Methods of treatment of infections using bacteria
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11147844-B2
Publication Date
2021-10-19
Expiration Date
Abstract
The present disclosure relates generally to compositions, dosage forms, and methods for preventing and treating infections. The compositions include intact and substantially non-viable Gram-negative bacterial cells which have been treated to reduce lipopolysaccharide (LPS)-associated endotoxin activity, which surprisingly have increased activity to trigger immune cell production of cytokines.
Core Innovation
The invention relates to a method for treating or inhibiting an infection in a patient by administering a composition comprising a plurality of intact and substantially non-viable Salmonella and/or Escherichia cells. The Salmonella or Escherichia cells are treated to result in about a 75% to 99% reduction of lipopolysaccharide (LPS)-associated endotoxin activity when measured by the Limulus Amebocyte Lysate (LAL) assay as compared to untreated, wild-type Salmonella or Escherichia cells.
Although the treated composition reduces LPS-associated endotoxin activity to the stated extent, it unexpectedly increases cytokine induction in human PBMCs. The disclosed framework includes evaluating endotoxin/pyrogenicity and comparing the cytokine response versus mono-specific Toll-like receptor (TLR) agonists, using cytokine panels and Luminex cytokine/Chemokine assays.
For the disclosed therapeutic application, the infection is by hepatitis B virus (HBV) or human immunodeficiency virus (HIV). Animal outcomes described include inhibition of HBV with delayed onset compared to entecavir, longer-lasting effect after cessation, and synergy when combined with indomethacin for suppression of HBsAg, HBeAg, and HBcAg.
For HIV, delayed HIV viral-load inhibition is described in humanized NOD/SCID/IL-2Rγnull (NCG) mice after stopping treatment.
Claims Coverage
The partial content provides one independent claim, with additional dependent claims refining the method by further quantitative and compositional constraints and by specifying an optional second therapeutic agent for infections by HBV or HIV. The independent claim has 3 main inventive feature areas.
Intact and substantially non-viable Salmonella or Escherichia cell composition
Administering to a patient an effective amount of a composition comprising a plurality of intact and substantially non-viable Salmonella and/or Escherichia cells.
LPS-associated endotoxin activity reduced by 75% to 99% by LAL
Treating the Salmonella and/or Escherichia cells to result in about 75% to 99% reduction of lipopolysaccharide (LPS)-associated endotoxin activity when measured by the Limulus Amebocyte Lysate (LAL) assay as compared to untreated, wild-type Salmonella and/or Escherichia cells.
Infection by HBV or HIV treated by the composition
Using the method to treat or inhibit an infection in the patient, where the infection is by hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
Across the provided independent claim, the inventive method is defined by administering an effective amount of intact, substantially non-viable Salmonella and/or Escherichia cells, where the treatment yields about a 75% to 99% reduction of LPS-associated endotoxin activity by the LAL assay, for treating infections caused by HBV or HIV.
Stated Advantages
A reduction of LPS-associated endotoxin activity of about 75% to 99% as measured by the Limulus Amebocyte Lysate (LAL) assay.
Unexpected increase of cytokine induction in human PBMCs despite reduction of LPS-associated endotoxin activity.
In vivo HBV inhibition with delayed onset compared to entecavir and longer-lasting effect after cessation.
Synergy with indomethacin for suppression of HBsAg, HBeAg, and HBcAg.
Delayed HIV viral-load inhibition in humanized NCG mice after stopping treatment.
Documented Applications
Treating or inhibiting an infection by hepatitis B virus (HBV) using an effective amount of a composition comprising intact and substantially non-viable Salmonella and/or Escherichia cells treated to reduce LPS-associated endotoxin activity by about 75% to 99% by LAL.
Treating or inhibiting an infection by human immunodeficiency virus (HIV) using an effective amount of a composition comprising intact and substantially non-viable Salmonella and/or Escherichia cells treated to reduce LPS-associated endotoxin activity by about 75% to 99% by LAL.
Interested in licensing this patent?