Patent Survey Research Articles

Lipid-based Nanocarriers for Drug Delivery and Targeting: a Patent Survey of Methods of Production and Characterization

Among the colloidal vectors proposed for the controlled delivery and targeting of drugs and other biologically active compounds, lipid-based nanocarriers are acquiring an increasing role due to a number of peculiar technological and physical features. Solid lipid nanoparticles, lipid nanocapsules, nanostructured lipid carriers, and drug-lipid conjugates are all examples of how it can be possible to combine the properties of the more acknowledged liposomal systems, such as biocompatibility and biodegradability, with the stability and compositional flexibility, distinctive of polymeric nanosystems. This article introduces recent patents, filed in years 2007-2013, that deal with novel or amended methods of production of the various types of lipid-based nanocarriers. Although a significant gap still remains between basic research and patenting activity in this field, many of the proposed methods can attain an industrial value. Furthermore, the critical analysis of these patents further supports the position that a general revision of patenting systems at an international level would be necessary for nanosized pharmaceutical systems.

Liquid mixers with magnetic stirrers (survey of patents)

Different alternatives for improving high-capacity mixers with the use of electromagnetic drives of mixing rods are considered. The advantages and shortcomings of the designs are considered.

Different Classes of CB2 Ligands Potentially Useful in the Treatment of Pain

The search of new drugs and targets to treat the pain is an intriguing challenge both for several companies and researchers from academia. In this context, since the modulation of the endocannabinoid system with the non selective phytocannabinoid Δ9-THC produces analgesia and potentiates opioid analgesia in animal models, CB2 ligands studies aimed to explore the involvement of endocannabinoid system in management of pain were started. Several selective CB2 receptor agonists exhibited analgesic activity in preclinical models of acute, inflammatory and neuropathic pain, therefore this class of modulators could be useful as analgesic agents for pain, migraine, inflammation and osteoarthritis. This review is an update of our previously manuscript "A survey of recent patents on CB2 agonists in the management of pain" and provides an overview of patents and advances in CB2 agonist studies in the treatment of pain.

Current Challenges in the Discovery of Novel Antibacterials from Microbial Natural Products

Microbial natural products have been for decades one of the most successful sources of drugs to treat infectious diseases. The high occurrence of resistances to all major classes of known antibiotics represents today a new challenge and new classes of antibacterial compounds are urgently needed to respond to this unmet clinical need. While natural products discovery programs have been gradually abandoned by big pharma, smaller biotechnology companies and other research organizations are taking the lead in the discovery of novel antibacterials. A survey of recent patents has shown that in spite of the efforts, few novel compounds are being developed that can overcome most of the emerging multi-resistant and pan-resistant pathogens. In order to respond to the current challenges of discovering novel antibiotics, new approaches are required to be developed to further exploit the microbial resources and their biosynthetic potential as an untapped source of novel metabolites. Strategies to mine microbial collections for orphan biosynthetic pathways and novel species thought to be uncultivable, are emerging as a need within antibacterial drug discovery programs, in combination with high throughput screening and chemical dereplication of novel compounds. Different innovative methods that are being developed to respond to the new challenges that are faced today by drug discovery programs will ensure the evolution of these strategies into a completely new framework that will address the renovated interest in the discovery of novel classes of antibiotics.

The a to Z of Pharmaceutical Cocrystals: A Decade of Fast-Moving New Science and Patents

From aspirin to zoledronic acid, pharmaceutical cocrystals emerged in the past decade as a promising new weapon in the arsenal of drug development. Resurgence of interest in multicomponent crystal compositions has led to significant advances in the science of cocrystal design and discovery. These advances have built upon crystal engineering, which provides a deep understanding of supramolecular interactions between molecules that govern crystal packing and physicochemical properties of crystalline materials. Concomitantly, the patent landscape of pharmaceutical cocrystals developed rapidly in the last decade. This review presents a broad survey of patents issued in the area of pharmaceutical cocrystals. In addition, the review contains analyses of key patents in the area involving compositions and methodologies. Along the way, the main events of the past decade representing a renaissance of cocrystals of pharmaceutical materials are chronicled. Future directions in the area are discussed in light of key pending patent applications and recent publications of seminal interest.

