Il-13 antibodies for treatment of atopic dermatitis

Abstract

The present invention provides methods, uses, and pharmaceutical compositions of antibodies that bind to human IL-13 ("anti-IL-13 antibodies") for the treatment of atopic dermatitis, for example in patients to which praliupreumab has been previously administered.

Description

[0001] Sequence Listing

[0002] This application is submitted with a sequence listing in ST.26 XML format. The sequence listing is provided as a file named "30602_WO Sequence Listing ST26" created on February 8, 2024 and is 12 kilobytes in size. The sequence listing information in ST.26 XML format is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention relates to methods, uses, and pharmaceutical compositions of antibodies that bind to human IL-13 ("anti-IL-13 antibodies") for treating atopic dermatitis, for example, in patients who have previously been administered dupilumab. Background Art

[0004] Atopic dermatitis (AD) is a chronic, heterogeneous inflammatory skin disease caused by impaired skin barrier function and dysregulated immune responses. Clinically, AD is characterized by xerosis, an erythematous, crusting rash, lichenification, a compromised skin barrier, and intense pruritus (Bieber T., N Engl J Med 2008;358:1483–94). AD patients have a high disease burden, and their quality of life is significantly impacted. In one study, AD was shown to have a greater negative impact on patients' psychological well-being than diabetes and hypertension (Zuberbier T et al., J Allergy Clin Immunol 2006;118:226–32). Patients with moderate to severe AD have a higher incidence of social dysfunction and sleep disturbances, which are directly correlated with disease severity (Williams H et al., J Allergy Clin Immunol 2008;121:947–54e15). Depression, anxiety, and social dysfunction affect not only AD patients but also their caregivers (Zuberbier T et al., J Allergy Clin Immunol 2006;118:226–32).

[0005] Interleukin (IL)-13 is a key mediator of inflammation in type 2 T helper (Th2) cells, signaling through the heterodimeric receptors IL-4Rα / IL-13Rα1. Multiple lines of evidence suggest that IL-13 is a key pathogenic component of AD. Increased IL-13 expression has been reported in AD skin (Hamid Q et al., J Allergy Clin Immunol 98:225-31

[1996] ; Jeong CW et al., Clin Exp Allergy 33:1717-24

[2003] ; Tazawa T et al., Arch Dermatol Res 295:459-64

[2004] ; Neis MM et al., J Allergy Clin Immunol 118:930-7

[2006] ; Suárez-Fariñas M et al., J Allergy Clin Immunol 132:361-70

[2013] ; Choy DF et al., J Allergy Clin Immunol. 130:1335-43

[2012] ) and some reports suggest a relationship between IL-13 expression and disease severity (LaGrutta S et al., Allergy Clin Immunol 131:1340-135

[2013] ). IL-13 has also been reported to be increased in the serum of AD patients (Novak N et al., J Invest Dermatol 2002;119:870–5; WO2016149276), and several studies have reported an increase in IL-13-expressing T cells in the blood of AD patients (Akdis M et al., J Immunol 1997;159:4611–9; Aleksza M et al., Br J Dermatol 2002;147:1135–41; La Grutta S et al., Allergy 2005;60:391–5).

[0006] Due to the heterogeneous nature of the disease, patients have diverse treatment needs. Treatment options for AD include avoidance of contact, moisturizing the skin during bathing, and the use of emollients and anti-inflammatory therapies such as topical corticosteroids (TCS). For many patients, TCS treatment provides some degree of symptom relief but does not adequately control their disease. In addition, the use of TCS is associated with many comorbidities and limitations, including a high patient burden. Long-term use of TCS is not recommended due to the risk of skin atrophy, depigmentation, acneiform rash, and risks associated with systemic absorption (e.g., hypothalamic pituitary axis effects, Cushing's disease).

[0007] For patients with persistent moderate to severe AD who have an inadequate response to TCS, there are a number of escalation treatment options (Ring J et al. J Eur Acad Dermatol Venereol 2012;26:1176–93; Schneider L et al. J Allergy Clin Immunol 2013;131:295–9. e1-27). Escalation options include topical calcineurin inhibitors (TCIs), phototherapy, and immunosuppressants such as oral corticosteroids, cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil. Immunosuppressants, such as cyclosporine A, affect both humoral and cellular immune responses, which can lead to increased susceptibility to infection and reduced cancer immune surveillance.

[0008] Dupilumab is a monoclonal antibody that inhibits IL-4 and IL-13 signaling and is approved for the treatment of patients with moderate to severe AD. Dupilumab is the first biologic indicated for patients with moderate to severe AD who are inadequately controlled with topical therapies or for whom topical therapies are not medically indicated. Some patients treated with dupilumab may show a limited or partial response to treatment, or even no response at all. Other patients may show an initial response to treatment but lose the response over time. Still others are found to be intolerant to or have side effects from dupilumab. Additionally, in real-world practice, other patients discontinue treatment due to issues such as cost or lack of access to the medication (e.g., insurance). Overall, a large number of patients do not continue dupilumab treatment during the course of their chronic disease (Simpson et al. 2016, N Engl J Med., 375:2335-2348; Marniquet et al. 2022, Br J Dermatol. 186: 733-734; Faiz et al. 2019, J Am Acad Dermatol., 81:143-51).

[0009] There remains an unmet medical need for safer and more effective therapies and treatment regimens for moderate to severe AD, particularly for patients who have been previously treated with dupilumab. Summary of the Invention

[0010] Provided herein are methods, uses, and pharmaceutical compositions for treating atopic dermatitis using anti-IL-13 antibodies. In some embodiments, provided herein are methods and uses of anti-IL-13 antibodies for treating atopic dermatitis, for example, in patients who have previously been administered dupilumab.

[0011] In one aspect, provided herein are methods for treating moderate to severe atopic dermatitis in a patient in need who has previously been administered dupilumab, comprising administering to the patient an antibody that binds human IL-13. In some embodiments, provided herein are methods for treating moderate to severe atopic dermatitis, comprising selecting a patient who has previously been administered dupilumab and administering to the patient an antibody that binds human IL-13. In some embodiments, the patient discontinues dupilumab due to no response, partial response, or loss of response. In some embodiments, the patient discontinues dupilumab due to intolerance or adverse events. In some embodiments, the patient discontinues dupilumab for other reasons.

[0012] In some embodiments, provided herein are methods of treating moderate to severe atopic dermatitis comprising selecting a patient with moderate to severe atopic dermatitis who was previously administered dupilumab and discontinued dupilumab due to non-response, partial response, or loss of response, and administering to the patient an antibody that binds human IL-13.

[0013] In some embodiments, provided herein are methods of treating moderate to severe atopic dermatitis comprising selecting a patient with moderate to severe atopic dermatitis who was previously administered dupilumab and discontinued dupilumab due to intolerance or an adverse event, and administering to the patient an antibody that binds human IL-13.

[0014] In some embodiments, the patient has moderate to severe atopic dermatitis for at least one year. In some embodiments, moderate to severe atopic dermatitis is determined by the American Academy of Dermatology Consensus Criteria. In some embodiments, before administering the antibody, the patient's eczema area and severity index (EASI) score is 16 or higher, the investigator's overall assessment (IGA) score is 3 or higher, and more than 10% of the body surface area (BSA) is affected by atopic dermatitis. In some embodiments, the patient has not responded well to topical corticosteroids. In some embodiments, the patient is 12 years old or older.

[0015] Also provided herein are methods for treating moderate to severe atopic dermatitis, comprising selecting a patient who: (i) is 12 years of age or older; (ii) has had chronic atopic dermatitis for more than one year according to the American Academy of Dermatology consensus criteria; (iii) has an EASI score of 16 or higher; (iv) has an IGA score of 3 or higher; (v) has more than 10% of its body surface area affected by atopic dermatitis; (vi) has had an inadequate response to topical corticosteroids; and (vii) has previously been administered dupilumab, wherein the patient discontinued dupilumab due to (1) no response, partial response, or loss of response or (2) intolerance or adverse event; and administering to the patient an antibody that binds to human IL-13.

[0016] In another aspect, provided herein is an antibody that binds to human IL-13 for use in treating moderate to severe atopic dermatitis in a patient who has previously been administered dupilumab. In some embodiments, provided herein is an antibody that binds to human IL-13 for use in treating moderate to severe atopic dermatitis in a patient who has previously been administered dupilumab and has discontinued dupilumab due to no response, partial response, or loss of response. In some embodiments, provided herein is an antibody that binds to human IL-13 for use in treating moderate to severe atopic dermatitis in a patient who has previously been administered dupilumab and has discontinued dupilumab due to intolerance or adverse events. In some embodiments, the patient is: (1) 12 years of age or older; (2) has had chronic atopic dermatitis for more than one year according to the American Academy of Dermatology consensus criteria; (3) has an EASI score of 16 or higher; (4) has an IGA score of 3 or higher; (5) has more than 10% of the BSA affected by atopic dermatitis; and (6) has had an inadequate response to topical corticosteroids.

[0017] In another aspect, provided herein are uses of antibodies that bind to human IL-13 for the manufacture of a medicament for the treatment of moderate to severe atopic dermatitis in patients who have previously been treated with dupilumab. Also provided herein are uses of antibodies that bind to human IL-13 for the manufacture of a medicament for the treatment of moderate to severe atopic dermatitis in patients who have previously been treated with dupilumab and who have discontinued dupilumab due to no response, partial response, or loss of response. Also provided herein are uses of antibodies that bind to human IL-13 for the manufacture of a medicament for the treatment of moderate to severe atopic dermatitis in patients who have previously been treated with dupilumab and who have discontinued dupilumab due to intolerance or adverse events. In some embodiments, the patient is: (1) 12 years of age or older; (2) has had chronic atopic dermatitis for more than one year according to the American Academy of Dermatology consensus criteria; (3) has an EASI score of 16 or higher; (4) has an IGA score of 3 or higher; (5) has more than 10% of the BSA affected by atopic dermatitis; and (6) has had an inadequate response to topical corticosteroids.

[0018] In some embodiments, patients discontinue dupilumab due to no response, partial response, or loss of response. In some embodiments, patients discontinue dupilumab due to intolerance or adverse events. In some embodiments, patients discontinue dupilumab due to no response. In some embodiments, patients discontinue dupilumab due to a partial response. In some embodiments, patients discontinue dupilumab due to loss of response. In some embodiments, patients discontinue dupilumab for at least four weeks. In some embodiments, patients discontinue dupilumab for at least eight weeks.

