WO2025221995A1

WO2025221995A1 - Treatment of eosinophilic esophagitis with anti-tslp antibody

Info

Publication number: WO2025221995A1
Application number: PCT/US2025/025157
Authority: WO
Inventors: Joseph SHERRILL; Scott CAVENEY
Original assignee: Amgen Inc; MedImmune LLC
Current assignee: Amgen Inc; MedImmune LLC
Priority date: 2024-04-17
Filing date: 2025-04-17
Publication date: 2025-10-23
Anticipated expiration: 2026-10-17
Also published as: WO2025221247A1

Abstract

The present disclosure, relates, in general, to methods of treating eosinophilic esophagitis (EOE) using an antibody specific for thymic stromal lymphopoietin (TSLP).

Description

TREATMENT OF EOSINOPHILIC ESOPHAGITIS WITH ANTI-TSLP ANTIBODY

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present claims priority from International Patent application No. PCT/US2024/024850, filed April 17, 2024, herein incorporated by reference in its entirety.

FIELD OF THE DISCLOSURE

[0002] The present disclosure relates, in general, to methods of treating eosinophilic esophagitis (EOE) using an antibody specific for thymic stromal lymphopoietin (TSLP).

INCORPORATION BY REFERENCE OF MATERIAL SUBMITTED ELECTRONICALLY

[0003] Incorporated by reference in its entirety is a computer-readable nucleotide/amino acid sequence listing submitted concurrently herewith and identified as follows: Filename: 70137A_SeqListing.xml; Size: 15,407 bytes; Created: April 17, 2025.

BACKGROUND

[0004] Eosinophilic esophagitis (EOE) is a rare, chronic inflammatory disorder for which there are few approved treatments. Thymic stromal lymphopoietin (TSLP) is a pro- inflammatory epithelial cytokine. TSLP genetic variants are associated with EOE risk and esophageal TSLP mRNA and protein levels are increased in patients with active disease. Tezepelumab, a human monoclonal antibody approved for the treatment of severe asthma, specifically binds to and blocks the activity of TSLP.

[0005] TSLP, along with the other epithelial “alarmins”, IL-25 and IL-33, activates Type 2 innate lymphoid cells (ILC2) and other inflammatory cell (including mast cells, basophils, and macrophages), thus promoting T2 inflammation by up-regulating Type 2 cytokines in response to an epithelial insult (e.g., pollutants, microbes, cigarette smoke, bacterial and viral infections, mechanical injury, trauma and pro-inflammatory cytokines etc.) (Camelo et al 2017).

[0006] Tezepelumab (also known as AMG 157) (Gilliet, et al., J Exp Med 2003; 197:1059- 63) is a fully human monoclonal antibody (immunoglobulin G2A) that targets TSLP, which promotes inflammatory responses to environmental stimuli through its activities on multiple pathways, including (but not limited to) activities on dendritic cells (Gilliet, et al., 2003;

Soumelis et al., Nat Immunol. 3:673-680, 2002; Reche, et al., J Immunol 2001 ; 167:336-43) and mast cells (Allakhverdi et al., J Exp Med. 204:253-258, 2007). By binding to TSLP, tezepelumab prevents its interaction with the TSLP receptor complex and inhibits multiple downstream inflammatory pathways.

SUMMARY

[0007] The anti-TSLP antibody described herein addresses an unmet need in patients with EOE in which other medications may not control symptoms.

[0008] In one aspect, the disclosure provides a method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein the antibody comprises: a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0009] Also provided is a method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or, c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2. [0010] In various embodiments, the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:10.

[0011] In various embodiments, the antibody is administered every 2 weeks. In various embodiments, the antibody is administered every 4 weeks. In various embodiments, the antibody is administered at a dose of 210 mg. In various embodiments, the antibody is administered at a dose of 420 mg. In various embodiments, the antibody is an lgG2 antibody. In various embodiments, the antibody is a human igG2 antibody.

[0012] The disclosure also provides a method for treating eosinophilic esophagitis (EOE) in a subject comprising administering anti-TSLP antibody or antibody variant in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2;

[0013] The disclosure provides a method for treating eosinophilic esophagitis (EOE) in a subject comprising administering an anti-TSLP antibody or antibody variant in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0014] The disclosure further provides a method for eosinophilic esophagitis (EOE) in a subject comprising selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0015] Also contemplated is a method for treating eosinophilic esophagitis (EOE) in a subject comprising selecting a subject in need of treatment for EOE, administering an anti- TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2. [0016] In various embodiments, the sequence of amino acids is at least about 80%, 85%, 90% 95%, 96%, 97%, 98%, 99% or more identical to the heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO: 10 or at least about 80%, 85%, 90% 95%, 96%, 97%, 98%, 99% or more identical to the light chain variable region domain comprising the amino acid sequence set forth in SEQ ID NO: 12. It is contemplated that heavy chain variable region sequences less than 100% identical to SEQ ID NO: 10 retain the CDR amino acid sequences set forth in SEQ ID NOs: 6-8, and light chain variable region sequences less than 100% identical to SEQ ID NO: 12 retain the CDR amino acid sequences set forth in SEQ ID NOs: 3-5.

[0017] In various embodiments, the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:10.

[0018] In various embodiments, the antibody or antibody variant is administered every 4 weeks.

[0019] In various embodiments, the antibody or antibody variant is administered at a dose of 420 mg every 2 weeks. In various embodiments, the antibody or antibody variant is administered at a dose of 420 mg every 4 weeks. In various embodiments, the antibody or antibody variant is administered at a dose of 210 mg every 2 weeks. In various embodiments, the antibody or antibody variant is administered at a dose of 210 mg every 4 weeks.

[0020] In various embodiments, the antibody is administered at a dose of 420 mg every 2 weeks. In various embodiments, the antibody is administered at a dose of 420 mg every 4 weeks. In various embodiments, the antibody is administered at a dose of 210 mg every 2 weeks. In various embodiments, the antibody is administered at a dose of 210 mg every 4 weeks. In various embodiments, the antibody is an lgG2 antibody. In various embodiments, the antibody is a human igG2 antibody.

[0021] In various embodiments, the disclosure provides a method of treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody has a full- length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14. Also contemplated is a method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

[0022] In various embodiments, the subject is also receiving treatment with proton pump inhibitors, corticosteroids, glucocorticoids, or combinations thereof.

[0023] In various embodiments the corticosteroids are oral corticosteroids (OCS) or inhaled corticosteroids (ICS) which are swallowed topical corticosteroids (STC). In various embodiments, the corticosteroids are one or more of prednisone, prednisolone, deflazacort, fluticasone, budesonide, ciclesonide, or combinations thereof.

[0024] In various embodiments, the method comprises administering an anti-TSLP antibody or antibody variant in conjunction with proton pump inhibitors (P Pls), glucocorticoids, corticosteroids, or combinations thereof.

[0025] In various embodiments, the subject is unresponsive to STC.

[0026] In various embodiments, the anti-TSLP antibody variant has substantially similar pK characteristics as tezepelumab-ekko in humans.

[0027] In various embodiments, the antibody or antibody variant is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

[0028] In various embodiments, the anti-TSLP antibody or antibody variant thereof is bivalent and selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a recombinant antibody, an antigen-binding antibody fragment, a single chain antibody, a monomeric antibody, a diabody, a triabody, a tetrabody, a Fab fragment, an IgG 1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

[0029] In one embodiment, the anti-TSLP antibody variant is selected from the group consisting of a Fab fragment, a single domain antibody, an scFv, wherein the dose is adjusted such that the binding sites are equimolar to those dosed by bivalent antibodies.

[0030] In various embodiments, the anti-TSLP antibody is an anti-TSLP antibody derivative.

[0031] In various embodiments, the antibody is an lgG2 antibody.

[0032] In one embodiment, the antibody or antibody variant is a human antibody.

[0033] In various embodiments, the antibody is tezepelumab. In various embodiments, tezepelumab is an lgG2 antibody. In various embodiments, tezepelumab has the full length heavy and light chain amino acid sequences set out in SEQ ID NOs: 13 and 14, respectively. In various embodiments, the tezepelumab is tezepelumab-ekko.

[0034] In various embodiments, the antibody or antibody variant further is administered to the subject in a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient.

[0035] In various embodiments, the subject is suffering from asthma, atopic dermatitis, allergic rhinitis/sinusitis, environmental allergies, and/or food allergies.

[0036] In various embodiments, the subject is an adult or an adolescent.

[0037] It is further contemplated that administration of the anti-TSLP antibody or antibody variant decreases levels of Th2 cytokines in the subject.

[0038] In various embodiments, the method improves one or more measures of EOE in a subject selected from the group consisting of histologic response of peak esophageal eosinophils per HPF count of < 6 across all available esophageal levels, EOE Endoscopic Reference Score (EREFS) (including esophageal edema, rings, exudates, furrows, and stricture), EOE-Histological Scoring System (EOE-HSS) grade score and EOE-HSS stage score (including eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis) and Dysphagia Symptom Questionnaire (DSQ) score.

[0039] In one embodiment, the administration improves one or more symptoms of EOE as measured by patient diary. Examples of a patient diary include, but are not limited to, Dysphagia Symptom Questionnaire (DSQ) score.

[0040] In various embodiments, treatment with anti-TSLP antibody or antibody variant modulates the levels of one or more biomarkers of EOE, including, serum biomarkers, urine biomarkers (e.g., markers of mast cell activation tetranor PGDM, 11 b-PGF2a, and t-MlAA), cytokines, IgE, CCL17, CCL18, CCL22, and RNA transcriptional changes in esophageal epithelium. In various embodiments, treatment with anti-TSLP reduces the level of Th2 cytokines. In various embodiments, the treatment modulates (reduces or moderates) levels of or activity of one or more of IL-4, IL-5, IL-13, IL-17, IL-22, IL-23, IL-31 , IL-33, or combinations thereof.

[0041] Also provided herein is a method for reducing the number of eosinophils per high- power microscopy field (HPF) in a subject having EOE, comprising administering an anti- TSLP antibody or antibody variant in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0042] Further provided is a method of reducing the number of eosinophils per high-power field (HPF) (e.g., HPF microscopy) in a subject having EOE comprising administering an anti-TSLP antibody or antibody variant in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

[0043] Also contemplated is a method of reducing the number of eosinophils per high- power field (HPF) (e.g., HPF microscopy) in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0044] Also provided is a method of reducing the number of eosinophils per high-power field (HPF) (e.g., HPF microscopy) in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

[0045] Also contemplated is a method of reducing the number of eosinophils per high- power field (HPF) (e.g., HPF microscopy) in a subject comprising, administering an anti- TSLP antibody or antibody variant to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0046] Also provided is a method of reducing the number of eosinophils per high-power field (HPF) (e.g., HPF microscopy) in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

[0047] In various embodiments, the eosinophils per HPF (eos/HPF) count is reduced to < 6 across all available esophageal levels in a subject receiving treatment.

[0048] Also provided herein is a method for reducing dysphagia and/or Dysphagia Symptom Questionnaire (DSQ) score in a subject having EOE comprising administering an anti-TSLP antibody or antibody variant in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2. [0049] Further provided is a method for reducing dysphagia and/or Dysphagia Symptom Questionnaire (DSQ) score in a subject having EOE comprising administering an anti-TSLP antibody or antibody variant in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

[0050] Also contemplated is a method for reducing dysphagia and/or Dysphagia Symptom Questionnaire (DSQ) score in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0051] Also provided is a method for reducing dysphagia and/or Dysphagia Symptom Questionnaire (DSQ) score in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

[0052] Also contemplated is a method for reducing dysphagia and/or Dysphagia Symptom Questionnaire (DSQ) score in a subject comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0053] Also provided is a method for reducing dysphagia and/or Dysphagia Symptom Questionnaire (DSQ) score in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

[0054] Provided herein is a method a method of reducing the frequency of EOE exacerbation in a subject having EOE comprising selecting a subject in need of treatment for EOE, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0055] Further contemplated is a method of reducing the frequency of EOE relapse in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b). [0056] In various embodiments, the disclosure provides a method of treating eosinophilic esophagitis (EOE) in a subject in need thereof comprising administering to an anti-TSLP antibody to the subject in a dose of 210 mg or 420 mg as described herein administered every 2 weeks to every 4 weeks. In various embodiments, the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14. In various embodiments, the antibody is tezepelumab.

