Recent developments in C5/C5a inhibitors

Complement factor 5a (C5a) is formed upon complement system activation in response to infection, injury or disease. Whilst C5a is a potent mediator of immune and inflammatory processes, excessive production or inadequate regulation of C5a has been implicated in the pathogenesis of numerous immuno-inflammatory diseases, predominantly through experimental studies utilising animal models of disease. Both acute and chronic conditions may benefit from C5a inhibition, including rheumatoid arthritis, inflammatory bowel disease, asthma, psoriasis, haemorrhagic shock and neurodegenerative conditions. The potentially broad clinical application for treatments that inhibit the activity of C5a at C5a receptors and the large global market for anti-inflammatory therapeutics have made C5a and the C5a receptor attractive targets for academic and commercial drug development programmes. in the past 5 years, interest in C5a as a drug target has grown substantially, and this activity has resulted in a collection of patents and scientific papers reporting novel C5a and C5a receptor inhibitors and antagonists, and generated a secondary stream of patent applications broadly claiming the use of C5/C5a inhibitors as a method of treating various immune and inflammatory conditions. This paper will review the physiology and pathophysiology of C5a and discuss the development of C5a and C5a receptor inhibitors in light of the recent scientific and patent literature.

PARCERIA ENTRE UNIVERSIDADE E ENTIDADES EMPRESARIAIS NO GRANDE ABC PAULISTA: A INTEGRAÇÃO ENSINO-PESQUISA E A PRÁTICA EMPRESARIAL

O Brasil situa-se, no início da década de 2010, dentro de um sistema econômico mundial que apresenta características de ampla globalização dos mercados e alta competitividade das organizações que compõe esse sistema, e que sinalizam a necessidade de profissionais que sejam agentes de mudança nesses contextos dinâmicos e repletos de desafios. Na maioria dos países, a maturidade do sistema de inovação está ligada ao investimento em Pesquisa e Desenvolvimento (P&D) e ao volume de geração de Propriedade Intelectual (PI). O Brasil, apesar de apresentar um Produto Interno Bruto (PIB) concentrado nos setores de agropecuária e de serviços, revela um nível de inovação gerado pelo setor produtivo e o seu consequente investimento em P&D muito baixos em comparação com a evolução desse mesmo PIB, denotando com isso que as empresas buscam, em seus países de origem, soluções já desenvolvidas e patenteadas para seu desenvolvimento ou procuram transferir a responsabilidade de produzir registros e patentes de inovações à academia. A integração da cultura acadêmica com a cultura empresarial é capaz de gerar benefícios mútuos, melhorando a competitividade do país; em outras palavras, é uma maneira de transformar o conhecimento em riqueza. Este trabalho relacionando os conceitos ensino-pesquisa e prática empresarial pretende estudar, sob o enfoque da realidade apresentada pelos Planos Estratégicos Regionais (PER) da Região do Grande ABC Paulista e das diretrizes do Plano Nacional de Pós-Graduação 2011-2020 (PNPG 2011-2020), o processo de integração do conhecimento científico existente entre as Entidades Empresariais (E-E) e as Universidades dessa mesma região. Através da metodologia de pesquisa de estudo de caso, analisaram-se as estratégias propostas pelas universidades e a prática do setor empresarial e as possíveis barreiras apontadas como restrições às interações entre eles. Nosso estudo enfocou a análise da relação entre esses dois atores e apontou as principais barreiras para a otimização dessa parceria, tais como o acesso a recursos, o aumento da competitividade via aumento da credibilidade na relação Universidade Empresa (U-E), o reconhecimento das realidades regionais e o latente descompasso entre o pensamento acadêmico e a realidade empresarial. Além disso, constatou-se a necessidade de uma mais ampla discussão, disseminação e implementação dos documentos setoriais, regionais e nacionais que regulam, esclarecem e fornecem bases estratégicas para o desenvolvimento da relação U-E, como forma de otimização do processo de transformação do conhecimento em riqueza social.