[0019] In some embodiments, the antibody binds to human IL-13 with high affinity and blocks signaling through active IL-4Rα / IL-13Rα1 heterodimers. In some embodiments, the antibody that binds to human IL-13 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: a HCDR1 comprising SEQ ID NO: 1, a HCDR2 comprising SEQ ID NO: 2, and a HCDR3 comprising SEQ ID NO: 3, and the VL comprises: a LCDR1 comprising SEQ ID NO: 4, a LCDR2 comprising SEQ ID NO: 5, and a LCDR3 comprising SEQ ID NO: 6. In some embodiments, the antibody that binds to human IL-13 comprises: a VH comprising SEQ ID NO: 7 and a VL comprising SEQ ID NO: 8. In some embodiments, the antibody that binds to human IL-13 comprises: a heavy chain comprising SEQ ID NO: 9 and a light chain comprising SEQ ID NO: 10. In some embodiments, the antibody that binds human IL-13 is lebrikizumab.

[0020] In some embodiments, the antibody that binds to human IL-13 is administered to the patient subcutaneously. In some embodiments, the antibody that binds to human IL-13 is administered to the patient subcutaneously at 250 mg or 500 mg. In some embodiments, the antibody that binds to human IL-13 is administered to the patient subcutaneously once every two weeks.

[0021] In some embodiments, the patient is treated with an antibody that binds to human IL-13 for a treatment period of about 16 to 24 weeks. In some embodiments, the patient is treated with an antibody that binds to human IL-13 for a treatment period of about 16 weeks. In some embodiments, the patient is treated with an antibody that binds to human IL-13 for a treatment period of about 24 weeks. In some embodiments, the patient is treated with a 500 mg loading dose of an antibody that binds to human IL-13 in weeks 0 and 2, and the patient is treated with subsequent doses of 250 mg of an antibody that binds to human IL-13 every two weeks for the remainder of the treatment period.

[0022] In some embodiments, the patient is further treated for a maintenance period, e.g., for up to 36 weeks. In some embodiments, the patient is treated with a maintenance dose of 250 mg of an antibody that binds to human IL-13 every two weeks during the maintenance period. In some embodiments, the patient is treated with a maintenance dose of 250 mg of an antibody that binds to human IL-13 every four weeks during the maintenance period. In some embodiments, the patient is treated with a maintenance dose of 250 mg of an antibody that binds to human IL-13 every eight weeks during the maintenance period.

[0023] In some embodiments, the methods provided herein further comprise determining one or more of the following characteristics of the patient before and after the treatment period and / or the maintenance period: Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Face-Investigator's Global Assessment (F-IGA), Pruritus Numeric Rating Scale (NRS) score, Modified Total Lesion Symptom Scale, Sleep Loss Scale, Skin Pain NRS score, Severity Scoring of Atopic Dermatitis (SCORAD), Dermatology Life Quality Index (DLQI) or Children Dermatology Life Quality Index (CDLQI) score, Atopic Dermatitis Control Tool (ADCT), Participant-Reported Satisfaction Questionnaire, Fitzpatrick Skin Phototype Assessment Scale, Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis (WPOSI) score. The WPAI-AD, the Patient-Oriented Eczema Measure (POEM), the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L), and the PROMIS (Patient-Reported Outcomes Measurement Information System) Anxiety and Depression Scale were used.

[0024] In some embodiments, the methods, uses, and pharmaceutical compositions described herein further comprise administering one or more topical corticosteroids to the patient. Thus, antibodies that bind to human IL-13 are also provided herein for administration separately, simultaneously, or sequentially in combination with one or more topical corticosteroids. In some embodiments, the topical corticosteroid is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone. In some embodiments, the topical corticosteroid is administered concurrently with the antibody. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Schematic diagram of the study design described in Example 1.

[0026] Figure 2 Schematic diagram of the study design described in Example 2. n = number of patients; Q2W = every 2 weeks; SC = subcutaneous; W = week. The screening window was 30 days. A loading dose of 500 mg of nerolizumab was administered subcutaneously at baseline (Week 0) and Week 2. A safety follow-up visit was conducted at Week 34, or approximately 12 weeks after the last injection of the study intervention. DETAILED DESCRIPTION

[0027] Provided herein are methods, uses, and pharmaceutical compositions for treating atopic dermatitis using anti-IL-13 antibodies. In some embodiments, provided herein are methods and uses of anti-IL-13 antibodies for treating atopic dermatitis, for example, in patients who have previously been administered dupilumab.

[0028] In one aspect, provided herein are methods for treating moderate to severe atopic dermatitis in a patient in need who has previously been administered dupilumab, comprising administering to the patient an antibody that binds human IL-13. In some embodiments, provided herein are methods for treating moderate to severe atopic dermatitis, comprising selecting a patient who has previously been administered dupilumab and administering to the patient an antibody that binds human IL-13. In some embodiments, the patient discontinues dupilumab due to no response, partial response, or loss of response. In some embodiments, the patient discontinues dupilumab due to intolerance or adverse events. In some embodiments, the patient discontinues dupilumab for other reasons. In some embodiments, the patient discontinues dupilumab for at least four weeks. In some embodiments, the patient discontinues dupilumab for at least eight weeks.

[0029] In some embodiments, provided herein are methods for treating moderate to severe atopic dermatitis, comprising selecting a patient with moderate to severe atopic dermatitis who has previously been treated with dupilumab and discontinued dupilumab due to no response, partial response, or loss of response, and administering to the patient an antibody that binds to human IL- 13. In some embodiments, the patient discontinued dupilumab for at least four weeks. In some embodiments, the patient discontinued dupilumab for at least eight weeks.

[0030] In some embodiments, provided herein are methods for treating moderate to severe atopic dermatitis, comprising selecting a patient with moderate to severe atopic dermatitis who has previously been treated with dupilumab and discontinued dupilumab due to intolerance or an adverse event, and administering to the patient an antibody that binds to human IL- 13. In some embodiments, the patient discontinued dupilumab for at least four weeks. In some embodiments, the patient discontinued dupilumab for at least eight weeks.

[0031] In some embodiments, the patient has moderate to severe atopic dermatitis for at least one year. In some embodiments, moderate to severe atopic dermatitis is determined by the American Academy of Dermatology consensus criteria. In some embodiments, before administering the antibody, the patient's Eczema Area and Severity Index (EASI) score is 16 or higher, the Investigator's Global Assessment (IGA) score is 3 or higher, and more than 10% of the body surface area (BSA) is affected by atopic dermatitis. In some embodiments, the patient has an inadequate response to topical corticosteroids. In some embodiments, the patient is 12 years old or older.

[0032] Also provided herein are methods for treating moderate to severe atopic dermatitis, comprising selecting a patient who is: (i) 12 years of age or older; (ii) has had chronic atopic dermatitis for more than one year according to the American Academy of Dermatology consensus criteria; (iii) has an EASI score of 16 or higher; (iv) has an IGA score of 3 or higher; (v) has more than 10% of its body surface area affected by atopic dermatitis; (vi) has had an inadequate response to topical corticosteroids; and (vii) has previously been treated with dupilumab, wherein the patient discontinued dupilumab due to (1) no response, partial response, or loss of response or (2) intolerance or adverse events; and administering to the patient an antibody that binds to human IL-13. In some embodiments, the patient discontinued dupilumab due to no response, partial response, or loss of response. In some embodiments, the patient discontinued dupilumab due to intolerance or adverse events. In some embodiments, the patient discontinued dupilumab due to no response or partial response. In some embodiments, the patient discontinues dupilumab due to loss of response. In some embodiments, the patient discontinues dupilumab for at least four weeks. In some embodiments, the patient discontinues dupilumab for at least eight weeks.

[0033] In some embodiments, moderate to severe atopic dermatitis can be determined by the American Academy of Dermatology Criteria for the Diagnosis and Evaluation of Atopic Dermatitis (Eichenfield et al., J Am Acad Dermatol. 2014;70(2):338-351). Necessary features that must be present for a diagnosis of AD include pruritus and acute, subacute, or chronic eczema consisting of a typical morphology and an age-specific pattern or a history of chronicity or recurrence. Age-specific patterns include involvement of the face, neck, and extensor muscles in infants and children; current or past flexural lesions in any age group; and sparing of the groin and axillary areas. Important features that are seen in most cases and support a diagnosis of AD include early age of onset, atopicity (personal and / or family history and / or IgE reactivity), and xerosis. Clinical associations that help suggest the diagnosis of AD but are too nonspecific for use in research and epidemiological studies to define or detect AD include atypical vascular reactions, such as facial pallor, white dermographism, and delayed blanch response, keratosis pilaris or pityriasis alba or palmar hyperkeratosis or ichthyosis, ocular or periorbital changes, other regional manifestations, such as perioral changes or periauricular lesions, and increased perifollicular keratosis or lichenification or prurigo lesions. The diagnosis of AD also depends on the exclusion of pathologies such as scabies, seborrheic dermatitis, contact dermatitis (irritant or allergic), ichthyosis, cutaneous T-cell lymphoma, psoriasis, photosensitive skin disorders, immunodeficiency disorders, or erythroderma of other etiologies.

[0034] The severity of atopic dermatitis can also be determined by the "Hanifin and Rajka criteria," as described in the Hanifin and Rajka diagnostic criteria in Acta Derm Venereol (Stockh) 1980; Suppl 92:44-7; or by the "Rajka and Langeland criteria" as described in Rajka G and Langeland T, Acta Derm Venereol (Stockh) 1989; 144(Suppl):13-4.

