Probiotic compositions containing clostridiales for inhibiting inflammation
Inventors
Berry, David • Kaplan, Johanne • Rahman, Shaila
Assignees
PharmaBiome AG • Evelop Biosciences Inc • Flagship Pioneering Inc
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9610307-B2
Publication Date
2017-04-04
Expiration Date
Abstract
Pharmaceutical compositions containing microbial entities are described herein. The pharmaceutical compositions may optionally contain or be used in conjunction with one or more prebiotics. Uses of the pharmaceutical compositions to treat or prevent disorders of the local or systemic microbiome in a subject are also provided.
Core Innovation
The invention relates to a pharmaceutical composition comprising an isolated population of anti-inflammatory bacterial cells consisting essentially of 3 or more strains of anti-inflammatory bacteria, selected from specified strains, and a pharmaceutically acceptable excipient or carrier. Each selected strain is capable of increasing secretion of Interleukin 10 (IL-10) by a population of human peripheral blood mononuclear cells (PBMCs) in vitro.
A key aspect is that the isolated population increases IL-10 secretion by PBMCs by at least 80% or more relative to each strain individually. Exemplary strain sets include Blautia producta together with Ruminococcus torques and one or more strains selected from Eubacterium rectale, Ruminococcus obeum, and Eubacterium ventriosum, as well as Blautia producta, Eubacterium ventriosum, and Coprococcus comes, or Ruminococcus torques, Eubacterium ventriosum, and Blautia ovatus.
The disclosure also addresses immunological anti-inflammatory activity by modulation of human PBMC cytokines, including decreases in pro-inflammatory cytokines such as IFN-γ, IL-12p70, IL-1α, IL-6, IL-8, TNFα, and MCP1/MIP1α/MIP1β, and/or increases in anti-inflammatory cytokines such as IL-10, IL-13, IL-4, IL-5, and TGFβ. The background framing of the problem is the presence of autoimmune or inflammatory disorders and related inflammatory states such as graft-versus-host disease (GVHD), in which cytokine patterns are implicated.
Claims Coverage
The independently claimed subject matter covers pharmaceutical compositions with an isolated population of anti-inflammatory bacterial cells consisting essentially of 3 or more strains, where each included strain increases IL-10 secretion by PBMCs in vitro and the combined population achieves an IL-10 increase of at least 80% relative to each strain individually. There are three independent claims in the provided set, each corresponding to a specific set of named bacterial strains or options among named strains plus a pharmaceutically acceptable excipient or carrier.
Three-strain anti-inflammatory bacterial population that increases IL-10 secretion by PBMCs in vitro
A pharmaceutical composition comprising an isolated population of anti-inflammatory bacterial cells consisting essentially of 3 or more strains of anti-inflammatory bacteria, wherein the 3 or more strains comprise Blautia producta, Ruminococcus torques, and one or more strains selected from Eubacterium rectale, Ruminococcus obeum, and Eubacterium ventriosum, wherein each strain selected for inclusion is capable of increasing secretion of Interleukin 10 (IL-10) by a population of human peripheral blood mononuclear cells (PBMCs) in vitro, and wherein the isolated population increases IL-10 secretion by PBMCs by at least 80% or more relative to each strain individually; and a pharmaceutically acceptable excipient or carrier.
Anti-inflammatory bacterial population including Blautia producta, Eubacterium ventriosum, and Coprococcus comes that increases IL-10 secretion by PBMCs in vitro
A pharmaceutical composition comprising an isolated population of anti-inflammatory bacterial cells consisting essentially of 3 or more strains of anti-inflammatory bacteria, wherein the 3 or more strains comprise Blautia producta, Eubacterium ventriosum and Coprococcus comes, wherein each strain selected for inclusion is capable of increasing secretion of Interleukin 10 (IL-10) by a population of peripheral blood mononuclear cells (PBMCs) in vitro, and wherein the isolated population increases IL-10 secretion by PBMCs by at least 80% or more relative to each strain individually; and a pharmaceutically acceptable carrier.
Anti-inflammatory bacterial population including Ruminococcus torques, Eubacterium ventriosum, and Blautia ovatus that increases IL-10 secretion by PBMCs in vitro
A pharmaceutical composition comprising an isolated population of anti-inflammatory bacterial cells consisting essentially of 3 or more strains of anti-inflammatory bacteria, wherein the 3 or more strains comprise Ruminococcus torques, Eubacterium ventriosum and Blautia ovatus, wherein each strain selected for inclusion is capable of increasing secretion of Interleukin 10 (IL-10) by a population of peripheral blood mononuclear cells (PBMCs) in vitro, and wherein the isolated population increases IL-10 secretion by PBMCs by at least 80% or more relative to each strain individually; and a pharmaceutically acceptable carrier.
Across the independently claimed compositions, the central inventive coverage is the use of an isolated population of anti-inflammatory bacterial cells consisting essentially of 3 or more specified strains where each strain can increase IL-10 secretion by PBMCs in vitro and the overall mixture increases IL-10 secretion by at least 80% relative to each strain individually, with a pharmaceutically acceptable excipient or carrier. The independent claims differ by the named strain sets included, or options among named strains, within the required 3+ strain composition.
Stated Advantages
Increases IL-10 secretion by PBMCs by at least 80% or more relative to each strain individually.
Enables immunological anti-inflammatory cytokine modulation in human PBMCs, including reducing pro-inflammatory cytokines and/or increasing anti-inflammatory cytokines.
The composition is a pharmaceutical composition comprising anti-inflammatory bacterial cells with IL-10 increasing capability in vitro.
Documented Applications
Treatment of autoimmune or inflammatory disorders, including graft-versus-host disease (GVHD).
Use in contexts related to autoimmune or inflammatory disorders and cytokine modulation in human PBMCs.
Interested in licensing this patent?