Recent Patents on Anti-Infective Drug Discovery - Volume 6, Issue 1, 2011

The World Health Organization has classified the leishmaniasis as a major tropical disease. An effective vaccine is not available and the chemotherapy is the only effective way to treat all forms of disease. Currently, the therapy is toxic, expensive and the resistance has emerged as a serious problem, which has compelled the search for new antileishmanial agents. The aim of this article is to review the recent advances in antileishmanial drugs. In addition, patents from 01/1969 to 12/2009 were analyzed. After initial review, 867 patents were classified as vaccines, immunomodulators and drugs. Among them, the major percent was reached by the drugs, accounting for 68% of the patents. In this review, 580 patents were listed, reviewed and classified according the approach of the inventors in the expansion of antileishmanial drug discovery. In this moment, the scenario of leishmaniasis chemotherapy is more promising than ever. Nevertheless, advances in the understanding of new metabolic pathways and drug targets in the parasite could offer new alternatives to treatment of leishmaniasis.

Drug resistance in tuberculosis (TB) is a serious problem compromising both the treatment and control programs. Poor usage of the available anti TB drugs has led to progressive drug resistance-multi drug resistance (MDR), extensively drug-resistance (XDR) and even total drug resistance (TDR). While drug sensitive TB is completely curable, MDR-TB is difficult to treat, XDR and TDR are often fatal. Non availability of new drugs to treat drug resistant cases further complicates the problem. The Global Alliance for Tuberculosis Drug Developments, a non-profit organization with the World Health Organization (WHO) as a partner was formed in February 2000 for the development of new drugs. In the last decade this venture has resulted in several promising new antituberculosis drugs like TMC207 (diaryquinoline), PA-824 (nitroimidazo-oxazine), OPC-67683 (nitroimidazo-oxazole) and SQ 109 (diamine compound). Drug resistance in TB is a man made problem. Therefore, while global efforts towards new drug development must continue it is equally important to have a well defined community approach to prevent the emergence of drug resistance to the existing and newer drugs. The present review article discusses some recent drug patents for the treatment of tuberculosis and the appropriate community approach to prevent and treat drug resistant TB.

Invasive fungal infections are a leading cause of mortality, especially in immunocompromised patients. Therapy is made difficult by the limited number of antifungal agents currently available which mostly target ergosterol in fungal cell membranes. The paucity of targets allows the development of cross resistance to all drugs with a common target. This highlights the need to develop new therapeutic strategies for fungal disease including agents with novel mechanisms of action. Heat shock protein 90 stabilizes calcineurin which regulates response to stress, allowing for calcineurin dependent stress responses required to survive exposure to antifungal drugs. Heat shock protein 90 inhibition abrogates calcineurin dependent stress responses, changing fungistatic drugs to fungicidal. Targeting a highly conserved protein that has a vital role in many cellular signaling pathways, reduces the potential for emergence of resistance to heat shock proteins inhibitors. This article will review recent patents in novel heat shock protein inhibitor therapy, such as efungumab, which diminish the emergence of antifungal drug resistance and enable greater efficacy of existing antifungals.

Although carbapenem antibiotics are one of the most effective agents in the treatment of nosocomial infections caused by Gram-negative bacteria, their use is threatened by the emergence of antibiotic resistance. The bacterial resistance to carbapenems parallels their increasing use and has dramatic clinical implications such as increase in mortality and cost of care. This article reviews recently published patents claiming for carbapenem antibacterial agents. New forms including crystalline forms with high oral bioavailability and modified spectrum including methicillinresistant Staphylococci are some of new patents described in this review.

Viral gastroenteritis presents a major public health concern worldwide. It is mostly a disease of young children. However, acquired immunity may wane and symptomatic infection can also occur in adults. Furthermore, asymptomatic adults may promote the spread of infections by shedding virus in their stools. This review covers the four most common causes of adult viral gastroenteritis, Calicivirirdae (predominantly noroviruses), astroviruses, enteric adenoviruses and rotaviruses focussing on their epidemiologic, structural, pathogenic and clinical aspects. In addition, current and future prevention and treatment options are discussed, including recent patents. While specific inhibitors of viral replication are currently not available, we summarized non-specific anti-viral agents and potential targets for the most important adult pathogen, Norovirus. Special emphasis is put on current and future vaccines.

Seriously compromised patients may acquire deep airway ailments by Gram positive, commensal bacteria including Kytococcus and Rothia, pathogenic tracts of which still remain quite unexplored. Resistances they express have been poorly investigated over the years, and no published guidelines for susceptibility testing and antibiotic therapy exist. We would therefore revise the current knowledge about these opportunistic organisms' clinical impact, as well as discuss on recent patents focusing on lung infection management. Particularly, these deal with the use of inhalatory vancomycin, even as lipidic complex, that appears a promising adjunctive treatment to systemic antimicrobials.

The patents annotated in this section have been selected from various patent databases. These recent patents are relevant to the articles published in this journal issue, categorized by therapeutic areas/targets and therapeutic agents related to antiinfective drug discovery.