[0035] Antibodies suitable for the methods and uses provided herein have been previously described, e.g., in WO2005062967. In some embodiments, the antibodies bind to human IL-13 with high affinity and block signaling through active IL-4Rα / IL-13Rα1 heterodimers. In some embodiments, the antibodies that bind to human IL-13 comprise a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: a HCDR1 comprising SEQ ID NO: 1, a HCDR2 comprising SEQ ID NO: 2, and a HCDR3 comprising SEQ ID NO: 3, and the VL comprises: a LCDR1 comprising SEQ ID NO: 4, a LCDR2 comprising SEQ ID NO: 5, and a LCDR3 comprising SEQ ID NO: 6. In some embodiments, the antibodies that bind to human IL-13 comprise: a VH comprising SEQ ID NO: 7 and a VL comprising SEQ ID NO: 8. In some embodiments, an antibody that binds to human IL-13 comprises: a heavy chain comprising SEQ ID NO: 9 and a light chain comprising SEQ ID NO: 10. In some embodiments, the antibody that binds to human IL-13 is lerezumab. The amino acid sequence of lerezumab is provided in Table 1. C-terminal cleavage of IgG antibodies can occur when one or both C-terminal amino acids are removed from the heavy chain of an IgG antibody. For example, a C-terminal lysine (K), if present, can be truncated or truncated from the heavy chain. The penultimate glycine (G) can also be truncated or truncated from the heavy chain. N-terminal amino acid modifications of IgG can also occur. For example, an N-terminal glutamine (Q) or glutamic acid (E) can spontaneously cyclize to pyroglutamic acid (pE). SEQ ID NO: 9 reflects these potential modifications of the lerezumab heavy chain.

[0036] Table 1. Sequences of levofloxacin monoclonal antibodies

[0037]

[0038] An anti-IL-13 antibody (e.g., lerezumab) can be formulated with a suitable carrier or excipient into a pharmaceutical composition suitable for administration to a patient. For example, an anti-IL-13 antibody (e.g., lerezumab) can be formulated in a pharmaceutical composition as described in WO 2013 / 066866. The pharmaceutical composition may contain 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, or 500 mg of the anti-IL-13 antibody. In some embodiments, the pharmaceutical composition contains 250 mg or 500 mg of the anti-IL-13 antibody. In some embodiments, the concentration of the anti-IL-13 antibody in the pharmaceutical composition is between 100 mg / mL and 150 mg / mL, for example, 125 mg / mL. The pharmaceutical composition may also contain 5 mM to 40 mM histidine acetate buffer at a pH of 5.4 to 6.0. In some embodiments, the pharmaceutical composition further comprises a polyol (e.g., a sugar) at a concentration between 100 mM and 200 mM and / or a surfactant (e.g., polysorbate 20) at a concentration between 0.01% and 0.1%. In one embodiment, the pharmaceutical composition comprises 125 mg / mL of an anti-IL-13 antibody (e.g., nerolizumab), 20 mM histidine acetate buffer at pH 5.7, 175 mM sucrose, and 0.03% polysorbate 20.

[0039] In some embodiments, the anti-IL-13 antibody is administered to the patient subcutaneously. The anti-IL-13 antibody can be administered to the patient at a dosing frequency of about once a week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, or once every eight weeks. In some embodiments, the anti-IL-13 antibody is administered to the patient once every two weeks. In some embodiments, the anti-IL-13 antibody is administered to the patient once every four weeks. In some embodiments, the anti-IL-13 antibody is administered to the patient once every eight weeks.

[0040] In some embodiments, the anti-IL-13 antibody is administered to the patient using a subcutaneous administration device. The subcutaneous administration device can be selected from a prefilled syringe, a disposable pen injection device, a microneedle device, a microinfusion device, a needle-free injection device, or an automatic injector device. Various subcutaneous administration devices (including automatic injector devices) are known in the art and are commercially available. Exemplary devices include, but are not limited to, prefilled syringes (e.g., BD HYPAK SCF® from Becton Dickinson, READYFILL TM and STERIFILL SCF TM CLEARSHOT from Baxter TMcopolymer prefilled syringes; and Daikyo Seiko CRYSTAL ZENITH® prefilled syringes available from West Pharmaceutical Services); disposable pen injection devices, such as the BD Pen from Becton Dickinson; ultrasharp and microneedle devices (such as the INJECT-EASE TM and microinfusion device; and H-PATCH available from Valeritas TM ); and needle-free injection devices (e.g., BIOJECTOR® and IJECT® available from Bioject; and SOF-SERTER® and patch devices available from Medtronic). In some embodiments, the subcutaneous administration device is an autoinjector device described in WO 2008 / 112472, WO 2011 / 109205, WO 2014 / 062488, and / or WO 2016 / 089864.

[0041] In some embodiments, the patient is treated with an anti-IL-13 antibody for a treatment period of about 16 to 24 weeks (e.g., 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks). In some embodiments, the patient is treated with an anti-IL-13 antibody for a treatment period of about 16 weeks. In some embodiments, the patient is treated with an anti-IL-13 antibody for a treatment period of about 24 weeks. In some embodiments, the patient is treated with a 500 mg loading dose of the anti-IL-13 antibody at weeks 0 and 2, and then the patient is treated with a 250 mg dose of the anti-IL-13 antibody every two weeks for the remainder of the treatment period.

[0042] In some embodiments, the patient is further treated with an anti-IL-13 antibody for a maintenance period, e.g., for up to 36 weeks (e.g., about 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, 24 weeks, 28 weeks, 32 weeks, 36 weeks). In some embodiments, the patient is treated with a 250 mg maintenance dose of the anti-IL-13 antibody every two weeks during the maintenance period. In some embodiments, the patient is treated with a 250 mg maintenance dose of the anti-IL-13 antibody every four weeks during the maintenance period. In some embodiments, the patient is treated with a 250 mg maintenance dose of the anti-IL-13 antibody every eight weeks during the maintenance period.

[0043] Before, during, and after the treatment and / or maintenance period, the patient can be assessed for one or more features of the Atopic Dermatitis Disease Severity Measure (ADDSM), which identify certain signs, symptoms, characteristics, or parameters that are associated with atopic dermatitis and can be assessed quantitatively or qualitatively. Exemplary ADDSMs include, but are not limited to, the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Facial Investigator Global Assessment (F-IGA), Pruritus Numeric Rating Scale (NRS) score, Modified Total Lesion Symptom Scale, Sleep Loss Scale, Skin Pain NRS score, Severity Score for Atopic Dermatitis (SCORAD), Dermatology Life Quality Index (DLQI) or Children's Dermatology Life Quality Index (CDLQI) score, Atopic Dermatitis Control Tool (ADCT), participant-reported satisfaction questions, Fitzpatrick Skin Phototype Assessment Scale, Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis (WPAI-AD), Patient-Oriented Eczema Measure (POEM), European Quality of Life 5 Dimensions 5 Levels Scale (EQ-5D-5L), and PROMIS (Patient-Reported Outcomes Measurement Information System) Anxiety and Depression Scale.

[0044] ADDSM can be measured at baseline (before administration of the antibody) and at one or more time points after administration of the antibody. For example, ADDSM can be measured at the end of week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12, week 13, week 14, week 15, week 16, or more after the initial treatment with the antibody. The difference between the ADDSM value at a particular time point after the start of treatment and the ADDSM value at baseline is used to determine whether ADDSM has improved (e.g., decreased).

[0045] The "Eczema Area and Severity Index" or "EASI" is a 20-item investigator-reported scale that assesses two dimensions of AD: the extent of disease in four body regions (head or neck, trunk, upper extremities, and lower extremities) and four clinical signs (erythema, induration or papules, excoriation, and lichenification). The severity of clinical signs is assessed on a scale of 0 (absent) to 3 (severe). The scores for each of the four body regions are summed. The percentage of BSA allocated to each body part is 10% for the head or neck, 20% for the upper extremities, 30% for the trunk, and 40% for the lower extremities. Each subtotal score is multiplied by the BSA represented by that region. In addition, each body region is assigned a regional score from 0 to 6, depending on the percentage of skin in that area affected by AD: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each body area score is multiplied by the affected area. The resulting EASI ranges from 0 to 72 points, with the highest score indicating worse severity of AD (Hanifin et al., Exp Dermatol. 2001; 10: 11-18).

[0046] The "Investigator Global Assessment" or "IGA" is a single-item scale reported by the investigator that rates the severity of the participant's AD (Simpson E et al. J Am Acad Dermatol. 2020;83(3):839-846). The IGA consists of a 5-point scale ranging from 0 (clear) to 4 (severe), and the score is selected using the descriptor that best describes the overall appearance of the lesion at a given time point (see Table 2).

[0047] Table 2. Investigator's Overall Assessment

[0048]

[0049] Body surface area (BSA) is an investigator-reported assessment that estimates the extent of disease or skin involvement in a participant's AD. BSA is expressed as a percentage of total body surface area and reported by body location. BSA was determined by the investigator using the approximately 1% BSA rule for the palm of the patient's hand. The recall period for this assessment was the current time.

[0050] The Facial Investigator Global Assessment (F-IGA) is an investigator-administered single-item scale that rates the severity of AD on the participant's face. The F-IGA consists of a 5-point scale ranging from 0 (no abnormality) to 4 (severe), and the score is selected using descriptors that best describe the overall appearance of the facial lesions at a given time point.

[0051] The "SCORAD" index is a 9-item investigator- and participant-reported assessment for adults and adolescents that assesses 3 areas: extent, severity, and subjective symptoms (Stalder J., Taieb A., Consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23-31). The extent of AD (1 item) is assessed by the investigator as a percentage of each defined body area and the sum of all areas is reported. The maximum score is 100%. The recall period for this scale is the current time. The severity of 6 specific symptoms of AD is assessed by the investigator: erythema, edema or papules, oozing or crusting, excoriation, lichenification, and dryness are assessed by the investigator using a 4-point scale (i.e., none = 0, mild = 1, moderate = 2, severe = 3), with a maximum possible total score of 18 points. The recall period for this scale is the current time. Subjective symptoms of pruritus and sleep loss (two items) were assessed by participants using a 10-cm visual analog scale. Participants or caregivers recorded symptoms (itching and sleeplessness) on a visual analog scale, where 0 represents no symptoms and 10 represents the worst symptom imaginable, with a maximum possible score of 20. This scale was used for the last three days. The maximum possible SCORAD score, calculated based on these three domains, was 103. Higher scores indicate worse or more severe disease.

[0052] The modified Total Symptom Scale is an investigator-reported scale that combines assessments of hand eczema (HE) lesion severity (erythema, edema, scaling, fissures, hyperkeratosis or lichenification, and blistering) with the intensity of itch or pain (Bissonnette et al., J Eur Acad Dermatol Venereol. 2010;24(s3):1-20) to assess symptom severity. This composite score assigns 0 (mild) to 3 (severe) to each component, resulting in a maximum disease severity of 21 points. The recall period for this scale is the current time. It has been used as a secondary endpoint in studies investigating alitretinoin for the treatment of HE (Ruzicka et al., Br J Dermatol. 2008;158(4):808-817; Fowler et al., JDrugs Dermatol. 2014;13(10):1198-204).

