Methods of treating inflammatory diseases by blocking Galectin-3
Inventors
Sun, Dongxu • GORDON, Catherine A. • Shchors, Ksenya • Wang, Yan • Tsai, Tsung-Huang • Leong, Yew Ann
Assignees
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Publication Number
US-12281166-B2
Publication Date
2025-04-22
Expiration Date
Abstract
Disclosed herein are methods, antibodies, and compositions for disrupting an interaction between Galectin-3 (Gal3) and viral proteins, such as proteins of the SARS-CoV-2 virus or other coronaviruses, or viral-associated host proteins. Further disclosed herein are methods, medicaments, and compositions for the treatment of a disease or a disorder in a subject, such as the treatment of a viral infection, or treatment of a fibrosis, such as lung fibrosis, that develop as a sequela of a viral infection, or cytokine release syndrome. Further disclosed herein are methods, medicaments, and compositions for the treatment of an inflammatory disease or disorder, such as inflammation of the lungs or systemic lupus erythematosus, which may be associated with neutrophil activity, in a subject. Also disclosed herein are pharmaceutical antibody formulations for the treatment of a disease, such as a coronavirus infection.
Core Innovation
The invention relates to decreasing or inhibiting inflammation in a subject by administering an effective amount of an anti-Gal3 antibody or binding fragment thereof. The anti-Gal3 antibody or binding fragment includes a light chain variable region with specified V_L-CDR1, V_L-CDR2, and V_L-CDR3 and a heavy chain variable region with specified V_H-CDR1, V_H-CDR2, and V_H-CDR3, with multiple specific CDR sequence combinations identified using SEQ ID NOs.
Administration of the anti-Gal3 antibody or binding fragment decreases or inhibits neutrophil activation and/or migration, decreases or inhibits cleavage of CD62L expressed by neutrophils, and decreases or inhibits IL-8 production in the subject. The treatment also decreases the number of neutrophils and/or modulates expression of myeloperoxidase (MPO), growth-related oncogene α (GROα)/keratinocytes-derived chemokine (KC), Ly6c1, INOS, IL-6, TNFα, IL-1B, Col1A1, aSMA, TGFβ, VEGFA, VEGFB, or any combination thereof.
The invention is associated with treatment of inflammation, including lung inflammation and autoimmune disease. The disclosed supporting content also references coronavirus infection and COVID-19-related mechanisms involving Gal3 and anti-Gal3 interactions, as well as inflammation readouts in mouse models including elastase-induced COPD and reduced SLE autoantibodies.
Claims Coverage
The provided claim set includes 1 independent claim. The claim centers on an anti-Gal3 antibody or binding fragment defined by specific V_L and V_H CDR SEQ ID NO combinations, with one principal inventive concept tied to neutrophil-associated inflammation outcomes and biomarker modulation.
Anti-Gal3 variable region defined by enumerated V_L and V_H CDR SEQ ID sets
The anti-Gal3 antibody or binding fragment comprises a light chain variable region with V_L-CDR1, V_L-CDR2, and V_L-CDR3 and a heavy chain variable region with V_H-CDR1, V_H-CDR2, and V_H-CDR3, wherein the CDRs are selected from the specified SEQ ID NO combinations.
Inflammation reduction via neutrophil activation and migration inhibition
Administration of an effective amount decreases or inhibits neutrophil activation and/or migration in the subject, decreases or inhibits cleavage of CD62L expressed by neutrophils, decreases or inhibits IL-8 production, decreases the number of neutrophils, and/or modulates expression of MPO, GROα/KC, Ly6c1, INOS, IL-6, TNFα, IL-1B, Col1A1, aSMA, TGFβ, VEGFA, VEGFB, or any combination thereof.
Overall, the independent claim coverage centers on anti-Gal3 antibodies or binding fragments with specified CDR-defined variable regions, and on therapeutic efficacy measured through decreases or inhibition of neutrophil activation, migration, CD62L cleavage, IL-8 production, neutrophil number, and modulation of specified inflammatory and biomarker expressions.
Stated Advantages
Decreases or inhibits inflammation in a subject.
Decreases or inhibits neutrophil activation and/or migration.
Decreases or inhibits cleavage of CD62L expressed by neutrophils.
Decreases or inhibits IL-8 production.
Decreases the number of neutrophils.
Modulates expression of myeloperoxidase (MPO), GROα/KC, Ly6c1, INOS, IL-6, TNFα, IL-1B, Col1A1, aSMA, TGFβ, VEGFA, VEGFB, or any combination thereof.
May decrease or inhibit the production of autoantibodies.
Documented Applications
Decreasing or inhibiting inflammation in a subject.
Treatment of lung inflammation, including COPD, pneumonitis, asthma, sarcoidosis, pulmonary fibrosis, histiocytosis, bronchiolitis obliterans, or any combination thereof.
Treatment of autoimmune disease, including systemic lupus erythematosus (SLE), Graves' disease, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, celiac disease, or any combination thereof.
Assessment of improvement after administering treatment by detecting one or more biomarkers or inflammation outcomes such as neutrophil CD62L cleavage, IL-8 production, number of neutrophils, and modulation of listed biomarkers.
Decreasing production of autoantibodies.
Coronavirus infection and COVID-19-related mechanisms involving Gal3 and anti-Gal3 interactions.
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