[0057] In various embodiments, the disclosure provides a method of treating eosinophilic esophagitis (EOE) in a subject in need thereof comprising administering to the subject between 210 mg and 420 mg of anti-TSLP antibody as described herein administered over a period of two to four weeks. In various embodiments, the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14. In various embodiments, the antibody is tezepelumab.

[0058] In various embodiments, the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14. In various embodiments, the antibody is tezepelumab.

[0059] In another embodiment, the disclosure provides a method for reducing the number of eosinophils in the esophagus of a subject comprising administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0060] Also provided is a method for reducing the number of eosinophils in the esophagus of a subject comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b)

[0061] In another embodiment, the disclosure provides a method of reducing inflammation in the esophagus of a subject in need thereof comprising administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0062] Also provided is a method for reducing inflammation in the esophagus of a subject in need thereof comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

[0063] In another embodiment, the disclosure provides a method reducing fibrosis associated with inflammation of the esophagus in a subject in need thereof comprising administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0064] Also provided is a method of reducing fibrosis associated with inflammation of the esophagus in a subject in need thereof comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b). [0065] In various embodiments, the subject has EOE.

[0066] In another aspect, the disclosure provides a composition comprising an anti-TSLP antibody or antibody variant for treating eosinophilic esophagitis (EOE) in a subject, wherein the composition is administered in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, the antibody comprising a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and, b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

[0067] Also provided is a composition comprising an anti-TSLP antibody or antibody variant for treating eosinophilic esophagitis (EOE) in a subject, wherein the composition is administered in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP , the antibody comprising: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and, b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

[0068] Further provided is use of a composition comprising an anti-TSLP antibody or antibody variant in the manufacture of a medicament for treating eosinophilic esophagitis (EOE) in a subject, wherein the composition is in a dose of 210 mg to 420 mg for administration at an interval of every 2 weeks or 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, the antibody comprising a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0069] Also provided is use of a composition comprising an anti-TSLP antibody or antibody variant in the preparation of a medicament for treating eosinophilic esophagitis (EOE), wherein the composition is in a dose of 210 mg to 420 mg for administration at an interval of every 2 weeks or 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, the antibody comprising a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and, b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or, c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0070] In various embodiments, the light chain variable domain comprises the amino acid sequence set forth in in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

[0071] In various embodiments, the composition for treating eosinophilic esophagitis (EOE) in a subject comprises an anti-TSLP antibody, wherein the antibody is administered in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14. In another embodiment, a composition for treating eosinophilic esophagitis (EOE) in a subject comprises an anti-TSLP antibody, wherein the antibody is administered in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

[0072] The disclosure further provides for use of a composition comprising an anti-TSLP antibody in the preparation of a medicament for treating eosinophilic esophagitis (EOE), wherein the composition is in a dose of 210 mg for administration at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14. In another embodiment, disclosed is use of a composition comprising an anti-TSLP antibody in the preparation of a medicament for treating eosinophilic esophagitis (EOE), wherein the composition is in a dose of 420 mg for administration at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

[0073] In various embodiments, the composition is a pharmaceutical composition comprising an anti-TSLP antibody or variant thereof and one or more pharmaceutically acceptable carriers or excipients. In various embodiments, the composition comprises an anti-TSLP antibody and a surfactant, proline, and a buffer. In some embodiments, the surfactant is polysorbate 80. In various embodiments, the buffer is selected from the group consisting of: succinate, glutamate, histidine, and acetate. In various embodiments, the formulation is at pH between 4.5 and 6.8.

[0074] In various embodiments, the composition comprises anti-TSLP antibody and one or more basic amino acids (e.g., arginine, histidine or lysine) or salt thereof, or a calcium or magnesium salt, and a surfactant (e.g., polysorbate 20 or polysorbate 80). In various embodiments, the formulation is at pH between 4.5 and 6.8.

[0075] In various embodiments, the antibody or antibody variant is administered every 4 weeks. In various embodiments, the antibody or antibody variant is administered at a dose of 420 mg.

[0076] In various embodiments, the antibody is an lgG2 antibody. In various embodiments the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14. In various embodiments, the antibody is tezepelumab. [0077] In various embodiments, the antibody or antibody variant is administered every 4 weeks. In various embodiments, the antibody or antibody variant is administered at a dose of 420 mg every 2 weeks. In various embodiments, the antibody or antibody variant is administered at a dose of 420 mg every 4 weeks. In various embodiments, the antibody or antibody variant is administered at a dose of 210 mg every 4 weeks.

[0078] It is contemplated that the dosing and antibody and antibody variant types referenced above apply to each method, composition or use contemplated herein.

[0079] In various embodiments, the antibody or antibody variant is administered to the subject in a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient.

[0080] In various embodiments, the administration delays the time to a EOE exacerbation or relapse compared to a subject not receiving the anti-TSLP antibody. In various embodiments, the administration reduces the severity of a EOE exacerbation or relapse compared to a subject not receiving the anti-TSLP antibody.

[0081] In various embodiments, the administration is subcutaneous. In various embodiments, the administration is intravenous.

[0082] Syringes, e.g., single use or pre-filled syringes, sterile sealed containers, e.g. vials, bottle, vessel, and/or kits or packages comprising any of the foregoing antibodies or compositions, optionally with suitable instructions for use, are also contemplated for use in the methods. In various embodiments, the administration is via pre-filled syringe or autoinjector. In various embodiments, the auto-injector is an Ypsomed YpsoMate® device.

[0083] It is understood that each feature or embodiment, or combination, described herein is a non-limiting, illustrative example of any of the aspects of the invention and, as such, is meant to be combinable with any other feature or embodiment, or combination, described herein. For example, where features are described with language such as “one embodiment”, “some embodiments”, “certain embodiments”, “further embodiment”, “specific exemplary embodiments”, and/or “another embodiment”, each of these types of embodiments is a non-limiting example of a feature that is intended to be combined with any other feature, or combination of features, described herein without having to list every possible combination. Such features or combinations of features apply to any of the aspects of the invention. Where examples of values falling within ranges are disclosed, any of these examples are contemplated as possible endpoints of a range, any and all numeric values between such endpoints are contemplated, and any and all combinations of upper and lower endpoints are envisioned. [0084] The headings herein are for the convenience of the reader and not intended to be limiting. Additional aspects, embodiments, and variations of the invention will be apparent from the Detailed Description and/or Drawings and/or claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0085] Figure 1 . Enrichment of TSLP gene lists in patients with EoE. *p < 0.05; **p < 0.01 ; ***p < 0.001 ; ****p < 0.000. EOE, eosinophilic esophagitis; GSVA, gene set variation analyses; mDC, myeloid dendritic cell; ns, not significant (p > 0.05); STCs, swallowed topical corticosteroid; TSLP, thymic stromal lymphopoietin.

[0086] Figure 2. Amino acid and nucleotide sequences of TSLP and anti-TSLP antibody.

DETAILED DESCRIPTION

[0087] This present disclosure investigates TSLP-mediated gene expression changes in patients with EOE and the effects of anti-TSLP antibody, e.g., tezepelumab, as a treatment for EOE. It is hypothesized that inhibition of upstream TSLP by tezepelumab will be effective in reducing esophageal inflammation in patients with EOE and reducing histological symptoms of EOE.

Definitions

[0088] Unless otherwise stated, the following terms used in this application, including the specification and claims, have the definitions given below.

[0089] As used in the specification and the appended claims, the indefinite articles “a” and “an” and the definite article “the” include plural as well as singular referents unless the context clearly dictates otherwise.

[0090] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. The following references provide one of skill with a general definition of many of the terms used in this disclosure include, but are not limited to: Singleton etal., DICTIONARY OF MICROBIOLOGY AND MOLECULAR BIOLOGY (2d Ed. 1994); THE CAMBRIDGE DICTIONARY OF SCIENCE AND TECHNOLOGY (Walker Ed., 1988); THE GLOSSARY OF GENETICS, 5th Ed., R. Rieger et al. (Eds.), Springer Verlag (1991); and Hale & Marham, THE HARPER COLLINS DICTIONARY OF BIOLOGY (1991). [0091] The term “about” or “approximately” means an acceptable error for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined. In certain embodiments, the term “about” or “approximately” means within 1 , 2, 3, or 4 standard deviations. In certain embodiments, the term “about” or “approximately” means within 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.05% of a given value or range. Whenever the term “about” or “approximately” precedes the first numerical value in a series of two or more numerical values, it is understood that the term “about” or “approximately” applies to each one of the numerical values in that series.

[0092] The term “eosinophilic esophagitis” or “EOE” as used herein refers to a chronic inflammatory disease that results in inflammation and increased eosinophils in the esophagus, which can result in fibrosis and obstructed swallowing (dysphagia) in patients with EOE.

[0093] The term “EOE exacerbation” as used herein refers to an acute increase in EOE symptoms, and/or relapse of symptoms and may warrant a change in regular medication.

[0094] The term “worsening of EOE” refers to new or increased symptoms and/or signs (examination) that can be either concerning to the subject having EOE (subject-driven) or related to a Patient Daily Diary alert or Patient Reported Outcome (diary-driven).

[0095] The term “cytokine” as used herein refers to one or more small (5-20 kD) proteins released by cells that have a specific effect on interactions and communications between cells or on the behavior of cells, such as immune cell proliferation and differentiation. Functions of cytokines in the immune system include, promoting influx of circulating leukocytes and lymphocytes into the site of immunological encounter; stimulating the development and proliferation of B cells, T cells, peripheral blood mononuclear cells (PBMCs) and other immune cells; and providing antimicrobial activity. Exemplary immune cytokines, include but are not limited to, IL-1 , IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL- 12, IL-13, IL-15, IL17A, IL-17F, IL-18, IL-21 , IL-22, IL-23, IL-31 , IL-33, interferon (including IFN alpha, beta, and gamma), tumor necrosis factor (including TNF alpha, beta), transforming growth factor (including TGF alpha, beta), granulocyte colony stimulating factor (GCSF), granulocyte macrophage colony stimulating factor (GMCSF) and thymic stromal lymphopoietin (TSLP).

[0096] A “T helper (Th) 1 cytokine” or “Th 1 -specific cytokine” refers to cytokines that are expressed (intracellularly and/or secreted) by Th1 T cells, and include IFN-g, TNF-a, and IL- 12. A “Th2 cytokine” or “Th2-specific cytokine” refers to cytokines that are expressed (intracellularly and/or secreted) by Th2 T cells, including IL-4, IL-5, IL-13, and IL-10. A“Th17 cytokine” or “Th17-specific cytokine” refers to cytokines that are expressed (intracellularly and/or secreted) by Th17 T cells, including IL-17A, IL-17F, IL-22 and IL-21 . Certain populations of Th17 cells express IFN-g and/or IL-2 in addition to the Th17 cytokines listed herein. A polyfunctional CTL cytokine includes IFN-g, TNF-a, IL-2 and IL-17.

[0097] The term “specifically binds” is "antigen specific", is “specific for”, “selective binding agent", “specific binding agent”, “antigen target” or is “immunoreactive” with an antigen refers to an antibody or polypeptide that binds a target antigen with greater affinity than other antigens of similar sequence. It is contemplated herein that the agent specifically binds target proteins useful in identifying immune cell types, for example, a surface antigen (e.g., T cell receptor, CD3), a cytokine (e.g., TSLP, IL-4, IL-5, IL-13, IL-17, IFN-g, TNF-a) and the like. In various embodiments, the antibody specifically binds the target antigen, but can cross-react with an ortholog of a closely related species, e.g., an antibody may bind human protein and also bind a closely related primate protein.

[0098] The term “antibody” or “immunoglobulin” refers to a tetrameric glycoprotein that consists of two heavy chains and two light chains, each comprising a variable region and a constant region. “Heavy Chains” and “Light Chains” refer to substantially full-length canonical immunoglobulin light and heavy chains (see e.g., Immunobiology, 5th Edition (Janeway and Travers et al., Eds., 2001). Antigen-binding portions may be produced by recombinant DNA techniques or by enzymatic or chemical cleavage of intact antibodies. The term “antibody” includes monoclonal antibodies, polyclonal antibodies, chimeric antibodies, human antibodies, and humanized antibodies. For the purposes of the claims of the present invention, the term “antibody” and “anti-TSLP antibody” refer to a tetrameric glycoprotein that consists of two heavy chains and two light chains, each comprising a variable region and a constant region and having an IgG 1 , lgG2, lgG3 or lgG4 Fc region.