[0053] The Numeric Rating Scale (NRS) for Itch is a single, daily 11-point scale reported by participants. Participants use the NRS for Itch to rate the severity of their worst itching in the past 24 hours, with 0 indicating "no itching" and 10 indicating "the worst itching imaginable". The assessment will be recorded daily by the participant. The minimum clinically important change is 3 points. (Yosipovitch et al., Br J Dermatol. 2019;181(4):761-769). Participants will use an electronic diary at home to record their itch assessment daily. The initial electronic diary record of the NRS for Itch should be completed on at least 4 of the 7 days before baseline.

[0054] The skin pain NRS is an 11-point scale reported by the participant, fixed between 0 and 10, where 0 means "no pain" and 10 means "the worst pain imaginable". The overall severity of the participant's skin pain is indicated by selecting the number that best describes the worst skin pain in the past 24 hours (Newton L et al., J Patient Rep Outcomes. 2019 Jul 16; 3:42; Silverberg et al., Health Qual Life Outcomes. 2021; 19(1): 247). Assessments will be recorded daily by the participant.

[0055] The Sleep Loss Scale is a single-item daily scale reported by participants that measures the degree of sleep loss due to itching interference from the previous night. The Sleep Loss Scale is rated on a 5-point Likert scale (0 [not at all] to 4 [unable to sleep at all]). Assessments are recorded daily by participants. The minimum clinically important change is 3 points (Yosipovitch et al., 2021, Content Validity And Assessment Of The Psychometric Properties AndScore Interpretation Of A Pruritus Numeric Rating Scale In Atopic Dermatitis. Revolutionizing Atopic Dermatitis - December 2021). Participants record itch assessments daily at home using an electronic diary. The initial electronic diary record of the Sleep Loss Scale was completed for at least 4 days within 7 days before baseline.

[0056] The Dermatology Life Quality Index (DLQI) is a 10-item participant-reported adult QoL questionnaire covering six domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). The recall period for this scale is "last week". Response categories include "not at all", "a little", "a lot", and "very", with corresponding scores of 0, 1, 2, and 3, respectively, and no response (or "not relevant") is scored as 0. Scores range from 0 to 30, with higher scores indicating greater impairment of QoL. A DLQI total score of 0 to 1 is considered to have no effect on the participant's HRQoL (Hongbo et al., 2005), and a change of 4 points from baseline is considered the minimal clinically important difference cutoff (Khilji et al. 2002, Br J Dermatol.; 147:25-54; Basra et al. 2015, Dermatology.; 230(1):27-33).

[0057] For adolescents under 16 years of age at baseline, the Children's DLQI (CDLQI) was used, which is based on a different set of 10 questions from the DLQI (Lewis-Jones MS, Finlay AY. British Journal of Dermatology, 1995;132:942-949), and should continue to be completed during the study period.

[0058] The Atopic Dermatitis Control Tool (ADCT) is a simple, brief tool reported by patients for adults and adolescents that assesses 6 symptoms and effects associated with AD in the past week: overall severity of symptoms, number of days with severe itching, intensity of interference, sleep problems, impact on daily activities, and impact on mood or emotion. Each of the 6 Atopic Dermatitis Control Tool items has a score range of 0 (no problem) to 4 (worst), rating the severity of each concept; the total score range is 0 to 24, which is the sum of the answers to all items. A score of ≥ 7 points is obtained as the critical value for identifying participants as "out of control". The critical value of meaningful within-person change is estimated to be 5 points (Simpson et al., BMC Dermatol. 2019; 19(1): 15; Pariser et al., Curr Med Res Opin. 2020; 36(3): 367-376).

[0059] The participant-reported satisfaction question asked, “How satisfied are you with this treatment's ability to treat your skin condition?” Response options ranged from 1 (not satisfied) to 5 (completely satisfied).

[0060] The Patient-Oriented Eczema Measure (POEM) is a 7-item scale that assesses disease severity in children and adults. Participants respond to questions about the frequency of 7 symptoms (itching, sleep disturbance, bleeding, oozing / exudation, cracking, flaking, and dryness / roughness) in the past week. Response categories include "never a day," "1 to 2 days," "3 to 4 days," "5 to 6 days," and "every day," with corresponding scores of 0, 1, 2, 3, and 4, respectively. Scores range from 0 to 28, with higher total scores indicating greater disease severity (Charman et al., Arch Dermatol. 2004; 140(12): 1513-1519). High scores indicate poor quality of life.

[0061] The European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L, EuroQol Research Foundation) is a standardized 5-item self-management tool used as a measure of health outcomes. The scale provides a simple descriptive overview of health status and a single index value, which can be used for clinical and economic assessment of health care and population health surveys. The European Quality of Life 5-Dimension 5-Level Scale assesses 5 dimensions of health: mobility, self-care, daily activities, pain / discomfort, and anxiety / depression. The 5L version scores each dimension with 5 levels: no problems, minor problems, moderate problems, severe problems, and inability to perform / extreme problems. A total of 3125 health states are possible. In addition to health summaries, a single health state index value can be derived based on a formula that assigns weights to each level of each dimension. The range of this index value is between less than 0 (where 0 is a health state equivalent to death; negative values ​​are considered worse than death) and 1 (perfect health status). In addition, the EQ visual analog scale records the respondent's self-rated health status on a vertical scale (0 to 100) visual analog scale. Participants rated their perceived health from 0 (worst health imaginable) to 100 (best health imaginable). Combined with the health status data, this provided a composite picture of the respondent's health status.

[0062] The Fitzpatrick Skin Phototype Assessment Scale is a clinician-rated scale based on the participant's skin reaction to sun exposure and baseline skin pigmentation. The Fitzpatrick Skin Phototype scale ranges from I to VI, with a score of I indicating "always burns, never tans, and has a fair complexion," and a score of VI indicating "never burns, tans easily, and has a dark complexion" (High et al. 2012, Dermatology (3rd ed.), China: Elsevier; 2012: p. 8). Researchers will follow the descriptive terms included in this protocol when recording Fitzpatrick Skin Phototype. The sun sensitivity measure will represent each participant's Fitzpatrick scale score. The recall period for this scale is the current time.

[0063] The Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis (WPAI-AD) is a 6-item participant-reported questionnaire that records impairment caused by AD in adolescents and adults over the past 7 days. The Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis consists of 6 items divided into 4 areas: absenteeism (missed work time), overtime (work impairment or reduced work efficiency), work efficiency loss (total work impairment or absenteeism plus overtime), and activity impairment. Absenteeism, overtime, and work efficiency will only be reported by those who are currently employed (paid work) at the time the scale is completed. The recall period for this scale is the past 7 days. Scores are calculated as percentage impairment (Reilly et al., Pharmacoeconomics. 1993; 4(5): 353-365), where higher scores indicate greater impairment and lower efficiency.

[0064] PROMIS (Patient Reported Fever Outcome Measurement Information System) is a set of personalized measures to assess and monitor the physical, mental, and social health of adults and children (PROMIS WWW). PROMIS measures include anxiety and depression short forms, which assess participants' symptoms over the previous week. It can be used in the general population and individuals with chronic diseases.

[0065] The PROMIS Anxiety Scale assesses self-reported fear (fear, panic), anxious distress (worry, dread), hypervigilance (tense, tense, restless), and somatic symptoms related to vigilance (rapid heartbeat, dizziness) (PROMIS Anxiety 2019, available at https: / / www.healthmeasures.net / images / PROMIS / manuals / PROMIS_Anxiety_Scoring_Manual.pdf). The PROMIS Anxiety Short Form (8 questions, 8a v2.0) can be used for self-reporting in children (aged 8 to <18 years) and for parents / caregivers acting as proxy reporters for their children (aged 5 years and older). Children younger than 5 years do not need to complete this assessment. Both the child self-report and proxy-report versions assess anxiety over the past 7 days. Response options range from 1 = never; 2 = rarely; 3 = sometimes; 4 = often; and 5 = almost always. Total raw scores are converted to T-scores, with higher scores indicating more severe anxiety.

[0066] The PROMIS Depression Scale assesses self-reported negative emotions (sadness, guilt), self-criticism (self-criticism, feelings of worthlessness), social cognitions (loneliness, disconnection from relationships), and decreased positive emotions and engagement (loss of interest, meaning, and goals) (PROMIS Depression 2019, available at https: / / www.healthmeasures.net / images / PROMIS / manuals / PROMIS_Depression_Scoring_Manual.pdf). The PROMIS Depression Short Form (8av2.0 and 6a v2.0) can be used for self-reporting by children (aged 8 to <18 years) and for parents / caregivers acting as proxy reporters for their children (aged 5 years and older). Children younger than 5 years do not need to complete this assessment. Both the child self-report and proxy-report versions assess depression in the "past 7 days." Response options range from 1 = never; 2 = rarely; 3 = sometimes; 4 = often; and 5 = almost always. Total raw scores are converted to T scores, with higher scores indicating more severe depression.

[0067] In some embodiments, the patient's EASI score is determined after the treatment period (e.g., week 16 or week 24). In some embodiments, the patient's EASI score determined after the treatment period is reduced by 50% or more compared to the EASI score determined before the administration of the first loading dose of the antibody, meaning that the patient has reached "EASI 50". In some embodiments, the patient's EASI score determined after the treatment period is reduced by 75% or more compared to the EASI score determined before the administration of the first loading dose of the antibody, meaning that the patient has reached "EASI 75". In some embodiments, the patient's EASI score determined after the treatment period is reduced by 90% or more compared to the EASI score determined before the administration of the first loading dose of the antibody, meaning that the patient has reached "EASI 90".

[0068] In some embodiments, the patient's IGA score is determined after the treatment period. In some embodiments, the patient's IGA score determined after the treatment period is 0 or 1, and the IGA score determined after the treatment period is reduced by 2 points or more compared to the IGA score determined before administration of the first loading dose of the antibody.

[0069] In some embodiments, the patient's pruritus NRS score is determined after the treatment period. In some embodiments, the patient's pruritus NRS score determined after the treatment period is reduced by 4 points or more compared to the pruritus NRS score determined before administration of the first loading dose of the antibody.

