Acylated active agents and methods of their use for the treatment of autoimmune disorders
Inventors
Taylor, Steven John • Kim, Mi-Jeong • NUDEL, Kathleen • Briggs, Timothy F. • Yasuda, Koji • Buckbinder, Leonard • LANTER, Bernard • PECK, Spencer Cory • Snedeker, Cheri • SHE, Angela • ALEXANDER, Jessica • LIANG, Anna • Liu, Jenny • GUNASEKERA, Dinara • Berry, David Arthur • CASEY, JR., John Patrick • Moarefi, Amir H.
Assignees
Flagship Pioneering Innovations V Inc • Flagship Pioneering Inc
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Publication Number
US-12115178-B2
Publication Date
2024-10-15
Expiration Date
Abstract
Disclosed herein are acylated active agents and methods of their use, e.g., for modulating an autoimmunity marker or for treating an autoimmune disorder.
Core Innovation
The invention relates to acylated bioactive agents having a specified chemical structure, including acylated catechin polyphenols, acylated mesalamines, acylated shikimic acid, acylated carotenoids, acylated ellagic acid or ellagic acid analogues, acylated hydroxybenzoic acids, and acylated sugars. The structures define fatty-acyl, ketone/pre-ketone, amino-acid metabolite substituted groups, and linkage options including ester, amide, glycosidic, carbonate, and carbamate linkers.
The acylated compounds are configured to modulate biological responses in a subject by administering an effective amount of the compound or a pharmaceutically acceptable salt thereof. The described response profile includes modulation of an autoimmunity marker and associated immune and inflammatory factors, such as changes involving CYP1A1 mRNA level, CD4+ CD25+ Treg cell count, short chain fatty acids level, mucus secretion, and additional immune and inflammatory markers.
The document further describes treating autoimmune disorders by administering the same structural acylated compounds. The autoimmune modulation and treatment readouts include increases and decreases in gastrointestinal and immune biomarkers, including gastrointestinal inflammation, gastrointestinal permeability, gastrointestinal bleeding, abdominal pain, frequency of bowel movements, immune mediators including cytokines, chemokines, signaling proteins, enzymes, oxidative stress-related biomarkers, IgA, calprotectin, and lipocalin-2.
Claims Coverage
The independent claims define two methods using a compound of a specified structure, or a pharmaceutically acceptable salt, to modulate an autoimmunity marker or to treat an autoimmune disorder. The inventive features are expanded by dependent claims to disease contexts and biomarker readouts, including oral administration and specific gastrointestinal, immune, and inflammatory response profiles.
Administering a specified-structure compound to modulate an autoimmunity marker
A method of modulating an autoimmunity marker in a subject by administering to the subject an effective amount of a compound of the structure, or a pharmaceutically acceptable salt thereof.
Administering a specified-structure compound to treat an autoimmune disorder
A method of treating an autoimmune disorder in a subject suffering from the autoimmune disorder, the method comprising administering to the subject an effective amount of a compound of the structure, or a pharmaceutically acceptable salt thereof.
Overall, claim coverage centers on in vivo use of a compound of a specified structure, or a pharmaceutically acceptable salt, for autoimmunity marker modulation and autoimmune disorder treatment. Dependent claims narrow the disease context to ulcerative colitis and Crohn’s disease, specify oral administration, and add detailed biomarker and clinical response directions including CYP1A1 mRNA level, Treg-related changes, short chain fatty acids and mucus secretion, and reductions in multiple immune and inflammatory markers.
Stated Advantages
Modulates an autoimmunity marker in a subject.
Treats an autoimmune disorder in a subject suffering from the autoimmune disorder.
Alters immune and inflammatory biomarkers and gastrointestinal biomarkers, including increases and decreases as specified.
Includes oral administration for the described methods.
Improved organoleptic properties for oral delivery.
Documented Applications
Modulating an autoimmunity marker in a subject.
Treating an autoimmune disorder in a subject.
Autoimmunity modulation or treatment in ulcerative colitis.
Autoimmunity modulation or treatment in Crohn’s disease.
Modulating an autoimmunity marker in a subject, including association with ulcerative colitis or Crohn’s disease.
Treating autoimmune disorders in subjects, including ulcerative colitis and Crohn’s disease, with post-administration immune, inflammatory, gastrointestinal, and clinical readouts.
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