A Survey of Recent Patents on CB2 Agonists in the Management of Pain

Pain, a homeostatic and protective mechanism which can go awry in disease states and therefore needs treatment, is a complex and differentiated sensorial perception which may be classified as physiological, inflammatory and neuropathic. Chronic pain represents a major health problem throughout the world, thus several companies and researchers have embarked on the search for new drugs and targets to treat the disease. The different types of receptors in the CNS involved in the mediation of analgesia include the cannabinoid receptors: in particular, CB2 modulators seem to represent a new potential class of analgesic. This review covers recent patents and advances in CB2 agonist studies in the management of pain.

Italian patent foramen ovale survey (I.P.O.S.): Early results

Summary Background Percutaneous patent foramen ovale (PFO) closure is gaining wide acceptance. Aims of the study were to analyse clinical practice regarding PFO closure in Italy, to study indications, devices, results, and the follow-up of large series of patients treated by percutaneous PFO closure. Methods and patients Italian patent foramen ovale survey (IPOS) is a prospective, observational, multi-centric survey that uses a web-based database. The survey lasted 12 months, (November 2007–October 2008). 50 centres participated. Ongoing follow-up will continue up to 36 months. 1035 patients (m.a. 46 years, 60% females) were included in the registry. Most subjects were treated due to a previous history of TIA/ischemic stroke (∼80% of patients). PFO diagnosis and right-to-left shunt (RLS) were assessed by contrast-enhanced transesophageal (cTEE) and/or transthoracic echocardiography and/or transcranial doppler. An aneurysm of the interatrial septum was associated in 41% of patients. Intraprocedural monitoring was assessed by using cTEE and fluoroscopy in 70% and intracardiac echocardiography in 30% of subjects. Procedures were performed under general anesthesia and local anesthesia/conscious sedation in 54% and 46% of patients respectively. The most used device for PFO closure was Amplatzer (∼70% of cases). Results The procedure was successful in all patients. Early complications occurred in 24/1035 patients (2.3%): 12/24 (50%) of them had cardiac arrhythmias, 1 subject had a TIA. Data regarding both clinical and cardio-neurosonological follow-up were assessed in 444/1035 (43%) subjects. The rate of neurological events and cardiac and extra-cardiac complications were around 3% and 9% up to the 24-month follow-up respectively. A large permanent residual RLS and no RLS were observed in less than 1% and in ∼82% of patients at the 1-year follow-up, respectively. Conclusions Our data confirm that percutaneous PFO closure is a safe procedure. Early complications and those during follow-up are mostly related to arrhythmias. Longer follow-up is under way.

Trends in Nanotechnology Patents Applied to the Health Sector

The aim of the article is to present a method for identifying trends in patent applications for nanotechnology applied to the health sector around the world, based on the International Patent Classification. This classification divides the sector into: dental care, drugs, diagnostic kits, and medical apparatus & medical care. The Derwent database was mined for patent documents using nanotechnology terms associated with the IPC subclasses from the health subsectors. The number of patents was found to be rising, led by the United States, particularly universities and R centers. In the dental care subsector, nanotechnology was found to be used in composite material for manufacturing dental appliances. In drugs, the focus is on the use of nanoparticulate compositions comprising agents that are useful for a variety of diseases. In diagnostic kits, nanostructures have been patented that are capable of detecting target analytes. Meanwhile, in medical apparatus & medical care, patent applications have been made for nanocapsules and/or nanocomposite materials inserted in devices and guide catheters. A study was also made of patents in Brazil, where the same assignees and the same country (United States) as in the survey of global patents were found to be the leading patent applicants / holders.

