Methods for treating pulmonary disease using inter-alpha inhibitor proteins
Inventors
Lim, Yow-Pin • Spero, Denice • Andrews, Richard
Assignees
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Publication Number
US-12285471-B2
Publication Date
2025-04-29
Expiration Date
Abstract
The invention features methods for treating or preventing pulmonary diseases, including acute respiratory distress syndrome (ARDS) and pneumonia, in a subject in need thereof that involve administering to the subject inter-alpha inhibitor proteins (IαIps), including, e.g., inter-alpha inhibitor (IαI) and/or pre-alpha inhibitor (PαI).
Core Innovation
The disclosure relates to methods and preferred embodiments for treating or preventing pulmonary diseases, including acute respiratory distress syndrome (ARDS) and pneumonia, in a subject in need thereof. The methods comprise administering inter-alpha inhibitor proteins (IαIPs) to the subject, where the IαIPs comprise inter-alpha inhibitor (IαI) and and/or pre-alpha inhibitor (PαI) and are in physiological proportions.
The disclosure addresses inflammation and damage in the lung associated with ARDS and pneumonia, including damage mediated by histones and histone/IαI/PαI complexes and by complement activation. It links disease severity and patient selection to oxygenation and critical-care criteria, including PaO2/FiO2 values and ICU/severity criteria, as well as clinical criteria such as bilateral opacities and ventilatory support needs.
The disclosure further ties therapeutic assessment and selection to biomarker-guided assessment of circulating IαI/PαI and histone species, including histone and histone/IαI/PαI complexes, and inflammatory mediators such as TNF-α, IL-6, IL-10, and complement components including C1–C9 and C5a. Therapeutic goals described include reducing inflammation and fluid, inhibiting complement activation and histone-mediated damage, and reducing hospitalization, death, and ventilation needs.
Claims Coverage
The independent claim is clm-00001. It specifies four principal inventive features in combination: treating ARDS or pneumonia in an adult human, selecting a defined oxygenation severity (PaO2/FiO2 of about 300 mm Hg or less), administering IαIPs prior to development of sepsis, and using IαIPs comprising IαI and PαI in physiological proportions.
Treating ARDS or pneumonia with inter-alpha inhibitor proteins
A method of treating acute respiratory distress syndrome (ARDS) or pneumonia in a subject in need thereof comprises administering inter-alpha inhibitor proteins (IαIPs) to the subject.
Adult human oxygenation severity criterion
The subject is an adult human with a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) of about 300 mm Hg or less.
Administration prior to development of sepsis
The method comprises administering the IαIPs to the subject prior to development of sepsis.
IαIPs comprising IαI and PαI in physiological proportions
The IαIPs comprise IαI and PαI, wherein the IαI and PαI are in physiological proportions.
Across the independent claim, the inventive coverage centers on administering IαIPs containing IαI and PαI in physiological proportions to an adult human with defined hypoxemia severity for treating ARDS or pneumonia, with administration occurring prior to development of sepsis.
Stated Advantages
Reducing inflammation and fluid.
Inhibiting complement activation and histone-mediated damage.
Reducing hospitalization and death.
Reducing ventilation needs.
Documented Applications
Treating ARDS in a subject with ARDS after a lung insult, with biomarker and inflammatory-marker context and outcome effects described for ARDS-related inflammation and fluid reduction.
Treating pneumonia using IαIPs with subject selection based on oxygenation severity and related clinical context.
Preparing a subject for a lung transplant using the disclosed approach in the document’s example scenarios.
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