METHODS FOR TREATING A PULMONARY FIBROTIC DISEASE, ANTI-OSMRB ANTIBODY, USE OF AN ANTI-OSMRB ANTIBODY AND THERAPEUTICALLY EFFECTIVE AMOUNT OF (A) AN ANTI-OSMRB ANTIBODY AND (B) AN ANTI-IL-6 RECEPTOR ANTIBODY

Abstract

The disclosure provides methods for treating pulmonary fibrotic disorders, including idiopathic pulmonary fibrosis, by administering to patients therapeutically effective doses and dosing regimens of an anti-OSM receptor β antibody, such as vixarelimab, or anti-OSM receptor β antibody, such as vixarelimab, in combination with an anti-IL-6 antibody or an anti-IL-6 receptor agonisτ, such as tocilizumab.

Description

1 / 97 “METHODS FOR TREATING A FIBROTIC PULMONARY DISEASE, ANTI-OSMRB ANTIBODY, USE OF AN ANTI-OSMRB ANTIBODY AND THERAPEUTICALLY EFFECTIVE AMOUNT OF (A) AN ANTIBODY ANTI OSMRB AND (B) AN ANTI-IL-6 RECEPTOR ANTIBODY” Cross-reference to related orders

[0001] This application claims priority and benefit of U.S. Provisional Application No. 63 / 488,933, filed March 7, 2023, the contents of which are incorporated by reference in their entirety herein. Technical Field

[0002] This disclosure relates to the field of treatment of fibrotic lung disease, such as idiopathic pulmonary fibrosis (IPF), using an anti-OSMRe antibody, such as vixarelimab, or a combination of an anti-OSMRe antibody (e.g., vixarelimab) and an anti-IL-6 receptor antibody (e.g., tocilizumab). Sequence Listing

[0003] This application contains a Sequence Listing that was submitted electronically in XML format and is incorporated herein by reference in its entirety. The said XML copy, created on March 7, 2024, is named 000218-0086-WO1_SL.xml and is 16,183 bytes in size. Background

[0004] Fibrotic interstitial lung diseases (FILDs) are a heterogeneous group of diffuse parenchymal lung disorders characterized by excessive deposition of extracellular matrix components, leading to irreversible loss of lung function (Wijsenbeek and Cottin, 2020, N Engl J Med, 383:958-968). FILDs associated with connective tissue disease and idiopathic pulmonary fibrosis (IPF) are two of the most common fibrotic FILDs. Petition 870250079694, dated 05 / 09 / 2025, pp. 125 / 267 2 / 97 with an estimated prevalence of 12.1 and 8.2 cases per 100,000, respectively (Duchemann et al., 2017, Eur Respir J, 50:1602419). Among patients with non-IPF fibrotic lung diseases, 30%–40% have a progressive fibrosing course (Wijsenbeek et al., 2019, Curr Med Res Opin, 35:2015–2024), leading to chronic disability and premature death. Recent updates to world society guidelines have established the concept of progressive pulmonary fibrosis, defined as non-IPF fibrotic lung diseases that meet at least two of the three progression criteria (worsening of symptoms, radiological progression, and physiological progression) occurring in the last year without an alternative explanation (Raghu et al. 2022).

[0005] Pirfenidone and nintedanib are currently the only approved pharmacological therapies for the treatment of IPF (Raghu et al., 2022, Am J Respir Crit Care Med, 205:e18-e47). The rate of decline in forced vital capacity (FVC) is slower in patients treated with pirfenidone and nintedanib. However, neither treatment halts disease progression nor improves any objective measures of disease status (Nathan et al., 2016, Thorax, 71:429-435). Therefore, disease progression and respiratory decline are inevitable. Thus, the need for new treatment approaches remains.

[0006] Given the need for effective therapies in the treatment and slowing of the progression of pulmonary fibrotic disorders, methods for using anti-OSMRe antibodies to treat pulmonary fibrotic disorders such as IPF and SSc-ILD are provided in this document. Brief Description of the Disclosure

[0007] In one aspect, a method is provided for administering to an individual in need thereof a therapeutically effective dose of an anti-OSMRp (oncostatin M receptor) antibody.

[0008] In a second aspect, a method is provided for Petition 870250079694, dated 05 / 09 / 2025, pp. 126 / 267 3 / 97 treat a pulmonary fibrotic disease. In some embodiments, the method comprises administering to an individual in need thereof a therapeutically effective dose of an anti-OSMRe (oncostatin M receptor beta) antibody. In some embodiments, the pulmonary fibrotic disease is selected from the group consisting of progressive pulmonary fibrosis (PPF), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis-associated interstitial lung disease (SSc-ILD). In some embodiments, the pulmonary fibrotic disease is progressive pulmonary fibrosis (PPF). In some embodiments, the pulmonary fibrotic disease is idiopathic pulmonary fibrosis (IPF). In some embodiments, the pulmonary fibrotic disease is systemic sclerosis-associated interstitial lung disease (SSc-ILD).

[0009] In a third aspect, a method is provided for increasing FVC in an individual suffering from a pulmonary fibrotic disorder. In some embodiments, the method comprises administering a therapeutically effective dose of anti-OSMRe antibody to an individual in need thereof.

[0010] In a fourth aspect, a method is provided for increasing the distance walked, as measured in the 6MWT, by an individual suffering from a pulmonary fibrotic disorder. In some embodiments, the method comprises administering a therapeutically effective dose of anti-OSMRe antibody to an individual in need thereof.

[0011] In a fifth aspect, a method is provided for reducing the frequency of cough, as measured by an ambulatory digital device for continuous cough detection, in an individual suffering from a pulmonary fibrotic disorder. In some embodiments, the method comprises administering a therapeutically effective dose of anti-OSMRe antibody to an individual in need thereof.

[0012] In a sixth aspect, a method is provided for dealing Petition 870250079694, dated 05 / 09 / 2025, pp. 127 / 267 4 / 97 an inflammatory disease. In some embodiments, the method comprises administering to an individual in need a therapeutically effective dose of an anti-OSMRp antibody (oncostatin M beta receptor).

[0013] In some embodiments, according to any of the above aspects, the anti-OSMRp antibody inhibits the activation of the OSMRp pathway by oncostatin M (OSM) and / or interleukin-31 (IL-31). In some embodiments, according to any of the above aspects, the anti-OSMRp antibody inhibits the activation of the OSMRp pathway by oncostatin M (OSM) and interleukin-31 (IL-31).

[0014] In some embodiments, according to any of the above aspects, the anti-OSMRp antibody comprises a variable heavy chain (VH) domain comprising SEQ ID NO:7 and a variable light chain (VL) domain comprising SEQ ID NO:8. In some embodiments, according to any of the above aspects, the anti-OSMRp antibody comprises a heavy chain (HC) comprising SEQ ID NO:5 and a light chain (LC) comprising SEQ ID NO:6. In some embodiments, according to any of the above aspects, the anti-OSMRp antibody is vixarelimab.

[0015] In some embodiments, according to any of the above aspects, the therapeutically effective dose is about 360 mg to 720 mg of anti-OSMRp antibody. In some embodiments, according to any of the above aspects, the therapeutically effective dose is 360 mg of anti-OSMRp antibody. In some embodiments, according to any of the above aspects, the anti-OSMRp antibody is administered once a week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once a month. In some embodiments, according to any of the above aspects, the anti-OSMRp antibody is administered once a week. In some embodiments, according to any of the above aspects, the anti-OSMRp antibody is administered once every 2 weeks. In Petition 870250079694, dated 05 / 09 / 2025, pp. 128 / 267 5 / 97 In some embodiments, according to any of the above aspects, the anti-OSMRe antibody is administered once every 3 weeks. In some embodiments, according to any of the above aspects, the anti-OSMRe antibody is administered once every 4 weeks. In some embodiments, according to any of the above aspects, the anti-OSMRe antibody is administered once a month.

[0016] In some embodiments, according to any of the above aspects, the method comprises administering to the individual 360 mg, 540 mg, or 720 mg of the anti-OSMRe antibody once every 1 week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once a month. In preferred embodiments, according to any of the above aspects, the method comprises administering to the individual 360 mg of the anti-OSMRe antibody approximately once every 2 weeks, wherein the anti-OSMRe antibody is vixarelimab.

[0017] In some embodiments, according to any of the above aspects, the individual does not receive a loading dose of anti-OSMRe antibody.

[0018] In some embodiments, according to any of the above aspects, the anti-OSMRe antibody is administered subcutaneously. In other embodiments of any of the above aspects, the anti-OSMRe antibody is administered intravenously.

[0019] In some embodiments, according to any of the above aspects, the method comprises treating the individual, wherein the individual, before treatment with the anti-OSMRe antibody, has a predicted forced vital capacity (%FVC) percentage of about 35% to 90%, about 35% to 75%, about 35% to 50%, about 45% to 55%, about 30% to 60%, about 50% to 90%, about 50% to 75%, about 40% to 45%, about 40% to 50%, about 45% to 50%, or about 45% to about 50%. In some embodiments, Petition 870250079694, dated 05 / 09 / 2025, pp. 129 / 267 6 / 97 according to any of the aspects above, the individual has a %FVC of approximately 45% of predicted. In some realizations, according to any of the aspects above, %FVC is measured using spirometry.

[0020] In some embodiments, according to any of the above aspects, the individual has a forced expiratory volume in 1 second (FEV1) to FVC ratio of about 0.35 to 0.70, about 0.50 to 0.70, about 0.60 to 0.70, about 0.35 to 0.50, about 0.40 to 0.50, about 0.50 to 0.60, about 0.60 to 0.70, about 0.70 to 0.80, before treatment with anti-OSMRe antibody. In some embodiments, according to any of the above aspects, the individual has an FEV1-FVC ratio of about 0.70 to 0.80.

[0021] In preferred realizations, according to any of the above aspects, the individual has forced vital capacity (FVC) of about 45% predicted or greater and a forced expiratory volume in 1 second (FEV1) to FVC ratio greater than about 0.70 before treatment with the anti-OSMRe antibody.

[0022] In some embodiments, according to any of the above aspects, the method comprises treating an individual with a pulmonary fibrotic disorder, wherein administration of the anti-OSMRe antibody dose to the individual results in a change in FVC in the individual, wherein the change is a measure of the absolute change in FVC in milliliters (ml) over a treatment period beginning at the time of the first administration of the anti-OSMRe antibody until the time a subsequent dose of the anti-OSMRe antibody is administered. In some embodiments, according to any of the above aspects, the change in FVC during the treatment period is a decrease in FVC of less than 25 ml, 50 ml, 75 ml, 100 ml, 125 ml, 150 ml, 175 ml, 200 ml, 225 ml, or 250 ml, or an increase in FVC of at least 25 ml, 50 ml, 75 ml, 100 ml, 125 ml, 150 ml, 175 ml, 200 ml, 225 ml, or 250 ml. In some embodiments, according to any of the above aspects, the Petition 870250079694, dated 05 / 09 / 2025, pp. 130 / 267 7 / 97 anti-OSMRe antibody is administered every 2 weeks at a dose of approximately 360 mg, and the change in FVC during the time period is a decrease in FVC of less than 25 ml, 50 ml, 75 ml, 100 ml, 125 ml, 150 ml, 175 ml, 200 ml, 225 ml, or 250 ml, or an increase in FVC of at least 25 ml, 50 ml, 75 ml, 100 ml, 125 ml, 150 ml, 175 ml, 200 ml, 225 ml, or 250 ml. In some embodiments, according to any of the above aspects, the treatment period is approximately 6 weeks, approximately 12 weeks, approximately 24 weeks, approximately 36 weeks, approximately 48 weeks, approximately 60 weeks, or approximately 72 weeks. In some outcomes, depending on any of the aspects mentioned above, the treatment period is approximately 52 weeks.

[0023] In some embodiments, according to any of the above aspects, the method comprises treating an individual with a pulmonary fibrotic disorder, wherein administration of the anti-OSMRe antibody dose to the individual results in an alteration in the lung diffusion capacity for carbon monoxide adjusted for hemoglobin (DLCO[Hb]) in the individual. In some embodiments, according to any of the above aspects, the method is sufficient to produce an increase in DLCO[Hb] compared to a baseline, wherein the baseline measurement is made before administration. In some embodiments, according to any of the above aspects, the method is sufficient to produce an increase in the predicted percentage of DLCO (DLco%) compared to the baseline measurement.In some embodiments, according to any of the above aspects, the predicted increase in DLco or DLco% is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or 90% above the respective baseline measurement during a treatment period. In some embodiments, according to any of the above aspects, the treatment period is approximately 6 weeks, approximately 12 weeks, approximately 24 weeks, approximately 36 weeks, approximately 48 weeks, or approximately 60 weeks. Petition 870250079694, dated 05 / 09 / 2025, pp. 131 / 267 8 / 97 approximately 72 weeks. In some realizations, according to any of the aspects above, the treatment period is approximately 52 weeks.

[0024] In some embodiments, according to any of the above aspects, the method comprises treating an individual with a pulmonary fibrotic disorder, wherein administration of the anti-OSMRp antibody dose to the individual results in a change in the distance walked by the individual in the 6-minute walk test (6MWT), wherein the change is the difference in the distance walked by the individual in the 6MWT performed at 2 time points in a treatment period, wherein the first time point is at the first administration of the anti-OSMRp antibody and the second time point is the time when a subsequent dose of the anti-OSMRp antibody is administered. In some embodiments, according to any of the above aspects, the anti-OSMRp antibody is administered every 2 weeks at a dose of approximately 360 mg.In some realizations, according to any of the above aspects, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 5%, 10%, 15%, 20%, 25%, or 30%, or an increase of at least about 5%, 10%, 15%, 20%, 25%, or 30%. In some realizations, according to any of the above aspects, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 5%, 10%, 15%, 20%, 25%, or 30%. In some realizations, according to any of the above aspects, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 5%, 10%, 15%, 20%, 25%, or 30%.In some embodiments, according to any of the aspects above, the treatment period is approximately 6 weeks, approximately 12 weeks, approximately 24 weeks, approximately 36 weeks, approximately 48 weeks, approximately 60 weeks, or approximately 72 weeks. In some embodiments, according to any of the aspects above, the period of... Petition 870250079694, dated 05 / 09 / 2025, pp. 132 / 267 9 / 97 treatment lasts approximately 52 weeks.

[0025] In some embodiments, according to any of the above aspects, the method comprises treating an individual with a pulmonary fibrotic disorder, wherein administration of the anti-OSMRp antibody dose to the individual results in a decrease in quantitative pulmonary fibrosis on a high-resolution computed tomography (HRCT) scan in the individual. In some embodiments, according to any of the above aspects, the method is sufficient to produce a decrease in quantitative pulmonary fibrosis on HRCT compared to a baseline, wherein the baseline measurement is taken before administration. In some embodiments, according to any of the above aspects, the decrease in quantitative pulmonary fibrosis on HRCT is at least 1%, 2%, 3%, 4%, 5%, 8%, 10%, 12%, 15%, 20%, or 30% below the respective baseline measurement over a treatment period.In some embodiments, according to any of the aspects above, the treatment period is approximately 6 weeks, approximately 12 weeks, approximately 24 weeks, approximately 36 weeks, approximately 48 weeks, approximately 60 weeks, or approximately 72 weeks. In some embodiments, according to any of the aspects above, the treatment period is approximately 52 weeks.

[0026] In some embodiments, according to any of the above aspects, the method comprises treating the individual with a pulmonary fibrotic disorder, wherein the administration of the anti-OSMRp antibody dose to the individual results in a reduction in cough frequency. In some embodiments, according to any of the above aspects, the reduction in cough frequency is measured by an ambulatory digital device for continuous cough detection.

[0027] In some realizations, according to any of the above aspects, the individual has been diagnosed with or determined to suffer from Petition 870250079694, dated 05 / 09 / 2025, pp. 133 / 267 10 / 97 one or more pulmonary fibrotic disorders. In some embodiments, according to any of the above aspects, the pulmonary fibrotic disorder is idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) (alternatively referred to as pulmonary fibrosis associated with interstitial lung disease (PF-ILD)).

[0028] In some embodiments, according to any of the above aspects, PPF is chronic fibrosing ILD (CF-ILD) with a progressive phenotype, interstitial lung disease (ILD), systemic sclerosis-associated interstitial lung disease (SSc-ILD), drug-induced ILD, hypersensitivity pneumonitis, interstitial pneumonia with autoimmune features (IPAF), fibrosing interstitial pneumonia, and unclassifiable ILD. In some embodiments, according to any of the above aspects, pulmonary fibrotic disorder is a chronic fibrosing interstitial lung disease with a progressive phenotype.

[0029] In some embodiments, according to any of the above aspects, pulmonary fibrosis is associated with one or more of the following: usual interstitial pneumonia, idiopathic interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis associated with interstitial lung disease, acute interstitial pneumonia, nonspecific interstitial pneumonia, sarcoidosis, cryptogenic organizing pneumonia, eosinophilic pneumonia, infection, exposure to occupational or environmental agents, smoking, drug- or radiation-induced interstitial lung disease, rheumatic disease-associated interstitial lung disease, lymphoid interstitial pneumonia, pleuropulmonary fibroelastosis, Langerhans cell pulmonary histiocytosis, systemic sclerosis-associated interstitial lung disease, Hermansky-Pudlak syndrome, and telomeropathy.

[0030] In some realizations, according to any of the above aspects, the individual has not been diagnosed or is not suffering from a Petition 870250079694, dated 05 / 09 / 2025, pp. 134 / 267 11 / 97 Inflammatory bowel disease.

[0031] In some realizations, according to any of the above aspects, the individual has not been diagnosed with, or is not presenting with, a fibrotic skin disease such as prurigo nodularis (PN) or atopic dermatitis (AD).

[0032] In some embodiments, according to any of the above aspects, the anti-OSMRe antibody is administered in combination with a second therapeutic agent. In some embodiments, according to any of the above aspects, the second therapeutic agent is a therapeutic agent indicated for a pulmonary fibrotic disease or disorder. In some embodiments, according to any of the above aspects, the second therapeutic agent is an antifibrotic. In preferred embodiments, according to any of the above aspects, the second therapeutic agent is pirfenidone or nintedanib.

[0033] In some embodiments, according to any of the above aspects, the anti-OSMRe antibody is administered before, during, or after administration with the second therapeutic agent. In other embodiments of any of the above aspects, the second therapeutic agent is an anti-IL-6 antibody or an anti-IL-6 receptor agonist. In other embodiments, according to any of the above aspects, the second therapeutic agent is an anti-IL-6 antibody or an anti-IL-6 receptor antibody. In some embodiments, according to any of the above aspects, the heavy chain of the anti-IL-6 antibody or the anti-IL-6 receptor antibody comprises the amino acid sequence of SEQ ID NO: 13. In some embodiments, according to any of the above aspects, the light chain of the anti-IL-6 antibody or the anti-IL-6 receptor antibody comprises the amino acid sequence of SEQ ID NO: 14.In some embodiments, according to any of the above aspects, the anti-IL-6 antibody or the anti-IL-6 receptor antibody is tocilizumab. In some embodiments, according to any of the... Petition 870250079694, dated 05 / 09 / 2025, pp. 135 / 267 12 / 97 aspects above, the anti-IL-6 antibody or the anti-IL-6 receptor antibody comprises the six CDRs of tocilizumab.

[0034] In some embodiments, according to any of the above aspects, the anti-OSMRe antibody is administered to the individual after the individual has been treated with the second therapeutic agent for at least 1 week, 1 month, 6 months, 1 year, 3 years, or 5 years.

[0035] In a seventh aspect, the present disclosure provides a method for treating pulmonary fibrotic disease in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of (a) an anti-OSMRe antibody and (b) an anti-IL-6 receptor antibody. In some embodiments, pulmonary fibrotic disease is selected from the group consisting of progressive pulmonary fibrosis (PPF), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis-associated interstitial lung disease (SSc-ILD). In some embodiments, pulmonary fibrotic disease is progressive pulmonary fibrosis (PPF). In some embodiments, pulmonary fibrotic disease is idiopathic pulmonary fibrosis (IPF). In some embodiments, pulmonary fibrotic disease is systemic sclerosis-associated interstitial lung disease (SSc-ILD).

[0036] In an eighth aspect, the present disclosure provides a method for treating an inflammatory and / or fibrotic lung disease in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of (a) an anti-OSMRe antibody and (b) an anti-IL-6 receptor antibody.

[0037] In some embodiments, according to any of the above aspects, the anti-OSMRe antibody comprises a variable heavy chain (VH) domain comprising SEQ ID NO:7 and a variable light chain (VL) domain comprising SEQ ID NO:8. In some embodiments, according to any of the above aspects, the anti-OSMRe antibody Petition 870250079694, dated 05 / 09 / 2025, pp. 136 / 267 13 / 97 comprises a heavy chain (HC) comprising SEQ ID NO:5 and a light chain (LC) comprising SEQ ID NO:6. In some embodiments, according to either of the above aspects, the anti-OSMRe antibody is vixarelimab. The anti-OSRMp antibody may be administered at any of the doses disclosed in this document, at any of the dosing frequencies disclosed in this document, or at any combination of dose and frequency disclosed in this document.

[0038] In some embodiments, according to any of the above aspects, the heavy chain of the IL-6 receptor antibody comprises the amino acid sequence SEQ ID NO: 13. In some embodiments, according to any of the above aspects, the IL-6 receptor antibody comprises the amino acid sequence SEQ ID NO: 14. In some embodiments, according to any of the above aspects, the IL-6 receptor antibody is tocilizumab. In some embodiments, according to any of the above aspects, the IL-6 receptor antibody comprises the six CDRs of tocilizumab.

