Therapeutics for Drug-Resistant Bacterial Infections: Inhibitors of Bacterial RNA Polymerase

Invention Summary:

Bacterial infectious diseases kill 100,000 persons each year in the US and 11 million persons each year worldwide, representing nearly a fifth of deaths each year worldwide.  For six decades, antibiotics have been our bulwark against bacterial infectious diseases.  However, now this bulwark is collapsing.  For all major bacterial pathogens, strains resistant to at least one current antibiotic have arisen, and, for several bacterial pathogens, strains resistant to all current antibiotics have arisen.

There is an urgent national and international need for new classes of antibacterial agents effective against bacterial pathogens resistant to current antibacterial agents.

Rutgers researchers have identified five new "drug targets" within the structure of bacterial RNA polymerase, the enzyme that carries out bacterial gene expression.  Each of these new targets can serve as a binding site for compounds that inhibit bacterial gene expression and thereby kill bacteria.  Each of these new targets is present in all bacterial species, and thus compounds that bind to these new targets are active against a broad spectrum of bacterial species.  Each of these new targets is different from targets of current antibiotics, and thus compounds that bind to these new targets are not cross resistant with current antibiotics.  For each of these new targets, Rutgers researchers have identified at least one "lead compound" that binds to the new target and have characterized the activity of the lead compound.  Several of the lead compounds exhibit exceptionally high promise, exhibiting potent activity against a broad spectrum of priority public health bacterial pathogens and priority biodefense bacterial pathogens (including the pathogens responsible for tuberculosis, staph infections, strep infections, anthrax, and plague), and exhibiting no cross resistance with current antibiotics.

Market Application:

• Treatment of bacterial infections (particularly drug-resistant and multi-drug-resistant bacterial infections)

Advantages:

• First-in-class compounds
• Novel targets and mechanisms
• Broad-spectrum antibacterial activity
• Active against drug-resistant strains
• Active against both replicating and non-replicating bacteria
• Active against biofilms
• Bactericidal
• Additive effects when administered in combination
• Suppressed resistance emergence when administered in combination

Intellectual Property & Development Status:

• Large patent portfolio containing both issued and pending patents on targets, methods, compositions of matter and uses
• Advanced lead compounds with in vivo proof of concept in animal infection models for four of the five new targets