Biotechnology Start-up Companies Research Articles

In the business of base editors: Evolution from bench to bedside.

With the advent of recombinant DNA technology in the 1970s, the idea of using gene therapies to treat human genetic diseases captured the interest and imagination of scientists around the world. Years later, enabled largely by the development of CRISPR-based genome editing tools, the field has exploded, with academic labs, startup biotechnology companies, and large pharmaceutical corporations working in concert to develop life-changing therapeutics. In this Essay, we highlight base editing technologies and their development from bench to bedside. Base editing, first reported in 2016, is capable of installing C•G to T•A and A•T to G•C point mutations, while largely circumventing some of the pitfalls of traditional CRISPR/Cas9 gene editing. Despite their youth, these technologies have been widely used by both academic labs and therapeutics-based companies. Here, we provide an overview of the mechanics of base editing and its use in clinical trials.

Exploring the cutting edge in RNA-based cell line selection

<div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://bioinsights.blob.core.windows.net/uploads/Susan Shafstein head shot 2017 copy.jpg" data-image="1"></div><div class="author-det"> <b>Susan Sharfstein</b> is a Professor of Nanobioscience at SUNY Polytechnic Institute in Albany, New York. Professor Sharfstein received her BS in chemical engineering with honors from Caltech in 1987 and her PhD in chemical engineering from UC Berkeley in 1993. She received an NIH fellowship to pursue postdoctoral studies, initially at UC Berkeley and subsequently at UCLA Medical School. Dr Sharfstein joined the faculty at the University of Toledo in Bioengineering in 1996. In 2001, she joined the Department of Chemical and Biological Engineering at Rensselaer Polytechnic Institute. In 2010, she joined the faculty at SUNY Polytechnic Institute. Professor Sharfstein’s research interests include mammalian and microbial cell bioprocessing, control of protein glycosylation, metabolic engineering, biosensing, and development of systems for high-throughput screening. She is the author of over 70 papers and book chapters in the fields of biotechnology and bioprocessing. </div></div></div><div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://bioinsights.blob.core.windows.net/uploads/Tenenbaum copy.png" data-image="1"></div><div class="author-det"> <b>Scott Tenenbaum</b> is the Head of Nanobioscience and the Laboratory of RNA Nanotechnology at the College of Nanoscale Science and Engineering at the SUNY-Polytechnic Institute. He received his PhD in Microbiology and Immunology from Tulane University Medical Center and did his post-doctoral training at Duke University Medical Center, where he helped pioneer RIP-Chip/Seq technology and the field of ‘Ribonomics’, which is the genomic-scale study of post-transcriptional gene regulation. Dr Tenenbaum holds 19 issued or pending patents which have served as the basis for 4 biotechnology start-up companies including his most recent, sxRNA Technologies, Inc. in the NY Capital Region. He has been awarded numerous honors, including The Judith Graham Pool Fellowship, The James A. Wilson, M.D. Fellow in Cancer Award; The Robert M. and Barbara R. Bell Basic Science of Cancer Award; The SUNY Golden Apple Teaching Award; The SUNY-Research Foundation Rising Star Award; and most recently, The SUNY Excellence in Research Award. Dr Tenenbaum has had numerous NIH and NSF grants, maintaining continuous federal funding since 2004. The focus of his research lab is RNA and RNA-binding proteins and he is currently developing an RNA ‘nano-switch’ platform technology called sxRNA to be used as a molecular tool, a diagnostic and as a therapeutic. </div></div></div>

How Should Start-Up Biotechnology Companies Manage Learning and Generate the Necessary Knowledge to Achieve an Alliance-Based Stage of Growth

Ethical drugs can take hundreds of millions of dollars and over 10 years to bring to market. Start-up biotechnology companies are recognized for their unique exploration and then exploitation in the development of future drugs. However, these potential new drugs are highly unpredictable and require a broad scope of inquiry. Significant and complex knowledge along with openness to learning is required because of the unusually high risk and uncertainty of biotechnology. After initial start-up, biotechnology companies often form a strategic partnership with an established pharmaceutical company to get additional funding and incorporate needed later stage development knowledge.&#x0D; To conclude an alliance, a company needs to develop learning processes that transition the organization to the next stage of growth. These processes advance the technology sufficiently to conclude a strategic deal. Effective learning enhances exploitation of knowledge needed to generate unique insights and understandings related to the development of a new drug.&#x0D; This paper examines seven biotechnology companies and identifies key processes that should optimize “effective learning” to enhance the probability of creating the necessary new knowledge needed for a start-up to achieve an alliance stage of growth. Despite a majority of the companies successfully reaching the scaling-up stage of growth, some ultimately fail due to a lack of one or more the explored factors.&#x0D;  &#x0D;  