[0039] In a ninth aspect, the present disclosure provides a method for treating pulmonary fibrotic disease in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of vixarelimab and tocilizumab. In some embodiments, pulmonary fibrotic disease is selected from the group consisting of progressive pulmonary fibrosis (PPF), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis-associated interstitial lung disease (SSc-ILD). In some embodiments, pulmonary fibrotic disease is progressive pulmonary fibrosis (PPF). In some embodiments, pulmonary fibrotic disease is idiopathic pulmonary fibrosis (IPF). In some embodiments, pulmonary fibrotic disease is systemic sclerosis-associated interstitial lung disease (SSc-ILD). Vixarelimab may be administered at any of the doses. Petition 870250079694, dated 05 / 09 / 2025, pp. 137 / 267 14 / 97 disclosed in this document, at any of the dosage frequencies disclosed in this document or at any combination of dose and frequency disclosed in this document.

[0040] In a tenth aspect, the present disclosure provides a method for treating an inflammatory and / or fibrotic lung disease in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of vixarelimab and tocilizumab. Vixarelimab may be administered at any of the doses disclosed in this document, at any of the dosing frequencies disclosed in this document, or at any combination of dose and frequency disclosed in this document.

[0041] In some embodiments, the anti-OSMR antibody (e.g., vixarelimab) and the anti-IL-6 receptor antibody (e.g., tocilizumab) are administered simultaneously. In some embodiments, the anti-OSMR antibody (e.g., vixarelimab) and the anti-IL-6 receptor antibody (e.g., tocilizumab) are administered sequentially. In some embodiments, the anti-OSMR antibody (e.g., vixarelimab) is administered before the anti-IL-6 receptor antibody (e.g., tocilizumab). In some embodiments, the anti-OSMR antibody (e.g., vixarelimab) is administered after the anti-IL-6 receptor antibody (e.g., tocilizumab). In some embodiments, the anti-OSMR antibody (e.g., vixarelimab) and the anti-IL-6 receptor antibody (e.g., tocilizumab) are administered in the same combination.In some embodiments, the anti-OSMRe antibody (e.g., vixarelimab) and the anti-IL-6 receptor antibody (e.g., tocilizumab) are administered in different compositions. Brief Description of the Figures

[0042] Figure 1 provides the results of the analysis of Petition 870250079694, dated 05 / 09 / 2025, pp. 138 / 267 15 / 97 sequencing of scRNA from lung tissue isolated from a human individual diagnosed with idiopathic pulmonary fibrosis shows OSM expression in macrophages and OSMR3 expression in epithelial cells, single smooth muscle cell (SMC) types, fibroblasts, and endothelial cells.

[0043] Figure 2A provides the results of treating a mouse model of pulmonary fibrosis with either a control antibody or an anti-OSM antibody.

[0044] Figure 2B provides the results of antibody treatment in neutrophils in bronchoalveolar lavage fluid from mice sacrificed on Day 24, as shown in the right panel.

[0045] Figure 3A provides the total hydroxyproline (total OHP, ug / half lung) in lung tissue that was measured on day 24.

[0046] Figure 3B demonstrates that 'Nova' hydroxyproline (Nova OHP, ug / half lung) in lung tissue was measured in mice treated with deuterated water on day 24. The graphs show mean ± SD with 5 to 25 mice per group. P-value calculated by t-test. * P<0.05.

[0047] Figures 4A-4F show the results of lung tissue recovery in mice on day 14 post-BLM.

[0048] Figure 4A provides the results of weekly body weight monitoring expressed as a % of baseline weight.

[0049] Figure 4B shows the survival rate of mice 25 days post-BLM.

[0050] Figure 4C shows the tissue volume (TV) on day 22 post-BLM. RNA was extracted and used for RNA sequencing.

[0051] Figure 4D provides tissue remodeling genes relevant to the disease and expressed in relation to control mice treated with PBS. The graph shows individual mice with mean. * P<0.05. Petition 870250079694, dated 05 / 09 / 2025, pp. 139 / 267 16 / 97

[0052] Figure 4E provides tissue remodeling genes relevant to the disease and expressed in relation to control mice treated with PBS. The graph shows individual mice with mean. * P<0.05.

[0053] Figure 4F provides the main Ingenuity pathway analyses (IPA) for mice treated with isotype and anti-OSM post-BLM.

[0054] Figure 5 demonstrates PK / PD after a single IV dose of vixarelimab to determine the effective concentration (Ceff) in a non-human primate (NHP) itch model. Vixarelimab (KPL-716) was administered intravenously (IV) on day 1; 6 animals were treated per dose group. Itching events are calculated as post-IL-31 challenge events minus pre-IL-31 challenge events. The lower quantification threshold = 0.04 pg / ml. Vixarelimab concentrations in the same dosing regimens were simulated and correlated with the reduction in rhIL-31-induced itching, verifying a Ceff threshold of 5 to 8 μg / ml to inhibit pruritic responses in this model. The X-axis of each graph corresponds to the number of days after vixarelimab treatment (Pre-Tx = before treatment). The left Y-axis of each graph corresponds to the number of itching events, which is the pharmacodynamic effect.The right Y-axis of each graph corresponds to the serum concentration of vixarelimab (KPL-716) in μg / ml.

[0055] Figure 6 shows the results of the Phase 1b human clinical trial of AD treatment with vixarelimab, which involved IV administration of vixarelimab at doses of 0.3 mg / kg, 1.5 mg / kg, 7.5 mg / kg, 10 mg / kg, or 20 mg / kg and SC administration at doses of 1.5 mg / kg or 360 mg. Patients were monitored for safety, as well as for disease severity, pruritus intensity, and quality of life measures, including sleep quality. Study C001: Sustained efficacy lasted 6 to 8 weeks after a single IV dose of 7.5 mg / kg in patients with AD, which Petition 870250079694, dated 05 / 09 / 2025, pp. 140 / 267 17 / 97 appears to support the Ceff range of 5 to 8 μg / ml identified in an NHP IL-31 challenged model. Clinical studies in AD / PN (diseases caused by IL-31) further validate the Ceff range of 5 to 8 μg / ml.

[0056] Figure 7 shows simulated PK profiles. The simulation was performed with a preliminary population pharmacokinetics model of target-mediated drug disposition (TMDD) developed with available clinical PK data from healthy individuals and patients with prurigo nodularis (PN) or atopic dermatitis (AD).

[0057] Figure 8 provides the Phase 2 study design to evaluate efficacy, safety, and PK in idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease.

[0058] Figures 9A-9C demonstrate that IL-6-dependent CD64+ macrophage populations cause fibrotic disease.

[0059] Figure 9A provides total hydroxyproline (OHP Total, ug / half lung) in lung tissue, as measured on day 24. 4 to 8 mice per group. P-value calculated by t-test. Graphs show mean ± SD. * P<0.05.

[0060] Figure 9B provides gene expression measured in lung tissue by qRT-PCR. 4 to 8 mice per group. P-value calculated by t-test. Graphs show mean ± SD. * P<0.05.

[0061] Figure 9C provides FACS analysis of lung tissue on day 8 and day 24 of WT (Il6r+ / +) and IL-6-deficient (Il6r- / -) mice treated with saline or BLM, showing representative FACS plots (top) and numbers of CD64+ macrophages (CD45+CD11c+SigF+MHCII+CD11b+CD64+) per 105 CD45+ cells (bottom). 4 to 8 mice per group. P-value calculated by t-test. Plots show mean ± SD. * P<0.05.

[0062] Figure 10 demonstrates that IL-6 activates myeloid cells and Petition 870250079694, dated 05 / 09 / 2025, pp. 141 / 267 18 / 97 drives inflammatory and fibrotic programs. Monocyte-derived macrophages (MDMs) were generated from healthy donors and polarized with IL-4 and IL-13 + / - IL-6 for 24 hours. CCL18 mRNA and protein were measured using qRT-PCR and ELISA, respectively (n=7). Graphs show mean ± SD. * P<0.05.

[0063] Figure 11 provides transcript analysis of lung biopsies obtained from healthy controls (n=9) and patients with IPF (n=22). RNA-seq was performed and CD64, CCL2, and CCL18 transcripts were analyzed. P-values ​​were calculated using paired t-tests or Mann-Whitney tests. Graphs show mean ± SD. * P<0.05.

[0064] Figure 12 provides a transcript analysis of skin biopsies obtained from healthy controls (n=20) and patients with SSc (n=78). Transcripts of CD64, CCL2, and CCL18 measured. P-values ​​calculated by paired t-tests or Mann-Whitney. Graphs show mean ± SD. * P<0.05.

[0065] Figure 13 provides a transcript analysis of skin biopsies obtained from healthy controls (n=20) and patients with SSc (n=78). CD64, CCL2, and CCL18 transcripts were measured at baseline and after 24 weeks of treatment with PBO (n=44) or TCZ (n=40). P-values ​​were calculated using paired t-tests or Mann-Whitney tests. Graphs show mean ± SD. * P<0.05.

[0066] Figure 14A shows the RNA-seq results of OSM transcripts from lung biopsies obtained from healthy controls (n=9) and patients with IPF (n=22).

[0067] Figure 14B shows the RNA-seq results of OSM transcripts from skin biopsies obtained from healthy controls (n=20) and patients with SSc (n=78).

[0068] Figure 15A provides the results of SAEC, ENDO or Petition 870250079694, dated 05 / 09 / 2025, pp. 142 / 267 19 / 97 Primary human cultured FIB stimulated with recombinant human OSM.

[0069] Figure 15B provides the results of a comparative transcriptional analysis of primary human SAEC, ENDO, or FIB cultured after 24 hours of exposure to OSM.

[0070] Figures 16A-16D demonstrate that OSM mediates disease-relevant pathogenic responses in epithelial, endothelial, and fibroblast cells in an OSMR-dependent manner.

[0071] Figure 16A: Primary human SAEC, ENDO, or FIB cells were cultured and stimulated with rhOSM (10 ng / ml) for 15 minutes. Cells were treated with anti-OSMR (50 ug / ml) or anti-OSM (10 ug / ml) 120 minutes before OSM treatment. Cell lysates were recovered and pSTAT3Tyr705 was measured by MSD. P-value calculated by t-test. Graphs show mean ± SD. * P<0.05.

[0072] Figure 16B: Normal primary human lung FIB (NH-LF) or IPF-derived human lung FIB (IPF-LF) were cultured and stimulated with rhOSM (10 ng / ml). Some cells were treated with antiOSMR, at the indicated concentrations, 120 minutes before OSM treatment. Cell lysates were recovered and pSTAT3Tyr705 was measured by MSD. Data are expressed as % of remaining pSTAT3Tyr705.

[0073] Figure 16C: Primary human ENDO cells were cultured and stimulated with rhOSM (10 ng / ml). Some cells were treated with anti-OSMR, at the indicated concentrations, 120 minutes before OSM treatment. Cell lysates were recovered and pSTAT3Tyr705 was measured by MSD. Data are expressed as % of remaining pSTAT3Tyr705.

[0074] Figure 16D: Primary human ENDO cells were cultured and stimulated with rhOSM (10 ng / ml) for 15 minutes. Cells were treated with anti-OSMR (50 ug / ml) or anti-LIFR (50 ug / ml) 120 minutes before OSM treatment. Cell lysates were recovered and the Petition 870250079694, dated 05 / 09 / 2025, pp. 143 / 267 20 / 97 pSTAT3Tyr705 was measured by MSD. P-value calculated by t-test. Graphs show mean ± SD. * P<0.05.

[0075] Figure 17 demonstrates that OSM-induced endothelial cell disruption and permeability can be completely prevented with anti-OSMR antagonism. Primary human ENDO cells were cultured and permeability was assessed after treatment with rhOSM (10 ng / ml). Cells were treated with anti-OSMR (50 ug / ml) or anti-LIFR (50 ug / ml) 120 minutes before OSM treatment. P-value calculated by t-test. Graphs show mean ± SD. * P<0.05.

[0076] Figure 18 demonstrates that OSM-induced IL-6 and CCL2 / MCP1 secretion from pulmonary endothelial cells was largely OSMR-dependent rather than LIFR-dependent. Primary human ENDO cells were cultured and stimulated with rhOSM (10 ng / ml) for 24 hours with anti-OSMR (50 ug / ml) or anti-LIFR (50 ug / ml) for 120 minutes before OSM treatment and throughout treatment. IL-6 and CCL2 / MCP1 were measured by Luminex® in supernatants. P-value calculated by t-test. Graphs show mean ± SD. * P<0.05.

[0077] Figure 19 demonstrates that OSM disrupts SAEC integrity with a significant increase in permeability. Primary human SAECs were cultured and permeability was assessed after treatment with rhOSM (10 ng / ml). Cells were treated with anti-OSMR (50 ug / ml) or anti-LIFR (50 ug / ml) 120 minutes before OSM treatment. P-value calculated by t-test. Graphs show mean ± SD. * P<0.05.

[0078] Figure 20 demonstrates that OSM induced collagen secretion from primary human fibroblasts in an OSMR-dependent manner. Primary human FIB cells were cultured and stimulated with rhOSM (10 ng / ml) for 72 hours. The cells were treated with anti-OSMR (50 ug / ml) or anti-LIFR (50 ug / ml) 120 minutes before OSM treatment. The secretion of Petition 870250079694, dated 05 / 09 / 2025, pp. 144 / 267 21 / 97 collagen (COL) was stained and evaluated using CellInsight CX7 in the one-flask scar assay. P-value calculated by t-test. Graphs show mean ± SD. * P<0.05.

[0079] Figure 21 demonstrates that OSM-induced chemokine production from PCLS depends on OSMR, not LIFR. Precision-cut lung slices (PCLS) were prepared and stimulated with rhOSM (10 ng / ml) for 24 hours with anti-OSMR (50 ug / ml) or anti-LIFR (50 ug / ml) 120 minutes before OSM treatment and throughout treatment. CCL3 and CCL4 were measured by Luminex® in supernatants. P-value calculated by t-test. Graphs show mean ± SD. * P<0.05.

[0080] Figure 22A shows the changes in body weight of WT C57BL / 6J mice that received intratracheal saline solution (PBS) or bleomycin (BLM) on days 0, 2, and 4. Mice received isotype control antibody, anti-OSM mAb + isotype, anti-IL-6R mAb + isotype, or anti-IL-6R mAb + anti-OSMR (500 µg / mouse every 3 days, starting on day -1). Body weight was monitored weekly.

[0081] Figure 22B shows the survival of WT C57BL / 6J mice that received intratracheal saline (PBS) or bleomycin (BLM) on days 0, 2, and 4. Mice received isotype control antibody, anti-OSM mAb + isotype, anti-IL-6R mAb + isotype, or anti-IL-6R mAb + anti-OSMR (500 µg / mouse every 3 days, starting on day -1). Mice with >25% weight loss were sacrificed.

[0082] Figure 22C provides the tissue volume (TV) on day 22 of WT C57BL / 6J mice that received intratracheal saline (PBS) or bleomycin (BLM) on days 0, 2, and 4. Mice received isotype control antibody, anti-OSM + isotype mAb, anti-IL-6R + isotype mAb, or anti-IL-6R + anti-OSMR mAb (500 µg / mouse every 3 days, starting on day -1). 5-25 mice per group. P-value calculated by t-test. Graphs Petition 870250079694, dated 05 / 09 / 2025, pp. 145 / 267 22 / 97 show mean ± SD. * P<0.05.

[0083] Figure 23A shows new hydroxyproline (New OHP, µg / half lung) in lung tissue measured in mice treated with deuterated water on day 24. 5-25 mice per group. Lung pathology (fibrosis score) was assessed blindly. Lung tissue was retrieved on day 24 for sectioning and pathology assessment.

[0084] Figure 23B provides representative sections stained with Mason's trichrome. 5-25 mice per group. P-value calculated by t-test. Graphs show individual mice and mean ± SD. * P<0.05.

[0085] Figure 24 provides total and differential cell counts (macrophages, Mac; lymphocytes, Lym; neutrophils, Neut) of mice that received bronchoalveolar lavage (BAL). 5-25 mice per group. P-value calculated by t-test. Graphs show mean ± SD. * P<0.05. Detailed Description

[0086] The practice of the methods, as well as the preparation and use of the compositions in this document, employ, unless otherwise indicated, conventional techniques in molecular biology, biochemistry, chromatin structure and analysis, computational chemistry, cell culture, recombinant DNA, and related fields, to the extent possible. These techniques are fully explained in the literature.

[0087] The term “in the present document” means the entire application.

[0088] It should be understood that any of the embodiments described herein, including those described in different aspects of the disclosure and different parts of the specification (including embodiments described only in the Examples), may be combined with one or more other embodiments disclosed herein, unless explicitly rejected or deemed inappropriate. The combination of embodiments is not limited Petition 870250079694, dated 05 / 09 / 2025, pp. 146 / 267 23 / 97 to the specific combinations claimed through the multiple dependent claims.

[0089] Any published publications, patents and patent applications mentioned are specifically incorporated by reference herein. In case of conflict, this specification, including its specific definitions, shall prevail.

[0090] Throughout this specification, the word “comprise” or variations such as “comprises” or “comprising”, which is synonymous with “including”, “containing” or “characterized by”, is inclusive or open-ended and does not exclude additional elements or method steps not mentioned.

[0091] Throughout the specification, where compositions are described as having, including, or comprising (or variations thereof) specific components, it is contemplated that the compositions may also consist essentially of, or be comprised of, the aforementioned components. Similarly, when methods or processes are described as having, including, or comprising specific process steps, the processes may also consist essentially of, or be comprised of, the aforementioned processing steps. Furthermore, it should be understood that the order of the steps or the order in which certain actions are performed is irrelevant, provided that the compositions and methods described herein remain operable. Additionally, two or more steps or actions may be performed simultaneously.

[0092] The term “consisting of” excludes any element, step or ingredient not specifically recited.

[0093] The term “consisting essentially of” limits the scope of a disclosure to the materials or steps specified and those that do not materially affect the basic and novel feature(s) of the disclosure.

[0094] Any example(s) following the term “for example” or “by Petition 870250079694, dated 05 / 09 / 2025, pp. 147 / 267 The example "24 / 97" is not intended to be exhaustive or limiting.

[0095] The articles “a”, “an”, “the”, and “the” are used in this document to refer to one or more than one (i.e., at least one) grammatical object of the article. For example, “an element” means one element or more than one element.

[0096] The term “or”, as used in this document, should be understood as “and / or”, unless the context clearly indicates otherwise.

[0097] Although the ranges and numerical parameters that define the broad scope of the disclosure are approximations, the numerical values ​​presented in the specific examples are reported to the greatest possible accuracy. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in its respective test measurements. Furthermore, all ranges disclosed in this document should be understood as encompassing any and all sub-ranges included therein. For example, a stated range of “1 to 10” should be considered as including any and all sub-ranges between (and including) the minimum value of 1 and the maximum value of 10; that is, all sub-ranges beginning with a minimum value of 1 or more, for example, 1 to 6.1, and ending with a maximum value of 10 or less, for example, 5.5 to 10. Disclosure of a range should also be considered as disclosure of the outcomes of that range.

[0098] Illustrative methods and materials are described herein, although similar or equivalent methods and materials may also be used in the practice or testing of this application. The materials, methods, and examples are for illustrative purposes only and are not intended to be limiting. Definitions

[0099] The following terms, except where otherwise indicated Petition 870250079694, dated 05 / 09 / 2025, pp. 148 / 267 25 / 97 form, should be understood as having the following meanings:

[0100] As used in this document, the term “approximately” or “about,” when applied to one or more values ​​of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term “approximately” or “about” refers to a range of values ​​that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less in any direction (greater or less than) the stated reference value, unless otherwise indicated or evident from the context (except where such number exceeds 100% of a possible value). The reference to “about” a value or parameter in this document includes (and describes) realizations that are directed to that value or parameter. For example, the description that refers to “about X” includes the description of “X”. Numerical ranges include the numbers that define the range.

[0101] As used in this document, the term “biomarker” refers to an indicator of, for example, an individual’s pathological state, which can be detected in a biological sample from the individual. Biomarkers include molecular markers based on DNA, RNA, and proteins.

[0102] As used in this document, the term “diagnosis” refers to the identification or classification of a molecular or pathological state, disease, or condition. For example, “diagnosis” may refer to the identification of a particular type of condition (such as idiopathic pulmonary fibrosis or usual interstitial pneumonia (“UIP”)). “Diagnosis” may also refer to the classification of a particular subtype of a condition (such as idiopathic pulmonary fibrosis), for example, by histopathological or radiographic criteria or by molecular characteristics (for example, a subtype characterized by the expression of one or a combination of particular genes or proteins). Petition 870250079694, dated 05 / 09 / 2025, pp. 149 / 267 26 / 97 encoded by genes). The term “suffering from” or “experiencing,” as used in this document, may refer to an individual who has not received a formal diagnosis of a disease or disorder but exhibits several of the symptoms that could lead to a formal diagnosis of the disease or disorder.

[0103] As used in this document, the term “diagnostic aid” refers to methods that assist in making a clinical determination as to the presence or nature of a particular type of symptom or condition (such as idiopathic pulmonary fibrosis). For example, a method to assist in the diagnosis of a condition (such as idiopathic pulmonary fibrosis) might include measuring the expression of certain genes in a biological sample from an individual.

