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Therapeutic bacteriophage compositions

A phage and composition technology, applied in the field of phage composition, can solve the problems of MRSA infection that is difficult to treat with conventional antibiotics

Pending Publication Date: 2020-01-21
ARMATA PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

MRSA infection extremely difficult to treat with conventional antibiotics

Method used

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  • Therapeutic bacteriophage compositions
  • Therapeutic bacteriophage compositions
  • Therapeutic bacteriophage compositions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] Phage group assembly (assembly)

[0098] A composition (group) of four phages Sa87, J-Sa36, J-Sa37 and Sa83, which together have broad activity against a group of recent multiple S. aureus clinical isolates (unpublished data), was used in animal research. In an exemplary method, phage lysates were prepared using production hosts SPS1216 and SPS1226, which do not release endogenous prophage during the production cycle. Grow the culture to OD in the bioreactor prior to phage addition 600 is 0.2. Continue to incubate at 37°C and read absorbance at least every 60 minutes. The culture is harvested after bacterial lysis and impurities are separated from the phage by several filtration steps followed by a chromatography step that reduces debris such as host cell proteins and host cell DNA. After purification, use a spin column ( Ultra 15-100kDa, Merck Millipore, Darmstadt, Germany) additionally concentrated the lysate such that the final phage titer was ≥1×10 11 PFU / m...

Embodiment 2

[0100] bacterial strain

[0101] Inoculate frozen stocks of Staphylococcus aureus UNT109-3 and UNT144-3 (obtained from the UNT culture collection center) into Trypticase TM Soy Broth (BBL TM Laboratories)+5% defibrinated sheep blood (TSBb) and incubated at 37°C for 18 hours (shaking). After 18 hours, the culture was diluted 1:10 into fresh TSBb and incubated for a further 5 hours before being diluted in fresh TSB for inoculation into mice.

Embodiment 3

[0103] Evaluation of Staphylococcus aureus virulence in a mouse model of pneumonia

[0104]The sensitivity of two S. aureus clinical isolates UNT109-3 (NRS234, native valve endocarditis) and UNT144-3 that have been used in animal models of infection was assessed relative to a single phage and a panel of 4 phages. In some embodiments, both strains are fully susceptible to the group as well as to individual phages Sa87, J-Sa36 and Sa83. Phage Sa87, J-Sa36 and Sa83 showed improved efficacy against UNT109-3 compared to phage J-Sa37. The virulence of both strains was then assessed in a murine lung infection model. Female Hsd:ICR(CD1) mice (Harlan Laboratories, Houston, TX) were administered 150 and 100 mg / kg cyclophosphamide on days 4 and 1 before infection to reduce their neutropenia. Groups of 5 mice were then anesthetized by intraperitoneal (IP) injection of 0.15 mL of a mixture of ketamine hydrochloride (100 mg / kg body weight) and xylazine (10 mg / kg body weight). Once anes...

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Abstract

The present invention relates to a bacteriophage composition comprising one or more (suitably two or more, or three) bacteriophages selected from Sa87, J-Sa36, or Sa83, or mutants thereof. Also encompassed are the use of said bacteriophage compositions for medical or non-medical applications, as well as kits, bandages, and wound dressings comprising said bacteriophage compositions.

Description

technical field [0001] The present invention relates to compositions of bacteriophages, and their use in medical and non-medical applications. Background technique [0002] In recent years, the widespread use of antimicrobial agents, usually in the form of small molecule (chemical) antibiotics such as penicillin or tetracycline, has led to a large increase in antibiotic resistant bacterial strains. Mutations that confer antibiotic resistance, or genes encoding antibiotic resistance enzymes, such as penicillinase, are becoming more common in disease-causing bacteria worldwide. For example, methicillin-resistant Staphylococcus aureus (MRSA) bacteria is an increasingly common form of infection that often occurs after surgery or other invasive treatments in clinical settings. MRSA infections are extremely difficult to treat with conventional antibiotics. [0003] Due to the increased prevalence of pathogenic bacteria exhibiting resistance to antimicrobial agents, especially so...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/76A61P31/04
CPCA61K35/76A61P31/04A61K2300/00C12N7/00C12N2795/00032
Inventor 凯伦·乔伊·肖桑德拉·P·莫拉莱斯吉莉安·默恩斯黛博拉·A·兰金弗伦克·斯姆雷卡尔
Owner ARMATA PHARMA INC