FDA Clears Genetic Lab Test for Warfarin Sensitivity

The U.S. Food and Drug Administration today cleared for marketing a new genetic test that will help physicians assess whether a patient may be especially sensitive to the blood-thinning drug warfarin (Coumadin), which is used to prevent potentially fatal clots in blood vessels.

One-third of patients receiving warfarin metabolize it quite differently than expected and experience a higher risk of bleeding. Research has shown that some of the unexpected response to warfarin depends on variants of two genes, CYP2C9 and VKORC1. The Nanosphere Verigene Warfarin Metabolism Nucleic Acid Test detects some variants of both genes.

"Today’s action offers physicians the first FDA cleared genetic test for warfarin sensitivity, which is another step in our commitment to personalized medicine,” said Daniel Schultz, M.D., director, FDA’s Center for Devices and Radiological Health. “With this test, physicians may be able to use genetic information along with other clinical information to treat their patients.”

Warfarin can be a difficult drug to use because the optimal dose varies depending on many risk factors, including a patient's diet, age, and the use of other medications. Rapidly achieving the correct dose is important. Patients who receive doses that are higher than needed to correctly thin the blood are at risk of life-threatening bleeding. Those who receive doses that are too low may remain at risk of life-threatening blood clots.

Warfarin is the second most common drug, after insulin, implicated in emergency room visits for adverse drug events.

In August, FDA approved updated labeling for Coumadin, the brand name version of warfarin, explaining that people with variations of the genes CYP2C9 and VKORC1 may respond differently to the drug. Manufacturers of generic warfarin are adding similar information to their products' labeling.

Physicians and other health care professionals who prescribe warfarin regularly check to see if the drug is working properly by ordering a test called the PT or prothrombin time that evaluates the blood's ability to clot properly. The results are measured in seconds and compared with the expected value in healthy people, known as the International Normalized Ratio or INR.

The Nanosphere test is not intended to be a stand-alone tool to determine optimum drug dosage, but should be used along with clinical evaluation and other tools, including INR, to determine the best treatment for patients.

FDA cleared the test based on results of a study conducted by the manufacturer of hundreds of DNA samples as well as on a broad range of published literature. In a three site study, the test was accurate in all cases where the test yielded a result; 8 percent of the tests could not identify which genetic variants were present.

The new test was cleared for use on the Verigene System, a clinical laboratory test system. Both products are manufactured by Nanosphere Inc., Northbrook, Ill.

Biotech investment on the rise

Author: Liu King-pong

Taiwan's biotechnology and pharmaceutical industry received a boost in September from MediVas LLC, a drug and biological delivery system developer based in San Diego, California. The U.S. firm announced Sept. 20 that it has selected Taiwan as the site for its Asian operations.

"Taiwan has probably the most dynamic economy in Asia and its way of doing business is very similar to that in the United States," said Kenneth Carpenter, president and chief executive officer of MediVas. "But, most importantly, the Taiwan government has committed to making the biotech and pharmaceutical industry a trillion dollar business," he added, referring to the government's strong support for the development of biotechnology. The remarks came at the Sept. 20 grand opening ceremony of MediVas Asia Corp.

Carpenter's optimistic statement is the result of the close cooperation between the government and the local biotechnology industry. This trend was recently highlighted with a statement made by Ho Mei-yueh, chairwoman of the Council for Economic Planning and Development. She announced Sept. 14 that the state-owned National Development Fund would invest US$20 million in TaiMed Biologics Co., a new biotech firm focusing on AIDS drugs.

TaiMed Biologics' competitive advantage lies in that it has acquired the patent from the U.S.-based Genentech Inc. for its lead clinical product, TNX-355. The drug shows promise as an effective treatment for AIDS patients and those infected with HIV. The patent rights to a product with such potential no doubt prompted Ho to indicate that the establishment of TaiMed Biologics marked a breakthrough in Taiwan's biotech industry.

MediVas' business, unlike most biotech and pharmaceutical firms, focuses mainly on changing the way pharmaceuticals are delivered. Its technology platform uses protein-like polymeric biomaterials to make drug and biological delivery more effective.

What makes the new investment in Taiwan more significant is that MediVas Asia's facility on the island will focus on the development of so-called "super-generic" drugs, Huang Bor-fuei, director of the industry promotion and marketing department at the Development Center for Biotechnology, stated Sept. 22.

Self-described as the matchmaker between MediVas and Taiwan, Huang pointed out that the firm defines super-generics as drugs whose original patents have expired but would be re-patented by MediVas Asia. "This re-patenting is a result of improving or modifying the delivery of the drug. Such modification has several advantages, including longer duration of drug effectiveness, less undesirable side effects and changes in the method of administration," he said.