[0104] As used in this document, the term “prognosis” is used herein to refer to the prediction of the likelihood of survival over time, as well as one or more disease symptoms attributable to a condition (such as idiopathic pulmonary fibrosis) that worsen over time.

[0105] As used in this document, the term “initial dose” or “loading dose” generally refers to an initial dose of a therapeutic agent administered to a patient or individual and followed by one or more maintenance doses of the same. Usually, a single loading dose is administered, but multiple loading doses are contemplated in this document. Typically, the amount of loading dose(s) administered exceeds the amount of maintenance dose(s) administered.

[0106] As used in this document, the term “maintenance” dose refers in this document to one or more doses of a therapeutic agent administered to the patient during a treatment period. Typically, maintenance doses are administered at spaced treatment intervals, such as approximately every week. Petition 870250079694, dated 05 / 09 / 2025, pp. 150 / 267 27 / 97 approximately every 2 weeks, approximately every 3 weeks, or approximately every 4 weeks, preferably every 3 weeks. An example maintenance dose for subcutaneous vixarelimab is 360 mg.

[0107] As used in this document, the term “sample” refers to a composition obtained from or derived from an individual of interest that contains a cellular and / or other molecular entity that is to be characterized and / or identified, for example, based on physical, biochemical, chemical, and / or physiological characteristics. For example, the phrase “disease sample” and its variations refer to any sample obtained from an individual of interest that is expected or known to contain the cellular and / or molecular entity to be characterized. A “tissue” or “cell sample” refers to a collection of similar cells obtained from a tissue of an individual or patient.The source of the tissue or cell sample may be solid tissue from a fresh, frozen, and / or preserved organ or tissue sample, biopsy, or aspirate; blood or any blood constituents; body fluids such as cerebrospinal fluid, amniotic fluid, peritoneal fluid, or interstitial fluid; cells from any point in the individual's gestation or development. The tissue sample may also consist of primary or cultured cells or cell lines. Optionally, the tissue or cell sample is obtained from a diseased tissue / organ. The tissue sample may contain compounds that are not naturally mixed with tissue in nature, such as preservatives, anticoagulants, buffers, fixatives, nutrients, antibiotics, and the like.

[0108] As used in this document, the terms “control”, “control cohort”, “reference sample”, “reference cell”, “reference tissue”, “control sample”, “control cell” and “control tissue” refer to a sample, cell or tissue obtained from a source that is Petition 870250079694, dated 05 / 09 / 2025, pp. 151 / 267 28 / 97 known, or believed to be unaffected, by the disease or condition for which a disclosure method or composition is being used to identify. The control may include one or more controls. In one embodiment, a reference sample, reference cell, reference tissue, control sample, control cell, or control tissue is obtained from a healthy part of the body of the same individual or patient in whom a disease or condition is being identified using a disclosure composition or method. In another embodiment, a reference sample, reference cell, reference tissue, control sample, control cell, or control tissue is obtained from a healthy part of the body of an individual who is not the subject or patient in whom a disease or condition is being identified using a disclosure composition or method.

[0109] The terms “amino acid” and “amino acid identity,” as used in this document, refer to one of the 20 naturally occurring amino acids that are encoded by DNA and RNA.

[0110] The term “amino acid substitution” or “substitution,” as used in this document, refers to the replacement of an amino acid at a particular position in a parent polypeptide sequence with a different amino acid. In particular, in some embodiments, the substitution is for an amino acid that does not naturally occur at the particular position, nor does it occur naturally within the organism or in any organism. For example, the E272Y substitution refers to a variant polypeptide, in this case an Fc variant, in which glutamic acid at position 272 is replaced with tyrosine. For clarity, a protein that has been designed to alter the nucleic acid coding sequence but not alter the initial amino acid (e.g., swapping CGG (which codes for arginine) for CGA (which still codes for arginine) to increase host organism expression levels) is not an amino acid substitution; that is, despite the creation Petition 870250079694, dated 05 / 09 / 2025, pp. 152 / 267 29 / 97 of a new gene that codes for the same protein, if the protein has the same amino acid at the particular position with which it started, it is not considered an amino acid substitution.

[0111] The terms “amino acid insertion”, “amino acid addition” or “addition” or “insertion”, as used in this document, refer to the addition of an amino acid sequence at a particular position in a parent polypeptide sequence. For example, -233E, _233E or 233E designates a glutamic acid insertion after position 233 and before position 234. Additionally, -233ADE, _233ADE or 233ADE designates an AlaAspGlu insertion after position 233 and before position 234.

[0112] The term “amino acid deletion” or “deletion,” as used in this document, refers to the removal of an amino acid sequence at a particular position in a parent polypeptide sequence. For example, E233- or E233#, E233( ), E233_ or E233del designate a deletion of glutamic acid at position 233. Additionally, EDA233-, EDA233_ or EDA233# designates a deletion of the GluAspAla sequence beginning at position 233.

[0113] As used in this document, the term “antibody” or “Ab” refers to an immunoglobulin molecule (e.g., whole antibodies, antibody fragment, or modified antibodies) capable of recognizing and binding to a specific target or antigen, such as a carbohydrate, polynucleotide, lipid, polypeptide, etc., through at least one antigen recognition site located in the variable region of the immunoglobulin molecule. As used in this document, the term “antibody” is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, human antibodies, engineered antibodies (including antibodies Petition 870250079694, dated 05 / 09 / 2025, pp. 153 / 267 30 / 97 humanized antibodies, fully human antibodies, chimeric antibodies, single-chain antibodies, artificially selected antibodies, CDR-granted antibodies, etc.), monospecific antibodies and multispecific antibodies (e.g., bispecific antibodies, wherein bispecific antibodies each have at least two binding sites and bind specifically to two different antigens or to the same antigen at two different epitopes) and antibody fragments that retain the desired antigen-binding activity. In some embodiments, “antibody” and / or “immunoglobulin” (Ig) refers to a polypeptide comprising at least two heavy (H) chains (about 50–70 kDa) and two light (L) chains (about 25 kDa), optionally interconnected by disulfide bonds. In some embodiments, the antibody is a full-length antibody. There are two types of light chain: λ and κ.In humans, the λ and κ light chains are similar, but only one type is present in each antibody. The heavy chains are classified as mu, delta, gamma, alpha, or epsilon and define the antibody isotype as IgM, IgD, IgG, IgA, and IgE, respectively. See, in general, Fundamental Immunology Chapter 7 (Paul, W., ed., 2nd ed. Raven Press, NY. (1989)). The methods, uses, and compositions for use disclosed in this document use IgG antibodies.

[0114] The terms “nucleic acid”, “polynucleotide” and “oligonucleotide” are used interchangeably and refer to a polymer of deoxyribonucleotide or ribonucleotide, in linear or circular conformation and in single or double strand form. For the purposes of this disclosure, these terms should not be interpreted as limiting with respect to the length of a polymer.

[0115] The term “complementarity-determining region” or “CDR”, as used in this document, refers to each of the regions of a variable antibody domain that are hypervariable in Petition 870250079694, dated 05 / 09 / 2025, pp. 154 / 267 31 / 97 sequence and which determine the specificity of antigen binding, for example, “hypervariable regions” or (“HVRs”).

[0116] Generally, monospecific antibodies comprise six CDRs: three in the HV (H1, H2, H3) and three in the LV (L1, L2, L3). Multispecific antibodies generally comprise several sets of six CDRs. For example, a bispecific antibody generally comprises at least two sets of six CDRs. Exemplary CDRs in this document include: (a) hypervariable loops occurring at amino acid residues 26 (L1), 50 52 (L2), 91 96 (L3), 26 32 (H1), 53 55 (H2) and 96 101 (H3) (Chothia and Lesk, J. Mol. Biol. 196:901 917 (1987)); (b) CDRs occurring at amino acid residues 24 34 (L1), 50 56 (L2), 89 97 (L3), 31 35b (H1), 50 65 (H2) and 95 102 (H3) (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991)); and (c) antigen contacts occurring at amino acid residues 27c 36 (L1), 46 55 (L2), 89 96 (L3), 30 35b (H1), 47 58 (H2) and 93 101 (H3) (MacCallum et al. J. Mol. Biol. 262: 732 745 (1996)).

[0117] The term “individual” is used in this document interchangeably with “patient” to refer to an individual to be treated. The individual is a mammal (e.g., human, non-human primate, rat, mouse, cow, horse, pig, sheep, goat, dog, cat, etc.). The individual may be a clinical patient, a clinical trial volunteer, an experimental animal, etc. The individual may be suspected of having or be at risk of having a condition (such as idiopathic pulmonary fibrosis) or be diagnosed with a condition (such as idiopathic pulmonary fibrosis). The individual may also be suspected of having or be at risk of having a lung disease or be diagnosed with a lung disease, such as, for example, hypersensitivity pneumonitis, cryptogenic organizing pneumonia, diffuse alveolar damage, Petition 870250079694, dated 05 / 09 / 2025, pages 155 / 267 32 / 97 chronic obstructive pulmonary disease, chronic bronchitis, pulmonary emphysema, pulmonary arterial hypertension, nonspecific interstitial pneumonitis, interstitial lung disease associated with systemic sclerosis, or interstitial lung disease associated with collagen vascular disease. In some embodiments, the individual to be treated according to this disclosure is a human.

[0118] As used in this document, “treat,” “treatment,” and “relief” refer to measures whose objective is to prevent or delay (reduce) the target pathological condition or disorder or to alleviate some of the symptoms of the disorder. Those who need treatment may include those who already have the disorder, as well as those likely to have it, those at risk of having it, and those in whom the disorder should be prevented. In some embodiments, the individual who needs treatment already has the disorder.For example, an individual is considered successfully "treated" for idiopathic pulmonary fibrosis or systemic sclerosis-associated interstitial lung disease if, after receiving a therapeutic agent, the individual exhibits an observable and / or measurable decrease or change from baseline and / or a measurable rate of change from baseline over time (e.g., over 3 months (12 weeks), or 6 months (24 weeks), or 9 months (36 weeks), or 12 months (1 year, 52 weeks)) in one or more of the following: forced vital capacity (FVC), lung diffusion capacity for carbon monoxide (DLco), an individual-reported outcome tool such as A Tool to Assess Quality of Life in Idiopathic Pulmonary Fibrosis (ATAQ-IPF) or the EuroQol 5Dimension Questionnaire (EQ-5D), St.George's Respiratory Questionnaire (SRGQ), 6-minute walk distance (6MWD), resting oxygen flow rate, radiographic findings on high-resolution computed tomography (HRCT) of the lung, including quantitative pulmonary fibrosis score (QLF), serum biomarkers including CXCL14, periostin, CCL18 (chemokine ligand 18 (CC motif)), YKL40 (yellow-like protein). Petition 870250079694, dated 05 / 09 / 2025, pp. 156 / 267 33 / 97 chitinase-3; CHI3L1), COMP (cartilage oligomeric matrix protein), OPN (osteopontin), CCL13 (chemokine ligand 13 (CC motif)).

[0119] “Administering” or “administration of” a substance, compound, or agent to an individual refers to the contact of that substance, compound, or agent with the individual or with a cell, tissue, organ, or body fluid of the individual. For example, a compound or agent may be administered intravenously or subcutaneously. In some embodiments, a “combination” or “combination therapy” refers to the administration of more than one therapeutic agent. When more than one substance, compound, or agent is being administered, the administration may be simultaneous or sequential. “Simultaneous administration” refers to the administration of multiple therapeutic agents at the same time. The therapeutic agents administered simultaneously may be co-formulated or mixed before administration. “Sequential administration” refers to the administration of multiple therapeutic agents at different times in order to obtain overlapping results.For example, two therapeutic agents may be administered on the same day in two separate injections. Alternatively, one agent may be injected on one day, and the second on a subsequent day. Sequential administration is not limited to cases where more than one therapeutic agent is present in the individual's body. For example, if a first therapeutic agent expands the individual's T-cell population, and a second therapeutic agent directs the individual's T cells to a tumor, then the two agents may be administered sequentially if the second agent is administered at a time when the individual's T-cell population is still expanded, even if no therapeutic agent from the first agent remains in the individual's body. Administration may also be performed, for example, once, multiple times, and / or over one or more prolonged periods. Petition 870250079694, dated 05 / 09 / 2025, pp. 157 / 267 34 / 97 can be direct, including in self-administration, or indirect, including in the act of prescribing a drug. For example, as used in this document, a physician who instructs an individual to self-administer a drug, or to have the drug administered by another person, and / or who provides an individual with a prescription for a drug is administering the drug to the individual.

[0120] An “effective amount” refers to an amount that is effective, at the dosages and for the time periods required, to achieve the desired therapeutic or prophylactic result. The term “therapeutically effective amount” refers to an amount that is effective in “relieving” or “treating” a disease or disorder in an individual. A therapeutically effective amount of a therapeutic agent may vary depending on factors such as the disease state, age, sex, and weight of the individual, and the ability of the antibody to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or harmful effects of the therapeutic agent are offset by the therapeutically beneficial effects. A “prophylactically effective amount” refers to an amount that is effective, at the dosages and for the time periods required, to achieve the desired prophylactic result.Normally, but not necessarily, once a prophylactic dose is used in individuals before or at an earlier stage of the disease, the prophylactically effective amount will be less than the therapeutically effective amount. "Chronic" administration refers to the continuous administration of the agent(s), as opposed to acute administration, in order to maintain the initial therapeutic effect (activity) for a long period of time. "Intermittent" administration is treatment that is not given consecutively without interruption, but rather is cyclical in nature.

[0121] As used in this document, the terms “polypeptide”, “peptide” and “protein” are used interchangeably to refer to a polymer of amino acid residues. The expression of an antibody in Petition 870250079694, dated 05 / 09 / 2025, pages 158 / 267 35 / 97 A cell can result from the delivery of the antibody protein to the cell or from the delivery of a polynucleotide encoding the antibody to a cell, wherein the polynucleotide is transcribed and the transcript is translated to generate the antibody. Trans-splicing, polypeptide cleavage, and polypeptide ligation may also be involved in the expression of a protein in a cell. The methods for delivering polynucleotides and polypeptides to cells are known in the art.

[0122] The term “package insert” is used to refer to the instructions normally included in commercial packaging of therapeutic products that contain information on the indications, use, dosage, administration, combination therapy, contraindications and / or warnings relating to the use of such therapeutic products.

[0123] The term “variable region” or “variable domain” refers to the domain of an antibody heavy chain or light chain that is involved in antibody binding to the antigen. The variable domains of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved structural regions (FRs) and three hypervariable regions (HVRs). (See, for example, Kindt et al. Kuby Immunology, 6th ed., WH Freeman and Co., page 91 (2007).) A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind to a particular antigen can be isolated using a VH or VL domain from an antigen-binding antibody to submit a library of complementary VL or VH domains to screening, respectively. See, for example, Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991).

[0124] The term “OSM”, as used herein, refers to oncostatin M. The term “IL-31”, as used herein Petition 870250079694, dated 05 / 09 / 2025, pp. 159 / 267 Document 36 / 97 refers to interleukin-31. Both OSM and IL-31 are well-known cytokines that are members of the IL-6 superfamily. The term “OSMR,” as used in this document, refers to the oncostatin M receptor and is also referred to in this document as “ISMRβ” or “Type II OSMR.” OSM is a member of the type I cytokine receptor family. OSMRβ heterodimerizes with glycoprotein 130 (also known in this document as gp130) to form the type II OSMR, which transduces OSM-induced signaling events. OSMRβ also heterodimerizes with the IL-31 receptor A (IL31RA) to form the IL-31 receptor, which transduces IL-31-induced signaling events. An exemplary human OSMRp amino acid sequence is provided in GenBank accession number NP_003990.

[0125] As used in this document, “IL-6”, “IL6” or “Interleukin 6” may be used interchangeably and refer to a four-helix α protein belonging to a family of cytokines. IL-6 acts as a pro-inflammatory cytokine and an anti-inflammatory myokine.

[0126] As used in this document, “tocilizumab” refers to a recombinant humanized monoclonal antibody that binds to the human interleukin-6 receptor (IL-6R), listed in Proposed List 90 of International Nonproprietary Names for Pharmaceuticals (INN) (WHO Drug Information, Vol. 18, No. 1, 2004, p. 66) and with heavy chain and light chain amino acid sequences listed under CAS Registry Number 375823-41-9. It is an IgG1 (gamma 1, kappa) antibody with two heavy chains and two light chains forming two antigen-binding sites. In a preferred embodiment, the heavy chain and light chain amino acid sequences of tocilizumab comprise SEQ ID NOs: 13 and 14, respectively. Tocilizumab is also known technically as "Actemra®" or "RoActemra®". Petition 870250079694, dated 05 / 09 / 2025, pp. 160 / 267 37 / 97

[0127] As used in this document, the term “vixarelimab” refers to a monoclonal antibody targeting the oncostatin M receptor beta (OSMRe), which mediates interleukin-31 (IL-31) and oncostatin M protein (OSM) signaling with the heavy chain and light chain amino acid sequences listed in List 85 of International Nonproprietary Names for Pharmaceuticals (INN) (WHO Drug Information, Vol. 35, No. 1, 2021, pp. 228-229). In some embodiments, vixarelimab comprises a heavy chain with the amino acid sequence SEQ ID NO:1 and a light chain with the amino acid sequence SEQ ID NO:2. Vixarelimab is also known in some non-patent publications as “KPL-716.” General

[0128] Two predominant unmet needs have emerged in the treatment of interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF) and systemic sclerosis with ILD (SSc-ILD): preserving lung function and halting progressive fibrosis. Tocilizumab (an anti-IL6R antibody) was recently approved for the treatment of SScILD. Although tocilizumab has been shown to prevent the decline in lung function, there is still a growing need to identify and develop therapeutics to halt progressive fibrosis.

[0129] IL-11 has recently emerged as an important contributor to pulmonary, hepatic, and cardiac fibrosis. See, for example, Schafer, S., et al. IL-11 is a crucial determinant of cardiovascular fibrosis. Nature 552, 110-115 (2017); Ng, B., et al. Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Sci Transi Med 11 (2019); and Effenberger, M., et al. Interleukin-11 causes alcohol-related liver disease in humans and mice. Gut 72, 168-179 (2023). Consequently, inventors have considered IL-11 as a potential target for interrupting fibrosis. Petition 870250079694, dated 05 / 09 / 2025, pp. 161 / 267 38 / 97 progressive. However, although IL-11 has been observed to contribute to airway inflammation in vivo (data not shown) and induce inflammatory cytokine responses in lung fibroblasts in vitro (data not shown), IL-11 did not appear to have fibrogenic properties in lung in vivo or with lung-derived fibroblasts in vitro (data not shown).

[0130] Oncostatin M (OSM) has been associated both positively and negatively with fibrosis. Surprisingly, however, the requirement for OSM and OSMR signaling in pulmonary fibrosis does not appear to have been tested technically, genetically, or pharmacologically. As described in more detail in the Examples below, OSM orchestrated the response to lung injury, contributing to epithelial and endothelial cell disruption, myofibroblast activation, and fibrosis. In humans, OSM binds to gp130 and heterodimerizes with one of two receptors, OSMR or LIFR, for signal transduction. As demonstrated in the Examples below, of the two receptors, it is OSMR, not LIFR, that acts as the dominant receptor complex used by OSM in a disease-relevant context. Furthermore, OMSR antagonism alone was almost sufficient to mitigate OSM-induced pSTAT3 phosphorylation in fibroblasts and epithelial cells.The roles of OSM and IL-6 in ILD have been shown in this document to be non-overlapping. Consequently, the experiments and data presented herein demonstrate that inhibition of the OSM / OSMRe pathway can be used to halt progressive fibrosis in patients with ILD. VIXARELIMAB AND INHIBITION OF THE OSM / OSMRB PATHWAY VIXARELIMAB

[0131] Vixarelimab is a monoclonal antibody that targets OSMRe (oncostatin M (OSM) receptor) (described as “Ab2” in U.S. Patent No. 9,593,163 (hereinafter, “Patent 163”), the contents of which are incorporated herein by reference. Petition 870250079694, dated 05 / 09 / 2025, pp. 162 / 267 39 / 97 totality). OSMRe is a cytokine receptor subunit that heterodimerizes with the IL-31 alpha receptor (IL-31 Ra) or gp130 to form two distinct receptors for two distinct cytokines, interleukin-31 (IL-31) and OSM, respectively, each mediating signaling pathways involved in inflammation and fibrosis (Mozaffarian et al. 2008; Marden et al. 2020; Yaseen et al. 2020; Kuzumi et al.

