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Publication Number
US-12448461-B2
Publication Date
2025-10-21
Expiration Date
Abstract
The present invention is directed to methods and compositions for modulating ABCB5+ stem cell activity. The invention also relates to assays and reagents for manipulating and characterizing compounds that modulate ABCB5+ cell signaling.
Core Innovation
The patent describes ABCB5 as a receptor for PIP2/PIP3 that modulates stem-cell and cancer-stem-cell activity through an ABCB5-PIP2 pathway and downstream PI3K/AKT signaling. It further connects ABCB5 functional activity to cellular outcomes including tumor growth, angiogenesis, and drug resistance.
The disclosed approach includes therapeutic and screening concepts aimed at enhancing or inhibiting ABCB5-PIP2 binding. It identifies PIP2 agonists and antagonists/competitive ligands, including PtdIns-(1,2-dioctanoyl), and anti-ABCB5 antibodies as means to modulate ABCB5-PIP2 interactions.
The document reports that functional blockade of ABCB5 reduces the PIP3/PIP2 ratio and disrupts the PI3K/AKT axis, which is associated with decreased tumor growth, angiogenesis, and drug resistance, including vemurafenib resistance. It also identifies a novel PIP2 functional analog/variant accumulated in ABCB5 knockout tissue, [PIP2 (6:0/18:0)-H]- (formula C33H65O19P3; total fatty acid chain 24:0), and states it is a preferred physiological substrate for ABCB5-dependent phosphorylation to PIP3.
Claims Coverage
The partial content includes two independent claims. Each independent claim is directed to a composition comprising a synthetic phospholipid with defined fatty-acid chain lengths, with one claim adding a specific molecular formula and the other adding a stated functional effect on the ABCB5-PIP2 pathway.
Synthetic phospholipid with defined asymmetric fatty-acid chain lengths and specified formula
A composition comprising a synthetic phospholipid having two fatty acids with carboxyl-linked carbon atom chains identified by R1 and R2, where R1 and R2 are independent in chain length, one of R1 or R2 has a length at least twice as long as the other, and the phospholipid has formula C33H65O19P3.
Synthetic phospholipid composition that enhances ABCB5-PIP2 pathway
A composition comprising a synthetic phospholipid having two fatty acids with carboxyl-linked carbon atom chains identified by R1 and R2, where one of R1 or R2 has a length at least twice as long as the other, and wherein the composition enhances the ABCB5-PIP2 pathway.
Across the independent claims, the coverage is directed to synthetic phospholipid compositions defined by asymmetric fatty-acid chain-length relationships. The claim set further differs by requiring either a specified molecular formula or a functional statement that the composition enhances the ABCB5-PIP2 pathway.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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