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US 2022/0257670 A1Published application
Methods and products for treatment of gastrointestinal disorders
AssigneeFinch Therapeutics Holdings LLC
InventorsMark SMITH, Anh-Thu Elaine VO, Rotem SADOVSKY, John HENSKE, Ylaine GERARDIN, Sonia TIMBERLAKE
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Abstract
Described herein are compositions and methods for the delivery of microbial therapeutics useful for the treatment of disorders related to intestinal dysbiosis.
Claims27
A method of preparing a therapeutic bacterial isolate, the method comprising:
- (i) providing a preparation of bacteria from fecal material from
- (a) a group of healthy subjects,
- (b) a group of patients with a gastrointestinal disease or disorder, and
- (c) a group of patients having clinical remission of one or more symptoms of the gastrointestinal disease or disorder following treatment of each patient of the group of patients with a fecal microbiota transplant,
- (ii) analyzing 16S rRNA sequences from the preparation of bacteria, and
- (iii) isolating a bacterial isolate from stool of a human donor that comprises a 16S rRNA sequence that is at least 97% identical to a 16S rRNA sequence of a bacterial strain from the preparation of bacteria that is
- (a) enriched in a group of healthy subjects over a group of patients with the gastrointestinal disease or disorder;
- and/or
- (b) correlated with clinical remission of one or more symptoms of the gastrointestinal disease or disorder in a group of patients following treatment of each patient of the group of patients with the fecal microbiota transplant,
- wherein a cross-sectional combined p-value of the bacterial isolate is less than 1×10−14.
7 more elements
A method of preparing a microbial cocktail comprising a first and second bacterial isolate, the method comprising:
- (i) isolating multiple bacterial isolates from human stool;
- (ii) performing a first functional assay comprising:
- (a) contacting a population of eukaryotic cells with the bacterial isolates,
- (b) measuring an IL-10:IL-12 ratio and an IL-10:TNF-alpha ratio, and
- (c) identifying as the first bacterial isolate a bacterial isolate capable of inducing an IL-10:IL-12 ratio of at least about 50:1 or an IL-10:TNF-alpha ratio of at least about 1:1 when incubated with a population of eukaryotic cells,
- (iii) performing a second functional assay comprising:
- (a) measuring a level of a short chain fatty acid (SCFA) produced by the bacterial isolates, and
- (b) identifying as the second bacterial isolate a bacterial isolate that produces the SCFA at a concentration of at least about 10 mM, and
- (iv) combining the first and second bacterial isolates to produce the microbial cocktail.
6 more elements
Dependencies are inferred from the claim text.