"For example, you might take the drug once a week instead of once a day, or you can stop taking a drug by injection and start to take it orally," he explained.

MediVas Asia had talked to local pharmaceutical firms about joint development of super-generics. Local pharmaceutical companies typically focus on production of low-margin generic drugs, however, and did not embrace MediVas' plans.

"Although local firms showed interest, they were slow to act, perhaps due to a risk-aversion mindset and an overly conservative culture of avoiding change," said Huang.

According to Huang, China and India are usually seen as the only new emerging biotech markets in Asia. Taiwan is not associated with advances in biotechnology and is often overlooked. Huang took a different view, however. "I believe a sustainable technology is important in making biotech and pharmaceuticals our twin-star industries for our future economy," he stated. "A powerful platform technology can enable the improvement or even the creation of a variety of new products that can help the whole industry, and that is where our true niche lies."

Using the analogy of a fishing pole and a fish, Huang explained the value of a powerful platform technology. "MediVas' drug-delivery system can deliver more than one successful product, in the same way a fishing pole can deliver a continuous supply of fish. In the long run, more than being a successful company, MediVas will have positive economic impact on Taiwan's biotech industry."

MediVas Asia would set up its own research-and-development center in Taiwan and the company would establish its manufacturing facilities for super-generic production within a year, Huang revealed.

Write to Liu King-pong at kpliu@mail.gio.gov.tw

New research into plant colours sheds light on antioxidants

Scientists have made an important advance in understanding the genetic processes that give flowers, leaves and plants their bright colours. The knowledge could lead to a range of benefits, including better understanding of the cancer-fighting properties of plant pigments and new, natural food colourings. The research is highlighted in the new issue of Business from the Biotechnology and Biological Sciences Research Council (BBSRC).

The scientists, at the John Innes Centre and Institute of Food Research in Norwich, have pinpointed a key group of enzymes involved in the production of plant pigments. The pigments, called anthocyanins, are what give some plants the vivid colours that they use to attract insects and foraging animals. They also give plants protection against environmental stresses and disease. Hundreds of different anthocyanins exist in nature, all with slightly different chemical compositions. The international research team, supported by BBSRC, identified the genes responsible for the enzymes which chemically modify anthocyanins to alter their properties.

Prof Cathie Martin at the John Innes Centre who co-led the project explains: “Using a new strategy, we conducted biochemical studies on the brassica plant Arabidopsis. We found that a small number of genes responsible for the enzymes that chemically modify anthocyanins were ‘switched on’ when the plants were making anthocyanins in response to stress.

“When we transferred these genes to a tobacco plant, the colour of the tobacco flowers changed slightly, confirming that these genes, and the enzymes that they produce, were indeed responsible for modifying anthocyanins.

“What’s more, these anthocyanins that had been modified by the enzymes were more stable than those that hadn’t. This is significant because stabilised anthocyanins could be used as natural food colourants to replace many artificial colours used in various foods. This improved understanding of the genetics of anthocyanins also provides a better platform for studying their antioxidant properties, important in the fight against cancer, cardiovascular disease and age-related degeneration.”

Crucell grants Merck access to vaccine technology

Leiden, The Netherlands, September 10 2007 - Dutch biotechnology company Crucell N.V. announced today that Merck & Co., Inc. (Whitehouse Station, NJ) has exercised an option for the exclusive use of Crucell's PER.C6® technology and an option for access to Crucell's AdVac® vaccine technology in two infectious disease areas.

Mr. Jaap Goudsmit, Crucell's Chief Scientific Officer said: "We are excited about this technology agreement which represents a further expansion of the relationship between our company and Merck. Crucell's vaccine technologies, PER.C6® and AdVac®, are increasingly used by the vaccine industry to develop important novel vaccines for infectious diseases. This agreement further broadens the number of disease areas in which our technologies are used."

Under the terms of the agreement, Crucell acquires rights to certain cell-line technology developed by Merck for the manufacturing of recombinant proteins. The option and the related rights to certain technology developed by Merck originate from the cross-license agreement executed in December 2006 between Crucell and Merck. Specifics concerning the infectious disease indications remain undisclosed.