[0099] Antibody variants include antibody fragments and antibody like proteins with changes to structure of canonical tetrameric antibodies. Typically, antibody variants include V regions with a change to the constant regions, or, alternatively, adding V regions to constant regions, optionally in a non-canonical way. Examples include antibody fragments that can bind an antigen (e.g., Fab', F'(ab)2, Fv,), biparatopic and recombinant peptides comprising the forgoing as long as they exhibit the desired biological activity. Variants may comprise an Fc region from an IgG antibody, e.g., an IgG 1 , lgG2, lgG3 or lgG4 Fc region.

[00100] An antibody variant contemplated herein also includes antibody derivatives having the CDRs set out in SEQ ID NO: 3-8, but may have an amino acid change or chemical modification (e.g., oxidation, methylation) in a variable region amino acid of SEQ ID NO: 10 or 12, or a Fc region amino acid set out in SEQ ID NO: 13 or 14, as a result of manufacturing or purification procedures, or due to improvement in manufacturing or purification procedures. Antibody variants/derivatives of tezepelumab are described in PCT/US22/25994 (International Publication WO 2022/226339) and PCT/US22/25999 (International Publication WO 2022/226342), incorporated herein by reference in their entireties.

[00101] Antibody fragments include antigen-binding portions of the antibody including, inter alia, Fab, Fab', F(ab')2, Fv, domain antibody (dAb), complementarity determining region (CDR) fragments, CDR-grafted antibodies, or a variant or a derivative thereof, and polypeptides that contain at least a portion of an immunoglobulin that is sufficient to confer specific antigen binding to the polypeptide, such as one, two, three, four, five or six CDR sequences, as long as the antibody retains the desired biological activity.

[0100] “Valency” refers to the number of antigen binding sites on each antibody or antibody fragment that targets an epitope. A typical full length IgG molecule, or F(ab)2 is “bivalent” in that it has two identical target binding sites. A “monovalent’ antibody fragment such as a F(ab)’ or scFv with a single antigen binding site. Trivalent or tetravalent antigen binding proteins can also be engineered to be multivalent.

[0101] “Monoclonal antibody” refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts.

[0102] The term “inhibits TSLP activity” includes inhibiting any one or more of the following: binding of TSLP to its receptor; proliferation, activation, or differentiation of cells expressing TSLPR in the presence of TSLP; inhibition of Th2 cytokine production in a polarization assay in the presence of TSLP; dendritic cell activation or maturation in the presence of TSLP; and mast cell cytokine release in the presence of TSLP. See, e.g., US Patent 7982016 B2, column 6 and example 8 and US 2012/0020988 A1 , examples 7-10.

[0103] The term “sample” or "biological sample" refers to a specimen obtained from a subject for use in the present methods, and includes urine, whole blood, plasma, serum, saliva, sputum, skin or tissue biopsies, cerebrospinal fluid, peripheral blood mononuclear cells with in vitro stimulation, peripheral blood mononuclear cells without in vitro stimulation, gut lymphoid tissues with in vitro stimulation, gut lymphoid tissues without in vitro stimulation, gut lavage, bronchioalveolar lavage, nasal lavage, and induced sputum. [0104] The terms “treat”, “treating” and “treatment” refer to eliminating, reducing, suppressing or ameliorating, either temporarily or permanently, either partially or completely, a clinical symptom, manifestation or progression of an event, disease or condition associated with an inflammatory disorder described herein. As is recognized in the pertinent field, drugs employed as therapeutic agents may reduce the severity of a given disease state, but need not abolish every manifestation of the disease to be regarded as useful therapeutic agents. Similarly, a prophylactically administered treatment need not be completely effective in preventing the onset of a condition in order to constitute a viable prophylactic agent. Simply reducing the impact of a disease (for example, by reducing the number or severity of its symptoms, or by increasing the effectiveness of another treatment, or by producing another beneficial effect), or reducing the likelihood that the disease will occur or worsen in a subject, is sufficient. One embodiment of the invention is directed to a method for determining the efficacy of treatment comprising administering to a patient therapeutic agent in an amount and for a time sufficient to induce a sustained improvement over baseline of an indicator that reflects the severity of the particular disorder.

[0105] The term “therapeutically effective amount” refers to an amount of therapeutic agent that is effective to ameliorate or lessen symptoms or signs of disease associated with a disease or disorder.

Eosinophilic esophagitis

[0106] Based on the guidelines outlined in Dellon et al 2018, EOE is defined histologically by esophageal inflammation of > 15 EOS/HPF as obtained from biopsies from one location: either the proximal, mid, and/or distal esophagus and exclusion of secondary causes of esophageal eosinophilia. In addition to peak eosinophil count, additional histologic features may include eosinophil microabscesses, basal zone hyperplasia, dilated intercellular spaces, eosinophil surface layering, papillary elongation, and lamina propria fibrosis (Lucendo et al 2017). These diagnostic criteria are the same for both adults and adolescent patients.

[0107] Eosinophilic esophagitis is thought to be generally progressive, with persistent symptoms and inflammation leading to impairment of quality of life (QoL). Esophageal eosinophilic, mastocytic, and lymphocytic infiltrate causes symptoms of esophageal dysfunction (Lucendo et al 2017), and chronic eosinophilic inflammation is associated with tissue remodeling with fibrosis, which may result in strictures in the esophagus.

[0108] While the esophageal pathophysiology of EOE is consistent between children and adults, the symptoms of esophageal dysfunction may be reported differently in these patient populations. Common between adults and adolescent patients are symptoms of dysphagia and food impaction (Dellon et al 2014, Dellon et al 2017, Dellon and Liacouras 2014). Patients with EOE also commonly have high rates of concurrent allergic diatheses, especially food sensitization, compared with the general population (Liacouras et al 2011).

[0109] A systematic literature review and meta-analysis for the period up to September 2018 published by Navarro et al 2019 concluded that the prevalence of EOE across North America and Europe was 42.2 per 100000 (95% Cl, 31.1 to 55) in the adult population, and 34.4 per 100000 (95% Cl, 22.3 to 49.2) in the pediatric population. Navarro et al 2019 reported pooled incidence rates of EOE in North America and Europe of 4.4 per 100000 (95% Cl, 2.8 to 6.4) in the overall population, and 6.6 per 100000 (95% Cl, 3.0 to 11 .7) in the pediatric population. Eosinophilic esophagitis is recognized to be more frequent in males than females. Eosinophilic esophagitis prevalence is also reported to vary by ancestry. A retrospective study of the demographics of EOE from over 30 million individuals’ electronic healthcare records in US-based healthcare systems found 7840 diagnoses of EOE with 89.3% in Caucasians, 6.1% in African Americans, and 5.6% in Asian backgrounds (Mansoor and Cooper 2016). These data supported earlier results of a retrospective analysis of 208 EOE cases in North Carolina where 82% were Caucasian and 12% African American (Sperry et al 2012). African American patients were younger at presentation and less likely to have esophageal rings present. Between countries, EOE prevalence also differs with EOE identified in 2.4% to 6% of individuals undergoing an EGD (for any cause) in the US, while only diagnosed in < 0.4% of individuals undergoing EGD in China (Dellon and Hirano 2018). Yet in all cohorts, the prevalence of EOE is recognized to be increasing.

[0110] Overall, epidemiological studies suggest an increase in the incidence and prevalence of EOE over the last 2 decades. However, there is significant variability in the prevalence of EOE dependent on the study location, population, and methodology including the EOE case definition.

[0111] There are few products approved for the treatment of the disease: JORVEZA® (orodispersible budesonide tablet), which was approved for the treatment of EOE in adults in the EU in 2018 (Diver et al 2021 , Dr. Falk Pharma GmbH 2018), in Australia in 2020 (Dr. Falk Pharma Australia Pty Ltd 2020), and in Canada in 2021 (AV IR Pharma Inc. 2017); and DUPIXENT® (dupilumab), which was approved in US in 2022 for patients with EOE aged 12 years and older, weighing at least 40 kg (Sanofi and Regeneron Pharmaceuticals, Inc 2022). However, not all patients respond to these therapies (approximately 15% of patients in the Phase III orodispersible budesonide study did not achieve remission at 12 weeks; approximately 40% of patients in the dupilumab Phase III study did not achieve remission at 24 weeks). Additionally, some patients taking orodispersible budesonide develop intolerable side-effects (Lucendo et al 2019).

[0112] Dietary elimination of possible food allergens can be effective, but the evidence for this is short term and can present challenges with longer-term compliance and effectiveness over time. Esophageal dilation may be used as an effective therapy in symptomatic patients with strictures that persist despite medical or dietary therapy. Although considered minimally invasive, esophageal dilation may cause bruising, soreness, and difficulty swallowing after the procedure and has an inherent risk of perforation and even mediastinitis. Moreover, dilation does not address esophageal inflammation associated with EOE (Hirano et al 2020a). Because of ongoing fibrotic processes that persist in the tissue of the esophagus, patients may require repeated dilations over time. As EOE is chronic and symptoms recur when treatments are discontinued, maintenance therapy should be considered in all patients (Dellon et al 2013).

[0113] Dupilumab, a dual inhibitor of IL-4 and IL-13 signaling, is the only biologic approved (in the US) for the treatment of EOE. Studies in patients with EOE have shown evidence of the efficacy of IL-4 receptor inhibition and esophageal tissue eosinophil depletion following treatment with dupilumab (Hirano et al 2020b). In a Phase III study, dupilumab showed significant improvements in clinical, endoscopic, histologic, symptomatic, and molecular measures of EOE (Dellon et al 2020b, Chehade et al 2021 , Rothenberg et al 2022).

[0114] Eosinophilic and mastocytic inflammation is central to the pathophysiology of EOE; hence, therapies that target one or more of these cell types, such as tezepelumab, which selectively blocks TSLP from interacting with its heterodimeric receptor, may provide a safe and effective treatment option for patients with EOE. The prominent accumulation and activation of pro-inflammatory eosinophils and mast cells in the esophagus of EOE patients and their pathogenic role in nonclinical modeling suggests that an approach with the potential to act both upstream and downstream in the esophageal inflammatory cascade, as provided by tezepelumab, may prove beneficial in the improvement of dysphagia, histology, and EGD macroscopic disease scores, as well as other markers of disease activity.

[0115] The key goals of treatment for EOE are to decrease the signs and symptoms of the disease. These goals can be achieved by reducing esophageal eosinophilic inflammation. It is presumably through persistent esophageal eosinophilic inflammation that patients with EOE have an increased risk of progression to fibrostenosis and an increased potential for complications from food impactions (Warners et al 2018). Reducing the progression of esophageal eosinophilic inflammation to esophageal fibrosis may lead to avoidance of stricture formation and subsequent lower need for esophageal dilation, failure to thrive in children, and improvement in patient QoL.

TSLP

[0116] Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that is produced in response to pro-inflammatory stimuli and drives allergic inflammatory responses primarily through its activity on dendritic cells (Gilliet, J Exp Med. 197:1059-1067, 2003; Soumelis, Nat Immunol. 3:673-680, 2002; Reche, J Immunol. 167:336-343, 2001), mast cells (Allakhverdi, J Exp Med. 204:253-258, 2007) and CD34+ progenitor cells. TSLP signals through a heterodimeric receptor consisting of the interleukin (IL)-7 receptor alpha (IL-7Ra) chain and a common y chain-like receptor (TSLPR) (Pandey, Nat Immunol. 1 :59- 64, 2000; Park, J Exp Med. 192:659-669, 2000).

[0117] Tezepelumab selectively blocks TSLP from interacting with its heterodimeric receptor. In asthma, another eosinophilic-driven disease, tezepelumab has demonstrated important benefits in both a Phase lib study (PATHWAY; Corren et al 2017) and a Phase III study (NAVIGATOR; Menzies-Gow et al 2021) in reducing exacerbations and improving lung function, asthma control, and asthma-related QoL. Tezepelumab has been shown to decrease eosinophilic infiltration of the bronchial submucosa in asthma patients through bronchoscopy biopsy (CASCADE; Diver et al 2021). TSLP-driven eosinophilic inflammation is a central finding in EOE. By blocking the interaction of TSLP with its heterodimeric receptor and interfering with multiple downstream inflammatory pathways, tezepelumab has the potential to reduce the initiation and persistence of esophageal eosinophilia and inflammation which are important factors in the histologic pathogenesis of EOE.

