Methods and compositions relating to microbial treatment and diagnosis of disorders
Inventors
Cutcliffe, Colleen • Eid, John S. • Bullard, James H. • SCHICKLBERGER, Marcus F.
Assignees
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Publication Number
US-10842830-B2
Publication Date
2020-11-24
Expiration Date
Abstract
The present disclosure provides methods, systems, compositions, and kits to address the need for microbiome-related treatment of health conditions and disease. The present disclosure provides for treatment of metabolic conditions using microbial compositions.
Core Innovation
The document describes dosage forms for microbial therapeutics that include defined combinations of microorganisms and protective formulation components. In particular, the formulations are based on a first microbe, a second microbe, and a third microbe, where each microbe is characterized by a 16S rRNA sequence identity threshold relative to reference 16S rRNA sequences of Akkermansia muciniphila, Eubacterium hallii, and Clostridium beijerinckii. The formulations further comprise an enteric coating, or an effective amount of a preservative.
The document also describes growth-media formulations and additives used to support microbial growth, including components such as trace minerals, vitamins, salts or buffers, and anaerobic growth conditions. Media examples include GYTveg and PYGveg formulations intended to enhance microbial density and improve acid buffering, and the document further describes pharmaceutical formulation options for microbial therapeutics, including stability and presentation formats such as lyophilized or freeze-dried microbes and spores.
The invention relates to microbiome-based therapeutic and diagnostic approaches for metabolic disorders, including obesity, insulin insensitivity, and Type 2 diabetes mellitus. It provides pharmaceutical compositions that include isolated or purified microbial populations formulated as dosage forms, and it also describes microbiome profiling and diagnostic scoring concepts using strain-level resolution approaches and algorithmic scoring, with performance metrics such as sensitivity/specificity/ROC.
Claims Coverage
Independent claim clm-00001 is directed to a dosage form that includes three specific microbes defined by 16S rRNA sequence identity, together with either an enteric coating or an effective amount of a preservative. Dependent claims add further refinements such as tighter 16S rRNA identity thresholds, quantitative CFU constraints, and specific presentation/processing format limitations.
Three defined microbes identified by 16S rRNA sequence identity
A dosage form comprising a first microbe comprising a 16S rRNA sequence comprising at least 97% sequence identity to a 16S rRNA sequence of Akkermansia muciniphila; a second microbe comprising a 16S rRNA sequence comprising at least 97% sequence identity to a 16S rRNA sequence of Eubacterium hallii; and a third microbe comprising a 16S rRNA sequence comprising at least 97% sequence identity to a 16S rRNA sequence of Clostridium beijerinckii.
Enteric coating or preservative in the dosage form
Wherein the dosage form comprises an enteric coating, or an effective amount of a preservative.
Quantitative CFU constraint for the third microbe
The dosage form comprises at least 1×10^5 CFUs of said third microbe.
Higher quantitative CFU requirement across the microbe set
The dosage form comprises at least 1×10^7 CFUs of said first microbe, said second microbe, or said third microbe.
Powder presentation of the microbes
The microbes are in a powder form in said dosage form.
Lyophilized processing state of the microbes
The first microbe, second microbe, or third microbe are lyophilized.
Tightened 16S rRNA identity for the first microbe
The first microbe's 16S rRNA sequence comprises at least 99% sequence identity to the 16S rRNA sequence of Akkermansia muciniphila.
Overall, claim coverage centers on a dosage form containing a defined three-microbe set characterized by 16S rRNA sequence identity thresholds and combined with an enteric coating or an effective amount of a preservative, with dependent refinements specifying CFU levels, presentation/processing format, and tightened sequence identity constraints.
Stated Advantages
Improved growth media increase peak bacterial density.
Media-dependent short-chain fatty acid quantification is reported to match predicted genomic function.
Preclinical-style examples report weight loss and improved glucose tolerance in diet-induced obese mice.
Documented Applications
Oral delivery of microbial therapeutics using an enteric coating directed to the ileum/upper colon.
Use in diet-induced obese mice, with reported outcomes including weight loss and improved glucose tolerance.
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