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News Article | June 21, 2017

About Lilly's Biotechnology Center and the Company's Presence in San Diego The center features a new technologically-advanced laboratory and an additional 180,000 square feet of working space, which is an increase of 145 percent compared to the former facility. In addition to the center's established presence in preclinical and clinical immunology research, the new space allows for closer partnership between Lilly experts in biotechnology, discovery chemistry and research technologies while also fostering external collaborations. "Being in the San Diego area for the last 13 years has been a game changer for us, specifically in the arena of discovering medicines for hard-to-treat autoimmune conditions," said Thomas F. Bumol, Ph.D., senior vice president of biotechnology and immunology research at Lilly. "With compounds such as Taltz® (ixekizumab) for psoriasis, we've not only provided patients with a new treatment option, but we've also moved the needle for advancing science." As a pioneer in automated organic synthesis, Lilly is creating the Lilly Life Science Studio in San Diego. Building upon Lilly's Automated Synthesis Laboratory in Indianapolis, the new facility will allow researchers across the globe to remotely design, synthesize and screen investigational molecules in an unprecedented manner. Using the power of automation, the Lilly Life Sciences Studio will shape the next generation of drug discovery and expand the reach of individual scientists to test new ideas, while reducing the cost and minimizing the environmental impact of our research activities. "Investing in drug discovery and development is critical to maintaining an ecosystem that encourages and promotes innovation. Our expansion in San Diego is a prime example of investing in a research success story," said Jan Lundberg, Ph.D., executive vice president for science and technology and president of Lilly Research Laboratories. "Expanding our presence in San Diego will not only help us discover and deliver innovative medicines faster, but will also help us achieve our goal of launching 20 new medicines in 10 years." San Diego has long been an important location for Lilly. In 2004 Lilly acquired Applied Molecular Evolution, Inc. before establishing the Lilly San Diego Biotechnology Center in 2009, located near the University of California, San Diego, among other prominent biomedical research institutes. Since its establishment, the center has created more than 100 jobs with more than 200 scientists currently working in various research activities. "Congratulations to Lilly on the expansion of its new Biotechnology Center, which will double its drug research and development in San Diego, create high-quality jobs, and encourage collaboration on groundbreaking therapies that improve patient care and lower costs," said Representative Scott Peters (D-CA 52nd Congressional District). "San Diego's life sciences industry is changing the face of medicine and companies like Lilly are driving this innovation." About Lilly's U.S. Research and Development Investment Nearly $250 million of Lilly's $850 million capital investments will be dedicated to supporting its research and development centers around the U.S., including the center in San Diego, in 2017.  Lilly's other U.S. research centers are located in Indianapolis, Indiana; Cambridge, Massachusetts; New York, New York; and Philadelphia, Pennsylvania. In 2017, Lilly plans to spend approximately $5 billion on global R&D, nearly $4 billion of which will be invested in U.S. based programs, including projects with many of California's leading biomedical research institutions. "This investment doesn't come without risk. America's biopharmaceutical leadership is driven by a free-market economy that rewards innovation," said Ricks. "Today, there are multiple public policy threats to our business that would discourage or reduce our investment in the U.S. and the state. We are committed to working with policymakers and stakeholders to ensure our efforts to deliver new innovative medicines to patients are not threatened." About Eli Lilly and Company Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at  and C-LLY This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about the benefits of the Lilly Biotechnology Center in San Diego, California and other planned capital projects, and reflects Lilly's current beliefs. However, as with any such undertaking, there are substantial risks and uncertainties in the processes of pharmaceutical research and development, and capital project implementation and completion. Among other things, there can be no guarantee that the projects will be completed on the anticipated timeline or at all or that Lilly will realize the expected benefits of the projects. For further discussion of these and other risks and uncertainties, please see Lilly's latest Forms 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements. To view the original version on PR Newswire, visit:

Tessier P.M.,Rensselaer Polytechnic Institute | Wu J.,Rensselaer Polytechnic Institute | Dickinson C.D.,San Diego Biotechnology
Expert Opinion on Drug Delivery | Year: 2014

Subcutaneous delivery of concentrated monoclonal antibodies (mAbs) is complicated by the propensity of mAbs to self-associate at elevated concentrations, which can lead to undesirable solution properties such as aggregation and abnormally high viscosity. Therefore, the selection of mAb candidates with low propensity to self-associate during early antibody discovery can significantly reduce challenges that may occur later during antibody development. However, it is difficult to use conventional biophysical methods for measuring weak mAb self-interactions during antibody discovery given the large number of antibody candidates as well as their low concentrations and purities. Nevertheless, significant progress has been made recently in adapting conventional biophysical methods as well as developing new ones for early identification of mAbs with low self-association propensities, which we highlight in this editorial. These advances should improve the selection of mAb candidates suitable for the extreme requirements of concentrated formulations necessary for subcutaneous delivery of therapeutic antibodies. © Informa UK, Ltd.

