66 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:66, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:84 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:84. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:66, and V L The V L It contains the amino acid sequence SEQ ID NO:84.
[0135] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:66 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:66, and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:85 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:85. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:66, and V L The V L It contains the amino acid sequence SEQ ID NO:85.
[0136] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:67 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:67, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:84 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:84. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:67, and V L The V L It contains the amino acid sequence SEQ ID NO:84.
[0137] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:67 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:67, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:85 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:85. In some embodiments, the anti-TSLP antibody comprises V H The VH Contains the amino acid sequence SEQ ID NO:67, and V L The V L It contains the amino acid sequence SEQ ID NO:85.
[0138] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:68 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:68, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:84 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:84. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:68, and V L The V L It contains the amino acid sequence SEQ ID NO:84.
[0139] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:68 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:68, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:85 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:85. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:68, and V L The V L It contains the amino acid sequence SEQ ID NO:85.
[0140] In some embodiments, the anti-TSLP antibody comprises VH The V H Contains the amino acid sequence SEQ ID NO:69 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:69, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:86 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:86. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:69, and V L The V L It contains the amino acid sequence SEQ ID NO:86.
[0141] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:70 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:70, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:87 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:87. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:70, and V L The V L It contains the amino acid sequence SEQ ID NO:87.
[0142] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:69 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:69, and VL The V L The antibody comprises the amino acid sequence SEQ ID NO:88 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:88. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:69, and V L The V L It contains the amino acid sequence SEQ ID NO:88.
[0143] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:71 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:71, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:89 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:89. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:71, and V L The V L It contains the amino acid sequence SEQ ID NO:89.
[0144] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:72 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:72, and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:90 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:90. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:72, and V L The V L It contains the amino acid sequence SEQ ID NO:90.
[0145] In some embodiments, the anti-TSLP antibody comprises V H The V H Includes: HC-CDR1, which contains SYGIX1 (SEQ ID NO: 108), wherein X1 is N or S; HC-CDR2, which contains VIX1PLX2X3VX4X5YAEKFQG (SEQ ID NO: 109), wherein X1 is V or I, X2 is V or L, X3 is G or D, X4 is T or P, and X5 is I or N; and HC-CDR3, which contains GX1EYFYWYFDL (SEQ ID NO: 110), wherein X1 is Q or A; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR)1, which includes X1GX2X3SDIGGYX4RVS (SEQ ID NO:111), wherein X1 is S or T, X2 is S or T, X3 is S, T, I or N, and X4 is N or D; LC-CDR2, which includes X1X2X3KRX4S (SEQ ID NO:112), wherein X1 is D, G or E, X2 is V, F or I, X3 is S or N, and X4 is P or S; and LC-CDR3, which includes X1SYAX2X3X4X5FX6X7 (SEQ ID NO:113), wherein X1 is S or T, X2 is G or S, X3 is T or G, X4 is D or H, X5 is T or I, X6 is I, G, V or A, and X7 is L, I or F.
[0146] In some embodiments, the anti-TSLP antibody comprises V H The V HIt comprises: HC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:2-3 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; HC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:10-12 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:19-20 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
[0147] In some embodiments, the anti-TSLP antibody comprises V H The V H It comprises: HC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:2-3; HC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:10-12; and HC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:19-20.
[0148] In some embodiments, the anti-TSLP antibody comprises V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:29-34 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:42-47 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-60 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
[0149] In some embodiments, the anti-TSLP antibody comprises V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:29-34; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:42-47; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-60.
[0150] In some embodiments, the anti-TSLP antibody comprises V H The V HContains: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:2-3 or variants thereof, the variants comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:10-12 or variants thereof, the variants comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:19-20 or variants thereof, the variants comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:29-34 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:42-47 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-60 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
[0151] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:2-3; HC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:10-12; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:19-20; and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:29-34; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:42-47; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-60.
[0152] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V HVariants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:29; LC-CDR2, which contains the amino acid sequence SEQ ID NO:42; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:54, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0153] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:29; LC-CDR2, which contains the amino acid sequence SEQ ID NO:42; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:54.
[0154] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:30; LC-CDR2, which contains the amino acid sequence SEQ ID NO:43; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:55, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0155] In some embodiments, the anti-TSLP antibody comprises V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:30; LC-CDR2, which contains the amino acid sequence SEQ ID NO:43; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:55.
[0156] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:31; LC-CDR2, which contains the amino acid sequence SEQ ID NO:44; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:56, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0157] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:31; LC-CDR2, which contains the amino acid sequence SEQ ID NO:44; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:56.
[0158] In some embodiments, the anti-TSLP antibody comprises V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:32; LC-CDR2, which contains the amino acid sequence SEQ ID NO:45; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:57, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0159] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:32; LC-CDR2, which contains the amino acid sequence SEQ ID NO:45; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:57.
[0160] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:11; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:33; LC-CDR2, which contains the amino acid sequence SEQ ID NO:45; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:58, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0161] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:11; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:33; LC-CDR2, which contains the amino acid sequence SEQ ID NO:45; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:58.
[0162] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:31; LC-CDR2, which contains the amino acid sequence SEQ ID NO:46; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:59, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0163] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:19; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:31; LC-CDR2, which contains the amino acid sequence SEQ ID NO:46; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:59.
[0164] In some embodiments, the anti-TSLP antibody comprises V H The VH Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:20, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:34; LC-CDR2, which contains the amino acid sequence SEQ ID NO:47; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:60, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0165] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:12; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:20; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:34; LC-CDR2, which contains the amino acid sequence SEQ ID NO:47; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:60.
[0166] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence shown in SEQ ID NOs:2-3, 10-12, 19-20 or variants thereof, said variants containing substitutions of up to about 5 amino acids; and V L The V L The antibody comprises the amino acid sequence shown in SEQ ID NOs:29-34, 42-47, 54-60 or variants thereof, wherein the variants comprise substitutions of up to about 5 amino acids. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequences shown in SEQ ID NOs:2-3, 10-12, 19-20; and V L The V L It contains the amino acid sequences shown in SEQ ID NOs:29-34, 42-47, 54-60.
[0167] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:2, 10, and 19, or V containing up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:29, 42, and 54, or V containing up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 19; and V L The V L It contains amino acid sequences SEQ ID NOs:29, 42 and 54.