Current Trends in β-Lactam Based β-Lactamases Inhibitors

The introduction of antibiotics to treat bacterial infections either by killing or blocking their growth has been accompanied by the development of resistance mechanism that allows the bacteria to survive and proliferate. In particular the successive series of β-lactams have selected several generations of β-lactamases including ESBLs, AmpC β-lactamases, KPC carbapenamases in Enterobacteriaceae, the metallo β-lactamases VIMs and IMPs, and very recently the threatening NDM-1 that confers resistance to virtually any clinically used antibiotic. The increasing use of carbapenems due to the spread of resistance to other existing antibacterial agents has facilitated the spread of resistance, especially in Acinetobacter spp. due to OXA- and metallo-carbapenemases. The pharmaceutical industry, that abandoned this field at the end of the nineties, is now trying to recover by developing some novel β-lactam antibiotics and novel β-lactamase-inhibitors, the latter to be used in combination with new as well as seasoned β-lactam antibiotics. This article provides a survey of patent and scientific literature for β-lactamase inhibitors discovered in the period 2006-2010.

Xanthine oxidase inhibitors: a patent survey

Introduction: Xanthine oxidase inhibitors are currently under scrutiny as attractive therapeutics for disorders such as hyperuricemia, gout, ulcers, cancer, ischemia, hypertension and oxidative damage. The fewer side effects of non-purine xanthine oxidase inhibitors, as compared to purine analogs, make them suitable for further research, which is evidenced by the fact that many articles and patents are now being published on them in the research domain.Areas covered: This review describes the patent literature covering both purine and non-purine analogs as xanthine oxidase inhibitors, up to December 2010, together with their recent highlights in pharmacology. Readers will gain an in-depth knowledge of patents covered and compounds discussed with their therapeutic use.Expert opinion: Several of the compounds which are discussed in this article have IC50 values which offer some advantages over existing molecules such as allopurinol. The available reports on X-ray crystal structures of xanthine oxidase will certainly be beneficial for the design and synthesis of novel xanthine oxidase inhibitors of diverse chemotypes.

Extraction of Volatile Oils by Supercritical Fluid Extraction: Patent Survey

This review will cover the application of supercritical of fluid extraction (SFE) for obtaining volatile oils (VOs) from aromatic, spice and medicinal plants. A brief discussion of advantages and disadvantages of SFE for obtaining these very complex mixtures of substances will be presented. The chemical profile of volatiles oils obtained by SFE will be compared with that obtained by the conventional process, that is, steam distillation. Applications of SFE to obtain clove and chamomile volatiles oils based on the LASEFI's experience will also be considered. Finally, we will successively detail the patent evolution over time involving extraction of VOs by SFE that have been claimed.

Competing Pathways for the Decarbonisation of Road Transport: A Comparative Analysis of Electric and Hydrogen Vehicles

Both hydrogen and electric vehicles (HVs and EVs) have received widespread attention as key options for decoupling road transport from the environmental and energy security risks posed by climate change and oil dependency. However, considerable uncertainty remains as to which of these technologies will succeed in the long term. This study contributes to policy debates surrounding technological change and decarbonisation in road transport by focusing on the role of evolutionary change processes in the development and commercialisation of new vehicle/fuel configurations, such as technological learning effects captured in niche markets and technology spillovers arising from unrelated sectors such as consumer electronics and power generation. The study draws on a mix of patent analysis, field research and extensive literature surveys to confirm the hypothesis that EVs have greater potential to achieve market dominance, not because of any inherent technical or environmental advantage, but because of their wider scope to link up to such evolutionary change processes. For instance, EV infrastructure can be expanded and optimised incrementally as the number of EVs grows, starting with the large number of households with adequate off-street charging facilities. In contrast, HVs require major ‘initiating’ investments in refuelling networks with few opportunities to leverage existing hydrogen infrastructure. The development of EVs also has greater potential to benefit from technological linkages to power source markets such as consumer electronics, which share a similar requirement for high energy density electricity storage, and from niche and hybrid applications such as ‘commuter’ BEVs and PHEVs, which incentivise market-driven R&D and investments in the EV mobility chain. In summary, the main factor differentiating EVs from HVs is the possibility to realise a systemic transition through small incremental steps, without the need for major decisions or infrastructure and technology developments to be made prior to commercialisation.