[0132] Vixarelimab is one of 3 anti-OSMRβ antibodies generated and described in patent '163 that have been shown using in vitro cell assays to block signaling via human OSMRβ. The assays, described at least in Examples 2 and 3 of patent '163, demonstrate that the three anti-OSMRβ antibodies (“Ab1”, “Ab2”, and “Ab3”) were each a potent inhibitor of OSM-mediated signaling and IL-31-mediated signaling. The heavy chain and light chain sequences are provided in Table 1 below. In preferred embodiments, the preferred anti-OSMRβ antibody for the treatment of pulmonary fibrotic disorders, as described herein, is vixarelimab. Table 1 SEQ ID NO. VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECP PCPAPPVAGPSVFLFPKPKPKDTLMISRTPEVTCVVVDVSH EDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREP QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK Cadeia Leve de Ab1 2 QSVLTQPPSASGTPGQRVTISCSGSSSNVGSNTVSWYQ QLPGTAPKLLIYTNNRRPSGVPDRFSGSKSGTSASLAISG LQ SEDEADYFCAALDDSLNGVVFGGGTKLTVLGQPKAAPSV TLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPV K AGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQV -ri ιι-^ο-r» <ni / -ru«n-rnon Petition 870250079694, de 05 / 09 / 2025, pág. 163 / 267 40 / 97 SEQ ID NO Sequence Variable domain of Ab1 heavy chain 3 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQ ATGQGLEWMGWMNPNSGNTDYAQKFQGRVTMTRNISIS TAYIELSSLRSEDTAVYYCARDMVAANTDYYFYYGMDVW GQGTTVTVSS Variable domain of Ab1 light chain 4 QSVLTQPPSASGTPGQRVTISCSGSSSNVGSNTVSWYQ QLPGTAPKLLIYTNNRRPSGVPDRFSGSKSGTSASLAISG LQSEDEADYFCAALDDSLNGVVFGGGTKLTVLG Heavy chain of Vixarelimab (“Ab2”) 5 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYEINWVRQ ATGQGLEWMGWMNPNSGYTGYAQKFQGRVTMTRDTSI STAYMEMSSLRSEDTAVYYCARDIVAANTDYYFYYGMDV WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPC PPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV SQEDPEVQFNWYVDGVEVHNAKTKPREEQFQSTYRVVS VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPR EPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPG Vixarelimab Light Chain (“Ab2”) 6 QSVLTQPPSASGTPGQRVTISCSGSNSNIGSNTVNWYHQ LPGTAPKLLIYNINKRPSGVPDRFSGSKSGSSASLAISGLQSEDEADYYCSTWDDSLDGVVFGGGTKLTVLGQPKAAPS VTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSP VKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSC QVTHEGSTVEKTVAPTECS Variable heavy chain domain of Vixarelimab (“Ab2”) 7 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYEINWVRQ ATGQGLEWMGWMNPNSGYTGYAQKFQGRVTMTRDTSI STAYMEMSSLRSEDTAVYYCARDIVAANTDYYFYYGMDV WGQGTTVTVSS Variable light chain domain of Vixarelimab (“Ab2”) 8 QSVLTQPPSASGTPGQRVTISCSGSNSNIGSNTVNWYHQ LPGTAPKLLIYNINKRPSGVPDRFSGSKSGSSASLAISGLQ SEDEADYYCSTWDDSLDGVVFGGGTKLTVLG Heavy chain of Ab3 9 QVHLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQ APGQGLEWMGWLSTYSGNTNYAQKLQGRVTMTTDTSTS TAYMELRSLRSDDTAVYYCARGNFYYYGMDVWGQGTTV TVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSN FGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPV AGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQF NWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDW LNGKEYKCK VSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK Light chain ofAb3 10 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQ KPGQAPRLLIFGASSRATGIPDRFSGSGSGTDFTLTISRLE PEDFAVYYCQQYGSSPPITFGQGTRLEIKRTVAAPSVFIFP PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT HQGLSSPVTKSFNRGEC Petition 870250079694, dated 05 / 09 / 2025, pp. 164 / 267 41 / 97 SEQ ID NO Sequence Ab3 Heavy Chain Variable Domain 11 QVHLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQ APGQGLEWMGWLSTYSGNTNYAQKLQGRVTMTTDTSTS TAYMELRSLRSDDTAVYYCARGNFYYYGMDVWGQGTTV TVSS Ab3 Light Chain Variable Domain 12 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQ KPGQAPRLLIFGASSRATGIPDRFSGSGSGTDFTLTISRLE PEDFAVYYCQQYGSSPPITFGQGTRLEIKR

[0133] In some embodiments, the anti-OSMRe antibody is Ab1. In some embodiments, the heavy chain comprises the amino acid sequence SEQ ID NO: 1. In some embodiments, the light chain comprises the amino acid sequence SEQ ID NO: 2. In some embodiments, the variable domain of the heavy chain comprises the amino acid sequence SEQ ID NO: 3. In some embodiments, the variable domain of the light chain comprises the amino acid sequence SEQ ID NO: 4. In some embodiments, the heavy chain comprises the amino acid sequence SEQ ID NO: 1 and the light chain comprises the amino acid sequence SEQ ID NO: 2.

[0134] In some embodiments, the anti-OSMRe antibody is vixarelimab (“Ab2”). In some embodiments, the heavy chain comprises the amino acid sequence of SEQ ID NO: 5. In some embodiments, the light chain comprises the amino acid sequence of SEQ ID NO: 6. In some embodiments, the variable domain of the heavy chain comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the variable domain of the light chain comprises the amino acid sequence of SEQ ID NO: 8. In some embodiments, the heavy chain comprises the amino acid sequence of SEQ ID NO: 5 and the light chain comprises the amino acid sequence of SEQ ID NO: 6.

[0135] In some embodiments, the anti-OSMRe antibody is Ab3. In some embodiments, the heavy chain comprises the amino acid sequence SEQ ID NO: 9. In some embodiments, the light chain Petition 870250079694, dated 05 / 09 / 2025, pages 165 / 267 42 / 97 comprises the amino acid sequence of SEQ ID NO: 10. In some embodiments, the variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 11. In some embodiments, the variable light chain domain comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the heavy chain comprises the amino acid sequence of SEQ ID NO: 9 and the light chain comprises the amino acid sequence of SEQ ID NO: 10. IL-31

[0136] IL-31 is a T-cell derived cytokine that appears to be involved in the cutaneous and epithelial signs and symptoms observed in pruritus, skin inflammation, and airway hypersensitivity (Kabashima and Irie, 2021, Front in Med, 8:638-325; Dillon et al, 2004, Nat Immunol, 5:752-760). Vixarelimab has been used in clinical studies in patients diagnosed with AD or PN. The phase 2 clinical studies of vixarelimab (ClinicalTrials.gov identifiers NCT03816891 and NCT03858634) include a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy, safety, tolerability, PK, and immunogenicity of subcutaneously administered vixarelimab in individuals with prurigo nodularis (PN) presenting with pruritus. The results of these previous clinical studies of vixarelimab yielded safety and efficacy data in inflammatory and hyperkeratotic skin disorders.Regarding the role of IL-31 in pulmonary fibrotic disorders, IL-31 treatment in mice resulted in significant fibrosis in the central area of ​​the lung (Yaseen et al., 2020, Rheumatology, 59:2625-2636), while loss of IL-31 signaling in a mouse model of pulmonary fibrosis attenuated collagen deposition and the decline in lung function (Yombo et al., 2021, Front Immunol, 12:s645717). OSM

[0137] OSM is a cytokine from the IL-6 superfamily and is expressed Petition 870250079694, dated 05 / 09 / 2025, pages 166 / 267 43 / 97 in a variety of immune cells, including activated T cells, monocytes, dendritic cells, neutrophils, activated mast cells, and eosinophils (Wallace et al., 1999, J Immunol, 162:5547-5555; Stawski and Trojanowska, 2019, Connect Tissue Res, 60:40-49). OSM signaling can be initiated by binding to one of two types of OSM receptors: the type I receptor complex (LIFRb / gp130) or the type II receptor complex (OSMRe / gp130).

[0138] The OSM protein is increased in bronchoalveolar lavage (BAL) samples from patients with IPF and SSc-ILD compared to healthy controls (Mozaffarian et al. 2008). Data show that OSM mRNA increases in the lungs of IPF patients compared to controls (e.g., see Example 1 in this document). Viral overexpression or delivery of recombinant OSM to the lungs of mice is sufficient to induce inflammation and fibrotic remodeling (Mozaffarian et al. 2008; Wong et al. 2014). Furthermore, OSM increases the survival and proliferation of lung fibroblasts and promotes collagen production (Scaffidi et al. 2002). The data show that OSM inhibition using an anti-OSM antibody or OSM genetic deletion in a bleomycin model of pulmonary fibrosis leads to a reduction in lung injury and collagen deposition (e.g., see Example 2 in this document).

[0139] Furthermore, interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc), an autoimmune disorder characterized by fibrosis of the skin and other organ systems. Pulmonary fibrosis present in SSc patients is an important prognostic indicator for SSc patients and the most common cause of death in these patients. OSM is upregulated in CD8+ T cells in the lungs of SSc and ILD patients compared to patients without lung disease or healthy controls (Luzina et al., 2003, Arthritis Rheum, 48:2262-2274). Petition 870250079694, dated 05 / 09 / 2025, pages 167 / 267 44 / 97 VIXARELIMAB FOR THE TREATMENT OF PULMONARY PHLOBAL DISORDERS

[0140] Although previous clinical studies with vixarelimab in patients suffering from skin disorders such as PN have demonstrated safety and some efficacy, there are no clinical data describing the treatment of patients with pulmonary fibrosis with an anti-OSMRe antibody such as vixarelimab, which blocks OSM and IL-31 signaling. It is important to emphasize that dosing the antibody to achieve therapeutic activity in patients suffering from fibrotic lung disorders remains a challenge, considering the unknown impact of anti-OSMRe antibody exposure to OSMRe on cell surfaces in the pulmonary environment compared to the skin. In fact, the translation of IL-31-induced pruritic indications to OSM-induced fibrosis is particularly unpredictable.

[0141] As described in this document, PK / PD modeling (e.g., Dua et al., 2014, CPT Pharmacometrics Syst. Pharmacol, 4:324-337) was used to predict a therapeutically effective dose of an anti-OSMRe antibody for the treatment of pulmonary fibrotic disorders, including, without limitation, IPF and SSc-ILD. The modeling was based, in part, on in vitro potency assays, preclinical PK / PD studies, and dose pharmacokinetic data tested in phase 1 and 2 trials with patients with AD and PN (see, for example, Example 3 in this document). This disclosure provides methods for treating pulmonary fibrotic disorders by administering an anti-OSMRe antibody to an individual in need thereof, wherein the anti-OSMRe antibody binds to the extracellular domain of the OSMRe protein and blocks type II OSMR signaling by OSM and IL31. In preferred embodiments, the dosage regimen for vixarelimab antibody administration is 360 mg every 2 weeks.In some applications, the patient does not receive a loading dose.

[0142] Furthermore, without being bound by theory, it is considered that Petition 870250079694, dated 05 / 09 / 2025, pp. 168 / 267 45 / 97 Blocking the activation of OSM at the type II receptor without inhibiting the type I OSMRe receptor may provide a better safety profile in patients receiving the anti-OSMRβ antibody, as described in this document. For example, binding of the therapeutic antibody to the OSMRβ subunit of the type II receptor allows continued OSM signaling through the type I receptor. In some embodiments, administration of an anti-OSMRβ antibody to an individual suffering from a fibrotic disease causes no more than a mild case of anemia or does not cause an unsafe elevation of thrombopoietin and / or erythropoietin.

[0143] Consequently, the present disclosure provides methods for administering vixarelimab, or another anti-OSMRβ antibody that inhibits OSM and IL-31 signaling, to treat a pulmonary fibrotic disorder in a patient. In some embodiments, the disorder is idiopathic pulmonary fibrosis (IPF). In some embodiments, the disorder is SSc-ILD. In some embodiments, the antibody can be administered subcutaneously.

[0144] In one aspect, a method is provided for treating a fibrotic lung disease. In some embodiments, the method comprises administering to an individual in need thereof a therapeutically effective dose of an anti-OSMRβ (oncostatin M receptor beta) antibody. In another aspect, the present disclosure provides the use of a therapeutically effective dose of an anti-OSMRβ (oncostatin M receptor beta) antibody in the manufacture of a medicament for the treatment of a fibrotic lung disease in an individual in need thereof. In a further aspect, the present disclosure provides a therapeutically effective amount of an anti-OSMRβ antibody for use in the treatment of a fibrotic lung disease in an individual in need thereof.In some realizations, pulmonary fibrotic disease is selected from the group consisting of progressive pulmonary fibrosis (PPF), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis-associated interstitial lung disease (SSc-ILD). In some. Petition 870250079694, dated 05 / 09 / 2025, pp. 169 / 267 In some realizations, pulmonary fibrotic disease is progressive pulmonary fibrosis (PPF). In some realizations, pulmonary fibrotic disease is idiopathic pulmonary fibrosis (IPF). In some realizations, pulmonary fibrotic disease is systemic sclerosis-associated interstitial lung disease (SSc-ILD).

[0145] In one aspect, a method is provided for increasing forced vital capacity (FVC) in an individual suffering from a pulmonary fibrotic disorder. In some embodiments, the method comprises administering a therapeutically effective dose of anti-OSMRe antibody to an individual in need thereof. In another aspect, the present disclosure provides the use of a therapeutically effective dose of an anti-OSMRe antibody (oncostatin M receptor beta) in the manufacture of a drug to increase forced vital capacity (FVC) in an individual suffering from a pulmonary fibrotic disorder. In a further aspect, the present disclosure provides a therapeutically effective amount of an anti-OSMRe antibody for use in increasing forced vital capacity (FVC) in an individual suffering from a pulmonary fibrotic disorder.

[0146] In one aspect, a method for increasing walking distance is provided, as measured in the 6-minute walk test (6MWT), by an individual suffering from a pulmonary fibrotic disorder. In some embodiments, the method comprises administering a therapeutically effective dose of anti-OSMRe antibody to an individual in need thereof. In another aspect, the present disclosure provides the use of a therapeutically effective dose of an anti-OSMRe antibody (oncostatin M receptor beta) in the manufacture of a medicament for increasing walking distance, as measured in the 6-minute walk test (6MWT), by an individual suffering from a pulmonary fibrotic disorder. In a further aspect, the present disclosure provides a therapeutically effective amount of an anti-OSMRe antibody for use in increasing walking distance. Petition 870250079694, dated 05 / 09 / 2025, pp. 170 / 267 47 / 97 covered, as measured in the 6-minute walk test (6MWT), by an individual suffering from a fibrotic lung disorder.

[0147] In one aspect, a method for reducing cough frequency is provided, as measured by an ambulatory digital device for continuous cough detection, by an individual suffering from a pulmonary fibrotic disorder. In some embodiments, the method comprises administering a therapeutically effective dose of anti-OSMRe antibody to an individual in need thereof. In another aspect, the present disclosure provides the use of a therapeutically effective dose of an anti-OSMRe antibody (oncostatin M beta receptor) in the manufacture of a medicament for reducing cough frequency, as measured by an ambulatory digital device for continuous cough detection, by an individual suffering from a pulmonary fibrotic disorder.In a further aspect, the present disclosure provides a therapeutically effective amount of an anti-OSMRe antibody for use in reducing cough frequency, as measured by an ambulatory digital device for continuous cough detection, in an individual suffering from a fibrotic lung disorder.

[0148] In one aspect, a method for treating an inflammatory disease is provided. In some embodiments, the method comprises administering to an individual in need thereof a therapeutically effective dose of an anti-OSMRe antibody (oncostatin M beta receptor). In another aspect, the present disclosure provides the use of a therapeutically effective dose of an anti-OSMRe antibody (oncostatin M beta receptor) in the manufacture of a medicament for treating an inflammatory disease in an individual in need thereof. In a further aspect, the present disclosure provides a therapeutically effective amount of an anti-OSMRe antibody for use in the treatment of an inflammatory disease in an individual in need thereof. Petition 870250079694, dated 05 / 09 / 2025, pp. 171 / 267 48 / 97

[0149] In some realizations, according to any of the aspects above, the individual is human. Combined Therapies

[0150] According to this disclosure, vixarelimab or other anti-OSMRe antibodies that bind to OSMRe and block IL-31 and OSM signaling can be used alone or in combination with other agents in therapy. For example, an anti-OSMRe antibody (e.g., vixarelimab) can be co-administered with at least one additional therapeutic agent.

[0151] In some embodiments, vixarelimab or other anti-OSMRe antibodies that bind to OSMRe and block IL-31 and OSM signaling are used in combination with an interleukin ligand or receptor antagonist. In some embodiments, the interleukin ligand or receptor antagonist is an interleukin-6 (IL-6) ligand or receptor antagonist. In some embodiments, the IL-6 receptor ligand or antagonist is an anti-IL-6 antibody. In some embodiments, the IL-6 receptor ligand or antagonist is an anti-IL-6 receptor antibody. In some embodiments, the anti-IL-6 receptor antibody is tocilizumab or sarilumab. In some embodiments, the anti-IL-6 receptor antibody is tocilizumab. In some embodiments, the anti-IL-6 receptor antibody is sarilumab.

[0152] In certain embodiments, an individual receives an anti-OSMRe antibody from the dissemination in combination with a therapeutic agent for the treatment of IPF. Certain therapeutic agents have been previously described as candidates or agents for the treatment of IPF. They have been described in the published literature and are reviewed, for example, in Rafli et al., J. Thorac. Dis (2013) 5(1):48-73. Such agents include agents that have antioxidant, immunosuppressive and / or anti-inflammatory activities, such as N-acetylcysteine; agents that have antifibrotic, anti-inflammatory and / or antioxidant activities, Petition 870250079694, dated 05 / 09 / 2025, pp. 172 / 267 49 / 97 such as pirfenidone, an orally administered pyridine that has been approved for clinical use in the treatment of IPF; or a tyrosine kinase inhibitor, such as nintedanib; or an antibody against integrin ανβ6 (e.g., STX-100); agents that inhibit connective tissue growth factor (CTGF), such as an anti-CTGF antibody (e.g., FG-3019); agents that inhibit somatostatin receptors, such as somatostatin analogs (e.g., SOM230, octreotide); Agents that inhibit IL-13, IL-4, and CCL2, such as an anti-IL13 antibody (e.g., QAX576, tralokinumab, lebrikizumab), an anti-IL4 antibody, a combined anti-IL13 / anti-IL4 agent (e.g., a bispecific anti-IL13 / anti-IL4 antibody, such as SAR156597), an anti-IL-6 inhibitor (e.g., tocilizumab, sarilumab), an anti-CCL2 antibody (e.g., CNTO888); agents that have antiangiogenic, immunomodulatory, and / or anti-inflammatory activities, such as thalidomide or minocycline;Agents that inhibit the enzyme lysyl oxidase-like 2 (LOXL2), such as an anti-LOXL2 antibody (e.g., GS-6624 [simtuzumab]); agents that inhibit angiogenesis, such as the tyrosine kinase inhibitor, BIBF 1120, tetrathiomolybdate; agents that inhibit extracellular matrix deposition and / or disrupt collagen deposition, such as doxycycline; agents that target the renin-angiotensin system, such as losartan; and other agents with antiproliferative and / or antifibrotic activities, such as carbon monoxide.

[0153] The aforementioned combination therapies encompass combined administration (in which two or more therapeutic agents are included in the same formulation or in separate formulations) and separate administration, wherein the administration of the anti-OSMRe antibody may occur before, simultaneously with, and / or after the administration of the additional therapeutic agent or agents. In some embodiments, the administration of the anti-OSMRe antibody (e.g., vixarelimab) and the administration of an additional therapeutic agent (e.g., an anti-IL-6 inhibitor (e.g., Petition 870250079694, dated 05 / 09 / 2025, pp. 173 / 267 50 / 97 tocilizumab, sarilumab)) occur approximately one month apart, or approximately one, two, or three weeks apart, or approximately one, two, three, four, five, or six days apart. In some embodiments, administration of the anti-OSMRe antibody (e.g., vixarelimab) and administration of an additional therapeutic agent (e.g., tocilizumab) occur approximately one month apart. In one embodiment, administration of the anti-OSMRp antibody (e.g., vixarelimab) and administration of an additional therapeutic agent (e.g., tocilizumab) occur approximately one week apart. In one embodiment, administration of the anti-OSMRp antibody (e.g., vixarelimab) and administration of an additional therapeutic agent (e.g., tocilizumab) occur approximately two weeks apart.In one embodiment, administration of the anti-OSMRp antibody (e.g., vixarelimab) and administration of an additional therapeutic agent (e.g., tocilizumab) occur approximately three weeks apart. In one embodiment, administration of the anti-OSMRp antibody (e.g., vixarelimab) and administration of an additional therapeutic agent (e.g., tocilizumab) occur approximately one day apart. In one embodiment, administration of the anti-OSMRp antibody (e.g., vixarelimab) and administration of an additional therapeutic agent (e.g., tocilizumab) occur approximately two days apart. In one embodiment, administration of the anti-OSMRp antibody (e.g., vixarelimab) and administration of an additional therapeutic agent (e.g., tocilizumab) occur approximately three days apart.In one embodiment, administration of the anti-OSMRp antibody (e.g., vixarelimab) and administration of an additional therapeutic agent (e.g., tocilizumab) occur approximately four days apart. In another embodiment, administration of the anti-OSMRp antibody (e.g., vixarelimab) and administration of an additional therapeutic agent (e.g., tocilizumab) occur approximately four days apart. Petition 870250079694, dated 05 / 09 / 2025, pp. 174 / 267 51 / 97 example, tocilizumab) occur approximately five days apart. In one embodiment, administration of the anti-OSMRp antibody (e.g., vixarelimab) and administration of an additional therapeutic agent (e.g., tocilizumab) occur approximately six days apart.

