IL-13 antibodies for the treatment of atopic dermatitis

Abstract

Provided herein are methods, uses, and pharmaceutical compositions of antibodies that bind human IL-13 ("anti-IL-13 antibodies") for treating atopic dermatitis, for example, in patients previously treated with dupilumab.

Description

[Technical Field]

[0001] (Sequence Listing) This application has been submitted with a Sequence Listing in ST.26 XML format. The Sequence Listing is provided as a file titled "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.

[0002] FIELD OF THE INVENTION The present invention relates to methods, uses, and pharmaceutical compositions of antibodies that bind human IL-13 ("anti-IL-13 antibodies") for treating atopic dermatitis, for example, in patients previously treated with dupilumab. [Background technology]

[0003] Atopic dermatitis (AD) is a chronic, heterogeneous inflammatory skin disorder caused by skin barrier dysfunction and dysregulated immune responses. Clinically, AD is characterized by dry skin, erythematous crusted rash, lichenification, skin barrier disorders, and intense pruritus (Bieber T., N Engl J Med 2008;358:1483-94). Patients with AD have a high disease burden, and their quality of life is significantly affected. One study showed that AD has a greater negative impact on patients' mental health 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 prevalence of social dysfunction and sleep disorders, which is directly related to the severity of the disease (Williams H, et al., J Allergy Clin Immunol 2008;121:947-54.e15). 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).

[0004] Interleukin (IL)-13 is a key mediator of T-helper type 2 (Th2) inflammation and signals through the heterodimeric receptor IL-4Rα / IL-13Rα1. A summary of several lines of evidence suggests that IL-13 is a major pathogenic component in AD. Increased expression of IL-13 has been consistently 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] ; Suarez-Farinas 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 (La Grutta S, et al., Allergy 60:391-5

[2005] ). Increased IL-13 has also been reported in the serum of AD patients (Novak N, et al., J Invest Dermatol 2002;119:870-5; WO 2016149276), 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).

[0005] Due to the heterogeneous nature of the disease, patients have diverse treatment needs. Treatment approaches for AD include trigger avoidance, moisturizing the skin through bathing, and the use of anti-inflammatory therapies such as emollients and topical corticosteroids (TCS). In many patients, treatment with TCS provides some symptomatic relief but does not adequately control the patient's disease. In addition, TCS use is associated with many comorbidities and limitations, including a high patient burden. Long-term application of TCS is not recommended due to the risk of skin atrophy, pigmentation disorders, and acneiform rash, as well as risks associated with systemic absorption (e.g., hypothalamic-pituitary axis effects, Cushing's disease).

[0006] For patients with persistent, moderate-to-severe AD who do not adequately respond to TCS, several step-up treatment options are available (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). Step-up options include topical calcineurin inhibitors (TCIs), phototherapy, and immunosuppressants such as oral corticosteroids, cyclosporine, azathioprine, methotrexate, and mycophenolate. Immunosuppressants such as cyclosporine A affect both humoral and cellular immune responses, potentially leading to increased susceptibility to infection and decreased cancer immunosurveillance.

[0007] Dupilumab, a monoclonal antibody that inhibits IL-4 and IL-13 signaling, has been approved for the treatment of patients with moderate to severe AD. Dupilumab was the first biologic available for patients with chronic, moderate to severe AD for whom topical treatments provided insufficient control or were medically inadvisable. Some patients treated with dupilumab may have a limited or partial response to treatment, or even no response at all. Other patients may show an initial response to treatment but lose response over time. Still other patients have been found to be intolerant to or have adverse effects on dupilumab. Furthermore, in actual clinical practice, other patients discontinue treatment due to issues such as cost or loss of access to the drug (e.g., insurance). In summary, a significant number of patients do not continue dupilumab treatment over 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).

[0008] There remains an unmet medical need for safer and more effective therapies and treatment regimens for moderate to severe AD, especially for patients previously treated with dupilumab. Summary of the Invention

[0009] Provided herein are methods, uses, and pharmaceutical compositions of anti-IL-13 antibodies for treating atopic dermatitis. In some embodiments, provided herein are methods and uses of anti-IL-13 antibodies for treating atopic dermatitis, e.g., in patients previously treated with dupilumab.

[0010] In one aspect, provided herein is a method of treating moderate to severe atopic dermatitis in a patient in need thereof who has previously been administered dupilumab, comprising administering to the patient an antibody that binds human IL-13. In some embodiments, provided herein is a method 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 discontinued dupilumab due to no response, partial response, or loss of response. In some embodiments, the patient discontinued dupilumab due to intolerance or an adverse event. In some embodiments, the patient discontinued dupilumab for other reasons.

[0011] In some embodiments, provided herein are methods for treating moderate to severe atopic dermatitis, the method comprising: selecting a patient with moderate to severe atopic dermatitis who has previously been administered dupilumab and who has discontinued dupilumab due to non-response, partial response, or loss of response; and administering to the patient an antibody that binds human IL-13.

[0012] In some embodiments, provided herein are methods for treating moderate to severe atopic dermatitis, the method comprising: selecting a patient with moderate to severe atopic dermatitis who has previously been administered dupilumab and who has discontinued dupilumab due to intolerance or an adverse event; and administering to the patient a pharmaceutical composition comprising an antibody that binds to human IL-13.

[0013] 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 Common Criteria. In some embodiments, the patient has an Eczema Area and Severity Index (EASI) score of 16 or greater, an Investigator Global Assessment (IGA) score of 3 or greater, and more than 10% of the body surface area (BSA) affected by atopic dermatitis prior to administration of the antibody. In some embodiments, the patient has had an inadequate response to topical corticosteroids. In some embodiments, the patient is 12 years of age or older.

[0014] Also provided herein is a method for treating moderate to severe atopic dermatitis, comprising selecting a patient who: (i) is 12 years of age or older; (ii) has chronic atopic dermatitis for more than one year according to the American Academy of Dermatology Common Criteria; (iii) has an EASI score of 16 or greater; (iv) has an IGA score of 3 or greater; (v) has more than 10% of the body surface area affected by atopic dermatitis; (vi) has had an inadequate response to topical corticosteroids; or (vii) has previously received dupilumab, and the patient discontinued dupilumab due to: (1) non-response, partial response, or loss of response; or (2) intolerance or an adverse event; and administering to the patient an antibody that binds human IL-13.

[0015] In another aspect, provided herein is an antibody that binds human IL-13 for use in treating moderate to severe atopic dermatitis in patients previously administered dupilumab. In some embodiments, provided herein is an antibody that binds human IL-13 for use in treating moderate to severe atopic dermatitis in patients previously administered dupilumab and who discontinued dupilumab due to non-response, partial response, or loss of response. In some embodiments, provided herein is an antibody that binds human IL-13 for use in treating moderate to severe atopic dermatitis in patients previously administered dupilumab and who discontinued dupilumab due to intolerance or adverse events. In some embodiments, patients (1) are 12 years of age or older, (2) have chronic atopic dermatitis for more than one year according to the American Academy of Dermatology Common Criteria, (3) have an EASI score of 16 or greater, (4) have an IGA score of 3 or greater, (5) have more than 10% of their BSA affected by atopic dermatitis, or (6) have had an inadequate response to topical corticosteroids.

[0016] In another aspect, provided herein is the use of an antibody that binds human IL-13 in the manufacture of a medicament for the treatment of moderate to severe atopic dermatitis in patients previously administered dupilumab. Also provided herein is the use of an antibody that binds human IL-13 in the manufacture of a medicament for the treatment of moderate to severe atopic dermatitis in patients previously administered dupilumab and who have discontinued dupilumab due to non-response, partial response, or loss of response. Also provided herein is the use of an antibody that binds human IL-13 in the manufacture of a medicament for the treatment of moderate to severe atopic dermatitis in patients previously administered dupilumab and who have discontinued dupilumab due to intolerance or adverse events. In some embodiments, patients (1) are 12 years of age or older, (2) have chronic atopic dermatitis for more than one year according to the American Academy of Dermatology Common Criteria, (3) have an EASI score of 16 or greater, (4) have an IGA score of 3 or greater, (5) have more than 10% of their BSA affected by atopic dermatitis, or (6) have had an inadequate response to topical corticosteroids.

