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Docket #: S20-368

Highly concentrated phage therapy suspensions stabilized with annexin V

Stanford researchers have developed high-titer bacteriophage and annexin V formulations for rapid, more effective phage therapy against bacterial infection.

Multi-drug resistant bacteria are a growing threat that is driving innovation in phage therapies as new antibacterials with high specificity and negligible side effects. However, key issues remain, including the risk of phage-resistant mutations arising in bacteria and a tendency for phage to precipitate out of solution.

The inventors have developed a phage therapy formulation that overcomes these challenges using annexin V, an enzymatically inert human protein that has already been tested in clinical trials. Annexin V binds to the negatively charged bacteriophage coat, stabilizing phage preparations of up to 1012 plaque forming units per milliliter (pfu/ml), instead of the standard 107 to 108 pfu/ml. These highly concentrated preparations potentially allow direct phage lysis, which would speed up treatment and therefore reduce the chance of resistance mutations.

Stage of Development
In vitro/in vivo. The formulation rapidly resolves otherwise-lethal Pseudomonas aeruginosa wound infection in mice.

Applications

  • Stabilized, highly concentrated phage and annexin V preparations for:
    • Antibacterial phage therapy
    • Radiolabeled studies of bacterial infection biodistribution

Advantages

  • More concentrated phage potentially facilitates:
    • Direct phage lysis, also known as "lysis from without"
    • Faster treatment
    • Reduced chance of resistance mutations
  • Less frequent phage precipitation
  • Easier shipment and long-term storage

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