Compositions and methods for treating or preventing clostridium difficile infection, neutropenia, cardiovascular disease, asthma, and/or cancer
AssigneeVedanta Biosciences, Inc.
InventorsEmily Crossette, Amanda Prince
Life of this patent
Estimating the term…
Abstract
Provided herein are methods and compositions for treating and/or preventing recurrent Clostridium difficile infection (rCDI), neutropenia, cardiovascular disease (e.g., atherosclerosis and/or stroke), asthma, and/or cancer involving administering to a subject a pharmaceutical composition comprising a purified bacterial mixture.
Claims43
A method of treating or preventing recurrent Clostridium difficile infection (rCDI) in a subject, the method comprising administering to the subject a composition comprising a purified bacterial mixture, the purified bacterial mixture comprising:
- (i) a bacterial strain belonging to Clostridium bolteae;
- (ii) a bacterial strain belonging to Anaerotruncus colihominis;
- (iii) a bacterial strain belonging to Sellimonas intestinalis;
- (iv) a bacterial strain belonging to Clostridium symbiosum;
- (v) a bacterial strain belonging to Blautia producta;
- (vi) a bacterial strain belonging to Dorea longicatena;
- (vii) a bacterial strain belonging to Clostridium innocuum;
- and
- (viii) a bacterial strain belonging to Flavonifractor plautii,
- wherein a concentration of fecal calprotectin in a sample of the subject is not substantially increased for at least 1 week after administration of the composition, relative to a baseline concentration of fecal calprotectin prior to administration of the composition.
A method of treating or preventing recurrent Clostridium difficile infection (rCDI) in a subject, the method comprising administering to the subject a composition comprising a purified bacterial mixture, the purified bacterial mixture comprising:
- (i) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 1;
- (ii) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 2;
- (iii) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 3;
- (iv) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 4;
- (v) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 5;
- (vi) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 6;
- (vii) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 7;
- and
- (viii) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 8,
- wherein a concentration of fecal calprotectin in a sample of the subject is not substantially increased for at least 1 week after administration of the composition, relative to a baseline concentration of fecal calprotectin prior to administration of the composition.
The method of any one of the preceding claims, wherein the concentration of fecal calprotectin in the sample of the subject does not exceed 140%, 130%, 120%, or 110% of the baseline concentration of fecal calprotectin in the subject.
The method of any one of the preceding claims, wherein the concentration of fecal calprotectin is not substantially increased over a period of at least 2, 3, 4, 5, 6, 7, or 8 weeks following administration of the composition.
The method of any one of the preceding claims, wherein the baseline concentration of fecal calprotectin is a fecal calprotectin concentration in a baseline sample of the subject obtained 48 hours or fewer prior to administration of the composition.
The method of any one of the preceding claims, wherein the method further comprises measuring the concentration of fecal calprotectin in one or more samples of the subject after administration of the composition.
The method of any one of the preceding claims, wherein the method further comprises identifying the subject as having an elevated concentration of fecal calprotectin, if the level of fecal calprotectin is increased relative to the baseline concentration, and administering one or more additional doses of the composition to the subject.
A method of treating and/or preventing a condition in a subject, the method comprising administering to the subject a composition comprising a purified bacterial mixture, the purified bacterial mixture comprising:
- (i) a bacterial strain belonging to Clostridium bolteae;
- (ii) a bacterial strain belonging to Anaerotruncus colihominis;
- (iii) a bacterial strain belonging to Sellimonas intestinalis;
- (iv) a bacterial strain belonging to Clostridium symbiosum;
- (v) a bacterial strain belonging to Blautia producta;
- (vi) a bacterial strain belonging to Dorea longicatena;
- (vii) a bacterial strain belonging to Clostridium innocuum;
- and
- (viii) a bacterial strain belonging to Flavonifractor plautii,
- wherein the condition is selected from the group consisting of neutropenia, cardiovascular disease, asthma, and cancer.
A method of treating and/or preventing a condition in a subject, the method comprising administering to the subject a composition comprising a purified bacterial mixture, the purified bacterial mixture comprising:
- (i) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 1;
- (ii) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 2;
- (iii) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 3;
- (iv) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 4;
- (v) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 5;
- (vi) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 6;
- (vii) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 7;
- and
- (viii) a bacterial strain comprising a 16S rDNA sequence with at least 97% sequence identity to the nucleotide sequence of SEQ ID NO:
- 8,
- wherein the condition is selected from the group consisting of neutropenia, cardiovascular disease, asthma, and cancer.
The method of any one of the preceding claims, wherein the composition induces neutrophil differentiation in the subject.
The method of any one of the preceding claims, wherein the composition increases circulating neutrophil abundance in the subject.
The method of any one of the preceding claims, wherein the composition inhibits infiltration of neutrophils into an intestinal lumen of the subject.
The method of any one of the preceding claims, wherein the composition induces proliferation and/or accumulation of regulatory T cells (Tregs) in the subject.
The method of any one of the preceding claims, wherein the composition promotes tissue repair in the subject.
The method of any one of the preceding claims, wherein the composition induces production of a protein selected from the group consisting of calprotectin, IL-5, IL-9, IL-10, IL-12(p70), IL-20, IL-23, IL-28A, IL-33, thymic stromal lymphopoietin (TSLP), thrombopoietin (TPO), macrophage inflammatory protein-1 alpha (MIP-1α), monocyte chemotactic protein 3 (MCP3), leukemia inhibitory factor (LIF), interferon-gamma (IFN-γ), fractalkine, and eotaxin-3, in the subject.
The method of any one of the preceding claims, wherein the composition induces production of calprotectin in the subject.
The method of any one of the preceding claims, wherein the purified bacterial mixture consists of:
- (i) a bacterial strain comprising a 16S rDNA sequence with at least 99% sequence identity to the nucleotide sequence of SEQ ID NO:
- 1;
- (ii) a bacterial strain comprising a 16S rDNA sequence with at least 99% sequence identity to the nucleotide sequence of SEQ ID NO:
- 2;
- (iii) a bacterial strain comprising a 16S rDNA sequence with at least 99% sequence identity to the nucleotide sequence of SEQ ID NO:
- 3;
- (iv) a bacterial strain comprising a 16S rDNA sequence with at least 99% sequence identity to the nucleotide sequence of SEQ ID NO:
- 4;
- (v) a bacterial strain comprising a 16S rDNA sequence with at least 99% sequence identity to the nucleotide sequence of SEQ ID NO:
- 5;
- (vi) a bacterial strain comprising a 16S rDNA sequence with at least 99% sequence identity to the nucleotide sequence of SEQ ID NO:
- 6;
- (vii) a bacterial strain comprising a 16S rDNA sequence with at least 99% sequence identity to the nucleotide sequence of SEQ ID NO:
- 7;
- and
- (viii) a bacterial strain comprising a 16S rDNA sequence with at least 99% sequence identity to the nucleotide sequence of SEQ ID NO:
- 8.
The method of any one of the preceding claims, wherein the bacterial strains are lyophilized or spray-dried.
The method of any one of the preceding claims, wherein one or more of the bacterial strains are in spore form.
The method of any one of the preceding claims, wherein the composition is a pharmaceutical composition comprising the purified bacterial mixture and a pharmaceutically acceptable excipient.
The method of any one of the preceding claims, wherein the subject is a human.
Dependencies are inferred from the claim text.