[0017] In some embodiments, the patient discontinued dupilumab due to non-response, partial response, or loss of response. In some embodiments, the patient discontinued dupilumab due to intolerance or an adverse event. In some embodiments, the patient discontinued dupilumab due to non-response. In some embodiments, the patient discontinued dupilumab due to partial response. In some embodiments, the patient discontinued dupilumab due to loss of response. In some embodiments, the patient discontinued dupilumab for at least 4 weeks. In some embodiments, the patient discontinued dupilumab for at least 8 weeks.

[0018] In some embodiments, the antibody binds to human IL-13 with high affinity and blocks signaling through the active IL-4Ralpha / IL-13Ralpha1 heterodimer. 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 an HCDR1 comprising SEQ ID NO: 1, an HCDR2 comprising SEQ ID NO: 2, and an HCDR3 comprising SEQ ID NO: 3, and the VL comprises an LCDR1 comprising SEQ ID NO: 4, an LCDR2 comprising SEQ ID NO: 5, and an 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 to human IL-13 is lebrikizumab.

[0019] In some embodiments, the antibody that binds human IL-13 is administered subcutaneously to the patient. In some embodiments, the antibody that binds human IL-13 is administered subcutaneously to the patient at 250 mg or 500 mg. In some embodiments, the antibody that binds human IL-13 is administered subcutaneously to the patient once every two weeks.

[0020] In some embodiments, patients are treated with an antibody that binds human IL-13 for a treatment period of about 16 to 24 weeks. In some embodiments, patients are treated with an antibody that binds human IL-13 for a treatment period of about 16 weeks. In some embodiments, patients are treated with an antibody that binds human IL-13 for a treatment period of about 24 weeks. In some embodiments, patients are treated with a loading dose of 500 mg of an antibody that binds human IL-13 at weeks 0 and 2, and subsequent doses of 250 mg of an antibody that binds human IL-13 every two weeks for the remainder of the treatment period.

[0021] In some embodiments, the patient is further treated for a maintenance period, e.g., 36 weeks. In some embodiments, the patient is treated with a maintenance dose of 250 mg of an antibody that binds human IL-13 once 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 human IL-13 once 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 human IL-13 once every eight weeks during the maintenance period.

[0022] 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), Facial Investigator's Global Assessment (F-IGA), Pruritus Numerical Rating Scale (NRS) score, Modified Lesion Symptom Scale, Sleep Deprivation Scale, Skin Pain NRS score, Severity Assessment of Atopic Dermatitis (SCORAD), Dermatology Life Quality Index (DLQI) or Pediatric Dermatology Life Quality Index (CDLQI) score, Atopic Dermatitis Control Status Questionnaire (ADCT), Participant Reported Satisfaction Questionnaire, Fitzpatrick Photometric Skin Rating Scale, Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis (WPAI-AD), Patient-Oriented Eczema Measure (POEM), European Quality of Life-Five Dimensions-Five Levels (EQ-5D-5L), and PROMIS (Patient-Reported Outcomes Measurement Information System) Anxiety and Depression scales.

[0023] In some embodiments, the methods, uses, and pharmaceutical compositions described herein further comprise administering one or more topical corticosteroids to a patient. Accordingly, also provided herein are antibodies that bind to human IL-13 for separate, simultaneous, or sequential administration 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 simultaneously with the antibody. [Brief explanation of the drawings]

[0024] [Figure 1] FIG. 1 is a schematic diagram of the study design described in Example 1. [Figure 2] FIG. 1 is a schematic diagram of the study design described in Example 2 (n=number, Q2W=every 2 weeks, SC=subcutaneous, W=week. The screening period is 30 days. A loading dose of 500 mg lebrikizumab will be administered SC at baseline (week 0) and week 2. A safety follow-up visit will occur at week 34, or approximately 12 weeks after the last study intervention injection. DETAILED DESCRIPTION OF THE INVENTION

[0025] Provided herein are methods, uses, and pharmaceutical compositions of anti-IL-13 antibodies for treating atopic dermatitis. In some embodiments, provided herein are methods and uses of anti-IL-13 antibodies for treating atopic dermatitis, e.g., in patients previously treated with dupilumab.

[0026] In one aspect, provided herein is a method of treating moderate to severe atopic dermatitis in a patient in need thereof who has previously received dupilumab, comprising administering to the patient an antibody that binds human IL-13. In some embodiments, provided herein is a method for treating moderate to severe atopic dermatitis, comprising selecting a patient who has previously received dupilumab and administering to the patient an antibody that binds 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 an adverse event. In some embodiments, the patient discontinued dupilumab for other reasons. In some embodiments, the patient discontinued dupilumab for at least 4 weeks. In some embodiments, the patient discontinued dupilumab for at least 8 weeks.

[0027] 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 administered dupilumab and who has discontinued dupilumab due to non-response, partial response, or loss of response, and administering to the patient an antibody that binds human IL-13. In some embodiments, the patient has discontinued dupilumab for at least 4 weeks. In some embodiments, the patient has discontinued dupilumab for at least 8 weeks.

[0028] 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 administered dupilumab and who has discontinued dupilumab due to intolerance or an adverse event, and administering to the patient a pharmaceutical composition comprising an antibody that binds human IL-13. In some embodiments, the patient has discontinued dupilumab for at least 4 weeks. In some embodiments, the patient has discontinued dupilumab for at least 8 weeks.

[0029] 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 Common Criteria. In some embodiments, the patient has an Eczema Area and Severity Index (EASI) score of 16 or greater, an Investigator Global Assessment (IGA) score of 3 or greater, and more than 10% of the body surface area (BSA) affected by atopic dermatitis prior to administration of the antibody. In some embodiments, the patient has had an inadequate response to topical corticosteroids. In some embodiments, the patient is 12 years of age or older.

[0030] 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 chronic atopic dermatitis for more than one year according to the American Academy of Dermatology Common Criteria; (iii) has an EASI score of 16 or greater; (iv) has an IGA score of 3 or greater; (v) has more than 10% of the body surface area affected by atopic dermatitis; (vi) has had an inadequate response to topical corticosteroids; or (vii) has previously received dupilumab, and the patient discontinued dupilumab due to: (1) non-response, partial response, or loss of response; or (2) intolerance or adverse events; and administering to the patient an antibody that binds human IL-13. In some embodiments, the patient discontinued dupilumab due to non-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 non-response or partial response. In some embodiments, the patient discontinued dupilumab due to loss of response. In some embodiments, the patient discontinued dupilumab for at least 4 weeks. In some embodiments, the patient discontinued dupilumab for at least 8 weeks.

[0031] In some embodiments, moderate to severe atopic dermatitis can be determined by the American Academy of Dermatology Criteria for the Diagnosis and Assessment of Atopic Dermatitis (Eichenfield et al., J Am Acad Dermatol. 2014;70(2):338-351). Essential features that must be present for a diagnosis of AD include pruritus and a history of acute, subacute, or chronic eczema with a typical morphology and age-specific pattern, or a chronic or recurrent illness. Age-specific patterns include: involvement of the face, neck, and extensor muscles in infants and children, current or previous flexor involvement in any age group, and sparing of the groin and axillary areas. Key features are present in most cases and support a diagnosis of AD, including early age at onset, atopy (personal and / or family history, and / or IgE reactivity), and dryness. Clinical correlates that help suggest a diagnosis of AD but are too nonspecific to be used to define or detect it for research and epidemiological studies include atypical vascular responses such as facial pallor, white dermatographia, and delayed pallor, other local findings such as keratosis pilaris or pityriasis alba or hyperlinear palms or ichthyosis, ocular or periorbital changes, perioral changes or periauricular lesions, and perifollicular accentuation or lichenification or prurigo lesions. The diagnosis of AD also depends on excluding conditions such as scabies, seborrheic dermatitis, contact dermatitis (irritant or allergic), ichthyosis, cutaneous T-cell lymphoma, psoriasis, photosensitive dermatosis, immunodeficiency disorders, or erythroderma of other causes.

[0032] The severity of atopic dermatitis is determined by the "Hanifin and Rajka criteria" described in the diagnostic criteria of Hanifin and Rajka, Acta Derm Venereol (Stockh) 1980;Suppl 92:44-7, or by Rajka G and Langeland T, Acta Derm Venereol (Stockh) 1989;144(Suppl):13-4.