[0070] In another aspect, provided herein is an antibody that binds to human IL-13 for use in treating moderate to severe atopic dermatitis in a patient who has previously been administered dupilumab. In some embodiments, provided herein is an antibody that binds to human IL-13 for use in treating moderate to severe atopic dermatitis in a patient who has previously been administered dupilumab and has discontinued dupilumab due to no response, partial response, or loss of response. In some embodiments, provided herein is an antibody that binds to human IL-13 for use in treating moderate to severe atopic dermatitis in a patient who has previously been administered dupilumab and has discontinued dupilumab due to intolerance or adverse events. In some embodiments, the patient is: (1) 12 years of age or older; (2) has had chronic atopic dermatitis for more than one year according to the American Academy of Dermatology consensus criteria; (3) has an EASI score of 16 or higher; (4) has an IGA score of 3 or higher; (5) has more than 10% of the BSA affected by atopic dermatitis; and (6) has had an inadequate response to topical corticosteroids. In some embodiments, the antibody is administered to the patient subcutaneously.

[0071] In another aspect, provided herein are uses of antibodies that bind to human IL-13 for the manufacture of a medicament for treating moderate to severe atopic dermatitis in patients who have previously been treated with dupilumab. Also provided herein are uses of antibodies that bind to human IL-13 for the manufacture of a medicament for treating moderate to severe atopic dermatitis in patients who have previously been treated with dupilumab and who have discontinued dupilumab due to no response, partial response, or loss of response. Also provided herein are uses of antibodies that bind to human IL-13 for the manufacture of a medicament for treating moderate to severe atopic dermatitis in patients who have previously been treated with dupilumab and who have discontinued dupilumab due to intolerance or adverse events. In some embodiments, the patient is: (1) 12 years of age or older; (2) has had chronic atopic dermatitis for more than one year according to the American Academy of Dermatology consensus criteria; (3) has an EASI score of 16 or higher; (4) has an IGA score of 3 or higher; (5) has more than 10% of the BSA affected by atopic dermatitis; and (6) has had an inadequate response to topical corticosteroids. In some embodiments, the antibody is administered to the patient subcutaneously.

[0072] In some embodiments, the methods and purposes described herein further include applying one or more topical corticosteroids to the patient. Exemplary topical corticosteroids include but are not limited to triamcinolone acetonide, hydrocortisone and the combination of triamcinolone acetonide and hydrocortisone. Triamcinolone acetonide is usually formulated in an emulsifiable paste at a concentration of 0.1%, and hydrocortisone is usually formulated in an emulsifiable paste at a concentration of 1% or 2.5%. Some topical corticosteroids are considered to have very high efficacy, such as betamethasone dipropionate (betamethasone dipropionate), clobetasol propionate (clobetasol propionate), diflorasone diacetate (diflorasone diacetate), fluocinonide (fluocinonide) and halobetasol propionate (halobetasol propionate). Some topical corticosteroids are considered to have high efficacy, such as amcinonide (amcinonide), desoximetasone (desoximetasone), halcinonide (halcinonide) and triamcinolone acetonide. Certain topical corticosteroids are considered to have moderate efficacy, such as betamethasone valerate, clocortolone pivalate, fluocinolone acetonide, flurandrenolide, fluocinolone acetonide, fluticasone propionate, hydrocortisone butyrate, hydrocortisone valerate, mometasone furoate, and prednicarbate. Certain topical corticosteroids are considered to have low efficacy, such as alclometasone dipropionate, desonide, and hydrocortisone. TCS can be applied to the affected area once a day, twice a day, three times a day, or as needed. In some embodiments, topical corticosteroids are not effective in controlling the patient's disease. In some embodiments, the topical corticosteroid is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone. In some embodiments, the topical corticosteroid is administered simultaneously or sequentially with the anti-IL-13 antibody. In some embodiments, the topical corticosteroid is administered simultaneously with the anti-IL-13 antibody. Thus, antibodies that bind to human IL-13 are also provided herein for separate, simultaneous, or sequential administration in combination with one or more topical corticosteroids.

[0073] As used herein, the terms “a,” “an,” “the,” and similar terms used in the context of the disclosure (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.

[0074] As used herein, the term "about" means within a reasonable approximation of the stated value, for example, + or - 10% of the stated value.

[0075] As used herein, the term "administering" or "administering" refers to administering an antibody, compound, or composition directly to a subject, including treating a subject with the antibody, compound, or composition.

[0076] As used herein, the term "adverse event" refers to any untoward medical occurrence in a participant to whom a drug is administered and which does not necessarily have a causal relationship with the study intervention. Thus, an adverse event can be any unfavorable and unexpected sign (including abnormal laboratory findings), symptom, or disease (new or worsening) temporally associated with the use of a drug, whether or not related to the drug.

[0077] The term "antibody" as used herein refers to an immunoglobulin molecule that binds to an antigen. Embodiments of antibodies include monoclonal antibodies, polyclonal antibodies, human antibodies, humanized antibodies, chimeric antibodies, or conjugated antibodies. Antibodies can be of any class (e.g., IgG, IgE, IgM, IgD, IgA) and any subclass (e.g., IgG1, IgG2, IgG3, IgG4).

[0078] An exemplary antibody is an immunoglobulin G (IgG) type antibody composed of four polypeptide chains: two heavy chains (HC) and two light chains (LC) cross-linked via interchain disulfide bonds. The amino terminal portion of each of the four polypeptide chains includes a variable region having about 100 to 125 or more amino acids that is primarily responsible for antigen recognition. The carboxyl terminal portion of each of the four polypeptide chains contains a constant region that is primarily responsible for effector function. Each heavy chain is composed of a heavy chain variable region (VH) and a heavy chain constant region. Each light chain is composed of a light chain variable region (VL) and a light chain constant region. IgG isotypes can be further divided into subclasses (e.g., IgG1, IgG2, IgG3, and IgG4).

[0079] The VH and VL regions can be further subdivided into hypervariable regions, called complementarity determining regions (CDRs), interspersed with more conserved regions called framework regions (FRs). CDRs are exposed on the surface of the protein and are regions important for the antigen-binding specificity of the antibody. Each VH and VL is composed of three CDRs and four FRs, arranged in the following order from amino-terminus to carboxyl-terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. Herein, the three CDRs of the heavy chain are referred to as "HCDR1, HCDR2, and HCDR3" and the three CDRs of the light chain are referred to as "LCDR1, LCDR2, and LCDR3". The CDRs contain most of the residues that form specific interactions with the antigen. Assignment of amino acid residues to CDRs can be performed according to well-known schemes, including those described by Kabat (Kabat et al., "Sequences of Proteins of Immunological Interest", National Institutes of Health, Bethesda, Md. (1991)), Chothia (Chothia et al., "Canonical structures for the hypervariable regions of immunoglobulins", Journal of Molecular Biology, 196, 901-917 (1987); Al-Lazikani et al., "Standard conformations for the canonical structures of immunoglobulins", Journal of Molecular Biology, 273, 927-948 (1997)), North (North et al., "A New Clustering of Antibody CDR Loop Conformations", Journal of Molecular Biology, 274, 927-948 (1997)), and North et al., "A New Clustering of Antibody CDR Loop Conformations", Journal of Molecular Biology. Biology, 406, 228-256 (2011)) or IMGT (International ImMunoGeneTics database available at www.imgt.org; see Lefranc et al., Nucleic Acids Res. 1999; 27:209-212).

[0080] Exemplary embodiments of the antibodies of the present disclosure also include antibody fragments or antigen-binding fragments comprising at least a portion of an antibody that retains the ability to specifically interact with an antigen, such as Fab, Fab', F(ab')2, Fv fragments, scFv, scFab, disulfide-linked Fv (sdFv), Fd fragments, and linear antibodies.

[0081] As used herein, unless otherwise indicated, the term "binding" means the ability of a protein or molecule to form a chemical bond or attractive interaction with another protein or molecule, which brings the two proteins or molecules into proximity as determined by common methods known in the art.

[0082] As used herein, the term "disease flare" refers to an increase in signs and / or symptoms that leads to an escalation of therapy, which may be a dose increase, a switch to a higher potency class of medication, or the initiation of another medication.

[0083] The term "high affinity" as used herein refers to the binding strength of an antibody to human IL-13, with an equilibrium dissociation constant (K D ) is less than about 10 -8 M, for example 10 -15 M to 10 -8 M, or 10 -12 M to 10 -9 M.

[0084] The term "human IL-13" refers to human interleukin-13 (also known as P600), an immunomodulatory cytokine produced primarily by activated Th2 cells. There are two known isoforms of human IL-13: isoform a and isoform b. As used herein, the term "human IL-13" refers collectively to all human IL-13 isoforms. The amino acid sequence of human IL-13 isoform a can be found in NCBI Accession No. NP_002179.2. The amino acid sequence of human IL-13 isoform b can be found in NCBI Accession No. NP_001341922.1.

[0085] As used herein, the term "no response" or "non-response" means that the patient's atopic dermatitis does not improve at all or improves by less than 25% after treatment, for example, the patient's skin and / or itching does not improve at all or improves by less than 25% of the peak response to dupilumab (e.g., as measured by the EASI score for skin and / or the NRS score for itch).

[0086] As used herein, the term "partial response" means that the patient's atopic dermatitis improves only partially with treatment, e.g., the patient's skin and / or itch improves by only 25 to 50% of the peak response to dupilumab (e.g., as measured by the EASI score for skin and / or the NRS score for itch).

[0087] As used herein, the term "loss of response" refers to a patient who initially responds to treatment but subsequently loses response, e.g., a patient's skin and / or itch initially improves after treatment with dupilumab (e.g., as measured by the EASI score for skin and / or the NRS score for itch), but then worsens.

[0088] As used herein, the term "intolerance" refers to an unacceptable adverse event in response to treatment. For example, a patient discontinued dupilumab due to: allergic reaction; new or worsening ocular surface disease (including but not limited to conjunctivitis); new or worsening facial dermatitis; new or worsening injection site reaction; new or worsening inflammatory arthritis; new or worsening psoriatic dermatitis; new or worsening alopecia areata.

[0089] As used herein, the term "inadequate response" refers to failure to achieve good disease control of atopic dermatitis (e.g., failure to achieve IGA ≤ 2 or EASI-75) after treatment for the duration recommended in the product's prescribing information, or the occurrence of a disease flare of atopic dermatitis during treatment.

[0090] As used herein, the term "patient" refers to a human patient.

