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-12083151-B2
Publication Date
2024-09-10
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 invention provides a synergistic, defined bacterial composition comprising a first species of isolated bacterium and a second species of isolated bacterium, specifically Clostridium symbiosum and Clostridium orbiscindens. The composition further includes a capsule that encapsulates both bacterial species, and Clostridium orbiscindens is defined by a 16S rDNA sequence that is at least 97% identical to SEQ ID NO: 548.
The bacterial species are capable of inhibiting Clostridium difficile growth as measured by a CivSim assay. The compositions also address gastrointestinal dysbiosis by inhibiting or decreasing growth and/or colonization of gastrointestinal pathogens, including C. difficile and multi-drug resistant bacteria, and the bacterial interactions are described as inhibitory, cytotoxic, cytostatic, and synergistic.
The system is described with processing and manufacturing themes including banking, production, preservation, lyophilization, enteric coating, single dose units, kits, and spores. The bacterial species can also be formulated for populating the gastrointestinal tract of a subject.
Claims Coverage
The independent claims cover three main inventive areas and include two recurring inventive features: species pairing of Clostridium symbiosum and Clostridium orbiscindens, and functional performance against C. difficile. The claims also require a capsule, a 16S rDNA identity constraint for Clostridium orbiscindens, and CivSim assay inhibition and/or gastrointestinal tract populating.
Capsule-encapsulated Clostridium symbiosum and Clostridium orbiscindens composition with CivSim inhibition
A composition comprising Clostridium symbiosum and Clostridium orbiscindens and a capsule encapsulating both species, where Clostridium orbiscindens comprises a 16S rDNA sequence at least 97% identical to SEQ ID NO: 548 and the species are capable of inhibiting C. difficile growth as measured by a CivSim assay.
Single dose unit with capsule encapsulating synergistic Clostridium species for CivSim inhibition and gastrointestinal tract populating
A single dose unit comprising a capsule encapsulating Clostridium symbiosum and Clostridium orbiscindens, where the species are capable of inhibiting C. difficile growth as measured by a CivSim assay and/or populating the gastrointestinal tract of a subject, and where Clostridium orbiscindens comprises a 16S rDNA sequence at least 97% identical to SEQ ID NO: 548.
Method of producing the defined bacterial composition by combining Clostridium symbiosum and Clostridium orbiscindens
A method of producing a bacterial composition by combining isolated Clostridium symbiosum and isolated Clostridium orbiscindens, where Clostridium orbiscindens comprises a 16S rDNA sequence at least 97% identical to SEQ ID NO: 548 and the species are capable of inhibiting C. difficile growth and/or populating the gastrointestinal tract of a subject.
Coverage is anchored in capsule-based delivery of a two-species Clostridium combination, with Clostridium orbiscindens defined by a 16S rDNA identity relative to SEQ ID NO: 548. The independent claims also require functional activity against C. difficile, measured by a CivSim assay and/or linked to gastrointestinal tract populating.
Stated Advantages
Enables inhibiting C. difficile growth as measured by a CivSim assay.
Supports inhibiting and/or decreasing growth and/or colonization of gastrointestinal pathogens including C. difficile.
Enables populating the gastrointestinal tract of a subject.
Documented Applications
Using a CivSim assay to measure inhibition of Clostridium difficile growth for the defined bacterial combinations.
Populating the gastrointestinal tract of a subject with the defined bacterial species.
Application of the system in evaluating efficacy using an in vivo mouse model involving antibiotic treatment followed by a C. difficile challenge [procedural detail omitted for safety].
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