Loading patent…
AssigneeRx3 Pharmaceuticals
InventorsVickie Brown-Driver, Kedar GC, John Finn, Robert Haselbeck, Mark Hilgers, Karen Shaw, Mark Stidham
Estimating the term…
The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a β-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.
A method for treating bacterial infections in a subject comprising administering to a subject in need thereof, an antibacterially effective combination of a □-lactam antibiotic and an inhibitor of bacterial MurB enzyme.
A method for treating bacterial infections in a subject comprising administering to a subject or animal in need thereof, an antibacterially effective combination of a β-lactam antibiotic and an inhibitor of a bacterial peptidoglycan biosynthesis enzyme.
(canceled)
5-26. (canceled)
A method of discovering synergists for antibiotics, comprising:
The method of claim 26, wherein the antisense nucleic acid is transcribed from an inducible promoter.
37-40. (canceled)
A method of identification of a compound as an inhibitor of a bacterial peptidoglycan biosynthesis enzyme, selected from GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, or UppS by selecting compounds from a compound library or natural product library using a bacteria culture in the presence of an antibiotic at a concentration 20% or less than the MIC of the antibiotic, scoring compounds that kill the bacteria only in the presence of the sub-MIC level of the antibiotic, and testing the selected compounds for inhibition of any bacterial peptidoglycan biosynthesis enzyme, selected from GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS in an in vitro enzyme assay.
42-52. (canceled)
A method of identifying synergists for antibiotics:
A method for generating, detecting and using DNA fragments representing a microbial gene or gene of interest that, when ectopically expressed in the antisense orientation within a certain target microorganism, cause post-transcriptional inhibition of expression specific to the gene or genes of interest within the microorganism.
59-76. (canceled)
Dependencies are inferred from the claim text.