Recent Patents on Anti-Infective Drug Discovery (v.7, #2)

Background: Maxillofacial and head & neck infections often jeopardize patients' lives. Regional intracranial spread to the cavernous sinus, but also to the mediastinum is common for those left untreated. The divergence of the upper peptic and respiratory tracts from the pharynx, the presence of the brain vasculature, the fine sensory instruments for vision, hearing and taste-smell, and the unique feature of mucosa directly attached to facial bones in the paranasal sinuses, oral cavity and external auditory meatus make this region the most exposed to infections in the human body. Special immune mechanisms have evolved in this area, however infections are still very common. Methods & Results: We review the unique pathophysiological features of maxillofacial and head & neck infections. We describe novel investigational anti-infective agents, and analyze their potential clinical utility with regard to mechanisms of action and site preference. Discussion: We emphasize on the need for more antimicrobial drug research and discuss on the current skews in pharmaceutical research and manufacturing practices that make new categories of antimicrobial drugs an exceptional entity. Drug patents may need to be expanded both longitudinally in terms of time period but also squarely, potentially including the drug class in the patent rather than the drug itself. Clinicians need to be aware of these limitations and prescribe antibiotics to their patients with parsimony.

Tyrosine kinase inhibitors (TKIs) have dramatically improved the outcome of renal cell carcinoma (RCC) patients. The use of these agents requires early and appropriate management of side effects such as hematologic adverse events (HAE), in order to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations. Beyond the increased infective risk, myelosuppression contributes to TKI-related fatigue, thus reducing both patients’ quality of life and overall survival (OS). However, the frequency and severity of myelosuppression vary among sunitinib, sorafenib, pazopanib and axitinib, based on their different kinase selectivity. Their activity against fms-related tyrosine kinase 3 (FLT3 or CD135) and c-kit, which are essential for survival and differentiation of hemopoietic progenitor cells, is critical to determine the hematologic toxicity profiles. This review describes the molecular mechanisms underlying the TKI effects exerted on hematopoiesis and immune response and related recent patents, of drugs already approved or still under evaluation in RCC, highlighting the potential impact of these effects on tumor response to treatment.

The antimicrobial effects of free fatty acids are well recognised and these compounds can prevent the growth of or directly kill bacteria, fungi and other microbes by affecting multiple cellular targets, including the cell membrane and components found therein. Moreover, fatty acids exert detrimental effects on microbial pathogens by interfering with mechanisms of virulence, such as preventing biofilm formation and inhibiting the production of toxins and enzymes. The antimicrobial properties of free fatty acids can be exploited for the preservation of perishable products, such as food and cosmetics, and for the prevention and treatment of infections. These safe natural products are particularly useful in circumstances where antimicrobial activity is required but where the use of conventional antibiotics is undesirable or forbidden. This review focuses on the most promising prospects for exploiting the antimicrobial properties of free fatty acids for applications in various industries. The benefits of using fatty acids as antimicrobial agents are discussed and relevant recent patents are highlighted.

Herbal products have gained considerable interest among the pharmaceutical companies and consumers due to the minimal side effects associated with them. The bioflavanoids present in these products are the key players in modulating their effects. Several therapeutic effects have been attributed to the bioflavanoids present in green tea and turmeric. Antimicrobial activity is one among the spectrum of activities they exhibit. Curcumin and catechins, the principle components of turmeric and green tea respectively have virucidal and virustatic actions. An antimicrobial composition consisting of extracts from green tea and turmeric have shown to be highly potent against various microbes, especially viruses. In the present review, we have discussed the patents and the antiviral effects of curcumin and catechins. The antimalarial effect of curcumin has also been discussed.

Essential oils derived from aromatic plants possess useful properties concerning human health, such as antibacterial, antiviral and antifungal activities. They can be used as natural alternatives to synthetic preparations to prevent and treat infectious diseases caused by multidrug resistant microorganisms. They are used successfully to treat respiratory tract, digestive system and skin infections. Many of them may be applied in anticancer therapy, cardiovascular and nervous system disorders, as well as to reduce the level of cholesterol and decrease and regulate the glucose level. Due to their ability to stimulate adrenal and estrogen hormone production and their antimicrobial properties, they are useful in the treatment of gynecological diseases. Oils are commonly used in the food and cosmetic industry. The present paper describes recent patents concerning potential uses of essential oils in human health and treatment of diseases.

A number of recent studies revealed that successful treatment of the patients with MDR/XDR- TB was not achieved due to high resistant rates to many second-line drugs such as kanamycin and prothionamide including poor adherence of the lengthy treatment. Many new drugs and compounds such as benzothiazinones, meropenem, PA-824, isoflavonoids, rhein, PNU-100480, TMC207, SQ109, OPC-67683, AZD5847, and linezolid are currently in development pipeline. According to very few patents in new compounds and drugs against MDR/XDRMycobacterium tuberculosis bacilli have been currently introduced, so inventors must be encouraged to contribute to this area worldwide.

Clostridium difficile infection (CDI) has emerged as a significant challenge to the healthcare system. The availability of anti-cancer chemotherapeutic regimens has contemporaneously resulted in a larger population of patients who are susceptible to CDI. The outbreak of a novel, hypervirulent, resistant strain, NAP-1/027 as well as resistance to antibiotic therapy have further contributed to an increase in prevalence as well as in disease severity. Recent data show high fatality rates in cancer patients with CDI. In this review, we have discussed the incidence, epidemiology, pathophysiology, clinical signs and symptoms and therapeutic guidelines for patients who are on chemotherapy and present with CDI and highlighted clinical reports documenting severe CDI associated with chemotherapeutic agents such as methotrexate, 5FU, cisplatin, carboplatin, paclitaxel, vinorelbine and cyclophosphamide. The review article also has the discussion of patents pertaining to infections caused by Clostridium difficile in cancer patients. We underscore the urgent need for early recognition and diagnosis of CDI in cancer patients and for the design and implementation of randomized clinical trials of new treatment modalities in the management of chemotherapy- associated CDI.

Patent Selections: by Bentham Publishers (171-172).
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.