[0154] In some embodiments, the anti-OSMRp antibody (e.g., vixarelimab) is administered to the individual after the individual has been treated with the second therapeutic agent (e.g., tocilizumab) for at least 1 week. In some embodiments, the anti-OSMRp antibody (e.g., vixarelimab) is administered to the individual after the individual has been treated with the second therapeutic agent (e.g., tocilizumab) for at least 1 month. In some embodiments, the anti-OSMRp antibody (e.g., vixarelimab) is administered to the individual after the individual has been treated with the second therapeutic agent (e.g., tocilizumab) for at least 6 months. In some embodiments, the anti-OSMRp antibody (e.g., vixarelimab) is administered to the individual after the individual has been treated with the second therapeutic agent (e.g., tocilizumab) for at least 1 year.In some embodiments, the anti-OSMRp antibody (e.g., vixarelimab) is administered to the individual after the individual has been treated with the second therapeutic agent (e.g., tocilizumab) for at least 3 years. In some embodiments, the anti-OSMRp antibody (e.g., vixarelimab) is administered to the individual after the individual has been treated with the second therapeutic agent (e.g., tocilizumab) for at least 5 years. IL-6

[0155] Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In some embodiments, the anti-OSMRp antibody is administered before, during, or after administration with the second therapeutic agent. In some embodiments, the anti-OSMRp antibody is administered before administration with the second Petition 870250079694, dated 05 / 09 / 2025, pp. 175 / 267 52 / 97 therapeutic agent. In some embodiments, the anti-OSMRe antibody is administered during administration with the second therapeutic agent. In some embodiments, the anti-OSMRe antibody is administered after administration with the second therapeutic agent. In some embodiments, the second therapeutic agent is an anti-IL-6 antibody or an IL-6 receptor antagonist. In some embodiments, the second therapeutic agent is an anti-IL-6 antibody or an anti-IL-6 receptor antibody.

[0156] In some embodiments, the heavy chain of the anti-IL-6 antibody or anti-IL-6 receptor antagonist comprises the amino acid sequence SEQ ID NO: 13. In some embodiments, the light chain of the anti-IL-6 antibody or anti-IL-6 receptor antagonist comprises the amino acid sequence SEQ ID NO: 14. In some embodiments, the heavy chain of the anti-IL-6 receptor antibody comprises the amino acid sequence SEQ ID NO: 13. In some embodiments, the light chain of the anti-IL-6 receptor antibody comprises the amino acid sequence SEQ ID NO: 14. In some embodiments, the heavy chain of the anti-IL-6 receptor antibody comprises the amino acid sequence SEQ ID NO: 13, and the light chain of the anti-IL-6 receptor antibody comprises the amino acid sequence SEQ ID NO: 14. In other embodiments, the anti-IL-6 antibody or the anti-IL-6 receptor antibody is tocilizumab.In some embodiments, the anti-IL-6 antibody or the anti-IL-6 receptor antagonist comprises the six CDRs of tocilizumab. In other embodiments, the anti-IL-6 receptor antibody is tocilizumab. In some embodiments, the anti-IL-6 receptor antibody comprises the six CDRs of tocilizumab.

[0157] In some embodiments of any of the above methods, the method further comprises the administration of a therapeutically effective amount of tocilizumab. Tocilizumab (Actemra® / RoActemra®) is a humanized recombinant anti-human monoclonal antibody targeted at the target drug. Petition 870250079694, dated 05 / 09 / 2025, pp. 176 / 267 53 / 97 against soluble and membrane-bound IL-6R, which inhibits signaling mediated by IL-6. Table 2 SEQ ID NO Sequência Cadeia pesada de tocilizumabe 13 EVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPP GRGLEWIGYISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSV TAADTAVYYCARSLARTTAMDYWGQGSLVTVSSASTKGPSVF PLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKV DKKVEPKSCDKTHTCPPCPAPELLGGPSVFLEPPKPKDTLMIS RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVESC SVMHEALHNHYTQKSLSLSPG Cadeia leve de tocilizumabe 14 DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKA PKLLIYYTSRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQGNTLPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTAS VVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTY SLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[0158] In one aspect, the present disclosure provides a method for treating pulmonary fibrotic disease in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of (a) an anti-OSMRp antibody and (b) an anti-IL-6 receptor antibody. In another aspect, the present disclosure provides the use of a therapeutically effective amount of (a) an anti-OSMRp antibody and (b) an anti-IL-6 receptor antibody in the manufacture of a medicament for the treatment of pulmonary fibrotic disease in an individual in need thereof. In a further aspect, the present disclosure provides a therapeutically effective amount of (a) an anti-OSMRp antibody and (b) an anti-IL-6 receptor antibody for use in the treatment of pulmonary fibrotic disease in an individual in need thereof.In some realizations, pulmonary fibrotic disease is selected from the group consisting of progressive pulmonary fibrosis (PPF), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis-associated interstitial lung disease (SSc-ILD). In some. Petition 870250079694, dated 05 / 09 / 2025, pp. 177 / 267 In some realizations, pulmonary fibrotic disease is progressive pulmonary fibrosis (PPF). In some realizations, pulmonary fibrotic disease is idiopathic pulmonary fibrosis (IPF). In some realizations, pulmonary fibrotic disease is systemic sclerosis-associated interstitial lung disease (SSc-ILD).

[0159] In one aspect, the present disclosure provides a method for treating an inflammatory and / or fibrotic lung disease in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of (a) an anti-OSMRe antibody and (b) an anti-IL-6 receptor antibody. In another aspect, the present disclosure provides the use of a therapeutically effective amount of (a) an anti-OSMRe antibody and (b) an anti-IL-6 receptor antibody in the manufacture of a medicament for the treatment of an inflammatory and / or fibrotic lung disease in an individual in need thereof. In a further aspect, the present disclosure provides a therapeutically effective amount of (a) an anti-OSMRe antibody and (b) an anti-IL-6 receptor antibody for use in the treatment of an inflammatory and / or fibrotic lung disease in an individual in need thereof.

[0160] In one aspect, the present disclosure provides a method for treating pulmonary fibrotic disease in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of vixarelimab and tocilizumab. In another aspect, the present disclosure provides the use of a therapeutically effective amount of vixarelimab and tocilizumab in the manufacture of a medicament for the treatment of pulmonary fibrotic disease in an individual in need thereof. In a further aspect, the present disclosure provides a therapeutically effective amount of vixarelimab and tocilizumab for use in the treatment of pulmonary fibrotic disease in an individual in need thereof. In some embodiments, pulmonary fibrotic disease is selected from the group consisting of fibrosis. Petition 870250079694, dated 05 / 09 / 2025, pp. 178 / 267 55 / 97 progressive pulmonary fibrosis (PPF), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis-associated interstitial lung disease (SSc-ILD). In some embodiments, pulmonary fibrotic disease is progressive pulmonary fibrosis (PPF). In some embodiments, pulmonary fibrotic disease is idiopathic pulmonary fibrosis (IPF). In some embodiments, pulmonary fibrotic disease is systemic sclerosis-associated interstitial lung disease (SSc-ILD). Vixarelimab can be administered at any of the doses disclosed herein, at any of the dosing frequencies disclosed herein, or at any combination of dose and frequency disclosed herein.

[0161] In one aspect, the present disclosure provides a method for treating an inflammatory and / or fibrotic lung disease in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of vixarelimab and tocilizumab. In another aspect, the present disclosure provides the use of a therapeutically effective amount of vixarelimab and tocilizumab in the manufacture of a medicament for the treatment of an inflammatory and / or fibrotic lung disease in an individual in need thereof. In a further aspect, the present disclosure provides a therapeutically effective amount of vixarelimab and tocilizumab for use in the treatment of an inflammatory and / or fibrotic lung disease in an individual in need thereof.Vixarelimab can be administered at any of the doses disclosed in this document, at any of the dosing frequencies disclosed in this document, or at any combination of dose and frequency disclosed in this document.

[0162] In some realizations, according to any of the aspects above, the individual is human. Administration and Formulation

[0163] An anti-OSMRe antibody from disclosure (and any Petition 870250079694, dated 05 / 09 / 2025, pp. 179 / 267 56 / 97 (additional therapeutic agent) can be administered by any suitable means, including subcutaneous or intravenous injections, or parenteral or intrapulmonary administration and, if desired for local treatment, intralesional administration. Parenteral infusions include intramuscular, intravenous, intra-arterial, intraperitoneal or, preferably for anti-OSMRe, subcutaneous administration. Dosing can be done by any suitable route, for example, by injections, as well as by subcutaneous or intravenous routes, depending in part on whether administration is brief or chronic. In preferred embodiments, the administration of an anti-OSMRe antibody described herein is by subcutaneous route. Various dosing regimens, including, without limitation, single or multiple administrations at various time points, bolus administration and pulse infusion are contemplated herein.

[0164] Disclosure anti-OSMRe antibodies would be formulated, dosed, and administered in a manner consistent with good medical practice. Factors to be considered in this context include the particular disorder to be treated, the particular mammal to be treated, the clinical condition of the individual patient, the cause of the disorder, the agent delivery site, the use of administration, the administration schedule, and other factors known to physicians. The antibody may optionally be formulated with one or more agents currently used to prevent or treat the disorder in question. The effective amount of these other agents depends on the amount of antibodies present in the formulation, the type of disorder or treatment, and other factors discussed above.They are generally used at the same dosages and by the same routes of administration described in this document, or approximately 1 to 99% of the dosages described in this document, or at any dosage and by any route that is empirically / clinically determined to be appropriate.

[0165] For the prevention or treatment of diseases, the dosage Petition 870250079694, dated 05 / 09 / 2025, pp. 180 / 267 The appropriate use of a disclosure antibody (when used alone or in combination with one or more other additional therapeutic agents) will depend on the type of disease being treated, the type of antibody, the severity and course of the disease, whether the antibody is administered for preventive or therapeutic purposes, prior therapy, the patient's medical history and response to the antibody, and the attending physician's judgment.

[0166] The antibody is administered to the patient either all at once or over a series of treatments, depending on the type and severity of the disease. An example dosage of anti-OSMR antibody would be in the range of approximately 360 to 720 mg. Therefore, one or more doses of 360 mg, 540 mg, or 720 mg may be administered to the patient. In some embodiments, the anti-OSMR antibody is administered at a dose of 360 mg. In some embodiments, the anti-OSMR antibody is administered at a dose of 540 mg. In some embodiments, the anti-OSMR antibody is administered at a dose of 720 mg. These doses may be administered intermittently, for example, weekly, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the anti-OSMR antibody is administered once a week. In some embodiments, the anti-OSMR antibody is administered once every 2 weeks. In some embodiments, the anti-OSMRe antibody is administered once every 3 weeks.In some embodiments, the anti-OSMRe antibody is administered once every 4 weeks. In some embodiments, the anti-OSMRe antibody is administered once a month. A higher initial loading dose, followed by one or more lower doses, may be administered. However, other dosing regimens may be useful. In some embodiments, the anti-OSMRe is not administered at a higher initial loading dose. The progress of this therapy is easily monitored by conventional techniques and assays.

[0167] In preferred realizations, the method comprises Petition 870250079694, dated 05 / 09 / 2025, pp. 181 / 267 58 / 97 administer the anti-OSMR antibody at a dose of 360 mg to the patient every 2 weeks. In some embodiments, the method comprises administering 360 mg of the anti-OSMR antibody to the individual once every 1 week. In some embodiments, the method comprises administering 360 mg of the anti-OSMR antibody to the individual once every 3 weeks. In some embodiments, the method comprises administering 360 mg of the anti-OSMR antibody to the individual once every 4 weeks. In some embodiments, the method comprises administering 360 mg of the anti-OSMR antibody to the individual once a month. In some embodiments, the method comprises administering 540 mg of the anti-OSMR antibody to the individual once every 1 week. In some embodiments, the method comprises administering 540 mg to the individual once every 2 weeks. In some embodiments, the method comprises administering 540 mg of the anti-OSMR antibody to the individual once every 3 weeks.In some embodiments, the method comprises administering 540 mg of anti-OSMRe antibody to the individual once every 4 weeks. In some embodiments, the method comprises administering 540 mg of anti-OSMRe antibody to the individual once a month. In some embodiments, the method comprises administering 720 mg of anti-OSMRe antibody to the individual once every 1 week. In some embodiments, the method comprises administering 720 mg of anti-OSMRe antibody to the individual once every 2 weeks. In some embodiments, the method comprises administering 720 mg of anti-OSMRe antibody to the individual once every 3 weeks. In some embodiments, the method comprises administering 720 mg of anti-OSMRe antibody to the individual once every 4 weeks. In some embodiments, the method comprises administering 720 mg of anti-OSMRe antibody to the individual once a month.

[0168] In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRe antibody, has a predicted forced vital capacity (%FVC) of approximately Petition 870250079694, dated 05 / 09 / 2025, pp. 182 / 267 59 / 97 35% to 90%. In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRp antibody, has a predicted FVC percentage of approximately 35% to 75%. In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRp antibody, has a predicted FVC percentage of approximately 35% to 50%. In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRp antibody, has a predicted FVC percentage of approximately 45% to 55%. In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRp antibody, has a predicted FVC percentage of approximately 30% to 60%. In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRp antibody, has a predicted FVC percentage of approximately 50% to 90%.In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRp antibody, has a predicted FVC percentage of approximately 50% to 75%. In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRp antibody, has a predicted FVC percentage of approximately 40% to 45%. In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRp antibody, has a predicted FVC percentage of approximately 40% to 50%. In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRp antibody, has a predicted FVC percentage of approximately 45% to 50%. In some embodiments, the method comprises treating the individual, wherein the individual, prior to treatment with the anti-OSMRp antibody, has a predicted FVC percentage of approximately 45% to approximately 50%.In other realizations, the individual has a FVC of approximately 45% of predicted. In some realizations, the %FVC is measured using... Petition 870250079694, dated 05 / 09 / 2025, pp. 183 / 267 60 / 97 spirometry.

[0169] In some embodiments, the individual has a forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio of approximately 0.35 to 0.70 before treatment with the anti-OSMR antibody. In some embodiments, the individual has an FEV1 to FVC ratio of approximately 0.50 to 0.70 before treatment with the anti-OSMR antibody. In some embodiments, the individual has an FEV1 to FVC ratio of approximately 0.60 to 0.70 before treatment with the anti-OSMR antibody. In some embodiments, the individual has an FEV1 to FVC ratio of approximately 0.35 to 0.50 before treatment with the anti-OSMR antibody. In some embodiments, the individual has an FEV1 to FVC ratio of approximately 0.40 to 0.50 before treatment with the anti-OSMR antibody. In some realizations, the individual has an FEV1 to FVC ratio of approximately 0.50 to 0.60 before treatment with the anti-OSMRe antibody.In some realizations, the individual has an FEV1 to FVC ratio of approximately 0.60 to 0.70 before treatment with the anti-OSMRe antibody. In some realizations, the individual has an FEV1 to FVC ratio of approximately 0.70 to 0.80 before treatment with the anti-OSMRe antibody. In other realizations, the individual has an FEV1 to FVC ratio of approximately 0.70 to 0.80 before treatment with the anti-OSMRe antibody. In preferred realizations, the individual has an FVC of approximately 45% of predicted or greater. In preferred realizations, the individual has an FEV1 to FVC ratio greater than approximately 0.70 before treatment with the anti-OSMRe antibody.

[0170] In some embodiments, after administration of the anti-OSMRe antibody, the change in FVC is a decrease in FVC of less than 25 ml. In some embodiments, after administration of the anti-OSMRe antibody, the change in FVC is a decrease in FVC of less than 50 ml. In some embodiments, after administration of the anti-OSMRe antibody, the change in FVC is a decrease in FVC of less than 75 ml. In some Petition 870250079694, dated 05 / 09 / 2025, pp. 184 / 267 In 61 / 97 realizations, after administration of the anti-OSMR antibody, the change in FVC is a decrease in FVC of less than 100 ml. In some realizations, after administration of the anti-OSMR antibody, the change in FVC is a decrease in FVC of less than 125 ml. In some realizations, after administration of the anti-OSMR antibody, the change in FVC is a decrease in FVC of less than 150 ml. In some realizations, after administration of the anti-OSMR antibody, the change in FVC is a decrease in FVC of less than 175 ml. In some realizations, after administration of the anti-OSMR antibody, the change in FVC is a decrease in FVC of less than 200 ml. In some realizations, after administration of the anti-OSMR antibody, the change in FVC is a decrease in FVC of less than 225 ml. In some studies, after administration of the anti-OSMRe antibody, the change in FVC is a decrease in FVC of less than 250 ml.

[0171] In some embodiments, after administration of the anti-OSMRe antibody, the change in FVC is an increase in FVC of at least 25 ml. In some embodiments, after administration of the anti-OSMRe antibody, the change in FVC is an increase in FVC of at least 50 ml. In some embodiments, after administration of the anti-OSMRe antibody, the change in FVC is an increase in FVC of at least 75 ml. In some embodiments, after administration of the anti-OSMRe antibody, the change in FVC is an increase in FVC of at least 100 ml. In some embodiments, after administration of the anti-OSMRe antibody, the change in FVC is an increase in FVC of at least 125 ml. In some embodiments, after administration of the anti-OSMRe antibody, the change in FVC is an increase in FVC of at least 150 ml. In some studies, following administration of the anti-OSMRe antibody, the change in FVC is an increase in FVC of at least 175 ml.In some studies, after administration of the anti-OSMRe antibody, the change in FVC is an increase in FVC of at least 200 ml. In some studies, after... Petition 870250079694, dated 05 / 09 / 2025, pp. 185 / 267 62 / 97 administration of anti-OSMRe antibody, the change in FVC is an increase in FVC of at least 225 ml. In some embodiments, after administration of anti-OSMRe antibody, the change in FVC is an increase in FVC of at least 250 ml. In some embodiments, after administration of anti-OSMRe antibody, the change in FVC is an increase in FVC of up to 500 ml.

[0172] In some embodiments, the method is sufficient to produce an increase in the predicted percentage of DLCO (DLco%) compared to the baseline measurement. In some embodiments, the increase in predicted DLco or DLco% is at least 5% above the respective baseline measurement during a treatment period. In some embodiments, the increase in predicted DLco or DLco% is at least 10% above the respective baseline measurement during a treatment period. In some embodiments, the increase in predicted DLco or DLco% is at least 15% above the respective baseline measurement during a treatment period. In some embodiments, the increase in predicted DLco or DLco% is at least 20% above the respective baseline measurement during a treatment period. In some embodiments, the increase in predicted DLco or DLco% is at least 25% above the respective baseline measurement during a treatment period.In some realizations, the predicted increase in DLco or DLco% is at least 30% above the respective baseline measurement during a treatment period. In some realizations, the predicted increase in DLco or DLco% is at least 35% above the respective baseline measurement during a treatment period. In some realizations, the predicted increase in DLco or DLco% is at least 40% above the respective baseline measurement during a treatment period. In some realizations, the predicted increase in DLco or DLco% is at least 45% above the respective baseline measurement during a treatment period. In some realizations, the predicted increase in DLco or DLco% is at least 50%. Petition 870250079694, dated 05 / 09 / 2025, pp. 186 / 267 63 / 97 above the respective baseline measurement during a treatment period. In some realizations, the predicted increase in DLco or DLco% is at least 55% above the respective baseline measurement during a treatment period. In some realizations, the predicted increase in DLco or DLco% is at least 60% above the respective baseline measurement during a treatment period. In some realizations, the predicted increase in DLco or DLco% is at least 65%. In some realizations, the predicted increase in DLco or DLco% is at least 70% above the respective baseline measurement during a treatment period. In some realizations, the predicted increase in DLco or DLco% is at least 75% above the respective baseline measurement during a treatment period. In some realizations, the predicted increase in DLco or DLco% is at least 80% above the respective baseline measurement during a treatment period.In some embodiments, the predicted increase in DLco or DLco% is at least 90% above the respective baseline measurement during a treatment period. In some embodiments, the predicted increase in DLco or DLco% is at least 100% above the respective baseline measurement during a treatment period. In some embodiments, the predicted increase in DLco or DLco% is at least 110% above the respective baseline measurement during a treatment period. In some embodiments, the predicted increase in DLco or DLco% is at least 120% above the respective baseline measurement during a treatment period. In some embodiments, the predicted increase in DLco or DLco% is no more than 100% above the respective baseline measurement during a treatment period. In some embodiments, the predicted increase in DLco or DLco% is no more than 110% above the respective baseline measurement during a treatment period.In some realizations, the increase in DLco or DLco% predicted is no more than 120% above the respective baseline measurement during a period of... Petition 870250079694, dated 05 / 09 / 2025, pp. 187 / 267 64 / 97 treatment. In some realizations, the increase in DLco or predicted DLco% is no more than 130% above the respective baseline measurement during a treatment period. In some realizations, the increase in DLco or predicted DLco% is no more than 140% above the respective baseline measurement during a treatment period.

[0173] In some embodiments, the method is sufficient to reduce a predicted decrease in the percentage of DLco (DLco%) compared to the baseline measurement. In some embodiments, the predicted decrease in DLco or DLco% is less than 5% below the respective baseline measurement during a treatment period. In some embodiments, the predicted decrease in DLco or DLco% is less than 7% below the respective baseline measurement during a treatment period. In some embodiments, the predicted decrease in DLco or DLco% is less than 10% below the respective baseline measurement during a treatment period. In some embodiments, the predicted decrease in DLco or DLco% is less than 15% below the respective baseline measurement during a treatment period. In some embodiments, the predicted decrease in DLco or DLco% is less than 20% below the respective baseline measurement during a treatment period.

