Methods and compositions for treating inflammatory conditions associated with infectious disease

Inventors

Pettine, Kenneth Allen • HICOK, Kevin • MOSELEY, Timothy Alexander

Assignees

Direct Biologics LLC

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Publication Number

US-12590310-B2

Patent

Publication Date

2026-03-31

Expiration Date


Abstract

Disclosed are methods of treating perianal fistula a subject by administering a therapeutic MSC secretome product made by a method comprising culturing bone marrow-derived MSCs under conditions that include oxygen tension below 5% and a culture media with a pH below 7.

Core Innovation

The invention relates to a method of treating acute respiratory distress syndrome (ARDS) by administering a therapeutically effective amount of a bone marrow mesenchymal stem cell (MSC) secretome. The secretome comprises stem cell factor 1 (SCF1), ferritin protein, tissue inhibitor of metalloproteinases 1 (TIMP1), and insulin-like growth factor binding protein-4 (IGFBP-4).

The disclosed approach includes using an MSC secretome that can comprise extracellular vesicles (EVs) and/or exosomes as part of the therapeutic composition. The document further describes combinations with additional listed biomolecules, including proteins and microRNAs (miRNAs) intended to modulate inflammatory and immune-associated pathways relevant to infectious-disease inflammatory syndromes.

The document additionally describes preparing or producing the MSC secretome product by culturing bone-marrow MSCs under oxygen tension and reduced-pH conditions. It discusses proposed mechanisms involving microRNAs and proteins, including modulation of pathways associated with infection and downstream hyperinflammation, bradykinin pathway-related factors, and elements associated with ACE2 and TMPRSS2, as well as mediators related to cytokine storm and neutrophil extracellular traps (NETosis).

Claims Coverage

The independent claim provides a treatment method for ARDS using an MSC secretome composition defined by specific protein components and an inflammation reduction readout. The family summary indicates that dependent claims primarily refine the composition form, optional included entities, and formulation/processing constraints, and expand measurable biomarker or functional effects.

Treating ARDS with a defined MSC secretome composition

Administering to the subject a therapeutically effective amount of a bone marrow mesenchymal stem cell (MSC) secretome that comprises stem cell factor 1 (SCF1), ferritin protein, tissue inhibitor of metalloproteinases 1 (TIMP1), and insulin-like growth factor binding protein-4 (IGFBP-4), wherein the treating comprises reducing inflammation as demonstrated by a reduction in C-reactive protein (CRP), ferritin, and D-dimer.

Overall claim coverage centers on ARDS treatment via administration of a bone marrow MSC secretome having SCF1, ferritin protein, TIMP1, and IGFBP-4, with inflammation reduction demonstrated by reduced CRP, ferritin, and D-dimer. The dependent claims, as described, further cover specific EV/extracellular vesicle forms and sizes and expanded biomarker and miRNA composition options, as well as formulation and production-related constraints.

Stated Advantages

Reducing inflammation in the subject as demonstrated by a reduction in C-reactive protein (CRP), ferritin, and D-dimer.

Documented Applications

Treating acute respiratory distress syndrome (ARDS) in a subject in need thereof.

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