[0091] Term used herein " topical corticosteroid " or " TCS " comprise I group, II group, III group and IV group topical corticosteroid.According to the Anatomical Therapeutic Chemical (ATC) Classification System of World Health Organization of the World Health Organization, corticosteroid is classified as weak (I group), medium effect (II group) and potent (III group) and very potent (IV group) based on their activity compared with hydrocortisone.The effect of IV group TCS (very potent) is as many as 600 times of hydrocortisone and comprises clobetasol and halcinonide.The effect of III group TCS (potent) is 50 to 100 times of hydrocortisone and includes but not limited to betamethasone valerate, betamethasone dipropionate, diflucortolone valerate, 17-hydrocortisone butyrate, mometasone furoate and methylprednisolone acetate (methylprednisolone aceponate). Group II TCS (moderate potency) are 2 to 25 times more potent than hydrocortisone and include, but are not limited to, clobetasone butyrate and triamcinolone acetonide. Group I TCS (weak or mild) include hydrocortisone, prednisolone, and methylprednisolone.

[0092] As used herein, "treatment," "treat," or "treating" refers to all methods by which the progression of a condition or disease disclosed herein can be slowed, controlled, delayed, or stopped, or the symptoms of a condition or disease can be ameliorated, but does not necessarily mean that all conditions or disease symptoms are completely eliminated. Treatment includes the administration of a protein or nucleic acid or vector or composition for the treatment of a disease or condition in a patient, especially a human.

[0093] Example

[0094] Example 1. A randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of neratumumab combined with topical corticosteroids (TCS) in patients with moderate to severe atopic dermatitis (KGAD)

[0095] This is a 16-week, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the safety and efficacy of nerolizumab plus TCS therapy compared with placebo plus TCS therapy for the treatment of moderate to severe AD. Figure 1 middle.

[0096] During the 16-week treatment period, approximately 225 patients were stratified and randomly assigned in a 2:1 ratio to receive either 250 mg of nerolizumab (with a loading dose of 500 mg at baseline (Week 0) and Week 2) or placebo subcutaneously (SC) every 2 weeks (Q2W). All study drug injections were administered in the clinic. All patients started TCS treatment at baseline and could be tapered or discontinued as needed based on treatment response.

[0097] After the Week 16 visit, patients were offered the option to continue treatment in a separate long-term extension (LTE) study. Patients who terminated early or chose not to participate in the long-term extension study were followed for safety approximately 12 weeks after their last study drug injection.

[0098] Study objectives and endpoints

[0099] Primary endpoint:

[0100] For the FDA, the primary efficacy endpoint was the percentage of patients with an IGA score of 0 or 1 who achieved a ≥2-point decrease from baseline to week 16.

[0101] For EMA, the following coprimary endpoints were used: (1) the percentage of patients with an IGA score of 0 or 1 who had a ≥2-point decrease from baseline to week 16; and (2) the percentage of patients who achieved EASI-75 (≥75% decrease in EASI score from baseline) at week 16.

[0102] Secondary End Points

[0103] Table 3 below lists the secondary endpoints of this study.

[0104] Table 3. Secondary End Points

[0105]

[0106] Statistical analyses were performed for the primary and secondary endpoints.

[0107] Patient population

[0108] Inclusion Criteria: Patients must meet all of the following criteria to be eligible for this study:

[0109] 1. Adults and adolescents (≥12 years to <18 years old and weighing ≥40 kg).

[0110] 2. Chronic AD has existed for ≥1 year before the screening visit (according to the American Academy of Dermatology consensus criteria).

[0111] 3. Eczema Area and Severity Index (EASI) score ≥16 at baseline visit.

[0112] 4. At the baseline visit, the investigator's global assessment (IGA) score is ≥3 (0 to 4 scale).

[0113] 5. At the baseline visit, AD affected body surface area (BSA) ≥ 10%.

[0114] 6. History of inadequate response to topical medications.

[0115] 7. A stable dose of non-medicated topical moisturizer applied at least twice daily for ≥7 days prior to the baseline visit.

[0116] 8. Complete an electronic diary for pruritus and sleep loss for at least 4 of the 7 days prior to randomization.

[0117] 9. Willing and able to comply with all clinical visits and study-related procedures and questionnaires.

[0118] 10. For women of childbearing potential: agree to abstain from sex or use highly effective contraception during treatment and for at least 18 weeks after the last dose of nerolizumab or placebo.

[0119] 11. If male patients have sexual intercourse with females of reproductive potential, they must agree to use effective barrier contraception during the study and for at least 18 weeks after the last dose of the study drug.

[0120] 12. Provide signed informed consent / permission form.

[0121] Exclusion criteria: Patients who meet any of the following criteria will be excluded from this study.

[0122] 1. Participated in previous clinical studies of Lerezotinib.

[0123] 2. History of allergic reaction as defined by the Sampson criteria (Sampson 2006).

[0124] 3. Treatment with topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), or phosphodiesterase-4 inhibitors (e.g., crisaborole) within 1 week prior to the baseline visit.

[0125] 4. Treatment with any of the following medications within 4 weeks prior to the baseline visit:

[0126] a. Immunosuppressive / immunomodulatory drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.);

[0127] b. Phototherapy and photochemotherapy (PUVA) for AD.

[0128] 5. The following treatments were performed before the baseline visit:

[0129] a. Within 8 weeks or, if known, 5 half-lives of the investigational drug, whichever is longer.

[0130] b. Use dupilumab within 8 weeks.

[0131] c. Use of B cell-depleting biologics, including rituximab, within 6 months.

[0132] d. Use of other biologics within 5 half-lives (if known) or 16 weeks, whichever is longer.

[0133] 6. Use of prescription moisturizer within 7 days of baseline visit.

[0134] 7. Regular use of a tanning room / tanning studio (more than 2 visits per week) within 4 weeks of the screening visit.

[0135] 8. Treatment with live (attenuated) vaccines within 12 weeks of the baseline visit or planned during the study.

[0136] 9. Uncontrolled chronic diseases that may require large amounts of oral corticosteroids, such as concurrent severe uncontrolled asthma (defined by an ACQ-5 score ≥1.5 or a history of ≥2 asthma exacerbations requiring systemic [oral and / or parenteral] corticosteroids or hospitalization for >24 hours in the past 12 months).

[0137] 10. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to the baseline visit, or superficial skin infection within 1 week prior to the baseline visit.

[0138] 11. Evidence of active acute or chronic hepatitis (as defined by the Centers for Disease Control and Prevention, Department of Health and Human Services) or known cirrhosis.

[0139] 12. Diagnosed with active internal parasitic infections or at high risk for these infections.

[0140] 13. History of known or suspected immunosuppression, including a history of invasive opportunistic infections (e.g., tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis), despite resolution of the infection; or unusually frequent, recurrent, or prolonged infections, as determined by the investigator.

[0141] 14. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening.

[0142] 15. Any clinically significant laboratory results from chemistry, hematology, or urinalysis tests obtained at the screening visit in the investigator's opinion.

[0143] 16. The presence of skin comorbidities that may interfere with study assessments.

[0144] 17. History of malignant tumor (including mycosis fungoides) within 5 years before the screening visit, except for completely cured carcinoma in situ of the cervix, completely cured and regressed non-metastatic squamous or basal cell carcinoma of the skin.

[0145] 18. Serious concomitant illness that the investigator judges would adversely affect the patient's participation in the study. Any other medical or psychological condition that the investigator believes may suggest a new and / or underdeveloped disease, may impose unreasonable risks on the study patient due to the patient's participation in this clinical trial, may make the patient's participation unreliable, or may interfere with study assessments.

[0146] 19. Women who are pregnant or breastfeeding, or who plan to become pregnant or breastfeed during the study.

[0147] 20. TCS has produced significant side effects (e.g., intolerance to treatment, allergic reactions, significant skin atrophy, and systemic effects) that would prohibit further use, as assessed by the investigator or treating physician.

[0148] Study Drug:

[0149] Lerezumab was supplied as a sterile liquid solution containing 125 mg / mL lerezumab, histidine acetate, sucrose, polysorbate 20, and sterile water for injection, pH 5.4 to 6.0. The placebo solution was identical in appearance and content, except for the absence of lerezumab. All study medications (lerezumab and placebo) were supplied in sterile prefilled syringes with preassembled needle safety devices (PFS-NSDs). Each prefilled syringe was intended for subcutaneous (SC) administration of a single 2 mL dose (250 mg).

[0150] Outcomes in patients previously treated with dupilumab

[0151] In this study, 211 patients were randomized in a 2:1 ratio to receive either nerolizumab plus TCS (N=145) or placebo plus TCS (N=66). Twenty patients randomized to nerolizumab plus TCS and nine patients randomized to placebo plus TCS reported prior exposure to dupilumab. Among these 29 patients, the reasons for discontinuing dupilumab were loss of response or inadequate response (14 patients), drug intolerance (1 patient), or other (14 patients). Other reported reasons for discontinuation included patient decision, affordability, and treatment availability.

[0152] Among patients treated with levitra plus TCS, baseline characteristics were comparable between the overall levitra-treated population (N=145) and the subpopulation previously exposed to dupilumab (N=20). Of the 20 patients previously exposed to dupilumab, 13 presented with an IGA of 3 and 7 presented with an IGA of 4. The mean body surface area (standard deviation [SD]) reported at baseline was 37.3 (15.7). The mean (SD) baseline scores for the EASI and pruritus NRS were 25.9 (8.1) and 7.8 (1.9), respectively. Patients previously exposed to dupilumab had a longer mean (SD) duration since onset of AD compared with those not previously exposed to dupilumab (27.0 [22.5] vs 21.0 [17.4], respectively).

[0153] At week 16, among patients treated with neratumumab plus TCS who had previously been exposed to dupilumab, 6 of 18 patients achieved a 2-point improvement on IGA 0 / 1, 13 of 18 patients achieved an EASI-75, and 8 of 15 patients achieved a 4-point improvement on the pruritus NRS. One patient reported using a high-potency rescue or systemic medication.

[0154] The results of this subgroup analysis suggest that patients previously exposed to dupilumab are likely to respond to nerezumab plus TCS. nerezumab may provide clinically meaningful improvement in atopic dermatitis in patients who have previously received dupilumab but have not responded to it or who are intolerant to dupilumab.