[0174] In some realizations, the treatment period is about 6 weeks. In some realizations, the treatment period is about 12 weeks. In some realizations, the treatment period is about 24 weeks. In some realizations, the treatment period is about 36 weeks. In some realizations, the treatment period is about 48 weeks. In some realizations, the treatment period is about 60 weeks. In some realizations, the treatment period is about 72 weeks. In other realizations, the treatment period is about 52 weeks. Petition 870250079694, dated 05 / 09 / 2025, pp. 188 / 267 65 / 97

[0175] In some embodiments, the method comprises treating an individual with a pulmonary fibrotic disorder, wherein administration of a dose of anti-OSMRe antibody to the individual results in a change in the distance walked by the individual in the 6-minute walk test (6MWT), wherein the change is the difference in the distance walked by the individual in the 6MWT performed at 2 time points in a treatment period, wherein the first time point is at the first administration of the anti-OSMRe antibody and the second time point is the time when a subsequent dose of the anti-OSMRe antibody is administered. In some embodiments, the difference in the distance walked by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 5%. In some embodiments, the difference in the distance walked by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 10%.In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 15%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 20%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 25%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 30%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 40%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 50%.In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 25 m. In some realizations, a. Petition 870250079694, dated 05 / 09 / 2025, pp. 189 / 267 In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 35 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a decrease of less than about 50 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 5%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 10%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 15%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 20%.In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 25%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 30%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 40%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 50%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of about 5% to about 50%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of about 5% to about 40%.In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of about 5% to about 30%. In some realizations, the difference in distance covered... Petition 870250079694, dated 05 / 09 / 2025, pp. 190 / 267 The difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 5% to approximately 20%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 5% to approximately 10%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 10% to approximately 50%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 10% to approximately 40%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 10% to approximately 30%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 10% to approximately 20%.In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 20% to approximately 50%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 20% to approximately 40%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 20% to approximately 30%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 30% to approximately 50%. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 30% to approximately 40%. In some studies, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 40% to approximately 50%.

[0176] In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is a Petition 870250079694, dated 05 / 09 / 2025, pp. 191 / 267 68 / 97 increase of at least about 5 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 10 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 15 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 20 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 25 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 30 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 35 m.In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 40 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at least about 45 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of at most about 50 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of about 5 m to about 50 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of about 10 m to about 50 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of about 20 m to about 50 m.In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase of approximately 30 m. Petition 870250079694, dated 05 / 09 / 2025, pp. 192 / 267 69 / 97 approximately 50 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase from approximately 40 m to approximately 50 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase from approximately 10 m to approximately 40 m. In some realizations, the difference in distance covered by the individual in the 6MWT performed at the 2 time points is an increase from approximately 20 m to approximately 30 m.

[0177] In some respects, a method is provided for increasing the distance walked, as measured in the 6MWT, by an individual suffering from a pulmonary fibrotic disorder, comprising administering a dose of an anti-OSMRe antibody to the individual.

[0178] In some embodiments, the individual has been diagnosed or determined to have one or more pulmonary fibrotic disorders. In some embodiments, the pulmonary fibrotic disorder is idiopathic pulmonary fibrosis (IPF). In some embodiments, the pulmonary fibrotic disorder is progressive pulmonary fibrosis (PPF) (alternatively called pulmonary fibrosis associated with interstitial lung disease (PF-ILD)). In some embodiments, PPF is chronic fibrosing ILD (CF-ILD). In some embodiments, PPF is CF-ILD with a progressive phenotype. In some embodiments, PPF is interstitial lung disease (ILD). In some embodiments, PPF is systemic sclerosis-ILD ​​(SSc-ILD). In some embodiments, PPF is drug-induced ILD. In some embodiments, PPF is hypersensitivity pneumonitis. In some embodiments, PPF is interstitial pneumonia with autoimmune features (IPAF). In some formulations, PPF is fibrosing interstitial pneumonia.In some realizations, PPF is an unclassifiable ILD. In some realizations, pulmonary fibrotic disorder is a chronic fibrosing interstitial lung disease with a progressive phenotype. Petition 870250079694, dated 05 / 09 / 2025, pp. 193 / 267 70 / 97

[0179] In some embodiments, pulmonary fibrosis is associated with one or more of the following: usual interstitial pneumonia, idiopathic interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis associated with interstitial lung disease, acute interstitial pneumonia, nonspecific interstitial pneumonia, sarcoidosis, cryptogenic organizing pneumonia, eosinophilic pneumonia, infection, exposure to occupational or environmental agents, smoking, drug- or radiation-induced interstitial lung disease, rheumatic disease-associated interstitial lung disease, lymphoid interstitial pneumonia, pleuropulmonary fibroelastosis, Langerhans cell pulmonary histiocytosis, systemic sclerosis-associated interstitial lung disease, Hermansky-Pudlak syndrome, and telomeropathy. In some embodiments, pulmonary fibrosis is associated with usual interstitial pneumonia. In some embodiments, pulmonary fibrosis is associated with idiopathic interstitial pneumonia.In some embodiments, pulmonary fibrosis is associated with desquamative interstitial pneumonia. In some embodiments, pulmonary fibrosis is associated with respiratory bronchiolitis associated with interstitial lung disease. In some embodiments, pulmonary fibrosis is associated with acute interstitial pneumonia. In some embodiments, pulmonary fibrosis is associated with nonspecific interstitial pneumonia. In some embodiments, pulmonary fibrosis is associated with sarcoidosis. In some embodiments, pulmonary fibrosis is associated with cryptogenic organizing pneumonia. In some embodiments, pulmonary fibrosis is associated with eosinophilic pneumonia. In some embodiments, pulmonary fibrosis is associated with infection. In some embodiments, pulmonary fibrosis is associated with occupational exposure. In some embodiments, pulmonary fibrosis is associated with exposure to environmental agents. In some embodiments, pulmonary fibrosis is associated with smoking.In some cases, pulmonary fibrosis is associated with interstitial lung disease. Petition 870250079694, dated 05 / 09 / 2025, pp. 194 / 267 71 / 97 drug-induced. In some embodiments, pulmonary fibrosis is associated with radiation-induced interstitial lung disease. In some embodiments, pulmonary fibrosis is associated with rheumatic disease-associated interstitial lung disease. In some embodiments, pulmonary fibrosis is associated with lymphoid interstitial pneumonia. In some embodiments, pulmonary fibrosis is associated with pleuropulmonary fibroelastosis. In some embodiments, pulmonary fibrosis is associated with pulmonary Langerhans cell histiocytosis. In some embodiments, pulmonary fibrosis is associated with systemic sclerosis-associated interstitial lung disease. In some embodiments, pulmonary fibrosis is associated with Hermansky-Pudlak syndrome. In some embodiments, pulmonary fibrosis is associated with telomeropathy.

[0180] In some realizations, the individual has not been diagnosed with or is not suffering from an inflammatory bowel disease. In some realizations, the individual has not been diagnosed with or is not suffering from a fibrotic skin disease. In some realizations, the individual has not been diagnosed with or is not presenting with pruritus nodules. In some realizations, the individual has not been diagnosed with AD or is not suffering from it. Illustrative Achievements

[0181] The specific achievements of the disclosure are set out in the following numbered paragraphs: 1. A method for treating a fibrotic lung disease comprising administering to an individual in need thereof a therapeutically effective dose of an anti-OSMRe antibody (oncostatin M beta receptor); 2. Anti-OSMRe antibody for use in the treatment of a fibrotic lung disease in an individual who requires it; 3. Use of an anti-OSMRe antibody in the manufacture of a Petition 870250079694, dated 05 / 09 / 2025, pp. 195 / 267 72 / 97 pharmaceutical composition to treat a fibrotic lung disease in an individual who needs it; 4. Method, according to embodiment 1, the anti-OSMRe antibody for use, according to embodiment 2, or the use, according to embodiment 3, wherein the pulmonary fibrotic disease is selected from the group consisting of progressive pulmonary fibrosis (PPF), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis-associated interstitial lung disease (SSc-ILD); 5. Method, according to embodiment 1 or 4, the anti-OSMRe antibody for use, according to embodiment 2 or 4, or the use, according to embodiment 3 or 4, wherein the anti-OSMRe antibody inhibits OSMR type II signaling by OSM and IL-31; 6. Method, according to any of embodiments 1, 4 and 5, the anti-OSMRe antibody for use, according to any of embodiments 2, 4 and 5, or the use, according to any of embodiments 3 to 5, wherein the anti-OSMRe antibody is vixarelimab; 7. Method, according to any one of embodiments 1 and 4 to 6, the anti-OSMRe antibody for use, according to any one of embodiments 2 and 4 to 6, or the use, according to any one of embodiments 3 to 6, wherein the therapeutically effective dose is about 360 mg to 720 mg of the anti-OSMRe antibody; 8. Method, according to any of embodiments 1 and 4 to 7, the anti-OSMRe antibody for use, according to any of embodiments 2 and 4 to 7, or the use, according to any of embodiments 3 to 7, wherein the therapeutically effective dose is 360 mg of the anti-OSMRe antibody; 9. Method, according to any one of embodiments 1 and 4 to 8, the anti-OSMRe antibody for use, according to any one of embodiments 2 and 4 to 8, or the use, according to any one of embodiments 3 to 8, in which the therapeutically effective dose of the anti-OSMRe antibody is administered a Petition 870250079694, dated 05 / 09 / 2025, pp. 196 / 267 73 / 97 once a week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once a month; 10. Method, according to any of embodiments 1 and 4 to 9, the anti-OSMRe antibody for use, according to any of embodiments 2 and 4 to 9, or the use, according to any of embodiments 3 to 9, in which the therapeutically effective dose of the anti-OSMRe antibody is administered once every 2 weeks; 11. Method, according to either of realizations 1 and 4 a 10, the anti-OSMRe antibody for use, according to any of embodiments 2 and 4 to 10, or the use, according to any of embodiments 3 to 10, wherein the therapeutically effective dose of the anti-OSMRe antibody is administered subcutaneously or intravenously; 12. Method, according to any of the realizations 1 and 4 to 11, the anti-OSMRe antibody for use, according to any of embodiments 2 and 4 to 11, or the use, of any of embodiments 3 to 11, wherein the therapeutically effective dose of the anti-OSMRe antibody is administered subcutaneously; 13. Method, according to any of the realizations 1 and 4 to 12, the anti-OSMR antibody for use, according to any of embodiments 2 and 4 to 12, or the use, according to any of embodiments 3 to 12, wherein before treatment with the anti-OSMR antibody the individual has a percentage of predicted forced vital capacity (%FVC) of about 35% to 90%, about 35% to 75%, about 35% to 50%, about 45% to 55%, about 30% to 60%, about 50% to 90%, about 50% to 75%, about 40% to 45%, about 40% to 50%, about 45% to 50% or about 45% to about 50%; 14. Method, according to any of the realizations 1 and 4 to 13, the anti-OSMRe antibody for use, according to any of embodiments 2 and 4 to 13, or the use, according to any of embodiments Petition 870250079694, dated 05 / 09 / 2025, pp. 197 / 267 74 / 97 to 13, in which before treatment with the anti-OSMR antibody the individual has a forced expiratory volume in 1 second (FEV1) to FVC ratio of approximately 0.35 to 0.70, approximately 0.50 to 0.70, approximately 0.60 to 0.70, approximately 0.35 to 0.50, approximately 0.40 to 0.50, approximately 0.50 to 0.60, approximately 0.60 to 0.70, approximately 0.70 to 0.80; 15. Method, according to any one of embodiments 1 and 4 to 14, of anti-OSMRe antibody for use, according to any one of embodiments 2 and 4 to 14, or use, according to any one of embodiments 3 to 14, wherein administration of the dose of anti-OSMRe antibody to the individual results in a change in FVC in the individual, wherein the change is a measure of the absolute change in FVC in milliliters (ml) over a treatment period beginning at the time of the first administration of the anti-OSMRe antibody until the time a subsequent dose of the anti-OSMRe antibody is administered; 16. Method, the anti-OSMR antibody for use or use, according to embodiment 15, in which the change in FVC during the treatment period is a decrease in FVC of less than 25 ml, 50 ml, 75 ml, 100 ml, 125 ml, 150 ml, 175 ml or 200 ml, 225 ml or 250 ml or an increase in FVC of at least 25 ml, 50 ml, 75 ml, 100 ml, 125 ml, 150 ml, 175 ml or 200 ml, 225 ml or 250 ml; 17. Method, according to any one of embodiments 1 and 4 to 16, of anti-OSMRe antibody for use, according to any one of embodiments 2 and 4 to 16, or use, according to any one of embodiments 3 to 16, wherein administration of a dose of anti-OSMRe antibody to the individual results in an increase in DLCO[Hb] in the individual, wherein the change is a measure of the absolute change in DLCO[Hb] over a treatment period beginning at the time of the first administration of anti-OSMRe antibody until the time a subsequent dose of anti-OSMRe antibody is administered; Petition 870250079694, dated 05 / 09 / 2025, pp. 198 / 267 75 / 97 18. Method, anti-OSMRe antibody for use, or use, according to embodiment 17, in which the change in DLCO[Hb] during the treatment period is an increase of at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80% or 90%; 19. Method, according to any one of embodiments 1 and 4 to 18, of anti-OSMRe antibody for use, according to any one of embodiments 2 and 4 to 18, or use, according to any one of embodiments 3 to 18, wherein administration of the dose of anti-OSMRe antibody to the individual results in a change in the distance walked by the individual in the 6-minute walk test (6MWT), wherein the change is a measure of the distance walked by the individual in the 6MWT over a treatment period beginning at the time of the first administration of the anti-OSMRe antibody until the time a subsequent dose of the anti-OSMRe antibody is administered; 20. Method, the anti-OSMR antibody for use or use, according to embodiment 19, in which the change in distance during the treatment period is an increase of at least 5%, 10%, 15%, 20%, 25% or 30%; 21. Method, the anti-OSMRe antibody for use or use, according to embodiment 19, in which the change in distance during the treatment period is a decrease of less than about 5%, 10%, 15%, 20%, 25% or 30%; 22. Method, according to any of embodiments 1 and 4 to 21, the anti-OSMR antibody for use in any of embodiments 2 and 4 to 21, or the use of any of embodiments 3 to 21, wherein administration of the dose of anti-OSMR antibody to the individual results in a change in cough relative to baseline, wherein the change is a measure of cough frequency over a treatment period beginning at the time of first administration of the anti-OSMR antibody until the time a subsequent dose of the anti-OSMR antibody is administered, wherein the Petition 870250079694, dated 05 / 09 / 2025, pp. 199 / 267 76 / 97 change is a reduction in cough frequency, and cough is measured by an ambulatory digital device for continuous cough detection; 23. Method, the anti-OSMR antibody for use or use, according to any of embodiments 15 to 22, wherein the treatment period is approximately 6 weeks, approximately 12 weeks, approximately 24 weeks, approximately 36 weeks, approximately 48 weeks, approximately 60 weeks or approximately 72 weeks; 24. Method, according to any of embodiments 1 and 4 to 23, of anti-OSMR antibody for use, according to any of embodiments 2 and 4 to 23, or use, according to any of embodiments 3 to 23, in which anti-OSMR antibody is administered to the individual in combination with a second therapeutic agent; 25. Method, the anti-OSMRe antibody for use, or the use, according to embodiment 24, wherein the second therapeutic agent is a therapeutic agent indicated for a pulmonary fibrotic disease or disorder; 26. Method, the anti-OSMRe antibody for use or use according to embodiment 24 or 25, wherein the second therapeutic agent is pirfenidone or nintedanib; 27. Method, the anti-OSMRe antibody for use, or the use, according to embodiment 24 or 25, wherein the second therapeutic agent is an anti-IL-6 antibody or an anti-IL-6 receptor antibody; 28. Method, the anti-OSMRe antibody for use, or the use, according to embodiment 27, in which the anti-IL-6 receptor antibody is tocilizumab; 29. Method, the anti-OSMRe antibody for use, or the use, according to embodiment 27, wherein the anti-IL-6 antibody or the anti-IL-6 receptor antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 13; 30. Method, the anti-OSMRe antibody for use, or the use, according to Petition 870250079694, dated 05 / 09 / 2025, pages 200 / 267 77 / 97 with realization 27, wherein the anti-IL-6 antibody or the anti-IL-6 receptor antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 14; 31. Method, the anti-OSMRe antibody for use, or the use, according to embodiment 27, wherein the anti-IL-6 antibody or the anti-IL-6 receptor antibody comprises the six CDRs of tocilizumab; 32. Method, according to any of embodiments 1 and 4 to 31, the anti-OSMR antibody for use, according to any of embodiments 2 and 4 to 31, or the use, according to any of embodiments 3 to 31, wherein the individual is human; 33. A method for treating a fibrotic lung disease in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of (a) an anti-OSMRp antibody and (b) an anti-IL-6 receptor antibody; 34. Therapeutically effective amount of (a) an anti-OSMRP antibody and (b) an anti-IL-6 receptor antibody for use in the treatment of a fibrotic lung disease in an individual who requires it; 35. Use of a therapeutically effective amount of (a) an anti-OSMRp antibody and (b) an anti-IL-6 receptor antibody in the manufacture of a drug to treat a fibrotic lung disease in an individual who needs it; 36. Method, according to embodiment 33, anti-OSMRp and anti-IL-6 receptor antibodies for use, according to embodiment 34, or use, according to embodiment 35, wherein the anti-OSMRp antibody comprises a variable heavy chain (VH) domain comprising SEQ ID NO:7 and a variable light chain (VL) domain comprising SEQ ID NO:8; 37. Method, anti-OSMRp antibodies and anti-IL-6 receptor antibodies Petition 870250079694, dated 05 / 09 / 2025, pages 201 / 267 78 / 97 for use, or use, according to embodiment 36, wherein the antiOSMRe antibody comprises a heavy chain (HC) comprising SEQ ID NO:5 and a light chain (LC) comprising SEQ ID NO:6; 38. Method, according to embodiment 33, anti-OSMRe antibodies and anti-IL-6 receptor antibodies for use, according to embodiment 34, or use, according to embodiment 35, wherein the anti-OSMRe antibody is vixarelimab; 39. Method, according to any of embodiments 33 and 36 to 38, anti-OSMRe and anti-IL-6 receptor antibodies for use, according to any of embodiments 34 and 36 to 38, or use, according to any of embodiments 35 to 38, wherein the heavy chain of the anti-IL-6 receptor antibody comprises the amino acid sequence of SEQ ID NO: 13, and the light chain of the anti-IL-6 receptor antibody comprises the amino acid sequence of SEQ ID NO: 14; 40. Method, according to any of embodiments 33 and 36 to 38, the anti-OSMRe antibodies and the anti-IL-6 receptor antibody for use, according to any of embodiments 34 and 36 to 38, or the use, according to any of embodiments 35 to 38, wherein the anti-IL-6 receptor antibody is tocilizumab; 41. Method, according to any of embodiments 33 and 36 to 38, the anti-OSMRe antibodies and the anti-IL-6 receptor antibody for use, according to any of embodiments 34 and 36 to 38, or the use, according to any of embodiments 35 to 38, wherein the anti-IL-6 receptor antibody comprises the six CDRs of tocilizumab; 42. Method, according to embodiment 33, anti-OSMRe antibodies and anti-IL-6 receptor antibodies for use, according to embodiment 34, or use, according to embodiment 35, wherein the anti-OSMRe antibody is vixarelimab and the anti-IL-6 receptor antibody is tocilizumab; Petition 870250079694, dated 05 / 09 / 2025, pp. 202 / 267 79 / 97 43. Method, according to any of embodiments 33 and 36 to 42, anti-OSMRe antibodies and anti-IL-6 receptor antibodies for use, according to any of embodiments 34 and 36 to 42, or use, according to any of embodiments 35 to 42, wherein pulmonary fibrotic disease is selected from the group consisting of progressive pulmonary fibrosis (PPF), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis-associated interstitial lung disease (SSc-ILD); 44. Method, anti-OSMRe antibodies and anti-IL-6 receptor antibodies for use, or use, according to embodiment 43, in which pulmonary fibrotic disease is IPF; 45. Method, according to any of embodiments 33 and 36 to 44, of anti-OSMRe antibodies and anti-IL-6 receptor antibodies for use, according to any of embodiments 34 and 36 to 44, or the use, according to any of embodiments 35 to 44, in which the anti-OSMRe antibody and the anti-IL-6 receptor antibody are administered simultaneously; 46. ​​Method, according to any of embodiments 33 and 36 to 44, of anti-OSMRe antibodies and anti-IL-6 receptor antibodies for use, according to any of embodiments 34 and 36 to 44, or the use, according to any of embodiments 35 to 44, in which the anti-OSMRe antibody and the anti-IL-6 receptor antibody are administered sequentially; 47. Method, according to any of embodiments 33 and 36 to 45, of anti-OSMRe antibodies and anti-IL-6 receptor antibodies for use, according to any of embodiments 34 and 36 to 45, or the use, according to any of embodiments 35 to 45, in which the anti-OSMRe antibody and the anti-IL-6 receptor antibody are administered in the same composition; 48. Method, according to any of embodiments 33, 36 to 44 and 46, anti-OSMRe antibodies and anti-IL-6 receptor antibodies for use, according to any of embodiments 34, 36 to 44 and 46, or use, according to Petition 870250079694, dated 05 / 09 / 2025, pp. 203 / 267 80 / 97 any of the realizations 35 to 44 and 46, in which the anti-OSMRe antibody and the anti-IL-6 receptor antibody are administered in different compositions; and 49. Method, according to any of embodiments 33, 36 to 44 and 46 to 48, anti-OSMRe antibodies and anti-IL-6 receptor antibodies for use, according to any of embodiments 34, 36 to 44 and 46 to 48, or use, according to any of embodiments 35 to 44 and 46 to 48, wherein the individual is human. Examples

[0182] Disclosure shall be further understood by reference to the following examples, which are intended to be purely illustrative of the disclosure contained in this document. The present disclosure is not limited in scope by the embodiments exemplified, which are intended only to illustrate unique embodiments of the disclosure. Example 1. Expression of OSM and OSMR in IPF

[0183] As shown in Figure 1, scRNA sequencing analysis of lung tissue isolated from a human individual diagnosed with IPF shows OSM expression in macrophages and OSMRe expression in epithelial cells, single smooth muscle cell types (SMCs), fibroblasts, and endothelial cells. Expression levels are positively correlated with increased shadowing darkness. These data show that, in the lung tissue of individuals suffering from IPF, both OSM and OSMRe are expressed, and it is reasonable to assume that OSMRe activation after OSM binding occurs in IPF. Example 2. Blocking the OSM reduces lung injury and inflammation.

