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-9415101-B2
Publication Date
2016-08-16
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
Low-cost vaccine/adjuvant formulations are described for preventing and treating gram-negative infections, including multi-drug resistant E. coli urinary tract infections. The formulations center on a synthetically produced Toll-like receptor 4 agonist identified as a phosphorylated hexaacyl disaccharide (PHAD). The PHAD is formulated as an aqueous buffered suspension together with phosphatidylcholine and a selected phosphate buffer to provide room-temperature stability.
The phosphate buffer is selected from sodium phosphate dibasic, sodium phosphate monobasic, potassium phosphate monobasic, potassium phosphate dibasic, and mixtures thereof, with a concentration from 10 mM to about 50 mM. The compositions are substantially free of saline (NaCl), substantially free of cholesterol, and substantially free of metabolizable oils, and are stable when exposed to room temperature for 60 or more days.
The PHAD/phosphatidylcholine buffered compositions are described as not requiring lyophilization and as being stable up to about 37 C for extended periods, with stated stability duration at room temperature. The compositions are said to reduce injection-site and systemic reactions while enhancing immune responses to antigens associated with urinary tract infections, including FimH/FimCH, and to support vaccine use with antigens derived from influenza virus.
Claims Coverage
The partial set includes two independent claims covering a buffered adjuvant/pharmaceutically acceptable composition and a vaccine composition that uses the same PHAD/phosphatidylcholine/phosphate-buffer adjuvant system together with an antigen. Four inventive features are identified across the claims, centered on the PHAD of Formula I, phosphatidylcholine, the selected phosphate buffer, and saline-free stability or antigen incorporation.
Buffered composition with PHAD of Formula I and phosphatidylcholine in a selected phosphate buffer
A composition comprising the compound of Formula I or pharmaceutically acceptable salts thereof together with phosphatidylcholine and a phosphate buffer selected from sodium phosphate dibasic, sodium phosphate monobasic, potassium phosphate monobasic, potassium phosphate dibasic, and mixtures thereof, wherein the phosphate buffer concentration is from 10 mM to about 50 mM.
Substantially free of saline and stable for at least 60 days at room temperature
The composition is substantially free of saline and stable when exposed to room temperature for 60 or more days.
Vaccine composition with an adjuvant formulation comprising PHAD of Formula I and phosphatidylcholine in phosphate buffer
A vaccine composition comprising an adjuvant formulation and an effective amount of an antigen, wherein the adjuvant formulation comprises an effective amount of the compound of Formula I or pharmaceutically acceptable salts thereof, phosphatidylcholine, and a phosphate buffer selected from sodium phosphate dibasic, sodium phosphate monobasic, potassium phosphate monobasic, potassium phosphate dibasic, and mixtures thereof at a concentration from about 10 mM to about 50 mM.
Substantially free of saline in the vaccine composition
The vaccine composition is substantially free of saline.
Across the independent claims, coverage is directed to a PHAD of Formula I plus phosphatidylcholine formulation using a selected phosphate buffer at 10 mM to about 50 mM, with substantial freedom from saline. The composition claim requires room-temperature stability for 60 or more days, and the vaccine claim incorporates an antigen with the same PHAD/phosphatidylcholine/phosphate-buffer adjuvant system.
Stated Advantages
Reduced injection-site and systemic reactions.
Enhanced immune responses to antigens, including FimH/FimCH for UTI.
Stability without lyophilization, including stability when exposed to room temperature for extended periods.
Documented Applications
Preventing and treating gram-negative infections, including multi-drug resistant E. coli urinary tract infections.
Vaccine use with antigens associated with urinary tract infections, including FimH/FimCH and related constructs such as FimCH or truncated FimH.
Vaccine composition use with antigens derived from influenza virus.
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