[0033] Antibodies suitable for use in, and in the methods provided herein, have been previously described, for example, in WO2005062967. In some embodiments, the antibody binds human IL-13 with high affinity and blocks signaling through the active IL-4Ralpha / IL-13Ralpha1 heterodimer. In some embodiments, the antibody that binds human IL-13 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an HCDR1 comprising SEQ ID NO: 1, an HCDR2 comprising SEQ ID NO: 2, and an HCDR3 comprising SEQ ID NO: 3, and the VL comprises an LCDR1 comprising SEQ ID NO: 4, an LCDR2 comprising SEQ ID NO: 5, and an LCDR3 comprising SEQ ID NO: 6. In some embodiments, the antibody that binds 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 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. The amino acid sequence of lebrikizumab is provided in Table 1. C-terminal clipping of an IgG antibody can occur when one or two 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 clipped from the heavy chain. A penultimate glycine can similarly be truncated or clipped from the heavy chain. Modification of the N-terminal amino acid of an 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 lebrikizumab heavy chain.

[0034] [Table 1]

[0035] An anti-IL-13 antibody, such as lebrikizumab, 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, such as lebrikizumab, can be formulated in a pharmaceutical composition such as that described in WO 2013 / 066866. The pharmaceutical composition can 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 anti-IL-13 antibody concentration in the pharmaceutical composition is 100 mg / mL to 150 mg / mL, e.g., 125 mg / mL. The pharmaceutical composition can also contain 5 mM to 40 mM histidine acetate buffer, pH 5.4 to 6.0. In some embodiments, the pharmaceutical composition further comprises a polyol (e.g., a sugar) having a concentration of 100 mM to 200 mM, and / or a surfactant (e.g., polysorbate 20) having a concentration of 0.01% to 0.1%. In one embodiment, the pharmaceutical composition comprises 125 mg / mL of an anti-IL-13 antibody (e.g., lebrikizumab), 20 mM histidine acetate buffer, pH 5.7, 175 mM sucrose, and 0.03% polysorbate 20.

[0036] In some embodiments, the anti-IL-13 antibody is administered subcutaneously to the patient. The anti-IL-13 antibody may be administered to the patient at a dosing frequency of about once per week, once per two weeks, once per three weeks, once per four weeks, once per five weeks, once per six weeks, or once per eight weeks. In some embodiments, the anti-IL-13 antibody is administered to the patient once per two weeks. In some embodiments, the anti-IL-13 antibody is administered to the patient once per four weeks. In some embodiments, the anti-IL-13 antibody is administered to the patient once per eight weeks.

[0037] In some embodiments, the anti-IL-13 antibody is administered to the patient using a subcutaneous administration device. The subcutaneous administration device may be selected from a pre-filled syringe, a disposable pen injection device, a microneedle device, a microinfuser device, a needle-free injection device, or an auto-injector device. A variety of subcutaneous administration devices, including auto-injector devices, are known in the art and are commercially available. Exemplary devices include, but are not limited to, pre-filled syringes (e.g., BD HYPAK SCF®, READYFILL™, and STERIFILL SCF™ from Becton Dickinson, CLEARSHOT™ copolymer pre-filled syringes from Baxter, and Daikyo Seiko CRYSTAL ZENITH® pre-filled syringes available from West Pharmaceutical Services), disposable pen injection devices such as the BD Pen from Becton Dickinson, ultra-sharp and microneedle devices (e.g., INJECT-EASE™ and microinjection devices from Becton Dickinson, and H-PATCH™ available from Valeritas), 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 auto-injector device described in WO 2008 / 112472, WO 2011 / 109205, WO 2014 / 062488, and / or WO 2016 / 089864.

[0038] In some embodiments, the patient is treated with an anti-IL-13 antibody for a treatment period of about 16 to about 24 weeks, e.g., 16, 18, 20, 22, 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 loading dose of 500 mg of anti-IL-13 antibody at weeks 0 and 2, and subsequent doses of 250 mg of anti-IL-13 antibody every two weeks for the remainder of the treatment period.

[0039] In some embodiments, the patient is further treated with an anti-IL-13 antibody for a maintenance period of, for example, 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 maintenance dose of 250 mg of anti-IL-13 antibody once every two weeks during the maintenance period. In some embodiments, the patient is treated with a maintenance dose of 250 mg of anti-IL-13 antibody once every four weeks during the maintenance period. In some embodiments, the patient is treated with a maintenance dose of 250 mg of anti-IL-13 antibody once every eight weeks during the maintenance period.

[0040] Before, during, and after the treatment and / or maintenance period, the patient may be assessed for one or more features of the Atopic Dermatitis Disease Severity Scale (ADDSM), which determines certain signs, symptoms, characteristics, or parameters associated with atopic dermatitis and which may be assessed quantitatively or qualitatively. Exemplary ADDSMs include, but are not limited to, the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Facial Investigator's Global Assessment (F-IGA), Pruritus Numerical Rating Scale (NRS) score, Modified Lesion Symptom Scale-Sleep Deprivation Scale, Skin Pain NRS score, Severity Assessment of Atopic Dermatitis (SCORAD), Dermatology Life Quality Index (DLQI) or Pediatric Dermatology Life Quality Index (CDLQI) score, Atopic Dermatitis Control Status Questionnaire (ADCT), Participant Reported Satisfaction Questionnaire, Fitzpatrick Photometric Skin Rating Scale, Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis (WPAI-AD), Patient-Oriented Eczema Measure (POEM), European Quality of Life-Five Dimensions-Five Levels (EQ-5D-5L), and PROMIS (Patient-Reported Outcomes Measurement Information System) anxiety and depression scales.

[0041] 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 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 establish whether there has been an improvement (e.g., a decrease) in ADDSM.

[0042] The "Eczema Area and Severity Index," or "EASI," is an investigator-reported 20-item scale that assesses two aspects of AD: the extent of disease in four body regions (head / neck, trunk, upper and lower extremities), and four clinical signs (erythema, edema / papulation, excoriation, and lichenification). Clinical signs are rated for severity on a scale of 0 (absent) to 3 (severe). Scores are summed for each of the four body regions. The percentage of BSA assigned to each body part is 10% for the head / neck, 20% for the upper extremities, 30% for the trunk, and 40% for the lower extremities, respectively. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned to each body region depending on the percentage of AD-affected skin in that area: 0 (none), 1 (1%-9%), 2 (10%-29%), 3 (30%-49%), 4 (50%-69%), 5 (70%-89%), or 6 (90%-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 a worse severity of AD (Hanifin et al., Exp Dermatol. 2001;10:11-18).

[0043] The "Investigator Global Assessment," or "IGA," is an investigator-reported single-item measure for assessing participants' AD severity (Simpson E, et al. J Am Acad Dermatol. 2020;83(3):839-846). The IGA consists of a 5-point scale ranging from 0 (no abnormalities) to 4 (severe), with scores selected using descriptors that best describe the overall appearance of the lesions at a given time point (see Table 2).

[0044] Table 2. Investigator's overall assessment [Table 2]

[0045] Body surface area (BSA) is an investigator-reported assessment that estimates the participant's extent of AD disease or skin involvement. BSA is expressed as a percentage of total body surface and reported by body location. BSA is determined by the investigator using the rule that the palm of the participant's hand is approximately 1% BSA. The recall period for this assessment is current.

[0046] The Facial Investigator Global Assessment (F-IGA) is an investigator-administered single-item scale that assesses the severity of a participant's AD on the face. The IGA consists of a 5-point scale ranging from 0 (no abnormalities) to 4 (severe), and scores are selected using descriptors that best describe the overall appearance of facial lesions at a given time point.

[0047] The "Severity Assessment of Atopic Dermatitis," or "SCORAD" index, is an investigator- and participant-reported, nine-item assessment in both adult and adolescent participants that assesses three aspects: 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 (one item) is assessed by the investigator as a percentage of each defined body area and reported as the sum of all areas. The maximum score is 100%. The recall period for this scale is current. The severity of six specific symptoms of AD: erythema, edema / papulation, weeping / crusting, peeling, 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 present time. Subjective symptoms of pruritus and poor sleep (two items) are assessed by the participant via a 10-cm visual analog scale. Symptoms (itching and insomnia) are recorded by the participant or caregiver on the visual analog scale, with 0 being no symptoms and 10 being the worst symptoms imaginable, and the maximum possible score is 20. The recall period for this scale is over the last three days. The maximum possible SCORAD score calculated based on the above three aspects is 103. A higher score indicates a worse or more severe condition.

