Method for inhibiting STAT3 activity comprising administering Ssu72
Inventors
Cho, Mi-La • Park, Sung-Hwan • KWOK, Seung-Ki • CHOI, Jong-Young • Lee, Seung-Hun • SEO, Hyeon-Beom • Moon, Young-Mee • Park, Jin-Sil • PARK, Min-jung • Lee, Jin-kwan • Lee, Chang Woo
Assignees
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Publication Number
US-11628206-B2
Publication Date
2023-04-18
Expiration Date
Abstract
The present disclosure relates to a method for inhibiting a STAT3 activity comprising administering SSu72 protein.
Core Innovation
The invention relates to a pharmaceutical composition and therapeutic approach that uses Ssu72 to inhibit STAT3 activity in a subject in need thereof. The described mechanism centers on inhibiting STAT3 phosphorylation induced by IL-6, thereby reducing downstream inflammatory signaling associated with STAT3 activity.
The document further describes that inhibition of STAT3 activity leads to a decrease in inflammatory cytokines including IL-17, IL-21, IL-1β, IL-6, and IL-6R. In parallel, the approach increases immunoregulatory cytokines including IL-4 and IL-10, with downstream effects on immune cell populations and cytokine expression.
The document also describes gene- and protein-based embodiments of Ssu72, including Ssu72 protein and a polynucleotide encoding Ssu72 (SEQ ID NO:1/2). A STAT3/STAT3-pathway drug screening method is described using Ssu72 gene/protein and expression/activity measurement, with experimental evidence provided for effects in models of inflammatory autoimmune disease.
Claims Coverage
The independent claim set includes one independent method claim focused on inhibiting STAT3 activity via administration of Ssu72, with dependent claims specifying that the STAT3 activity is induced by IL-6 and that the subject suffers from rheumatoid arthritis. Across the claim set, the inventive features are centered on Ssu72 administration as the STAT3-inhibitory agent and on defining the biological context and patient indication.
Administering Ssu72 protein to inhibit STAT3 activity
A method for inhibiting a STAT3 activity by administering to a subject in need thereof a Ssu72 protein.
STAT3 activity induced by IL-6
The method wherein the STAT3 activity is induced by IL-6.
Subject suffering from rheumatoid arthritis
The method wherein the subject suffers from rheumatoid arthritis.
Overall, the claims are directed to inhibiting STAT3 activity through administration of an Ssu72 protein, with further narrowing to STAT3 activity induced by IL-6 and to subjects with rheumatoid arthritis.
Stated Advantages
Reduces inflammatory cytokines, including IL-17, IL-21, IL-1β, IL-6, and IL-6R.
Increases immunoregulatory cytokines including IL-4 and IL-10.
Reduces arthritis severity and joint inflammation/damage and decreases osteoclast markers.
Decreases Th17 and increases Treg cells in spleen/lymph nodes.
Decreases autoantibodies and increases IL-10–expressing B cells.
Documented Applications
Therapeutic inhibition of STAT3 activity in autoimmune/STAT3-mediated diseases including rheumatoid arthritis, including effects demonstrated in collagen-induced rheumatoid arthritis mouse models.
STAT3/STAT3-pathway drug screening using Ssu72 gene/protein and expression/activity measurement.
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