About Crucell
Crucell N.V. (Euronext, NASDAQ: CRXL; Swiss Exchange: CRX) is a biotechnology company focused on research, development and worldwide marketing of vaccines and antibodies that prevent and treat infectious diseases. Its vaccines are sold in public and private markets worldwide. Crucell's core portfolio includes a vaccine against hepatitis B, a fully-liquid vaccine against five important childhood diseases, and a virosome-adjuvanted vaccine against influenza. Crucell also markets travel vaccines, such as the only oral anti-typhoid vaccine, an oral cholera vaccine and the only aluminium-free hepatitis A vaccine on the market. The Company has a broad development pipeline, with several Crucell products based on its unique PER.C6® production technology. The Company licenses this and other technologies to the biopharmaceutical industry. Important partners and licensees include DSM Biologics, sanofi aventis, GSK and Merck & Co. Crucell is headquartered in Leiden (the Netherlands), with subsidiaries in Switzerland, Spain, Italy, Sweden, Korea and the US. The Company employs over a 1000 people. For more information, please visit www.crucell.com.

Prana to Raise A$7.0 million from Institutional and Professional Investors

Prana Biotechnology Limited (NASDAQ: PRAN / ASX: PBT), a biopharmaceutical company focused on the research and development of treatments for neurodegenerative disorders, today announced, subject to shareholder approval, a private placement of approximately 24.56 million new shares at a subscription price of A$0.285 (28.5 cents) per share, with a 2 for 6 free attaching option.

Prana will receive approximately A$7.0 million before allowing for issue costs from institutional and professional investors in Australia and the United States. The funds will be predominantly used for the ongoing development of its lead compound, PBT2, currently in a Phase IIa trial in patients with Alzheimer’s disease.

This trial, scheduled for completion in December 2007, is designed to advance the commercialization of Prana’s programs to develop novel treatments for neurodegenerative disorders.

“We are especially pleased to receive support from this group of investors, a number of whom have been strong supporters of the Company since inception,” commented Prana Chairman and Chief Executive Officer, Geoffrey Kempler. "This commitment reflects confidence in Prana and the potential of PBT2 as a disease modifying therapy for Alzheimer’s disease patients.”

The Phase IIa trial of PBT2 is a double-blind, placebo-controlled safety and tolerability study in patients with Alzheimer’s disease. PBT2 is Prana’s proprietary lead compound. The trial is well advanced, over 70% of study patients have been dosed and almost half of the target 80 patients have already completed the trial. “Given this progress, we are particularly pleased with the positive safety and tolerability demonstrated by PBT2 to date. We are on track to complete the trial by the end of the year and report results in the first quarter of 2008” said Mr Kempler.

New York based Brimberg & Co assisted with this transaction. The placement is subject to shareholder approval at an Extraordinary General Meeting, which is expected to occur on or about October 15, 2007. The Company will be seeking shareholder approval for the right to allot up to 35,087,700 shares with 2 for 6 attaching options which would raise up to $10 million if fully subscribed. The Company currently has firm commitments in place for $7.0 million of this total. The 2 attaching options, which will expire on 31 October and 30 November 2010 respectively, will be exercisable at A$0.37 cents and A$0.43 cents respectively.



About Prana Biotechnology Limited
Prana Biotechnology was established to commercialise research into Alzheimer's disease and other major age-related neurodegenerative disorders. The company was incorporated in 1997 and listed on the Australian Stock Exchange in March 2000 and listed on NASDAQ in September 2002. Researchers at prominent international institutions including The University of Melbourne, The Mental Health Research Institute (Melbourne) and Massachusetts General Hospital, a teaching hospital of Harvard Medical School, contributed to the discovery of Prana’s technology.

For further information, please visit the web site at www.pranabio.com.

Plants and stress; key players on the thin line between life and death revealed

Our crops are not doing well these days: too much water, too little sunlight... In short, they are suffering from stress. Scientists from VIB, associated with the Katholieke Universiteit Leuven (K.U.Leuven), have revealed a new mechanism demonstrating the intricate ways in which plants deal with stress. The newly discovered control system has a remarkable way of orchestrating the activity of hundreds of genes, forcing the plant into ‘safety mode’; the consumption of energy is contained while the organism is stimulated to mobilize reserves. This may have a negative impact on growth, but it allows the plant to temporarily safeguard itself against pernicious stress conditions. These findings also may prove to be useful beyond the case of plants, for the results are likely to be valuable in understanding disorders such as cancer and diabetes.

Life thanks to plants
Plants catch sunlight and use it as an energy source to produce sugars from CO2 and water. In doing so, they are at the very basis of the food chain. Ultimately, all life on earth depends upon this biochemical process: photosynthesis. Without plants, life as we know it today would simply not be possible. But what if things go wrong? When there is too little sunlight, for example? And what with other stressful conditions for plants? Environmental changes can compromise photosynthesis and exhaust energy supplies.

