Compositions and methods

Inventors

Afeyan, Noubar B. • McKenzie, Mary-Jane Lombardo • Litcofsky, Kevin Daniel • Cook, David N. • Henn, Matthew R. • von Maltzahn, Geoffrey

Assignees

Seres Therapeutics Inc

Abstract

Provided are defined bacterial compositions for the maintenance or restoration of a healthy microbiota in the gastrointestinal tract of a mammalian subject, and methods for populating the gastrointestinal tract of a subject. Provided also are bacterial formulations for oral or gastric administration to a mammalian subject in an effective amount for prevention or treatment of a gastrointestinal disease, disorder or condition.

Core Innovation

The invention provides an essentially capsule-encapsulating composition comprising a bacterial population of purified bacterial strains for treating a C. difficile infection in a mammalian subject. The bacterial population is present in an amount effective to treat the infection, and the capsule substantially encapsulates the bacterial population. The composition is directed to a multi-strain bacterial population rather than a single strain, with defined strain membership and a defined capsule encapsulation format.

The bacterial composition consists essentially of seven to nine purified bacterial strains, including Clostridium innocuum and Blautia producta as two of the strains. In some embodiments, the bacterial population is substantially encapsulated in an enteric coating, and the strains may be provided in spore form, vegetative form, lyophilized, or inactive forms. The composition is described for oral or gastric administration and for use in a mammalian subject.

The disclosure addresses C. difficile infection and associated clinical outcomes, including weight loss and toxin content. It also describes animal efficacy models and treatment-relevant clinical context, including a mouse model evaluation and a hamster relapse prevention model. The disclosure further includes characterization and analytical frameworks using 16S rRNA, OTU definitions, hypervariable regions, microbiota diversity assessment, and in vitro screening and quantification approaches.

Claims Coverage

The document provides independent claims directed to a capsule-encapsulated defined bacterial composition for treating a C. difficile infection in a mammalian subject. Across the claims, the inventive features center on seven to nine purified bacterial strains, including Clostridium innocuum and Blautia producta, and an amount effective to treat the infection.

Overall claim coverage centers on a capsule-containing, essentially encapsulated composition comprising seven to nine purified bacterial strains with Clostridium innocuum and Blautia producta included, in an amount effective to treat a C. difficile infection in a mammalian subject.

Stated Advantages

Documented Applications