Technological diversification within UK’s small serial innovators

This paper investigates the determinants of technological diversification among UK’s small serial innovators (SSIs). Using a longitudinal study of 339 UK-based small businesses accounting for almost 7000 patents between 1990 and 2006, this study constitutes the first empirical examination of technological diversification among SMEs in the literature. Results demonstrate that technological diversification is not solely a large firm activity, challenging the dominant view that innovative SMEs are extremely focused and specialised players with little technological diversification. Our findings suggest a nonlinear (i.e. inverse-U-shaped) relationship between the level of technological opportunities in the environment and the SSIs’ degree of technological diversification. This points to a trade-off between processes of exploration and exploitation across increasingly volatile technology regimes. The paper also demonstrates that small firms with impactful innovations focus their innovative activity around similar technological capabilities while firms that have introduced platform technologies in the past are more likely to engage in technological diversification.

The return of the Prince of Denmark: a survey on recent developments in the economics of innovation

It is well known that innovation is the engine that drives the growth machine of modern capitalist economies. Therefore, not surprisingly, substantial attention has been devoted by economists to the process behind the production of innovations. Three areas have recently emerged as relevant in the field. These are: the impact of spillovers on productivity; the different forms of R&D cooperation and the role of patents in fostering innovations when these are cumulative. In this paper I summarise the relevant literature in these three areas by discussing where the current literature stands and what are its future developments.

Gene delivery using cationic liposomes

The development of cationic liposomes for gene delivery has been ongoing for almost 20 years; however, despite extensive efforts to develop a successful therapeutic agent, there has been limited progress towards generating an effective pharmaceutical product. Since the introduction of N-(1-[2,3-dioley-loxy]propyl)-N,N,N-trimethylammonium chloride, an immense number of different cationic lipids have been synthesised and used to formulate cationic liposome - DNA complexes. Structural modification of the cationic lipids and the addition of components within the delivery system that can facilitate the fusion, cellular uptake and targeting of liposome - DNA complexes have all been used in a bid to enhance their transfection efficiency. Unfortunately, the overall impact of these improvements is still nominal, with the vast majority of clinical trials (∼ 85%) continuing to rely on more potent viral delivery of DNA despite their associated toxicity issues. Key characteristics of the most effective cationic liposomes for the delivery of plasmid DNA (from a consensus of the literature) is identified here and the problems of converting these attributes into an effective pharmaceutical product are outlined. © 2006 Informa UK Ltd.

Synthetic polymers for ophthalmic applications

The contact lens represents a well-established important class of biomaterials. This thesis brings together the literature, mostly Japanese and American patents, concerned with an important group of polymers, `rigid gas permeable contact lens materials'. A comparison is made of similarities in the underlying chemical themes, centring on the use of variants of highly branched siloxy compounds with polymerizable methacrylate groups. There is a need for standard techniques to assess laboratory behaviour in relation to in vitro performance. A major part of the present work is dedicated to the establishment of such standardised techniques. It is apparent that property design requirements in this field (i.e. oxygen permeability, surface and mechanical properties) are to some extent conflicting. In principle, the structural approaches used to obtain high oxygen permeability lead to surface properties that are less than ideal in terms of compatibility with tears. PMMA is known to have uniquely good (but not perfect) surface properties in this respect; it has been used as a starting point in attempting to design new materials that possess a more acceptable compromise of transport and surface properties for ocular use. Initial examination of the oxygen permeabilities of relatively simple alkyl methacrylates, show that butyl methacrylate which has a permeability some fifty times greater than PMMA, represents an interesting and hitherto unexplored group of materials for ophthalmic applications. Consideration was similarly given to surface modification techniques that would produce materials having the ability to sustain coherent tear film in the eye without markedly impairing oxygen transport properties. Particular attention is paid to the use of oxygen plasma techniques in this respect. In conclusion, similar design considerations were applied to an extended wear hydrogel lens material in an attempt to overcome mechanical stability deficiencies which manifest themselves lq`in vivo' but not `in vitro'. A relatively simple structure modification, involving steric shielding of the amide substituent group, proved to be an effective solution to the problem.