Antibodies

[0118] It is contemplated that antibodies or antibody variants specific for TSLP are useful in the treatment of EOE.

[0119] Specific binding agents such as antibodies and antibody variants or fragments that bind to their target antigen, e.g., TSLP, are useful in the methods of the disclosure. In one embodiment, the specific binding agent is an antibody. The antibodies may be monoclonal (MAbs); recombinant; chimeric; humanized, such as complementarity-determining region (C DR) -grafted; human; antibody variants, including single chain; and/or bispecific; as well as fragments; variants; or derivatives thereof. Antibody fragments include those portions of the antibody that bind to an epitope on the polypeptide of interest. Examples of such fragments include Fab and F(ab') fragments generated by enzymatic cleavage of full-length antibodies. Other binding fragments include those generated by recombinant DNA techniques, such as the expression of recombinant plasmids containing nucleic acid sequences encoding antibody variable regions.

[0120] Monoclonal antibodies may be modified for use as therapeutics or diagnostics. One embodiment is a "chimeric" antibody in which a portion of the heavy (H) and/or light (L) chain is identical with or homologous to a corresponding sequence in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is/are identical with or homologous to a corresponding sequence in antibodies derived from another species or belonging to another antibody class or subclass. Also included are fragments of such antibodies, so long as they exhibit the desired biological activity. See U.S. Pat. No. 4,816,567; Morrison et al., 1985, Proc. Natl. Acad. Sci. 81 :6851- 55.

[0121] In another embodiment, a monoclonal antibody is a "humanized" antibody. Methods for humanizing non-human antibodies are well known in the art. See U.S. Pat. Nos. 5,585,089 and 5,693,762. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source that is non-human. Humanization can be performed, for example, using methods described in the art (Jones et al., 1986, Nature 321 :522-25; Riechmann et al., 1998, Nature 332:323-27; Verhoeyen et al., 1988, Science 239:1534-36), by substituting at least a portion of a rodent complementarity-determining region (CDR) or framework region for the corresponding regions of a human antibody. For example, with CDR-grafting, non-human CDR sequences are inserted into human framework regions (Lu et al. Journal of Biomedical Science (2020) 27:1).

[0122] Also encompassed by the disclosure are human antibodies and antibody variants (including antibody fragments) that bind TSLP. Human antibody refers to an antibody generated from human immunoglobulin sequences and comprising human variable and constant regions. Using transgenic animals (e.g., mice) that are capable of producing a repertoire of human antibodies in the absence of endogenous immunoglobulin production such antibodies are produced by immunization with a polypeptide antigen (i.e., having at least 6 contiguous amino acids), optionally conjugated to a carrier. See, e.g., Jakobovits et al., 1993, Proc. Natl. Acad. Sci. 90:2551-55; Jakobovits et al., 1993, Nature 362:255-58; Bruggermann et al., 1993, Year in Immuno. 7:33. See also PCT App. Nos. PCT/US96/05928 and PCT/US93/06926. Additional methods are described in U.S. Pat. No. 5,545,807, PCT App. Nos. PCT/US91/245 and PCT/GB89/01207, and in European Patent Nos. 546073B1 and 546073A1 . Human antibodies can also be produced by the expression of recombinant DNA in host cells or by expression in hybridoma cells, using phage display libraries, or by single B cell cloning (Lu et al. Journal of Biomedical Science (2020) 27:1 ). [0123] Chimeric, CDR grafted, and humanized antibodies and/or antibody variants are typically produced by recombinant methods. Nucleic acids encoding the antibodies are introduced into host cells and expressed using materials and procedures described herein. In a preferred embodiment, the antibodies are produced in mammalian host cells, such as CHO cells. Monoclonal (e.g., human) antibodies may be produced by the expression of recombinant DNA in host cells or by expression in hybridoma cells as described herein.

[0124] Antibodies and antibody variants (including antibody fragments) useful in the present methods comprise an anti-TSLP antibody comprising: a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and, b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody or antibody variant specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0125] Also contemplated is an antibody or antibody variant comprising a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and, b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody or antibody variant specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

[0126] Tezepelumab is an exemplary anti-TSLP antibody having: a. i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8.

[0127] Tezepelumab also comprises a light chain variable domain having the amino acid sequence set out in SEQ ID NO:12; encoded by a polynucleotide sequence set out in SEQ ID NO:11 ; and a heavy chain variable domain having the amino acid sequence set out in SEQ ID NQ:10, encoded by a polynucleotide sequence set out in SEQ ID NO:9.

[0128] Tezepelumab is an lgG2 antibody. The sequence of the full-length heavy chain and light chain of tezepelumab, including the lgG2 chain, is set out in SEQ ID NOs: 13 and 14, respectively.

[0129] Exemplary sequences of tezepelumab are also set out in US Patent 7,982,016 SEQ ID NOs: 13, 60, 105, 145, 173, 212; SEQ ID NOs: 361 and 363; and a light chain comprising a light chain variable domain comprising the amino acid sequence as set forth in SEQ ID NO:363 and a lambda light chain constant domain comprising the amino acid sequence as set forth in SEQ ID NO:369; and a heavy chain comprising a heavy chain variable domain comprising the amino acid sequence as set forth in SEQ ID NO:361 and an lgG2 heavy constant domain comprising the amino acid sequence as set forth in SEQ ID NO:365, herein incorporated by reference.

[0130] In various embodiments, anti-TSLP antibody derivatives are described in International Patent Publications WO 2022/226342 and WO 2022/226339, incorporated herein by reference in their entireties. Exemplary derivatives include tezepelumab antibodies that may have modifications after purification of antibody or after long term storage, including but not limited to, an isomerization derivative, a deamidation derivative, an oxidation derivative, a glycosylation derivative, disulfide isoform derivatives, and/or high molecular weight (HMW) species or antibody fragments. Exemplary derivatives may also be variants that have the amino acid sequences set out in SEQ ID NOs: 13-36 of WO2022/226342 as well as variants therein of SEQ ID NO: 3-8, e.g., including residues identified as possible sources of reduced stability in anti-TSLP antibody tezepelumab CDRs (SEQ ID NOs: 3-8) or in the variable region (SEQ ID NOs: 10 and 12), which include CDRH1 M34, CDRH2 W52, CDRH2 D54, CDRH2 N57, CDRH2 D62, CDRH3 W102, FRH1 N25, FRH1 N26, CDRL2 D49, CDRL2 D50, FRL2 N65, CDRL3 W90, CDRL3 D91 , CDRL3 S92,S93,S94, and/or CDRL3 D95. [0131] In various embodiments, the anti-TSLP antibody or antibody variant thereof is bivalent and selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a recombinant antibody, an antigen-binding antibody fragment, a single chain antibody, a monomeric antibody, a diabody, a triabody, a tetrabody, a Fab fragment, an IgG 1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

[0132] In various embodiments, the anti-TSLP antibody is bivalent and selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a recombinant antibody, an IgG 1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

[0133] It is contemplated that the antibody or antibody variant is an lgG2 antibody. Exemplary sequences for a human lgG2 constant region are available from the Uniprot database as Uniprot number P01859, incorporated herein by reference. Information, including sequence information for other antibody heavy and light chain constant regions is also publicly available through the Uniprot database as well as other databases well-known to those in the field of antibody engineering and production.

[0134] It is contemplated that the anti-TSLP antibody variant or anti-TSLP derivative has substantially similar pK characteristics as tezepelumab-ekko in humans.

[0135] In certain embodiments, derivatives of antibodies include tetrameric glycosylated antibodies wherein the number and/or type of glycosylation site has been altered compared to the amino acid sequences of a parent polypeptide. In certain embodiments, variants comprise a greater or a lesser number of N-linked glycosylation sites than the native protein. Alternatively, substitutions which eliminate this sequence will remove an existing N-linked carbohydrate chain. Also provided is a rearrangement of N-linked carbohydrate chains wherein one or more N-linked glycosylation sites (typically those that are naturally occurring) are eliminated and one or more new N-linked sites are created. Additional preferred antibody variants include cysteine variants wherein one or more cysteine residues are deleted from or substituted for another amino acid (e.g., serine) as compared to the parent amino acid sequence. Cysteine variants may be useful when antibodies must be refolded into a biologically active conformation such as after the isolation of insoluble inclusion bodies. Cysteine variants generally have fewer cysteine residues than the native protein, and typically have an even number to minimize interactions resulting from unpaired cysteines.

[0136] Desired amino acid substitutions (whether conservative or non-conservative) can be determined by those skilled in the art at the time such substitutions are desired. In certain embodiments, amino acid substitutions can be used to identify important residues of antibodies to human TSLP, or to increase or decrease the affinity of the antibodies to human TSLP described herein.

[0137] According to certain embodiments, preferred amino acid substitutions are those which: (1) reduce susceptibility to proteolysis, (2) reduce susceptibility to oxidation, (3) alter binding affinity for forming protein complexes, (4) alter binding affinities, and/or (4) confer or modify other physiochemical or functional properties on such polypeptides. According to certain embodiments, single or multiple amino acid substitutions (in certain embodiments, conservative amino acid substitutions) may be made in the naturally-occurring sequence (in certain embodiments, in the portion of the polypeptide outside the domain(s) forming intermolecular contacts). In certain embodiments, a conservative amino acid substitution typically may not substantially change the structural characteristics of the parent sequence (e.g., a replacement amino acid should not tend to break a helix that occurs in the parent sequence, or disrupt other types of secondary structure that characterizes the parent sequence). Examples of art-recognized polypeptide secondary and tertiary structures are described in Proteins, Structures and Molecular Principles (Creighton, Ed., W. H. Freeman and Company, New York (1984)); Introduction to Protein Structure (C. Branden and J. Tooze, eds., Garland Publishing, New York, N.Y. (1991)); and Thornton et al. Nature 354:105 (1991 ), which are each incorporated herein by reference.

[0138] It is contemplated that anti-TSLP antibodies useful to treat EOE as described herein, e.g., at 210 mg or 420 mg every 2 weeks or every 4 weeks, also include those described in the publications set out in Table 1 and described in WO2023098491A1 , WO2021155634A1 , WO2022166072A1 , WO2021043221 A1 , WO2022184074A1 , WO2021104053A1 , WO2023116925A1 , WO2021155861 A1 , WO2022116858A1 , WO2022117079A1 , WO2020244544A1 , WO2021152488A1 , WO2022253147A1 , W02023070948A1 , WO2023142309A1 , WO2022095689A1 , WO2021115240A1 , WO2022166739A1 and W02019100111 A1 , the disclosure of each of which is incorporated by reference herein.

Table 1

Methods of Administration

[0139] In one aspect, methods of the present disclosure include a step of administering a therapeutic anti-TSLP antibody or antibody variant described herein, optionally in a pharmaceutically acceptable carrier or excipient. In certain embodiments, the pharmaceutical composition is a sterile composition.

[0140] Contemplated herein are methods for treating EOE in a subject. In various embodiments, the method comprises selecting a subject in need of treatment for EOE, and administering an anti-TSLP antibody as described herein.

[0141] In various embodiments, the antibody is tezepelumab or tezepelumab variant or tezepelumab derivative.

[0142] It is contemplated that the subject to be treated is human. The subject may be an adult or an adolescent.

[0143] Therapeutic antibody (or antibody variant) compositions may be delivered to the patient at multiple sites. The multiple administrations may be rendered simultaneously or may be administered over a period of time. In certain cases it is beneficial to provide a continuous flow of the therapeutic composition. Additional therapy may be administered on a period basis, for example, hourly, daily, weekly, every 2 weeks, every 3 weeks, monthly, bimonthly, or at a longer interval.

[0144] In various embodiments, the amounts of therapeutic agent, such as a bivalent antibody having two TSLP binding sites, in a given dosage may vary according to the size of the individual to whom the therapy is being administered as well as the characteristics of the disorder being treated.

