Compositions for treating ectopic calcification disorders, and methods using same
Inventors
Braddock, Demetrios • DE LA CRUZ, Enrique
Assignees
Publication Number
US-12234489-B2
Publication Date
2025-02-25
Expiration Date
2036-11-21
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification.
Core Innovation
The invention provides compositions and methods for treating or preventing diseases and disorders associated with pathological calcification or pathological ossification. The clinical need arises from abnormal accumulation of calcium in soft tissues and abnormal bone formation, which contribute to serious diseases such as general arterial calcification of infancy (GACI), chronic kidney disease-related calcification, pseudoxanthoma elasticum (PXE), various forms of hypophosphatemic rickets, and others. Existing therapies such as bisphosphonates have limited efficacy and adverse effects, highlighting the need for novel approaches.
This invention is based on the discovery that ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3), an enzyme with potent ATP hydrolase activity, can elevate plasma pyrophosphate (PPi) levels when administered in soluble forms. ENPP3 catalyzes the hydrolysis of ATP to AMP and PPi, with properties comparable to ENPP1. Compositions of the invention include soluble ENPP3 polypeptides and fusion proteins (for example, fused to human IgG Fc or albumin domains) that, when administered to subjects with abnormally low plasma PPi or pathological calcification/ossification, can reduce calcification and raise circulating PPi to beneficial levels.
The methods include administering therapeutically effective amounts of soluble ENPP3 polypeptides or their fusion proteins systemically, locally, or regionally, to treat or prevent a range of diseases marked by pathological calcification or ossification. The invention also encompasses diagnostic approaches utilizing plasma PPi as a biomarker for identifying individuals at risk for these disorders, supporting both preventive and therapeutic strategies.
Claims Coverage
There are two independent claims, each addressing different therapeutic approaches for pathological calcification and pathological ossification using soluble ENPP3 polypeptides.
Treatment of pathological calcification of soft tissue with a soluble ENPP3 polypeptide
A method comprising administering to a subject in need thereof a therapeutically effective amount of a polypeptide that includes a soluble ENPP3 (ecto-nucleotide pyrophosphate/phosphodiesterase-3) polypeptide. - The polypeptide must be soluble. - The method specifically treats pathological calcification in the subject.
Treatment of pathological ossification with a soluble ENPP3 polypeptide
A method comprising administering to a subject in need thereof a therapeutically effective amount of a polypeptide that includes a soluble ENPP3 (ecto-nucleotide pyrophosphate/phosphodiesterase-3) polypeptide. - The polypeptide must be soluble. - The method specifically treats pathological ossification in the subject.
The inventive features are focused on the therapeutic use of soluble ENPP3 polypeptides to treat pathological calcification and ossification by administering effective amounts to affected subjects.
Stated Advantages
The invention provides novel compositions and methods that reduce the level of calcification and elevate plasma pyrophosphate (PPi) levels in individuals with abnormally low plasma PPi.
The compositions and methods are designed not to undesirably disturb other physiological processes.
The invention addresses diseases and disorders where previous treatments, such as bisphosphonates, have limited efficacy or severe toxicity.
Diagnostic use of plasma PPi as a biomarker enables identification of individuals at risk for diseases of calcification or ossification.
Documented Applications
Treatment or prevention of diseases and disorders associated with pathological calcification or ossification, including GACI, IIAC, PXE, OPLL, MWVC, ARHR2, ESRD, CKD-MBD, XLH, age-related osteopenia, CUA, hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, and age-related hardening of the arteries.
Treatment of pathological calcification of soft tissue present in diseases such as GACI, IIAC, aging-related hardening of arteries, progeria, PXE, MWVC, ESRD, CKD-MBD, and CUA.
Treatment of pathological ossification in diseases such as OPLL, ARHR2, XLH, age-related osteopenia, and hypophosphatemic rickets.
Use of plasma pyrophosphate as a biomarker to identify individuals at risk for ectopic calcification of soft tissues, medial vascular wall calcification, low bone mineral density, osteopenia, stroke, arthritis, and hereditary forms of rickets.
Interested in licensing this patent?