[0184] A mouse model of bleomycin-induced pulmonary fibrosis (BLM) (Sun et al., 2021, Sci Transl Med 13(605):eabe0407; Sun et al., 2019, JCI Insight. 2019;4(14):e128674) was used Petition 870250079694, dated 05 / 09 / 2025, pages 204 / 267 81 / 97 to conduct experiments demonstrating the effects of blocking OSM signaling by administering anti-OSM antibody. Male C57BL / 6J mice were dosed with 0.25 U / kg of bleomycin intratracheally three times (Day 0, Day 2, Day 4). Mice were treated with either a control or anti-OSM antibody twice weekly, beginning on Day -4 with the last dose on Day 22 before the end of the study on Day 24 after intratracheal administration of bleomycin (Day 0). Specifically, antibody treatments consisted of injection of either a control anti-gp120-mIgG2a antibody (800 µg) or an anti-OSM-mIgG2a antibody (mouse IgG2a, injected as a mixture of 500 µg anti-OSM-mIgG2a and 300 µg anti-gp120-mIgG2a antibody). The disease could progress until day 24, at which point the mice were sacrificed for outcome assessment. Lung injury was measured using micro-CT lung imaging on day 22.The increase in tissue volume (mm3) reflects the increase in lung lesions and disease in mice treated with bleomycin (see Figure 2A). Neutrophil infiltration in the lung after bleomycin-induced injury was measured in bronchoalveolar lavage (BAL) fluid on day 24 (see Figure 2B). The increase in tissue volume reflects the increase in lung lesions and disease in mice treated with bleomycin. This effect was reduced with anti-OSM treatment. Furthermore, WT mice treated with BLM that received anti-OSM blocking antibodies showed significantly less total and new hydroxyproline deposited in the lung compared to control antibodies-treated mice (see Figures 3A and 3B).

[0185] To formally test the need for OSM in BLM-induced pulmonary fibrosis, Osm+ / -+ and Osm- / - mice received a bleomycin solution (0.75 U / kg (DNC# 0703-3155-01; TEVA)) prepared in PBS or saline solution, then instilled into the trachea. Bleomycin or control Petition 870250079694, dated 05 / 09 / 2025, pp. 205 / 267 82 / 97 saline solutions were administered equally in subtherapeutic doses over 3 separate days. Both Osm+ / -+ and Osm- / - mice showed similar weight loss (Figure 4A) and survival (Figure 4B) post-BLM; however, Osm- / - mice showed significantly less lung damage, as determined by changes in tissue volume (TV) (Figure 4C). In a separate group of mice, WT mice treated with BLM received either an anti-OSM blocking antibody or an isotype control. Transcriptional analysis of lung tissue from mice treated with anti-OSM identified a variety of fibrotic pathways that were reduced after OSM blockade, including significantly reduced extracellular matrix regulators (Timp1, Mmp10, -12, -13, -14, and -19) (Figure 4D), collagen regulatory and synthesizing genes (Col1a1, Col1a2, Col3a1, Ereg, Has2), and, most notably, Tnc, which encodes the potent profibrotic hexameric ECM glycoprotein, Tenascin-c48 (Figure 4E).Finally, pathway analysis revealed the extent of the benefit of OSM blockade, with many wound healing and fibrotic pathways (“wound healing”, “IPF signaling”, “pulmonary healing”, “hepatic fibrosis”) reduced (Figure 4F). Example 3. Selection of a Dose and Regimen for IPF and SSc-ILD

[0186] The effective target concentration (Ceff) was estimated based on a combination of non-clinical data from studies on itching in cynomolgus monkeys and clinical data from a phase 1 clinical study in individuals diagnosed with atopic dermatitis (AD) and adjusted based on in vitro potency differences between human skin keratinocytes and lung fibroblasts to generate an estimate of Ceff (Ceff,adj) adjusted for pulmonary fibrosis.

[0187] In a study on itching in cynomolgus monkeys, vixarelimab was used to inhibit scratching behavior, interpreted as a sign of pruritus, induced by a single intradermal administration of IL-31 Petition 870250079694, dated 05 / 09 / 2025, pages 206 / 267 83 / 97 recombinant human (rh) vaccine. Supraphysiological intradermal doses of rhIL-31 between 3 and 24 μg / kg were tested, and all induced itching, with 3 μg / kg resulting in a robust response with minimal variability. Administration of a single IV dose of vixarelimab (1, 3, or 10 mg / kg) resulted in a dose- and time-dependent reduction in rhIL-31-induced itching. Higher serum concentrations of vixarelimab resulted in greater inhibition of itching, and the duration of effect helped establish 5 to 8 μg / ml as the serum concentration threshold for vixarelimab efficacy in this model system.

[0188] Repeated subcutaneous administration of vixarelimab, 1 mg / kg weekly, 3 mg / kg biweekly, or 8 mg / kg monthly, demonstrated a prolonged and significant reduction in IL-31-induced scratching behavior. Monkeys were challenged with rhIL-31 by intradermal injection at various time points after vixarelimab injection. Itching events after hIL-31 challenge were reported for each group. Vixarelimab concentrations in the same dosing regimens were simulated and correlated with the reduction in rhIL-31-induced itching, verifying a Ceff threshold of 5 to 8 μg / ml to inhibit pruritic responses in this model (See Figure 5).

[0189] The Phase 1b human clinical trial of AD treatment with vixarelimab involved IV administration of vixarelimab at doses of 0.3 mg / kg, 1.5 mg / kg, 7.5 mg / kg, 10 mg / kg, or 20 mg / kg and SC administration at doses of 1.5 mg / kg or 360 mg. Patients were monitored for safety, as well as for disease severity, pruritus intensity, and quality of life measures, including sleep quality. Sustained efficacy was found to last 6 to 8 weeks after a single IV dose of 7.5 mg / kg in AD patients, supporting the Ceff of 5 to 8 ug / ml that was identified in the cyno study above (see Figure 6).

[0190] Independently, an in vitro potency study was Petition 870250079694, dated 05 / 09 / 2025, pages 207 / 267 The 84 / 97 study was conducted to compare the ability of vixarelimab to inhibit OSM-induced STAT3 phosphorylation in normal human primary lung fibroblasts, IPF-derived lung fibroblasts, and normal keratinocytes. This study allowed the use of the Ceff determined in the above cyno and human studies to be converted into an estimated adjusted Ceff (Ceff,adj) for use in a phase 2 study of vixarelimab in pulmonary fibrosis indications.

[0191] In vitro potency studies were performed as follows. Five primary human lung fibroblasts derived from normal donors, 5 human lung fibroblasts derived from patients with IPF, and 5 human keratinocytes derived from normal donors were acquired from Lonza (Basel, Switzerland). All primary cells were cultured in complete medium containing RPMI-1640 with 10% heat-inactivated fetal bovine serum, 2 mM L-glutamine, and 1% penicillin-streptomycin. Cells were seeded at 20,000 cells per well in a 96-well plate (Product No. 3595; Corning; Corning, NY) and incubated overnight in a 37°C incubator with 5% CO2. The following day, the antibody vixarelimab and OSM (Purification Lot PUR1BY00559; Genentech) were serially diluted 3 times from an initial final concentration of 50 ug / ml for a total of 10 dilutions in complete RPMI-1640 medium.To examine the inhibitory potency against different levels of OSM, normal human primary lung fibroblasts and fibroblast cells derived from patients with IPF were treated with 1 or 10 ng / ml of OSM (final concentration) in the presence of antibodies, and normal human primary keratinocytes were treated with 10 or 100 ng / ml of OSM (final concentration) in the presence of antibodies. Forty microliters of serially diluted vixarelimab antibody and 40 μL of OSM were mixed and incubated for 10 minutes at room temperature. Then, 50 μL of the mixture were added to each well of the assay plate. The assay plate was incubated at 37 °C for 15 minutes. After incubation, a. Petition 870250079694, dated 05 / 09 / 2025, pages 208 / 267 85 / 97 STAT3 phosphorylation was measured using the Phospo-STAT3 kit (Tyr705) (Catalog No. K150SVD-4; Mesoscale Discovery [MSD]; Gaithersburg, MD). The cell culture medium was removed from the plate and 60 μL of lysis buffer containing phosphatase and protease inhibitors was added. After 1 hour of incubation at 4 °C, 25 μL of cell lysate was transferred using a Biomek i5 automated workstation (Beckman Coulter; Indianapolis, IN) to an MSD plate that had been previously blocked and washed. The cell lysate was incubated at 4 °C overnight on a shaker. Next, the plate was washed 3 times with 200 μl per well of Tris buffer, followed by the addition of 25 μl of anti-phospho-STAT3 antibody labeled with SULFO-TAG™ in each well.After 1 hour of incubation at room temperature in a shaker, the plate was washed 3 times with 200 μl of Tris buffer per well, and 150 μl of surfactant-based reading buffer was added to each well before the plate was read on an MSD MESO SECTOR S 600 instrument. The percentage of inhibition of phosphorylated STAT3 (pSTAT3) (% inhibition) for each treatment condition was calculated using the following equation, where the maximum is the MSD signal from OSM only and the minimum is the MSD signal from RPMI-1640 medium only: pSTAT3 (% inhibition) = [1 - (MSD signal - minimum) + (maximum - minimum)] x 100

[0192] The pSTAT3 (% inhibition) was plotted as a function of antibody concentrations, and the data were fitted to a 4-parameter sigmoidal logistic model (4PL) using Prism (GraphPad; La Jolla, CA). The 50% inhibitory concentration (IC50) value for each donor was determined as the concentration that achieved 50% inhibition of maximum activity. The concentration leading to 90% of the maximum inhibitory response (90% inhibitory concentration; IC90) was calculated using modeled parameters.

[0193] The results show that vixarelimab consistently inhibits OSM-induced STAT3 phosphorylation in a panel of primary cells derived from human donors, including fibroblasts Petition 870250079694, dated 05 / 09 / 2025, pages 209 / 267 86 / 97 normal lung cells, IPF-derived lung fibroblasts, and normal keratinocytes. The mean and standard deviation of the IC50 and IC90 values ​​were determined by the concentration-response curve fitted to a 4PL sigmoidal model. The results are summarized in Table 3 below. Table 3 Cell Type [OSM] (ng / ml) Mean IC50 (ng / ml) Standard Deviation of IC50 Mean IC90 (ng / ml) Standard Deviation of IC90 Normal lung fibroblasts 1 13.04 7.36 135.31 40.67 Normal lung fibroblasts 10 88.17 39.7 948.07 593.49 IPF-derived lung fibroblasts 1 12.45 4.05 114.26 45.58 IPF-derived lung fibroblasts 10 56.11 15.61 347.52 152.39 Normal keratinocytes 10 4.95 3.31 234.99 158.41 Normal keratinocytes 100 45.05 32.44 1038.62 948.82

[0194] The results of the in vitro study were used to convert the Ceff of 8 ug / ml to a Ceff,adj of 20.4 ug / ml for pulmonary fibrosis, using a difference in the in vitro IC50 for OSM-induced pSTAT3 activation between keratinocytes and pulmonary fibroblasts.

[0195] Next, the PK profile of vixarelimab was simulated to estimate the estimated Cmin coverage of Ceff,adj, at various dosage levels. The simulation was performed with a preliminary target-mediated drug disposition (TMDD) population PK model developed with available clinical PK data from healthy individuals and patients with AD and PN. The PK profiles between healthy individuals and patient populations with AD and PN appeared comparable; however, the simulation incorporated a presumed worst-case increase in the target amount of 2-fold in patients with IPF compared to healthy individuals. The simulated PK profiles are illustrated in Figure 7.

[0196] This simulation showed that more than 90% of patients Petition 870250079694, dated 05 / 09 / 2025, pages 210 / 267 87 / 97 with IPF exhibit Cmin,ss above the estimated Ceff,adj after administration of 360 mg Q2W, regardless of assumed OSMRe levels in IPF patients. Less frequent dosing was also explored, but simulation results did not show sufficient Ceff,adj coverage. Specifically, a 360 mg Q4W dosing regimen provides coverage of <25% of patients above Ceff,adj. A 540 mg Q4W dosing regimen provides coverage of patients above Ceff,adj for >50% of patients with up to a 1.5-fold increase in OSMRe level, but this coverage drops to less than 50% if systemic OSMRe levels are assumed to increase 2-fold. These data support the selection of the 360 ​​mg Q2W dosage for IPF and SSc-ILD patients to provide target coverage for the majority of the patient population. Example 4. Phase 2 study to evaluate efficacy, safety, and PK in IPF and SSC-ILD

[0197] A Phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled, two-cohort study was designed to evaluate the efficacy, safety, and pharmacokinetics of vixarelimab in patients with IPF (Cohort 1) and in patients with SSc-ILD (Cohort 2). Cohort 1 will enroll approximately 200 patients with IPF (of whom up to 50 may be on concomitant standard of care antifibrotic therapy), and Cohort 2 will enroll approximately 60 to 120 patients with SSc-ILD (of whom up to 30 may be on concomitant standard of care anti-IL-6 therapy and up to 30 patients may be on concomitant standard of care with nintedanib). Each cohort will be analyzed separately. Up to approximately 290 patients with IPF and SSc-ILD may be enrolled in the OLE portion of the study.

[0198] Eligible patients will have an FVC (forced vital capacity) > 45% of predicted forced vital capacity and a forced expiratory volume in 1 second (FEV1) to FVC ratio > 0.70; a subset of Petition 870250079694, dated 05 / 09 / 2025, pages 211 / 267 88 / 97 patients will receive standard, stable care treatment for their condition.

[0199] In addition, patients in Cohort 1 will be between 40 and 85 years old and will have a documented diagnosis of IPF or (probable) IPF according to ATS / ERS / JRS / ALAT guidelines (Raghu et al. 2022). Patients with a clinical context suggestive of IPF and a high-resolution computed tomography (HRCT) pattern of usual interstitial pneumonia (UIP) or probable UIP are considered to have a diagnosis of IPF when biopsy is not available (Raghu et al. 2022). Patients will have an HRCT pattern consistent with the diagnosis of IPF, confirmed by central review of chest HRCT and central review of any available lung biopsy. For patients receiving pirfenidone or nintedanib treatment for IPF, they should have been treated for > 3 months with a stable dose for > 4 weeks prior to screening and during screening, with plans to continue treatment throughout the study period.For patients not receiving treatment with nintedanib or pirfenidone, these patients are treatment-naive or discontinued treatment > 4 weeks before screening and during screening, with no plans to initiate or restart therapy during the study period.

[0200] Patients in Cohort 2 will be between 18 and 85 years old and will have a documented initial diagnosis of systemic sclerosis (SSc) as defined using American College of Rheumatology / EULAR criteria (van den Hoogen et al. 2013), an HRCT pattern demonstrating >10% fibrosis, and evidence of progressive pulmonary fibrosis, defined as at least two of the following criteria occurring in the last year without alternative explanation (Raghu et al., 2022): worsening respiratory symptoms, and physiological evidence of disease progression by any of the following: absolute decline in FVC >5% predicted in 1 year of Petition 870250079694, dated 05 / 09 / 2025, pages 212 / 26789 / 97 follow-up; absolute decline in CLco (corrected for hemoglobin) > 10% predicted at 1 year of follow-up. Patients presenting radiological evidence of disease progression according to the ATS / ERS / JRS / ALAT 2022 guidelines (Raghu et al. 2022). For patients receiving anti-IL-6 treatment (e.g., tocilizumab) for SSc-ILD, they must have received treatment for > 3 months at a stable dose for > 4 weeks before and during screening and have no intention of altering or modifying their treatment regimen during the study. Patients not currently receiving anti-IL-6 treatment, such as treatment-naïve patients or those who discontinued treatment > 4 weeks before and during screening, with no plans to initiate or restart therapy during the study period.For patients treated with standard-of-care immunosuppressive agents permitted for their underlying skin disease (e.g., mycophenolate mofetil (MMF), methotrexate (MTX)), they will have a stable treatment dosage for > 3 months with a stable dose for > 4 weeks prior to screening, with no intention of altering or modifying their treatment regimen during the study period.

[0201] Exclusion criteria for all patients include those with a percentage of predicted FVC value showing improvement in the 6-month period prior to screening and including screening value, known post-bronchodilator response in FEVi and FVC (defined as a 12% and 200 ml increase)

[0202] After a screening period of up to 40 days, eligible patients within each cohort will be randomized 1:1 to receive subcutaneous (SC) injections of vixarelimab 360 mg or placebo Q2W for 26 doses over 52 weeks, followed by a follow-up visit approximately 9 weeks after the final dose. Randomization in Cohort 1 will be stratified by concomitant antifibrotic treatment and region, and the Petition 870250079694, dated 05 / 09 / 2025, pages 213 / 267 Randomization in Cohort 2 (90 / 97) will be stratified by concomitant anti-IL-6 treatment. Reviews

[0203] Patients will return to the clinic every 2 weeks until the treatment completion visit at Week 52 for vixarelimab administration and assessment of vital signs, adverse events, and concomitant medications, and every 4 weeks for spirometry (e.g., FVC and ratio (FEV1) to FVC), assessment of healthcare utilization, assessment of ILD exacerbations and hospitalizations, physical examinations, and certain laboratory tests. Other assessments, including the 6MWT (6-minute walk test), DLco, and patient-reported outcomes (PROs), will be performed less frequently. HRCT (high-resolution computed tomography) will be performed at screening (if an acceptable quality HRCT is not available within 3 months prior to randomization), at Week 12, and at Week 52, and samples for PK and ADA analysis will be collected throughout the study.In addition, patients in Cohort 2 will need to undergo a skin biopsy at baseline and at Week 52 and will be assessed using mRSS at various time points during the study. For patients in participating sites after Week 4, the study drug may be administered at alternating time points by a trained nurse practitioner in the patient's home or another suitable location if the patient has provided written informed consent to participate in mobile nursing visits (MN).

[0204] On dosing days, administration will occur after all scheduled safety and efficacy assessments for that visit have been completed. Patients will return to the clinic every 4 weeks until the treatment completion visit at Week 52 for assessments, including vital signs, spirometry (e.g., FVC and ratio (FEV1) to FVC), 6MWT, and Petition 870250079694, dated 05 / 09 / 2025, pages 214 / 267 91 / 97 PROs. HRCT will be performed at screening (if an acceptable quality HRCT is not available within 3 months prior to randomization), at Week 12, and at Week 52, and samples for PK and ADA analysis will be collected throughout the study. Additionally, patients in Cohort 2 will need to undergo a skin biopsy at baseline and at Week 52 and will be assessed using mRSS at various time points during the study.

[0205] Patients (including those who received placebo) who complete the 52-week treatment period will be invited to participate in an open-label extension study (OLE) to receive treatment with vixarelimab at the same dose and regimen for up to 1 year. Patients who are not enrolled in the OLE study will return to the clinic for a follow-up assessment approximately 9 weeks after the final dose (i.e., at Week 59) to ensure safety.

[0206] For both cohorts, the primary outcome is the absolute change from baseline to Week 52 in FVC (ml), and the primary secondary outcome is the change in 6MWT distance in meters at Week 52. Other secondary outcomes include absolute change from baseline to Week 52 in predicted FVC percentage; change from baseline to Week 52 in DLco[Hb]; time to disease progression, defined as time to first occurrence of absolute decline > 10% in predicted FVC percentage, relative decline > 15% in 6MWT distance, lung transplantation, or death; time to first acute exacerbation of ILD or suspected acute exacerbation of ILD, as determined by the clinical adjudication committee (CAC); change from baseline to Week 52 in quantitative pulmonary fibrosis on high-resolution computed tomography (HRCT) of the chest; and survival, as measured by all-cause mortality.

[0207] Patients who do not meet the criteria for Petition 870250079694, dated 05 / 09 / 2025, pages 215 / 267 92 / 97 participants in this study (screening failure) may qualify for a rescreening opportunity (for a total of two screenings per patient) at the investigator's discretion. Additionally, if a patient fails a test due to technical issues (e.g., hemolyzed lab sample that cannot be analyzed), the patient may repeat the test if still within the screening period. The investigator will maintain a record of the reasons for screening failure. The study design can be found in Figure 8. Open Extension Study

[0208] An open-label extension study (OLE) will be conducted, subject to approval by local Institutional Review Boards or Ethics Committees (IRBs / ECs) and relevant health authorities. Patients from Cohort 1 and Cohort 2 who complete the treatment period of the Phase 2 study (Example 4) by Week 52 will have the option to enroll in the OLE study and receive open-label vixarelimab treatment, if eligible and provided that the OLE study is open-label in their respective countries.

