Treatment of Clostridium difficile infection
Inventors
Schneider, Jessica • Kim, Yun-gi • Olle, Bernat • Reddy, Shilpa • Norman, Jason • Patarroyo, Juan
Assignees
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Publication Number
US-10555980-B2
Publication Date
2020-02-11
Expiration Date
Abstract
Provided herein are compositions and methods for the treatment or prevention of pathogenic infections.
Core Innovation
The invention provides a pharmaceutical composition and a method to suppress an abnormal or excessive immune response by administering a purified bacterial mixture to a subject. The mixture consists of 7 or more bacterial strains or 8 bacterial strains, and includes 16S rDNA sequences having at least 97% sequence identity to nucleic acid sequences selected from specified SEQ ID NOs. The approach uses defined, sequence-characterized bacterial strains as the active components in the composition.
The compositions include purified multi-strain bacterial mixtures with stringent sequence-defined inclusion criteria based on 16S rDNA sequence identity to specified SEQ ID NOs. The description also includes regulatory T cell proliferation and/or accumulation, and administration targeting the colon or intestine. The invention further includes formulation concepts using pharmaceutically acceptable excipients and delivery approaches.
The compositions are described as reducing Clostridium difficile toxin production (TcdB/Toxin B) and inhibiting growth/survival, while inducing regulatory T cell proliferation and/or accumulation. The document further refers to niche grafting and metabolite or short-chain fatty acid production as contributing to the observed outcomes, and includes a context of C. difficile infection/toxin.
Claims Coverage
Independent claims are provided for methods of suppressing an abnormal or excessive immune response by administering a pharmaceutical composition containing a purified multi-strain bacterial mixture. The inventive features focus on the number of bacterial strains and the 16S rDNA sequence identity to specified SEQ ID NOs, with one independent claim requiring 7 or more strains and the other requiring 8 strains; dependent claims further specify immunological mechanism, adjunct antibiotic pretreatment, and formulation or delivery constraints.
Purified bacterial mixture for immune suppression
Administering a pharmaceutical composition comprising a purified bacterial mixture to a subject in an amount sufficient to suppress an abnormal or excessive immune response.
16S rDNA sequence identity to specified SEQ ID NOs
The purified bacterial mixture includes bacterial strains comprising 16S rDNA sequences of at least 97% sequence identity to nucleic acid sequences selected from SEQ ID NO: 10, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21.
Purified bacterial mixture of 7 or more strains
The purified bacterial mixture consists of 7 or more bacterial strains comprising the specified 16S rDNA sequences.
Purified bacterial mixture of 8 strains
The purified bacterial mixture consists of 8 bacterial strains comprising the specified 16S rDNA sequences.
Across both independent claims, the core coverage is the administration of a purified bacterial mixture with 16S rDNA sequences having at least 97% identity to specified SEQ ID NOs, where one method requires 7 or more strains and the other requires exactly 8 strains. Dependent claim coverage further constrains mechanism and treatment features, including regulatory T cell proliferation and/or accumulation, optional antibiotic pretreatment, and colon delivery.
Stated Advantages
Suppresses an abnormal or excessive immune response.
Reduces Clostridium difficile toxin production (TcdB/Toxin B) and inhibits growth/survival.
Induces regulatory T cell proliferation and/or accumulation.
Documented Applications
Treating or preventing Clostridium difficile infection.
Managing immune-related conditions characterized as abnormal or excessive immune response by suppressing such responses in a subject.
Delivery to the colon, including pH sensitive compositions with enteric polymers, and oral administration in capsule form are disclosed.
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