Recent Patents on Anti-Infective Drug Discovery - Volume 5, Issue 1, 2010

Clostridium difficile infection (CDI) is a major concern for health care system and clinicians. Interest in C. difficile infection has increased recently due to an ongoing C. difficile epidemic with a hypervirulent strain and mortality. Disease due to C. difficile is responsible for substantial strain on the hospital system by increasing patients' length of stay and increasing costs. Present studies have demonstrated chemotherapeutic agents as an independent risk factor for CDI potentially leading towards serious morbidity and mortality. However, the current strategies lack randomized trials on management in chemotherapy-associated CDI. The changing face of the disease, emergence of more resistant strains, and the rising cancer incidence have heightened the need for identification of risk factors, rapid diagnosis including prompt identification of toxins, and management algorithms. This review focuses on recent insights on the epidemiology, diagnosis, current management, recent patents, and advances on treating strategies of CDI with reference to current studies.

With an aging and obese population, chronic wounds such as diabetic ulcers, pressure ulcers, and venous leg ulcers are of an increasingly relevant medical concern in the developed world. Identification of bacterial biofilm contamination as a major contributor to non-healing wounds demands biofilm-targeted strategies to treat chronic wounds. While the current standard of care has proven marginally effective, there are components of standard care that should remain part of the wound treatment regime including systemic and topical antibiotics, antiseptics, and physical debridement of biofilm and devitalized tissue. Emerging anti-biofilm strategies include novel, non-invasive means of physical debridement, chemical agent strategies, and biological agent strategies. While aging and obesity will continue to be major burdens to wound care, the emergence of wounds associated with war require investigation and biotechnology development to address biofilm strategies that manage multi-drug resistant bacteria contaminating the chronic wound. The article presents some of the recent patents related to anti-biofilm strategy in wound care.

Despite an increase in the variety of anti-retroviral agents in the market, there remains a need for novel agents to treat HIV 1 infected individuals, in order to overcome existing problems with adherence, toxicities, drug interactions and viral resistance. In this article, we will describe Pro 140, one of the recently developed class of anti-retroviral agent, the CCR5 co-receptor inhibitor. We will also describe several preclinical and clinical studies that have evaluated the efficacy, tolerability and toxicity profiles of Pro 140. We will also look at how its mechanism of action and mode of delivery may change the way patients take highly active anti-retroviral therapy. There are some promising patents discussed in this short review for the use of PRO 140 as CCR5 co-receptor inhibitor.

The double-edged sword of antibiotic use in the fight against disease has saved countless lives at the cost of an escalation in pathogenic bacteria with increased resistance to multiple antibiotic classes. Reduction of resistance is a complicated multi-step endeavor that requires a sustained international effort of reduced utilization, infection control and development of effective and economical antimicrobial agents. The carbapenems are β-lactam antibiotics that are stable to most β-lactamases. They have potent bactericidal activity against a wide range of Gram-positive and Gram-negative aerobic bacteria as well as against anaerobic bacteria, while being safe, efficacious and tolerable. The use of carbapenems in hospitals has therefore been restricted to the empirical treatment of critical patients with a variety of serious infections, e.g. nosocomial pneumonia, septicemia, meningitis and cystic fibrosis. This article reviews patents claiming carbapenem antibacterial agents published from 2004-2008.

The advent of gene silencing siRNA technology has created opportunities to develop therapeutics based on targeting the genomics of the disease state. Amongst the first applications of siRNA technology, antiviral applications have been quickly and extensively exploited allowing emergence of a range of antiviral therapeutic strategies. Patent activity has encompassed a range of the components required to utilize this technology ranging from the identification of susceptible genomic targets through to the development of vector systems to express the siRNA endogenously or the synthesis of stable RNA oligonucleotides for in vivo therapeutics. Indeed the primary focus of research effort in this area has been to overcome the challenge common to all of gene therapeutics - delivery of the oligonucleotide - to the diseased tissues and organs, sites of infection and/or sites of drug action. Here, we survey the development of siRNA therapeutics both in terms of the range of virus species targeted and the strategic approaches employed. Our study illustrates features commonly observed in the field of nucleic acid drug development. While in vitro studies provide a broad range of molecules and molecular targets for potential therapeutics, the field is severely limited in terms of safe, effective means to deliver the potential siRNA therapeutics in vivo, to the intracellular site of action.