Special feature: BioZone Leader Announcements 2017

BioanalysisVol. 9, No. 16 Special featureFree AccessSpecial feature: BioZone Leader Announcements 2017Amy Craddock & Sankeetha NadarajahAmy Craddock Future Science Group, Unitec House, 2 Albert Place, London N3 1QB, UKSearch for more papers by this author & Sankeetha Nadarajah Future Science Group, Unitec House, 2 Albert Place, London N3 1QB, UKSearch for more papers by this authorPublished Online:25 Aug 2017https://doi.org/10.4155/bio-2017-4987AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Bioanalysis Zone, the sister site of the journal Bioanalysis and online resource for the bioanalytical community is delighted to present its Zone Leaders for 2017. The Zone Leaders consists of key international figures within the bioanalytical community, who provide their expertise to help direct content for Bioanalysis Zone.The Zone Leaders act as an advisory expert panel and help promote open scientific dialogue by leading and encouraging discussion on the latest key topics in the field. You can view the Zone Leaders profiles below. To find out more about the Zone Leaders and what work they have done, please visit: https://bioanalysis-zone.com/zone-leaders/ Melanie AndersonMelanie Anderson is Principal Scientist at Merck Research Laboratories and runs a small group in the Clinical Regulated Bioanalysis Space. Melanie has over 15 years experience in both Pharma and CRO settings conducting LC–MS/MS analysis for quantitation of small molecules and peptides. Melanie has participated in US FDA inspections and contributed to regulatory filings. Additionally, Melanie has experience in noncompartmental pharmcokinetic analysis of atypical compounds.She received her BA in chemistry from Hastings College in 2002 and an MS in chemistry from Lehigh University in 2007. Melanie's scientific interests include analysis of unique matrices, unstable compounds, challenges in chromatographic separations and at-home microsampling approaches for regulated clinical trials. Recently, Melanie has evaluated and helped implement microsampling devices in animal- and human-regulated studies.Chad BriscoeChad Briscoe received his Bachelor of Science degree in chemistry from Alma College in Michigan and a Master's degree in analytical chemistry from the University of Michigan with a focus on the use of LC–MS/MS in protein and peptide analysis. Chad's Doctorate of Philosophy at the University of Nebraska was focused on studies of protein binding via affinity LC–MS/MS and computer simulations.Chad is currently the Executive Director of Bioanalytical Science at PRA. He was previously the Director of Bioanalysis at the Lincoln site of MDS Pharma services. He has become well known in the bioanalytical community on diverse issues such as the use of advanced LC–MS/MS technology applied to high-throughput analysis, system suitability in high-throughput LC–MS/MS and bioanalytical software validation. He has recently been an invited speaker at the Land O’ Lakes Bioanalytical Conference, the Applied Biosystems ASMS User's Meeting and the Boston Society's APA and APS Meetings. Recently, Chad was also the chair of the Global Bioanalysis Consortium's Analytical Instrument Qualification Team and the column editor for the Journal of Bioanalysis column, Management and Leadership. Chad was previously with Dow Corning where he specialized in LC–MS/MS techniques and high-resolution MS and GC solutions. He is also on the planning committees and has been a past chairperson for the Land O Lakes Bioanalytical Meeting, Clinical and Pharmaceutical Solutions Through Analysis Meeting and the Boston Society's Applied Pharmaceutical Software Meeting.Stephanie CapeStephanie Cape is the Associate Director of Bioanalytical Scientific Operations at Covance (WI, USA). She received her BS in chemistry from University of IL-Urbana/Champaign in 2003 and her PhD in analytical chemistry from the University of Wisconsin-Madison in 2007. Dr Cape's graduate research was focused on developing high-resolution mass spectrometric methods to enable discovery, characterization, imaging and quantitation of neuropeptides.Stephanie joined the field of regulated bioanalysis as a method development/validation chemist, initially at PPD and subsequently at Covance. Within the Covance Bioanalytical team, she has held a variety of leadership roles including oversight of bioanalytical study direction, validation and method development. Additionally, Stephanie serves as the primary operational lead for on-site regulatory inspections and participates in aligning global standard operating procedures and best practices to industry standards.Timothy GarrettTimothy Garrett earned his Bachelor's in chemistry from the University of Georgia (GA, USA) in 1999. After working in industry for a couple of years, he returned to school for graduate study at the University of Florida (FL, USA) where he became a Doctor of Philosophy in 2006. Dr Garrett then translated to an assistant professor position in the College of Medicine at the University of Florida, and assumed operations at the Biomedical Mass Spectrometry facility. He has focused his work on expanding the use of MS in clinical sciences through education, analysis and collaboration.At present, Dr Garrett has collaborated with over 30 faculty members at the University of Florida. Dr Garrett is currently Assistant Professor in the Department of Pathology, Immunology and Laboratory Medicine at the University of Florida. He is the Director of the high-throughput MS metabolomics core of the Southeast Center for Integrated Metabolomics and works closely with University of Florida PathLabs to grow and expand MS services for diagnostics.Thomas HammondThomas Hammond graduated in 2006 with a BSc in pharmacology from the University of Newcastle upon Tyne (UK). Following a year of working in industry at both AstraZeneca and Ferring Pharmaceuticals, Tom returned to academia to undertake both his MRes and PhD. Under the guidance of Dr Dominic Williams and Professor Kevin Park at the MRC Centre for Drug Safety at the University of Liverpool and Gerry Kenna of AstraZeneca, Tom spent the majority of his MRes investigating the role of Kupffer cells in drug-induced liver injury. Upon progression to his PhD, Tom's research focus developed into investigating the interaction of acyl glucuronide metabolites of carboxylic acid drugs with protein. This work culminated in the first mass spectrometric identification of acyl glucuronide metabolites covalently bound to human serum albumin isolated from patients receiving diclofenac therapy. This finding reinforces anxiety over acyl glucuronidation as a metabolic pathway of toxicological consequence.Tom's other research interests throughout his PhD included pharmacokinetics (PK) and