Recent Patents on Anti-Infective Drug Discovery (v.8, #3)

Topical Antimicrobials for Burn Infections - An Update by Mert Sevgi, Ani Toklu, Daniela Vecchio, Michael R. Hamblin (161-197).
The relentless rise in antibiotic resistance among pathogenic bacteria and fungi, coupled with the high susceptibilityof burn wounds to infection, and the difficulty of systemically administered antibiotics to reach damaged tissue,taken together have made the development of novel topical antimicrobials for burn infections a fertile area of innovationfor researchers and companies. We previously covered the existing patent literature in this area in 2010, but the notableprogress made since then, has highlighted the need for an update to bring the reader up to date on recent developments.New patents in the areas of topically applied antibiotics and agents that can potentiate the action of existing antibioticsmay extend their useful lifetime. Developments have also been made in biofilm-disrupting agents. Antimicrobial peptidesare nature's way for many life forms to defend themselves against attack by pathogens. Silver has long been known to bea highly active antimicrobial but new inorganic metal derivatives based on bismuth, copper and gallium have emerged.Halogens such as chlorine and iodine can be delivered by novel technologies. A variety of topically applied antimicrobialsinclude chitosan preparations, usnic acid, ceragenins and XF porphyrins. Natural product derived antimicrobials such astannins and essential oils have also been studied. Novel techniques to deliver reactive oxygen species and nitric oxide insitu have been developed. Light-mediated techniques include photodynamic therapy, ultraviolet irradiation, blue light,low-level laser therapy and titania photocatalysis. Passive immunotherapy employs antibodies against pathogens and theirvirulence factors. Finally an interesting new area uses therapeutic microorganisms such as phages, probiotic bacteria andprotozoa to combat infections.

Novel Quercetin Glycosides as Potent Anti-MRSA and Anti-VRE Agents by Abugafar M.L. Hossion, Kenji Sasaki (198-205).
Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibioticsand at least 23,000 people die each year as a direct result of these infections (Threat report 2013). Vancomycin isan FDA approved antibiotic and is growing importance in the treatment of hospital infections, with particular emphasis onits value to fight against methicillin-resistant Staphylococcus aureus (MRSA). The increasing use of vancomycin to treatinfections caused by the Gram-positive MRSA in the 1970s selected for drug-resistant enterococci, less potent thanstaphylococci but opportunistic in the space vacated by other bacteria and in patients with compromised immune systems.The dramatic rise of antibiotic-resistant bacteria over the past two decades has stressed the need for completely novelclasses of antibacterial agents. This paper reports the recent patent review on the strategy for finding novel quercetinglycosidetype antibacterial agents against vancomycin-resistant bacterial strains.

At this moment, over half million patients suffer from multi-drug resistant tuberculosis (MDR-TB) accordingto the data from the WHO. A large majority is terminally ill with essentially incurable pulmonary tuberculosis. Thisherein mini-review provides the experimental and observational evidence that a specific phenothiazine, thioridazine, willcontribute to cure any form of drug-resistant tuberculosis. This antipsychotic agent is no longer under patent protection forits initial use. The reader is informed on the recent developments in patenting this compound for “new use” with a specialemphasis on the aspects of drug-resistance. Given that economic motivation can stimulate the use of this drug as an antitubercularagent, future prospects are also discussed.

The continuing HIV epidemic has driven advancements in antiretroviral therapy. New therapeutic targets havebeen identified over the past years, one of which has been the Integrase enzyme. This is responsible for integrating HIVpro-DNA into the host cell genome and has proved a successful drug target.;Efforts have also been made to improve the pharmacokinetic parameters of current drug therapy and utilise these techniquesin maximising drug therapeutic effect whilst minimising adverse events. An exciting example of new technologiesis that of nanotechnology where drugs can be specifically targeted to certain tissues and drug delivery can be improved byutilising biological molecules and structures.;Pre-exposure prophylaxis is also an area of much interest currently both on an individual and population level. Complianceis however a major issue with daily medication to prevent HIV acquisition as has been demonstrated with contraceptiveagents. However if long acting compounds can be developed, compliance can be improved.;The patent drug currently being developed through nanotechnology as an analogue of Dolutegravir, GSK1265744 LAP(Long Acting Parenteral) has shown promise as a Long Acting Integrase Inhibitor with potential action both as a therapeuticagent but also in pre-exposure prophylaxis. The favourable pharmacokinetic profile and therapeutic efficacy in comparisonto other compounds of the same class demonstrate it to be a promising advance. However given current limitationsin study material, further randomised studies with long term follow up are required to fully evaluate the value of thepatent drug GSK1265744 LAP in action in both seropositive and seronegative individuals.

Patent Selections: (219-220).