[0048] The Modified Lesion Symptom Scale is an investigator-reported scale that combines assessment of hand eczema (HE) lesion severity (erythema, edema, scaling, fissures, hyperkeratosis or lichen, and vesicles) with the intensity of pruritus or pain to assess symptom severity (Bissonnette et al., J Eur Acad Dermatol Venereol. 2010;24(s3):1-20). This composite score assigns a score of 0 (mild) to 3 (severe) for each component, giving a maximum disease severity of 21. The recall period for this assessment is current. It has been used as a secondary endpoint in studies investigating alitretinoin in HE (Ruzicka et al., Br J Dermatol. 2008;158(4):808-817; Fowler et al., J Drugs Dermatol. 2014;13(10):1198-204).

[0049] The Pruritus Numerical Rating Scale (NRS) is a participant-reported, single-item, daily, 11-point scale. The Pruritus NRS is used by participants to rate the severity of their worst itch over the past 24 hours, with 0 indicating "no itch" and 10 indicating "worst imaginable itch." Ratings are recorded daily by participants. The minimal clinically important change is 3 points. (Yosipovitch et al., Br J Dermatol. 2019;181(4):761-769) Participants record daily itch ratings at home using an electronic diary. The initial Pruritus NRS electronic diary entry should be completed at least 4 of the 7 days prior to baseline.

[0050] The Cutaneous Pain NRS is a participant-reported, 11-point horizontal scale anchored from 0 to 10, with 0 indicating "no pain" and 10 indicating "the worst pain imaginable." Participants' overall severity of their skin pain is indicated by selecting the number that best represents their worst level of 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). Ratings are recorded daily by participants.

[0051] The sleep deprivation scale is a participant-reported, single-item, daily scale that measures the degree of sleep deprivation due to itch interference over the last night. The sleep deprivation scale is rated on a 5-point Likert scale (0 [no problem at all] to 4 [no sleep at all]). Ratings are recorded daily by participants. The minimal clinically important change is 3 points (Yosipovitch et al. 2021, Content Validity And Assessment Of The Psychometric Properties And Score Interpretation Of A Pruritus Numeric Rating Scale In Atopic Dermatitis. Revolutionizing Atopic Dermatitis - December 2021). Participants record daily itch ratings at home using an electronic diary. The initial electronic diary entry for the sleep deprivation scale should be completed at least 4 of the 7 days prior to baseline.

[0052] The Dermatology Life Quality Index (DLQI) is a participant-reported, 10-item adult QoL questionnaire covering six domains: symptoms and emotions, daily activities, leisure, work and school, relationships, and treatment. The recall period for this scale is over the "last week." Response categories include scores of 0, 1, 2, and 3, corresponding to "not at all," "a little," "quite a bit," and "very much," respectively; an unanswered (or "does not apply") response is scored as 0. Scores range from 0 to 30, with higher scores indicating greater impairment of QoL. A DLQI total score of 0–1 is considered to have no effect on participants' HRQoL (Hongbo et al. 2005), and a 4-point change from baseline is considered the minimal clinically important difference threshold (Khilji et al. 2002, Br J Dermatol.;147:25–54; Basra et al. 2015, Dermatology.;230(1):27–33).

[0053] For adolescents under 16 years of age at baseline, the Children's DLQI (CDLQI) was used, which is based on a set of 10 questions that is different from the DLQI (Lewis-Jones MS, Finlay AY. British Journal of Dermatology, 1995;132:942-949), and they should continue to complete the CDLQI for the duration of the study.

[0054] The Atopic Dermatitis Control Status Questionnaire (ADCT) is a simple, brief, patient-reported tool for adults and adolescents that assesses six AD-related symptoms and effects over the past week: overall symptom severity, days with intense itch episodes, intensity of bother, sleep problems, impact on daily activities, and impact on mood or emotions. Each of the six Atopic Dermatitis Control Status Questionnaire items has a score range from 0 (no problem) to 4 (worst) and assesses the severity of each concept. The total score ranges from 0 to 24 and is the sum of responses to all items. A score of ≥7 points was derived as the threshold for identifying participants as "not controlled." The threshold for significant intra-individual change was 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).

[0055] The participant-reported satisfaction question asks, "How satisfied are you with this treatment's ability to treat your skin condition?" Response options range from 1 (not satisfied) to 5 (completely satisfied).

[0056] The Patient-Oriented Eczema Measure (POEM) is a seven-item scale assessing disease severity in children and adults. Participants answer questions about the frequency of seven symptoms (itching, sleep disturbance, bleeding, weeping / oozing, cracking, peeling, and dryness / chapping) over the past week. Response categories include "none," "1-2 days," "3-4 days," "5-6 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 severity (Charman et al., Arch Dermatol. 2004;140(12):1513-1519). Higher scores indicate poorer quality of life.

[0057] The European Quality of Life-Five Dimensions-Five Levels (EQ-5D-5L, EuroQol Research Foundation) is a standardized, five-item, self-administered instrument for use as a measure of health outcomes. It provides a simple descriptive profile and a single index value for health status that can be used in clinical and economic evaluations of health care and population health surveys. The European Quality of Life-Five Dimensions-Five Levels assesses five dimensions of health: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. The 5L version scores each dimension on five levels: no problems, slight problems, moderate problems, serious problems, and unable to perform / extreme problems. A total of 3,125 health states are possible. In addition to the health profile, a single health state index value can be derived based on a formula that weights each level in each dimension. This index value ranges from <0 (where 0 is a health state equivalent to death and negative values ​​are rated worse than death) to 1 (perfect health). Additionally, the EQ visual analogue scale scores respondents' self-rated health on a vertically graduated (0-100) visual analogue scale. Participants rate their perceived health from 0 (worst imaginable health) to 100 (best imaginable health). Together with the health status data, it provides a composite picture of the respondent's health status.

[0058] The Fitzpatrick Skin Phototype Scale is a clinician-assessed scale based on participants' skin response to sun exposure and baseline skin pigmentation. Fitzpatrick Skin Phototype ranges from I to VI, with a score of I indicating "always burns, never tans, and has a white skin tone," and a score of VI indicating "never burns, tans very easily, and has a dark skin tone" (High et al. 2012, Dermatology (3rd ed.). China: Elsevier; 2012: pp. 8). When recording the Fitzpatrick Skin Phototype, investigators will follow the descriptive terms included in this protocol. The sun sensitivity scale represents each participant's Fitzpatrick scale score. The recall period for this assessment is the present time.

[0059] The Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis (WPAI-AD) is a participant-reported, six-item questionnaire that records impairment due to AD over the past seven days in adolescents and adults. The Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis consists of six items grouped into four domains: absenteeism (work time lost), sickness work (impairment at work / reduced effectiveness at work), work productivity loss (overall work impairment / absenteeism and sickness work), and activity impairment. Absenteeism, sickness work, and work productivity are reported only by those currently employed (in paid work) at the time of scale completion. The scale's recall period covers the past seven days. Scores are calculated as percentage impairment (Reilly et al., Pharmacoeconomics. 1993;4(5):353-365), with higher scores indicating greater impairment and less productivity.

[0060] PROMIS (Patient-Reported Outcomes Measurement Information System) is a set of person-centered scales that assess and monitor physical, mental, and social health in adults and children (PROMIS WWW). PROMIS scales include short versions of anxiety and depression, which assess participants' symptoms over the past week. It can be used in the general population and in individuals living with chronic conditions.

[0061] The PROMIS Anxiety scale assesses the following items: self-reported fear (fear, panic), distressing anxiety (worry, fear), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (palpitations, 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) is available for children's self-report (ages 8 to <18 years) and for parents / caregivers acting as proxy reporters for children (younger than 5 years). Children under 5 years of age do not complete this assessment. Both the child self-report and proxy-report versions assess anxiety "in the past 7 days." Response options range from 1 = never to 2 = rarely, 3 = sometimes, 4 = often, and 5 = almost always. The total raw score was converted into a T-score, with higher scores representing greater anxiety.

[0062] The PROMIS Depression scale assesses the following items: self-reported negative mood (sadness, guilt), self-view (self-criticism, feelings of worthlessness), social cognition (loneliness, feelings of interpersonal alienation), and diminished positive affect and engagement (loss of interest, meaning, and purpose) (PROMIS Depression 2019, available at https: / / www.healthmeasures.net / images / PROMIS / manuals / PROMIS_Depression_Scoring_Manual.pdf). The PROMIS Depression Short Form (8a v2.0 and 6a v2.0) is available for children to self-report (ages 8-18 years) and for parents / caregivers to serve as proxy reporters for children (younger than 5 years). Children under 5 years of age do not 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 to 2 = rarely, 3 = sometimes, 4 = often, and 5 = almost always. Total raw scores were converted to T scores, with higher scores representing greater depression.