the utility of continuous intravenous drug infusion models in preclinical toxicology. Following completion of his PhD, Tom won a Postdoctoral Fellowship award from the International Fellowship Program on Integrative Kidney Physiology and Pathophysiology allowing him to undertake a position under the guidance of Professor Alex Odermatt. In this position, Tom's research focuses primarily on the utility of untargeted mass-spectrometric serum proteome profiling to understand mechanisms responsible for the development of vascular calcification in chronic kidney disease patients, and development of targeted mass-spectrometric methods for the quantification and validation of potential biomarkers of renal injury.Martijn HilhorstMartijn Hilhorst studied analytical chemistry at the University of Amsterdam followed by a PhD period at the University of Groningen (both in The Netherlands) where he developed strategies for the determination of impurities in drugs using electrokinetic separation techniques. After a 6-month postdoctoral position in the field of therapeutic drug monitoring with LC–MS/MS, he worked as a research scientist in the field of lab automation, drug discovery and proteomics for over 6 years. Martijn is now active for 12 years in bioanalysis and is currently leading a group of scientists responsible for the development of bioanalytical LC–MS/MS methods. He is a (co)-author of several publications and speaker on international conferences.Fan JinFan Jin joined Covance China as Director of Bioanalytical Chemistry in 2008. She is responsible for LC–MS/MS group and immunochemistry group within the Bioanalytical lab. Fan led a group of scientists and set up the GLP-compliant bioanalytical process in China. As Test Facility Management of Bioanalytical Lab, she helped host several regulatory inspections including OECD, MHRA and CFDA GLP inspections. Fan is also an active member of Covance Global Bioanalytical Leadership Team.Fan has over 11 years of experience with pharmaceutical companies and 11 years with CROs. Before joining Covance, Fan was the VP of Operations at a small US CRO in Shanghai, where she managed the operations and growth of laboratory including bioanalytical chemistry, pharmaceutical analysis and formulation development. Additionally, Fan has worked at Pfizer global R&D in (CT, USA) and (CA, USA) for 11 years with increased responsibilities. Fan has new drug development experience and excellent working knowledge in managing operations in China.Fan has an MS in Chemistry from University of Massachusetts at Boston. She also has an MS from the School of Public Health, Harvard University.Rafael LucenaRafael Lucena is Professor of Analytical Chemistry at the University of Córdoba (Spain). His research is mainly focused on microextraction techniques and the role that nanoparticles and composites may play in analytical chemistry. He has co-authored 80 scientific articles, three book chapters and he has edited one book and a special journal issue dedicated to the topic. He is also engaged with science divulgation. In fact, he is the editor of Microextraction Tech blog and collaborates with several resources.Robert MacNeillRobert MacNeill received his Bachelor's degree with Honors in chemistry from Heriot Watt University (Edinburgh) and then his MSc in analytical chemistry from the University of Huddersfield, both in the UK. Robert is also a Chartered Chemist and Member of the Royal Society of Chemistry. With 20 years of experience in all aspects of quantitative bioanalytical LC–MS/MS method development; 11 of these years were spent in heading method development activities within HLS/Envigo and a regular author and peer reviewer for the journal Bioanalysis, Robert is a recognized expert and innovator in the field.In his current role Robert coordinates all LC–MS/MS method development and associated trainings, takes the lead in keeping abreast of innovation and technological development in the industry, leads in-house research projects and performs technical writing for the purpose of producing publications.Roland MeestersRoland Meesters earned his PhD degree at the Erasmus University Rotterdam, The Netherlands. During his doctorate, he studied the ‘Application of MALDI-triple quadrupole mass spectrometry for the quantification of small molecules in biomedical research’. He holds the post of Adjunct Professor of Analytical Chemistry at the Los Andes University in Bogota DC, Colombia and is a senior lecturer of analytical and general chemistry at Inholland University of Applied Sciences in Amsterdam, The Netherlands.He is responsible for teaching bioanalytical chemistry and other chemistry related courses. The focus of his research is on bioanalytical sciences where he has a strong interest in metabolomics, therapeutic drug monitoring and PK modeling and in the role of metabolites in biological processes and in diseases. He is editor of the peer-reviewed open access Journal of Applied Bioanalysis. He has published approximately 40 peer-reviewed articles in the last years.Laura MercoliniLaura Mercolini is Assistant Professor in Medicinal Chemistry at the University of Bologna, Italy since 2012 and is the Head of the Pharmaco-Toxicological Analysis Laboratory at the Department of Pharmacy and Biotechnology. Her research activity deals with the development of innovative strategies for the analysis of psychotropic compounds in biological and nonbiological samples. She has published more than 60 peer-reviewed papers, one patent and given approximately 160 communications to national and international events, meetings and schools. She graduated with Master's degree in chemistry and pharmaceutical technologies and got PhD in pharmaceutical sciences at the University of Bologna.Marco MichiDr Marco Michi (Master's degree in analytical and physical chemistry) is a technology leader and Scientific Officer at Aptuit Verona, Italy. He has 15 years of bioanalysis experience working for pharmaceutical and CRO companies. During these years, he mainly worked in quantitative determination of small molecules in a regulatory environment. In his actual position, he has the responsibility of the implementation of new technologies, problem solving, regulatory compliance and scientific overview. He defines the best bioanalytical processes, the new instrumentation to be purchased and new strategic investments. He is also experienced in computer system validation and has designed and implemented a LIMS bespoke application liaising QA and IT departments.James MundayJames Munday gained his DPhil at the University of Oxford, UK, working in the field of cellular and molecular immunology. He then went on to do his postdoctoral studies at the Mount Sinai School of Medicine (NY, USA) where he published his work on transcription