[0168] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:2, 10, and 19, or V containing up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:30, 43, and 55, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 19; and V L The V L It contains amino acid sequences SEQ ID NOs:30, 43 and 55.
[0169] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:2, 10, and 19, or V containing up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:31, 44, and 56, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V HContains amino acid sequences SEQ ID NOs:2, 10, and 19; and V L The V L It contains the amino acid sequences SEQ ID NOs:31, 44 and 56.
[0170] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:2, 10, and 19, or V containing up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ IDNOs:32, 45, and 57, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 19; and V L The V L It contains the amino acid sequences SEQ ID NOs:32, 45 and 57.
[0171] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:3, 11, and 19, or V containing up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:33, 45, and 58, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:3, 11, and 19; and V L The V L It contains the amino acid sequences SEQ ID NOs:33, 45 and 58.
[0172] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:3, 10, and 19, or V containing up to 5 amino acid substitutions. H Variant; and V L The V LContaining amino acid sequences SEQ ID NOs:31, 46, and 59, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:3, 10, and 19; and V L The V L It contains the amino acid sequences SEQ ID NOs:31, 46 and 59.
[0173] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:3, 12, and 20, or V containing up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:34, 47, and 60, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:3, 12, and 20; and V L The V L It contains the amino acid sequences SEQ ID NOs:34, 47 and 60.
[0174] In some embodiments, the anti-TSLP antibody comprises V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:73-78 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:91-97 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0175] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains V as shown in SEQ ID NO:73 of the amino acid sequence H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V HContains V as shown in SEQ ID NO:74, an amino acid sequence H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:75 of the amino acid sequence H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:76 of the amino acid sequence H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:77 of the amino acid sequence H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:78 H It contains one, two, or three HC-CDRs.
[0176] In some embodiments, the anti-TSLP antibody comprises V L The V L Contains V as shown in SEQ ID NO:91 L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody comprises V as shown in SEQ ID NO:92 of the amino acid sequence. L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains V L The V L Contains V as shown in the amino acid sequence SEQ ID NO:93 L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains V L The V L Contains V as shown in the amino acid sequence SEQ ID NO:94 L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains V L The V L Contains V as shown in SEQ ID NO:95, an amino acid sequence LIt may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains V L The V L Contains V as shown in the amino acid sequence SEQ ID NO:96 L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains V L The V L Contains V as shown in SEQ ID NO:97 of the amino acid sequence L It may contain one, two, or three LC-CDRs.
[0177] In some embodiments, the anti-TSLP antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:73. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:91. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:74. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:91. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:75. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:91. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:73. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:92. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V.H It contains V as shown in the amino acid sequence SEQ ID NO:73. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:93. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:73. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:94. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:76. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:95. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:77. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:96. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:78. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:97. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0178] In some embodiments, the anti-TSLP antibody comprises V H The V HContains any of the amino acid sequences shown in SEQ ID NOs:73-78 or variants thereof, said variants having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:73-78, and V L The V L The antibody comprises any of the amino acid sequences shown in SEQ ID NOs:91-97 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:91-97. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:73-78, and V L The V L It contains any of the amino acid sequences shown in SEQ ID NOs:91-97.
[0179] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:73 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:73, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:91 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:91. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:73, and V L The V L It contains the amino acid sequence SEQ ID NO:91.
[0180] In some embodiments, the anti-TSLP antibody comprises V H The V HContains the amino acid sequence SEQ ID NO:74 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:74, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:91 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:91. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:74, and V L The V L It contains the amino acid sequence SEQ ID NO:91.
[0181] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:75 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:75, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:91 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:91. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:75, and V L The V L It contains the amino acid sequence SEQ ID NO:91.
[0182] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:73 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:73, and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:92 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:92. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:73, and V L The V L It contains the amino acid sequence SEQ ID NO:92.
[0183] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:73 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:73, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:93 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:93. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:73, and V L The V L It contains the amino acid sequence SEQ ID NO:93.
[0184] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:73 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:73, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:94 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:94. In some embodiments, the anti-TSLP antibody comprises V H The VH Contains the amino acid sequence SEQ ID NO:73, and V L The V L It contains the amino acid sequence SEQ ID NO:94.
[0185] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:76 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:76, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:95 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:95. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:76, and V L The V L It contains the amino acid sequence SEQ ID NO:95.
[0186] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:77 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:77, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:96 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:96. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:77, and V L The V L It contains the amino acid sequence SEQ ID NO:96.
[0187] In some embodiments, the anti-TSLP antibody comprises VH The V H Contains the amino acid sequence SEQ ID NO:78 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:78, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:97 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:97. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:78, and V L The V L It contains the amino acid sequence SEQ ID NO:97.
[0188] In some embodiments, the anti-TSLP antibody comprises V H The V H The HC-CDR1 contains NYX1MT (SEQ ID NO: 114), where X1 is D or G; HC-CDR2 contains SITFASSYIYYADSVKG (SEQ ID NO: 13); and HC-CDR3 contains GGGAYX1GGSLDV (SEQ ID NO: 115), where X1 is H or Y; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR)1, which includes RSSQSLLHX1X2X3YTYLH (SEQ ID NO:116), wherein X1 is I or S, X2 is N or Y, and X3 is G or E; LC-CDR2, which includes LVSX1RAS (SEQ ID NO:117), wherein X1 is H or Y; and LC-CDR3, which includes EQTLQTPX1X2 (SEQ ID NO:118), wherein X1 is Y or F, and X2 is S or T.
[0189] In some embodiments, the anti-TSLP antibody comprises V H The V HIt comprises: HC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:4-5 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; HC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:13 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:21-22 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
[0190] In some embodiments, the anti-TSLP antibody comprises V H The V H It comprises: HC-CDR1, which contains the amino acid sequences shown in SEQ ID NOs:4-5; HC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:13; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:21-22.
[0191] In some embodiments, the anti-TSLP antibody comprises V L The V L The formulation comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:35-37 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:48-49 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:61-63 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
[0192] In some embodiments, the anti-TSLP antibody comprises V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:35-37; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:48-49; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:61-63.