[0145] In exemplary treatments, the anti-TSLP antibody or antibody variant is administered in a dose range of about 210 mg to about 420 mg per dose. In various embodiments, the anti-TSLP antibody or antibody variant may be administered at a dose of about 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410 or 420 mg per dose. These concentrations may be administered as a single dosage form or as multiple doses. The above doses are given every two weeks or every four weeks. In various embodiments, the anti-TSLP antibody or antibody variant is administered at a single dose of 420 mg every two weeks or every four weeks. In various embodiments, the anti-TSLP antibody or antibody variant is administered at a single dose of 420 mg every four weeks. In various embodiments, the anti-TSLP antibody or antibody variant is administered at a single dose of 210 mg every two weeks or every four weeks. In various embodiments, the anti-TSLP antibody or antibody variant is administered at a single dose of 210 mg every four weeks. In various embodiments, the disclosure provides methods of treating eosinophilic esophagitis (EOE) in a subject in need thereof comprising administering to the subject between 210 mg and 420 mg of anti-TSLP antibody as described herein administered over a period of two to four weeks.

[0146] For antibody variants, the amount of antibody variant should be such that the number of TSLP binding sites that are in the dose have an equimolar number of TSLP binding sites to canonical bivalent antibody described above.

[0147] It is contemplated that the anti-TSLP antibody or antibody variant is administered every 2 weeks or every 4 weeks for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more. In various embodiments, the administration is subcutaneous or intravenous. In various embodiments, the administration is subcutaneous.

[0148] Treatment with the anti-TSLP antibody or antibody variant is contemplated to improve one or more measures of EOE including decrease in peak esophageal eosinophils per HPF (eos/hpf) count of < 6 across all available esophageal levels, EOE Endoscopic Reference Score (EREFS) (including esophageal edema, rings, exudates, furrows, and stricture), EOE- Histological Scoring System (EOE-HSS) grade score and EOE-HSS stage score (including eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis), esophageal fibrosis, dysphagia and Dysphagia Symptom Questionnaire (DSQ) score.

[0149] In one embodiment, the administration improves one or more symptoms of EOE including, but not limited to, DSQ score, histological measures, such as number or severity of strictures, Histological Scoring System (EOE-HSS) grade score and EOE-HSS stage score.

[0150] In various embodiments, the peak eos/HPF in treated patients decreases to at least < 15 eos/HPF.

[0151] In various embodiments, treatment with anti-TSLP modulates the levels of one or more biomarkers of EOE, including, serum biomarkers, urine biomarkers (e.g., markers of mast cell activation tetranor PGDM, 11 b-PGF2a, and t-MlAA), cytokines, IgE, CCL17, CCL18, CCL22, and RNA transcriptional changes in esophageal epithelium. In various embodiments, treatment with anti-TSLP reduces the level of Th2 cytokines. In various embodiments, the treatment modulates levels of or activity of IL-4, IL-5, IL-13, IL-17, IL-22, IL-23, IL-31 , and/or IL-33, or combinations thereof.

[0152] In various embodiments, treatment with the anti-TSLP antibody delays the time to a EOE exacerbation or relapse compared to a subject not receiving the anti-TSLP antibody. In various embodiments, treatment results in remission of EOE. In various embodiments, the treatment reduces esophageal inflammation.

[0153] Also contemplated in the present disclosure is the administration of multiple agents, such as an antibody composition in conjunction with a second agent as described herein, including but not limited to an anti-inflammatory agent, antibiotic or EOE therapy, such as leukotriene inhibitor, glucocorticoids, proton pump inhibitor (PPI), potassiumcompetitive acid blockers, or swallowed topical corticosteroids (STC).

[0154] Exemplary leukotriene inhibitors include montelukast, zafirlukast and zileuton.

[0155] In various embodiments, the subject is also receiving treatment with corticosteroids. In various embodiments the swallowed topical corticosteroids are selected from the group consisting of budesonide, fluticasone mometasone, deflazacort, prednisone, prednisolone, ciclesonide, and beclomethasone or combinations thereof.

[0156] In various embodiments, the method comprises administering anti-TSLP antibody or antibody variant in conjunction with a co-administered therapy, e.g., PPI, or STC.

[0157] In various embodiments, the subject is unresponsive to treatment with STCs.

Formulations

[0158] In some embodiments, the disclosure contemplates use of pharmaceutical compositions comprising a therapeutically effective amount of an anti-TSLP antibody or antibody variant together with a pharmaceutically acceptable diluent, carrier, solubilizer, emulsifier, preservative, and/or adjuvant. In addition, the disclosure provides methods of treating a subject by administering such pharmaceutical composition.

[0159] In certain embodiments, acceptable formulation materials preferably are nontoxic to recipients at the dosages and concentrations employed. In certain embodiments, the pharmaceutical composition may contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolality, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. In such embodiments, suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodium sulfite or sodium hydrogen-sulfite); buffers (such as borate, bicarbonate, Tris-HCI, citrates, phosphates or other organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin); fillers; monosaccharides; disaccharides; and other carbohydrates (such as glucose, sucrose, mannose or dextrins); proteins (such as serum albumin, gelatin or immunoglobulins); coloring, flavoring and diluting agents; emulsifying agents; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt-forming counterions (such as sodium); preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid or hydrogen peroxide); solvents (such as glycerin, propylene glycol or polyethylene glycol); sugar alcohols (such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as pluronics, PEG, sorbitan esters, polysorbates such as polysorbate 20, polysorbate, triton, tromethamine, lecithin, cholesterol, tyloxapal); stability enhancing agents (such as sucrose or sorbitol); tonicity enhancing agents (such as alkali metal halides, preferably sodium or potassium chloride, mannitol sorbitol); delivery vehicles; diluents; excipients and/or pharmaceutical adjuvants. See, REMINGTON'S PHARMACEUTICAL SCIENCES, 18" Edition, (A. R. Genrmo, ed.), 1990, Mack Publishing Company.

[0160] A suitable vehicle or carrier may be water for injection, physiological saline solution or artificial cerebrospinal fluid, possibly supplemented with other materials common in compositions for parenteral administration. Neutral buffered saline or saline mixed with serum albumin are further exemplary vehicles. In specific embodiments, pharmaceutical compositions comprise Tris buffer of about pH 7.0-8.5, or acetate buffer of about pH 4.0-5.5, and may further include sorbitol or a suitable substitute therefor.

[0161] The formulation components are present preferably in concentrations that are acceptable to the site of administration. In certain embodiments, buffers are used to maintain the composition at physiological pH or at a slightly lower pH, typically within a pH range of from about 4.5 to about 8. Including about 4.5, about 4.6, about 4.7, about 4.8, about 4.9., about 5.0, about 5.1 , about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1 , about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1 , about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, and about 8.0.

[0162] In various embodiments, the anti-TSLP antibody or antibody variant is in a formulation containing one or more basic amino acids (e.g., arginine, histidine or lysine) or salt thereof, or a calcium or magnesium salt, and a surfactant. In various embodiments, the formulation comprises 0.005% (w/v) to about 0.015% (w/v) polysorbate 20 or polysorbate 80. In various embodiments, the formulation is at pH between 4.5 and 6.8. In various embodiments, the antibody or antibody fragment in the formulation is at a concentration of greater than 110 mg/ml, e.g., from about 110 mg/ml to about 250 mg/ml, e.g., from about 140 mg/ml to about 250 mg/ml, from about 160 mg/mL to about 250 mg/mL, or from about 140 mg/mL to about 210 mg/mL, or about 180 mg/ml or about 210 mg/ml. The formulation may be stored at 2° to 8° C or -20° to -70° C. Exemplary formulations are described in coowned application PCT/US2021/17880, incorporated herein by reference.

[0163] In various embodiments, the anti-TSLP antibody or antibody variant is in a formulation comprising greater than about 100 mg/mL of an anti-TSLP antibody, a surfactant, proline, and a buffer. In exemplary instances, the surfactant, e.g., polysorbate 80, is present in the composition at a concentration about 0.005% (w/v), 0.010% (w/v), or 0.015% (w/v). In exemplary aspects, the composition comprises equal to or less than about 3.0% (w/v) proline, e.g., about 2.4% (w/v) to about 2.8% (w/v) proline or about 2.5% (w/v) to about 2.8% (w/v) proline. In exemplary instances, the proline is L-proline. In certain aspects, proline is the only amino acid present in the composition. In exemplary aspects, the buffer is selected from the group consisting of: succinate, glutamate, histidine, and acetate. In some embodiments, the buffer is acetate. In exemplary aspects, the composition comprises about 1 mM to about 50 mM buffer, e.g., about 10 mM to about 30 mM buffer, optionally, about 15 mM to about 30 mM buffer, about 20 mM to about 30 mM buffer, or about 10 mM to about 25 mM buffer. Exemplary formulations are described in coowned application PCT/US2021/018561 , incorporated herein by reference.

[0164] In various embodiments, the anti-TSLP antibody or antibody variant is administered in a dose of 110 mg/mL in 10 mM acetate, 3.0% (w/v) L-proline, 0.01 % (w/v) polysorbate 80, at pH 5.2. In various embodiments, tezepelumab is administered in a dose of 110 mg/mL in 10 mM acetate, 3.0% (w/v) L-proline, 0.01 % (w/v) polysorbate 80, at pH 5.2.

[0165] When parenteral administration is contemplated, the therapeutic compositions for use may be provided in the form of a pyrogen-free, parenterally acceptable aqueous solution comprising the desired anti-TSLP antibody in a pharmaceutically acceptable vehicle. A particularly suitable vehicle for parenteral injection is sterile distilled water in which the antibody is formulated as a sterile, isotonic solution, properly preserved. In certain embodiments, the preparation can involve the formulation of the desired molecule with an agent, such as injectable microspheres, bio-erodible particles, polymeric compounds (such as polylactic acid or polyglycolic acid), beads or liposomes, that may provide controlled or sustained release of the product which can be delivered via depot injection. In certain embodiments, hyaluronic acid may also be used, having the effect of promoting sustained duration in the circulation. In certain embodiments, implantable drug delivery devices may be used to introduce the antibody. In various embodiments, the administration may be via pre- filled syringe or autoinjector. In various embodiments, the auto-injector is an Ypsomed YpsoMate®. In various embodiments, the auto-injector is disclosed in WO 2018/226565, WO 2019/094138, WO 2019/178151 , WO 20120/072577, W02020/081479, WO 2020/081480, PCT/US20/70590, PCT/US20/70591 , PCT/US20/53180, PCT/US20/53179, PCT/US20/53178, or PCT/US20/53176.

Kits

[0166] As an additional aspect, the disclosure includes kits which comprise one or more compounds or compositions packaged in a manner which facilitates their use to practice methods of the disclosure. In one embodiment, such a kit includes a compound or composition described herein, packaged in a container such as a sealed bottle or vessel, with a label affixed to the container or included in the package that describes use of the compound or composition in practicing the method. Preferably, the compound or composition is packaged in a unit dosage form for administration as described herein. The kit may further include a device suitable for administering the composition according to a specific route of administration or for practicing a screening assay. Preferably, the kit contains a label that describes use of the antibody composition.

[0167] Additional aspects and details of the disclosure will be apparent from the following examples, which are intended to be illustrative rather than limiting.

EXAMPLES

Example 1 — Biomarkers of EOE and TSLP

[0168] This analysis aimed to determine whether TSLP-mediated gene expression changes are enriched in patients with EOE to understand whether tezepelumab could be a potential treatment for EOE.

[0169] Gene signature analyses were performed to generate TSLP gene lists from two independent transcriptomic data sets obtained from: 1) bronchial brushings at week 28 from patients with moderate-to-severe, uncontrolled asthma treated with tezepelumab in the phase 2 CASCADE study (NCT03688074); and 2) human myeloid dendritic cells treated ex vivo with recombinant TSLP for 24 hours. Using these TSLP gene lists, gene set variation analyses were performed on publicly available gene expression data from esophageal biopsies in healthy individuals and patients with chronic esophagitis, active untreated EOE, inactive treated EOE (responsive to swallowed topical corticosteroids [STCs]) and active treated EOE (unresponsive to STCs). [0170] The TSLP gene lists were composed of 18 upregulated genes and 32 downregulated genes in bronchial brushings from CASCADE, and 183 upregulated and 161 downregulated genes in myeloid dendritic cells (Figure 1). The TSLP gene lists identified were enriched in patients with active EOE, including those unresponsive to STCs, compared with healthy individuals. Compared with patients with inactive treated EOE, TSLP gene lists were enriched in patients with active EOE that was unresponsive to STCs. These data support the clinical evaluation of tezepelumab in the treatment of EOE, which is being conducted in an ongoing phase III study (NCT05583227), e.g., as described in Example 2.