factor regulation of hematopoiesis and vasculogenesis. Following on from his academic career, he moved into industry posts at Celltech, UCB and Quotient Bioresearch. His current role is Senior Scientific Director at Covance where he has extensive experience of supporting large molecule drug development programs with a variety of analytical assays for assessing PK, ADA, PD and biomarkers. James has had an active role in European bioanalysis forum working with other members to seek alignment on a broad array of bioanalytical topics including science, procedures, business tools and technology and regulatory issues.Stephanie Pasas-FarmerDr Stephanie Pasas-Farmer is the President and Founder of BioData Solutions, LLC, a consulting firm that offers R&D, regulatory and commercial consulting services to early stage pharmaceutical and biological drug development organizations in the field of bioanalysis. Their services include operational program management, data review and analysis, regulatory compliance planning, in addition to market development guidance. She specializes in discovery and regulated bioanalysis of pharmaceuticals, biologics, biosimilars and the hybrid technology antibody–drug conjugates. She brings extensive expertise in both quantitative and qualitative bioanalysis using various bioanalytical techniques including LC–MS/MS and ligand-binding assays, among others.With more than 13 years of bioanalytical chemistry and DMPK experience, Dr Pasas-Farmer has held a range of scientific, business management and operational leadership positions across contract research and global pharmaceutical organizations as well as a start-up biotechnology companies. Most recently, she served as Senior Director of Biologics Services for Frontage Laboratories where she led a team of scientists focused on the support of large molecule and antibody drug conjugate programs using LBA, LC–MS/MS and cell-based assays. Previously, she was Director of client services at Frontage. In this role, she served as a key liaison between clients and bioanalytical operations, holding responsibility for technical feasibility, proposal development and client support needs.Earlier career roles included management responsibility for quality control functions of bioanalytical laboratory operations in addition to business development and research scientist positions. Dr Pasas-Farmer earned her Doctor of Philosophy and Master of Science degrees with honors in pharmaceutical chemistry from the University of Kansas (KS, USA). She received Bachelor of Science degree in chemistry from St. Mary's College of Notre Dame, France.Dr Pasas-Farmer is a frequent contributor to peer-reviewed publications and industry conferences on current bioanalytical and pharmaceutical industry topics. In addition, she has taken on steering committee and leadership positions for multiple professional and scientific conferences (Chair of Regulated Session APA 2017, Chair-elect of Land O'Lakes 2019).Tim SangsterTim Sangster is a well-travelled bioanalytical chemist having worked in Scotland, Italy, England, America and finally back to Scotland to head up the bioanalysis and immunology department for Charles River, Edinburgh 8 years ago. During his travels, he has gained experience in both CROs and pharmaceutical companies supporting drug development from a bioanalytical perspective from discovery through to market.Currently Tim's main scientific focus is in the use of microsampling to reduce and refine toxicology study designs as well as applying it to other application areas and also the use of LC–MS in the analysis of macromolecules.Scott SummerfieldHaving studied for PhD and postdoctoral fellowship in proteomics, Scott Summerfield moved into the field of regulated bioanalysis in 1997 when joining SmithKline Beecham. In 2001, he moved to Neuroscience Drug Discovery to lead a bioanalytical team supporting PK, in vitro DMPK and metabolite identification work. In 2009, he returned to the regulated bioanalytical group, initially as a section leader and subsequently as site head and currently as WW Head of Bioanalysis at GlaxoSmithKline (GSK).Scott has experience of small and molecule bioanalysis as well as leading both bioanalytical and discovery and development project teams across GSK.Amanda WilsonAmanda Wilson is the Director and GLP Test Facility Manager for the preclinical bioanalysis and toxicokinetics department in the drug safety and metabolism function at AstraZeneca. Amanda started her career in the 1990s as a bioanalytical scientist at Fisons Pharmaceuticals and has spent over 20 years in the pharmaceutical industry working in a variety of DMPK disciplines supporting both small and large molecule projects. Amanda has managed DMPK multidisciplinary teams delivering data for regulatory submission and as a former Director in Clinical Pharmacology and DMPK, Amanda ran a team delivering GLP/GCP bioanalytical data to early-phase projects. Amanda, in her current role, has the responsibility for the delivery of bioanalysis data and toxicokinetic evaluation for non-GLP investigational toxicology and pivotal (GLP) toxicology examination of small molecules and nucleotide therapeutics. Amanda's team, based in the UK and Sweden, employ analytical endpoints including LC–MS/MS and ligand-binding technologies and oversee the externalization of preclinical bioanalytical projects throughout the project lifecycle. The bioanalysis and toxicokinetics team also provides scientific and regulatory compliance guidance to the AZ externalization in the clinical development functions.Eric J WoolfDr Eric Woolf currently directs the Clinical Regulated Bioanalysis Group of Merck Research Laboratories (PA, USA). He received his BA in chemistry from LaSalle College in 1982 and PhD in analytical chemistry from Seton Hall University in 1986. From 1986 to 1990 he was a member of the Drug Metabolism/PK department of Berlex Laboratories. He joined Merck Research Laboratories in 1990 as a research fellow. Dr Woolf and his group have supported numerous clinical development projects that have led to the successful registration of Merck compounds. Since 1986, he has authored or co-authored over 50 research papers pertaining to bioanalysis and PK. His major research interests include the utilization of novel HPLC approaches in bioanalysis and the bioanalysis of unstable compounds.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.No writing assistance was utilized in the production of this manuscript.FiguresReferencesRelatedDetails Vol. 9, No. 16 Follow us on social media for the latest updates Metrics History Published online 25 August 2017 Published in print August 2017 Information© 2017 Future Science LtdFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Variants of Epistemic Capitalism

