Orally administered composition to lower serum methionine levels and method of use
Inventors
Han, Qinghong • Li, Shukuan • Tan, Yuying • Kawaguchi, Kei • Hoffman, Robert M. • Chawla, Sant
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11001826-B2
Publication Date
2021-05-11
Expiration Date
Abstract
A composition and method for lowing serum and plasma levels of methionine by oral administration. The composition includes a recombinant methioninase enzyme and a cofactor (pyridoxal-L-phosphate). Methods of use describe methods for treatment of cancer, including malignant melanoma, by oral administration of the methioninase composition. Methods for chronic suppressive therapy of melanoma and other cancers are described. Because reduction of plasma methionine levels is effective in treating other conditions, including diabetes and conditions associated with aging, the use of the methods described herein includes treatment of these and other conditions.
Core Innovation
The invention relates to an orally administered recombinant methioninase (rMETase) composition together with the cofactor pyridoxal-L-phosphate (PLP) to lower serum/plasma methionine and thereby suppress tumor growth. The method uses oral methioninase enzyme administration and oral administration of a PLP-containing fluid.
The problem addressed is that tumors and other conditions are associated with methionine dependence (MET dependence/methionine dependence), and lowering methionine is expected to suppress tumor growth and related disease processes. The background discussion contrasts dietary methionine restriction and parenteral dosing, and frames the need for an orally effective recombinant methioninase plus cofactor regimen.
The disclosed use includes malignant melanoma and Ewing’s sarcoma, and additional conditions described in the document include insulin-resistant diabetes mellitus and age-related metabolic and tissue degenerative changes. The document reports that oral rMETase combined with PLP in drinking water reduces plasma/tumor MET levels and is associated with tumor growth suppression, and references a melanoma PDOX patient-derived model and formulation/administration approach.
Claims Coverage
The partial content includes three independent claims. Across the independent claims, a shared inventive core is the oral administration of a methioninase-enzyme composition together with an orally administered fluid comprising pyridoxal-L-phosphate, with the independent claims differing by the specific condition being treated or reversed.
Oral methioninase composition with oral pyridoxal-L-phosphate fluid for malignancy growth suppression
Administering, orally, a composition comprising methioninase enzyme; and administering, orally, fluid comprising pyridoxal-L-phosphate.
Oral methioninase composition with oral pyridoxal-L-phosphate fluid for insulin resistant diabetes mellitus treatment
Administering, orally, a composition comprising methioninase enzyme; and administering, orally, fluid comprising pyridoxal-L-phosphate.
Oral methioninase composition with oral pyridoxal-L-phosphate fluid for reversing age-related metabolic and tissue degenerative changes
Administering, orally, a composition comprising methioninase enzyme; and administering, orally, fluid comprising pyridoxal-L-phosphate.
All independent claims are directed to methods that administer a methioninase enzyme composition orally and administer an oral fluid containing pyridoxal-L-phosphate, with the intended therapeutic or modifying outcome specified as malignancy growth suppression, treatment of insulin resistant diabetes mellitus, or reversing age-related metabolic and tissue degenerative changes.
Stated Advantages
Suppressing tumor growth by lowering serum/plasma methionine (MET reduction).
Reducing plasma/tumor MET levels in the described oral rMETase plus PLP context.
No observed body weight loss in the described PDOX melanoma mouse study.
No animal deaths in the described PDOX melanoma mouse study.
Documented Applications
Suppression of the growth of a malignancy within an individual, including malignant melanoma and Ewing’s sarcoma.
Treating insulin resistant diabetes mellitus.
Reversing age-related metabolic and tissue degenerative changes.
Interested in licensing this patent?