Synergistic bacterial compositions and methods of production and use thereof
Inventors
Henn, Matthew R. • von Maltzahn, Geoffrey • D'Onofrio, Anthony Mario • Litcofsky, Kevin Daniel • Berry, David Arthur • Cook, David N. • Afeyan, Noubar B. • Aunins, John Grant
Assignees
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Publication Number
US-11458174-B2
Publication Date
2022-10-04
Expiration Date
Abstract
Provided are therapeutic compositions containing Ecobiotic™ populations for prevention, treatment and reduction of symptoms associated with a dysbiosis of a mammalian subject such as a human.
Core Innovation
The document describes synergistic, defined bacterial ecobiotic compositions for preventing and/or treating gastrointestinal (GI) dysbiosis and inhibiting gastrointestinal pathogens, including Clostridium difficile (C. difficile). The compositions include first and second species of isolated bacteria that are capable of inhibiting C. difficile growth as measured by a CivSim assay.
A core aspect is a defined multi-species bacterial ecobiotic composition, including binary and ternary combinations and compositions with additional bacterial species. The document further describes combinations that include spore-forming bacteria and non-spore combinations, along with defined bacterial identity selection using 16S rRNA/16S rDNA operational taxonomic unit (OTU) selection and sequence similarity to SEQ ID NOs.
The compositions are described with capsule and/or spore-based dose unit concepts, including spore formulations and capsule encapsulation of one species, the other species, or both species. The document also includes formulation and use concepts such as enteric coating, kit formats with separated spore populations, and reported assay performance using CivSim assays with quantification and inhibition confidence intervals.
Claims Coverage
The provided claims content includes one independent claim and dependent claims that refine species identity, formulation attributes, route, and assay performance. The independent claim focuses on a defined two-species encapsulated composition where both species are capable of inhibiting C. difficile growth in a CivSim assay.
Two-species encapsulated ecobiotic composition for CivSim inhibition of C. difficile
A composition comprising a first species of isolated bacterium and a second species of isolated bacterium and a capsule, wherein the capsule encapsulates the first species, the second species, or both the first and second species of isolated bacterium, wherein the first species is Dorea longicatena and the second species is Clostridium orbiscindens, and wherein the first species and the second species are capable of inhibiting Clostridium difficile (C. difficile) growth as measured by a CivSim assay.
Inhibition with a defined CivSim confidence interval
Inhibiting C. difficile growth in the CivSim assay with a confidence interval of >99%.
Exact 16S rDNA identity for Dorea longicatena
Dorea longicatena comprises the 16S rDNA sequence specified as SEQ ID NO: 705.
Defined 16S rDNA identity for Clostridium orbiscindens
Clostridium orbiscindens contains a 16S rDNA sequence at least 99% identical to SEQ ID NO: 548.
Spore form of the composition
The first species, the second species, or both are provided in the form of spores.
Oral administration pharmaceutical formulation
A pharmaceutical formulation is formulated for oral administration.
The claims center on a capsule-encapsulated two-species composition using Dorea longicatena and Clostridium orbiscindens, with sequence-defined identity for Clostridium orbiscindens and both species capable of inhibiting C. difficile growth in a CivSim assay. Dependent claims further specify 16S rDNA identity levels, spore form, oral administration, and an inhibition confidence interval requirement.
Stated Advantages
Inhibits C. difficile growth as measured by a CivSim assay.
Inhibits C. difficile growth in the CivSim assay with a confidence interval of >99%.
Documented Applications
Preventing and/or treating GI dysbiosis using bacterial ecobiotic compositions.
Inhibiting gastrointestinal pathogens, including Clostridium difficile (C. difficile), using compositions capable of CivSim inhibition.
Using spore formulations and capsule-encapsulated bacterial compositions as described, including kit formats with separated spore populations.
Oral administration of a pharmaceutical formulation.
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