[0155] Example 2. A Study Evaluating the Safety and Efficacy of Lerelumab in Adult and Adolescent Participants with Moderate to Severe Atopic Dermatitis Previously Treated with KGBO

[0156] This trial was designed to evaluate the safety and efficacy of neratumumab in adult and adolescent participants with moderate to severe AD who had been previously treated or administered pilumab.

[0157] Figure 2 Schematic diagram of the study design. The trial had three study periods: a screening period (≤30 days before baseline); a treatment period (24 weeks); and a safety follow-up period (at Week 34 or approximately 12 weeks after the last treatment). During the 24-week treatment period, approximately 120 participants received a 500 mg loading dose of nerolizumab subcutaneously (SC) at baseline (Week 0) and Week 2, followed by 250 mg of nerolizumab every two weeks (Q2W).

[0158] Approximately 120 participants who had previously received or received dupilumab were enrolled in the study. Of those participants, approximately 80 enrolled participants discontinued dupilumab due to the following reasons: a) no response to treatment, b) partial response to treatment, or c) loss of response to treatment. Additionally, approximately 15 enrolled participants discontinued dupilumab due to intolerance or adverse events (AEs). Finally, approximately 25 enrolled participants discontinued dupilumab for other reasons (e.g., cost, insurance coverage, drug access, prior trial participation). Approximately 10% (n=12) of the participants were adolescents (12 to under 18 years of age, weighing at least 40 kg).

[0159] The objectives and endpoints of this study are listed in Table 4. Statistical analysis was performed on the endpoints.

[0160] Table 4. Objectives and End Points

[0161]

[0162] Patient population

[0163] Inclusion Criteria: Participants were eligible for inclusion in the study only if they met all of the following criteria:

[0164] 1. Participants must be ≥12 years of age (inclusive) when signing the informed consent / approval form. Adolescents (12 to 18 years of age) must have a baseline weight of ≥40 kg.

[0165] 2. All participants must have previously received excessive pilimumab treatment / administration and meet one of the following conditions:

[0166] a. Participants who discontinued dupilumab due to no response, partial response, or loss of efficacy must have previously been treated with dupilumab (at the labeled dose level) for at least 4 months.

[0167] b. Participants who discontinued dupilumab due to drug intolerance or AEs were allowed to participate in the study without a pre-defined duration of dupilumab treatment.

[0168] c. Participants who discontinued dupilumab for other reasons, such as cost or lack of access to dupilumab (e.g., insurance coverage), may participate in the study without a prior dupilumab treatment duration requirement.

[0169] 3. Participants with chronic AD (according to the American Academy of Dermatology consensus criteria; Eichenfield et al. 2014) who had chronic AD for ≥1 year before the screening visit.

[0170] 4. EASI ≥16 at baseline visit.

[0171] 5. IGA score ≥3 (0 to 4 scale) at baseline visit.

[0172] 6. AD affected body surface area (BSA) ≥10% at baseline visit.

[0173] 7. There is a history of inadequate response to topical medications; or it is determined that topical treatment is otherwise medically not recommended.

[0174] 8. Female participants of childbearing potential must agree to abstain from sex or use highly effective contraception during treatment and for at least 18 weeks after the last dose of study drug. Male participants are not required to use any contraceptive measures unless specific study requirements are met by local governments.

[0175] 9. Adult participants must provide signed informed consent. For adolescent participants: Parents or legal guardians must be able to read, understand, and provide written informed consent for their child to participate in this research.

[0176] Exclusion criteria: Participants were excluded from the study if they met any of the following criteria:

[0177] 1. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening.

[0178] 2. Active or chronic infection with hepatitis B virus (HBV) at the time of screening.

[0179] 3. Current hepatitis C virus (HCV) infection at the time of screening.

[0180] 4. Have uncontrolled chronic illness, as defined by the investigator, that may require multiple intermittent doses of oral corticosteroids at screening.

[0181] 5. Suffering from uncontrolled asthma

[0182] a. may require large doses of oral or systemic corticosteroids, or

[0183] b. Due to ≥1 exacerbation in the 12 months prior to baseline, the following actions are required:

[0184] • Systemic (oral and / or parenteral) corticosteroid therapy, or

[0185] • Hospitalization for >24 hours.

[0186] 6. Known cirrhosis and / or chronic hepatitis of any etiology.

[0187] 7. History of malignant tumor (including mycosis fungoides or cutaneous T-cell lymphoma) within 5 years prior to screening, except for completely cured cervical carcinoma in situ with no signs of recurrence in the past 12 weeks, and completely cured and regressed non-metastatic cutaneous squamous or basal cell carcinoma.

[0188] 8. Have been diagnosed with an active internal parasitic infection or are at high risk for these infections.

[0189] 9. History of known or suspected immunosuppression, including a history of invasive opportunistic infections (e.g., tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis carinii, and aspergillosis), even if the infection has resolved; or unusually frequent, recurrent, or prolonged infections, as determined by the investigator.

[0190] 10. Presence of skin comorbidities that may interfere with study assessments.

[0191] 11. Suffering from serious concomitant diseases that, according to the investigator's judgment, will adversely affect the participant's participation in the study.

[0192] 12. Any other medical or mental illness that the investigator believes may suggest a new and / or under-understood disease, may impose unreasonable risks on study participants due to participation in this clinical trial, may make the participant's participation unreliable, or may interfere with study assessments.

[0193] 13. Any of the following types of infections within 3 months after screening or any of these infections during the screening period:

[0194] a. severe (requiring hospitalization and / or treatment with intravenous or equivalent oral antibiotics);

[0195] b. Opportunistic (as defined in Winthrop et al. 2015);

[0196] c. Chronic (symptoms, signs, and / or treatment persist for 6 weeks or longer);

[0197] d. Recurrent (including but not limited to recurrent cellulitis and chronic osteomyelitis).

[0198] 14. Active or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to the baseline visit (baseline), or superficial skin infection within 1 week prior to the baseline visit.

[0199] 15. Dupilumab treatment within 4 weeks before baseline visit.

[0200] 16. Previously treated with tralokinumab.

[0201] 17. Treatment with topical agents (corticosteroids, calcineurin inhibitors, JAK inhibitors, or phosphodiesterase-4 inhibitors) within 2 weeks prior to the baseline visit.

[0202] 18. Treatment with any of the following medications within 4 weeks prior to the baseline visit:

[0203] 19. Systemic immunosuppressive / immunomodulatory drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate mofetil, IFN-γ, azathioprine, methotrexate, and other immunosuppressants);

[0204] 20. Small molecules (e.g., JAK inhibitors);

[0205] 21. Phototherapy and photochemotherapy for AD.

[0206] 22. Regular use of a tanning room / tanning studio (more than 2 visits per week) within 4 weeks of the Screening Visit (Visit 1).

[0207] 23. Currently receiving cumulative doses of allergen immunotherapy (allergy shots).

[0208] 24. Treatment with B-cell depleting biologics (including rituximab) within 6 months prior to baseline visit.

[0209] 25. Use of prescription moisturizer within 7 days of baseline visit.

[0210] 26. Received BCG vaccination or treatment within 4 weeks before the baseline visit, or intends to receive BCG vaccination or treatment during the study.

[0211] 27. Received any live attenuated vaccine within 4 weeks after the baseline visit, or intends to receive a live attenuated vaccine during the study or within 4 weeks after the last dose of the study intervention.

[0212] 28. NOTE: The following vaccines are not considered live vaccines: RNA vaccines, vaccines containing inactive viral components, and / or non-replicating viral vector vaccines.

[0213] 29. Use cannabis or cannabinoids to treat pruritus, pain, and / or AD.

[0214] 30. Laboratory results on chemistry or hematology tests obtained at the screening visit that are, in the opinion of the investigator, clinically significant.

[0215] 31. Currently participating in any other clinical study involving an investigational product or any other type of medical research that is determined to be scientifically or medically incompatible with this study.

[0216] 32. Treatment with investigational drug within 8 weeks or 5 half-lives (if known), whichever is longer, prior to the baseline visit.

[0217] 33. Received a dose of nerolizumab in any previous clinical study of nerolizumab.

[0218] Study Drug:

[0219] The pharmaceutical composition containing 2 mL of 125 mg / mL nerolizumab or placebo was provided in a sterile pre-filled syringe with a needle safety device (PFS-NSD) for subcutaneous administration to patients. The nerolizumab sequence is provided in Table 1. The placebo solution had the same appearance and volume as the active solution, except that it did not contain nerolizumab.

Claims

1. A method for treating moderate to severe atopic dermatitis, the method comprising: Select patients with moderate to severe atopic dermatitis who were previously treated with dupilumab and discontinued dupilumab due to nonresponse, partial response, or loss of response, and administering to the patient an antibody that binds to human IL-13, The antibody that binds to human IL-13 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: a HCDR1 comprising SEQ ID NO: 1, a HCDR2 comprising SEQ ID NO: 2, and a HCDR3 comprising SEQ ID NO: 3, and the VL comprises: a LCDR1 comprising SEQ ID NO: 4, a LCDR2 comprising SEQ ID NO: 5, and a LCDR3 comprising SEQ ID NO:

6.

2. A method for treating moderate to severe atopic dermatitis, the method comprising: Select patients with moderate to severe atopic dermatitis who were previously treated with dupilumab and discontinued dupilumab due to intolerance or adverse events, and administering to the patient an antibody that binds to human IL-13, The antibody that binds to human IL-13 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: a HCDR1 comprising SEQ ID NO: 1, a HCDR2 comprising SEQ ID NO: 2, and a HCDR3 comprising SEQ ID NO: 3, and the VL comprises: a LCDR1 comprising SEQ ID NO: 4, a LCDR2 comprising SEQ ID NO: 5, and a LCDR3 comprising SEQ ID NO:

6.

3. The method of claim 1 or 2, wherein the patient has suffered from moderate to severe atopic dermatitis for at least one year.

4. The method of any one of claims 1-3, wherein the moderate to severe atopic dermatitis is determined by the American Academy of Dermatology consensus criteria.

5. The method of any one of claims 1 to 4, wherein the patient has an Eczema Area and Severity Index (EASI) score of 16 or greater, an Investigator's Global Assessment (IGA) score of 3 or greater, and more than 10% of body surface area (BSA) affected by atopic dermatitis prior to administration of the antibody that binds to human IL-13.

