Metal-glycoprotein complexes and their use as chemotherapeutic compounds
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Assignees
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Publication Number
US-9737565-B2
Publication Date
2017-08-22
Expiration Date
Abstract
Compositions of the invention include glycoproteins, such as transferrin, and metal-based coordination complexes, which are preferably chemotherapeutic compounds and more preferably tunable photodynamic compounds. The compositions are useful as in vivo diagnostic agents, and as therapeutic agents for treating or preventing diseases including those that involve hyperproliferating cells in their etiology, such as cancer. Compositions of the invention are further capable of destroying microbial cells, such as bacteria, fungi, and protozoa, and destroying viruses.
Core Innovation
The invention relates to compositions comprising a metal-binding glycoprotein and a chemotherapeutic compound defined by formulas selected from formula (I), formula (VI), formula (VIIa), or formula (II). The metal-binding glycoprotein includes transferrin and other transferrin family glycoproteins such as lactoferrin, ovotransferrin, and melanotransferrin, and the chemotherapeutic compound includes osmium, ruthenium, or rhodium in at least one formula embodiment.
The compositions include hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof, and provide enhanced properties relative to the chemotherapeutic compound without the glycoprotein. These enhanced properties include increased uptake by cancer cells and tumors, increased efficacy and improved absorbance at wavelengths longer than 600 nm and at wavelengths less than or equal to 600 nm, and increased production of reactive oxygen species.
The document further describes increased photodynamic therapy effect under non-hypoxic conditions and under hypoxic conditions, together with increased LD50, increased MTD, increased photostability, and increased shelf-life. It also describes treating hyperproliferative-cell conditions by administering the composition and irradiating with light effective to activate the composition, and destroying microbial cells by contact with the composition and irradiation with light to activate the composition.
Claims Coverage
The independent claim coverage includes one composition claim that defines a metal-binding glycoprotein plus a chemotherapeutic transition-metal coordination compound by specific formulas, and requires at least one enhanced property relative to the chemotherapeutic compound without the glycoprotein. The inventive feature set includes enhanced uptake, wavelength-dependent efficacy and absorbance, reactive oxygen species production, photodynamic therapy effect under non-hypoxic and hypoxic conditions, and improved safety/performance metrics.
Metal-binding glycoprotein plus chemotherapeutic compound with defined formulas
A composition comprising a metal-binding glycoprotein; and a chemotherapeutic compound having a formula selected from formula (I), formula (VI), formula (VIIa), or formula (II), including hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof.
Enhanced properties relative to the chemotherapeutic compound without the glycoprotein
The composition has at least one enhanced property relative to the chemotherapeutic compound without the glycoprotein, including increased uptake by cancer cells, increased uptake by tumors, increased efficacy at wavelengths longer than 600 nm, increased efficacy at wavelengths less than or equal to 600 nm, improved absorbance at wavelengths longer than 600 nm, improved absorbance at wavelengths less than or equal to 600 nm, increased production of reactive oxygen species, increased photodynamic therapy effect under non-hypoxic conditions, increased photodynamic therapy effect under hypoxic conditions, increased LD50, increased MTD, increased photostability, and increased shelf-life.
The independent claim defines a composition combining a metal-binding glycoprotein with a transition-metal coordination chemotherapeutic compound defined by formulas (I), (VI), (VIIa), or (II) and requires that the composition provides at least one enhanced property versus the chemotherapeutic compound without the glycoprotein.
Stated Advantages
Increased uptake by cancer cells
Increased uptake by tumors
Increased efficacy at wavelengths longer than 600 nm
Increased efficacy at wavelengths less than or equal to 600 nm
Improved absorbance at wavelengths longer than 600 nm
Improved absorbance at wavelengths less than or equal to 600 nm
Increased production of reactive oxygen species
Increased photodynamic therapy effect under non-hypoxic conditions
Increased photodynamic therapy effect under hypoxic conditions
Increased LD50
Increased MTD
Increased photostability
Increased shelf-life
Documented Applications
Treating a disease associated with hyperproliferating cells by administering an effective amount of the composition to a subject and irradiating the subject with light effective to activate the composition to treat the disease.
Destroying microbial cells by contact with the composition and irradiating with light to activate the composition.
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