Wasserman S.R.,Argonne National Laboratory | Koss J.W.,Argonne National Laboratory | Sojitra S.T.,Argonne National Laboratory | Morisco L.L.,Argonne National Laboratory | Burley S.K.,San Diego Biotechnology
Trends in Pharmacological Sciences | Year: 2012

Synchrotron X-ray sources provide the highest quality crystallographic data for structure-guided drug design. In general, industrial utilization of such sources has been intermittent and occasionally limited. The Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beamline provides a unique alternative to traditional synchrotron use by pharmaceutical and biotechnology companies. Crystallographic experiments at LRL-CAT and the results therefrom are integrated directly into the drug discovery process, permitting structural data, including screening of fragment libraries, to be routinely and rapidly used on a daily basis as part of pharmaceutical lead discovery and optimization. Here we describe how LRL-CAT acquires and disseminates the results from protein crystallography to maximize their impact on the development of new potential medicines. © 2012 Elsevier Ltd. All rights reserved.

Watrous J.D.,University of California at San Diego | Alexandrov T.,University of Bremen | Dorrestein P.C.,University of California at San Diego | Dorrestein P.C.,San Diego Biotechnology
Journal of Mass Spectrometry | Year: 2011

Within the past decade, imaging mass spectrometry (IMS) has been increasingly recognized as an indispensable technique for studying biological systems. Its rapid evolution has resulted in an impressive array of instrument variations and sample applications, yet the tools and data are largely confined to specialists. It is therefore important that at this junction the IMS community begin to establish IMS as a permanent fixture in life science research thereby making the technology and/or the data approachable by non-mass spectrometrists, leading to further integration into biological and clinical research. In this perspective article, we provide insight into the evolution and current state of IMS and propose some of the directions that IMS could develop in order to stay on course to become one of the most promising new tools in life science research. © 2011 John Wiley & Sons, Ltd.

Ethell D.W.,Western University of Health Sciences | Ethell D.W.,San Diego Biotechnology
Journal of Alzheimer's Disease | Year: 2014

Plaques and tangles may be manifestations of a more substantial underlying cause of Alzheimer's disease (AD). Disease-related changes in the clearance of amyloid-β (Aβ) and other metabolites suggest this cause may involve cerebrospinal fluid (CSF) flow through the interstitial spaces of the brain, including an archaic route through the olfactory system that predates neocortical expansion by three hundred million years. This olfactory CSF conduit (OCC) runs from the medial temporal lobe (MTL) along the lateral olfactory stria, through the olfactory trigone, and down the olfactory tract to the olfactory bulb, where CSF seeps through the cribriform plate to the nasal submucosa. Olfactory dysfunction is common in AD and could be related to alterations in CSF flow along the OCC. Further, reductions in OCC flow may impact CSF hydrodynamics upstream in the MTL and basal forebrain, resulting in less efficient Aβ removal from those areas - among the first affected by neuritic plaques in AD. Factors that reduce CSF drainage across the cribriform plate and slow the clearance of metabolite-laden CSF could include aging-related bone changes, head trauma, inflammation of the nasal epithelium, and toxins that affect olfactory neuron survival and renewal, as well as vascular effects related to diabetes, obesity, and atherosclerosis - all of which have been linked to AD risk. Problems with CSF-mediated clearance could also provide a link between these seemingly disparate factors and familial AD mutations that induce plaque and tangle formation. I hypothesize that disruptions of CSF flow across the cribriform plate are important early events in AD, and I propose that restoring this flow will enhance the drainage of Aβ oligomers and other metabolites from the MTL. © 2014 - IOS Press and the authors. All rights reserved.

Hughes C.C.,San Diego Biotechnology | Fenical W.,San Diego Biotechnology
Chemistry - A European Journal | Year: 2010

The ocean contains a host of macroscopic life in a great microbial soup. Unlike the terrestrial environment, an aqueous environment provides perpetual propinquity and blurs spatial distinctions. Marine organisms are under a persistent threat of infection by resident pathogenic microbes including bacteria, and in response they have engineered complex organic compounds with antibacterial activity from a diverse set of biological precursors. The diluting effect of the ocean drives the construction of potent molecules that are stable to harsh salty conditions. Members of each class of metabolite'ribosomal and non-ribosomal peptides, alkaloids, polyketides, and terpenes'have been shown to exhibit antibacterial activity. The sophistication and diversity of these metabolites points to the ingenuity and flexibility of biosynthetic processes in Nature. Compared with their terrestrial counterparts, antibacterial marine natural products have received much less attention. Thus, a concerted effort to discover new antibacterials from marine sources has the potential to contribute significantly to the treatment of the ever increasing drug-resistant infectious diseases. Cures from the ocean: Marine organisms synthesize complex metabolites with antibacterial properties (see picture) to fend off co-occurring microbes. Representatives from each of five classes of natural products (ribosomal and non-ribosomal peptides, polyketides, alkaloids, and terpenes) isolated as new antibacterial metabolites from marine organisms are described (picture courtesy of X. Alvarez-Micó). © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