6. The method of any one of claims 1-5, wherein the patient has an inadequate response to topical corticosteroids.

7. The method of any one of claims 1-6, wherein the patient is 12 years of age or older.

8. A method for treating moderate to severe atopic dermatitis, the method comprising: Select a patient who: i. 12 years of age or above; ii. Chronic atopic dermatitis for more than one year according to the American Academy of Dermatology consensus criteria; iii. Have an EASI score of 16 or higher; iv. Have an IGA score of 3 or higher; v. More than 10% of body surface area affected by atopic dermatitis; vi. Inadequate response to topical corticosteroids; and vii. previously administered dupilumab, in which case the patient discontinued dupilumab due to (1) no response, partial response, or loss of response or (2) intolerance or adverse events, and administering to the patient an antibody that binds to human IL-13, The antibody that binds to human IL-13 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: a HCDR1 comprising SEQ ID NO: 1, a HCDR2 comprising SEQ ID NO: 2, and a HCDR3 comprising SEQ ID NO: 3, and the VL comprises: a LCDR1 comprising SEQ ID NO: 4, a LCDR2 comprising SEQ ID NO: 5, and a LCDR3 comprising SEQ ID NO:

6.

9. The method of claim 8, wherein the patient discontinues dupilumab due to non-response, partial response, or loss of response.

10. The method of claim 8, wherein the patient discontinues dupilumab due to intolerance or adverse events.

11. The method of any one of claims 1 and 3-9, wherein the patient discontinues dupilumab due to non-response.

12. The method of claim 11, wherein the patient's skin and / or pruritus do not improve at all or improve by less than 25% of the peak response to dupilumab.

13. The method of any one of claims 1 and 3-9, wherein the patient discontinues dupilumab due to a partial response.

14. The method of claim 13, wherein the patient's skin and / or pruritus improves by only 25% to 50% of the peak response to dupilumab.

15. The method of any one of claims 1 and 3-9, wherein the patient discontinues dupilumab due to loss of response.

16. The method of claim 15, wherein the patient's skin and / or pruritus initially improves but then worsens after treatment with dupilumab.

17. The method of any one of claims 1-16, wherein the patient discontinues dupilumab for at least four weeks.

18. The method of any one of claims 1-16, wherein the patient discontinues dupilumab for at least eight weeks.

19. The method of any one of claims 1-18, wherein the antibody that binds to human IL-13 comprises a VH comprising SEQ ID NO: 7 and a VL comprising SEQ ID NO:

8.

20. The method of any one of claims 1-19, wherein the antibody that binds to human IL-13 comprises a heavy chain comprising SEQ ID NO: 9 and a light chain comprising SEQ ID NO:

10.

21. The method of any one of claims 1-20, wherein the antibody that binds to human IL-13 is nerolizumab.

22. The method of any one of claims 1-21, wherein the antibody that binds human IL-13 is administered to the patient subcutaneously.

23. The method of any one of claims 1-22, wherein the antibody that binds to human IL-13 is administered to the patient subcutaneously at 250 mg or 500 mg.

24. The method of any one of claims 1-23, wherein the antibody that binds human IL-13 is administered to the patient subcutaneously once every two weeks.

25. The method of any one of claims 1-24, wherein the patient is treated with the antibody that binds human IL-13 for a treatment period of 16-24 weeks.

26. The method of any one of claims 1-25, wherein the patient is treated with the antibody that binds human IL-13 for a treatment period of 16 weeks.

27. The method of any one of claims 1-25, wherein the patient is treated with the antibody that binds human IL-13 for a treatment period of 24 weeks.

28. The method of any one of claims 1-27, wherein the patient is administered with the antibody that binds to human IL-13 at a loading dose of 500 mg at weeks 0 and 2, and with subsequent doses of 250 mg every two weeks for the remainder of the treatment period.

29. The method of any one of claims 1-28, further comprising determining the patient's EASI score after the treatment period.

30. The method of claim 29, wherein the EASI score determined after the treatment period is reduced by 75% or more compared to the EASI score determined before administration of the first loading dose of the antibody that binds to human IL-13.

31. The method of claim 29, wherein the EASI score determined after the treatment period is reduced by 90% or more compared to the EASI score determined before administration of the first loading dose of the antibody that binds to human IL-13.

32. The method of any one of claims 1-31, further comprising determining the patient's IGA score after the treatment period.

33. The method of claim 32, wherein the IGA score determined after the treatment period is 0 or 1, and the IGA score determined after the treatment period is reduced by 2 points or more compared to the IGA score determined before administration of the first loading dose of the antibody.

34. The method of any one of claims 1-33, further comprising determining the patient's Itch Numeric Rating Scale (NRS) score after the treatment period.

35. The method of claim 34, wherein the itch NRS score determined after the treatment period is reduced by 4 points or more compared to the itch NRS score determined before administration of the first loading dose of the antibody that binds to human IL-13.

36. The method of any one of claims 1-35, further comprising determining one or more of the following characteristics of the patient after the treatment period: i. Sleep Loss Scale; ii. Skin pain NRS score; iii. Severity Score of Atopic Dermatitis (SCORAD); iv. Dermatology Life Quality Index (DLQI) or Children's Dermatology Life Quality Index (CDLQI) score; v. Facial Investigator Global Assessment (F-IGA); vi. Modified Total Lesion Symptom Scale; vii. Atopic Dermatitis Control Tool (ADCT); viii. Participant-reported satisfaction issues; ix. Fitzpatrick Skin Phototype Assessment Scale; x. Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis (WPAI-AD); xi. Patient-Oriented Eczema Measure (POEM); xii. European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L); xiii. PROMIS (Patient-Reported Outcomes Measurement Information System) Anxiety and Depression Scale.

37. The method of any one of claims 25-36, wherein the patient is further treated in a maintenance period of up to 36 weeks.

38. The method of claim 37, wherein the patient is treated with the antibody that binds to human IL-13 at a maintenance dose of 250 mg once every two weeks during the maintenance period.

39. The method of claim 37, wherein the patient is treated with the antibody that binds to human IL-13 at a maintenance dose of 250 mg once every four weeks during the maintenance period.

40. The method of claim 37, wherein the patient is treated with the antibody that binds to human IL-13 at a maintenance dose of 250 mg once every eight weeks during the maintenance period.

41. The method of any one of claims 1-40, wherein the antibody that binds human IL-13 is administered to the patient using a subcutaneous administration device.

42. The method of claim 41, wherein the subcutaneous administration device is selected from a prefilled syringe, a disposable pen injection device, a microneedle device, a microinfusion device, a needle-free injection device, or an autoinjector device.

43. The method of any one of claims 1-42, wherein the method further comprises administering one or more topical corticosteroids to the patient.

44. The method of claim 43, wherein the one or more topical corticosteroids is triamcinolone acetonide, hydrocortisone, or a combination of triamcinolone acetonide and hydrocortisone.

45. The method of claim 43 or 44, wherein the one or more topical corticosteroids are administered concurrently with the antibody that binds human IL-13.

46. ​​An antibody that binds to human IL-13 for treating moderate to severe atopic dermatitis in a patient who was previously treated with dupilumab and discontinued dupilumab due to no response, partial response, or loss of response, wherein the antibody that binds to human IL-13 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: a HCDR1 comprising SEQ ID NO: 1, a HCDR2 comprising SEQ ID NO: 2, and a HCDR3 comprising SEQ ID NO: 3, and the VL comprises: a LCDR1 comprising SEQ ID NO: 4, a LCDR2 comprising SEQ ID NO: 5, and a LCDR3 comprising SEQ ID NO:

6.

47. An antibody that binds to human IL-13 for treating moderate to severe atopic dermatitis in a patient who was previously treated with dupilumab and discontinued dupilumab due to intolerance or adverse events, wherein the antibody that binds to human IL-13 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: a HCDR1 comprising SEQ ID NO: 1, a HCDR2 comprising SEQ ID NO: 2, and a HCDR3 comprising SEQ ID NO: 3, and the VL comprises: a LCDR1 comprising SEQ ID NO: 4, a LCDR2 comprising SEQ ID NO: 5, and a LCDR3 comprising SEQ ID NO:

6.

48. The antibody for use according to claim 46 or 47, wherein the patient: i. 12 years of age or above; ii. Chronic atopic dermatitis for more than one year according to the American Academy of Dermatology consensus criteria; iii. Have an EASI score of 16 or higher; iv. Have an IGA score of 3 or higher; v. More than 10% of the BSA is affected by atopic dermatitis; and vi. Inadequate response to topical corticosteroids.

49. The antibody for use according to any one of claims 46 to 48, wherein the antibody that binds to human IL-13 is for administration in separate, simultaneous or sequential combination with one or more topical corticosteroids.

50. Use of an antibody that binds to human IL-13 for the preparation of a medicament for treating moderate to severe atopic dermatitis in a patient who was previously administered dupilumab and discontinued dupilumab due to no response, partial response, or loss of response, wherein the antibody that binds to human IL-13 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: a HCDR1 comprising SEQ ID NO: 1, a HCDR2 comprising SEQ ID NO: 2, and a HCDR3 comprising SEQ ID NO: 3, and the VL comprises: a LCDR1 comprising SEQ ID NO: 4, a LCDR2 comprising SEQ ID NO: 5, and a LCDR3 comprising SEQ ID NO:

6.

51. Use of an antibody that binds to human IL-13 for the preparation of a medicament for treating moderate to severe atopic dermatitis in a patient who was previously treated with dupilumab and discontinued dupilumab due to intolerance or an adverse event, wherein the antibody that binds to human IL-13 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: a HCDR1 comprising SEQ ID NO: 1, a HCDR2 comprising SEQ ID NO: 2, and a HCDR3 comprising SEQ ID NO: 3, and the VL comprises: a LCDR1 comprising SEQ ID NO: 4, a LCDR2 comprising SEQ ID NO: 5, and a LCDR3 comprising SEQ ID NO:

6.

52. The use according to claim 50 or 51, wherein the patient: i. 12 years of age or above; ii. Chronic atopic dermatitis for more than one year according to the American Academy of Dermatology consensus criteria; iii. Have an EASI score of 16 or higher; iv. Have an IGA score of 3 or higher; v. More than 10% of the BSA is affected by atopic dermatitis; and vi. Inadequate response to topical corticosteroids.

53. The use of any one of claims 50-52, wherein the antibody that binds to human IL-13 is for separate, simultaneous or sequential administration in combination with one or more topical corticosteroids.

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