[0209] Patients should begin the OLE period on the same day as their Week 52 visit in the double-blind treatment period, after completing all necessary Week 52 assessments. Alternatively, the first dose in the OLE period may be administered up to 4 weeks (+ 5 days) after the last dose of the study drug in the double-blind treatment period. The first visit of the OLE period will be considered the OLE baseline. Patients will return to the clinic for scheduled visits to receive an additional 52 weeks of open-label vixarelimab 360 mg SC Q2W, and for assessments including vital signs, spirometry, and 6MWT until the OLE treatment completion visit. Patients will return to the clinic for a follow-up visit approximately 9 weeks after the final dose.

[0210] For each cohort in the OLE study, treatment efficacy will be determined by measuring the absolute change from baseline OLE to the Petition 870250079694, dated 05 / 09 / 2025, pp. 216 / 267 93 / 97 Week 52 OLE in FVC (ml); absolute change from baseline OLE to Week 52 OLE in 6MWT distance (in meters); absolute change from baseline OLE to Week 52 OLE as a percentage of predicted FVC; change from baseline OLE to Week 52 OLE in DLco[Hb]; change from baseline OLE to Week 52 OLE in quantitative pulmonary fibrosis on HRCT chest CT; and survival, as measured by all-cause mortality. For Cohort 2 only, change from baseline OLE to Week 52 OLE in cutaneous sclerosis, as measured by the modified Rodnan skin thickness scale (mRSS). Example 5. IL-6 stimulates the activation of CD64+ macrophages in murine pulmonary inflammation and fibrosis.

[0211] The role of IL-6 in the murine bleomycin (BLM)-induced lung injury, inflammation, and fibrosis model was investigated. IL-6 receptor knockout mice (Il6r- / - mice) showed reduced lung injury and inflammation on both day 8 and day 24 post-BLM (data not shown) with reduced hydroxyproline, an amino acid necessary for collagen biosynthesis (Figure 9A), along with reduced expression of the Collal and Col1a2 genes in the lung (Figure 9B). Correlating with the reduced disease in Il6r- / - mice, there was a reduction in the proportion and total number of CD64+ macrophages (CD45+CD11c+SiglecFMHCII+CD11b+CD64+) on both day 8 and day 24 post-BLM (Figure 9C), suggesting that IL-6 contributes to macrophage recruitment.

[0212] To determine whether these observations in murine macrophages were translated to human macrophages, we prepared human monocyte-derived macrophages with IL-4 / 13 and treated them with IL-6. As expected, IL-6 significantly increased the transcription and secretion of CCL18 (Figure 10), a chemokine known to be prognostic for worse outcome in ILD. Samples from patients with IPF and SSc-ILD demonstrated Petition 870250079694, dated 05 / 09 / 2025, pages 217 / 267 94 / 97 that the IL-6-regulated macrophage genes CD64, CCL2, and CCL18 were all significantly increased in the lung tissue of IPF patients (Figure 11) or in the skin of SSc-ILD patients (Figure 12). After 24 weeks of treatment with anti-IL-6R mAb (tocilizumab) in the clinic, there was a very clear and strong pharmacodynamic effect of these genes in the skin of SSc-ILD patients in a separate phase 2 clinical trial (Figure 13), suggesting that IL-6 regulated macrophage activation in these ILD patients. Therefore, IL-6 may contribute to the decline in lung function in ILD patients through an inflammatory macrophage-mediated activation pathway, and IL-6 and potentially macrophage-independent pathways may contribute to progressive fibrosis in ILD. Example 6. OSMR-dependent pathogenesis in human cells relevant to diseases.

[0213] To establish the role of OSMR in the pathogenesis of IPF and SSc, lung and skin biopsies were obtained from healthy patients and patients with IPF or SSc. RNA-sequential analysis of these biopsies demonstrated that OSM was elevated in lung tissue and skin due to IPF (Figure 14A) and SSc (Figure 14B). Primary human SAEC, endothelial cells, and fibroblasts in vitro were cultured and stimulated with recombinant human OSM (10 ng / ml) for 15 minutes. Cell lysates were recovered, and pSTAT3Tyr705 was measured by Mesoscale Discovery (MSD) assays. All three primary human cell types responded to OSM with significant STAT3 phosphorylation, regardless of whether the cells were derived from healthy patients or those with IPF (Figure 15A). A comparative transcriptional analysis of these 3 cell types was performed after 24 hours of exposure to OSM.Of the top 10 OSM-induced transcripts in each cell type, many were commonly upregulated across all cell types (CFI, JAK3, SOCS3, C1R, SPP1, IL1R1, CEBPD, GSDMC, etc.). Petition 870250079694, dated 05 / 09 / 2025, pages 218 / 267 95 / 97 NAMPT), with some notable specific cellular responses observed, including OSM-induced ENNP2 (Autotaxin) in SAEC, OSM-induced IL6 in endothelial cells, and OSM-induced S1PR1 in fibroblasts, all of which have clear roles in pulmonary fibrosis (Figure 15B).

[0214] OSM binds to gp130, which therefore heterodimerizes with OSMR or LIFR for signal transduction. To determine whether OSM-induced responses were mediated by OSMR or LIFR, a test was conducted to determine whether antagonizing only OSMR was sufficient to block OSM-induced responses in these 3 OSM-responsive and disease-relevant cell types. Using a newly generated human anti-OSMR blocking Ab, OSM-induced pSTAT3 was almost completely inhibited in SAEC and fibroblasts (Figure 16A), derived from healthy donors or IPF (Figure 16B). Blocking the OSMR Ab inhibited OSM-induced pSTAT3 in endothelial cells by approximately 50% (Figures 16A and 16C). The addition of anti-LIFR confirmed that OSM uses OSMR and LIFR for signaling in endothelial cells, with complete inhibition obtained when both mAbs were used (Figure 16D).These data indicate that OSMR antagonism alone is sufficient to almost completely mitigate OSM-induced pSTAT3 in fibroblasts and epithelial cells.

[0215] Next, it was determined whether OSM could cause damage to pulmonary endothelial cells and whether this depended on OSMR or LIFR. Indeed, OSM-induced endothelial cell disruption and permeability compromise barrier integrity, which could be completely avoided with anti-OSMR antagonism (Figure 17). Treatment with anti-LIFR mAb had little or no impact on OSM-induced permeability. Similarly, OSM-induced IL-6 and CCL2 / MCP1 secretion from pulmonary endothelial cells was largely OSMR-dependent rather than LIFR-dependent (Figure 18). Therefore, although OSM-induced pSTAT3 was only Petition 870250079694, dated 05 / 09 / 2025, pp. 219 / 267 96 / 97 partially mediated by OSMR, endothelial cell permeability and inflammatory cytokine production were predominantly mediated by OSMR. Similar studies were conducted with primary lung SAEC cultured in 3D organoids. Similar to endothelial cells, OSM can also disrupt SAEC integrity with a significant increase in permeability (Figure 19). OSM-induced SAEC permeability also depended on OSMR and not LIFR, in line with pSTAT3 data (Figure 16A). Taken together, these data indicate that OSM can disrupt the integrity of epithelial and endothelial cells, a potential pathogenic axis in ILD, and that this process depends on OSMR signaling.

[0216] Most impressively, OSM directly induced collagen (COL1) secretion from primary human fibroblasts. This process was also OSMR-dependent (Figure 20), providing direct mechanistic evidence for a potential role of OSM in human fibrotic diseases.

[0217] To determine whether OSMR is also required for OSM-induced responses in multicellular human lung explants, we stimulated precision-cut lung slices (PCLS) with OSM and treated these cultures with anti-OSMR or anti-LIFR blocking antibodies. Consistent with primary human monoculture systems, OSM-induced chemokine production (CCL3 and CCL4) from PCLS was OSMR-dependent, not LIFR-dependent (Figure 21), supporting the therapeutic targeting of OSMR to prevent OSM activity in human lung diseases. Collectively, these studies provide the biological rationale and mechanistic data to support the therapeutic development of an OSMR antagonist to treat fibrotic lung diseases. The proposed benefit of OSMR antagonism may be further enhanced with combined treatment with IL6R antagonists. Petition 870250079694, dated 05 / 09 / 2025, pages 220 / 267 97 / 97 Example 7. The combined antagonism of IL6 and OSM reduces LUNG INJURIES, INFLAMMATION, AND FIBROSIS.

[0218] Mice were treated with anti-IL-6R mAbs, a murine substitute for tocilizumab, anti-OSM mAbs, or a combination of both mAbs. Mice exposed to BLM, regardless of Ab treatment, lost weight (Figure 22A) with a small proportion of mice succumbing to BLM-induced disease (Figure 22B). Both anti-IL-6R and anti-OSM treatment reduced lung damage, as determined by changes in tissue volume (TV) (Figure 22C). The combination of anti-IL-6R and anti-OSM reduced tissue volume by approximately 60% (BLM+Iso, 140±18.3 mm3 compared to BLM+aIL6 / OSM, 60.2±9.2 mm3). The effects of the combined treatment extended to fibrotic outcomes, hydroxyproline measurements, and pathology scores (Figure 23A and Figure 23B).Furthermore, using airway infiltrates as a surrogate for inflammation, anti-IL-6R treatment reduced inflammation, but a greater effect, especially in reducing airway neutrophils, was observed in mice that received anti-IL-6R + anti-OSM (Figure 24). These data indicate that IL-6 and OSM contribute to lung injury, inflammation, and fibrosis induced by BLM in a non-overlapping manner.

[0219] Although the previous disclosure has been described in some detail by way of illustration and example for the sake of clarity, the descriptions and examples should not be construed as limiting the scope of the disclosure. The disclosures of all patents and scientific literature cited herein are expressly incorporated in their entirety by reference. Petition 870250079694, dated 05 / 09 / 2025, pages 221 / 267

Claims

1 / 8 Claims 1. METHOD FOR TREATING A PULMONARY FIBROTIC DISEASE, characterized by comprising administering to an individual in need thereof a therapeutically effective dose of an anti-OSMRe antibody (oncostatin M beta receptor).

2. ANTI-OSMRp ANTIBODY, characterized by being for use in the treatment of pulmonary fibrosis in an individual who requires it.

3. USE OF AN ANTI-OSMRp ANTIBODY, characterized by being for the manufacture of a pharmaceutical composition to treat a fibrotic lung disease in an individual who needs it.

4. METHOD, according to claim 1, anti-OSMRp antibody for use, according to claim 2, or use, according to claim 3, characterized by pulmonary fibrotic disease being selected from the group consisting of progressive pulmonary fibrosis (PPF), idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD).

5. METHOD, according to any one of claims 1 or 4, the anti-OSMRp antibody for use, according to any one of claims 2 or 4, or the use, according to any one of claims 3 or 4, characterized by the anti-OSMRp antibody inhibiting type II OSMR signaling by OSM and IL-31.

6. METHOD, according to any one of claims 1, 4 and 5, the anti-OSMRp antibody for use, according to any one of claims 2, 4 and 5, or the use, according to any one of claims 3 to 5, characterized in the anti-OSMRp antibody being vixarelimab.

7. METHOD, according to any one of claims 1 and 4 to 6, the anti-OSMRp antibody for use, according to any one of claims 2 and 4 to 6, or the use, according to any one of claims 3 to 6, characterized by the therapeutically effective dose being from about 360 mg to 720 mg of the anti-OSMRe antibody, preferably 360 mg of the anti-OSMRe antibody.

8. METHOD, according to any one of claims 1 and 4 to 7, the anti-OSMRe antibody for use, according to any one of claims 2 and 4 to 7, or the use, according to any one of claims 3 to 7, characterized by administration comprising administering the therapeutically effective dose once a week, once every 2 weeks, once every 3 weeks, once every 4 weeks or once a month, preferably once every 2 weeks.

9. METHOD, according to any one of claims 1 and 4 to 8, the anti-OSMRe antibody for use, according to any one of claims 2 and 4 to 8, or the use, according to any one of claims 3 to 8, characterized by administration comprising administering the therapeutically effective dose subcutaneously or intravenously, preferably subcutaneously.

10. METHOD, according to any one of claims 1 and 4 to 9, the anti-OSMRe antibody for use, according to any one of claims 2 and 4 to 9, or the use, according to any one of claims 3 to 9, characterized in that, before treatment with the anti-OSMRe antibody, the individual has a percentage of predicted forced vital capacity (%FVC) of about 35% to 90%, about 35% to 75%, about 35% to 50%, about 45% to 55%, about 30% to 60%, about 50% to 90%, about 50% to 75%, about 40% to 45%, about 40% to 50%, about 45% to 50%, or about 45% to about 50%.

11. METHOD, according to any of claims 1 and 4 to 10, the anti-OSMRe antibody for use, according to any of Petition 870250079694, dated 05 / 09 / 2025, p. 223 / 267 3 / 8 claims 2 and 4 to 10, or the use, according to any of claims 3 to 10, characterized in that, prior to treatment with the anti-OSMRe antibody, the individual has a forced expiratory volume in 1 second (FEV1) to FVC ratio of approximately 0.35 to 0.70, approximately 0.50 to 0.70, approximately 0.60 to 0.70, approximately 0.35 to 0.50, approximately 0.40 to 0.50, approximately 0.50 to 0.60, approximately 0.60 to 0.70, approximately 0.70 to 0.

80.

12. METHOD, according to any one of claims 1 and 4 to 11, the anti-OSMRe antibody for use, according to any one of claims 2 and 4 to 11, or the use, according to any one of claims 3 to 11, characterized in that administration of the dose of anti-OSMRe antibody to the individual results in a change in FVC in the individual, wherein the change is a measure of the absolute change in FVC in milliliters (ml) over a treatment period beginning at the time of the first administration of the anti-OSMRe antibody until the time a subsequent dose of the anti-OSMRe antibody is administered, optionally wherein the change in FVC during the treatment period is a decrease in FVC of less than 25 ml, 50 ml, 75 ml, 100 ml, 125 ml, 150 ml, 175 ml or 200 ml, 225 ml or 250 ml or an increase in FVC of at least 25 ml. ml, 50 ml, 75 ml, 100 ml, 125 ml, 150 ml, 175 ml or 200 ml, 225 ml or 250 ml.

13. METHOD, according to any one of claims 1 and 4 to 12, the anti-OSMRe antibody for use, according to any one of claims 2 and 4 to 12, or the use, according to any one of claims 3 to 12, characterized in that administration of the dose of anti-OSMRe antibody to the individual results in an increase in DLCO[Hb] in the individual, wherein the change is a measure of the absolute change in DLCO[Hb] over a treatment period beginning at the time of the first administration of the anti-OSMRe antibody until the time a subsequent dose of the anti-OSMRe antibody is administered, optionally wherein the change in Petition 870250079694, dated 05 / 09 / 2025, p. 224 / 267 4 / 8 DLco[Hb] during the treatment period is an increase of at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80% or 90%.

14. METHOD, according to any one of claims 1 and 4 to 13, the anti-OSMRe antibody for use, according to any one of claims 2 and 4 to 13, or the use, according to any one of claims 3 to 13, characterized in that administration of the dose of anti-OSMRe antibody to the individual results in a change in the distance walked by the individual in the 6-minute walk test (6MWT), wherein the change is a measure of the distance walked by the individual in the 6MWT over a treatment period beginning at the time of the first administration of the anti-OSMRe antibody until the time a subsequent dose of the anti-OSMRe antibody is administered, optionally wherein the change in distance during the treatment period is (a) an increase of at least 5%, 10%, 15%, 20%, 25% or 30%; or (b) a decrease of less than about 5%, 10%, 15%, 20%, 25% or 30%.

15. METHOD, according to any one of claims 1 and 4 to 14, the anti-OSMR antibody for use, according to any one of claims 2 and 4 to 14, or the use, according to any one of claims 3 to 14, characterized in that administration of a dose of anti-OSMR antibody to an individual results in a change in cough relative to baseline, wherein the change is a measure of cough frequency over a treatment period beginning at the time of the first administration of the anti-OSMR antibody until the time a subsequent dose of the anti-OSMR antibody is administered, wherein the change is a reduction in cough frequency, and wherein the cough is measured by an ambulatory digital device for continuous cough detection.

16. METHOD, anti-OSMRe antibody for use, or use, of Petition 870250079694, dated 05 / 09 / 2025, p. 225 / 267 5 / 8 in accordance with any of claims 13 to 15, characterized by the treatment period being about 6 weeks, about 12 weeks, about 24 weeks, about 36 weeks, about 48 weeks, about 60 weeks or about 72 weeks.

17. METHOD, according to any one of claims 1 and 4 to 16, the anti-OSMR antibody for use, according to any one of claims 2 and 4 to 16, or the use, according to any one of claims 3 to 16, characterized in the anti-OSMR antibody being administered to the individual in combination with a second therapeutic agent, optionally wherein the second therapeutic agent is a therapeutic agent indicated for a pulmonary fibrotic disease or disorder.

18. METHOD, anti-OSMRe antibody for use, or use, according to claim 17, characterized in that the second therapeutic agent is pirfenidone, nintedanib or an anti-IL-6 receptor antibody, such as tocilizumab.

19. METHOD, anti-OSMRe for use, or use, according to claim 18, characterized by the anti-IL-6 receptor antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 13 and a light chain comprising the amino acid sequence of SEQ ID NO:

14.

20. METHOD, anti-OSMRe for use, or use, according to claim 18, characterized by the anti-IL-6 receptor antibody comprising the six CDRs of tocilizumab.

21. METHOD FOR TREATING A PULMONARY FIBROTIC DISEASE in an individual in need thereof, the method characterized by comprising administering to the individual a therapeutically effective amount of (a) an anti-OSMRe antibody and (b) an anti-IL-6 receptor antibody.

22. THERAPEUTICLY EFFECTIVE QUANTITY OF (A) AN ANTI-OSMRB ANTIBODY AND (B) AN ANTI-IL-6 RECEPTOR ANTIBODY, characterized as being for use in the treatment of a fibrotic lung disease in an individual who needs it.

23. Use of a therapeutically effective amount of (a) an anti-OSMRe antibody and (b) an anti-IL-6 receptor antibody, characterized in that it is for the manufacture of a medicament to treat a fibrotic lung disease in an individual in need thereof.

24. METHOD, according to claim 21, anti-OSMRe and anti-IL-6 receptor antibodies for use, according to claim 22, or use, according to claim 23, characterized in the anti-OSMRe antibody comprising (a) a variable heavy chain (VH) domain comprising SEQ ID NO:7 and a variable light chain (VL) domain comprising SEQ ID NO:8; or (b) a heavy chain (HC) comprising SEQ ID NO:5 and a light chain (LC) comprising SEQ ID NO:

6.

25. METHOD, according to claim 21, anti-OSMRe and anti-IL-6 receptor antibodies for use, according to claim 22, or use, according to claim 23, characterized in the anti-OSMRe antibody being vixarelimab.

26. METHOD, according to any one of claims 21, 24 and 25, anti-OSMRe and anti-IL-6 receptor antibodies for use, according to any one of claims 22, 24 and 25, or use, according to any one of claims 23 to 25, characterized by the heavy chain of the anti-IL-6 receptor antibody comprising the amino acid sequence of SEQ ID NO: 13, and the light chain of the anti-IL-6 receptor antibody comprising the amino acid sequence of SEQ ID NO:

14.

27. METHOD, according to any one of claims 21, 24 and 25, anti-OSMRe and anti-IL-6 receptor antibodies for use, according to any one of claims 22, 24 and 25, or the use, according to Petition 870250079694, dated 05 / 09 / 2025, pp. 227 / 267 7 / 8 with any one of claims 23 to 25, characterized by the anti-IL-6 receptor antibody being tocilizumab.

28. METHOD, according to any one of claims 21, 24 and 25, anti-OSMRe and anti-IL-6 receptor antibodies for use, according to any one of claims 22, 24 and 25, or use, according to any one of claims 23 to 25, characterized by the anti-IL-6 receptor antibody comprising the six CDRs of tocilizumab.

29. METHOD, according to claim 21, anti-OSMR and anti-IL-6 receptor antibodies for use, according to claim 22, or use, according to claim 23, characterized in that the anti-OSMR antibody is vixarelimab and the anti-IL-6 receptor antibody is tocilizumab.

30. METHOD, according to any one of claims 21 and 24 to 29, anti-OSMRe and anti-IL-6 receptor antibodies for use, according to any one of claims 22 and 24 to 29, or use, according to any one of claims 23 to 29, characterized by pulmonary fibrotic disease being selected from the group consisting of progressive pulmonary fibrosis (PPF), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis-associated interstitial lung disease (SSc-ILD), preferably IPF.

31. METHOD, according to any one of claims 21 and 24 to 30, the anti-OSMRe and anti-IL-6 receptor antibodies for use, according to any one of claims 22 and 24 to 30, or the use, according to any one of claims 23 to 30, characterized by the anti-OSMRe antibody and the anti-IL-6 receptor antibody being administered simultaneously or sequentially.

32. METHOD, according to any one of claims 21 and 24 to 31, the anti-OSMRe and anti-IL-6 receptor antibodies for use, according to any one of claims 22 and 24 to 31, or the use, according to Petition 870250079694, dated 05 / 09 / 2025, page 228 / 267 8 / 8 with any one of claims 23 to 31, characterized by the anti-OSMRe antibody and the anti-IL-6 receptor antibody being administered in the same composition or in different compositions.

33. METHOD, according to any one of claims 1, 4 to 21 and 24 to 32, the anti-OSMRe antibody for use, according to any one of claims 2 and 4 to 20, the anti-OSMRe and anti-IL-6 receptor antibodies for use, according to any one of claims 22 and 24 to 32, or the use, according to any one of claims 3 to 20 and 23 to 32, characterized by the individual human being. Petition 870250079694, dated 05 / 09 / 2025, p. 229 / 267

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