[0171] Gene lists indicative of elevated TSLP activity were enriched in patients with active EOE (untreated or unresponsive). These data suggest that blocking TSLP with tezepelumab may be a therapeutic option for EOE.

[0172] Example 2 — A Phase 3 Study to Evaluate the Effect of Tezepelumab in

Eosinophilic Esophagitis (EOE)

[0173] The first evidence suggesting a role for TSLP in EOE pathogenesis involved the identification of genetic risk variants in the TSLP locus and demonstration of increased TSLP gene expression in the esophagus of patients with EOE that is influenced by the TSLP SNP genotype (Rothenberg et al 2010), a linkage replicated in studies using genome-wide and candidate gene approaches (Sherrill et al 2010, Kottyan et al 2014). Esophageal levels of both TSLP messenger RNA and protein are elevated in EOE, and it has been shown that TSLP gene expression in the esophagus returns to baseline levels during disease remission (Noti et al 2013). Recombinant TSLP has shown to be sufficient to drive esophageal eosinophilia and structural changes in the esophageal tissue (e.g., thickening and fibrosis) in an aeroallergen-induced mouse model of EOE (Collins et al 2017, Collison et al 2015).

[0174] Both adults and children with EOE often suffer from comorbid atopic disorders such as asthma, food allergy, and environmental allergies, all of which are linked to TSLP (Martin et al 2018, Durrani et al 2018). Importantly, the association of TSLP SNPs with EOE risk, independent of atopic co-morbidities, has been supported using multiple methodologies, including covariate analyses and comparisons to non-EOE atopic control cohorts (Rothenberg et al 2010, Sherrill et al 2010, Kottyan et al 2014, Martin et al 2018). In prior asthma studies, tezepelumab has reduced blood eosinophils in both adolescents and adults (Menzies-Gow et al 2021), and reduction in blood eosinophils may correlate with EOE disease activity and esophageal tissue eosinophils (Colson et al 2014, Konikoff et al 2006, Rodnguez-Sanchez et al 2001). Tezepelumab has also been demonstrated to significantly reduce submucosal eosinophils in the airways of severe asthma participants compared to placebo (Diver et al 2021). [0175] The aim of this global Phase III study is to investigate the use of tezepelumab as a treatment for patients with EOE. This study will evaluate the efficacy and safety of tezepelumab 210 mg every 4 weeks (Q4W) and tezepelumab 420 mg Q4W administered subcutaneously (SC) using an accessorized pre-filled syringe (APFS) versus placebo in adult and adolescent participants with EOE.

[0176] Approximately 360 participants (composed of approximately 36 adolescents and approximately 324 adults) are randomized 1 :1 :1 to receive either 210 mg tezepelumab, 420 mg tezepelumab, or placebo, administered SC Q4W. Each participant will receive 2 injections at each visit: the 210 mg arm will receive one active and one placebo injection; the 420 mg arm will receive 2 active injections; the placebo arm will receive 2 placebo injections. Randomization will be stratified by region (Asia vs Rest of World), age category (adults vs adolescents), and baseline swallowed topical corticosteroids (STC) use (yes vs no). The study consists of a screening/run-in period of 2 to 8 weeks and a 52-week randomized double-blind placebo-controlled treatment period. After completion of the treatment period, participants will be eligible to participate in an optional 24-week active treatment extension period, followed by a 12-week off-treatment safety follow-up period. Participants who choose not to participate in the optional active treatment extension period will participate in a 12- week off treatment safety follow-up period following completion of the 52-week treatment period.

[0177] Inclusion criteria for the study:

[0178] 1. Participant must be 12 to 80 years of age inclusive, at the time of signing the informed consent/assent.

[0179] 2. Weight > 40 kg at Visit 1 .

[0180] 3. Previously established diagnosis of EOE by EGD and esophageal biopsy.

[0181] 4. Participants who have symptomatic EOE as defined by a history of on average at least 2 episodes of dysphagia (any severity of food going down slowly or being stuck in the throat) per week in the 4 weeks prior to Visit 1 .

[0182] 5. Must have been on stabilized diet for at least 8 weeks prior to Visit 1 and be willing to remain on stabilized diet during the course of the study (stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups).

[0183] 6. May be on any background medication for EOE, for example PPI and/or STC, during the course of the study, as long as background medications have been stable for at least 8 weeks prior to the screening/run-in period (Visit 1 ) and there is agreement not to change background medication or dosage unless medically indicated, during the screening/run-in and treatment period.

[0184] 7. Participants should have previously documented standard of care treatment, which could include PPI and/or STC and/or diet.

[0185] 8. Participants currently on leukotriene inhibitors and/or steroid treatments for asthma or allergies that are inhaled or administered intranasally, must report a stable dose for at least 4 weeks prior to the screening/run-in period (Visit 1).

[0186] 9. Participants with either of the following: (a) If a medication for EOE (for example PPI and/or STC) is discontinued prior to the screening/run-in, there should be a washout period of at least 8 weeks prior to Visit 1 . (b) Discontinuation of any marketed biologic (monoclonal or polyclonal antibody) should have a washout period of 4 months or 5 half-lives prior to Visit 1 , whichever is longer.

[0187] 10. At randomization, participant must have the diagnosis of active EOE confirmed during the screening period of this study by a centrally read esophageal biopsy (confirmed diagnosis defined as an eosinophil count of > 15 EOS/HPF at 2 or more esophageal levels). Two to four biopsies should be obtained from both the proximal and distal esophagus. Two to four biopsies can be taken from the mid-esophagus for additional evaluation.

[0188] 11 . At randomization, participant must have been adherent to daily diary assessments: (a) Must have completed 70% of daily diary entries between Visit 1 and Visit 2 AND (b) Must have at least 8 non-missing DSQ daily scores in the 14 days prior to randomization.

[0189] 12. At randomization, participant must have symptomatic EOE as defined by > 4 episodes of dysphagia (DSQ > 2) over the 2 weeks prior to randomization, documented in an eDiary, of which > 2 episodes require liquids, coughing, or gagging, vomiting or medical attention to obtain relief (DSQ > 3).

[0190] 13. At randomization, participant must have remained on stabilized diet between Visit 1 and Visit 2.

[0191] Exclusion criteria include:

[0192] 1 . Other gastrointestinal disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, celiac disease, EGE, EG, eosinophilic enteritis, colitis, diverticulitis, irritable bowel syndrome, or other clinically significant gastrointestinal conditions as per investigator discretion.

[0193] 2. Eosinophilic granulomatosis with polyangiitis vasculitis.

[0194] 3. Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation at screening.

[0195] 4. Use of a feeding tube or having a pattern of not eating solid food > 3 days of the week. Solid food is defined as food that requires chewing before swallowing.

[0196] 5. Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood eosinophil count > 1500 eosinophils/pL.

[0197] 6. Esophageal dilation performed within 8 weeks prior to screening.

[0198] During screening/run-in and throughout the duration of the treatment period, the study participants should remain on stabilized diet for treatment of their EoE, unless a change is clinically indicated. Stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups. As an inclusion criterion, participants must remain on a stabilized diet for at least 8 weeks prior to screening.

[0199] Tezepelumab is administered as a 110 mg/mL solution for injection in 10 mM acetate, 3.0% (w/v) L-proline, 0.01% (w/v) polysorbate 80, pH 5.2 given 210 mg once every 4 weeks (Q4W) or 420 mg Q4W by SC injection. Placebo is administered 0.7% (w/v) sodium carboxy methyl cellulose in 10 mM acetate, 250 mM L-proline, 0.01% (w/v) polysorbate 80, pH 5.0, solution for injection, Q4W by SC injection.

[0200] ENDPOINTS AND ASSESSMENTS

[0201] Efficacy assessments

[0202] Tissue Eosinophil Counts and EOE-Histological Scoring System (EOE-HSS) One of the co-primary endpoints in the study is to assess histologic response of peak esophageal eosinophil per HPF count of < 6 across all available esophageal levels at Week 24. During the study, esophageal biopsies (4 to 6 biopsies from the distal esophagus: including 2 for biomarker analysis, 2-4 biopsies from the proximal esophagus and midesophageal locations) will be conducted. EGD and biopsies will be performed according to local medical practice. EOE-HSS is a histology scoring system for esophageal biopsies that evaluates 8 features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities are scored using a 4-point scale (0 normal; 3 maximum change) (Collins et al 2017).

[0203] EOE Endoscopic Reference Score (EOE EREFS) The EOE EREFS is a scoring system for assessing the presence and severity of the major endoscopic signs of EOE, including esophageal edema, rings, exudates, furrows, and stricture. The EOE EREFS will be evaluated at the time of each biopsy collection. [0204] Patient Reported Outcomes (PRO)

[0205] Between Visits 1 and 15, participants complete all PRO assessments using a handheld device. The handheld device will be programmed at Visit 1 with reminder alarms for the daily diary. Review of participant compliance with the assessment schedule, completion of any available assessments, and logging of the visit on the handheld device should be completed prior to other study procedures. Compliance with the assessment schedule should be reviewed weekly throughout the study.

[0206] Dysphagia Symptom Questionnaire (DSQ) The DSQ is a PRO measure validated for participants aged 12 and older with dysphagia related to EOE (Dellon et al 2013). The presence and severity of dysphagia symptoms in the past day are captured in a 4-item questionnaire. Questions 1 and 2 utilize yes/no response capture if the participant consumed solid food that day (yes/no; unscored) and instances of food going down slowly or becoming stuck in the throat or chest (scored 0 for no and 2 for yes). If the participant reports not eating solid food, then the DSQ is considered missing for that day. Question 3 asks about the severity of dysphagia, based on actions the participant took to relieve the dysphagia at its worst point during the day. It ranges from 0 (dysphagia cleared up on its own) to 4 (participant sought medical attention for dysphagia). Question 4 asks the participant to report the worst pain experienced while swallowing food over the past 24 hours (no pain [0] to very severe pain [4]). The total DSQ score ranges from 0 to 84, with a lower score indicating less severe dysphagia.

[0207] Questions 2 and 3 are the only questions that contribute to the total DSQ score. The score is calculated by multiplying the daily scores of questions 2 and 3 by 14 days and dividing by the number of days in the past 14 days with no missing data. Question 4 is a standalone item intended to be evaluated separately. Using anchor-based methods, the MCID and CID in DSQ score (mean absolute change) were estimated to be -6.5 points and -13.5 points, respectively (Hudgens et al 2017). Using DSQ Question 2, dysphagia-free days over each 28-day period following randomization will also be summarized.

[0208] Pediatric Eosinophilic Esophagitis Symptom Severity Module, Version 2, Children and Teens Report (PEESS) The PEESS is a 20-item assessment of EoE symptom severity and frequency validated for use in participants aged 8 to 18 years. The recall period is 1 month. The first 18 questions alternate between a question about a given symptom’s frequency (never, almost never, sometimes, often, almost always) and a question about the symptom’s severity (face rating scale with drawings representing not bad at all, a little bad, kind of bad, bad, very bad). The remaining 2 questions ask about frequency of eating less food than others and frequency of needing more time to eat than others. The overall score ranges from 0 to 100, with higher scores representing more severe and frequent EoE symptoms.

[0209] Statistical Methods

[0210] Approximately 360 participants composed of approximately 36 adolescents and approximately 324 adults are randomized in a 1 :1 :1 ratio to tezepelumab 210 mg Q4W, tezepelumab 420 mg Q4W, or matching placebo Q4W. The sample size will provide > 95% power to detect a treatment difference of -8 (standard deviation = 15) between a tezepelumab dose and placebo for the co-primary endpoint of the change from baseline in Dysphagia Symptom Questionnaire (DSQ) score at Week 24 at a 2-sided alpha level of 2.5%. Assuming a responder rate of 5% in the placebo, the sample size will provide > 99% power to detect a 50% difference (odds ratio = 23.2) between a tezepelumab dose and placebo for the co-primary endpoint of histologic response at Week 24 at a 2-sided alpha level of 2.5%.