[0063] In some embodiments, the patient's EASI score is determined after the treatment period, e.g., at 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 administration of the first loading dose of the antibody, meaning the patient has achieved an "EASI50." 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 administration of the first loading dose of the antibody, meaning the patient has achieved an "EASI75." 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 administration of the first loading dose of the antibody, meaning the patient has achieved an "EASI90."

[0064] 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 or more points compared to the IGA score determined before administration of the first loading dose of the antibody.

[0065] 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 or more points compared to the pruritus NRS score determined before administration of the first loading dose of the antibody.

[0066] In another aspect, provided herein is an antibody that binds human IL-13 for use in treating moderate to severe atopic dermatitis in patients previously administered dupilumab. In some embodiments, provided herein is an antibody that binds human IL-13 for use in treating moderate to severe atopic dermatitis in patients previously administered dupilumab and who discontinued dupilumab due to non-response, partial response, or loss of response. In some embodiments, provided herein is an antibody that binds human IL-13 for use in treating moderate to severe atopic dermatitis in patients previously administered dupilumab and who discontinued dupilumab due to intolerance or adverse events. In some embodiments, the patient (1) is 12 years of age or older, (2) has chronic atopic dermatitis for more than one year according to the American Academy of Dermatology Common Criteria, (3) has an EASI score of 16 or greater, (4) has an IGA score of 3 or greater, (5) has more than 10% of the BSA affected by atopic dermatitis, or (6) has had an inadequate response to topical corticosteroids. In some embodiments, the pharmaceutical composition is for subcutaneous administration to the patient.

[0067] In another aspect, provided herein is the use of an antibody that binds human IL-13 in the manufacture of a medicament for the treatment of moderate to severe atopic dermatitis in patients previously administered dupilumab. Also provided herein is the use of an antibody that binds human IL-13 in the manufacture of a medicament for the treatment of moderate to severe atopic dermatitis in patients previously administered dupilumab and who have discontinued dupilumab due to non-response, partial response, or loss of response. Also provided herein is the use of an antibody that binds human IL-13 in the manufacture of a medicament for the treatment of moderate to severe atopic dermatitis in patients previously administered dupilumab and who have discontinued dupilumab due to intolerance or adverse events. In some embodiments, the patient (1) is 12 years of age or older, (2) has chronic atopic dermatitis for more than one year according to the American Academy of Dermatology Common Criteria, (3) has an EASI score of 16 or greater, (4) has an IGA score of 3 or greater, (5) has more than 10% of the BSA affected by atopic dermatitis, or (6) has had an inadequate response to topical corticosteroids. In some embodiments, the pharmaceutical composition is for subcutaneous administration to the patient.

[0068] In some embodiments, the methods and uses described herein further comprise administering one or more topical corticosteroids to the patient. Exemplary topical corticosteroids include, but are not limited to, triamcinolone acetonide, hydrocortisone, and a combination of triamcinolone acetonide and hydrocortisone. Triamcinolone acetonide is typically formulated in cream at a concentration of 0.1%, and hydrocortisone is typically formulated in cream at a concentration of 1% or 2.5%. Certain topical corticosteroids, such as betamethasone dipropionate, clobetasol propionate, diflorasone acetate, fluocinonide, and halobetasol propionate, are considered to be highly potent. Certain topical corticosteroids, such as amcinonide, desoximetasone, halcinonide, and triamcinolone acetonide, are considered to be highly potent. Certain topical corticosteroids, such as betamethasone valerate, clocortolone pivalate, fluocinolone acetonide, flurandrenolide, fluocinonide, fluticasone propionate, hydrocortisone butyrate, hydrocortisone valerate, mometasone furoate, and prednicarbate, are considered to be medium-potency. Certain topical corticosteroids, such as alclometasone dipropionate, desonide, and hydrocortisone, are considered to be low-potency. TCS can be applied to the affected area once daily, twice daily, three times daily, or as needed. In some embodiments, the patient's condition is inadequately controlled by 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 simultaneously or sequentially with the anti-IL-13 antibody. In some embodiments, a topical corticosteroid is administered simultaneously with the anti-IL-13 antibody. Accordingly, also provided herein are antibodies that bind to human IL-13 for separate, simultaneous, or sequential administration in combination with one or more topical corticosteroids.

[0069] As used herein, the terms "a," "an," "the," and similar terms as used in the context of this disclosure (particularly in the context of the claims) should be construed to cover both the singular and the plural unless otherwise indicated or clearly contradicted by context.

[0070] The term "about" as used herein means sufficiently close to the stated value, for example, ±10% of the stated value.

[0071] As used herein, the term "administer" or "administering" refers to administering an antibody, compound, or composition directly to a subject, and includes treating a subject with the antibody, compound, or composition.

[0072] As used herein, the term "adverse event" refers to any untoward medical occurrence in a participant administered a medicinal product, which does not necessarily have a causal relationship to the study intervention. Thus, an adverse event can be any untoward and unintended sign (including abnormal laboratory findings), symptom, or disease temporarily associated with the use of a medicinal product, whether or not related to the medicinal product.

[0073] As used herein, the term "antibody" refers to an immunoglobulin molecule that binds to an antigen. Antibody embodiments include monoclonal, polyclonal, human, humanized, chimeric, or conjugated antibodies. The antibody may be of any class (e.g., IgG, IgE, IgM, IgD, IgA) and any subclass (e.g., IgG1, IgG2, IgG3, IgG4).

[0074] 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 contains a variable region of about 100 to 125 amino acids or more that is primarily responsible for antigen recognition. The carboxy-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 may be further divided into subclasses (e.g., IgG1, IgG2, IgG3, and IgG4).

[0075] The VH and VL regions can be further subdivided into hypervariable regions, termed complementarity determining regions (CDRs), interspersed with more conserved regions, termed framework regions (FRs). The CDRs are exposed on the surface of the protein and are critical regions of the antibody for antigen-binding specificity. Each VH and VL is composed of three CDRs and four FRs, arranged from the amino terminus to the carboxy terminus in the order FR1, CDR1, FR2, CDR2, FR3, CDR3, and 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.The assignment of amino acid residues to CDRs can be performed using the methods of 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, 406, 228-256 (2011)), or IMGT (the international ImMunoGeneTics This can be done according to well-known schemes, including those described in the database (available at www.imgt.org; Lefranc et al., Nucleic Acids Res. 1999;27:209-212).

[0076] Exemplary embodiments of the antibodies of the present disclosure also include antibody fragments or antigen-binding fragments that comprise 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.

[0077] As used herein, the terms "bind" and "binds," unless otherwise specified, are intended to mean the ability of a protein or molecule to form a chemical bond or attractive interaction with another protein or molecule, bringing the two proteins or molecules into proximity as determined by common methods known in the art.

[0078] The term "flare" as used herein refers to an increase in signs and / or symptoms that leads to an increase in therapy, which may be an increase in dosage, a switch to a higher potency class of drug, or the initiation of another drug.

[0079] The term "high affinity" as used herein means that the affinity is greater than or equal to about 10 -8 Less than M, e.g., 10 -15 M~10 -8 M or 10 -12 M~10 -9 The equilibrium dissociation constant (K D ) refers to the strength of binding of an antibody to human IL-13.

[0080] The term "human IL-13" refers to human interleukin-13 (also known as P600), an immunoregulatory cytokine produced primarily by activated Th2 cells. There are two known human IL-13 isoforms: 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 at NCBI accession number NP_002179.2. The amino acid sequence of human IL-13 isoform b can be found at NCBI accession number NP_001341922.1.

[0081] As used herein, the term "non-response" or "non-responsive" refers to no improvement or less than 25% improvement in a patient's atopic dermatitis in response to treatment, e.g., no improvement or less than 25% improvement in the patient's skin and / or itch (e.g., as measured by the EASI score for skin and / or the Pruritus NRS score for itch) at peak response to dupilumab.

[0082] As used herein, the term "partial response" refers to a patient's atopic dermatitis only partially improving in response to treatment, e.g., a patient's skin and / or itch only improving by between 25-50% (e.g., as measured by the EASI score for skin and / or the Pruritus NRS score for itch) at peak response to dupilumab.

[0083] As used herein, the term "loss of response" refers to a patient who initially responded but then loses response to treatment, e.g., the patient's skin and / or itch initially improve (e.g., as measured by EASI score for skin and / or Pruritus NRS score for itch) but then worsen after dupilumab treatment.

