Synergistic bacterial compositions and methods of production and use thereof

Inventors

Henn, Matthew R.von Maltzahn, GeoffreyD'Onofrio, Anthony MarioLitcofsky, Kevin DanielBerry, David ArthurCook, David N.Afeyan, Noubar B.Aunins, John Grant

Assignees

Seres Therapeutics Inc

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Publication Number

US-11458173-B2

Patent

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 invention relates to a composition comprising a first species of isolated bacterium and a second species of isolated bacterium, together with a capsule that encapsulates the first species, the second species, or both. The first species is Lachnospiraceae_bacterium_5_1_57FAA and the second species is Clostridium orbiscindens. The bacterial species are defined by 16S rDNA sequence identity thresholds to specified reference sequences.

Lachnospiraceae_bacterium_5_1_57FAA comprises a 16S rDNA sequence that is at least 97% identical to the 16S rDNA sequence set forth in SEQ ID NO: 979. Clostridium orbiscindens comprises a 16S rDNA sequence that is at least 97% identical to SEQ ID NO: 548. The core concept links the defined two-species composition and the presence of a capsule to an inhibitory functional outcome against C. difficile.

The inhibition is measured by a CivSim assay, which is used as the stated basis for establishing that the first species and the second species are capable of inhibiting C. difficile growth. The claim set coverage further reflects dependent refinements that adjust CivSim inhibition performance, tighten 16S rDNA identity thresholds, and specify spore form and enteric coating.

Claims Coverage

The independent claim is focused on a two-species bacterial composition with capsule encapsulation, where both species are identity-defined by 16S rDNA similarity to specified SEQ ID references and are functionally defined by inhibiting C. difficile growth in a CivSim assay. The claim coverage includes 9 inventive features.

Capsule-encapsulated two-species defined bacterial composition

A composition comprising a first species of isolated bacterium and a second species of isolated bacterium and a capsule that encapsulates the first species, the second species, or both, wherein the first species is Lachnospiraceae_bacterium_5_1_57FAA and the second species is Clostridium orbiscindens.

16S rDNA identity-defined Lachnospiraceae_bacterium_5_1_57FAA

Lachnospiraceae_bacterium_5_1_57FAA comprises a 16S rDNA sequence that is at least 97% identical to the 16S rDNA sequence set forth in SEQ ID NO: 979.

16S rDNA identity-defined Clostridium orbiscindens

Clostridium orbiscindens comprises a 16S rDNA sequence that is at least 97% identical to SEQ ID NO: 548.

CivSim-assay inhibition of C. difficile growth

The first species and the second species are capable of inhibiting C. difficile (C. difficile) growth as measured by a CivSim assay.

High-confidence CivSim inhibition performance

The first species and the second species inhibit C. difficile growth in the CivSim assay with a confidence interval greater than 99%.

Spore form of one or both species

The first species, the second species, or both are provided in spore form.

Tightened 16S rDNA threshold for Lachnospiraceae_bacterium_5_1_57FAA

The composition includes the Lachnospiraceae_bacterium_5_1_57FAA, which has a 16S rDNA sequence at least 98% identical to SEQ ID NO: 979.

Tightened 16S rDNA threshold for Clostridium orbiscindens

The composition includes Clostridium orbiscindens having a 16S rDNA sequence at least 98% identical to SEQ ID NO: 548.

Enteric coated composition

The claimed composition is further formulated with an enteric coating.

Overall, the claim set coverage centers on a capsule-encapsulated composition containing two specifically defined isolated bacterial species, each defined by 16S rDNA sequence identity to specified SEQ ID references, and functionally defined by inhibition of C. difficile growth measured by a CivSim assay. Dependent refinements further constrain the CivSim inhibition confidence interval, tighten 16S identity thresholds, specify spore form, and add enteric coating.

Stated Advantages

Inhibiting C. difficile growth as measured by a CivSim assay.

Inhibition of C. difficile growth in the CivSim assay with a confidence interval greater than 99%.

Documented Applications

No documented applications found

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