Compositions and methods for suppressing pathogenic organisms
Inventors
Caballero, Silvia • Felix, Cintia
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12053495-B2
Publication Date
2024-08-06
Expiration Date
Abstract
Provided herein are compositions and methods for the suppression of multi-drug resistant organisms. Provided herein are compositions and methods for treating diseases or disorders associated with bacterial colonization or treating diseases or disorders associated with an immune response induced by bacteria. Also provided herein are compositions and methods for suppressing colonization of the intestine of subject with oral microbiome bacteria.
Core Innovation
The disclosed invention relates to a composition comprising multiple purified bacterial strains, each defined by a 16S rDNA sequence having at least 99% sequence identity with specified nucleic acid sequences designated as SEQ ID NOs. The composition is lyophilized and is grounded in 16S rDNA sequence-identity and alignment comparisons against a 16S rDNA database to identify closest related bacterial species.
The disclosure frames the problem as clearance or suppression of CRE and VRE, suppression or prevention of colonization by oral microbiome bacteria, and associated multidrug-resistant organisms. It also references inflammatory bowel disease, ulcerative colitis, Crohn’s disease, and disease-associated immune outcomes including IFN-γ, IL-2, IL-12, STAT4, T-bet, Foxp3, regulatory T cells, and Th17.
The document further describes approaches that compare fecal microbiota treatment (FMT) and a stool fraction library (SFL), including spore-forming (SP) fraction and non-spore forming (NSP) fraction. It also addresses in vivo testing of defined multi-strain compositions, including D14 NSF-36 and D14-23 subsets, and states that the compositions can be provided in lyophilized or spray-dried forms with intestinal delivery formats, including enteric coating and delayed release using pH-sensitive polymers.
Claims Coverage
The relevant independent claim coverage centers on a lyophilized multi-strain bacterial composition defined by at least 99% 16S rDNA sequence identity to specified SEQ ID NOs. Dependent claims add pharmaceutical formulation, delivery-route, quantity, and additional sequence-defined strain features.
Lyophilized multi-strain composition defined by 16S rDNA identity to specific SEQ ID NOs
A composition comprising multiple purified bacterial strains, where each strain includes a 16S rDNA sequence having at least 99% sequence identity with the nucleic acid sequence of specified SEQ ID NOs, and wherein the bacterial strains are lyophilized.
Pharmaceutical composition with a pharmaceutically acceptable excipient
A pharmaceutical composition formed by combining the composition with a pharmaceutically acceptable excipient.
Oral or rectal pharmaceutical composition delivery
A pharmaceutical composition formulated for either oral or rectal delivery.
Minimum number of purified bacterial strains
The composition includes purified bacterial strains at least as many as one of specified thresholds, from at least 9 up to at least 36.
CFU range per bacterial strain
The composition contains 1×10^7 to 1×10^10 colony forming units per bacterial strain.
Additional SEQ ID-defined purified bacterial strains
A composition defined as containing purified bacterial strains whose 16S rDNA sequences have at least 99% sequence identity to the nucleic acid sequences of SEQ ID NO: 23 and SEQ ID NO: 25.
Overall claim coverage centers on a lyophilized composition containing multiple purified bacterial strains, each defined by 16S rDNA sequence identity to specified SEQ ID NOs, with dependent claims narrowing the composition by excipients, delivery route, minimum number of strains, CFU range, and inclusion of additional SEQ ID-defined strains.
Stated Advantages
Suppression or prevention of colonization by oral microbiome bacteria and multidrug-resistant organisms.
Association with inhibiting pathogens and/or reducing pathogen survival and colonization.
Synergy among strains through nutrient use, niche colonization, and metabolite provision.
Documented Applications
Efficacy in mouse models of CRE/VRE clearance using fecal microbiota treatment (FMT) and a stool fraction library (SFL).
Use of spore-forming (SP) fraction and non-spore forming (NSP) fraction to assess fraction composition and clearance-related outcomes.
In vivo testing of defined multi-strain compositions, including D14 NSF-36 and D14-23 subsets, for CRE clearance outcomes in mouse models.
In vitro/competition assays against specific Klebsiella pneumoniae strains to assess antagonistic/clearance-related effects.
Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease.
Other Th1-associated inflammatory disorders.
Non-alcoholic steatohepatitis (NASH).
Primary sclerosing cholangitis (PSC).
Non-alcoholic fatty liver disease (NAFLD).
GERD.
Interested in licensing this patent?