Compositions of vaccines and adjuvants and methods for the treatment of urinary tract infections
Inventors
Eldridge, Gary • Martin, Steven M
Assignees
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Publication Number
US-9504743-B2
Publication Date
2016-11-29
Expiration Date
Abstract
This invention describes novel adjuvant compositions and formulations with excellent stability at refrigerated and room temperatures and up to and about 37° C. that can be produced at remarkably low costs. This invention describes novel vaccine compositions and formulations to treat and prevent urinary tract infections caused by gram-negative bacteria including Escherichia coli and multi-drug resistant E. coli. This invention also describes methods of administration of said novel vaccine compositions and formulations and methods of treatment to prevent and treat urinary tract infections caused by gram-negative bacteria including E. coli and multi-drug resistant E. coli.
Core Innovation
The invention relates to a composition comprising one or more specified compounds, phosphatidylcholine, and a citrate buffer from about 10 mM to about 50 mM. The composition contains less than 30 mM NaCl and is stable when exposed to a range of temperature from 19°C to 25°C for 60 or more days.
The invention further provides vaccine-related formulations where an adjuvant formulation includes an effective amount of one or more specified compounds together with phosphatidylcholine and a citrate buffer from about 10 mM to about 50 mM, in combination with an antigen and an effective amount of the antigen.
The disclosed studies emphasize PHAD-containing compositions in conjunction with DPPC and buffers, including forced degradation and TOF-MS analyses indicating that formulations prevent acyl-chain loss degradation pathways for PHAD and related materials. Multiple PHAD formulation studies emphasize unexpected stability of citrate/succinate/phosphate-buffered DPPC/PHAD compositions under room temperature through approximately 37°C, together with formulation homogeneity and particle-size constraints supported by accelerated stability data and stability targets.
Claims Coverage
The patent provides three independent claims. Each independent claim centers on a buffered composition including phosphatidylcholine and citrate buffer within a specified concentration range, with stability and NaCl limitations in the composition claims, and a vaccine composition claim that combines the adjuvant formulation with an antigen.
Citrate-buffered phosphatidylcholine composition with low NaCl and temperature stability
A composition comprising one or more of the following compounds; phosphatidylcholine; and a citrate buffer from about 10 mM to about 50 mM, wherein the composition contains less than 30 mM NaCl, and is stable when exposed to a range of temperature from 19°C to 25°C for 60 or more days.
Vaccine composition with adjuvant formulation containing citrate-buffered phosphatidylcholine
A vaccine composition comprising an adjuvant formulation and an effective amount of an antigen, wherein the adjuvant formulation comprises an effective amount of one or more of the following compounds; phosphatidylcholine; and a citrate buffer from about 10 mM to about 50 mM.
Across the independent claims, the core claim coverage is directed to citrate-buffered phosphatidylcholine compositions containing one or more specified compounds, with citrate concentration in about 10 mM to about 50 mM, and in the composition claims, with less than 30 mM NaCl and stability at 19°C to 25°C for 60 or more days; a further independent claim applies this adjuvant formulation within a vaccine composition including an antigen.
Stated Advantages
The composition is stable when exposed to a range of temperature from 19°C to 25°C for 60 or more days.
The composition contains less than 30 mM NaCl.
The composition provides an adjuvant formulation for a vaccine composition.
Reduced severe injection-site/systemic reactions.
Enables room-temperature shipment without lyophilization.
Documented Applications
UTI treatment and/or prevention context for urinary tract infections caused by gram-negative bacteria, including multidrug-resistant E. coli, using a vaccine composition that includes an adjuvant formulation comprising PHAD or PtHA compounds plus phosphatidylcholine and citrate buffer.
Vaccine formulation studies including adjuvant formulation with an antigen.
In vitro potency assay demonstrating HRP binding to FimH via ELISA with mannose-binding dependence.
Preclinical immunogenicity/toxicity in rabbits.
UTI efficacy in mice.
Human clinical interim safety/immunogenicity comparisons.
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