Synergistic bacterial compositions and methods of production and use thereof
Inventors
Henn, Matthew R. • Litcofsky, Kevin Daniel • D'Onofrio, Anthony Mario • Ohsumi, Toshiro K. • McKenzie, Mary-Jane Lombardo • von Maltzahn, Geoffrey • Cook, David N. • Berry, David Arthur • Afeyan, Noubar B. • Aunins, John Grant
Assignees
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Publication Number
US-11918612-B2
Publication Date
2024-03-05
Expiration Date
Abstract
Provided are therapeutic compositions containing microbial populations for prevention, treatment and reduction of symptoms associated with a dysbiosis of a mammalian subject such as a human.
Core Innovation
The invention provides a composition comprising a capsule that encapsulates a first species, a second species, and a third species of isolated bacterium capable of forming a spore, and the first species, the second species, and the third species are not identical. In a representative embodiment, the first species is Clostridium orbiscindens, the second species is Clostridium bolteae, and the third species is Lachnospiraceae bacterium 5_1_57FAA.
Clostridium orbiscindens comprises a 16S rDNA sequence that is at least 97% identical to the sequence set forth in SEQ ID NO: 609, and dependent refinements specify corresponding 16S rDNA sequence identity constraints for Clostridium bolteae and Lachnospiraceae bacterium 5_1_57FAA. A combination of the first species, the second species, and the third species is capable of decreasing and/or inhibiting the growth and/or colonization of at least one type of pathogenic bacteria.
The disclosed scope relates to treating and/or preventing dysbiosis in the gastrointestinal tract microbiome by inhibiting pathogenic bacteria, including Clostridium difficile and other GI pathogens. The document additionally supports an enterically coated capsule and purified spore populations within pharmaceutical formulations and kits.
Claims Coverage
The claim coverage centers on an independent capsule-encapsulated, three-species spore-forming bacterial composition with specified taxonomic identities, 16S rDNA identity constraints, and the capability to decrease and/or inhibit pathogenic bacterial growth and/or colonization. Five inventive features are identified across the provided claim content, with dependent refinements including synergistic inhibition and an enterically coated capsule.
Capsule-encapsulated three non-identical spore-forming bacteria
A composition comprising a capsule encapsulating a first species, a second species, and a third species of isolated spore-forming bacteria, wherein the first species, the second species, and the third species are not identical.
Specified three species with 16S rDNA identity
The first species is Clostridium orbiscindens, the second species is Clostridium bolteae, and the third species is Lachnospiraceae bacterium 5_1_57FAA, wherein Clostridium orbiscindens comprises a 16S rDNA sequence that is at least 97% identical to SEQ ID NO: 609, with dependent refinements specifying comparable 16S rDNA sequence identity constraints for the other species.
Decreasing and/or inhibiting pathogenic bacteria growth and/or colonization
A combination of the first species, the second species, and the third species is capable of decreasing and/or inhibiting the growth and/or colonization of at least one type of pathogenic bacteria.
Synergistic inhibition by the combined three species
The combination of the first species, the second species, and the third species can synergistically inhibit the growth and/or colonization of at least one pathogenic bacteria type.
Enterically coated capsule
The composition is provided in a capsule that is enterically coated.
Overall, the claim set covers a capsule-encapsulated, non-identical three-species spore-forming bacterial composition with specified taxa and 16S rDNA identity constraints, configured to decrease and/or inhibit pathogenic bacteria growth and/or colonization, including embodiments with synergistic inhibition and an enterically coated capsule.
Stated Advantages
Decreases and/or inhibits the growth and/or colonization of at least one type of pathogenic bacteria.
Synergistically inhibits the growth and/or colonization of at least one pathogenic bacteria type.
Treating and/or preventing dysbiosis in the gastrointestinal tract microbiome by inhibiting pathogenic bacteria, including Clostridium difficile and other GI pathogens.
Documented Applications
Treating and/or preventing dysbiosis in the gastrointestinal tract microbiome, including dysbiosis associated with C. difficile associated diarrhea.
Decreasing and/or inhibiting growth and/or colonization of Clostridium difficile and other GI pathogens, including antibiotic-resistant groups.
Use in vitro CivSim competition screening and qPCR quantification, and in vivo murine C. difficile models for evaluating inhibition and synergy.
Therapeutic use in pharmaceutical formulations, kits with purified spore populations, and comestible products.
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