Capitalist dynamics in knowledge production are not limited to situations in which economic interests influence researchers’ practices. Building on laboratory studies and the French “pragmatic” tradition in sociology, this article proposes an approach to tackle more pervasive capitalist logics at work in contemporary research and their consequences. It uses the term epistemic capitalism to denote the accumulation of capital, as worth made durable, through the act of doing research, in and beyond academia. In doing so, it conceptualizes capitalism primarily not as a system of circulation and accumulation of monetary value but rather as a cultural way of producing, attributing, and accumulating specific forms of worth, which need not be monetary. Empirically, the article studies variants in epistemic capitalism by addressing the differing role of the accumulation of different forms of capital and the regimes connected to it in two institutional settings in Austria, academic life science laboratories and biotechnology start-up companies. Concluding, it argues that analytically dissociating the concept of capitalism from its link to economic value allows a finer-grained cultural analysis of the importance and effects of processes of accumulation in contemporary research. It ends with discussing the normative implications of these findings for debates about the commercialization of academia.

Founding angels as early stage investment model to foster biotechnology start-ups

As a rule, in biotechnology and other technologies, a gap exists between innovations coming from academic research and the commercialisation of the results, which is a serious barrier for innovation processes. This article investigates the role of founding angels as an early stage investment model, which has been applied in North America for a number of years and is now also being established in Europe. Focus is the commercialisation of pre-seed and seed stage technologies developed at universities and research institutions. Founding angels close the gap by actively founding and building up biotechnology start-up companies, together with scientists, typically before the engagement of business angels and venture capital. For providing business expertise and day-to-day operational support they are not compensated monetarily, but with an equity share of the new company. This article analyses the approach and investment strategy of founding angels and contains case studies from Germany and Switzerland showing how this business model is realised.

