Medical use

Abstract

The present invention relates to pharmaceutical compositions comprising from about 100 mg to about 300 mg of an antigen binding protein which binds to IL-5. Compositions and antigen binding proteins of the invention are useful in the treatment of chronic obstructive pulomary disease (COPD) and can be administered about once every 6 months.

Description

[0001] MEDICAL USE

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to an antigen binding protein, e.g. an antibody, which binds to IL-5 for use in the treatment of chronic obstructive pulmonary disease (COPD). The present invention further relates to a method of treating COPD by administering an antigen binding protein, e.g. an antibody, which binds to IL-5.

[0004] BACKGROUND TO THE INVENTION

[0005] Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterised by chronic respiratory symptoms (dyspnea, cough, sputum production and / or exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and / or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction (Celli, 2022). COPD is usually progressive and associated with an enhanced chronic inflammatory response, in the airways and the lung. Exposure to noxious particles or gases predominantly due to cigarette smoking is an important risk factor for COPD worldwide. Other risk factors include occupational and environmental exposures, respiratory infections, socio-economic status and genetic predisposition. While the disease course is marked by progressive deterioration in airflow, it is punctuated by acute exacerbations of COPD (AECOPD) which contribute to the overall disease severity and which increase in frequency as the disease worsens (Vogelmeier, 2017; Barnes, 2015). In addition to the increased risk of morbidity and mortality associated with COPD exacerbations, these events place a significant economic burden on healthcare systems which is predicted to increase with the increasing global disease prevalence (Halpin, 2017; Perera, 2012; Toy, 2010).

[0006] A subset of COPD patients have evidence of Type 2 inflammation characterised by elevated blood and sputum eosinophils; circulating Th2 cells; innate lymphoid cells (ILC2) and elevated Type 2 cytokines (IL-4, IL-5 & IL-13) (Barnes, 2018; Christenson, 2015). Up to 40% of COPD patients have an inflammatory pattern that includes elevated sputum eosinophils (Brightling, 2005; Saha, 2006). In these patients, the blood eosinophil count (BEC) has been identified as a predictor of response to therapies targeting type 2 inflammation.

[0007] IL-5 is a dominant cytokine driving T2 pathological inflammation through multiple cell types (Bischoff, 1990; Maspero 2021 ; Ochi, 2000 and Stone 2010). Based on the observation that airway eosinophilic inflammation is associated with COPD exacerbations (Bafadhel, 2011 ; Bafadhel, 2017) and that reducing Type 2 inflammation may attenuate COPD exacerbations, anti-interleukin-5 (anti-IL-5) therapy may reduce exacerbations in a COPD patient population. In light of the above, it is clear that there is a need for more effective and convenient treatments for COPD. In particular, there exists a need for an efficacious treatment for COPD, that improves patient compliance and / or has a reduced dosing profile.

[0008] SUMMARY OF THE INVENTION

[0009] The present invention provides an antigen binding protein which binds to human IL- 5 comprising a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 for use in the treatment of chronic obstructive pulmonary disease (COPD) in a patient, wherein the antigen binding protein is to be administered to the patient at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months.

[0010] BRIEF DESCRIPTION OF DRAWINGS

[0011] FIG. 1. MATINEE Summary of study population

[0012] FIG. 2. MATINEE Annualized rate of moderate / severe exacerbations

[0013] FIG. 3. MATINEE Time to first moderate / severe exacerbation

[0014] FIG. 4. MATINEE Exacerbations requiring ED / hospital visit

[0015] FIG. 5. MATINEE CAT Responder analysis

[0016] FIG. 6. MATINEE E-RS: COPD Responder analysis

[0017] FIG. 7. MATINEE SGRQ Responder analysis

[0018] FIG. 8. MATINEE Moderate / severe exacerbations by subgroup: Smoking status

[0019] FIG. 9. MATINEE Moderate / severe exacerbations by subgroup: Symptoms of Chronic Bronchitis

[0020] DETAILED DESCRIPTION OF THE INVENTION

[0021] DEFINITIONS

[0022] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0023] The singular terms "a", "an", and "the" include plural referents unless context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise. The term "plurality" refers to two or more. The term “at least one” refers to one or more.

[0024] Additionally, numerical limitations given with respect to concentrations or levels of a substance, such as solution component concentrations or ratios thereof, are intended to be approximate. Unless specified otherwise, where a numerical range is provided, it is inclusive, i.e. , the endpoints are included.

[0025] "About" as used herein when referring to a measurable value such as an amount and the like, is meant to encompass variations of ±20% or ±10%, including ±5%, ±1%, and ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods.

[0026] The term "antigen binding protein" as used herein refers to antibodies, antibody fragments and other protein constructs which are capable of binding to an antigen.

[0027] The term “antibody” is used herein in the broadest sense to refer to molecules with an immunoglobulin-like domain (for example IgG, IgM, IgA, IgD or IgE) and includes monoclonal, recombinant, polyclonal, chimeric, human, humanised, multispecific antibodies, including bispecific antibodies, and heteroconjugate antibodies; a single variable domain (e.g. a domain antibody (DAB)), antigen binding antibody fragments, Fab, F(ab’)2, Fv, disulphide linked Fv, single chain Fv, disulphide-linked scFv, diabodies, TANDABS, etc. and modified versions of any of the foregoing (for a summary of alternative “antibody” formats see Holliger and Hudson, Nature Biotechnology, 2005, Vol 23, No. 9, 1126-1136). Alternative antibody formats are also contemplated and include alternative scaffolds in which the one or more CDRs of the antigen binding protein can be arranged onto a suitable non-immunoglobulin protein scaffold or skeleton, such as an affibody, a SpA scaffold, an LDL receptor class A domain, an avimer or an EGF domain. The antibody may be derived from rat, mouse, primate {e.g., cynomolgus, Old World monkey or Great Ape), human or other sources such as nucleic acids generated using molecular biology techniques which encode an antibody molecule.

[0028] The antigen binding protein may comprise a constant region, which may be of any isotype or subclass. The constant region may be of the IgG isotype, for example, IgGi, lgG2, IgGs, lgG4 or variants thereof. The antigen binding protein constant region may be IgGi.

[0029] The antigen binding protein may comprise one or more modifications selected from a mutated constant domain such that the antibody has enhanced effector functions / ADCC and / or complement activation. The antigen binding proteins of the invention can be used in any of the pharmaceutical compositions, dosage regimens, or method of treatments of the invention. The antigen binding proteins can be antibodies, for example I gGi antibodies.

[0030] The term “interleukin-5” or “IL- 5” as used herein includes human IL-5 comprising the amino acid sequence shown in SEQ ID NO: 11.

[0031] The term “interleukin-5 receptor” or “IL-5R” as used herein includes human IL-5 Receptor Subunit Alpha Isoform 1 comprising the amino acid sequence shown in SEQ ID NO: 12.

[0032] The term “binds”, as used herein in relation to antigen binding proteins means that the antigen binding protein binds to a target antigen as well as a discrete domain, or discrete amino acid sequence, within a target antigen with no or insignificant binding to other (for example, unrelated) proteins. This term, however, does not exclude the fact that the antigen binding proteins may also be cross-reactive with closely related molecules (for example, those with a high degree of sequence identity or from another genera or species). The antigen binding proteins described herein may bind to human IL-5 with at least 2, 5, 10, 50, 100, or 1000-fold greater affinity than they bind to closely related molecules.

[0033] By “isolated”, it is intended that the molecule, such as an antigen binding protein, is removed from the environment in which it may be found in nature. For example, the molecule may be purified away from substances with which it would normally exist in nature.

[0034] The terms “VH” and “VL” are used herein to refer to the heavy chain variable region and light chain variable region, respectively, of an antigen binding protein.

[0035] “CDRs” are defined as the complementarity determining region amino acid sequences of an antigen binding protein. These are the hypervariable regions of immunoglobulin heavy and light chains. There are three heavy chain and three light chain CDRs (or CDR regions) in the variable portion of an immunoglobulin. Thus, "CDRs" as used herein refers to all three heavy chain CDRs, all three light chain CDRs, all heavy and light chain CDRs, or at least one CDR and wherein the at least one CDR is CDRH3. Framework regions follow each of these CDR regions. Acceptable heavy chain variable region and light chain variable region framework 1 , framework 2 and framework 3 regions are readily recognized by those of ordinary skill in the art. Acceptable heavy chain constant regions (including hinge regions) and light chain constant regions are readily recognized by those of ordinary skill in the art as well. Acceptable antibody isotypes are similarly readily recognized by those of ordinary skill in the art.

[0036] Throughout this specification, amino acid residues in variable domain sequences and full length antibody sequences are numbered according to the Kabat numbering convention. Similarly, the terms “CDR”, “CDRL1”, “CDRL2”, “CDRL3”, “CDRH1”, “CDRH2”, “CDRH3” used in the specification follow the Kabat numbering convention.

[0037] It will be apparent to those skilled in the art that there are alternative numbering conventions for amino acid residues in variable domain sequences and full length antibody sequences. There are also alternative numbering conventions for CDR sequences, for example those set out according to the Chothia numbering convention. The structure and protein folding of the antibody may mean that other residues are considered part of the CDR sequence and would be understood to be so by a skilled person.

[0038] Other numbering conventions for CDR sequences available to a skilled person include “AbM” (University of Bath) and “contact” (University College London) methods. The minimum overlapping region using at least two of the Kabat, Chothia, AbM and contact methods can be determined to provide the “minimum binding unit”. The minimum binding unit may be a sub-portion of a CDR.

[0039] The term “chronic obstructive pulmonary disease” or “COPD” as used herein means a heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnea, cough, sputum production and / or exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and / or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction.

[0040] A diagnosis of COPD in a subject may be made according to the guidance provided by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) document (2024 update).

[0041] In pulmonary function testing, a post-bronchodilator FEVi / FVC ratio of <0.7 is commonly considered diagnostic for COPD. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) system categorises airflow limitation into stages (see Table 1).

[0042] Table 1. GOLD grades and severity of airflow obstruction in COPP (based on post- bronchodilator FEV1)

[0043] Initial pharmacological treatment of COPD may be based on GOLD ABE category as shown in Table 2 (adapted from GOLD, 2023 update). Table 2. Initial pharmacological treatment based on GOLD ABE category. mMRC: modified Medical Research Council dyspnea questionnaire; CAT: COPD

[0044] Assessment Test

[0045] The term “pharmaceutical composition” as used herein means a composition suitable for administration to a patient.

