Compositions and methods for treating cholestatic disease
Inventors
NANDAKUMAR, Madhumitha • LIOU, ALICE PEIYU • HALVORSEN, ELIZABETH MORITZ • McKenzie, Gregory • O'Brien, Edward J. • Cook, David
Assignees
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Publication Number
US-11701394-B2
Publication Date
2023-07-18
Expiration Date
Abstract
The invention provides compositions and methods for use in the treatment and prevention of cholestatic diseases.
Core Innovation
The invention relates to administering, to a subject in need thereof, compositions comprising viable bacteria that modulate bile acid metabolism in cholestatic disease or condition. The compositions comprise a first bacterial species and a second bacterial species, wherein the first bacterial species and the second bacterial species are not the same, and the bacteria are selected from fecal-derived or designed consortia associated with bile-transforming activities including bile salt hydrolase activity, oxidation, and 7α-dehydroxylation.
The invention further specifies bacterial selection based on 16S rDNA sequence identity thresholds against reference sequences, including SEQ ID NO reference sequences. The described bacterial consortia include defined taxa and may include optional spore and vegetative forms, configured to alter primary and secondary bile acid profiles.
In cholestatic disease contexts, the invention addresses therapeutic outcomes including reducing a side effect of a treatment and enhancing efficacy of a treatment for a cholestatic disease or condition. The described approaches include combination approaches with pharmaceuticals such as ursodeoxycholic acid and/or obeticholic acid, with the goal of improving efficacy and/or reducing side effects, including pruritus, by lowering required dosing frequency or amount.
Claims Coverage
The document provides two independent claims directed to two different treatment objectives: reducing a side effect and enhancing efficacy, each using a composition of two different bacterial species selected from a specified list. Across the independent claims, the main inventive features comprise a two-species bacterial composition for cholestatic disease or condition, with dependent refinements adding 16S rDNA sequence identity threshold constraints and additional treatment-side-effect limitations, including pruritus and lithocholic acid constraints.
Reducing a cholestatic treatment side effect using two different selected bacterial species
A method of reducing a side effect of a treatment for a cholestatic disease or condition in a subject in need thereof by administering a composition comprising a first bacterial species and a second bacterial species, wherein the first bacterial species and the second bacterial species are not the same, and wherein the first bacterial species and the second bacterial species are selected from the listed bacterial species capable of enhancing the efficacy of the treatment, such that the treatment can be administered to the subject at a lower dose, at reduced frequency, or both.
Enhancing treatment efficacy using two different selected bacterial species
A method of enhancing an efficacy of a treatment for a cholestatic disease or condition in a subject in need thereof by administering to the subject the treatment and a composition comprising a first bacterial species and a second bacterial species, wherein the first bacterial species and the second bacterial species are not the same, and wherein the first bacterial species and the second bacterial species are selected from the listed bacterial species.
Across the independent claims, the inventive approach is centered on administering two different selected bacterial species from a defined list for cholestatic disease or condition, either to reduce a treatment side effect or to enhance the efficacy of the treatment. Dependent claims narrow the bacterial species by 16S rDNA sequence identity to specified SEQ ID NO references and further refine the objectives by specifying pruritus, specifying UDCA and/or OCA for the treatment, and constraining the bacterial effect on lithocholic acid levels.
Stated Advantages
The treatment can be administered at a lower dose, at reduced frequency, or both.
Reduction of a side effect of the treatment for a cholestatic disease or condition.
Enhancement of the efficacy of a treatment for a cholestatic disease or condition.
Documented Applications
Reducing pruritus as a side effect of a treatment for a cholestatic disease or condition by administering a two-species bacterial composition selected from the listed species.
Enhancing the efficacy of a treatment for a cholestatic disease or condition by co-administering the treatment with a composition comprising two different selected bacterial species.
Use of the treatment including ursodeoxycholic acid and/or obeticholic acid in combination with the two-species bacterial composition for cholestatic disease or condition.
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