Microalgal biomass production: challenges and realities

The maximum quantum yield (Φ (max)), calculated from the maximum chlorophyll a specific photosynthetic rate divided by the quantum absorption per unit chlorophyll a, is 8 photons or 0.125 mol C per mol Quanta light energy. For the average solar radiation that reaches the earth's surface this relates to a photosynthetic yield of 1.79 g(dw) m(-2) day(-1) per percentage photosynthetic efficiency and it could be doubled for sunny, dry and hot areas. Many factors determine volumetric yields of mass algal cultures and it is not simply a question of extrapolating controlled laboratory rates to large scale outdoor production systems. This is an obvious mistake many algal biotechnology start-up companies make. Closed photobioreactors should be able to outperform open raceway pond cultures because of the synergistic enhancement of a reduced boundary layer and short light/dark fluctuations at high turbulences. However, this has not been shown on any large scale and to date the industrial norm for very large production systems is open raceway production ponds. Microalgal biomass production offers real opportunities for addressing issues such as CO(2) sequestration, biofuel production and wastewater treatment, and it should be the preferred research emphasis.

Can in vitro assessment provide relevant end points for cognitive drug programs?

Several start-up biotechnology companies have been created with the primary intent of developing cognitive enhancers. In addition, established pharmaceutical companies also frequently focus their efforts on cognitive drug discovery. In many instances, the rationale and evidence for these endeavors are based largely on in vitro assessments. In particular, the experimental paradigm, know as long-term potentiation (LTP), a cellular model of synaptic plasticity and memory encoding, is being increasing used preclinically for assessing potential nootropic drugs in vitro. Central to this thinking is the idea that the modulation of LTP and/or glutamate receptors are the key criteria that must be met for the development of cognitive enhancers. However, programs targeting the NMDA receptor, a glutamate receptor subtype, over the years have been less than fruitful. In addition, skeptics criticize the relevance of some in vitro tests such as LTP for simulating human cognitive function. Given these considerations, one may wonder if in vitro assessments in general, and the LTP paradigm in particular, provide relevant end points for cognitive drug discovery and development programs. The focus of this article is to address this question and to present evidence as to why in vitro assessment is still critical to the success of any cognitive drug program.

Trends in biotechnology and biosafety in Brazil

Biotechnology is a Brazilian priority, and has been recognized for its potential to promote sustainable development. The Government recently announced an ambitious program for Science and Technology, which includes strategies to develop modern biotechnology, continuing three decades of public investments on capacity building and infrastructure, aimed principally at the development of technologies applied to health, agriculture and the environment (MCT, 2008). Research initiatives have focused on genomics, proteomics, genetically modified organisms (GMOs), gene therapy, stem cells, bio-fuels and nanotechnology, among other biotechnological topics. Research projects in Brazil have been mainly developed in public universities and institutions funded by federal and state agencies, with a minor participation from the private sector (Silveira et al., 2004). Genomics, an area of considerable success in the country, was launched a decade ago by S. Paulo State Research Foundation (FAPESP), with the organization of a virtual institute, called ONSA, comprising several laboratories with the main task of sequencing the genome of the citrus pathogenic bacterium Xylella fastidiosa (Simpson et al., 2000). The success of this genomic network stimulated biotechnology startup companies and projects with the focus on other genomes, such as sugarcane and coffee, including functional genomics and proteomics. Following in the footsteps of the ONSA network, the Ministry of Science and Technology created a National Genome Project Consortium involving institutions located in the major regions of the country, with the task of sequencing eight microbial and two plant genomes. Recently, they concluded the sequence of Chromobacterium violaceum,

Share Structure and Entrepreneurship in UK Biotechnology Companies: An Empirical Study

Biotechnology start-up companies are dependent on investment to discover and develop their products, and often get that investment from venture capital groups (VCs). VCs almost always invest in liquidation preference shares, which provides them with upside enhancement and downside protection, and they impose detailed management controls on the company through shareholder veto provisions. This has been suggested as laying the company open to “investor opportunism”, actions which drive the company to actions or strategies which, while enhancing the investor's short-term shareholding value, damages the company as a whole and restricts its long-term prospects in the US. This paper reports on an analysis of the effect of the combination of complex share structures with multiple levels of liquidation preference (the norm in UK biotechnology companies) and of comprehensive investor control over the company's management. We find the same problems occurring in UK biotechnology companies as Fried and Ganor found in the US, with examples of companies being prevented from achieving exits, raising investment rounds and being driven to mergers which add no value to the enterprise. This both reduces the value of investee companies (an issue that VCs should address) and reduces the willingness of entrepreneurs and business angels to create new companies for VCs to invest in. This is made worse by the chronic underinvestment in UK high-tech start-ups. Examination of a number of potential solutions finds few of them are workable, but that requiring companies to disclose contracts that effectively transfer the power of directors to non-director shareholders could have some benefit.