[0046] The term “therapeutically effective amount” as used herein means an amount of an agent (such as an antigen binding protein or a pharmaceutical composition), which provides a therapeutic benefit in the treatment or management of one or more symptoms of COPD. Examples of such treatment or management of one or more symptoms of COPD include:

[0047] 1) Reduction in annualised rate of moderate or severe COPD exacerbations

[0048] 2) Reduction in the time to first moderate or severe COPD exacerbation

[0049] 3) Reduction in the anualised rate of COPD exacerbations leading to ED visit or hospitalisation

[0050] 4) Change from baseline in St Georges Respiratory Questionnaire (SGRQ) score

[0051] 5) Change from basline in daily symptom scores using the Evaluating Respiratory Symptoms in COPD questionnaire

[0052] Therapeutically effective amounts and treatment regimens are generally determined empirically and may be dependent on factors, such as the age, weight, and health status of the patient and disease or disorder to be treated. Such factors are within the purview of the attending physician.

[0053] As used herein, the term “treatment” refers to ameliorating or stabilising the specified condition, reducing or eliminating the symptoms of the condition, slowing or eliminating the progression of the condition, and preventing or delaying reoccurrence of the condition in a previously afflicted patient or subject. As is recognised in the art, drugs employed as therapeutic agents in methods of treatment may reduce the severity of a given disease state, but need not abolish every manifestation of the disease to be regarded as useful therapeutic agents. Simply reducing the impact of a disease (for example, by reducing the number or severity of its symptoms, or by increasing the effectiveness of another treatment, or by producing another beneficial effect), or reducing the likelihood that the disease will occur (for example by delaying the onset of the disease) or worsen in a subject, is sufficient.

[0054] As used herein, the term "patient" refers to a human. The terms “individual”, “subject” and “patient” are used herein interchangeably. The patient may be an adult (>18 years).

[0055] As used herein, the phrase “once every 6 months” means that in a typical 6 month period consisting of about 183 days, a subject is administered a dose of the antigen binding protein of the invention on one day only and on the other days the subject is not administered a dose of the antigen binding protein of the invention. Administration of once every 6 months may also be referred to as “Q26W” (which refers to administration once every 26 weeks). References herein to “about once every 6 months” refer to an intended dosage regime of once every 6 months, but with the allowance of patient compliance, therefore allowing up to a four week variation depending upon patient scheduling.

[0056] As used herein, the term “annualised rate of exacerbations” refers to the number of COPD exacerbations that occur over a year (i.e., 52-week period). In some cases where the patient follow-up period is more or less than 52 weeks, the number of exacerbations is normalized to an annual rate.

[0057] If desired, the effective dose of an antibody or antigen binding protein of the disclosure (e.g., as a pharmaceutical composition) may be administered as a unit dosage form.

[0058] STATEMENT OF THE INVENTION

[0059] The present invention provides an antigen binding protein which binds to human IL- 5 comprising a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 for use in the treatment of COPD in a patient.

[0060] The present invention provides an antigen binding protein which binds to human IL- 5 comprising a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 for use in the treatment of COPD in a patient, wherein the antigen binding protein is to be administered to the patient at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months.

[0061] The present invention provides a method of treating COPD comprising administering to a patient an antigen binding protein which binds to IL-5 comprising a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months.

[0062] The present invention provides an antigen binding protein which binds to human IL- 5 comprising a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 for use in reducing the exacerbation rate of COPD in a patient, wherein the antigen binding protein is to be administered to the patient at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months.

[0063] The present invention provides a method of reducing the exacerbation rate of COPD comprising administering to a patient an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months. The exacerbation rate may be the annualised rate of moderate or severe COPD exacerbations.

[0064] The present invention provides a method of treating COPD in a patient, the method comprising: a) identifying a patient with COPD; and b) administering about 100 mg to about 300 mg of an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, to the patient about once every 26 weeks or about once every 6 months; whereby the COPD in the patient is treated.

[0065] The present invention also provides methods of decreasing the absolute blood eosinophil count in a COPD patient using the antigen binding protein of the present disclosure. In one embodiment, the method of decreasing the absolute blood eosinophil count in a COPD patient comprises administering to a patient an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months. A decrease in the absolute blood eosinophil count in a COPD patient may be determined by: a) making a first measurement of an absolute blood eosinophil count in the COPD patient; b) making a second measurement of an absolute blood eosinophil count in the COPD patient after administering to the subject a therapeutically effective amount of the antigen binding protein; and c) comparing the first measurement and second measurement to determine effectiveness of therapy.

[0066] In one embodiment, the antigen binding protein comprises a heavy chain variable region sequence having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 3; and / or a light chain variable region sequence having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 4. In one embodiment, the antigen binding protein comprises a heavy chain variable region sequence having at least about 90% identity for example about 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 3; and / or a light chain variable region sequence having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 4, wherein the heavy chain variable region has the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and the light chain variable region has the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10. In one embodiment, the antigen binding protein comprises a heavy chain variable region sequence having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 3; and a light chain variable region sequence having at least about 90% identity for example about 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 4. In one embodiment, the antigen binding protein comprises a heavy chain variable region sequence having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 3; and a light chain variable region sequence having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 4, wherein the heavy chain variable region has the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and the light chain variable region has the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10. In one embodiment, the antigen binding protein comprises a heavy chain variable region sequence having the amino acid sequence shown in SEQ ID NO: 3; and a light chain variable region sequence having the amino acid sequence shown in SEQ ID NO: 4.

[0067] The antigen binding protein may be an antibody. The antigen binding protein may comprise an Fc domain. The antigen binding protein may comprise a heavy chain Fc domain. The antigen binding protein may comprise an IgG 1 , lgG2, lgG3 or lgG4 Fc domain. The antigen binding protein may comprise a human lgG1 , lgG2, lgG3 or lgG4 Fc domain. The antigen binding protein may comprise an IgG 1 Fc domain. The antigen binding protein may comprise a human I gG 1 Fc domain. The antigen binding protein may also comprise a heavy chain Fc domain (e.g., an IgG 1 Fc) comprising a tyrosine residue at position 252, a threonine residue at position 254 and a glutamic acid residue at position 256. The antigen binding protein may comprise a human lgG1 Fc domain comprising a tyrosine residue at position 252, a threonine residue at position 254 and a glutamic acid residue at position 256. The numbering of the amino acids in the heavy chain Fc domain (i.e., a tyrosine residue at position 252, a threonine residue at position 254 and a glutamic acid residue at position 256) was derived using Ell numbering, as described in: Edelman et al. (1969) Proc. Natl. Acad. USA, 63: 78-85 [PMID: 5257969], The antigen binding protein may comprise a human IgG 1 Fc domain comprising a tyrosine residue at position 252 (EU numbering), a threonine residue at position 254 (EU numbering) and a glutamic acid residue at position 256 (EU numbering).

[0068] The antigen binding protein may further comprise a heavy chain FR4 amino acid sequence as shown in SEQ ID NO: 13.

[0069] In one embodiment, the antigen binding protein comprises a heavy chain variable region sequence having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 3; and a light chain variable region sequence having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 4, wherein the heavy chain variable region has the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and the light chain variable region has the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 and wherein the antigen binding protein comprises an lgG1 Fc domain comprising a tyrosine residue at position 252, a threonine residue at position 254 and a glutamic acid residue at position 256.

[0070] In one embodiment, the antigen binding protein comprises a heavy chain having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 1 and a light chain having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity the amino acid sequence shown in SEQ ID NO: 2. In one embodiment, the antigen binding protein comprises a heavy chain having at least about 90% identity for example about 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 1 and a light chain having at least about 90% identity for example about 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity the amino acid sequence shown in SEQ ID NO: 2, wherein the heavy chain has the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and the light chain has the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10. In one embodiment, the antigen binding protein comprises a heavy chain having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity to the amino acid sequence shown in SEQ ID NO: 1 and a light chain having at least about 90% identity for example about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.5%, 100% identity the amino acid sequence shown in SEQ ID NO: 2, wherein the heavy chain has the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and the light chain has the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 and wherein the antigen binding protein comprises an lgG1 Fc domain comprising a tyrosine residue at position 252, a threonine residue at position 254 and a glutamic acid residue at position 256. In one embodiment, the antigen binding protein comprises a heavy chain having the amino acid sequence shown in SEQ ID NO: 1 and a light chain having the amino acid sequence shown in SEQ ID NO: 2.

[0071] In one embodiment, the antigen binding protein is depemokimab.

[0072] The dose of antigen binding protein may be about 300 mg. The antigen binding protein may be administered to the patient at a dose of about 300 mg once every 26 weeks or once every 6 months. The antigen binding protein may be administered to the patient at a dose of about 300 mg once every 26 weeks. The dose of antigen binding protein may be about 100 mg to about 200 mg. The antigen binding protein may be administered to the patient at a dose of about 100 mg to about 200 mg once every 26 weeks or once every 6 months. The antigen binding protein may be administered to the patient at a dose of about 100 mg to about 200 mg once every 26 weeks. The dose of antigen binding protein may be about 200 mg. The antigen binding protein may be administered to the patient at a dose of about 200 mg once every 26 weeks or once every 6 months. The antigen binding protein may be administered to the patient at a dose of about 200 mg once every 26 weeks. The dose of antigen binding protein may be about 100 mg. The antigen binding protein may be administered to the patient at a dose of about 100 mg once every 26 weeks or once every 6 months. The antigen binding protein may be administered to the patient at a dose of about 100 mg once every 26 weeks. The dose of antigen binding protein may be 100 mg. The antigen binding protein may be administered to the patient at a dose of 100 mg once every 26 weeks or once every 6 months. The antigen binding protein may be administered to the patient at a dose of 100 mg once every 26 weeks.

[0073] In one embodiment, an effective amount of antigen binding protein is to be administered subcutaneously to the patient.

[0074] In one embodiment, depemokimab is for use in the treatment of chronic obstructive pulmonary disease (COPD) in a patient, wherein depemokimab is to be administered subcutaneously to the patient at a dose of 100 mg once every 26 weeks.

[0075] In one embodiment, the patient is an adult. In one embodiment, the patient is an adult > 40 years of age. In one embodiment, the patient is an adult >40 to <75 years of age. In one embodiment, the patient is an adult > 40 to <80 years of age.

[0076] In one embodiment, the patient has COPD with type 2 inflammation. In one embodiment, the patient has moderate to severe COPD with type 2 inflammation. In one embodiment, the patient has COPD with type 2 inflammation characterised by an eosinophilic phenotype. In one embodiment, the patient has COPD with an eosinophilic phenotype. In one embodiment, the patient has moderate to severe COPD with an eosinophilic phenotype.