[0084] As used herein, the term "intolerance" refers to an intolerable adverse event in response to treatment. For example, a patient discontinued dupilumab due to anaphylaxis; new onset or worsening of ocular surface disease (including, but not limited to, conjunctivitis); new onset or worsening of facial dermatitis; new onset or worsening of injection site reaction; new onset or worsening of inflammatory arthritis; new onset or worsening of psoriasiform dermatitis; new onset or worsening of alopecia areata.

[0085] As used herein, the term "inadequate response" refers to the failure to achieve good disease control of atopic dermatitis (e.g., failure to achieve IGA≦2 or EASI-75) after use of treatment for the period recommended by the product prescribing information, or the occurrence of atopic dermatitis flares during treatment.

[0086] As used herein, the term "patient" refers to a human patient.

[0087] As used herein, the term "topical corticosteroid" or "TCS" includes Group I, Group II, Group III, and Group IV topical corticosteroids. According to the World Health Organization's Anatomical Therapeutic Chemical (ATC) Classification System, corticosteroids are classified into weak (Group I), moderately potent (Group II), potent (Group III), and very potent (Group IV) based on their activity relative to hydrocortisone. Group IV TCS (very potent) are up to 600 times more potent than hydrocortisone and include clobetasol and halcinonide. Group III TCS (potent) are 50 to 100 times more potent than hydrocortisone and include, but are not limited to, betamethasone valerate, betamethasone dipropionate, diflucortolone valerate, hydrocortisone-17-butyrate, mometasone furoate, and methylprednisolone aceponate. Class II TCS (moderately potent) are 2 to 25 times more potent than hydrocortisone and include, but are not limited to, clobetasone butyrate and triamcinolone acetonide. Class I TCS (weak or mild) include hydrocortisone, prednisolone, and methylprednisolone.

[0088] As used herein, "treatment" or "treating" refers to any process that may slow, control, retard, or halt the progression of, or ameliorate the symptoms of, a disorder or disease disclosed herein, but does not necessarily indicate the complete elimination of all disorder or disease symptoms. 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, particularly a human. [Example]

[0089] Example 1. A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of lebrikizumab when used in combination with topical corticosteroid (TCS) treatment in patients with moderate to severe atopic dermatitis (KGAD) This is a randomized, double-blind, placebo-controlled, parallel-group study with a duration of 16 weeks. The study is designed to evaluate the safety and efficacy of lebrikizumab when used in combination with TCS treatment compared to placebo in combination with TCS treatment for moderate to severe AD. The study design is shown in Figure 1.

[0090] In each study, approximately 225 patients will be stratified and randomized 2:1 to receive either 250 mg of lebrikizumab (a 500 mg loading dose given at baseline (week 0) and week 2) by subcutaneous (SC) injection every two weeks (Q2W) or placebo for a 16-week treatment period. All study drug injections will be administered in clinic. TCS treatment will begin at baseline in all patients and may be tapered or stopped, as needed, based on treatment response.

[0091] After completing the 16-week visit, patients will be offered the option to continue treatment in a separate long-term extension (LTE) study. Patients who terminate early or elect not to enter the long-term extension study will undergo safety follow-up approximately 12 weeks after their last study drug injection.

[0092] Research goals and evaluation items Primary endpoint: According to the FDA, the primary efficacy endpoint is the percentage of patients with an IGA score of 0 or 1 and a ≥ 2-point reduction from baseline to week 16.

[0093] According to the EMA, the primary efficacy endpoints will be as follows: (1) the percentage of patients with an IGA score of 0 or 1 and a reduction of ≥ 2 points from baseline to week 16, and (2) the percentage of patients achieving EASI-75 (≥ 75% reduction from baseline in EASI score) at week 16.

[0094] Secondary endpoints Table 3 below lists the secondary endpoints of this study.

[0095] Table 3. Secondary endpoints [Table 3]

[0096] Statistical analyses will be performed for the primary and secondary endpoints.

[0097] Patient population Inclusion Criteria: Patients must meet all of the following criteria to be eligible to participate in this study: 1. Adults and adolescents (ages 12 to 18 years, weight 40 kg or more). 2. Chronic AD (according to the American Academy of Dermatology common diagnostic criteria) for at least one year prior to the screening visit. 3. Eczema Area and Severity Index (EASI) score ≥ 16 at the baseline visit. 4. Investigator Global Assessment (IGA) score ≥ 3 (scale of 0 to 4) at the baseline visit. 5. AD coexistence in body surface area (BSA) ≥ 10% at the baseline visit. 6. History of inadequate response to treatment with topical medications. 7. Applying a stable dose of a non-medicated topical moisturizer at least twice daily for ≥ 7 days prior to the baseline visit. 8. Completed an electronic diary of pruritus and sleep loss for at least 4 of the 7 days prior to randomization. 9. Willing and able to comply with all clinic visit and study-related procedures and questionnaires. 10. For females of childbearing potential, agree to remain abstinent or use highly effective contraception during treatment and for at least 18 weeks after the last dose of lebrikizumab or placebo. 11. Male patients must agree to use an effective barrier method of contraception during the study and for a minimum of 18 weeks after the last dose of study drug if they are sexually active with a female of childbearing potential. 12. Provide a signed informed consent / assent form.

[0098] Exclusion Criteria: Patients who meet any of the following criteria will be excluded from the study. 1. Participation in previous lebrikizumab clinical studies. 2. History of anaphylaxis as defined by the Sampson criteria (Sampson 2006). 3. Treatment with topical corticosteroids, calcineurin inhibitors, or phosphodiesterase-4 inhibitors, e.g., crisaborole, within 1 week prior to the baseline visit. 4. Treatment with any of the following medications within 4 weeks prior to the baseline visit: Immunosuppressive / immunomodulatory agents (e.g., systemic corticosteroids, cyclosporine, mycophenolate mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.), b. Phototherapy and photochemotherapy (PUVA) for AD. 5. Treatment prior to the Baseline Visit with: a. Investigational drug within 8 weeks or 5 half-lives (if known), whichever is longer. b. Dupilumab within 8 weeks. c. B-cell depleting biologics, including rituximab, within 6 months. d. Other biologics with 5 half-lives (if known) or less than 16 weeks, whichever is longer. 6. Use of prescription moisturizers within 7 days of the baseline visit. 7. Regular use of tanning booths / parlors (more than two visits per week) within 4 weeks of the screening visit. 8. Treatment with live (attenuated) vaccines within 12 weeks of the baseline visit or planned during the study. 9. Uncontrolled chronic disease that may require oral corticosteroid bursts, e.g., comorbid severe uncontrolled asthma (defined by ACQ-5 score ≥ 1.5 or a history of ≥ 2 asthma exacerbations within the past 12 months requiring systemic [oral and / or parenteral] corticosteroid treatment or hospitalization for > 24 hours). 10. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, anthelmintics, antiprotozoals, or antifungals within 2 weeks prior to the baseline visit, or a superficial skin infection within 1 week prior to the baseline visit. 11. Evidence of active acute or chronic hepatitis (as defined by the Department of Health & Human Services Centers for Disease Control and Prevention) or known cirrhosis. 12. Diagnosed active endoparasitic infections or high risk of these infections. 13. Known or suspected history of immunosuppression, including a history of invasive opportunistic infection (e.g., tuberculosis (TB), histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis, and aspergillosis) despite resolution of the infection, or unusually frequent, recurrent, or prolonged infections as determined by the investigator. 14. History of human immunodeficiency virus (HIV) infection or positive HIV serology at the time of screening. 15. Any clinically significant laboratory results from chemistry, hematology, or urinalysis obtained at the screening visit, in the opinion of the investigator. 16. Presence of cutaneous comorbidities that may interfere with study evaluation. 17. History of malignancy, including mycosis fungoides, within 5 years prior to the screening visit, except for cured in situ cervical cancer, cured and resolved non-metastatic squamous cell carcinoma or basal cell carcinoma of the skin. 18. Severe intercurrent illness that, in the investigator's judgment, would adversely affect the patient's participation in the study. Any other medical or psychological condition that, in the investigator's opinion, may suggest a new and / or poorly understood disease, may present an undue risk to the study patient for the patient's participation in this clinical trial, may make the patient's participation unreliable, or may interfere with study evaluation. 19. Pregnant or breastfeeding women, or women who plan to become pregnant or breastfeed during the study. 20. Had significant adverse reactions to TCS (e.g., intolerance to treatment, hypersensitivity reactions, significant skin atrophy, and systemic effects) assessed by the investigator or treating physician that would prevent further use.