[0193] In some embodiments, the anti-TSLP antibody comprises V H The V HContains: HC-CDR1, comprising the amino acid sequence shown in any of SEQ ID NOs:4-5 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR2, comprising the amino acid sequence shown in SEQ ID NO:13 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:21-22 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:35-37 or variants thereof, the variants comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:48-49 or variants thereof, the variants comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:61-63 or variants thereof, the variants comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).
[0194] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:4-5; HC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:13; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:21-22; and V L The V L It comprises: LC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:35-37; LC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:48-49; and LC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:61-63.
[0195] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:21, or the V HVariants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:35; LC-CDR2, which contains the amino acid sequence SEQ ID NO:48; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:61, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0196] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:21; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:35; LC-CDR2, which contains the amino acid sequence SEQ ID NO:48; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:61.
[0197] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:22, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:36; LC-CDR2, which contains the amino acid sequence SEQ ID NO:48; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0198] In some embodiments, the anti-TSLP antibody comprises V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:22; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:36; LC-CDR2, which contains the amino acid sequence SEQ ID NO:48; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:62.
[0199] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:5; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:22, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:37; LC-CDR2, which contains the amino acid sequence SEQ ID NO:49; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:63, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0200] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:5; HC-CDR2, which contains the amino acid sequence SEQ ID NO:13; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:22; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:37; LC-CDR2, which contains the amino acid sequence SEQ ID NO:49; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:63.
[0201] In some embodiments, the anti-TSLP antibody comprises V H The V HContains the amino acid sequence shown in SEQ ID NOs:4-5, 13, 21-22 or variants thereof, said variants comprising substitutions of up to about 5 amino acids; and V L The V L The antibody comprises the amino acid sequence shown in SEQ ID NOs:35-37, 48-49, 61-63 or variants thereof, wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequences shown in SEQ ID NOs:4-5, 13, 21-22; and V L The V L It contains the amino acid sequences shown in SEQ ID NOs:35-37, 48-49, and 61-63.
[0202] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:4, 13, and 21, or V containing up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:35, 48, and 61, or V containing up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:4, 13, and 21; and V L The V L It contains the amino acid sequences SEQ ID NOs:35, 48 and 61.
[0203] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:4, 13, and 22, or containing V with up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:36, 48, and 62, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:4, 13, and 22; and V L The V LIt contains the amino acid sequences SEQ ID NOs:36, 48 and 62.
[0204] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:5, 13, and 22, or containing V with up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:37, 49, and 63, or containing V with up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:5, 13, and 22; and V L The V L It contains amino acid sequences SEQ ID NOs:37, 49 and 63.
[0205] In some embodiments, the anti-TSLP antibody comprises V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:79-81 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:98-100 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0206] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains V as shown in SEQ ID NO:79 of the amino acid sequence H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:80, an amino acid sequence H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in SEQ ID NO:81 of the amino acid sequence H It contains one, two, or three HC-CDRs.
[0207] In some embodiments, the anti-TSLP antibody comprises V L The V L Contains V as shown in SEQ ID NO:98, an amino acid sequence L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody comprises V as shown in SEQ ID NO:99 of the amino acid sequence. L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody contains V L The V L Contains V as shown in SEQ ID NO:100, an amino acid sequence L It may contain one, two, or three LC-CDRs.
[0208] In some embodiments, the anti-TSLP antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:79. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:98. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:80. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:99. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:81. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:100. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0209] In some embodiments, the anti-TSLP antibody comprises V H The V HContains any of the amino acid sequences shown in SEQ ID NOs:79-81 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:79-81, and V L The V L The antibody comprises any of the amino acid sequences shown in SEQ ID NOs:98-100 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:98-100. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:79-81, and V L The V L It contains any of the amino acid sequences shown in SEQ ID NOs:98-100.
[0210] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:79 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:79, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:98 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:98. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:79, and V L The V L It contains the amino acid sequence SEQ ID NO:98.
[0211] In some embodiments, the anti-TSLP antibody comprises V H The V HContains the amino acid sequence SEQ ID NO:80 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:80, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:99 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:99. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:80, and V L The V L It contains the amino acid sequence SEQ ID NO:99.
[0212] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:81 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:81, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:100 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:100. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:81, and V L The V L It contains the amino acid sequence SEQ ID NO:100.
[0213] In some embodiments, the anti-TSLP antibody comprises V H The V HThe HC-CDR1 contains SYAIS (SEQ ID NO: 6); HC-CDR2 contains MX1X2PLLGVTX3YAEKFQG (SEQ ID NO: 119), where X1 is L or I, X2 is V or I, and X3 is N or D; and HC-CDR3 contains GGX1NYLYWYFDL (SEQ ID NO: 120), where X1 is S or T; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR) 1, which contains TGTSSDIGGYNRX1S (SEQ ID NO:121), wherein X1 is V or I; LC-CDR 2, which contains X1VSKRPS (SEQ ID NO:122), wherein X1 is D or E; and LC-CDR 3, which contains SX1YAGTDTFVL (SEQ ID NO:123), wherein X1 is S or A.
[0214] In some embodiments, the anti-TSLP antibody comprises V H The V H It comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:6 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; HC-CDR2, which comprises the amino acid sequence shown in any of SEQ ID NOs:14-15 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3, which comprises the amino acid sequence shown in any of SEQ ID NOs:23-24 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
[0215] In some embodiments, the anti-TSLP antibody comprises V H The V H It comprises: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:6; HC-CDR2, which contains the amino acid sequence shown in any of SEQ ID NOs:14-15; and HC-CDR3, which contains the amino acid sequence shown in any of SEQ ID NOs:23-24.
[0216] In some embodiments, the anti-TSLP antibody comprises V L The V LIt comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:31, 38 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:42, 45 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:60, 64 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
[0217] In some embodiments, the anti-TSLP antibody comprises V L The V L It includes: LC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:31 and 38; LC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:42 and 45; and LC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:60 and 64.
[0218] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:6 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:14-15 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:23-24 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and V L The V L The formulation comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:31, 38 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises any of the amino acid sequences shown in SEQ ID NOs:42, 45 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:60, 64 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
[0219] In some embodiments, the anti-TSLP antibody comprises V HThe V H Contains: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:6; HC-CDR2, which contains the amino acid sequence shown in any of SEQ ID NOs:14-15; HC-CDR3, which contains the amino acid sequence shown in any of SEQ ID NOs:23-24; and V L The V L It includes: LC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:31 and 38; LC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:42 and 45; and LC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:60 and 64.