[0211] Histologic Response Rate The proportion of participants achieving histologic response of peak esophageal eosinophil per HPF count of < 6 across all available esophageal levels at Week 24 will be compared between each tezepelumab dose and placebo using CMH test controlling for region (Asia vs Rest of World), age category (adults vs adolescents), baseline STC use (yes vs no), and baseline strictures (yes vs no). Participants with strictures severe enough to prevent easy passage of a standard EGD or any critical esophageal stricture that requires dilation are excluded from the study but participants with milder strictures may be enrolled. The baseline stricture status is considered prognostic and adjusted in addition to the stratification factors. Strata may be pooled in case of sparse data and the pooling strategy will be described in the SAP. The results of the analysis will be presented using an odds ratio, together with its associated 95% Cis and 2-sided p-value. Participants receiving rescue therapy or discontinued IP due to reasons related to the treatment prior to Week 24 will be considered as non- responders. Missing biopsy data due to other reasons at Week 24 will be imputed assuming MAR.

[0212] Change from Baseline in DSQ Score The change from baseline in DSQ score at Week 24 will be compared between each tezepelumab dose and placebo using an ANCOVA model. The model will include the baseline value, randomized treatment group, region (Asia vs Rest of World), age category (adults vs adolescents), baseline STC use (yes vs no), and baseline strictures (yes vs no). The baseline stricture status is considered prognostic and included in the model. The model will be used to estimate the mean change from baseline at Week 24 for each treatment group and the difference versus placebo, with corresponding 95% confidence limits. A p-value, corresponding to a 2-sided test, will be presented to compare each tezepelumab dose and placebo treatment groups. For participants who receive rescue therapy or discontinued IP due to reasons related to the treatment, a Ml procedure assuming return-to-baseline will be used to impute the DSQ score after the intercurrent events. Missing DSQ scores due to other reasons will be imputed assuming MAR. Rubin’s rule will be applied to combine analysis results (point estimates and standard errors) from the imputed datasets.

[0213] Analysis of Secondary Efficacy Endpoints The key secondary endpoints of change from baseline in centrally read EOE EREFS at Week 24, change from baseline in EOE -HSS grade score at Week 24, and change from baseline in EOE -HSS stage score at Week 24 will be analyzed using the same ANCOVA model described for the DSQ co-primary endpoint.

[0214] Numerous modifications and variations of the invention as set forth in the above illustrative examples are expected to occur to those skilled in the art. Consequently only such limitations as appear in the appended claims should be placed on the invention.

References

[0215] Abonia et al., J Allergy Clin Immunol. 2010 Jul;126(1 ):140-9.

[0216] Aceves et al., J Allergy Clin Immunol. 2007;119(1 ):206-12.

[0217] Allakhverdi et al., J Exp Med. 2007;204(2):253-8.

[0218] AstraZeneca Pharmaceuticals LP. Tezepelumab-ekko (TEZSPIRE™) US Prescribing Information. 2021

[0219] AV IR Pharma Inc. Orodispersible budesonide tablet (JORVEZA®) Product Monograph Including Patient Medication Information. 2017

[0220] Bolton et al., Am J Gastroenterol. 2020;115(2):224-33.

[0221] Chehade et al., J Pediatr Gastroenterol Nutr. 2007;45(3):319-28.

[0222] Chehade et al., UEG Week 2021 Poster Presentations. United European Gastroenterol J 2021 ;9(S8):286 (abstract P0046).

[0223] Collins et al., Dis Esophagus. 2017;30(3) :1 -8.

[0224] Collison et al., J Allergy Clin Immunol. 2015;136(4):971 -82.

[0225] Colson et al., J Allergy Clin Immunol Pract. 2014;2(5):587-93.

[0226] Corren et al., N Engl J Med. 2017;377( 10):936-46.

[0227] Cui et al., Biometrics. 1999;55(3):853-7.

[0228] Dellon et al., Am J Gastroenterol. 2013;108(5):679-92.

[0229] Dellon et al., Gastrointest Endosc. 2014;79(4):577-85.e4.

[0230] Dellon et al., Gastroenterology. 2017;152(4):776-86.e5.

[0231] Dellon et al., Gastroenterology 2018;155(4):1022-33.

[0232] Dellon et al., Presented at: Digestive Disease Week®; June 2-5, 2018: Washington, DC, US.

[0233] Dellon et al., N Engl J Med. 2020;383(17):1624-34.

[0234] Dellon et al., American College of Gastroenterology (ACG) Virtual Annual Meeting. October 23-28, 2020

[0235] Dellon and Hirano, Gastroenterology. 2018;154(2):319-32. e3.

[0236] Dellon and Liacouras, Gastroenterology. 2014;147(6):1238-54.

[0237] Diver et al., Lancet Respir Med. 2021 ;9(11):1299-312. [0238] Dr. Falk Pharma GmbH. Orodispersible budesonide tablet (JORVEZA®) Summary of Product Characteristics. 2018

[0239] Dr. Falk Pharma Australia Pty Ltd. Australian Product Information - JORVEZA® (Budesonide) Orally Disintegrating Tablets. 2021

[0240] Durrani et al., Clin Rev Allergy Immunol. 2018;55( 1 ):56-64.

[0241] Ebina-Shibuya and Leonard, Nat Rev Immunol. 2022 Jun 1 :1-14

[0242] Eigenmann et al., J Physiol. 2017;595(24):7311 -30.

[0243] Emson et al.. J Asthma Allergy. 2021 ;14:91-9.

[0244] European Medicines Agency. Tezspire. 2022

[0245] Food and Drug Administration. Eosinophilic Esophagitis: Developing Drugs for Treatment Guidance for Industry. 2020

[0246] Gauvreau et al., N Engl J Med. 2014;370(22):2102-10.

[0247] Gilliet et al., J Exp Med. 2003;197(8):1059-63.

[0248] Griffiths et al., J Allergy Clin Immunol. 2022;149(2):AB14.

[0249] Hirano et al., Gastroenterology. 2019 ; 156(3):592-603.e10.

[0250] Hirano et al., Gastroenterology. 2020;158(6):1776-86.

[0251] Hirano et al., Gastroenterology. 2020;158(1 ):111-22. e10.

[0252] Hudgens et al., J Patient Rep Outcomes. 2017;1 (1 ):3.

[0253] Kirsch et al., Pediatr Gastroenterol Nutr. 2007;44(1 ):20-6.

[0254] Konikoff et al., Clin Gastroenterol Hepatol. 2006;4(11):1328-36.

[0255] Kottyan et al., Nat Genet. 2014;46(8):895-900.

[0256] Kroger et al., MMWR. 2011 ;60(2):1 -64.

[0257] Liacouras et al., J Allergy Clin Immunol. 2011 ;128(1 ):3-20.e6.

[0258] Lieberman et al., J Allergy Clin Immunol. 2010;126(3):477-80.e1-42.

[0259] Lucendo et al., United European Gastroenterol J. 2017;5(3):335-58.

[0260] Lucendo et al., Gastroenterology. 2019;157(1):74-86.e15.

[0261] Mansoor and Cooper, Dig Dis Sci. 2016;61 (10):2928-34.

[0262] Martin et al., J Allergy Clin Immunol. 2018;141 (5):1690-8. [0263] Menzies-Gow et al., N Engl J Med. 2021 ;384( 19) :1800-9.

[0264] Navarro et al., Aliment Pharmacol Ther. 2019;49(9) :11 16-25.

[0265] Noti al., Nat Med. 2013;19(8):1005-13.

[0266] QualityMetric, I. User's manual for the SF-36v2 Health Survey (3 ed.). 2011 . Lincoln, Rl.

[0267] Pham et al., Am J Respir Crit Care Med. 2019;199:A2677.

[0268] Reche et al., J Immunol. 2001 ;167(1 ):336-43.

[0269] Rodnguez-Sanchez et al., Rev Esp Enferm Dig. 2013;105(8):462-7.

[0270] Rothenberg et al., Nat Genet. 2010;42(4):289-91 .

[0271] Rothenberg et al., J Allergy Clin Immunol. 2022;149(2):AB312(abstract L02).

[0272] Sampson et al., J Allergy Clin Immunol. 2006 ; 117(2):391 -7.

[0273] Sanofi and Regeneron Pharmaceuticals, Inc. DUPIXENT® (dupilumab) prescribing information. 2022

[0274] Schoepfer et al., Gastroenterology. 2013;145(6):1230-6.e1 -2.

[0275] Shah and Betts, MAbs. 2013;5(2):297-305.

[0276] Sherrill et al., J Allergy Clin Immunol. 2010;126(1 ):160-5. e3.

[0277] Soumelis et al., Nat Immunol. 2002;3(7):673-80.

[0278] Spergel et al., J Allergy Clin Immunol. 2012; 129(2):456-63, 463.e1 -3.

[0279] Sperry et al., Am J Gastroenterol. 2012 ; 107(2):215-21 .

[0280] Straumann et al., J Allergy Clin Immunol. 2001 ;108(6):954-61 .

[0281] Straumann et al., Gastroenterology. 2003;125(6):1660-9.

[0282] Straumann et al., Gut. 2010;59(1 ) :21 -30.

[0283] Taft et al., Aliment Pharmacol Ther. 2011 ;34(7):790-8.

[0284] Warners et al., Am J Gastroenterol. 2018; 113(6):836-44.

Claims

What is Claimed:

1 . A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein the antibody comprises: a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising:

1. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

2. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:1 1 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

3. The method of claim 1 or 2, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

4. The method of any one of claims 1 to 3, wherein the antibody is administered every 2 weeks.

5. The method of any one of claims 1 to 4, wherein the antibody is administered every 4 weeks.

6. The method of any one of claims 1 to 5, wherein the antibody is administered at a dose of 210 mg.

7. The method of any one of claims 1 to 5, wherein the antibody is administered at a dose of 420 mg.

8. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody comprises: a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

9. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

10. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises: a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

11. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

12. The method of any one of claim 8 to 11 , wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

13. The method of claim 12, wherein the antibody further comprises an lgG2 domain.

14. The method of any one of the preceding claims, wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

15. The method of any one of the preceding claims, wherein the anti-TSLP antibody is selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a recombinant antibody, an IgG 1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

16. The method of any one of the preceding claims, wherein the antibody is an lgG2 antibody.

17. The method of any one of the preceding claims, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

18. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

19. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

20. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

21 . A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

22. The method of claim 20 or 21 , wherein the light chain variable domain comprises the amino acid sequence set forth in in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

23. The method of claim 22 wherein the antibody further comprises an lgG2 domain.

24. The method of any one of claims 20 to 23, wherein the antibody or antibody variant is administered every 2 weeks.

25. The method of any one of claims 20 to 23, wherein the antibody or antibody variant is administered every 4 weeks.

26. The method of any one of claims 20 to 25, wherein the antibody is an lgG2 antibody.

27. The method of any one of claims 20 to 26, wherein the antibody or antibody variant is administered at a dose of 210 mg.

28. The method of any one of claims 20 to 27, wherein the antibody or antibody variant is administered at a dose of 420 mg.

29. The method of any one of claims 20 to 28, wherein the antibody has a full- length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

30. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

31 . A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

32. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

33. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

34. The method of any one of claims 30 to 33, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

35. The method of claim 34, wherein the antibody further comprises an lgG2 domain.

36. The method of any one of claims 30 to 35, wherein the antibody or antibody variant is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

37. The method of any one of claims 30 to 36, wherein the anti-TSLP antibody or antibody variant thereof is bivalent and selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a recombinant antibody, an lgG1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

38. The method of any one of claims 30 to 37, wherein the antibody is an lgG2 antibody.

39. The method of any one of claims 30 to 38, wherein the antibody has a full- length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

40. The method of any one of claims 30 to 39, wherein the antibody or antibody variant is a human antibody.

41 . A method for treating eosinophilic esophagitis (EOE) in a subject in need thereof comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein the antibody comprises: a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

42. A method for treating eosinophilic esophagitis (EOE) in a subject in need thereof comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:1 1 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

43. The method of claim 41 or 42, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

44. The method of any one of claims 41 to 43, wherein the antibody is administered every 2 weeks.

45. The method of any one of claims 41 to 43, wherein the antibody is administered every 4 weeks.

46. The method of any one of claims 41 to 45, wherein the antibody is administered at a dose of 210 mg.

47. The method of any one of claims 41 to 45, wherein the antibody is administered at a dose of 420 mg.

48. The method of any one of claims 41 to 47, wherein the has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

49. A method for treating eosinophilic esophagitis (EOE) in a subject in need thereof comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

50. A method for treating eosinophilic esophagitis (EOE) in a subject in need thereof comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

51 . A method for treating eosinophilic esophagitis (EOE) in a subject in need thereof comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

52. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

53. The method of any one of claims 49 to 52, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

54. The method of any one of claims 49 to 53, wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

55. The method of any one of claims 49 to 54, wherein the has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

56. The method of any one of the preceding claims, wherein the antibody or antibody variant is administered to the subject in a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient.

