CD5 pharmaceutical compositions for the treatment of infectious and inflammatory processes of fungal origin
Inventors
Lozano Soto, Francisco • Vera Fernandez, Jorge
Assignees
Sepsia Therapeutics SL • Soto Francisco Lozano Dr • Hospital Clinic de Barcelona
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Publication Number
US-8404633-B2
Publication Date
2013-03-26
Expiration Date
Abstract
The present invention refers to pharmaceutical compositions comprising the soluble CD5 ectodomain and its use for the prevention and/or treatment of fungal infections and/or fungal sepsis, as well as inflammatory disorders of fungal origin.
Core Innovation
The invention relates to soluble CD5 ectodomain as a pharmaceutical for preventing and/or treating fungal infections and fungal sepsis and related inflammatory disorders. Soluble CD5 binds to fungal cell surfaces via β-glucans and induces fungal cell aggregation.
The document reports Ca2+-facilitated, dose-dependent, saturable binding of soluble CD5 ectodomain, with specificity versus bacterial PAMP-containing cell wall components. CD5 ectodomain domains retain fungal binding, and β-glucan and zymosan competitively inhibit binding.
The document further reports that membrane CD5 mediates zymosan-driven MAPK activation, including MEK/ERK phosphorylation. In vivo mouse data are provided where rshCD5 pretreatment reduces toxicity, leukocyte infiltration, IL-6/IL-1β levels, MPO activity, and increases survival in a zymosan-induced septic shock-like syndrome.
Claims Coverage
The provided claims include two independent claims, each centered on administering soluble CD5 ectodomain to patients with fungal infection and/or fungal sepsis, including reducing severity of disease. Across the independent claims, the coverage is organized into identifying a patient in need and administering soluble CD5 ectodomain.
Treating fungal infection and/or fungal sepsis by administering soluble CD5 ectodomain
Identifying a patient in need of treatment of fungal infection and/or fungal sepsis, and administering soluble CD5 ectodomain to the patient in need thereof.
Reducing the severity of fungal infection and/or fungal sepsis by administering soluble CD5 ectodomain
Identifying a patient in need of a reduction in the severity of fungal infection or fungal sepsis, and administering soluble CD5 ectodomain to the patient in need thereof.
In both independent claims, soluble CD5 ectodomain is administered following patient identification for fungal infection/fungal sepsis, with claim refinements in the provided dependents specifying particular fungal causes, pharmaceutical excipient/formulation features, and reduction focused on fungal septic shock.
Stated Advantages
Reduces toxicity in a zymosan-induced septic shock-like syndrome model.
Reduces leukocyte infiltration.
Reduces IL-6/IL-1β levels.
Reduces MPO activity.
Increases survival.
Documented Applications
Preventing and/or treating fungal infections and fungal sepsis and related inflammatory disorders using soluble CD5 ectodomain.
Use in reducing severity of fungal infection or fungal sepsis, including fungal septic shock.
A zymosan-induced septic shock-like syndrome application in a mouse model with rshCD5 pretreatment.
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