McDonald B.I.,San Diego Biotechnology | Ponganis P.J.,San Diego Biotechnology
Journal of Experimental Biology | Year: 2013

The management and depletion of O2 stores underlie the aerobic dive capacities of marine mammals. The California sea lion (Zalophus californianus) presumably optimizes O2 store management during all dives, but approaches its physiological limits during deep dives to greater than 300?m depth. Blood O2 comprises the largest component of total body O2 stores in adult sea lions. Therefore, we investigated venous blood O2 depletion during dives of California sea lions during maternal foraging trips to sea by: (1) recording venous partial pressure of O2 (PO2) profiles during dives, (2) characterizing the O2-hemoglobin (Hb) dissociation curve of sea lion Hb and (3) converting the PO2 profiles into percent Hb saturation (SO2) profiles using the dissociation curve. The O2-Hb dissociation curve was typical of other pinnipeds (P50=28±2mmHg at pH7.4). In 43% of dives, initial venous SO2 values were greater than 78% (estimated resting venous SO2), indicative of arterialization of venous blood. Blood O2 was far from depleted during routine shallow dives, with minimum venous SO2 values routinely greater than 50%. However, in deep dives greater than 4?min in duration, venous SO2 reached minimum values below 5% prior to the end of the dive, but then increased during the last 30-60?s of ascent. These deep dive profiles were consistent with transient venous blood O2 depletion followed by partial restoration of venous O2 through pulmonary gas exchange and peripheral blood flow during ascent. These differences in venous O2 profiles between shallow and deep dives of sea lions reflect distinct strategies of O2 store management and suggest that underlying cardiovascular responses will also differ. © 2013. Published by The Company of Biologists Ltd.

Sule S.V.,Rensselaer Polytechnic Institute | Dickinson C.D.,San Diego Biotechnology | Lu J.,Eli Lilly and Company | Chow C.-K.,Eli Lilly and Company | Tessier P.M.,Rensselaer Polytechnic Institute
Molecular Pharmaceutics | Year: 2013

A key challenge in developing therapeutic antibodies is their highly variable propensities to self-associate at high antibody concentrations (>50 mg/mL) required for subcutaneous delivery. Identification of monoclonal antibodies (mAbs) in the initial discovery process that not only have high binding affinity but also have high solubility and low viscosity would simplify the development of safe and effective antibody therapeutics. Unfortunately, the low purities, small quantities and large numbers of antibody candidates during the early discovery process are incompatible with current methods of measuring antibody self-association. We report a method (affinity-capture self-interaction nanoparticle spectroscopy, AC-SINS) capable of identifying mAbs with low self-association propensity that is robust even at low mAb concentrations (5-50 μg/mL) and in the presence of cell culture media. Gold nanoparticles are coated with polyclonal antibodies specific for human antibodies, and then human mAbs are captured from dilute antibody solutions. We find that the wavelength of maximum absorbance (plasmon wavelength) of antibody-gold conjugates - which red-shifts as the distance between particles is reduced due to attractive mAb self-interactions - is well correlated with light scattering measurements conducted at several orders of magnitude higher antibody concentrations. The generality of AC-SINS makes it well suited for use in diverse settings ranging from antibody discovery to formulation development. © 2013 American Chemical Society.

McDonald B.I.,San Diego Biotechnology | Ponganis P.J.,San Diego Biotechnology
Biology Letters | Year: 2012

Lung collapse is considered the primarymechanism that limits nitrogen absorption and decreases the risk of decompression sickness in deep-diving marine mammals. Continuous arterial partial pressure of oxygen (PO2) profiles in a free-diving female California sea lion (Zalophus californianus) revealed that (i) depth of lung collapse was near 225 m as evidenced by abrupt changes in PO2 during descent and ascent, (ii) depth of lung collapse was positively related to maximum dive depth, suggesting that the sea lion increased inhaled air volume in deeper dives and (iii) lung collapse at depth preserved a pulmonary oxygen reservoir that supplemented blood oxygen during ascent so that mean end-of-dive arterial PO2 was 74±17 mmHg (greater than 85% haemoglobin saturation). Such information is critical to the understanding and the modelling of both nitrogen and oxygen transport in diving marine mammals. © 2012 The Royal Society.

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