57. The method of any one of the preceding claims, wherein the subject is an adult or an adolescent.

58. The method any one of the preceding claims, wherein the method improves one or more measures of EOE in a subject selected from the group consisting of histologic response of peak esophageal eosinophils per HPF count of < 6 across all available esophageal levels, EoE Endoscopic Reference Score (EREFS), EoE- Histological Scoring System (EoE-HSS) grade score and EoE-HSS stage score and Dysphagia Symptom Questionnaire (DSQ) score.

59. The method of claim 58, wherein the EoE-HSS scoring measures eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis.

60. The method any one of the preceding claims, wherein the administration improves one or more symptoms of EOE as measured by a patient symptom diary.

61 . The method of any one of the preceding claims, wherein the antibody is an lgG2 antibody, and has the full length heavy and light chain sequences set out in SEQ ID NOs: 13 and 14, respectively.

62. The method of any one of the preceding claims wherein the subject is also receiving a co-administered therapy.

63. The method of claim 62, wherein the co-administered therapy is selected from the group consisting of a corticosteroid, proton-pump inhibitor, swallowed topical corticosteroid (STC), a leukotriene inhibitor and combinations thereof.

64. The method of any one of the preceding claims, wherein the subject is unresponsive to STC.

65. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

66. A method of reducing the reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

67. The method of claim 65 or 66, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

68. The method of claim 67, wherein the antibody further comprises an lgG2 domain.

69. The method of any one of claims 65 to 68, wherein the antibody is administered every 2 weeks.

70. The method of any one of claims 65 to 68, wherein the antibody is administered every 4 weeks.

71 . The method of any one of claims 65 to 70, wherein the antibody is administered at a dose of 210 mg.

72. The method of any one of claims 65 to 70, wherein the antibody is administered at a dose of 420 mg.

73. The method of any one of claims 65 to 72, wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

74. The method of any one of claims 65 to 73, wherein the anti-TSLP antibody is selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a recombinant antibody, an lgG1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

75. The method any one of claims 65 to 74, wherein the antibody is an lgG2 antibody.

76. The method of any one of claims 65 to 75, wherein the antibody is a human antibody.

77. The method of any one of claims 65 to 76, wherein the antibody has a full- length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

78. A method reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

79. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

80. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

81 . A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 2 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

82. The method of any one of claims 78 to 81 , wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

83. The method of claim 82, wherein the antibody further comprises an lgG2 domain.

84. The method of any one of claims 78 to 83, wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

85. The method of any one of claims 78 to 84, wherein the antibody has a full- length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

86. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

87. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

88. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

89. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

90. The method of claim 88 or 89, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

91 . The method of claim 90, wherein the antibody further comprises an lgG2 domain.

92. The method of any one of claims 88 to 91 , wherein the antibody or antibody variant is administered every 2 weeks.

93. The method of any one of claims 88 to 91 , wherein the antibody or antibody variant is administered every 4 weeks.

94. The method of any one of claims 88 to 93, wherein the antibody or antibody variant is administered at a dose of 210 mg.

95. The method of any one of claims 88 to 93, wherein the antibody or antibody variant is administered at a dose of 420 mg.

96. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

97. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

98. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

99. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein both binding sites of the antibody are identical binding sites that bind TSLP, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

100. The method of any one of claims 88 to 99, wherein the antibody or antibody variant is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

101. The method of any one of claims 88 to 100, wherein the anti-TSLP antibody or antibody variant is selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a recombinant antibody, an IgG 1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

102. The method any one of claims 88 to 101 , wherein the antibody or antibody variant is an lgG2 antibody.

103. The method of any one of claims 88 to 102, wherein the antibody or antibody variant is a human antibody.

104. The method of any one of claims 88 to 103, wherein the antibody has a full- length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

105. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, and wherein the antibody is a human lgG2 antibody.

106. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody or antibody variant to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), and wherein the antibody is a human lgG2 antibody.

107. The method of claim 105 or 106, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

108. The method of any one of claims 105 to 107, wherein the antibody is administered every 2 weeks.

109. The method of any one of claims 105 to 107, wherein the antibody is administered every 4 weeks.

110. The method of any one of claims 105 to 109, wherein the antibody is administered at a dose of 210 mg.

111. The method of any one of claims 105 to 109, wherein the antibody is administered at a dose of 420 mg.

112. The method of any one of claims 105 to 111 , wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

113. The method of any one of claims 105 to 112, wherein the has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

114. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

115. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody is a human lgG2 antibody.

116. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

1 17. A method of reducing the number of eosinophils per high-power field (HPF) in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:1 1 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID N0:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody is a human lgG2 antibody.

118. The method of any one of claims 114 to 117, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:10.

119. The method of any one of claims 114 to 118, wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

120. The method of any one of claims 114 to 119, wherein the antibody has a full- length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

121. A method for reducing dysphagia and/or Dysphagia Symptom Questionnaire (DSQ) score in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

122. A method for reducing dysphagia and/or Dysphagia Symptom Questionnaire (DSQ) score in a subject having EOE comprising, administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or every 4 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).

123. The method of claim 121 or 122, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

124. The method of claim 123, wherein the antibody further comprises an lgG2 domain.

125. The method of any one of claims 121 to 124, wherein the antibody is administered every 2 weeks.

126. The method of any one of claims 121 to 125, wherein the antibody is administered every 4 weeks.

127. The method of any one of claims 121 to 126, wherein the antibody is administered at a dose of 210 mg.

128. The method of any one of claims 121 to 126, wherein the antibody is administered at a dose of 420 mg.

129. The method of any one of claims 121 to 128, wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

130. The method of any one of claims 121 to 129, wherein the anti-TSLP antibody is selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a recombinant antibody, an lgG1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

131 . The method any one of claims 121 to 130, wherein the antibody is an lgG2 antibody.

132. The method of any one of claims 121 to 131 , wherein the antibody is a human antibody.

133. The method of any one of claims 121 to 132, wherein the antibody has a full- length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

134. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

135. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

136. The method of claim 134 or 135, wherein the light chain variable domain comprises the amino acid sequence set forth in in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

137. The method of claim 136, wherein the antibody further comprises an lgG2 domain.

138. The method of any one of claims 134 to 137, wherein the antibody is administered every 2 weeks.

139. The method of any one of claims 134 to 137, wherein the antibody is administered every 4 weeks.

140. The method of any one of claims 134 to 139, wherein the antibody is an lgG2 antibody.

141 . The method of any one of claims 134 to 140, wherein the antibody or antibody variant is administered at a dose of 210 mg.

142. The method of any one of claims 134 to 141 , wherein the antibody or antibody variant is administered at a dose of 420 mg.

143. The method of any one of claims 134 to 142, wherein the has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

144. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

145. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

146. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

147. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

148. The method of anyone of claims 144 to 147, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQ:10.

149. The method of claim 148, wherein the antibody further comprises an lgG2 domain.

150. The method of any one of claims 144 to 149, wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

151 . The method of any one of claims 144 to 150, wherein the anti-TSLP antibody is bivalent and selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a recombinant antibody, an IgG 1 antibody, an lgG2 antibody, an lgG3 antibody, and an lgG4 antibody.

152. The method of any one of claims 144 to 151 , wherein the antibody is an lgG2 antibody.

153. The method of any one of claims 144 to 152, wherein the antibody is a human antibody.

154. The method of any one of claims 144 to 153, wherein the has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

155. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

156. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

157. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

158. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

159. The method of claim 157 or 158, wherein the light chain variable domain comprises the amino acid sequence set forth in in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:10.

160. The method of any one of claims 157 to 159, wherein the antibody is administered every 2 weeks.

161 . The method of any one of claims 157 to 159, wherein the antibody is administered every 4 weeks.

162. The method of any one of claims 157 to 161 , wherein the antibody or antibody variant is administered at a dose of 210 mg.

163. The method of any one of claims 157 to 161 , wherein the antibody or antibody variant is administered at a dose of 420 mg.

164. The method of any one of claims 157 to 163, wherein the antibody has a full- length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

165. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

166. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 420 mg at an interval of every 4 weeks, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

167. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, and the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

168. A method for treating eosinophilic esophagitis (EOE) in a subject comprising, selecting a subject in need of treatment for EOE and administering an anti-TSLP antibody to the subject in a dose of 210 mg at an interval of every 4 weeks, and the antibody comprises a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11 ; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2, wherein the antibody is a human lgG2 antibody.

169. The method of anyone of claims 165 to 168, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:12 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NO:10.

170. The method of any one of claims 165 to 169, wherein the antibody is administered for a period of at least 4 months, 6 months, 9 months, 1 year, 2 years or more.

171 . The method of any one of claims 165 to 170, wherein the antibody has a full- length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

172. The method of any one of the preceding claims, wherein the administration is subcutaneous or intravenous.

173. A composition comprising an anti-TSLP antibody for use in treating eosinophilic esophagitis (EOE) in a subject, wherein the composition is administered in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein the antibody comprises a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

174. A composition comprising an anti-TSLP antibody for use in treating eosinophilic esophagitis (EOE) in a subject, wherein the composition is administered in a dose of 210 mg to 420 mg at an interval of every 2 weeks or 4 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NO:12; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:1 1 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NQ:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

175. Use of a composition comprising an anti-TSLP antibody in the manufacture of a medicament for treating eosinophilic esophagitis (EOE) in a subject, wherein the composition is in a dose of 210 mg to 420 mg for administration at an interval of every 2 weeks or 4 weeks, wherein the antibody comprises: a. a light chain variable domain comprising: i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3; ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4; ill. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and b. a heavy chain variable domain comprising: i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6; ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and ill. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.

176. Use of a composition comprising an anti-TSLP antibody in the preparation of a medicament for treating eosinophilic esophagitis (EOE), wherein the composition is in a dose of 210 mg to 420 mg for administration at an interval of every 2 weeks or 4 weeks, wherein the antibody comprises: a. a light chain variable domain selected from the group consisting of: i. a sequence of amino acids at least 80% identical to SEQ ID NOU 2; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NOU 1 ; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NOU 1 ; and b. a heavy chain variable domain selected from the group consisting of: i. a sequence of amino acids that is at least 80% identical to SEQ ID NO:10; ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9; ill. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29- 159 of SEQ ID NO:2.

177. The composition for use or use of any one of claims 173 to 176, wherein the light chain variable domain comprises the amino acid sequence set forth in SEQ ID NOU 2 and the heavy chain variable domain comprises the amino acid sequence set forth in SEQ ID NQU 0.

178. The composition for use or use of any one of claims 173 to 177, wherein the antibody is administered every 2 weeks.

179. The composition for use or use of any one of claims 173 to 177, wherein the antibody is administered every 4 weeks.

180. The composition for use or use of any one of claims 173 to 179, wherein the antibody is an lgG2 antibody.

181 . The composition for use or use of any one of claims 173 to 180, wherein the antibody or antibody variant is administered at a dose of 210 mg.

182. The composition for use or use of any one of claims 173 to 180, wherein the antibody or antibody variant is administered at a dose of 420 mg.

183. The composition for use or use of any one of claims 173 to 182, wherein the has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full- length light chain amino acid sequence set forth in SEQ ID NO: 14.

184. A composition for use in treating eosinophilic esophagitis (EOE) in a subject comprising an anti-TSLP antibody, wherein the antibody is administered in a dose of 210 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

185. A composition for use in treating eosinophilic esophagitis (EOE) in a subject comprising an anti-TSLP antibody, wherein the antibody is administered in a dose of 420 mg at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

186. Use of a composition comprising an anti-TSLP antibody in the preparation of a medicament for treating eosinophilic esophagitis (EOE), wherein the composition is in a dose of 210 mg for administration at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.

187. Use of a composition comprising an anti-TSLP antibody in the preparation of a medicament for treating eosinophilic esophagitis (EOE), wherein the composition is in a dose of 420 mg for administration at an interval of every 4 weeks, wherein the antibody has a full-length heavy chain amino acid sequence set forth in SEQ ID NO: 13 and a full-length light chain amino acid sequence set forth in SEQ ID NO: 14.