Food colours:a study of the effects of regulation

In the 1960s the benefits of government regulation of technology were believed to outweigh any costs. But recent studies have claimed that regulation has negative effects on innovation, health and consumer choice. This case study on food colours examines such claims. EFFECTS ON HEALTH were measured by allocating a hazard rating to each colour. The negative list of 1925 removed three harmful colours which were rapidly replaced, so the benefits were short-lived. Had a proposed ban been adopted in the 1860s it would have prevented many years exposure to hazardous mineral colours. The positive list of 1957 reduced the proportion of harmful coal tar dyes from 54% of the total to 20%. Regulations brought a greater reduction in hazard levels than voluntary trade action. Delays in the introduction of a positive list created a significant hazard burden. EFFECTS ON INNOVATION were assessed from patents and discovery dates. Until the 1950s food colours were adopted from textile colours. The major period of innovation for coal tar colours was between 1856 and 1910, finishing well before regulations were made in 1957, so regulations cannot be blamed for the decline. Regulations appear to have spurred the development of at least one new coal tar dye, and many new plant colours, creating a new sector of the dye industry. EFFECTS ON CONSUMER CHOICE were assessed by case studies. Coloured milk, for example, was banned despite its popularity. Regulations have restricted choice, but have removed from the market foods that were nutritionally impoverished and poor value for money. Compositional regulations provided health protection because they reduced total exposure to colours from certain staple foods. Restricting colours to a smaller range of foods would be an effective way of coping with problems of quality and imperfect toxicological knowledge today.

An analysis of progressive addition spectacles lens design by the use of interferometry

Progressive addition spectacle lenses (PALs) have now become the method of choice for many presbyopic individuals to alleviate the visual problems of middle-age. Such lenses are difficult to assess and characterise because of their lack of discrete geographical locators of their key features. A review of the literature (mostly patents) describing the different designs of these lenses indicates the range of approaches to solving the visual problem of presbyopia. However, very little is published about the comparative optical performance of these lenses. A method is described here based on interferometry for the assessment of PALs, with a comparison of measurements made on an automatic focimeter. The relative merits of these techniques are discussed. Although the measurements are comparable, it is considered that the interferometry method is more readily automated, and would be ultimately capable of producing a more rapid result.

Recent developments in particulate-based vaccines

Vaccines remain a key tool in the defence against major diseases. However, in the development of vaccines a trade off between safety and efficacy is required with newer vaccines, based on sub-unit proteins and peptides, displaying improved safety profiles yet suffering from low efficacy. Adjuvants can be employed to improve their potency, but currently there are only a limited number of adjuvant systems licensed for clinical use. Of the new adjuvants being investigated, particulate systems offer several advantages including: passive targeting to the antigen-presenting cells within the immune system, protection against adjuvant degradation, and ability for sustained antigen release. There has been a range of particulate vaccine delivery systems outlined in recent patents including polymer-based microspheres (which are generally more focused on the use of synthetic polymers, in particular the polyesters) and surfactant-based vesicles. Within these formulations, several patented systems are exploiting the use of cationic lipids which, despite their limitations in gene therapy, clearly offer strong potential as adjuvants. Within this review, the current range of particulate system technologies being investigated as potential adjuvants are discussed with regard to both their respective advantages and the potential hurdles which must be overcome for such systems to be converted into successful pharmaceutical products.

Future of contact lens usage

I was recently part of a small committee looking at higher qualifications in contact lens practice and the discussion turned to future technologies. There was mention of different materials and different applications of contact lenses. Drug delivery with contact lenses was discussed as this has been talked about in the literature for a while. The first paper I could find that talked about using contact lenses for drug delivery dates back over 40 years. There was a review paper in CLAE in 2008 that looked specifically at this too [1]. However, where are these products? Why are we not seeing them in the market place? Maybe the technology is not quite there yet, or maybe patents are prohibiting usage or maybe the market is not big enough to develop such products? We do have lenses on the market with slow release of lubricating agents but not therapeutic agents used for ocular or systemic conditions. Contact lenses with pathogen detectors may be part of our contact lens armoury of the future and again we can already see papers in the literature that have trialled this technology for glucose monitoring in diabetics or lactate concentration in the tear film. Future contact lenses may incorporate better optics based on aberration control and we see this starting to emerge with aspheric designs designed to minimise spherical aberration. Irregular corneas can be fitted with topography based designs and again this technology exists and is being used by some manufacturers in their designs already. Moreover, the topography based fitting of irregular corneas is certainly something we see a lot of today and CLAE has seen many articles related to this over the last decade or so. What about further into the future? Well one interesting area must the 3-dimensional contact lenses, or contact lenses with electronic devices built in that simulate a display screen. A little like the virtual display spectacles that are already sold by electronics companies. It does not take much of a stretch of the imagination to see a large electronic company taking this technology on and making it viable. Will we see people on the train watching movies on these electronic virtual reality contact lenses? I think we will, but when is harder to know.