[0220] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:6; HC-CDR2, which contains the amino acid sequence SEQ ID NO:14; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:23, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:38; LC-CDR2, which contains the amino acid sequence SEQ ID NO:42; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:60, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0221] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:6; HC-CDR2, which contains the amino acid sequence SEQ ID NO:14; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:23; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:38; LC-CDR2, which contains the amino acid sequence SEQ ID NO:42; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:60.
[0222] In some embodiments, the anti-TSLP antibody comprises VH The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:6; HC-CDR2, which contains the amino acid sequence SEQ ID NO:15; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:24, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:31; LC-CDR2, which contains the amino acid sequence SEQ ID NO:45; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:64, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.
[0223] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:6; HC-CDR2, which contains the amino acid sequence SEQ ID NO:15; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:24; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:31; LC-CDR2, which contains the amino acid sequence SEQ ID NO:45; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:64.
[0224] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence shown in SEQ ID NOs:6, 14-15, 23-24 or variants thereof, said variants containing substitutions of up to about 5 amino acids; and V L The V L The anti-TSLP antibody comprises the amino acid sequence shown in SEQ ID NOs:31, 38, 42, 45, 60, 64 or variants thereof, wherein the variants comprise substitutions of up to about 5 amino acids. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence shown in SEQ ID NOs:6, 14-15, 23-24; and V L The V LIt contains the amino acid sequences shown in SEQ ID NOs:31, 38, 42, 45, 60, and 64.
[0225] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:6, 14, and 23, or V containing up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:38, 42, and 60, or V containing up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:6, 14, and 23; and V L The V L It contains the amino acid sequences SEQ ID NOs:38, 42 and 60.
[0226] In some embodiments, the anti-TSLP antibody comprises V H The V H Containing amino acid sequences SEQ ID NOs:6, 15, and 24, or V containing up to 5 amino acid substitutions. H Variant; and V L The V L Containing amino acid sequences SEQ ID NOs:31, 45, and 64, or V containing up to 5 amino acid substitutions. L Variants. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains amino acid sequences SEQ ID NOs:6, 15, and 24; and V L The V L It contains the amino acid sequences SEQ ID NOs:31, 45 and 64.
[0227] In some embodiments, the anti-TSLP antibody comprises V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:82-83 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:101-102 LIt includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0228] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains V as shown in SEQ ID NO:82, an amino acid sequence H It may contain one, two, or three HC-CDRs. In some embodiments, the anti-TSLP antibody contains V H The V H Contains V as shown in the amino acid sequence SEQ ID NO:83 H It contains one, two, or three HC-CDRs.
[0229] In some embodiments, the anti-TSLP antibody comprises V L The V L Contains V as shown in SEQ ID NO:101, an amino acid sequence L It may contain one, two, or three LC-CDRs. In some embodiments, the anti-TSLP antibody comprises V as shown in SEQ ID NO:102 of the amino acid sequence. L It may contain one, two, or three LC-CDRs.
[0230] In some embodiments, the anti-TSLP antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:82. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:101. L It includes LC-CDR1, LC-CDR2, and LC-CDR3. In some embodiments, the anti-TSLP antibody includes V. H It contains V as shown in the amino acid sequence SEQ ID NO:83. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:102. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.
[0231] In some embodiments, the anti-TSLP antibody comprises V H The V HContains any of the amino acid sequences shown in SEQ ID NOs:82-83 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:82-83, and V L The V L The antibody comprises any of the amino acid sequences shown in SEQ ID NOs:101-102 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:101-102. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:82-83, and V L The V L It contains any of the amino acid sequences shown in SEQ ID NOs:101-102.
[0232] In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:82 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:82, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:101 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:101. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:82, and V L The V L It contains the amino acid sequence SEQ ID NO:101.
[0233] In some embodiments, the anti-TSLP antibody comprises V H The V HContains the amino acid sequence SEQ ID NO:83 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:83, and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:102 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:102. In some embodiments, the anti-TSLP antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:83, and V L The V L It contains the amino acid sequence SEQ ID NO:102.
[0234] In some embodiments, the functional epitope can be resolved using a combined alanine scanning technique. In this process, the combined alanine scanning technique can be used to identify the amino acids in the TSLP protein essential for interaction with anti-TSLP antibodies. In some embodiments, the epitope is conformational, and the epitope can also be identified using the crystal structure of an anti-TSLP antibody that binds to the TSLP protein.
[0235] In some embodiments, the amino acid substitutions described above are limited to the "Exemplary Substitutions" as shown in Table 4 of this application. In some embodiments, the amino acid substitutions are limited to the "Preferred Substitutions" as shown in Table 4 of this application.
[0236] In some embodiments, this application provides an antibody that competitively binds to TSLP with any of the anti-TSLP antibodies described herein. In some embodiments, an antibody capable of competitively binding to an epitope on TSLP with any of the anti-TSLP antibodies described herein is provided. In some embodiments, an anti-TSLP antibody is provided that contains V H and V L The anti-TSLP antibody molecule binds to the same epitope, wherein the V H Contains any of the amino acid sequences shown in SEQ ID NOs:65-83, and the V L Contains any of the amino acid sequences shown in SEQ ID NOs:84-102. In some embodiments, an anti-TSLP antibody is provided, which, together with V H and V L The anti-TSLP antibody competitively binds to TSLP, wherein the V HContains any of the amino acid sequences shown in SEQ ID NOs:65-83, and the V L It contains any of the amino acid sequences shown in SEQ ID NOs:84-102.
[0237] In some embodiments, a competition assay can be used to identify monoclonal antibodies that competitively bind to TSLP with the anti-TSLP antibody described herein. A competition assay can determine whether two antibodies bind to the same epitope by identifying identical or spatially overlapping epitopes or by one antibody competitively inhibiting the binding of another antibody to the antigen. In some embodiments, such a competing antibody binds to the same epitope as the antibody described herein. Some exemplary competition assays include, but are not limited to, conventional assays as described in Harlow and Lane (1988) Antibodies: A Laboratory Manual ch. 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). Detailed exemplary methods for resolving antibody-bound epitopes are described in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology vol. 66 (Humana Press, Totowa, NJ). In some embodiments, if each antibody blocks 50% or more of the binding of another antibody, they are said to bind to the same epitope. In some embodiments, the antibody competing with the anti-TSLP antibody described herein is a chimeric antibody, a humanized antibody, or a fully human antibody.