[0099] Study Drugs: Lebrikizumab is provided in a sterile liquid solution (pH 5.4-6.0) containing 125 mg / mL lebrikizumab, histidine acetate, sucrose, polysorbate 20, and sterile water for injection. The placebo solution is identical in appearance and content, except for the lebrikizumab. All study medications (lebrikizumab and placebo) are supplied as sterile prefilled syringes with preassembled needle-safety devices (PFS-NSDs). Each prefilled syringe is intended for a single 2 mL dose (250 mg) to be administered subcutaneously (SC).

[0100] Results for patients previously treated with dupilumab In this study, 211 patients were randomized 2:1 to receive lebrikizumab plus TCS (N=145) or placebo plus TCS (N=66). Prior exposure to dupilumab was reported in 20 patients randomized to lebrikizumab plus TCS and in 9 patients randomized to placebo plus TCS. Among these 29 patients, reasons for prior discontinuation of dupilumab were due to loss of response or inadequate response (14 patients), intolerance to medication (1 patient), or other (14 patients). Other reported reasons for discontinuation included eligibility, affordability, and availability of treatment.

[0101] In patients treated with lebrikizumab plus TCS, baseline characteristics were comparable between the overall lebrikizumab-treated population (N = 145) and the subpopulation with prior dupilumab exposure (N = 20). Of the 20 patients with prior dupilumab exposure, 13 patients had an IGA of 3 and 7 patients had an IGA of 4. The mean (standard deviation [SD]) body surface area reported at baseline was 37.3 (15.7). The mean (SD) baseline scores on the EASI and Pruritus NRS were 25.9 (8.1) and 7.8 (1.9), respectively. The mean (SD) duration since AD ​​onset was longer in patients with prior dupilumab experience compared with patients without prior dupilumab exposure (27.0 [22.5] vs. 21.0 [17.4], respectively).

[0102] In patients treated with lebrikizumab plus TCS with prior dupilumab exposure, IGA 0 / 1 with a 2-point improvement was achieved by 6 / 18 patients, EASI-75 was achieved by 13 / 18 patients, and Pruritus NRS 4-point improvement was achieved by 8 / 15 patients at week 16. Use of high-potency rescue or systemic medications was reported in one patient.

[0103] The results of this subpopulation analysis suggest that patients previously exposed to dupilumab are more likely to respond to lebrikizumab plus TCS. Lebrikizumab could provide clinically meaningful improvement in atopic dermatitis in patients who previously received dupilumab but failed or were intolerant to dupilumab.

[0104] Example 2. Study to Evaluate the Safety and Efficacy of Lebrikizumab in Adult and Adolescent Participants (KGBO) with Moderate to Severe Atopic Dermatitis Previously Treated with Dupilumab The study is designed to evaluate the safety and efficacy of lebrikizumab in adult and adolescent participants with moderate to severe AD who have been previously treated / administered dupilumab.

[0105] Figure 2 is a schematic diagram of the study design. The trial has three study periods: screening (≤30 days prior to baseline), treatment (24 weeks), and safety follow-up (week 34, or approximately 12 weeks after the last treatment). During the 24-week treatment period, approximately 120 participants will receive lebrikizumab subcutaneously (SC) at baseline (week 0) and at a loading dose of 500 mg at week 2, followed by 250 mg every two weeks (Q2W).

[0106] Approximately 120 participants previously treated / administered with dupilumab will be enrolled in this study. Among them, approximately 80 participants who discontinued dupilumab due to a) no response to treatment, b) partial response to treatment, or c) loss of response to treatment will be enrolled. Additionally, approximately 15 participants who discontinued dupilumab treatment due to intolerance or adverse events (AEs) will be enrolled. Finally, approximately 25 participants who discontinued dupilumab treatment for other reasons (e.g., cost, insurance coverage, access to medication, previous trial participation) will be enrolled. Approximately 10% of participants (n=12) will be adolescents (ages 12 to <18 years, weighing at least 40 kg).

[0107] Table 4 lists the objectives and endpoints of this study. Statistical analysis will be performed on the endpoints.

[0108] Table 4. Objectives and evaluation items [Table 4-1]

[0109] (Continued from Table 4) [Table 4-2]

[0110] Patient population Inclusion Criteria: Participants are eligible for inclusion in the study only if all of the following criteria apply: 1. Participants must be 12 years of age or older (inclusive) at the time of signing the informed consent / assent form. Adolescents (12-18 years of age) must weigh ≥ 40 kg at baseline. 2. All participants must have received prior treatment / administration with dupilumab, meeting one of the following conditions: a. Participants who discontinue dupilumab due to non-response, partial response, or loss of efficacy must have been previously treated with dupilumab (at the labeled dose level) for at least 4 months. b. Participants who discontinued dupilumab due to intolerance to the drug or AE may enter the study without requiring a prior length of dupilumab treatment. c. Participants who discontinue dupilumab due to cost of access to dupilumab or other reasons, such as loss of access (e.g., insurance coverage), may participate in the study without requiring a prior length of dupilumab treatment. 3. Participants with chronic AD (according to the American Academy of Dermatology Common Diagnostic Criteria; Eichenfield et al. 2014) for ≥1 year prior to the screening visit. 4. Have an EASI ≥ 16 at the baseline visit. 5. Have an IGA score ≥ 3 (on a scale of 0 to 4) at the baseline visit. 6. Have ≥10% body surface area (BSA) at the baseline visit. 7. History of an inadequate response to treatment with topical medications, or a determination that topical treatment is otherwise not medically advisable. 8. Female participants of childbearing potential must agree to remain abstinent 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 contraception except in accordance with specific local government study requirements. 9. Participants must provide signed informed consent. For minor participants, a parent or legal guardian must be able to read, understand, and provide written informed consent for their child to participate in this study.

[0111] Exclusion Criteria: Participants will be excluded from the study if any of the following criteria apply: 1. History of human immunodeficiency virus (HIV) infection or positive HIV serology at the time of screening. 2. Have infection or chronic infection with Hepatitis B virus (HBV) at the time of screening. 3. Have hepatitis C virus (HCV) infection at the time of screening. 4. Have an uncontrolled chronic disease at screening as defined by the investigator that may require multiple intermittent use of oral corticosteroids. 5. Have uncontrolled asthma. a. May require a burst of oral or systemic corticosteroids; or b. ≥ 1 exacerbation within 12 months prior to baseline requiring: ● Systemic (oral and / or parenteral) corticosteroid treatment, or ● >24 hour hospital stay. 6. Known cirrhosis and / or chronic hepatitis of any etiology. 7. History of malignancy (including fungal skin cancer or cutaneous T-cell lymphoma) present within 5 years prior to screening, excluding fully treated intraepithelial carcinoma of the cervix, fully treated and resolved nonmetastatic squamous cell carcinoma of the skin, or basal cell carcinoma, with no evidence of recurrence in the past 12 weeks. 8. Diagnosed with active internal parasitic infection or at high risk of such infection. 9. Known and suspected history of immunosuppression, including a history of invasive opportunistic infections, such as tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis, and aspergillosis, despite resolution of the infection, or known or suspected unusually frequent, recurrent, or prolonged infections, as determined by the investigator. 10. Presence of cutaneous comorbidities that may interfere with study evaluation. 11. Severe intercurrent illness(ies) that, in the judgment of the investigator, would adversely affect the participant's participation in the study. 12. Any other medical or psychological condition that, in the opinion of the investigator, may suggest a new and / or poorly understood disease, may present an undue risk to the study participant, may make the patient's participation unreliable, or may interfere with study evaluation, for the patient's participation in this clinical trial. 13. Have had any of the following types of infections within 3 months of screening or have any of these infections at the time of screening: a. Severe (requiring hospitalization and / or intravenous or equivalent oral antibiotic treatment), b. Opportunistic (as defined in Winthrop et al. 2015), c. Chronic (duration of symptoms, signs, and / or treatment for 6 weeks or more); d. Recurrent (including but not limited to recurrent cellulitis or chronic osteomyelitis). 14. Active or acute infection requiring treatment with a systemic antibiotic, antiviral, anthelmintic, antiprotozoal, or antifungal agent within 2 weeks prior to the baseline visit (Baseline), or a superficial skin infection within 1 week prior to the Baseline visit. 15. Dupilumab treatment within 4 weeks prior to the baseline visit. 16. Prior treatment with dupilumab or tralokinumab. 17. Treatment with topical medications (corticosteroids, calcineurin inhibitors, JAK inhibitors, or phosphodiesterase-4 inhibitors) within 2 weeks prior to the baseline visit. 18. Treatment with any of the following medications within 4 weeks prior to the baseline visit: 19. Systemic immunosuppressants / immunomodulators (e.g., systemic corticosteroids, cyclosporine, mycophenolate mofetil, IFN-γ, azathioprine, methotrexate, and other immunosuppressants). 20. Small molecules (e.g., JAK inhibitors). 21. Phototherapy and photochemotherapy for AD. 22. Regular use of tanning booths / parlors (more than two visits per week) within 4 weeks of the screening visit. 23. I am currently receiving increased dosages of allergen immunotherapy (allergy injections). 24. Treatment with B-cell depleting biologics, including rituximab, within 6 months prior to the baseline visit. 25. Use of prescription moisturizers within 7 days of the baseline visit. 26. Has received Bacillus Calmette-Guerin vaccination or treatment within 4 weeks prior to the baseline visit or intends to receive Bacillus Calmette-Guerin vaccination or treatment during the study. 27. Has received any live attenuated vaccine within <4 weeks of the baseline visit or intends to receive any live attenuated vaccine during the study or within 4 weeks after receiving the last dose of the study intervention. 28. Note: The following are not considered live vaccines: RNA vaccines, vaccines with inactivated viral elements, and / or non-replicating viral vector vaccines. 29. Use of cannabis or cannabinoids for the treatment of pruritus, pain, and / or AD. 30. Have significant laboratory results from chemistry or hematology tests at the screening visit, in the opinion of the investigator. 31. Currently enrolled in any other clinical research study, including investigational products or any other type of medical research, that is deemed scientifically or medically incompatible with this study. 32. Treatment with an investigational drug within 8 weeks or 5 half-lives (if known), whichever is longer, of the baseline visit. 33. Have received a dose of lebrikizumab in any previous lebrikizumab clinical study.