Biotechnology financing, not acquisitions, for filling the pharma pipeline – a sustaining strategy

The traditional model of start-up biotechnology companies was to invent, invest, build, partner and make a public offering. This model failed, following an era of investments in far reaching technologies, such as genomics and combinatorial chemistry, that did not yield near term products. In recent times, products that are at or near the clinical stage have again attracted investors to start-up biotechnology companies. After a short period of development, these biotechnology companies are bought by large pharma companies for high prices. If the product fails, the investment is simply written off and there is no backup compound developed, as the biotechnology company with the expertise and the accumulated knowledge of the program and products has been shut down. Most large pharma companies have also downsized exploratory programs. It remains the purview of government and a handful of ‘angel’ investors to fund new ideas. The pharma and biotechnology industry must re-examine this model and build an investment model that retains creativity and the entrepreneurial spirit that allows the time to yield multiple products.

Insect cell culture and biotechnology

The continued development of new cell culture technology is essential for the future growth and application of insect cell and baculovirus biotechnology. The use of cell lines for academic research and for commercial applications is currently dominated by two cell lines; the Spodoptera frugiperda line, SF21 (and its clonal isolate, SF9), and the Trichoplusia ni line, BTI 5B1-4, commercially known as High Five cells. The long perceived prediction that the immense potential application of the baculovirus-insect cell system, as a tool in cell and molecular biology, agriculture, and animal health, has been achieved. The versatility and recent applications of this popular expression system has been demonstrated by both academia and industry and it is clear that this cell-based system has been widely accepted for biotechnological applications. Numerous small to midsize startup biotechnology companies in North America and the Europe are currently using the baculovirus-insect cell technology to produce custom recombinant proteins for research and commercial applications. The recent breakthroughs using the baculovirus-insect cell-based system for the development of several commercial products that will impact animal and human health will further enhance interest in this technology by pharma. Clearly, future progress in novel cell and engineering advances will lead to fundamental scientific discoveries and serve to enhance the utility and applications of this baculovirus-insect cell system.

The SEC's enforcement programme on biotechnology's communications with the investment community

The proliferation of biotechnology start-up companies has led to increased scrutiny by the regulators of the securities markets. The author, a former head of a field office of the United States Securities and Exchange Commission, examines the growing cooperation among regulatory agencies in the U.S. and the basic structure of the disclosure and anti-fraud provisions of the U.S. securities laws. The author articulates the approaches that the SEC division of enforcement has taken to investigating and prosecuting violations of the securities laws by biotechnology companies and provides useful guidance for dealing with news that may impact the securities markets.

The SEC's enforcement programme on biotechnology's communications with the investment community

The proliferation of biotechnology start-up companies has led to increased scrutiny by the regulators of the securities markets. The author, a former head of a field office of the United States Securities and Exchange Commission, examines the growing cooperation among regulatory agencies in the U.S. and the basic structure of the disclosure and anti-fraud provisions of the U.S. securities laws. The author articulates the approaches that the SEC division of enforcement has taken to investigating and prosecuting violations of the securities laws by biotechnology companies and provides useful guidance for dealing with news that may impact the securities markets.

Crisis management in entrepreneurial biotechnology companies: an explorative case study

Biotechnology startup companies are often based on little more than a technology with the potential to contribute to the development of innovative products in the future. Failure of this technology leads to a life-threatening crisis for these firms; managers must react quickly to ensure survival of their companies. The existing literature does not provide information on how biotechnology startups successfully escape technology breakdown crises. In this work, we present an in-depth case study of a biopharmaceutical startup company that suffered and successfully escaped a technology breakdown crisis. We illustrate its project acquisition strategy as well as management of financial, organisational, human and social resources after the breakdown. Our findings have implications for managers of entrepreneurial biotechnology firms.

Administrative and research policies required to bring cellular therapies from the research laboratory to the patient's bedside