[0238] Exemplary anti-TSLP antibody sequences are shown in Tables 2 and 3, where CDRs are numbered according to the Kabat definition. Those skilled in the art will recognize that various known algorithms (Kabat definition) exist for predicting CDR locations and defining the variable regions of the antibody light and heavy chains. CDRs containing anti-TSLP antibodies as described herein, V H and / or V L Sequences, but antibodies based on prediction algorithms rather than those exemplified in the table below are also within the scope of this application.
[0239] Table 2. Exemplary anti-TSLP antibody CDR sequences
[0240]
[0241]
[0242]
[0243]
[0244]
[0245] Table 3. Exemplary Sequences
[0246]
[0247]
[0248]
[0249]
[0250]
[0251] TSLP
[0252] TSLP is an epithelial cell-derived cytokine constitutively expressed in the skin, intestine, lung, and thymus (HeR, et al., Ann NY Acad Sci 2010; 1183:13–24). The highest TSLP expression levels are observed in lung-derived and skin-derived epithelial cells (Ziegler SF, Curr Opin Immunol 2010; 22:795–799). TSLP was first identified as a distant homolog of IL-7 in the supernatant of the mouse thymic stromal cell line Z210R.1. Subsequent expression cloning revealed that mouse TSLP (mTSLP) is a member of the hematopoietic cytokine family (Sims JE, et al., J Exp Med 2000; 192:671–680). Sequence prediction revealed it to be a cytokine with a quadruple helix-like structure, possessing two N-glycosylation sites and six cysteine residues (Kashyap M, et al, J Immunol 2011; 187:1207–1211). Human TSLP (hTSLP) and mTSLP exhibited low homology, with only 43% amino acid identity (Reche PA, et al, J Immunol 2001; 167:336–343; Quentmeier H, et al, Leukemia 2001; 15:1286–1292).
[0253] Two isoforms of TSLP in mice, the short and long isoforms, have been described, but the functional outcomes of these variants remain unclear. In humans, the predominant isoform expressed under homeostatic conditions is the short TSLP, while the long TSLP is upregulated under inflammatory conditions (Fornasa G, et al, J Allergy Clin Immunol 2015; 136:413-22; Tsilingiri K, et al, Cell Mol Gastroenterol Hepatol 2017; 3:174-82). Furthermore, there is evidence that TSLP can be cleaved by several endogenous proteases under pathological conditions (Poposki JA, et al, J Allergy Clin Immunol 2017; 139:1559-67.e8; Nagarkar DR, et al, J Allergy Clin Immunol 2013; 132:593-600.e12). For example, in patients with celiac disease, furin, which is upregulated in patient biopsies, can cleave the long subtype of TSLP, producing 10 kDa and 4 kDa fragments on human peripheral blood mononuclear cells, which have different activities compared to mature TSLP (Biancheri P, et al, Gut 2016; 65:1670-80).
[0254] TSLP induces an innate hypersensitive immune response by targeting mDCs, mast cells, eosinophils, basophils, and NKT cells (Al-Shami A, et al, J Exp Med 2004; 200:159–168; Wu WH, et al, J Allergy Clin Immunol 2010; 126:290–299,299.e1–e4; Soumelis V, et al, Nat Immunol 2002; 3:673–680). Clearly, TSLP strongly upregulates the expression of MHC class II, CD54, CD80, CD83, CD86, and DC-lamp in mDCs (Liu YJ, J Exp Med 2006; 203:269–273). It is worth noting that, unlike CD40L and Toll receptor-like (TLR) ligands, TSLP does not stimulate mDCs to produce Th1 polarized cytokines (IL-12 and type 1 interferon) or pro-inflammatory cytokines (TNF-α, IL-1β and IL-6).
[0255] Recent evidence suggests that TSLP plays a crucial role in the pathology of allergic asthma and atopic dermatitis (AD). Emphasizing TSLP as a potential treatment for allergic diseases is compelling. Further analysis of the TSLP-mediated Th2 phenotypic immune response mechanism will provide new clues for this exploration. Furthermore, TSLP actively creates a Th2-allowed microenvironment, leading to further asthma development (Willart MA, et al., Allergol Int 2010; 59:95–103).
[0256] TSLP receptor (TSLPR)
[0257] The TSLP receptor (TSLPR) complex consists of TSLPR and IL-7 receptor α (IL-7R) (Park LS, et al, J Exp Med 2000; 192:659–670). TSLP binds to a heterodimeric receptor consisting of the IL-7 receptor α chain (IL-7Rα) and the TSLPR chain, which is closely associated with the common receptor γ chain (γc), to exert its biological activity across a wide range of cell types. TSLPR alone has a low affinity for TSLP, but the binding of TSLPR to IL-7Rα creates a high-affinity binding site for TSLP and triggers signal transduction (He R, et al, Ann NY Acad Sci 2010; 1183:13–24). The binding of the TSLPR and IL-7Rα chains leads to high-affinity binding and activation of signal transduction and transcriptional activators 3 (STAT3) and STAT5 (Pandey A, et al, Nat Immunol 2000; 1:59–64). The expression of the TSLPR transcript can be detected in early B cells and T cell progenitors, peripheral CD4+ T cells, mast cells and DCs in both species (He SH, et al, Clin Exp Immunol 2011; 165:29–37).
[0258] Therefore, the combination of neutralizing TSLP and TSLPR is a treatment method for diseases and conditions mediated by TSLP signaling.