The value of intellectual property to firms and society

Economists view intellectual property rights (IPRs) as policy tools for encouraging innovation, but they recognize that they can also inhibit competition. There are many types of IPRs and institutions concerned with their administration. We begin by outlining how these complex and varied rights are supposed to work and how they interact with other characteristics of firms and markets. We then survey the available literature on patents, trade marks, and copyright to assess the value of these IPRs to firms and the costs to firms of acquiring and defending their rights. The paper concludes with suggestions for topics requiring further research to inform public policy better.

The value of innovation:the interaction of competition, R&D and IP

This paper analyses market valuations of UK companies using a new data set of their R&D and IP activities (1989–2002). In contrast to previous studies, the analysis is conducted at the sectoral-level, where the sectors are based on the technological classification originating from Pavitt [Pavitt, K., 1984. Sectoral patterns of technical change. Research Policy 13, 343–373]. The first main result is that the valuation of R&D varies substantially across these sectors. Another important result is that, on average, firms that receive only UK patents tend to have no significant market premium. In direct contrast, patenting through the European Patent Office does raise market value, as does the registration of trade marks in the UK for most sectors. To explore these variations the paper links competitive conditions with the market valuation of innovation. Using profit persistence as a measure of competitive pressure, we find that the sectors that are the most competitive have the lowest market valuation of R&D. Furthermore, within the most competitive sector (‘science based’ manufacturing), firms with larger market shares (an inverse indicator of competitive pressure) also have higher R&D valuations, as well as some positive return to UK patents. We conclude that this evidence supports Schumpeter by finding higher returns to innovation in less than fully competitive markets and contradicts Arrow [Arrow, K., 1962. Economic welfare and the allocation of resources for invention. In: Nelson, R. (Ed.), The Rate and Direction of Inventive Activity. Princeton University Press, Princeton], who argued that, with the existence of IP rights, competitive market structure provides higher incentives to innovate.

Extra compensation for inventive employees:is our system equitable, unbiased and motivating?

There is a presumption that invention is good. It provides us with innovative goods, services and ways of doing things leading to greater employment, wealth and health. This article looks at the two recent UK cases regarding statutory extra compensation that may be awarded to employee inventors under the Patents Act 1977. Most universities worldwide and many companies have individual inventor reward schemes. Researchers now work in teams made up of both industry and academic researchers who are often based in different countries where different legal regimes apply. Is leaving the decision to award employees extra financial compensation up to individual companies unfair, unequal and de-motivating? Is having differing legislative systems in different European countries counter productive and a barrier to economic growth? There must be a balance between the inventor and the innovator. Do we have it right and if not what should it be? Legislation: Patents Act 1977 s.39 , s.40 , s.41 Cases: Kelly v GE Healthcare Ltd [2009] EWHC 181 (Pat); [2009] R.P.C. 12 (Ch D (Patents Ct)) Shanks v Unilever Plc [2010] EWCA Civ 1283; [2011] R.P.C. 12 (CA (Civ Div))

Trade marks, registered designs and the monopolisation of functional shapes:a consideration of Lego and Dyson

Legislation: Regulation 6/2002 on Community designs art.3(3)(e) Directive 98/71 on the legal protection of designs art.7(1) Cases: Dyson Ltd v Vax Ltd [2010] EWHC 1923 (Pat); [2011] Bus. L.R. 232 (Ch D (Patents Ct)) Lego Juris A/S v Office for Harmonisation in the Internal Market (Trade Marks and Designs) (OHIM) (C-48/09 P) Unreported September 14, 2010 (ECJ) *E.I.P.R. 60 In Lego, the Court of Justice of the European Union denied registration for an exclusively functional shape mark despite the availability of other shapes capable of fulfilling the same function and in Dyson v Vax Mr Justice Arnold established that a design can not be registered for a purely functional shape even though another shape could fulfil the same required function.