Bio Screening Industry News

Carlsbad, Calif., and Beltsville, Md., May 7, 2008 – In research demonstrating that RNA previously thought to have no biological relevance may be of use for therapeutic and diagnostic targets, Invitrogen Corporation (NASDAQ:IVGN), a provider of essential life science technologies for research, production and diagnostics, and BioServe, the leading provider of clinically annotated tissue samples and provider of molecular marker research services, today announced that their technologies identified noncoding RNAs that were differentially expressed in healthy and diseased tissue. These micro ribonucleic acid (miRNA) sequences were either up or down-regulated between matched samples of RNA isolated from healthy colon and colorectal cancer tissues.  Data was presented in a poster at the annual meeting for the American Association for Cancer Research.

Invitrogen researchers used RNA samples from BioServe’s OncoRNA (http://www.bioserve.com/products/oncoRNA.cfm) product line, a series of RNAs isolated from fresh-frozen, fully annotated tumor and adjacent normal tissues, to probe the Ncode(TM) Human miRNA microarray V3.  Ncode(TM) Profiler software identified miRNAs that were either up- or down-regulated in tumor versus healthy tissue, and researchers used quantitative PCR to validate the findings.

“Using the high quality RNA samples from BioServe, we were able to identify novel microRNA sequences that could potentially be involved in the generation of new tumor tissues, particularly in colorectal cancer,” said Chris Adams, research and development leader of Epigenetics at Invitrogen.  “If more stringently validated, these disease-related microRNAs may eventually serve as targets for diagnostic or therapeutic development.”

MicroRNAs are short RNA sequences that do not code for specific proteins but are extremely important in the regulation of gene expression; they are implicated in several disease states including cancer and heart disease.  Among the activity of miRNAs is the triggering of messenger RNA (mRNA) degradation and the inhibition of protein translation – the process of assembling amino acids into proteins based on the instructions contained in mRNA sequences.  Invitrogen’s Ncode(TM) Human miRNA microarray V3 consists of miRNA content from multiple sources, including the Sanger 10.0 miRNA database and novel miRNAs unavailable in public databases, giving users access to strong content for identification and study of miRNAs.

“MicroRNA is making headlines in drug discovery for its ability to fine tune the activity of genes and its part in the formation of cancer,” said Kevin Krenitsky, chief executive officer, BioServe. “This makes it all the more critical that researchers can be certain they are working with stable, highly annotated samples collected under rigorous ethical and scientific protocols. We created OncoRNA to respond to this need, providing bench-ready RNA for tomorrow’s discoveries.”

About BioServe

BioServe is a leader in the processing, development, and validation of diagnostic tests for the practice of personalized, predictive and preventive medicine. Leading pharma, biotech and diagnostic firms collaborate with BioServe to identify and validate markers that cause disease while correlating clinical and molecular data to develop new diagnostic tests promoting wellness around the world. BioServe offers the Global Repository(R), a growing library of over 600,000 human DNA, tissue and serum samples linked to detailed clinical and demographic data from 140,000 consented and anonymized patients from four continents. Leveraging BioServe’s robust genomic analytical services, technology, Global Repository and CLIA-certified laboratory, collaborators gain a complete, highly efficient platform for processing diagnostic test results and identifying genomic markers for powerful new assays. BioServe has headquarters in Beltsville, MD and Hyderabad, India. For more information please visit www.bioserve.com or call 301-470-3362.

About Invitrogen

Invitrogen Corporation (NASDAQ:IVGN) provides products and services that support academic and government research institutions and pharmaceutical and biotech companies worldwide in their efforts to improve the human condition. The company provides essential life science technologies for disease research, drug discovery, and commercial bioproduction. Invitrogen’s own research and development efforts are focused on breakthrough innovation in all major areas of biological discovery including functional genomics, proteomics, stem cells, cell therapy and cell biology — placing Invitrogen’s products in nearly every major laboratory in the world. Founded in 1987, Invitrogen is headquartered in Carlsbad, California, and conducts business in more than 70 countries around the world. The company employs approximately 4,700 scientists and other professionals and had revenues of approximately $1.3 billion in 2007. For more information, visit www.invitrogen.com.

Hamburg, Germany | Oxford, UK - Evotec AG (Frankfurt Stock Exchange: EVT) announced today that the Company and Ono Pharmaceutical Co., Ltd. (Osaka, Japan) signed a new drug discovery agreement targeting a protease chosen by Ono.