[0077] In one embodiment, the patient has symptoms of chronic bronchitis. In one embodiment, the patient does not have symptoms of chronic bronchitis. Chronic bronchitis may refer to having cough and phlegm for 3 or more months each year over the past 24 months, in the absence of other known cause of chronic cough. Chronic bronchitis may refer to having cough and phlegm for 3 or more months each year over the past 12 months, in the absence of other known cause of chronic cough.

[0078] In one embodiment, the patient is receiving maintenance therapy, optionally triple inhaled maintenance therapy. In one embodiment, the patient is receiving triple inhaled maintenance therapy at least 6 months prior to treatment. In one embodiment, the patient is on an ICS containing maintenance therapy, optionally triple or dual inhaler therapy.

[0079] In one embodiment, the patient has at least 2 moderate exacerbations in the 12 months prior to treatment. In one embodiment, the patient has at least 3 moderate exacerbations in the 12 months prior to treatment. In one embodiment, the patient has at least 4 moderate exacerbations in the 12 months prior to treatment. In one embodiment, the patient has at least 1 severe exacerbation in the 12 months prior to treatment.

[0080] In one embodiment, the COPD is uncontrolled COPD. In one embodiment, the patient has uncontrolled moderate to severe COPD with an eosinophilic phenotype. In one embodiment, the COPD is uncontrolled COPD defined by at least 2 moderate or at least 1 severe exacerbation in the 12 months prior to treatment. In one embodiment, the patient has uncontrolled COPD defined by at least 2 moderate or at least 1 severe exacerbation in the 12 months prior to treatment and has an eosinophilic phenotype. In one embodiment, the patient has inadequately controlled COPD and an eosinophilic phenotype.

[0081] Moderate exacerbations may be clinically significant exacerbations that require treatment with oral / systemic corticosteroids and / or antibiotics. Severe exacerbations may be clinically significant exacerbations that require in-patient hospitalization / emergency room (i.e., >24 hrs) or result in death.

[0082] In one embodiment, the patient has an elevated blood eosinophil count prior to treatment. In one embodiment, the patient has a persistently elevated blood eosinophil count prior to treatment. In one embodiment, the patient has a blood eosinophil count of >150 cells / pl. In one embodiment, the patient has a blood eosinophil count of >200 cells / pl. In one embodiment, the patient has a blood eosinophil count of >250 cells / pl. In one embodiment, the patient has a blood eosinophil count of >270 cells / pl. In one embodiment, the patient has a blood eosinophil count of >300 cells / pl. In one embodiment, the patient has a blood eosinophil count of >400 cells / pl. In one embodiment, the patient has a blood eosinophil count of >500 cells / pl. In one embodiment, the patient has a blood eosinophil count of >150 cells / pl prior to treatment. In one embodiment, the patient has a blood eosinophil count of >200 cells / pl prior to treatment. In one embodiment, the patient has a blood eosinophil count of >250 cells / pl prior to treatment. In one embodiment, the patient has a blood eosinophil count of >270 cells / pl prior to treatment. In one embodiment, the patient has a blood eosinophil count of >300 cells / pl prior to treatment. In one embodiment, the patient has a blood eosinophil count of >400 cells / pl prior to treatment. In one embodiment, the patient has a blood eosinophil count of >500 cells / pl prior to treatment.

[0083] In one embodiment, the patient has a blood eosinophil count of >150 cells / pl in the past 12 months. In one embodiment, the patient has (i) a blood eosinophil count of >300 cells / pl and (ii) a blood eosinophil count of >150 cells / pl in the past 12 months. In one embodiment, the patient has (i) a blood eosinophil count of >300 cells / pl prior to treatment and (ii) a blood eosinophil count of >150 cells / pl in the past 12 months.

[0084] In one embodiment, the patient has an eosinophilic phenotype with elevated blood eosinophil count at two timepoints at least 14 days apart. In one embodiment, the patient has (i) a blood eosinophil count of >300 cells / pl and (ii) a blood eosinophil count of >150 cells / pl, wherein the blood eosinophil counts are measured at least 14 days apart.

[0085] In one embodiment, the patient has a blood eosinophil count of >300 cells / pl in the past 12 months. In one embodiment, the patient has (i) a blood eosinophil count of >300 cells / pl in the past 12 months and (ii) a blood eosinophil count of >270 cells / pl at screening. In one embodiment, the patient has (i) a blood eosinophil count of >300 cells / pl in the past 12 months and (ii) a blood eosinophil count of >270 cells / pl prior to treatment.

[0086] In one embodiment, the COPD is according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). In one embodiment, the patient has GOLD E COPD. In one embodiment, the patient has moderate, severe or very severe COPD. In one embodiment, the patient has moderate COPD. In one embodiment, the patient has severe COPD. In one embodiment, the patient has moderate to severe COPD. In one embodiment, the patient has very severe COPD. In one embodiment, the patient has a high exacerbation risk. In one embodiment, the patient has a high exacerbation risk defined by at least 2 moderate or at least 1 severe exacerbation. In one embodiment, the patient has at least 2 moderate or 1 severe exacerbation in the past 12 months. In one embodiment, the patient has at least 2 moderate or 1 severe exacerbation in the 12 months prior to treatment. In one embodiment, the patient has GOLD A / B COPD. In one embodiment, the patient has 1 moderate exacerbation in the past 12 months. In one embodiment, the patient has 1 moderate exacerbation in the 12 months prior to treatment. In one embodiment, the patient has 1 moderate exacerbation in the past 12 months and has an elevated risk for exacerbations.

[0087] In one embodiment, moderate to severe COPD may be defined as:

[0088] • A clinically documented history of COPD as defined by the American Thoracic Society / European Respiratory Society for at least 1 year.

[0089] • A post-salbutamol FEV1 / FVC ratio of <0.70 and a post-salbutamol FEV1 >30% and <80% predicted normal values calculated with GLI-Global Race Neutral equations [Bowerman, 2023],

[0090] In one embodiment, the patient has moderate to severe COPD with frequent exacerbations. Moderate to severe COPD with frequent exacerbations may be defined as:

[0091] • A clinically documented history of COPD as defined by the American Thoracic Society / European Respiratory Society for at least 1 year

[0092] • A post-salbutamol FEV1 / FVC ratio of <0.70 and a post-salbutamol FEV1 >30% and <80% predicted normal values calculated with GLI-Global Race Neutral equations in line with the ATS recommendations (Bowerman, 2023)

[0093] • A well-documented history (e.g., medical record verification, including capturing of all prior biologic use) of at least 2 moderate or 1 severe exacerbation in the past 12 months: i. At least one qualifying exacerbation must have occurred while participant is on ICS plus LAMA plus LABA ii. Moderate exacerbations must have been treated with systemic corticosteroids iii. Severe exacerbations are those requiring hospitalization or observation

[0094] >24 hours in ED / urgent care facility.

[0095] In one embodiment, the patient has moderate to severe COPD with an elevated risk for exacerbations. An elevated risk for exacerbations may be defined as:

[0096] • A well-documented history (e.g., medical record verification) of only 1 moderate COPD exacerbation in the past 12 months. To qualify, this exacerbation must have been treated with systemic corticosteroids (with or without antibiotics) and must have occurred while the participant was on the same optimized background COPD therapy regimen.

[0097] AND

[0098] • The presence of at least 1 risk factor for future exacerbations / deterioration: o mMRC dyspnea score > 2 o CAT > 15 o Post-bronchodilator FEV1 < 50% predicted o Chronic bronchitis, defined as frequent cough and sputum production for at least 3 months in the past 12 months

[0099] In one embodiment, the patient has a CAT score of >10.

[0100] In one embodiment, the patient does not have asthma. In one embodiment, the patient does not have a past history or concurrent diagnosis of asthma. In one embodiment, the patient may have had childhood asthma that has resolved before the age of 18 years and has not recurred.

[0101] In one embodiment, the patient is a current smoker. In one embodiment, the patient is a former smoker. In one embodiment, the patient is a current or former cigarette smoker with a history of cigarette smoking of >10 pack-years. Former smokers may be defined as those who have stopped all smoking (including tobacco, marijuana, or e-cigarettes) for at least 6 months.

[0102] In one embodiment, the patient has a modified Medical Research Council (mMRC) score of less than 2. In one embodiment, the patient has a modified Medical Research Council (mMRC) score of at least 2.

[0103] In one embodiment, the patient is on COPD maintenance therapy. In one embodiment, the patient is on optimized inhaler therapy, optionally ICS plus LABA or LABA plus LAMA either as multiple inhalers or a single combination inhaler. In one embodiment, the patient is on optimized inhaler therapy, optionally ICS plus LAMA plus LABA either as multiple inhalers or a single combination inhaler. In one embodiment, the patient may be on adjunctive COPD therapies such as chronic macrolide antibiotics, PDE4 or PDE3-4 inhibitors, or chronic oral corticosteroids (up to 15 mg prednisone equivalent per day). In one embodiment, the patient does not have any other clinically significant lung disease.

[0104] In one embodiment, the patient has not previously been exposed to therapy targeting IL-5, IL-5R, IL-4R, IL-13, IL-33 or TSLP. In one embodiment, the patient has not previously been exposed to therapy targeting IL-5, IL-5R, IL-4R, IL-13, IL-33 or TSLP within 6 months or 5 half-lives. The therapy targeting IL-5, IL-5R, IL-4R, IL-13, IL-33 or TSLP may be a mAb.

[0105] In one embodiment, the antigen binding protein improves one or more symptoms of COPD. In one embodiment, the antigen binding protein results in one or more of the following:

[0106] 1) Reduction in annualised rate of moderate or severe COPD exacerbations

[0107] 2) Reduction in the time to first moderate or severe COPD exacerbation

[0108] 3) Reduction in the anualised rate of COPD exacerbations leading to emergency department (ED) visit or hospitalisation

[0109] 4) Change from baseline in St Georges Respiratory Questionnaire (SGRQ) score

[0110] 5) Change from basline in daily symptom scores using the Evaluating Respiratory Symptoms in COPD questionnaire

[0111] 6) Change from baseline in Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS: COPD) total score

[0112] The SGRQ total score may be measured using the SGRQ for COPD [SGRQ-C]. The SGRQ-C is a 40-item participant questionnaire, designed to measure health impairment by addressing the frequency of respiratory symptoms (questions 1-7) and the participant’s current state (questions 8-14). The questions are designed to be self-completed by the participant. The total score will be calculated by the symptoms, activity and impact score; and summarizing the impact of the disease on 0-100 rating scale and scores expressed as a percentage of overall impairment. Higher scores indicate greater impairment of health.