Plants control their own energy balance
Fortunately, plants have developed different mechanisms to detect and cope with 'stress’. Together with his American colleagues at Harvard Medical School (Boston, USA), VIB scientist Filip Rolland, associated with the Katholieke Universiteit Leuven, is uncovering a new system of detection and control. It is driven by KIN10 and KIN11. These ‘kinases’ – which are also found in human beings – react to energy shortages, when, for example, there is too little sunlight or too little sugar production. They control the activity of a broad network of genes, promoting the release of energy (catabolism) from alternative sources and blocking its assimilation (anabolism). In this way, the plant protects itself against stress conditions; like a really bad summer.

The key players: KIN10 & KIN11
The model organism for this study was Arabidopsis thaliana or thale cress. For decades, this small weed has been used as a model in molecular and genetic plant research. The scientists have tested numerous stress conditions that affect photosynthesis and energy production, such as darkness, herbicide treatment and flooding (lack of oxygen). By overexpressing the KIN10 gene, causing the plant to produce more of this protein, stress tolerance is increased and plants survive longer. By switching off these genes, their control function is eliminated.

With this research, the Flemish and American scientists have succeeded for the first time in attributing KIN10 and KIN11 a key role in the control of the plant energy budget and metabolism and thus the fragile balance between growth and survival; in short, the choice between life and death.

Are humans similar to plants?
The new insights gained by this study are not limited to the functioning of plants; they may also be important for human beings. KIN10 and KIN11, as ’fuel gauges’ controlling the expression of a whole set of genes, are also found in mammals. The results with plants, therefore, may play a pioneering role in discovering new functions of these proteins in disorders such as diabetes, cancer, obesitas, and aging.

Relevant scientific publication
The research findings are published in the leading scientific journal Nature (Baena-González et al., A central integrator of transcription networks in plant stress and energy signalling, Nature, 2007).

EU Court Rejects Austrian Biotech Ban

Yesterday, the European Court of Justice confirmed that statutory GMO-free regions are illegal. The Court dismissed the appeals of Upper Austria and the Austrian Government against their ban on the use of biotech crops in the region of Upper Austria.

“This is great news for farmers, for the scientific based risk assessment of the EFSA and for the EU biotech regulatory framework which the Member States put in place. Industry now calls on the region of Upper Austria to drop its illegal and unscientific opposition to approved biotech crops and allow Austrian farmers the choice to grow GMOs if they so wish.” said Johan Vanhemelrijck, Secretary General EuropaBio – the EU association for bioindustries. “Attempts to create so called “GMO-free regions” should be seen for what they are: a denial of the
freedom of choice for farmers and consumers.”

The Judgement says that practices like organic agriculture and small scale farming cannot be used as an argument to ban cultivation of approved biotech crops. Both the Commission and the Commissioner for Agriculture, Mariann Fischer Boel have stated in the past that “farmers should be able to produce in a traditional way, be it conventional or organic, according to the high quality and safety standards in the EU. And they should as well have the choice to produce
GM-crops, if they see advantages in doing so and find a market for them.” (1) Farmers can take official action against their region if it tries to stop them from cultivating EU approved biotech crops, while freedom of choice guarantees that individual or groups of farmers are free to cultivate conventional, organic or biotech crops. Today’s decision confirms that it is illegal for regional or national governments to impose bans and deprive individual farmers of the choice to grow biotech crops which have been approved for commercial cultivation in the EU.

New light-sensing ability discovered in disease-causing bacteria

The bacteria that cause brucellosis can sense light and use the information to regulate their virulence, according to a study in the August 24 issue of the journal Science. The discovery comes after 120 years of research into the disease, which causes abortions in livestock and fevers in humans. Researchers found that two other bacteria, including a species that attacks plants, sense light using the same type of protein structure, and at least 94 more species possess the code for it in their DNA.

"These bacteria have been very well studied for years, and no one knew they could sense light," said lead author Trevor Swartz, who initiated the study as a research scientist at the University of California, Santa Cruz. "Now it seems like it's a common thing rather than being an anomaly."

The ubiquity of the structure suggests that light may play a much more important role in bacterial life than has previously been recognized. And because the recurrent structure can be paired with a variety of signaling proteins, it gives organisms immense versatility in the ways they use light, Swartz said.

"We have bumped into an entirely new family of light receptors in nature," said coauthor Roberto Bogomolni, professor of chemistry and biochemistry at UCSC.