The collaboration applies Evotec’s proprietary fragment-based drug discovery platform, EVOlutionTM to identify novel, small molecular weight compounds active against a protease target. The platform integrates, among other things, protein X-ray crystallography, computational chemistry, structural biology, biochemical, and NMR based fragment screening in combination with its high-quality fragment libraries. In the collaboration it is combined with Evotec’s expertise in medicinal chemistry and ADMET to further characterize active compounds identified and optimize their potency and selectivity to generate molecules for subsequent progression into clinical trials.

Under the agreement, Ono will pay to Evotec initial payments (technology access fee) for access to Evotec’s fragment-based drug discovery platform, EVOlutionTM, research funding as well as success-based milestones based on the research progress.

Dr Mark Ashton, Executive Vice President Business Development Services at Evotec, said: “We are extremely pleased that Evotec’s capabilities in drug discovery and, in particular, our proprietary EVOlutionTM platform for fragment-based drug discovery, have been so highly regarded by Ono and that they have chosen us as their partner for this collaboration.  We are confident that Evotec will contribute to Ono’s drug discovery program.”

“We have the highest regards for the wide range of drug discovery technologies Evotec possesses and highly anticipate the collaboration will result in identifying a novel drug having high potentials” said Daikichi Fukushima, Ph.D., Managing Director, Research Headquarters at Ono.

Forward looking statements
Information set forth in this report contains forward-looking statements, which involve a number of risks and uncertainties. Such forward-looking statements include, but are not limited to, statements about the anticipated benefits of Evotec’s products and services, the payments that Evotec may receive under its collaboration agreement with Ono, the anticipated timing and results of Evotec’s clinical and pre-clinical programs, and other statements that are not historical facts. Evotec cautions readers that any forward-looking information is not a guarantee of future performance and that actual results could differ materially from those contained in the forward-looking information as a result of risks and uncertainties. These include risks and uncertainties relating to: Evotec’s ability to satisfy the research-based milestones under the agreement with Ono, Evotec’s ability to complete the merger because conditions to the closing of the merger may not be satisfied; the failure to successfully integrate the businesses of Evotec and Renovis; unexpected costs or liabilities resulting from the merger; the risk that synergies from the merger may not be fully realized or may take longer to realize than expected; disruption from the merger making it more difficult to maintain relationships with customers, employees or suppliers; competition and its effect on pricing, spending, third-party relationships and revenues; the need to develop new products and adapt to significant technological change; implementation of strategies for improving internal growth; development, use and protection of intellectual property; general worldwide economic conditions and related uncertainties; future legislative, regulatory, or tax changes as well as other economic, business and/or competitive factors; and the effect of exchange rate fluctuations on international operations.

The risks included above are not exhaustive. The Registration Statement on Form F-4 filed by Evotec with the Securities and Exchange Commission contains additional factors that could impact the combined company’s businesses and financial performance. The parties expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in the parties’ expectations or any change in events, conditions or circumstances on which any such statement is based.

Hamburg, Germany | Oxford, UK- Evotec AG (Frankfurt Stock Exchange: EVT) today announced that InterMune, Inc., has signed a second drug discovery contract with Evotec.

Evotec will support InterMune’s research efforts using their medicinal chemistry know-how. In addition, they will utilize their expertise and technologies in computational chemistry, protein production, X-Ray crystallography and ADMET to further characterize active compounds and optimize their potency and selectivity to generate lead molecules for subsequent progression into clinical trials.

This contract expands Evotec’s existing collaboration with InterMune which was initiated in early 2007. This collaboration applies Evotec’s fragment-based drug discovery platform, EVOlutionTM, in combination with their ultra-high-throughput screening (uHTS) technologies to InterMune’s targets.  To date new lead series have been identified for further optimization. Evotec also provides medicinal chemistry, secondary screening, protein production, X-ray crystallography and ADMET. The financial terms include a technology access fee for access to Evotec’s fragment-based drug discovery platform, EVOlutionTM, plus ongoing research funding.

“With the support of Evotec, InterMune has made considerable progress in their Hepatitis C drug discovery and development program. We are pleased that InterMune saw the value in our proprietary fragment-based drug discovery technology and that it has contributed to the success to their research efforts,” said Dr Mark Ashton, Executive Vice President Business Development Services at Evotec.

Gossypol:

• is a polyphenolic aldehyde that permeates cells and acts as an inhibitor for several dehydrogenase enzymes.
• is antimalarial being the selective inhibitor of Plasmodium falciparum (pfLDH over hLDHs), an essential enzyme for energy generation within malarial parasite.
• posesses proapoptotic properties, probably due to the regulation of the Bax and Bcl2.
• reversibly inhibits Calcineurin and binds to calmodulin.
• inhibits replication of the HIV-1 virus.
• an effective protein kinase C inhibitor.