[0113] E-RS: COPD consists of 11 items from the 14-item Exacerbations of Chronic Pulmonary Disease Tool - Patient Reported Outcomes (EXACT) instrument. E-RS: COPD is intended to capture information related to the respiratory symptoms of COPD, i.e., breathlessness, cough, sputum production, chest congestion, and chest tightness. The E-RS: COPD has a scoring range of 0 to 40, higher scores indicate more severe symptoms.

[0114] PHARMACEUTICAL COMPOSITION

[0115] In one embodiment, the antigen binding protein may be formulated within a pharmaceutical composition. In one embodiment, the pharmaceutical composition comprises the antigen binding protein and a pharmaceutically acceptable excipient. In one embodiment, the pharmaceutical composition comprises an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, and a pharmaceutically acceptable excipient.

[0116] In one embodiment, the pharmaceutical composition comprises about 100 mg to about 300 mg of the antigen binding protein, and a pharmaceutically acceptable excipient. In one embodiment, the pharmaceutical composition comprises about 100 mg to about 300 mg of an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, and a pharmaceutically acceptable excipient. In one embodiment, the pharmaceutical composition comprises about 100 mg of the antigen binding protein, and a pharmaceutically acceptable excipient. In one embodiment, the pharmaceutical composition comprises about 100 mg of an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, and a pharmaceutically acceptable excipient.

[0117] In one embodiment, the pharmaceutical composition comprises the antigen binding protein and an aqueous liquid formulation at about pH 6.0 comprising histidine, trehalose, arginine, EDTA and / or polysorbate 80. In one embodiment, the pharmaceutical composition comprises the antigen binding protein and an aqueous liquid formulation at about pH 6.0 comprising histidine, trehalose, arginine, EDTA and polysorbate 80. In one embodiment, the pharmaceutical composition comprises the antigen binding protein and an aqueous liquid formulation at about pH 6.0 comprising about 20 mM histidine, about 180 mM trehalose, about 40 mM arginine, about 0.05 mM EDTA and about 0.02% weight of polysorbate 80 to volume. In one embodiment, the pharmaceutical composition comprises an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 and an aqueous liquid formulation at about pH 6.0 copmrising about 20 mM histidine, about 180 mM trehalose, about 40 mM arginine, about 0.05 mM EDTA and about 0.02% weight of polysorbate 80 to volume. In one embodiment, the pharmaceutical composition comprises about 100 mg to about 300 mg of an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 and an aqueous liquid formulation at about pH 6.0 copmrising about 20 mM histidine, about 180 mM trehalose, about 40 mM arginine, about 0.05 mM EDTA and about 0.02% weight of polysorbate 80 to volume. In one embodiment, the pharmaceutical composition comprises about 100 mg of an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 and an aqueous liquid formulation at about pH 6.0 copmrising about 20 mM histidine, about 180 mM trehalose, about 40 mM arginine, about 0.05 mM EDTA and about 0.02% weight of polysorbate 80 to volume.

[0118] Pharmaceutical compositions may be presented in unit dose forms containing a predetermined amount of active ingredient per unit dose. Preferred unit dosage compositions are those containing the dose for an entire day or sub-dose, or an appropriate fraction thereof, of an active ingredient. Unit doses that contain a sub-dose of the recommended dose for a day may therefore be administered more than once in order to make up the total dose for a day. For example, if a dose on a particular day is 100 mg, this may be contained in one unit or in multiple units (e.g. 2 units each comprising 50 mg of active ingredient). In one embodiment, the pharmaceutical composition is in unit dosage form. PRE-FILLED SYRINGES

[0119] The disclosure also provides a pre-filled syringe comprising about 100mg to about 300 mg of an antigen binding protein of the disclosure. In one embodiment, there is provided a pre-filled syringe comprising a pharmaceutical composition as disclosed herein.

[0120] In one embodiment, the pre-filled syringe comprises about 100 mg to about 300 mg of antigen binding protein. In one embodiment, the pre-filled syringe comprises about 100 mg of antigen binding protein. In one embodiment, the pre-filled syringe comprises a pharmaceutical composition, wherein the pharmaceutical composition comprises the antigen binding protein and a pharmaceutically acceptable excipient.

[0121] In one embodiment, the pre-filled syringe is provided in a safety syringe device (SSD) or an autoinjector. Such devices are well known to a person skilled in the art.

[0122] CLAUSES

[0123] In summary, the disclosure includes:

[0124] 1. An antigen binding protein which binds to human IL-5 comprising a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 for use in the treatment of chronic obstructive pulmonary disease (COPD) in a patient, wherein the antigen binding protein is to be administered to the patient at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months.

[0125] 2. An antigen binding protein which binds to human IL-5 comprising a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 for use in reducing the exacerbation rate of COPD in a patient, wherein the antigen binding protein is to be administered to the patient at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months.

[0126] 3. The antigen binding protein for use according to clause 1 or 2, wherein the antigen binding protein comprises a heavy chain variable region sequence having at least about 90% identity to the amino acid sequence shown in SEQ ID NO: 3 and a light chain variable region sequence having at least about 90% identity to the amino acid sequence shown in SEQ ID NO: 4.

[0127] 4. The antigen binding protein for use according to any one of clauses 1-3, wherein the antigen binding protein comprises a heavy chain variable region sequence having the amino acid sequence shown in SEQ ID NO: 3 and a light chain variable region sequence having the amino acid sequence shown in SEQ ID NO: 4.

[0128] 5. The antigen binding protein for use according to any one of clauses 1 to 4, wherein the antigen binding protein is an antibody.

[0129] 6. The antibody for use according to clause 5, wherein the antibody comprises an I gG 1 Fc domain, optionally a human IgG 1 Fc domain.

[0130] 7. The antibody for use according to clause 6, wherein the IgG 1 Fc domain comprises a tyrosine residue at position 252, a threonine residue at position 254 and a glutamic acid residue at position 256.

[0131] 8. The antibody for use according to clause 7, wherein the antibody comprises a heavy chain having the amino acid sequence shown in SEQ ID NO: 1 and a light chain having the amino acid sequence shown in SEQ ID NO: 2.

[0132] 9. The antibody for use according to clause 8, wherein the antibody is depemokimab.

[0133] 10. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0134] 9, wherein the dose is about 100 mg, optionally 100 mg.

[0135] 11 . The antigen binding protein or antibody for use according to any one of clauses 1 to

[0136] 10, wherein the antigen binding protein or antibody is to be administered once every 26 weeks.

[0137] 12. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0138] 11 , wherein the antigen binging protein or antibody is depemokimab and wherein depemokimab is to be administered to the patient at a dose of 100 mg once every 26 weeks.

[0139] 13. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0140] 12, wherein the antigen binding protein or the antibody is to be administered subcutaneously to the patient.

[0141] 14. The antigen binding protein or antibody for use according to clause 13, wherein the antigen binding protein or the antibody is to be administered in a pre-filled syringe, optionally a safety syringe device (SSD) or an autoinjector.

[0142] 15. The antigen binding protein or antibody for use according to any one of clauses 1 to 14, wherein the antigen binding protein or antibody is in a pharmaceutical composition.

[0143] 16. The antigen binding protein or antibody for use according to clause 15, wherein the pharmaceutical composition comprises the antigen binding protein or antibody and an aqueous liquid formulation at about pH 6.0 comprising histidine, trehalose, arginine, EDTA and / or polysorbate 80.

[0144] 17. The antigen binding protein or antibody for use according to clause 16, wherein the pharmaceutical composition comprises the antigen binding protein or antibody and an aqueous liquid formulation at about pH 6.0 comprising about 20 mM histidine, about 180 mM trehalose, about 40 mM arginine, about 0.05 mM EDTA and about 0.02% weight of polysorbate 80 to volume.

[0145] 18. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0146] 17, wherein the COPD is moderate to severe COPD.

[0147] 19. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0148] 18, wherein the COPD is uncontrolled COPD.

[0149] 20. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0150] 19, wherein the patient has at least 2 moderate or at least 1 severe exacerbation in the 12 months prior to treatment.

[0151] 21 . The antigen binding protein or antibody for use according to any one of clauses 1 to 18, wherein the patient has an elevated risk for exacerbations.

[0152] 22. The antigen binding protein or antibody for use according to clause 21 , wherein the patient has 1 moderate exacerbation in the 12 months prior to treatment.

[0153] 23. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0154] 22, wherein the patient has type 2 inflammation.

[0155] 24. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0156] 23, wherein the patient has a blood eosinophil count of >150 cells / pl.

[0157] 25. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0158] 24, wherein the patient has a blood eosinophil count of >200 cells / pl.

[0159] 26. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0160] 25, wherein the patient has a blood eosinophil count of >250 cells / pl.

[0161] 27. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0162] 26, wherein the patient has a blood eosinophil count of >270 cells / pl.

[0163] 28. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0164] 27, wherein the patient has a blood eosinophil count of >300 cells / pl.

[0165] 29. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0166] 28, wherein the patient has not previously been exposed to therapy targeting IL-5, IL-5R, IL-4R, IL-13, IL-33 or TSLP.

[0167] 30. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0168] 29, wherein the COPD is according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). 31 . The antigen binding protein or antibody for use according to clause 30, wherein the patient has GOLD E COPD or GOLD A / B COPD.

[0169] 32. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0170] 31 , wherein the patient is an adult.

[0171] 33. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0172] 32, wherein the absolute blood eosinophil count in the COPD patient is reduced.

[0173] 34. The antigen binding protein or antibody for use according to any one of clauses 1 to

[0174] 33, wherein the patient’s COPD symptoms are improved.

[0175] 35. A method of treating COPD comprising administering to a patient an antigen binding protein which binds to human IL-5 comprising a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months.

[0176] 36. A method of reducing the exacerbation rate of COPD comprising administering to a patient an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months.

[0177] 37. A method of treating COPD in a patient, the method comprising: a) identifying a patient with COPD; and b) administering about 100 mg to about 300 mg of an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, to the patient about once every 26 weeks or about once every 6 months; whereby the COPD in the patient is treated. 38. A method of decreasing the absolute blood eosinophil count in a COPD patient comprising administering to a patient an antigen binding protein which binds to IL-5, wherein the antigen binding protein comprises a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10, at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months.

[0178] 39. The method according to any one of clauses 35 to 38, wherein the antigen binding protein comprises a heavy chain variable region sequence having the amino acid sequence shown in SEQ ID NO: 3 and a light chain variable region sequence having the amino acid sequence shown in SEQ ID NO: 4.