A Survey of Recent Patents on THz Radiation Sources

There is expanding interest in developing THz spectrum instruments for biochemical agent spectroscopy, environmental monitoring and medical imaging. This paper presents a brief review of recently published patents that target innovations for making improvements to THz radiation sources, which is one of the essential modules for building sensing and imaging systems. This analysis will summarize the novel physical aspects and/or innovative design methodology associated with each patent concept. The approaches presented include photonic crystal, ultrafast photoconductive switch, slow-wave structure, photo-mixing in piezoelectric material, stimulated Raman effect, multiquantum well multiplier, and Josephson Junction device.

5-HT2C receptor modulators: a patent survey

Importance of the field: The 5-HT2C receptor is a GPCR and is one of the 14 subtypes that constitute the serotonin receptor family. The 5-HT2C receptor is exclusively expressed in the CNS where it demonstrates a wide distribution and displays high-affinity interactions with a wide variety of psychiatric medications. Modulators of 5-HT2C have been implicated as a potential treatment for diseases of significant unmet medical need, including obesity, schizophrenia, depression, anxiety, Parkinson's disease, drug addiction, erectile dysfunction and urinary incontinence. Thus, there is a great interest in developing potent and selective 5-HT2C receptor modulators.Areas covered in this review: This review article highlights the research progress in 5-HT2C receptor modulators published in the patent literature between January 2003 and June 2010, giving emphasis to the medicinal chemist's standpoint.What the reader will gain: Readers will rapidly gain an overview of the various 5-HT2C receptor modulators reported in the patent literature in the past 8 years. Furthermore, the readers will learn which structure type can interact with the 5-HT2C receptor. In addition, the readers will be aware of the pharmaceutical companies that have been the main players in the field.Take home message: There is substantial evidence supporting the concept that a selective 5-HT2C receptor modulator should provide benefit in the treatment of a variety of CNS disorders. Although research efforts have identified several promising 5-HT2C receptor modulators that display high functional selectivity, further clinical efficacy and safety data are needed to prove their actual clinical utility. Therefore, the query for selectively acting 5-HT2C receptor modulators is still ongoing.

Update on lymphocyte specific kinase inhibitors: a patent survey

Importance of the field: Lck (p56lck or lymphocyte specific kinase) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence from knockout mice and human mutations demonstrates that Lck kinase activity is critical for T cell receptor (TCR)-mediated signaling, leading to normal T-cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection.Areas covered in this review: This review covers the patents, patent applications and associated publications for small molecule kinase inhibitors of Lck since 2005 and attempts to place them in context from a structural point of view.What the reader will gain: Readers will gain an overview of the structural classes and binding modes of Lck inhibitors, the major players in this area and an insight into the current state of the field.Take home message: The search for a potent and orally active inhibitor of Lck has been an intense area of research for a number of years. Despite tremendous efforts, the identification of a highly selective and potent Lck inhibitor suitable for use as an immunosuppressive agent remains elusive.

The expanding role of H1 antihistamines: a patent survey of selective and dual activity compounds 2005 – 2010

Importance of the field: Histamine plays a key role in physiological processes through its interaction with H1 – 4 histamine receptors. The H1 receptor is a key element in the pathophysiology of allergic responses. H1 antihistamine use is a key strategy for therapy in allergy.Areas covered in this review: Several new chemical entities with improved efficacy in allergic disease have been pursued. Addition of multiple antagonist activities in single compounds has been the focus of current research. Involvement of the H1 receptor in sleep has led to the evaluation of new compounds as sedative hypnotics.What the reader will gain: In all, 57 patents detail the evolution of new chemical entities. Dual H1–CC-chemokine receptor-3 and H1 – H3 antagonists have entered the clinic for allergic indications. Efforts to develop H1 antihistamines as sedative hypnotics have increased, with several compounds entering the clinic. The dual H1–5-HT2A antagonist doxepin has been approved for sleep disorders while another compound is currently in clinical trials.Take home message: The development of multiple activity H1 antihistamines in allergy has met with limited success due in part to a competitive commercial environment. New sedative hypnotics may show potential but will need to demonstrate significant benefits in an increasingly competitive landscape.

