Single-domain Antibodies Directed Against Gasdermin D and Their Use

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This patent discloses single-domain antibodies (also called nanobodies) specifically designed to bind to the protein gasdermin D (GSDMD). These nanobodies block the oligomerization of GSDMD, a process essential for the formation of plasma membrane pores that lead to a form of inflammatory cell death known as pyroptosis. By inhibiting this pathway, the antibodies can prevent or treat various inflammatory diseases and conditions. Furthermore, these nanobodies can be used as diagnostic tools to detect the presence of GSDMD oligomers, helping to identify diseases characterized by excessive inflammation.

Use CasesContent extracted from patent full text and abstract with AI.

• Therapeutic treatment of acute and chronic inflammatory diseases, including sepsis, atherosclerosis, inflammatory bowel disease, non-alcoholic steatohepatitis, and autoinflammatory syndromes.
• Reducing or preventing tissue damage associated with excessive inflammation in diseases such as Alzheimer’s disease, Parkinson’s disease, and type 1/2 diabetes.
• Targeted intervention in inflammatory cancers, e.g., lung cancer or cancers with pyroptosis involvement.
• Adjunct therapy to limit side-effects of cancer treatments (chemotherapy, radiotherapy) by preventing pyroptosis in healthy cells.
• Use as a molecular research tool to study GSDMD function, inflammasome biology, and cell death pathways.
• Development of diagnostic assays (e.g., sandwich ELISA, HTRF/FRET-based methods) to detect GSDMD oligomers in blood samples, supporting diagnosis and monitoring of inflammatory conditions.
• Development of cell or gene therapies delivering mRNA encoding these nanobodies for intracellular production in specific tissues experiencing inflammation.
• Design of companion diagnostics to predict or monitor responses to anti-inflammatory therapies.

BenefitsContent extracted from patent full text and abstract with AI.

• High specificity towards GSDMD, reducing off-target effects compared to traditional small-molecule inhibitors.
• Ability to selectively inhibit the final step in pyroptosis, providing a unique approach to modulating inflammation without broadly suppressing the immune system.
• Potential to transition pyroptotic cell death toward apoptosis, which is less inflammatory, thereby limiting tissue damage.
• Versatility as both a therapeutic and diagnostic tool, enabling personalized and targeted medicine strategies.
• Small size and stability of nanobodies allow for improved tissue penetration, rapid clearance, and various administration routes.
• Nanobodies can be manufactured recombinantly or delivered as mRNA, enabling flexible therapeutic platforms (including gene or cell therapies).
• Highly useful as research probes to dissect the mechanisms of membrane pore formation and cell death, possibly accelerating drug development for related conditions.
• Possibility to target and treat a broad range of conditions (from autoimmune to metabolic, infectious and neurodegenerative diseases) driven by inflammation.

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Patent Abstract

The present invention is concerned with single-domain antibodies directed against gasdermin D (GSDMD). The single-domain antibodies can be used in medical applications, preferably for preventing and/or treating an inflammatory disease or condition in a subject, and/or for determining the presence or absence of GSDMD oligomers in a sample obtained from a subject.