[0179] 40. The method according to any one of clauses 35 to 39, wherein the antigen binding protein comprises a heavy chain having the amino acid sequence shown in SEQ ID NO: 1 and a light chain having the amino acid sequence shown in SEQ ID NO: 2.

[0180] 41. The method according to any one of clauses 35 to 40, wherein the dose is about 100 mg, optionally 100 mg.

[0181] 42. The method according to one of clauses 35 to 41 , wherein the antigen binding protein is administered once every 26 weeks.

[0182] 43. The method according to any one of clauses 35 to 42, wherein the COPD is moderate to severe COPD.

[0183] 44. The method according to any one of clauses 35 to 43, wherein the COPD is uncontrolled COPD.

[0184] 45. The method according to any one of clauses 35 to 43, wherein the patient has an elevated risk for exacerbations.

[0185] EXAMPLES

[0186] EXAMPLE 1 : Modelling to investigate dosing for chronic obstructive pulmonary disease (COPP) study

[0187] The proposed depemokimab dose and dosing frequency of 100 mg every 26 weeks for the Phase 3 study in COPD was identified using model-informed drug development (MIDD) principles.

[0188] The desired blood eosinophils pharmacology was informed by the two pivotal Phase 3 trials with mepolizumab. Depemokimab targets the same IL5 epitope as mepolizumab. In the mepolizumab pivotal Phase 3 trials in COPD, the steady-state eosinophils reduction compared to baseline was 83% following mepolizumab 100 mg SC administered every 4 weeks. This reduction translated into geometric mean (95% PI) of blood eosinophils count at week 52 equal to 50 (9-279) cells / uL in the cohort receiving mepolizumab 100 mg SC administered every 4 weeks. This level of pharmacology was associated with clinical efficacy. In METREX Phase 3 pivotal study, the mean annual rate of moderate or severe exacerbations was 1.40 per year in the mepolizumab group versus 1.71 per year in the placebo group. In METREO Phase 3 pivotal study the mean annual rate of moderate or severe exacerbations was 1.19 per year in the 100-mg mepolizumab group, 1.27 per year in the 300-mg mepolizumab group and 1.49 per year in the placebo group. Overall, patients with an eosinophilic phenotype who were treated with 100 mg of mepolizumab had an annual rate of moderate or severe exacerbations that was consistently 18% to 20% lower than that among patients who received placebo. There was no evidence of greater effects of mepolizumab at higher doses.

[0189] The PK-blood eosinophils model used to support depemokimab dose selection is an updated model based on the indirect exposure - eosinophil model developed on data from 16 mepolizumab studies that collected pharmacokinetic samples, blood eosinophil count measurements and covariates during mepolizumab clinical development in various eosinophilic conditions and in healthy subjects. The model was parameterised in terms of baseline blood eosinophils (KRO), rate of elimination (KOUT), maximum inhibitory effect (Imax), concentration resulting in 50% of maximum inhibitory drug effect (IC50), and Hill coefficient (GAMA). Between subject variability was included on baseline blood eosinophil and maximum drug effect using an exponential model. Measured baseline blood eosinophil count was a covariate of KRO and Imax. Disease was covariates for KRO. This model was updated, maintaining the same model structure, to reflect the longer half-life and enhanced potency of depemokimab compared to mepolizumab. The model IC50 parameter, the between subject variability and the residual unexplained variability were estimated based on PK and eosinophil data from the single ascending dose Phase 1 Study with depemokimab in mild to severe asthma. The impact of the baseline eosinophil levels on the maximum achievable drug inhibitory response and on model-predicted baseline blood eosinophils was assumed to be the same between mepolizumab and depemokimab.

[0190] Simulation of depemokimab PK-blood eosinophils was based on the depemokimab PK model developed on data from depemokimab Phase 1 study and on the updated PK- blood eosinophils model. Simulated eosinophil levels at baseline reflected the geometric mean value in the subject of participants with baseline blood eosinophil count > 300 cells / pL observed in the Phase 3 mepolizumab COPD trials (Pavord et al. N Engl J Med 2017;377:1613-1629)

[0191] The dose and dosing frequency of depemokimab were selected to match Phase 3 mepolizumab-like blood eosinophil pharmacology in the same COPD population. Parameters were sampled from a multivariate normal distribution, centred on the estimated parameter values, with covariance reflecting the uncertainty of parameter estimates. Residual unexplained variability was included in the simulation. Results were summarised in terms of geometric mean and standard deviation of logs and 95% prediction interval.

[0192] EXAMPLE 2: Phase III COPD study of depemokimab (ENDURA-1 and ENDURA-2)

[0193] Two, randomized, double-blind, placebo-controlled, parallel group, multicentre studies will evaluate the efficacy and safety of depemokimab in adult patients with COPD with type 2 inflammation.

[0194] The aim of these studies is to investigate the efficacy and safety of depemokimab 100 mg SC given Q26W for a minimum of 52 weeks and a maximum of 104 weeks treatment period, as an add-on therapy in participants with uncontrolled moderate to severe COPD with an eosinophilic phenotype.

[0195] Study inclusion criteria require a BEC of >300 cells / pL at Screening Visit 0 or Visit 1 as well as an additional BEC of >150 cells / pL (either historical in the previous 12 months or taken during screening). If a participant does not meet the eligibility cut-off for BEC criteria, up to 2 retests are permitted prior to Visit 2. Participants must have a history of regular use of triple maintenance COPD therapy (as defined in Inclusion Criteria) for at least 6 months prior to Screening Visit 1 . Participants are also required to have a history of at least 2 moderate COPD exacerbations that were treated with systemic corticosteroids (IM, IV or oral), or at least 1 severe exacerbation requiring hospitalization in the 12 months prior to Screening Visit 1 and at least one of the exacerbations must have occurred while treated with ICS plus LAMA plus LABA.

[0196] All participants will continue optimized maintenance inhaled COPD therapy throughout the entire duration of the study regardless of intervention arm assignment.

[0197] Excluding screening and run-in periods, participants will remain in the study for at least 52 weeks and either up to 78 or 104 weeks, whichever visit aligns to the date of the last randomized participant is scheduled to complete their Week 52. The timing of the last randomized participant into the study will thus affect the timing of the Exit Visit for participants enrolled beyond 52 weeks. All participants will be expected to complete at least 52 weeks of the study. The last randomized participant will be scheduled to complete only 52 weeks of the study.

[0198] The study will consist of a screening Visit 0 and Visit 1 , a run-in period (>14 days) and a study intervention period (minimum 52 weeks and maximum of 104 weeks). After the run-in period, participants will be randomised 2:1 to receive either up to four doses of depemokimab 100 mg (Q26W), or placebo by subcutaneous (SC) injection. The doses of study intervention will be administered in the clinic and after all scheduled assessments are complete: the first dose at randomization visit (Visit 2, Week 0, Day 1), the second at Visit 9 (Week 26), the third and fourth doses will be administered at Visit 16 (Week 52) and Visit 22 (Week 78). Participants will be assessed at each scheduled visit (16 study visits) during the 52-Week treatment phase and for an additional 12 visits from Week 52 to Week 104.

[0199] If the participant has a qualifying historical BEC >150 cells / pL, Visit 0 may occur anytime from 0 to 28 days (0 to 4 weeks) before Visit 1. If the participant does not have a qualifying historical BEC, Visit 0 and Visit 1 must occur at least 14 days apart to allow for the appropriate time between eosinophil measurements. Assessments may be conducted at Visit 1 if not conducted at Visit 0.

[0200] Randomization Visit 2 must be performed at least 14 days after the start of Screening Visit 1. Results from Screening Visit 1 procedures must be available for review of randomization criteria. To be randomized, participants must demonstrate having elevated BEC at two timepoints (>300 cells / pL for one timepoint and >150 cells / pL for the other) at least 14 days apart.

[0201] The primary outcome variable will be annualized rate of moderate or severe COPD exacerbations. In addition, other efficacy measures will be time to first moderate / severe COPD exacerbation, quality of life using the St Georges Respiratory Questionnaire (SGRQ) for COPD (SGRQ-C) i.e. change from baseline in SGRQ total score (measured using the SGRQ-C) at Week 52, daily symptom scores using the Evaluating Respiratory Symptoms in COPD (E-RS:COPD) questionnaire i.e. change from baseline in E-RS: COPD total score at Week 52, the annualized rate of COPD exacerbations leading the Emergency

[0202] Department (ED) visit or hospitalization, and annualized rate of severe exacerbations.

[0203] Objectives and endpoints are summarised below: Objectives and endpoints for pre-specified pooled analysis is summarised below:

[0204] • Participants are eligible to be included in the study only if all of the following criteria apply: Participants must be >40 to <80 years of age, at the time of signing the informed consent form. • An eosinophilic phenotype with elevated BEC at two timepoints at least 14 days apart o If the participant has a documented historical BEC of >150 cells / pL in the 12 months prior to Screening Visit 0, they must have at least one additional BEC of >300 cells / pL from a sample collected at Screening Visit 0 or Screening Visit 1.

[0205] OR o If historical BEC is not available, the participant must have at least one BEC >300 cells / pL and the other >150 cells / pL among the samples collected at Screening Visit 0 or Screening Visit 1 .

[0206] • Moderate to severe COPD with frequent exacerbations, defined as: o A clinically documented history of COPD as defined by the American Thoracic Society / European Respiratory Society for at least 1 year o A post-salbutamol FEV1 / FVC ratio of <0.70 and a post-salbutamol FEV1 >30% and <80% predicted normal values calculated with GLI-Global Race Neutral equations in line with the ATS recommendations (Bowerman, 2023) at screening o A well-documented history (e.g., medical record verification, including capturing of all prior biologic use) of at least 2 moderate or 1 severe exacerbation in the 12 months prior to screening

[0207] ■ At least one qualifying exacerbation must have occurred while participant is on ICS plus LAMA plus LABA

[0208] ■ Moderate exacerbations must have been treated with systemic corticosteroids

[0209] ■ Severe exacerbations are those requiring hospitalization or observation >24 hours in ED / urgent care facility

[0210] • CAT score >10 at Visit 1 .

[0211] • Smoking status: Current or former cigarette smokers with a history of cigarette smoking of >10 pack-years at Screening. Former smokers are defined as those who have stopped all smoking (including tobacco, marijuana, or e-cigarettes) for at least 6 months prior to Screening Visit 1 .

[0212] • Participants should be on optimized inhaler therapy, defined as ICS plus LAMA plus LABA either as multiple inhalers or a single combination inhaler* for at least 6 months prior to Screening Visit 1.

[0213] *Note: Where intolerance or safety risk is documented for ICS, dual therapy LABA plus LAMA is allowed with prior discussion with the study medical monitor.