Read more about Gossypol

Washington University School of Medicine in St. Louis is launching a new effort to study infectious diseases that preferentially affect women. The center for Women’s Infectious Disease Research (cWIDR) will focus on issues such as:

• microorganisms that cause urinary tract infections (UTIs) and other conditions that make urination and intercourse painful or difficult

• infections that lead to premature delivery and vaginitis

• potential contributing roles for microorganisms in life-threatening conditions such as cancer, heart disease, neurodegenerative disorders and diabetes.

“Infectious diseases of women is a tremendously underserved area,” says Scott Hultgren, Ph.D., the Helen L. Stoever Professor of Molecular Microbiology and the center’s director and principal investigator. “UTIs, for example, are one of the most common bacterial infections in women. They’re not fatal, but we need new and improved therapeutics because they’re a very significant cause of suffering, lost work days and health-care expenses.”

According to Hultgren, the center continues a University tradition of innovation and leadership in microbiology and infectious diseases. Stephen Beverley, Ph.D., Marvin A. Brennecke Professor and head of molecular microbiology, founded the center’s predecessor, the Center for Infectious Disease Research (CIDR) in 1997. He recently stepped down as director of CIDR and designated Hultgren as his successor.

Hultgren’s research has long been focused on women’s health and infectious diseases, with studies funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Allergy and Infectious Diseases. He has also been active in the Office of Research on Women’s Health, an agency that coordinates and advises on women’s health research throughout the National Institutes of Health.

Given those interests and experiences, Hultgren decided to reconceptualize CIDR and its goals, altering the center’s name to reflect the changes.

The center for Woman’s Infectious Disease Research is part of the University’s BioMed 21 initiative, which is focusing efforts at Washington University on speedy translation of laboratory discoveries into new approaches for diagnosis and treatment of patients.

According to Larry J. Shapiro, M.D., executive vice chancellor for medical affairs and dean at the School of Medicine, studying gender-specific infections can reveal information that is helpful in a much broader range of diseases.

“Scott’s work with urinary tract infections has led to insight into how the bacteria that cause these infections sometimes defend themselves by cooperating to form a protective shield known as a biofilm,” he says. “Many common infections of both men and women employ this defense against antibiotics and the host immune system, and to improve treatment for these infections we have to devise medicines that can penetrate this shield.”

Other major infectious disease issues specific to women include interstitial cystitis or painful bladder syndrome, a condition estimated to afflict hundreds of thousands of females per year. Symptoms are similar to urinary tract infections and include frequent, painful urination and pain during intercourse. Diagnosis and treatment are difficult because scientists don’t yet know the cause of the condition.

Oral and vaginal infections with streptococcus and other bacteria have been linked to premature delivery in pregnant women. Michael Caparon, Ph.D., professor of molecular microbiology and co-director of the center for Woman’s Infectious Disease Research, plans to bring microbiologists and obstetricians to learn why and determine what can be done.

Fostering collaboration between different disciplines to create new perspectives on the big challenges of biomedicine is a primary goal of BioMed 21. Hultgren plans to establish many connections and collaborations between his center and other research centers, noting the potential for synergy provided by the Center of Genome Sciences and other research groups at the University.

“We see the center for Woman’s Infectious Disease Research as part of a multi-disciplinary network combining a powerful blend of microbial pathogenesis, genomics, structural biology, biochemistry and biophysics, and diverse imaging technologies,” Hultgren says.

As an example, Hultgren’s work with urinary tract infections led to detailed study of pili, fibers produced by the bacteria that cause the infections. Pili allow bacteria to adhere to and invade human tissues, and Hultgren’s laboratory has recently found that they help hold bacteria together in biofilms. These discoveries made it possible to design molecules that block pili formation and may one day lead to improved treatments.

Bacteria also manufacture fibers comprised of substances known as amyloids. Like pili, these materials contribute to biofilm formation and host cell colonization, but they’re much more well-known for the role they play in neurodegenerative disorders and other diseases. Hultgren hopes to recruit experts who can use bacteria to model amyloid formation and design compounds that block their assembly.

“Amyloid plaques in the brain are a primary characteristic of Alzheimer’s disease, a terrible disease affecting women and men, so we plan to offer the inhibitors we develop to neurologists as potential treatments for that disorder,” Hultgren says.

Researchers at the center for Woman’s Infectious Disease Research also will study whether microorganisms are playing a role in serious diseases not previously thought to be related to infection. As evidence of why a search for such connections might prove fruitful, Hultgren highlights the surprising discoveries that infectious agents are responsible for all stomach ulcers and most cervical cancers.

