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- Volume 5, Issue 2, 2010
Recent Patents on Anti-Infective Drug Discovery - Volume 5, Issue 2, 2010
Volume 5, Issue 2, 2010
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The Challenges of RSV Vaccines. Where do we Stand?
Authors: Andrew Fretzayas and Maria MoustakiThe most realistic way to control RSV infection would be the development of an effective and safe vaccine. A formalin-inactivated RSV vaccine was evaluated in infants and children in the 1960's which disappointingly was linked with aggravation of RSV disease following the natural infection. Two candidate vaccines with purified protein F, have been tested, in humans and have been considered safe and somewhat immunogenic in seropositive persons providing different levels of protection against RSV re-infection. Live attenuated RSV vaccines induce local and systemic immunity without producing enhanced disease upon exposure of the vaccinee to the wild virus. Plasmid DNA vaccines were also evaluated in mice and elicited balanced systemic and pulmonary Th1/Th2 response without inducing an atypical pulmonary inflammatory reaction following the RSV challenge in cotton rats. Gene gun vaccination, a method to overcome the problem of DNA quantity, has been associated with a Th-2 biased response. Recent patents, such as plant vaccines, combined vaccines, attempted to invent new techniques for the generation of safe and effective vaccines. The new RSV vaccines should overcome many obstacles before being established as effective vaccines for the control of RSV infections especially for the young infants who are more susceptible to the virus.
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Therapy of XDR TB with Thioridazine a Drug Beyond Patent Protection but Eligible for Patent “As New Use”
Authors: Leonard Amaral and Joseph MolnarMycobacterium tuberculosis that is resistant to Isoniazid (INH) and Rifampin (Rif) and hence, multi-drug resistant (MDR) has progressed to extensive drug resistant (XDR) status. XDR strains of Mycobacterium tuberculosis (XDR Mtb) are resistant, in addition to INH and Rif, to any fluoroquinolone, streptomycin and to any of the injectable anti-TB drugs kanamycin, amikacin and capreomycin. Therapy of the XDR TB patient, even under the best conditions, is problematic and at least 20% of XDR TB patients die within one year after diagnosis. Mortality among XDR TB patients co-infected with HIV or presenting with AIDS is considerably higher reaching levels of 80% or higher. Drugs that are to prove effective against XDR Mtb must be able to reach the organism at the site where it mainly residesthe pulmonary macrophage. However, experience tells us that no matter how effective a drug may be, it will be followed by resistance. We have been able to demonstrate that thioridazine, a neuroleptic in safe use for over forty years, enhances the killing of phagocytosed Mycobacterium tuberculosis regardless of its antibiotic susceptibility profile and cure the mouse of a Mycobacterium tuberculosis pulmonary infection. Most recently, others have employed our studies for the therapy of the XDR TB patient with thioridazine and cured 10 out of 12 XDR TB patients of an XDR Mtb infection. Although thioridazine is beyond patent protection, its use for the therapy of XDR TB is new and therefore, a patent may be sought for “use as an anti-XDR TB agent”.
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Surfactant Protein (SP)-A and SP-D as Antimicrobial and Immunotherapeutic Agents
More LessSurfactant protein (SP)-A and SP-D belong to the “Soluble C-type Lectin” family of proteins and are collectively known as “Collectins”. Based on their ability to recognize pathogens and to regulate the host defense, SP-A and SP-D have been recently categorized as “Secretory Pathogen Recognition Receptors”. SP-A and SP-D were first identified in the lung; the expression of SP-A and SP-D has also been observed at other mucosal surfaces, such as lacrimal glands, gastrointestinal mucosa, genitourinary epithelium and periodontal surfaces. Since the role of these proteins is not fully elucidated at other mucosal surfaces, the focus of this article is on lung-SP-A and SP-D. It has become clear from research studies performed over a number of years that SP-A and SP-D are critical for the maintenance of lung homeostasis and the regulation of host defense and inflammation. However, none of the surfactant preparations available for clinical use have SP-A or SP-D. A review is presented here on SP-A- and SP-D-deficiencies in lung diseases, the importance of the administration of SP-A and SP-D, and recent patents and research directions that may lead to the design of novel SP-A- or SP-D-based therapeutics and surfactants.