[0214] • Participants on adjunctive COPD therapies such as chronic macrolide antibiotics, PDE4 or PDE3-4 inhibitors, or chronic oral corticosteroids (up to 15 mg prednisone equivalent per day) may participate, provided they have been on these medications for 6 months, and on a stable dose for at least 3 months immediately prior to Screening Visit 1. These participants should remain on these therapies for the duration of the study.

[0215] • BMI >16 kg / m2

[0216] • Male or eligible female. o A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:

[0217] ■ Is a woman of non-childbearing potential (WONCBP), OR

[0218] ■ Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, from at least 14 days prior to the first dose of study intervention until at least 35 weeks after the last administered dose of study intervention.

[0219] • Capable of giving signed informed consent.

[0220] Participants are excluded from the study if any of the following criteria apply:

[0221] • Patients with a current or prior physician diagnosis of asthma* are excluded.

[0222] *A diagnosis of asthma should be based on both a history of typical respiratory symptoms combined with evidence of variable expiratory airflow limitation at the time of diagnosis consistent with GINA 2024 or other accepted guidelines.

[0223] • Other clinically significant lung disease: The Investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease. Participants with a1 -antitrypsin deficiency as the underlying cause of COPD are excluded. Also excluded are participants with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases.

[0224] • COPD stability: Participants with pneumonia, COPD exacerbation, or lower respiratory tract infection within the 4 weeks prior to Screening Visit 1 are excluded.

[0225] • Lung resection: Participants with a history of, or plan for lung volume reduction surgery I endobronchial valve procedure are excluded.

[0226] • Pulmonary rehabilitation: Participants in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening Visit 1 are excluded. Participants who are in the maintenance phase of a pulmonary rehabilitation program may participate. • Continuous oxygen: Patients requiring oxygen supplementation for more than 12 hours per day are excluded. Non-continuous (i.e., 12 hours or less per day) oxygen is permitted up to 2 L / min at screening.

[0227] • Cor pulmonale - resulting in right heart failure, severe pulmonary hypertension are excluded.

[0228] • Chronic hypercapnia requiring NIPPV use (including BiPAP or CPAP) are excluded.

[0229] • Unstable cardiovascular disease or arrhythmia.

[0230] • Vasculitis: Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis must be excluded prior to enrolment.

[0231] • Eosinophilic disease: Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic syndromes including EGPA (also known as Churg-Strauss Syndrome), or Eosinophilic Esophagitis.

[0232] • Parasitic Infection: Participants with a known, pre-existing parasitic infection within 6 months of Screening (Visit 1).

[0233] • Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to Screening Visit 1 (Participants that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded).

[0234] • Immunodeficiency: A known immunodeficiency other than that explained by use of corticosteroids (e.g., HIV).

[0235] • Liver disease: Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.

[0236] NOTE: Stable non-cirrhotic liver disease (including Gilbert’s syndrome, asymptomatic gallstones, and chronic stable hepatitis B (in whom HDV has been excluded) or C are acceptable if participant otherwise meets entry criteria

[0237] • Other concurrent medical condition: Participants with (historical or) current evidence of clinically significant, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Clinically significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or which could affect the efficacy or safety analysis if the disease / condition exacerbated during the study.

[0238] • Previous exposure to mAb(s) targeting IL-5 / 5R, I L-4R / I L-13, IL-33, or TSLP within 6 months or 5 half-lives (whichever is longer), prior to Screening Visit 1. • Previous documented treatment failure or non-response to anti-IL-5 / 5R or anti-IL- 4R / IL-13 therapy.

[0239] • Other mAbs: Participants who have received any mAb within 5 half-lives of Screening Visit 1.

[0240] • Investigational medications: Participants who have received an investigational drug within 30 days of Screening Visit 1 , or within 5 drug half-lives of the investigational drug, whichever is longer (this also includes investigational formulations of a marketed product).

[0241] • Oral corticosteroids: Participants who have received short term use of oral corticosteroids within 4 weeks of Visit 1.

[0242] • Previous randomization in the present study.

[0243] • Concurrent enrollment in another clinical trial.

[0244] • 12-lead ECG at Screening Visit 1 : Participants with a QTcF >450 msec (or QTcF >480 msec in participants with bundle branch block).

[0245] • Hypersensitivity: Participants with a known allergy or sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation in the study or intolerance to another monoclonal antibody or biologic including history of anaphylaxis to another biologic.

[0246] • Non-compliance: Participants at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.

[0247] • Questionable validity of consent: Participants with, conditions that will limit the validity of informed consent to participate in the study, e.g., uncontrolled psychiatric disease or intellectual deficiency.

[0248] • Drug or alcohol abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Screening Visit 1.

[0249] • Affiliation with Investigator Site: Is an Investigator, sub-investigator, study coordinator, employee of a participating Investigator or study site, or immediate family member that is involved in this study.

[0250] • Liver chemistry test: Participants who meet the following based on results from sample taken at Screening Visit 1 : o ALT >2x ULN o Total bilirubin >1.5xULN: For participants with Gilbert’s syndrome can be included with total bilirubin >1.5xULN as long as direct bilirubin is <1.5xULN. o Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice.

[0251] Note: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome, asymptomatic gallstones, and chronic stable hepatitis B [in whom Hepatitis D (HDV) has been excluded] or C are acceptable if participant otherwise meets entry criteria

[0252] EXAMPLE 3: Phase III COPP trial for mepolizumab (MATINEE)

[0253] MATINEE (NCT04133909) was a Phase III, randomized, multicenter, placebo- controlled, double-blind, parallel group trial assessing mepolizumab 100 mg, administered subcutaneously every four weeks for at least 52 weeks and up to 104 weeks, in addition to inhaled corticosteroid-based triple-inhaled therapy, in patients with COPD with type 2 inflammation characterized by an eosinophilic phenotype (blood eosinophil count >300 cells / pL at screening and >150 cells / pL within the 12 months prior to screening.) The primary outcome was the annualized rate of moderate or severe exacerbations. Time to first moderate or severe exacerbation, COPD Assessment Test (CAT) score, St George’s Respiratory Questionnaire (SGRQ) total score, Proportion of Evaluating Respiratory Symptoms in COPD (E-RS: COPD) and annualized rate of exacerbations requiring emergency department (ED) visit and / or hospitalization were also measured.

[0254] Trial population

[0255] Patients were required to be at least 40 years of age at Screening Visit 1 with a documented diagnosis of COPD for at least one year based on the American Thoracic Society / European Respiratory Society definition and had a ratio of forced expiratory volume in 1 second (FEVi) to forced vital capacity (FVC) of <0.70 pre- and post-salbutamol and a FE i >20% and <80% of the predicated value post-salbutamol. In the 12 months before screening patients were required to have at least two moderate (defined as clinically significant exacerbations that require treatment with oral / systemic corticosteroids with or without antibiotics) or at least one severe exacerbation (defined as clinically significant exacerbations that require inpatient hospitalisation [i.e. >24 h] or result in death) despite inhaled triple therapy and 12 months ICS-based maintenance therapy with at least three months history of ICS-based inhaler triple therapy (>500 mg / day fluticasone propionate or equivalent, plus LABA plus LAMA). Current or former smokers (>10 pack-years) were included. Participants with a history or concurrent diagnosis of asthma were excluded regardless of disease activity. The modified intention-to-treat (mITT) population consisted of all patients who received >1 dose. At screening Visit 0, patients are required to have a BEC >300 cells / pL and a BEC >150 cells / pL in the prior 12 months. Those without historical BEC >150 cells / pL were required to meet the threshold at Screening Visit 1 to be eligible. Patients who met these inclusion criteria entered a two-week run-in period.

[0256] Endpoints

[0257] The primary endpoint was the annualized rate of moderate or severe exacerbations, moderate defined as clinically significant exacerbations that require treatment with oral / systemic corticosteroids and or antibiotic treatment, and severe as clinically significant exacerbations that require >24 hours in-patient hospitalization or resulted in death, respectively. Secondary endpoints assessed were the time to first moderate or severe exacerbation, annualized rate of exacerbations requiring emergency department (ED) visit and / or hospitalization, the proportion of COPD Assessment Test (CAT) score responders at Week 52 (defined as a >2-unit reduction in CAT score from baseline, scores range from 0 to 40 units and higher scores indicate greater effect of disease), the proportion of St. George’s Respiratory Questionnaire (SGRQ) total score responders at Week 52 measured using the SGRQ questionnaire for COPD (defined as a >4-point reduction in SGRQ total score from baseline, scores range from 0 to 100 points and higher scores indicate worse health status) and the proportion of Evaluating Respiratory Symptoms in COPD (E-RS: COPD) responders at Weeks 48-52 (defined as >2-point reduction in total score from baseline, scores range from 0 to 40 units with higher scores indicating more severe disease). Change from baseline in prebronchodilator FEVi was also assessed.

[0258] The safety endpoints included adverse events and serious adverse events. Immunogenicity was also assessed. For patients continuing the study beyond 52 weeks, vital signs and clinical safety were taken at less frequent intervals in the second year than in the first.

[0259] Statistical Analysis

[0260] With an assumed exacerbation rate of 1.7 exacerbations per year in the placebo arm, it was estimated that 800 patients (400 patients / arm) would provide the trial with 90% power to detect a 23% reduction in the annualized rate of moderate / severe exacerbations with 100 mg mepolizumab at a two-sided 5% level of significance. An additional 44 patients were included to account for the loss of patient years’ data from those who withdrew early from the trial, accounting for 5.5% of patient-years data being missing. Blinded re- evaluations of the sample size were carried out prior to randomization of the 800thparticipant to assess whether 800 participants would continue to provide sufficient power for the study based on the blinded overall exacerbation rate estimated from the available data.

[0261] The primary population for analysis of efficacy data was the mITT population. The primary endpoint included all moderate / severe exacerbations reported from the start of treatment up to the exit visit, regardless of study treatment discontinuation not associated with disruptions / restrictions imposed by the COVID pandemic. Rate of moderate / severe exacerbations was assessed using a negative binomial model including both on- andoff- treatment exacerbations with covariates of smoking status (current versus former smoker), number of exacerbations in the previous year (<2, 3, >4 as ordinal), baseline disease severity (as % predicted post-bronchodilator FEVi) and geographic region, natural log of time was included as an offset variable. For time to first moderate / severe exacerbation a Cox’s proportional hazards model was used with the same covariates as for the primary endpoint. For the proportion of CAT score responders and SGRQ total score responders patients with missing values at Week 52 were included as non-responders and sensitivity analyses to the assumption regarding missing data were performed using multiple imputation methods based on mixed pattern models. Analysis was performed using logistic regression model adjusting for baseline CAT score, smoking status, and geographic region. Primary and multiple secondary endpoints were controlled for multiplicity using a fixed hierarchical testing procedure.