In a newer, more tentative link likely to be further probed at the center for Woman’s Infectious Disease Research, scientists have found that a receptor in the circulatory system responds to both fat deposits and bacterial infections. The receptor is believed to help summon an immune response when it detects the bacteria, and cardiologists speculate that its responsiveness to fat may mean the receptor is also triggering inflammatory responses that contribute to heart disease. If so, blocking the receptors could offer a new path to prevention.

To accelerate the search for new treatments for infectious diseases, Hultgren has established close ties with a local biotech firm, Sequoia Sciences, and with Tom Ellenberger, Ph.D., the Raymond H. Wittcoff Professor and head of Biochemistry and Molecular Biophysics.

“Tom has started a program for high-throughput screening of small molecules with pharmaceutical potential, and Sequoia has a library of approximately 250,000 antibacterial compounds isolated from plants in collaboration with the Missouri Botanical Garden,” Hultgren explains. “As we develop assays that help us know what we’re looking for in a treatment, we’ll be using those two resources to rapidly seek out compounds that meet our criteria.”

The new center and five new faculty positions will be supported in part by funding from the school’s Departments of Medicine, Molecular Microbiology, Infectious Diseases and Cardiology as well as general medical school resources and donors.

“If we can get a synergistic effect going on in terms of the interactions between these and other disciplines, then I really feel we’re going to be able to make a significant difference in women’s health,” Hultgren says.

BioSeek, based in Burlingame, will work with San Diego-based Amylin (NASDAQ: AMLN) on treatments for inflammatory diseases. The work will put Amylin’s proprietary drug compounds through BioSeek’s biological screening systems to seek useful drugs. BioSeek can choose two peptide compounds after screening and develop them if it wishes, paying milestones and royalties to Amylin if it does.

The two companies signed an earlier collaboration last year.

Peter Staple, BioSeek’s CEO, praised the deal as a source of money for his company, as well as a way to gain access to important compounds and research in inflammatory diseases.

Scientists have developed a novel strategy for tackling neurodegenerative diseases such as Huntington’s disease: encouraging an individual’s own cells to “eat” the malformed proteins that lead to the disease.

Huntington’s disease is one of a number of degenerative diseases marked by clumps of malformed protein in brain cells. Symptoms include abnormal movements, psychiatric disturbances like depression and a form of dementia. The gene responsible for the disease was discovered in 1993, leading to a better understanding of the condition and to improved predictive genetic testing, but it has yet to lead to any treatments that slow the neurodegeneration in Huntington’s patients.

Professor David Rubinsztein, a Wellcome Trust Senior Clinical Fellow at the University of Cambridge, has been studying the molecular biology underlying Huntington’s and other neurodegenerative diseases. Huntington’s occurs when a protein known as huntingtin builds up in the brain cells of patients, mainly in neurons in the basal ganglia and in the cerebral cortex. Normally, cells dispose of or recycle their waste material, including unwanted or mis-folded proteins, through a process known as autophagy, or “self-eating”.

“We have shown that stimulating autophagy in the cells , in other words, encouraging the cells to eat the malformed huntingtin proteins , can be an effective way of preventing them from building up,” says Professor Rubinsztein. “This appears to stall the onset of Huntington’s-like symptoms in fruit fly and mice, and we hope it will do the same in humans.”

Autophagy can be induced in mouse and fly models by administering the drug rapamycin, an antibiotic used as an immunosuppressant for transplant patients. However, administered over the long term, the drug has some side effects and Rubinsztein and colleagues are aiming to find safer ways of inducing autophagy long term.

Now, Professor Rubinsztein, together with Professor Stuart Schreiber’s lab at the Broad Institute of Harvard/MIT, Boston in the US, and Dr Cahir O’Kane’s group in the Department of Genetics at the University of Cambridge have found a way of identifying novel “small molecules” capable of inducing autophagy. The research is published today in the journal Nature Chemical Biology.

The screening process involves identifying small molecules that enhance or suppress the ability of rapamycin to slow the growth of yeast, though the selected molecules have no effects on yeast growth by themselves. Yeast is a single-celled organism and therefore less complex to study for initial screening purposes.

Three of the molecules that enhanced the growth-suppressing effects of rapamycin in yeast were also found to induce autophagy by themselves in mammalian cells independent of the action of rapamycin. These molecules enhanced the ability of the cells to dispose of mutant huntingtin in cell and fruit fly models and protect against its toxic effects.

“These compounds appear to be promising candidates for drug development,” says Professor Rubinsztein. “However, even if one of the candidates does prove to be successful, it will be a number of years off becoming available as a treatment. In order for such drugs to be useful candidates in humans, we will need to be able to get them into right places in the right concentrations, and with minimal toxicity. These are some of the issues we need to look at now.”

http://www.wellcome.ac.uk
Source: Medical Research News