Novel GABAB receptor positive modulators: a patent survey

Importance of the field: Positive allosteric modulators of GABAB receptors may have a similar potential as positive modulators of GABAA receptors, the benzodiazepines discovered in 1957. The discovery of positive allosteric modulators of GABAB receptors at Novartis in Basel in 2000 opened the way to search for compounds, which activate GABAB receptors without the drawbacks of full agonists, such as desensitization, tolerance, muscle-relaxant effects, hypothermia, and central and gastrointestinal side effects.Areas covered in this review: Numerous animal experiments point out that several indications can be addressed with positive modulators of GABAB receptors, such as depression, anxiety, schizophrenia, neuropathic and chronic pain and treatment of craving for drugs of abuse, such as alcohol, cocaine and nicotine. Peripherally acting compounds may be valuable drugs for the treatment of gastroesophageal reflux disease and irritable bowel syndrome.What the reader will gain: An overview on 19 patents in this field, of the different scaffolds for positive modulators of GABAB receptors and of the major players in the field.Take home message: The search for subtype selective benzodiazepine receptor ligands has proved to be extremely difficult. Positive modulators of GABAB receptors may provide novel anxiolytic drugs faster.

Negative Thermal Expansion Materials and Their Applications: A Survey of Recent Patents

Most materials expand on heating and contract on cooling. However, an increasing number of materials with negative thermal expansion (NTE) have been discovered in recent years. In this article, we review the patents related to the synthesis and applications of several important families of negative thermal expansion materials. Particular attention has been paid to the families of NTE materials with open framework structures consisting of corner-sharing polyhedra that are relatively rigid but flexible in rotation such as A(MO4)2 (A=Zr, Hf or combinations of them; M=W, Mo or combinations of them), A4+P2O7 (A is an element with valance of +4, A and P can also be partially replaced by other elements with charge balance), A2(MO4)3 (A=Sc, Y, Al, Lu etc. and may be partially substituted by other elements) and Zr2P2WO12, Ca1-xMxZr4P6O24 (M= Sr, Ba, Mg). Some patents with the family of NTE materials with a framework structure consisting of relatively soft polyhedra connected by stiff cyanide bridges such as Zn(CN)2 and Cd(CN)2, etc. and the family of the NTE materials of perovskite manganese nitrides whose NTE is driven by magnetovolume effect are also involved. The most important applications of the NTE materials are to compensate for undesired positive expansion of other materials, creating ceramics, composites or devices with controllable overall negative, zero or positive coefficient of thermal expansion. The patents related to these applications are reviewed. Some problems existing with particular materials or applications are commented. Keywords: Negative thermal expansion materials, negative thermal expansion ceramics, composites, low thermal expansion materials, zirconium tungstate, zirconnium molybdate, pyrophosphates, pyrovanadates, rare earth tungstate, rare earth molybdate, zirconium phosphate tungstate, sodium zirconium phosphate, zinc dicyanide, cadmium dicyanide, alkaline earth zirconium phosphates, perovskite manganese nitride

Negative Thermal Expansion Materials and Their Applications: A Survey of Recent Patents

Negative Thermal Expansion Materials and Their Applications: A Survey of Recent Patents

Novel technologies for the prevention and treatment of dental caries: a patent survey

Importance of the field: Dental caries is one of the most common preventable childhood diseases; people are susceptible to this ailment throughout their lifetime. In the US, 90% of late adolescents and young adults have dental caries, while 94% of all dentate adults had evidence of treated or untreated coronal caries. Dental caries is often not self-limiting and without proper care can progress until the tooth is destroyed.Areas covered in this review: In this paper, the etiology of dental caries is briefly introduced. It is followed by a thorough review of patents and literatures on the recent development of various novel technologies for the prevention and treatment of dental caries.What the reader will gain: Recent advances in anti-plaque agents, including chemoprophylactic agents, antimicrobial peptides, vaccines, probiotics/replacement therapy and sugar substitutes, and remineralization agents including fluorides and casein phosphopeptides are analyzed.Take home massage: Both the discovery of new anti-caries agents and the development of dentotropic delivery systems will be the future focus of this research field.