The receptor molecule contains a light-sensing region known as an LOV domain because it resembles similar units in other proteins that sense light, oxygen, or voltage, said coauthor and longtime collaborator Winslow Briggs, of the Carnegie Institution of Washington. The structure crops up in a variety of proteins, where it lends its light-sensing ability to the whole molecule. The light-sensing structure is very different from either the light-harvesting molecules of photosynthesis or the light-gathering pigments in our own eyes.

Full article here

Cardiocore Acquires Experienced Cardiac Safety Team Formerly with Gentiae

Cardiocore, a premier centralized cardiac safety testing laboratory, announced that it has hired former Gentiae Vice President of Cardiovascular Clinical Services, Polina Voloshko, MD. Cardiocore also acquired key members of Dr. Voloshko’s former staff. This core group includes cardiovascular physicians and technicians as well as project and data managers. Members of the team have worked together for 20 years, originally as part of the esteemed Ischemia Research and Education Foundation.

Dr. Voloshko joins Cardiocore’s scientific consulting team which includes two of the core lab industry’s founding fathers— Chief Medical Officer Lawrence Z. Satin, MD, FACC and Senior Cardiac Safety Consultant, Daniel B. Goodman, MD. With this addition, Cardiocore continues to expand its international scientific leadership, keeping pace with the company’s growing base of pharmaceutical and biotech clients.

Dr. Satin noted, “Cardiocore’s scientific team has overseen roughly a third of all the Thorough QT studies that have been performed to date. By bringing together the thought leadership from three top core labs, we have established a scientific foundation that is uniquely broad. We’ve combined the ‘best of the best’ approaches from across the industry to provide sponsors with unparalleled value.”

“When leading scientists like Polina Voloshko and Daniel Goodman become available in the cardiac testing industry,” added Cardiocore CEO Jennifer Cotteleer, “they are in a position to join any core lab they choose. Therefore, I am proud to see the most prominent experts repeatedly attracted to Cardiocore. They recognize us as the new industry leader, and they’re attracted to the scientific integrity we’ve established.”

“As a recent competitor,” explained Dr. Voloshko, “I can tell you that Cardiocore is setting the standard to which other core labs aspire. This organization delivers the highest quality science and the most thoughtful customer care in the cardiac testing industry. Speaking for myself and my colleagues, we are all delighted to become contributors to this top-quality operation.”

Dr. Voloshko brings 22 years of international experience as a cardiologist and researcher. In her role as Vice President of Medical Operations, she will perform protocol consulting, provide medical leadership and direct the company’s echocardiography services. She will be located in Cardiocore’s San Francisco, California office enabling close collaboration with West Coast life sciences customers.

About Cardiocore Cardiocore has provided superior centralized cardiac testing services to the pharmaceutical industry for 14 years. Services include centralized electrocardiographic (ECG) analysis, Holter monitoring, echocardiography, statistical analysis and consulting services such as protocol design. The company is experienced in design and implementation of Thorough QT Trials and cardiac safety and efficacy testing in Phase I, II and III clinical trials. These services are supported by the company’s CardioCorrect® system featuring the proprietary HolterGateway™ and CardioPortal™. Cardiocore’s U.S. headquarters is located in Bethesda, Maryland, its West Coast office is located in San Francisco, California, and its European subsidiary, Cardiocore Limited, is located in London, England.

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Einstein Researchers Use Novel Approach to Uncover Genetic Components of Aging

People who live to 100 or more are known to have just as many—and sometimes even more—harmful gene variants compared with younger people. Now, scientists at the Albert Einstein College of Medicine of Yeshiva University have discovered the secret behind this paradox: favorable “longevity” genes that protect very old people from the bad genes’ harmful effects. The novel method used by the researchers could lead to new drugs to protect against age-related diseases.

“We hypothesized that people living to 100 and beyond must be buffered by genes that interact with disease-causing genes to negate their effects,” says Dr. Aviv Bergman, a professor in the departments of pathology and neuroscience at Einstein and senior author of the study, which appears in the August 31 issue of PLoS Computational Biology.

To test this hypothesis, Dr. Bergman and his colleagues examined individuals enrolled in Einstein’s Longevity Genes Project, initiated in 1998 to investigate longevity genes in a selected population: Ashkenazi (Eastern European) Jews. They are descended from a founder group of just 30,000 or so people. So they are relatively genetically homogenous, which simplifies the challenge of associating traits (in this case, age-related diseases and longevity) with the genes that determine them.

Full story via Fierce Biotech