Echinocandins are an interesting group of antifungals that were originally discovered in the early 1970s. They are a group of lipopeptides produced by fungi which consists of a large number of structural analogs of echinocandin B, the first echinocandin to be structurally characterized. All clinically used echinocandins are produced semi-synthetically. The cyclic peptide nuclear core is retained while the acyl chain is replaced to minimize toxicity and expand their spectrum of activity. It was not until 2002 with the introduction of caspofungin (Cancidas) into the clinics that their true worth was realized. Since the introduction of caspofungin, two other echinocandins, micafungin (Mycamine) and anidulafungin (Eraxis) have been introduced. They all function by inhibiting an enzyme unique for fungal cell wall production, which presumably accounts for their minimal side-effects. In this review, topics pertaining to their production, structural diversity, and use in the clinic along with the recent patents are discussed.

In this review, we conducted a landscaping study of the therapeutic anti-influenza agents, limiting the scope by exclusion of vaccines. The resulting 2800 patent publications were classified into 23 distinct technological sectors. The mechanism of action, the promise and drawbacks of the corresponding technological sectors were explored on comparative basis. A set of quantitative parameters was defined based on landscaping procedure that appears to correlate with the practical success of a given class of therapeutics. Thus, the sectors not considered promising from the mechanistic side were also displaying low value of the classifying parameters. The parameters were combined into a probabilistic Marketing Prediction Score, assessing a likelihood of a given sector to produce a marketable product. The proposed analytical methodology may be useful for automatic search and assessment of technologies for the goals of acquisition, investment and competitive bidding. While not being a substitute for an expert evaluation, it provides an initial assessment suitable for implementation with large-scale automated landscaping.

A new rifamycin derivative 3-(4-cinnamyl-piperazinyl iminomethyl) rifamycin SV (T9) and its sodium salt (T11, Rifacinna®) were in vitro, in vivo, toxicologically and clinically investigated in comparison with rifampicin, rifapentine, rifabutin, rifalazil. Our experiments showed that Rifacinna exhibits excellent in vitro activity against Gram (+), Gram (-) aerobic, anaerobic pathogens and mycobacteria. Rifacinna is active against Staphylococcus, Streptococcus sp. including MRSA, with MIC90- 0.06 - 0.5mg/L; against Gram (+), Gram (-) anaerobes with MIC90 0.5 - 1mg/L; against Mycobacterium tuberculosis (MTB) with MIC90 0.062 mg/L; against MDR resistant MTB (25% - 30%) and Mycobacterium avium complex (MAC) strains with MICs 0.6-1.0mg/L. It shows high intraphagocytic activity against MAC strains (0.06-0.125mg/L). Single daily dose 10mg/kg provides complete erradication of mycobacteria in experimental generalized tuberculosis. Pharmacological studies established: excellent pharmacokinetic profile - following single oral dose 10mg/kg Tmax 5 - 6h, Cmax 5-9mg/L, T1/2 33-34 h; low toxicity; no teratogenic and embryotoxic effects. The clinical study of rifacinna shows higher therapeutic efficacy than rifampicin in patients with infiltrative, disseminated and cavitary form of pulmonary tuberculosis, good tolerability and safety profile. Some of the recent patents related to the treatment of tuberculosis are discussed in this review article.

Medicinal plants like pumpkin seed, thyme, onion, Nigella sativa, lemon balm, and stinging nettle are used extensively today. One of these plants used most intensively and widespread is garlic. In this context, fresh shape, powder state and oil of garlic have been used all around the world, especially in Far East for centuries. It is scientifically proven that garlic is effectively used in cardiovascular diseases as a regulator of blood pressure, with dropper effects on glycaemia and high blood cholesterol, against bacterial, viral, mycotic and parasitic infections. It's also known that garlic is a wonderful plant having the properties of empowering immune system, anti-tumour and antioxidant effects. In this article, the summary of properties of garlic and its use against bacterial diseases is given. This article is a short review of recent patents on antimicrobial effect of garlic.

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 area/targets and therapeutic agents related to anti-infective drug discovery.