[0262] Results

[0263] Patient population

[0264] In MATINEE, patients were recruited from October 2019 through August 2024. In total, 806 patients were randomized to either mepolizumab (N=402) or placebo (N=404). Of these, 804 were included in the mITT population (Fig. 1). Patient demographics and characteristics were balanced between treatment arms. Concomitant medications were not increased in patients treated with mepolizumab compared with those treated with placebo.

[0265] Exacerbations

[0266] Primary End Point

[0267] The annualized rate of moderate or severe exacerbations at Week 52 was significantly higher in the mepolizumab group at 0.80 (95% confidence interval [Cl], 0.70 to 0.92) versus the placebo group at 1.00 (0.88 to 1.14; rate ratio, 0.80; 95% Cl, 0.67 to 0.96; P=0.016) (Fig. 2).

[0268] Secondary End Points The time to first moderate or severe exacerbation in the mepolizumab versus placebo group was a median time of 202 versus 226 days, respectively (hazard ratio, 0.78; 95% Cl, 0.64;, 0.94 P=0.010) (Fig. 3). The annual rate of exacerbations leading to ED visit or hospitalization was significantly lower in the mepolizumab versus placebo group at 0.13 and 0.20, respectively (rate ratio, 0.65; 95% Cl, 0.44, 0.97; P=0.036) (Fig. 4).

[0269] Patient-reported outcomes

[0270] The proportion of CAT score responders at Week 52 in the mepolizumab versus placebo group was 41% vs 46% (hazard ratio, 0.81 ; 95% Cl, 0.60 to 1.09; P=0.161) (Fig. 5). The proportion E-RS: COPD responders in the mepolizumab group versus the placebo group was 31%% vs 34%% (hazard ratio; 1.17; 95% Cl, 0.87 to 1.57; P=0.291). (Fig. 6). The proportion of SGRQ responders at Week 52 responders was significantly greater for the mepolizumab group versus placebo (50% vs 46%; hazard ratio; 1.17; 95% Cl, 0.87 to 1.57; P=0.291) (Fig. 7).

[0271] Subgroup Analyses

[0272] The proportion of current smoker responders at Week 52 was significantly higher in the mepolizumab versus placebo group (0.68, 95% Cl), even compared to former smoker responders at Week 52 (0.83, 95% Cl). (Fig. 8).

[0273] The proportion of responders without symptoms of chronic bronchitis was significantly higher in the mepolizumab versus placebo group (0.73, 95% Cl), even compared to responders with symptoms of chronic bronchitis (0.80, 95% Cl). (Fig. 9)

[0274] Safety

[0275] The safety profile of mepolizumab was comparable to placebo, with a similar incidence of adverse events and serious adverse events between the mepolizumab and placebo groups.

[0276] EXAMPLE 4: Phase III COPD study of depemokimab (VIGILANT)

[0277] This multicenter, randomized, double-blind, parallel group, placebo-controlled study will investigate the efficacy and safety of early depemokimab initiation as add-on treatment in COPD patients with Type 2 inflammation.

[0278] The objective of this study is to investigate whether depemokimab, initiated in patients with COPD characterized by an eosinophilic phenotype who are at elevated risk for exacerbations with 1 moderate exacerbation in the prior year, will reduce the risk of future exacerbations and clinical deterioration. This population is ineligible for biologies under the current treatment paradigm.

[0279] This will be a randomized, placebo-controlled, parallel group, double-blind multicenter study evaluating depemokimab 100 mg SC + SoC compared with placebo + SoC given Q26W as a liquid formulation in a prefilled safety syringe injection. The study intervention period will be a minimum of 52 weeks up to a maximum duration of 156 weeks. Rescue therapy will be provisioned to the participants during the study.

[0280] Participants must have a blood eosinophil count (BEC) of >300 cells / pL at Screening or within the prior 12 months. If a prior BEC is used, participants are required to have BEC >270 cells / pL at Screening. If a participant does not meet the eligibility cut-off for BEC criteria, up to 2 retests are permitted prior to randomization. Participants must have had only 1 moderate COPD exacerbation in the 12 months prior to Screening treated with systemic corticosteroids (with or without antibiotics) and which must have occurred while the participant was on the same background COPD therapy regimen as when the participant attended Screening Visit 1 . In addition, the participants should have at least 1 risk factor for future exacerbations / deterioration:

[0281] • mMRC dyspnea score > 2 at Screening Visit 1

[0282] • CAT > 15 at Screening Visit 1

[0283] • Post-bronchodilator FEV1 < 50% predicted at Screening Visit 1

[0284] • Chronic bronchitis, defined as frequent cough and sputum production for at least 3 months in the 12 months prior to Screening Visit 1

[0285] Participants must have a history of regular use of optimized dual or triple maintenance COPD therapy for at least 3 months prior to Screening (Visit 1). All participants will continue optimized maintenance inhaled COPD therapy throughout the entire duration of the study regardless of intervention arm assignment.

[0286] Excluding screening and the run-in period, participants will remain in the study for at least 52 weeks and either up to 78, 104, 130 or 156 weeks, whichever visit aligns to the date of when the last randomized participant is scheduled to complete their Week 52 Visit. The timing of the last randomized participant into the study will thus affect the timing of the Exit Visit for ongoing participants. All participants will be expected to complete at least 52 weeks of the study and up to 156 weeks, depending on the time the participants enter the study. The last randomized participant will be scheduled to complete only 52 weeks of the study. The study will consist of a Screening Visit 1 , a run-in period (>14 days and <28 days) and a study intervention period (minimum 52 weeks and maximum of 156 weeks) followed by a post-intervention period consisting of an Exit Visit and a Follow-up Visit. At Visit 1 , Informed Consent must be obtained prior to initiating any study-related assessments. The randomization visit (Visit 2) must be performed at least 14 days after the start of Visit 1. Results from Visit 1 procedures must be available for review of randomization criteria. Participants will be randomized in a 1 :1 ratio in a blinded manner to receive up to six doses of either depemokimab 100 mg (Q26W), or placebo by SC injection. The doses of study intervention will be administered in the clinic and after all scheduled assessments are complete.

[0287] Randomization will be stratified by type of background inhaled therapy; specifically, ICS-containing (ICS+LABA, ICS+LABA+LAMA) and non-ICS containing (LAMA+LABA) therapy to ensure equal distribution within each stratum among the two treatment arms. Recruitment caps will be instituted to ensure at least 70% of participants are on ICS- containing therapy.

[0288] Objectives and endpoints are summarised below:

[0289] Participants are eligible to be included in the study if the following criteria apply:

[0290] • Participants must be >40 to <75 years of age, at the time of signing the informed consent form (ICF).

[0291] • An eosinophilic phenotype, defined as BEC >300 cells / pL at Screening Visit 1 or within the last 12 months. o Participants with BEC >300 within the past 12 months are required to have BEC >270 cells / pL at Screening Visit 1. • Moderate to severe COPD, defined as o A clinically documented history of COPD as defined by the American Thoracic Society / European Respiratory Society for at least 1 year. o A post-salbutamol FEV1 / FVC ratio of <0.70 and a post-salbutamol FEV1 >30% and <80% predicted normal values calculated with GLI-Global Race Neutral equations [Bowerman, 2023] at Visit 1.

[0292] • Elevated risk for exacerbations, defined as: o A well-documented history (e.g., medical record verification) of only 1 moderate COPD exacerbation in the 12 months prior to Screening Visit 1. To qualify, this exacerbation must have been treated with systemic corticosteroids (with or without antibiotics) and must have occurred while the participant was on the same optimized background COPD therapy regimen as when the participant attended Screening Visit 1 .

[0293] AND o The presence of at least 1 risk factor for future exacerbations / deterioration:

[0294] ■ mMRC dyspnea score > 2 at Screening Visit 1

[0295] ■ CAT > 15 at Screening Visit 1

[0296] ■ Post-bronchodilator FEV1 < 50% predicted at Screening Visit 1

[0297] ■ Chronic bronchitis, defined as frequent cough and sputum production for at least 3 months in the 12 months prior to Screening Visit 1

[0298] • Smoking status: Current or former cigarette smokers with a history of cigarette smoking of >10 pack-years at Screening. Former smokers are defined as those who have stopped all smoking (including tobacco, marijuana, or e-cigarettes) for at least 6 months prior to Visit 1.

[0299] • Optimized* dual (ICS+LABA or LABA+LAMA) or triple (ICS+LABA+LAMA) inhaler therapy as assessed by the investigator for at least 3 months prior to Visit 1.

[0300] *During Screening, the investigator should confirm that the background COPD therapy is appropriate for their level of COPD severity according to GOLD 2025 [Error! Reference source not found., 2025] or other accepted guidelines, and that there are no treatment changes expected between screening and randomization. The investigator or qualified delegate should review inhaler technique of participants at Screening Visit 1.

[0301] • Body mass index (BMI) >16 kg / m2.

[0302] • Male or eligible female.

[0303] Female participants:

[0304] A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: i. Is a woman of non-childbearing potential (WONCBP) OR ii. Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1 %, from at least 14 days prior and during the study intervention period and for at least 35 weeks after the last administered dose of study intervention.

[0305] • Capable of giving signed informed consent.

[0306] Participants are excluded from the study if the following criteria apply:

[0307] • Clinical manifestations of lung disease where primary diagnosis is not COPD are excluded. o Patients with a current or prior physician diagnosis of asthma are excluded. A diagnosis of asthma should be made by a healthcare provider, consistent with GINA 2024 or other accepted guidelines (i.e. , based on both a history of typical respiratory symptoms combined with evidence of variable expiratory airflow limitation). o Patients with childhood asthma are permitted, provided that childhood asthma has resolved before 18 years of age and has not recurred, and the Investigator has judged that COPD (and not asthma) is the diagnosis accounting for the clinical manifestations of the lung disease. o Participants with a1 -antitrypsin deficiency as the underlying cause of COPD are excluded. Also excluded are participants with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases.

[0308] • COPD severity: Participants with more than one moderate exacerbation, treated with corticosteroids or antibiotics (or both), or severe (requiring hospitalization or observation >24 hours in ED / urgent care facility) exacerbation in the past 12 months prior to Visit 1 are excluded.

[0309] • COPD stability: Participants with pneumonia, COPD exacerbation, or lower respiratory tract infection within the 4 weeks prior to Visit 1 are excluded.