[0259] Full-length anti-TSLP antibody
[0260] In some embodiments, the anti-TSLP antibody is a full-length anti-TSLP antibody. In some embodiments, the full-length anti-TSLP antibody is IgA, IgD, IgE, IgG, or IgM. In some embodiments, the full-length anti-TSLP antibody includes a constant IgG region, such as a constant region of IgG1, IgG2, IgG3, IgG4, or a variant thereof. In some embodiments, the full-length anti-TSLP antibody includes a λ light chain constant region. In some embodiments, the full-length anti-TSLP antibody includes a κ light chain constant region. In some embodiments, the full-length anti-TSLP antibody is a full-length human anti-TSLP antibody. In some embodiments, the full-length anti-TSLP antibody includes a mouse immunoglobulin Fc sequence. In some embodiments, the full-length anti-TSLP antibody includes an altered or otherwise modified Fc sequence to give it enhanced effector functions of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
[0261] Therefore, for example, in some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, the anti-TSLP antibody specifically binding to TSLP. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0262] In some embodiments, a full-length anti-TSLP antibody comprising an IgG2 constant region is provided, the anti-TSLP antibody specifically binding to TSLP. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0263] In some embodiments, a full-length anti-TSLP antibody comprising an IgG3 constant region is provided, the anti-TSLP antibody specifically binding to TSLP. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0264] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, the anti-TSLP antibody specifically binding to TSLP. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0265] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-6 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:7-15 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:16-24 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-24 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in ... The amino acid sequences shown in SEQ ID NOs:25-38 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), LC-CDR2, which contains amino acid sequences shown in SEQ ID NOs:39-49 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), and LC-CDR3, which contains amino acid sequences shown in SEQ ID NOs:50-64 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0266] In some embodiments, a full-length anti-TSLP antibody comprising an IgG2 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-6 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:7-15 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:16-24 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-24 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-24 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-24 or variants thereof, the heavy chain variable domain comprising: HC-CDR2 ... The amino acid sequences shown in SEQ ID NOs:25-38 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), LC-CDR2, which contains the amino acid sequences shown in SEQ ID NOs:39-49 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), and LC-CDR3, which contains the amino acid sequences shown in SEQ ID NOs:50-64 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0267] In some embodiments, a full-length anti-TSLP antibody comprising an IgG3 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-6 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:7-15 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:16-24 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-24 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in ... The amino acid sequences shown in SEQ ID NOs:25-38 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), LC-CDR2, which contains the amino acid sequences shown in SEQ ID NOs:39-49 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), and LC-CDR3, which contains the amino acid sequences shown in SEQ ID NOs:50-64 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0268] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-6 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:7-15 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:16-24 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-24 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in ... The amino acid sequences shown in SEQ ID NOs:25-38 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), LC-CDR2, which contains the amino acid sequences shown in SEQ ID NOs:39-49 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), and LC-CDR3, which contains the amino acid sequences shown in SEQ ID NOs:50-64 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0269] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-6, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 7-15, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 16-24, or variants thereof, wherein the variants contain at most about 3 (e.g., 1, 2, or 3) amino acid substitutions in the HC-CDR sequence; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 25-38, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 39-49, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 16-24, or variants thereof, wherein the heavy chain variable domain comprises: HC ...16-24, or variants thereof, wherein the heavy chain variable domain The amino acid sequences shown in NOs:50-64, or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3) in the HC-CDR sequence. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0270] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-6, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 7-15, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 16-24, or variants thereof, wherein the variants contain at most about 3 (e.g., 1, 2, or 3) amino acid substitutions in the HC-CDR sequence; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 25-38, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 39-49, and LC-CDR3 comprising SEQ ID NOs: 16-24, or variants thereof, wherein the heavy chain variable domain comprises: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 25-38, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 39-49, and LC-CDR3 comprising any of the amino acid sequences shown in ... The amino acid sequences shown in NOs:50-64, or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3) in the HC-CDR sequence. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0271] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:1-6, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:7-15, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:16-24; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:25-38, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:39-49, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:50-64. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0272] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:1-6, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:7-15, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:16-24; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:25-38, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:39-49, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:50-64. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0273] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising amino acid sequence SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:25, LC-CDR2 comprising amino acid sequence SEQ ID NO:39, and LC-CDR3 comprising amino acid sequence SEQ ID NO:50. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0274] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising amino acid sequence SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:25, LC-CDR2 comprising amino acid sequence SEQ ID NO:39, and LC-CDR3 comprising amino acid sequence SEQ ID NO:51. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0275] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising amino acid sequence SEQ ID NO:17; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:26, LC-CDR2 comprising amino acid sequence SEQ ID NO:40, and LC-CDR3 comprising amino acid sequence SEQ ID NO:52. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0276] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising amino acid sequence SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:27, LC-CDR2 comprising amino acid sequence SEQ ID NO:41, and LC-CDR3 comprising amino acid sequence SEQ ID NO:52. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0277] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:9, and HC-CDR3 comprising amino acid sequence SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:28, LC-CDR2 comprising amino acid sequence SEQ ID NO:39, and LC-CDR3 comprising amino acid sequence SEQ ID NO:52. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0278] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising amino acid sequence SEQ ID NO:18; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:27, LC-CDR2 comprising amino acid sequence SEQ ID NO:39, and LC-CDR3 comprising amino acid sequence SEQ ID NO:53. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0279] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:29, LC-CDR2 comprising amino acid sequence SEQ ID NO:42, and LC-CDR3 comprising amino acid sequence SEQ ID NO:54. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0280] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:30, LC-CDR2 comprising amino acid sequence SEQ ID NO:43, and LC-CDR3 comprising amino acid sequence SEQ ID NO:55. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0281] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:31, LC-CDR2 comprising amino acid sequence SEQ ID NO:44, and LC-CDR3 comprising amino acid sequence SEQ ID NO:56. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0282] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:32, LC-CDR2 comprising amino acid sequence SEQ ID NO:45, and LC-CDR3 comprising amino acid sequence SEQ ID NO:57. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0283] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:3, HC-CDR2 comprising amino acid sequence SEQ ID NO:11, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:33, LC-CDR2 comprising amino acid sequence SEQ ID NO:45, and LC-CDR3 comprising amino acid sequence SEQ ID NO:58. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0284] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:3, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:31, LC-CDR2 comprising amino acid sequence SEQ ID NO:46, and LC-CDR3 comprising amino acid sequence SEQ ID NO:59. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0285] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:3, HC-CDR2 comprising amino acid sequence SEQ ID NO:12, and HC-CDR3 comprising amino acid sequence SEQ ID NO:20; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:34, LC-CDR2 comprising amino acid sequence SEQ ID NO:47, and LC-CDR3 comprising amino acid sequence SEQ ID NO:60. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0286] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:4, HC-CDR2 comprising amino acid sequence SEQ ID NO:13, and HC-CDR3 comprising amino acid sequence SEQ ID NO:21; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:35, LC-CDR2 comprising amino acid sequence SEQ ID NO:48, and LC-CDR3 comprising amino acid sequence SEQ ID NO:61. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0287] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 containing amino acid sequence SEQ ID NO:4, HC-CDR2 containing amino acid sequence SEQ ID NO:13, and HC-CDR3 containing amino acid sequence SEQ ID NO:22; and b) a light chain variable domain comprising: LC-CDR1 containing amino acid sequence SEQ ID NO:36, LC-CDR2 containing amino acid sequence SEQ ID NO:48, and LC-CDR3 containing amino acid sequence SEQ ID NO:62. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0288] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:5, HC-CDR2 comprising the amino acid sequence SEQ ID NO:13, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:22; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:37, LC-CDR2 comprising the amino acid sequence SEQ ID NO:49, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:63. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0289] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:6, HC-CDR2 comprising the amino acid sequence SEQ ID NO:14, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:23; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:38, LC-CDR2 comprising the amino acid sequence SEQ ID NO:42, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:60. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0290] In some embodiments, a full-length anti-TSLP antibody comprising a constant region of IgG1 is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:6, HC-CDR2 comprising the amino acid sequence SEQ ID NO:15, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:24; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:31, LC-CDR2 comprising the amino acid sequence SEQ ID NO:45, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:64. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0291] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:25, LC-CDR2 comprising the amino acid sequence SEQ ID NO:39, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:50. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0292] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:25, LC-CDR2 comprising the amino acid sequence SEQ ID NO:39, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:51. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0293] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:17; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:26, LC-CDR2 comprising the amino acid sequence SEQ ID NO:40, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:52. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0294] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising amino acid sequence SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:27, LC-CDR2 comprising amino acid sequence SEQ ID NO:41, and LC-CDR3 comprising amino acid sequence SEQ ID NO:52. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0295] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:9, and HC-CDR3 comprising amino acid sequence SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:28, LC-CDR2 comprising amino acid sequence SEQ ID NO:39, and LC-CDR3 comprising amino acid sequence SEQ ID NO:52. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0296] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:18; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:27, LC-CDR2 comprising the amino acid sequence SEQ ID NO:39, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:53. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0297] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:29, LC-CDR2 comprising amino acid sequence SEQ ID NO:42, and LC-CDR3 comprising amino acid sequence SEQ ID NO:54. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0298] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:30, LC-CDR2 comprising amino acid sequence SEQ ID NO:43, and LC-CDR3 comprising amino acid sequence SEQ ID NO:55. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0299] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:31, LC-CDR2 comprising amino acid sequence SEQ ID NO:44, and LC-CDR3 comprising amino acid sequence SEQ ID NO:56. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0300] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:32, LC-CDR2 comprising amino acid sequence SEQ ID NO:45, and LC-CDR3 comprising amino acid sequence SEQ ID NO:57. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0301] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:3, HC-CDR2 comprising amino acid sequence SEQ ID NO:11, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:33, LC-CDR2 comprising amino acid sequence SEQ ID NO:45, and LC-CDR3 comprising amino acid sequence SEQ ID NO:58. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0302] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:3, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:31, LC-CDR2 comprising amino acid sequence SEQ ID NO:46, and LC-CDR3 comprising amino acid sequence SEQ ID NO:59. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0303] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:3, HC-CDR2 comprising amino acid sequence SEQ ID NO:12, and HC-CDR3 comprising amino acid sequence SEQ ID NO:20; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:34, LC-CDR2 comprising amino acid sequence SEQ ID NO:47, and LC-CDR3 comprising amino acid sequence SEQ ID NO:60. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0304] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:4, HC-CDR2 comprising amino acid sequence SEQ ID NO:13, and HC-CDR3 comprising amino acid sequence SEQ ID NO:21; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:35, LC-CDR2 comprising amino acid sequence SEQ ID NO:48, and LC-CDR3 comprising amino acid sequence SEQ ID NO:61. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0305] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:4, HC-CDR2 comprising amino acid sequence SEQ ID NO:13, and HC-CDR3 comprising amino acid sequence SEQ ID NO:22; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:36, LC-CDR2 comprising amino acid sequence SEQ ID NO:48, and LC-CDR3 comprising amino acid sequence SEQ ID NO:62. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0306] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:5, HC-CDR2 comprising the amino acid sequence SEQ ID NO:13, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:22; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:37, LC-CDR2 comprising the amino acid sequence SEQ ID NO:49, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:63. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0307] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:6, HC-CDR2 comprising the amino acid sequence SEQ ID NO:14, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:23; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:38, LC-CDR2 comprising the amino acid sequence SEQ ID NO:42, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:60. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0308] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:6, HC-CDR2 comprising the amino acid sequence SEQ ID NO:15, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:24; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:31, LC-CDR2 comprising the amino acid sequence SEQ ID NO:45, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:64. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0309] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises a heavy chain variable domain V. H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:65-83 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:65-83, and a light chain variable domain V. L The V LThe IgG1 comprises any of the amino acid sequences shown in SEQ ID NOs:84-102 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:84-102. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0310] In some embodiments, a full-length anti-TSLP antibody comprising an IgG2 constant region is provided, wherein the anti-TSLP antibody comprises a heavy chain variable domain V. H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:65-83 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:65-83, and a light chain variable domain V. L The V L The IgG2 comprises any of the amino acid sequences shown in SEQ ID NOs:84-102 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:84-102. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0311] In some embodiments, a full-length anti-TSLP antibody comprising an IgG3 constant region is provided, wherein the anti-TSLP antibody comprises a heavy chain variable domain V. H The V HContains any of the amino acid sequences shown in SEQ ID NOs:65-83 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:65-83, and a light chain variable domain V. L The V L The IgG3 comprises any of the amino acid sequences shown in SEQ ID NOs:84-102 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:84-102. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0312] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises a heavy chain variable domain V. H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:65-83 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:65-83, and a light chain variable domain V. L The V LThe IgG4 comprises any of the amino acid sequences shown in SEQ ID NOs:84-102, or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences in SEQ ID NOs:84-102. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0313] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises a heavy chain variable domain V. H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:65-83, and a light chain variable domain V. L The V L It comprises any of the amino acid sequences shown in SEQ ID NOs:84-102. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0314] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises a heavy chain variable domain V. H The V HContains any of the amino acid sequences shown in SEQ ID NOs:65-83, and a light chain variable domain V. L The V L The IgG4 comprises any of the amino acid sequences shown in SEQ ID NOs:84-102. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0315] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:65, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:84. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0316] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:65, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:85. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0317] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:66, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:84. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0318] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:66, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:85. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0319] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:67, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:84. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0320] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:67, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:85. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0321] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:68, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:84. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0322] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:68, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:85. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0323] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:69, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:86. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0324] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:70, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:87. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0325] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:69, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:88. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0326] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:71, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:89. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0327] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:72, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:90. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0328] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:73, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:91. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0329] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:74, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:91. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0330] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:75, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:91. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0331] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:73, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:92. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0332] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:73, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:93. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0333] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:73, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:94. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0334] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:76, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:95. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0335] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:77, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:96. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0336] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:78, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:97. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0337] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:79, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:98. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0338] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:80, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:99. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0339] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:81, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:100. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0340] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:82, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:101. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0341] In some embodiments, a full-length anti-TSLP antibody comprising an IgG1 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:83, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:102. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:124 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0342] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:65, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:84. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0343] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:65, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:85. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0344] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:66, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:84. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0345] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:66, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:85. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0346] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:67, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:84. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0347] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:67, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:85. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0348] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:68, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:84. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0349] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:68, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:85. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0350] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:69, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:86. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0351] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:70, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:87. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0352] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:69, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:88. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:127.
[0353] In some embodiments, a full-length anti-TSLP antibody comprising an IgG4 constant region is provided, wherein the anti-TSLP antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:71, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:89. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:125. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:126. In some embodiments, the light chain constant region comprises or ...
Claims
1. An isolated anti-TSLP antibody comprising: V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 1; HC-CDR2, with the amino acid sequence SEQ ID NO: 7; and HC-CDR3, with the amino acid sequence SEQ ID NO: 16; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 25; LC-CDR2, whose amino acid sequence is SEQ ID NO: 39; and LC-CDR3, whose amino acid sequence is SEQ ID NO:
50.
2. The isolated anti-TSLP antibody according to claim 1, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO: 65 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 65; and V L It contains the amino acid sequence SEQ ID NO: 84 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 84; (ii) V H It comprises the amino acid sequence SEQ ID NO: 65 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 65; and V L It contains the amino acid sequence SEQ ID NO: 85 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 85; (iii) V H It comprises the amino acid sequence SEQ ID NO: 66 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 66; and V L It contains the amino acid sequence SEQ ID NO: 84 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 84; (iv) V H It comprises the amino acid sequence SEQ ID NO: 66 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 66; and V L It contains the amino acid sequence SEQ ID NO: 85 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 85; (v) V H It comprises the amino acid sequence SEQ ID NO: 67 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 67; and V L It contains the amino acid sequence SEQ ID NO: 84 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 84; (vi) V H It comprises the amino acid sequence SEQ ID NO: 67 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 67; and V L It contains the amino acid sequence SEQ ID NO: 85 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 85; (vii) V H It comprises the amino acid sequence SEQ ID NO: 68 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 68; and V L It contains the amino acid sequence SEQ ID NO: 84 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 84; or (viii) V H It comprises the amino acid sequence SEQ ID NO: 68 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 68; and V L It contains the amino acid sequence SEQ ID NO: 85 or a variant thereof, the variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO:
85.
3. The isolated anti-TSLP antibody according to claim 1 or 2, wherein the Kd value of the anti-TSLP antibody binding to human TSLP is 0.1 pM to 1 nM.
4. The isolated anti-TSLP antibody according to claim 1 or 2, wherein the anti-TSLP antibody comprises an Fc fragment.
5. The isolated anti-TSLP antibody according to claim 4, wherein the anti-TSLP antibody is a full-length IgA, IgD, IgE, IgG or IgM antibody.
6. The isolated anti-TSLP antibody according to claim 5, wherein the anti-TSLP antibody is a full-length IgG1, IgG2, IgG3 or IgG4 antibody.
7. The isolated anti-TSLP antibody according to claim 1 or 2, wherein the anti-TSLP antibody is a chimeric, human, or humanized antibody.
8. The isolated anti-TSLP antibody according to claim 1 or 2, wherein the anti-TSLP antibody is an antigen-binding fragment selected from Fab, Fab', F(ab)'2, Fab'-SH, single-chain Fv (scFv), Fv fragment, or double-chain antibody (diabody).
9. An isolated nucleic acid molecule encoding the anti-TSLP antibody according to any one of claims 1-8.
10. A vector comprising the isolated nucleic acid molecule as described in claim 9.
11. An isolated host cell comprising the isolated anti-TSLP antibody of any one of claims 1-8, the nucleic acid molecule of claim 9, or the vector of claim 10.
12. A method for preparing anti-TSLP antibody, comprising: a) Culturing the isolated host cells as described in claim 11 under conditions that enable effective expression of anti-TSLP antibodies; and b) Obtain expressed anti-TSLP antibodies from host cells.
13. A pharmaceutical composition comprising the isolated anti-TSLP antibody of any one of claims 1-8, the nucleic acid molecule of claim 9, the vector of claim 10 or the isolated host cell of claim 11, and a pharmaceutically acceptable carrier.
14. Use of the isolated anti-TSLP antibody of any one of claims 1-8, the nucleic acid molecule of claim 9, the vector of claim 10, the isolated host cell of claim 11, or the pharmaceutical composition of claim 13 in the preparation of a medicament for treating a disease or condition in an individual with such need, wherein the disease or condition is selected from asthma, atopic dermatitis, allergic rhinitis, eosinophilic esophagitis (EoE), food allergy, chronic obstructive pulmonary disease (COPD), chronic sinusitis (CRS), or inflammatory bowel disease.