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Topical Antimicrobials for Burn Wound Infections
Throughout most of history, serious burns occupying a large percentage of body surface area were an almost certain death sentence because of subsequent infection. A number of factors such as disruption of the skin barrier, ready availability of bacterial nutrients in the burn milieu, destruction of the vascular supply to the burned skin, and systemic disturbances lead to immunosuppression combined together to make burns particularly susceptible to infection. In the 20th century the introduction of antibiotic and antifungal drugs, the use of topical antimicrobials that could be applied to burns, and widespread adoption of early excision and grafting all helped to dramatically increase survival. However the relentless increase in microbial resistance to antibiotics and other antimicrobials has led to a renewed search for alternative approaches to prevent and combat burn infections. This review will cover patented strategies that have been issued or filed with regard to new topical agents, preparations, and methods of combating burn infections. Animal models that are used in preclinical studies are discussed. Various silver preparations (nanocrystalline and slow release) are the mainstay of many approaches but antimicrobial peptides, topical photodynamic therapy, chitosan preparations, new iodine delivery formulations, phage therapy and natural products such as honey and essential oils have all been tested. This active area of research will continue to provide new topical antimicrobials for burns that will battle against growing multi-drug resistance.
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Treatment of Severe Cases of Pandemic (H1N1) 2009 Influenza: Review of Antivirals and Adjuvant Therapy
Authors: Shivanjali Shankaran, Kara Elam and Gonzalo M.L. BearmanThree worldwide influenza pandemics were reported in the 20th century: in 1918, 1957 and 1968. All three pandemics were caused by different sub-types of Influenza A viruses: H1N1, H2N2 and H3N2 respectively. In early March 2009, the first cases of influenza-like illness (ILI) were reported from Mexico. This strain was identified as influenza A/ H1N1 strain. Pandemic (H1N1) 2009 influenza most commonly causes a self-limited illness, however, significant morbidity and mortality were reported in the young, the obese and in pregnant women. The drugs of choice for treatment and prophylaxis of pandemic (H1N1) 2009 influenza are the neuraminidase inhibitors, Oseltamivir and Zanamivir. While a few cases of Oseltamivir-resistance are reported, these isolates still retained their susceptibility to the inhaled Neuraminidase inhibitor, Zanamivir. Pandemic (H1N1) 2009 influenza virus is routinely resistant to the adamantanes: Amantadine and Rimantadine. These agents should not be used for the treatment or prophylaxis of pandemic (H1N1) 2009 influenza. The FDA recently approved the emergency use of Peramivir, an intravenous neuraminidase inhibitor, for the treatment of patients with severe influenza. We discuss the use of available antivirals, as well as the effectiveness of adjunctive therapies with immunomodulatory and anti-inflammatory agents, such as immunoglobulins and statins, for the treatment and management of patients with severe H1N1 influenza. This review summarizes the recent patents for the use of antivirals in treatment of severe influenza.
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An Augmented Passive Immune Therapy to Treat Fulminant Bacterial Infections
Authors: Gowrisankar Rajam, Jacquelyn Sampson, George M. Carlone and Edwin W. AdesIn the early 1900s, passive immunization/antibody therapy was used to treat a variety of human ailments such as hypoimmunoglobulinemia, cancer and infectious disease. The advent of antibiotic therapy had relegated this type of therapy obsolete for treatment of infectious diseases. Emergence of multi-drug resistant pathogens along with novel monoclonal antibody production techniques has rekindled the interest in passive immunization (PI). An increase in the number of monoclonal antibody patent applications in the recent past suggests a renewed commercial interest in PI. Despite these developments, antibody therapy for infectious diseases has limitations including the need for large or frequent dosages. P4, a 28-amino acid peptide is a multi-lineage cellular activator. P4, along with infectious disease (i.e., pathogen) specific immunoglobulin, has been shown in vitro and in vivo in mice to potentiate innate immunity. This review will discuss the progress made in passive antibody therapy, the challenges still to be surmounted, and the potential expanded role of an immune-potentiating peptide (bio-molecule) in the quest to utilize and revitalize passive immunization.
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Bacterial Contamination of Platelets and Septic Transfusions: Review of the Literature and Discussion on Recent Patents About Biofilm Treatment
In spite of the improvements in transfusion safety occurred in the last decades, platelet septic transfusions still represent a cause for concern. Microbial screening of blood products cannot ensure transfusion sterility, so that pathogen inactivation methods and a timely management of infectious events actually play the most relevant role. Biofilm production has been associated to several human illnesses; also, it promotes bacterial adherence to platelet bags and colonization of recipient's catheter after transfusion. Therefore, facing biofilm communities is required to reduce the contamination risk and the occurrence of post-infusion events. In this context, the use of tigecycline as a wide-spectrum antibiofilm drug is discussed, along with recent patents about biofilm treatment by quorum-sensing blockers, bacteriophage-based therapy and antibiofilm oral compounds.
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Patent Selections:
More LessThe 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 anti-infective drug discovery.
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