[0310] • Lung resection: Participants with a history of, or plan for lung volume reduction surgery / endobronchial valve procedure are excluded.

[0311] • Pulmonary rehabilitation: Participants in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1 are excluded. Participants who are in the maintenance phase of a pulmonary rehabilitation program may participate. • Continuous oxygen: Patients requiring oxygen supplementation for COPD are excluded. Non-continuous (i.e., 12 hours or less per day) oxygen for sleep apnea is permitted up to 2 L / min at screening.

[0312] • Cor pulmonale - resulting in right heart failure, severe pulmonary hypertension are excluded.

[0313] • Chronic hypercapnia requiring non-invasive positive pressure ventilation (NIPPV) use including Bi-Level Positive Airway Pressure (BiPAP) or Continuous Positive Airway Pressure (CPAP) are excluded.

[0314] • Unstable cardiovascular disease or arrhythmia.

[0315] • Vasculitis: Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis must be excluded prior to enrolment.

[0316] • Eosinophilic disease: Participants with other conditions that could lead to elevated eosinophils such as hypereosinophilic syndromes including Eosinophilic Granulomatosis with Polyangiitis (EGPA, also known as Churg-Strauss Syndrome), or Eosinophilic Esophagitis.

[0317] • Parasitic Infection: Participants with a known, pre-existing parasitic infection within 6 months of Visit 1.

[0318] • Malignancy: A current malignancy or previous history of cancer which has been in remission for less than 12 months prior to Visit 1 (Participants that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded).

[0319] • Immunodeficiency: A known immunodeficiency other than that explained by use of corticosteroids (e.g., HIV).

[0320] • Other concurrent medical condition: Participants with (historical or) current evidence of clinically significant, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Clinically significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or which could affect the efficacy or safety analysis if the disease / condition exacerbated during the study.

[0321] • Other adjunctive therapies for COPD: Participants taking chronic macrolides, chronic oral corticosteroids, or PDE3 / 4 inhibitors in the past 12 months of Screening Visit 1 are excluded.

[0322] • Respiratory biologies: Previous exposure to mAb(s) targeting IL 5 / 5R, IL 4R / IL 13, IL 33, or TSLP. • Other monoclonal antibodies: Participants who have received any monoclonal antibody within 5 half-lives of Screening Visit 1.

[0323] • Investigational medications: Participants who have received an investigational drug within 30 days of Screening Visit 1 , or within 5 drug half-lives of the investigational drug, whichever is longer (this also includes investigational formulations of a marketed product).

[0324] • Oral corticosteroids: Participants who have received short term use of oral corticosteroids within 4 weeks of Screening Visit 1.

[0325] • Previous randomization in the present study is exclusionary.

[0326] • Concurrent enrollment in another clinical trial is exclusionary.

[0327] • Hypersensitivity: Participants with a known allergy or sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation in the study or intolerance to another monoclonal antibody or biologic including history of anaphylaxis to another biologic.

[0328] • Non-compliance: Participants at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.

[0329] • Questionable validity of consent: Participants with conditions that will limit the validity of informed consent to participate in the study, e.g., uncontrolled psychiatric disease or intellectual deficiency.

[0330] • Drug or alcohol abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.

[0331] • Affiliation with Investigator Site: Is an Investigator, sub-investigator, study coordinator, employee of a participating Investigator or study site, or immediate family member that is involved in this study.

[0332] • Liver chemistry test: Participants who meet the following based on results from sample taken at Visit 1 : o ALT >2x ULN. o Total bilirubin >1.5xULN: For participants with Gilbert’s syndrome can be included with total bilirubin >1.5xULN as long as direct bilirubin is <1.5xULN. o Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice.

[0333] • 12-lead ECG at Visit 1 : Participants with a QTcF >450 msec or QTcF >480 msec in participants with bundle branch block. o Participants are excluded if an abnormal ECG finding from the 12-lead ECG conducted at Visit 1 is considered to be clinically significant and would impact the participant’s participation during the study, based on the evaluation of the Investigator.

[0334] SEQUENCE LISTINGS

[0335] SEQ ID NO: 1 - Full length heavy chain

[0336] QVTLRESGPALVKPTQTLTLTCTVSGFSLTGSSVHWVRQPPGKGLEWLGVIWASGGTDYNSALMSRLSIS

[0337] KDTSRNQWLTMTNMDPVDTATYYCARDPPSGLLRLDYWGRGTLVTVSSASTKGPSVFPLAPSSKSTSG

[0338] GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSN

[0339] TKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVWDVSHEDPEVKFNWYV

[0340] DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

[0341] TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ

[0342] GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0343] SEQ ID NO: 2 - Full length light chain

[0344] DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLAWYQQKPGQPPKLLIYGASTRESGVPDRFSG

[0345] SGSGTDFTLTISSLQAEDVAVYYCQNVHSFPFTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLL

[0346] NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC

[0347] SEQ ID NO: 3 - VH sequence

[0348] QVTLRESGPALVKPTQTLTLTCTVSGFSLTGSSVHWVRQPPGKGLEWLGVIWASGGTDYNSALMSRLSIS

[0349] KDTSRNQWLTMTNMDPVDTATYYCARDPPSGLLRLDYWGRGTLVTVSS

[0350] SEQ ID NO: 4 - VL sequence

[0351] DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLAWYQQKPGQPPKLLIYGASTRESGVPDRFSG

[0352] SGSGTDFTLTISSLQAEDVAVYYCQNVHSFPFTFGGGTKLEIKR

[0353] SEQ ID NO: 5 - CDRH1

[0354] GSSVH

[0355] SEQ ID NO: 6 - CDRH2

[0356] VIWASGGTDYNSALMS

[0357] SEQ ID NO: 7 - CDRH3

[0358] DPPSGLLRLDY SEQ ID NO: 8 - CDRL1

[0359] KSSQSLLNSGNQKNYLA

[0360] SEQ ID NO: 9 - CDRL2

[0361] GASTRES

[0362] SEQ ID NO: 10 - CDRL3

[0363] QNVHSFPFT

[0364] SEQ ID NO: 11 - Human IL-5 (mature protein)

[0365] IPTEI PTSALVKETLALLSTH RTLLIAN ETLRIPVPVHKN HQLCTEEI FQGIGTLESQTVQGGTVERLFKN LS

[0366] LIKKYIDGQKKKCGEERRRVNQFLDYLQEFLGVMNTEWIIES

[0367] SEQ ID NO: 12 - Human IL-5 Receptor Subunit Alpha Isoform 1 (mature protein)

[0368] DLLPDEKISLLPPVNFTIKVTGLAQVLLQWKPNPDQEQRNVNLEYQVKINAPKEDDYETRITESKCVTILH KGFSASVRTILQNDHSLLASSWASAELHAPPGSPGTSIVNLTCTTNTTEDNYSRLRSYQVSLHCTWLVGT DAPEDTQYFLYYRYGSWTEECQEYSKDTLGRNIACWFPRTFILSKGRDWLAVLVNGSSKHSAIRPFDQLF ALHAIDQINPPLNVTAEIEGTRLSIQWEKPVSAFPIHCFDYEVKIHNTRNGYLQIEKLMTNAFISIIDDLSKY

[0369] DVQVRAAVSSMCREAGLWSEWSQPIYVGNDEHKPLREWFVIVIMATICFILLILSLICKICHLWIKLFPPIP APKSNIKDLFVTTNYEKAGSSETEIEVICYIEKPGVETLEDSVF

[0370] SEQ ID NO: 13 - Heavy chain FR4 sequence

[0371] WGRGTLVTVSS

Claims

70531 WQ01CLAIMS1. An antigen binding protein which binds to human IL-5 comprising a heavy chain variable region having the CDRH1 amino acid sequence shown in SEQ ID NO: 5, the CDRH2 amino acid sequence shown in SEQ ID NO: 6, and the CDRH3 amino acid sequence shown in SEQ ID NO: 7; and a light chain variable region having the CDRL1 amino acid sequence shown in SEQ ID NO: 8, the CDRL2 amino acid sequence shown in SEQ ID NO: 9, and the CDRL3 amino acid sequence shown in SEQ ID NO: 10 for use in the treatment of chronic obstructive pulmonary disease (COPD) in a patient, wherein the antigen binding protein is to be administered to the patient at a dose of about 100 mg to about 300 mg about once every 26 weeks or once every 6 months.

2. The antigen binding protein for use according to claim 1 , wherein the antigen binding protein comprises a heavy chain variable region sequence having at least about 90% identity to the amino acid sequence shown in SEQ ID NO: 3 and a light chain variable region sequence having at least about 90% identity to the amino acid sequence shown in SEQ ID NO: 4.

3. The antigen binding protein for use according to claim 1 or 2, wherein the antigen binding protein comprises a heavy chain variable region sequence having the amino acid sequence shown in SEQ ID NO: 3 and a light chain variable region sequence having the amino acid sequence shown in SEQ ID NO: 4.

4. The antigen binding protein for use according to any one of claims 1 to 3, wherein the antigen binding protein is an antibody.

5. The antibody for use according to claim 4, wherein the antibody comprises an IgG 1 Fc domain, optionally a human IgG 1 Fc domain.

6. The antibody for use according to claim 5, wherein the IgG 1 Fc domain comprises a tyrosine residue at position 252, a threonine residue at position 254 and a glutamic acid residue at position 256.

7. The antibody for use according to claim 6, wherein the antibody comprises a heavy chain having the amino acid sequence shown in SEQ ID NO: 1 and a light chain having the amino acid sequence shown in SEQ ID NO: 2.

8. The antibody for use according to claim 7, wherein the antibody is depemokimab.

9. The antigen binding protein or antibody for use according to any one of claims 1 to8, wherein the dose is about 100 mg, optionally 100 mg.

10. The antigen binding protein or antibody for use according to any one of claims 1 to9, wherein the antigen binding protein or the antibody is to be administered subcutaneously to the patient.

11. The antigen binding protein or antibody for use according to any one of claims 1 to10, wherein the antigen binding protein or antibody is in a pharmaceutical composition.

12. The antigen binding protein or antibody for use according to any one of claims 1 to11 , wherein the COPD is uncontrolled COPD.

13. The antigen binding protein or antibody for use according to any one of claims 1 to12, wherein the patient has at least 2 moderate or at least 1 severe exacerbation in the 12 months prior to treatment.

14. The antigen binding protein or antibody for use according to any one claims 1 to 13, wherein the patient has a blood eosinophil count of >150 cells / pl.

15. The antigen binding protein or antibody for use according to any one of claims 1 to 14, wherein the patient has a blood eosinophil count of >300 cells / pl.

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