[0112] Study Drugs: Pharmaceutical compositions containing 2 mL of 125 mg / mL lebrikizumab or placebo are supplied in sterile, pre-filled syringes with a pre-assembled needle safety device (PFS-NSD) for subcutaneous administration to patients. The lebrikizumab sequence is shown in Table 1. The placebo solution is identical in appearance and volume to the active solution, except that it does not contain lebrikizumab.

Claims

1. 1. A method of treating moderate to severe atopic dermatitis, said method comprising: Selecting patients with moderate to severe atopic dermatitis who had previously received dupilumab and had discontinued dupilumab due to non-response, partial response, or loss of response; administering to the patient an antibody that binds human IL-13; The method, 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 an HCDR1 comprising SEQ ID NO: 1, an HCDR2 comprising SEQ ID NO: 2, and an HCDR3 comprising SEQ ID NO: 3, and the VL comprises an LCDR1 comprising SEQ ID NO: 4, an LCDR2 comprising SEQ ID NO: 5, and an LCDR3 comprising SEQ ID NO:

6.

2. 1. A method of treating moderate to severe atopic dermatitis, said method comprising: To select patients with moderate to severe atopic dermatitis who had previously received dupilumab and had discontinued dupilumab due to intolerance or adverse events; administering to the patient an antibody that binds human IL-13; The method, 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 an HCDR1 comprising SEQ ID NO: 1, an HCDR2 comprising SEQ ID NO: 2, and an HCDR3 comprising SEQ ID NO: 3, and the VL comprises an LCDR1 comprising SEQ ID NO: 4, an LCDR2 comprising SEQ ID NO: 5, and an LCDR3 comprising SEQ ID NO:

6.

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

4. The method according to any one of claims 1 to 3, wherein the moderate to severe atopic dermatitis is determined according to the American Academy of Dermatology Common Diagnostic Criteria.

5. 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 human IL-13.

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

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

8. 1. A method of treating moderate to severe atopic dermatitis, said method comprising: i. be 12 years of age or older; ii. Have chronic atopic dermatitis according to the American Academy of Dermatology common diagnostic criteria for more than one year; iii. Have an EASI score of 16 or greater; iv. have an IGA score of 3 or greater; v. Having more than 10% of the body surface area affected by atopic dermatitis; vi. had an inadequate response to topical corticosteroids, and vii. Selecting patients who have previously received dupilumab and who have discontinued dupilumab due to (1) non-response, partial response, or loss of response, or (2) intolerance or adverse events; administering to the patient an antibody that binds human IL-13; The method, 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 an HCDR1 comprising SEQ ID NO: 1, an HCDR2 comprising SEQ ID NO: 2, and an HCDR3 comprising SEQ ID NO: 3, and the VL comprises an LCDR1 comprising SEQ ID NO: 4, an LCDR2 comprising SEQ ID NO: 5, and an LCDR3 comprising SEQ ID NO:

6.

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

10. 9. The method of claim 8, wherein the patient discontinued dupilumab due to intolerance or an adverse event.

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

12. 12. The method of claim 11, wherein the patient's skin and / or itch improves by no or less than 25% at peak response to dupilumab.

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

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

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

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

17. 17. The method of any one of claims 1-16, wherein the patient has discontinued dupilumab for at least 4 weeks.

18. 17. The method of any one of claims 1-16, wherein the patient has discontinued dupilumab for at least 8 weeks.

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

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

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

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

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

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

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

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

30. 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 human IL-13.

31. 30. 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 human IL-13.

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

33. 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 or more points compared to the IGA score determined before administration of the first loading dose of the antibody.

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

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

36. After said treatment period, said patient has the following characteristics: i. Sleep Deprivation Scale, ii. Skin Pain NRS score; iii. SCORAD Severity Rating System for Atopic Dermatitis; iv. Dermatology Life Quality Index (DLQI) score, Pediatric Dermatology Life Quality Index (CDLQI) score, v. Facial Investigator Global Assessment (F-IGA), vi. Modified Lesion Symptom Scale; vii. Atopic Dermatitis Control Status Questionnaire (ADCT), viii. Participant-reported satisfaction questionnaire; ix. Fitzpatrick Skin Photometric Rating Scale; x. Work Productivity and Activity Impairment Questionnaire - Atopic Dermatitis (WPAI-AD), xi. Patient Oriented Eczema Measurement (POEM), xii. European Quality of Life - Five Dimensions - Five Levels (EQ-5D-5L); xiii. PROMIS (Patient Reported Outcomes Measurement Information System) anxiety and depression scales.

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

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

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

40. 38. The method of claim 37, wherein the patient is treated with a maintenance dose of 250 mg of the antibody that binds human IL-13 once every 8 weeks during the maintenance period.

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

42. 42. The method of claim 41, wherein the subcutaneous administration device is selected from a pre-filled syringe, a disposable pen injection device, a microneedle device, a microinfuser device, a needle-free injection device, or an auto-injector device.

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

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

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

6.

47. 1. An antibody that binds to human IL-13 for use in treating moderate to severe atopic dermatitis in patients who have previously received dupilumab but have 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 an HCDR1 comprising SEQ ID NO: 1, an HCDR2 comprising SEQ ID NO: 2, and an HCDR3 comprising SEQ ID NO: 3, and the VL comprises an LCDR1 comprising SEQ ID NO: 4, an LCDR2 comprising SEQ ID NO: 5, and an LCDR3 comprising SEQ ID NO:

6.

48. 10. The method of claim 1, wherein the patient: i. be 12 years of age or older; ii. Have chronic atopic dermatitis according to the American Academy of Dermatology common diagnostic criteria for more than one year; iii. Have an EASI score of 16 or greater; iv. have an IGA score of 3 or greater; v. Having a BSA with more than 10% atopic dermatitis; 48. The antibody for use according to claim 46 or 47, in patients with an inadequate response to topical corticosteroids.

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

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

6.

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

6.

52. The patient: i. be 12 years of age or older; ii. Have chronic atopic dermatitis according to the American Academy of Dermatology common diagnostic criteria for more than one year; iii. Have an EASI score of 16 or greater; iv. have an IGA score of 3 or greater; v. Having a BSA with more than 10% atopic dermatitis; vi) The use of claim 50 or 51, wherein the patient has had an inadequate response to topical corticosteroids.

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

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