The research process is a balance between the inherent risks of new discoveries and the risks of research participant safety. Conflicts of interest, inherent to the research process, as well as those introduced by emerging cellular therapies, have the potential to compromise safety. The relationship of trust between the researcher and the clinical trial participant facilitates objective decision making, in the best interest of both parties. In the setup of each clinical trial, investigators incorporate ethical, political, legal, financial, and regulatory considerations as protocols are established. Responsibility to abide by these decisions ensures a systematic process and safeguards participants in this process. The integrity of the research process is strengthened by identifying potential conflicting issues with the guiding principles established in the protocols, which may threaten the objectivity of involved parties and jeopardize safety of the participants. The rapid pace and changing paradigms of new discoveries in cellular therapies exaggerate existing conflicts and introduce new ones. Ethical issues raised by emerging cellular therapies include the division of opinions regarding the use of embryonic and fetal tissue to develop stem cell lines for research, the individual versus professional conscience of a researcher, overselling of outcomes as a result of the researcher's desire to be the first to discover a cellular therapy, and therapeutic misconception resulting from a participant's desire for a miracle cure. The basic ethical issue of whether stem cells should be utilized as a cellular therapy raises heated debates because some believe that it is not acceptable to use fetal material as a source of research material for future cures and others feel equally as strong that inaction is unethical because it results in needless suffering and death owing to the absence of this research. Political issues include the divergent position statements of presidential administrations on cellular therapy, variations in individual state laws, and states becoming involved in research funding, such as California's Proposition 71. Legal concerns include expanding private litigation with diversity of lawsuits, expanding lists of defendants, and the use of class-action lawsuits in research cases. Ownership issues also arise in terms of intellectual property, patents, and ownership of stem cells collected from minors, as in umbilical cord blood donations. Situations that challenge the regulatory processes established to ensure participant safety include differences in reporting requirements for private- and public-funded research and the lack of adequate funding and resources to implement and support the institutional review board (IRB) process. Financial considerations influence the development of clinical protocols, because funding is often limited. Financial incentives, personal investment in companies funding research activities, and fundraising pressures may present potential conflicts. In addition, the increasing role of emerging biotechnology start-up companies and pharmaceutical companies in clinical research introduces additional financial considerations. Administrative policies are needed to address these possible conflicts and ensure research participant safety as cellular therapies progress from the research laboratories to the patient's bedside. Administrative policies to ensure minimum standards of quality for emerging products before human clinical trials, policies to enforce consistent reporting requirements for private and public cellular research, policies to minimize financial conflicts of interest, policies to strengthen implementation of the existing IRB process and to structure into the process a consistent, systematic review of these identified conflicts, and policies to limit private litigation will help to preserve the objectivity of the review process and ultimately increase participant safety.

Stanford's licensing and equity practices with biotechnology companies

Stanford University's Office of Technology Licensing (OTL) has a long history of licensing technologies to biotechnology start-up companies. This paper presents (1) examples of how the OTL works with biotechnology start-ups to negotiate licence agreements for Stanford-owned intellectual property, taking into account a new company's scarce financial resources and needs but their large intellectual property appetite; and (2) an analysis of the rate of success of biotechnology companies emerging from Stanford based on information obtained from the equity records at Stanford's OTL. OTL started taking equity more often in start-up companies in the mid-1990s and generally takes equity as part of most exclusive licences to early-stage companies.

Stanford's licensing and equity practices with biotechnology companies

Stanford University's Office of Technology Licensing (OTL) has a long history of licensing technologies to biotechnology start-up companies. This paper presents (1) examples of how the OTL works with biotechnology start-ups to negotiate licence agreements for Stanford-owned intellectual property, taking into account a new company's scarce financial resources and needs but their large intellectual property appetite; and (2) an analysis of the rate of success of biotechnology companies emerging from Stanford based on information obtained from the equity records at Stanford's OTL. OTL started taking equity more often in start-up companies in the mid-1990s and generally takes equity as part of most exclusive licences to early-stage companies.

Recognizing, appreciating, and capturing the tacit knowledge of R&amp;D scientists

AbstractOne of the most important assets of biopharmaceutical firms is the expertise of their R&amp;D scientists, and it is important that such intellectual assets be developed for competitive advantage. On the other hand, we have observed instances in which tacit knowledge—that which resides in the minds of scientists but is not yet communicated—was overlooked. For the biomedical sector, tacit knowledge is an important issue from the perspectives of retirement, recruitment, and turnover. As the National Science Foundation noted, (1) retirement of PhDs will dramatically increase over the next decade, and (2) between 1998 and 2008, the biological sciences are expected to have the highest job growth rate of the life sciences (35%). In addition, turnover among small, startup biotechnology companies can be a sizable fraction of total scientific employment. If the tacit knowledge of experienced scientists is not captured, in each of the above cases it may become a lost rather than a strategic asset. Our objective is to focus readers' attention on the tacit aspect of scientists' expertise and to suggest tactics for capturing and communicating that knowledge, for the strategic advantage of teams, departments, and organizations. Drug Dev. Res. 57:51–57, 2002. © 2002 Wiley‐Liss, Inc.

Technology transfer at EMBL

The European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, is set to become a major international centre for technology transfer. Late in 2000, the EMBL council gave the go-ahead for significant development of technology transfer at EMBL (see: www.embl-heidelberg.de). Funds will be provided to establish an International Technology Transfer Centre (ITTC) and Technology Transfer Fund designed to encourage European biotechnology start-up companies. The phase I ITTC building is expected to be complete in 2002. It will provide incubator facilities for start-up companies as well as training for scientists in technology-transfer issues. The building is being constructed by EMBL and will be leased to EMBLEM (EMBL Enterprise Management, essentially the commercial arm of EMBL), which is wholly owned by EMBL but operates independently. A proposed phase II will also be built depending on the initial demand for space in the phase I project.