11.23.2007
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Daily Democrat Online - UCD entomologist speaks on stifled research
Daily Democrat Online - UCD entomologist speaks on stifled research: "UCD entomologist speaks on stifled research
More focus on making money than on improving health and environment
Daily Democrat
Article Created: 11/23/2007 06:18:25 AM PST
University bureaucracies stifle research when they focus more on generating revenue than in fulfilling a public obligation to improve human health and the environment.
"That's a growing viewpoint of many interested in the technology transfer field," said UC Davis entomologist Bruce Hammock, who served as one of the speakers at the recent National Institutes of Environmental Health Sciences conference at the Berry Hill Plantation, South Boston, Va.
The two-day conference addressed a deepening concern among the multiple National Institutes of Health and the National Research Council of the National Academy of Sciences:
How to translate basic research effectively to improve human health and the environment.
The academic culture is "wonderful for innovation and training, but university bureaucracies are incompatible with translation," said Hammock, a distinguished professor of entomology who directs the UCD Superfund Basic Research Program of NIEHS.
Speaking on "Universities' Focus on Revenue Generation in Licensing Stifles Innovation: The Case to Modify the Bayh-Doles Act," Hammock said that "We as a nation have developed the most powerful innovation factory in human history but universities are poor at moving public
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sector innovation into the private sector for development and implementation."
The Bayh-Dole Act of 1980, co-authored by Sens. Birch Bayh (D-Indiana) and Sen. Robert Dole (R-Kansas), turned over the licenses for federally funded research projects to universities, but "an unintended consequence of this act was the generation of university technology transfer offices or TTOs," Hammock said.
The Kauffman Foundation, which Hammock described as "the largest entrepreunal 'think tank' in the United States," issued a report in April that said TTOs "have become gatekeepers" and "that in many cases, constrain the flow of inventions and frustrate faculty, entrepreneurs and industries."
The Kauffman Foundation report said the Bayh-Dole Act was intended "to speed up the process of moving technologies from the laboratory to the marketplace by clearing the way for universities to claim legal and, therefore, financial rights to federal government-funded innovations developed by their faculty. However, new layers of administration developed that centralized the process, narrowed the view of innovation as only patents, and emphasized revenue generation rather than volume of innovations the university commercializes."
Expanding on ideas expressed by the Kauffman Foundation and the American Chemical Society, Hammock told the scientific conference that "universities have great difficulty in determining the value of their own technologies due, in part, to the diversity of technologies developed. There is often a degree of arrogance among TTOs, resulting in hesitancy to solicit advice on establishing the value of a technology. As a result, they overlook important early state technology from young faculty while searching for 'home run' technologies from established investigators. Because TTOs are afraid of making bad decisions, the flow of the technology from the university is drastically delayed."
"Having failed to patent innovative technologies from young faculty, universities tend to spend far too much on the technology they do patent - trying to substitute very expensive language for research," Hammock said.
The UC Davis professor said a possible solution, suggested by the Kauffman Foundation, is for universities to move from the short-term profit model to a volume model where many technologies are patented at low cost and licensed rapidly.
The six-week clinical training is part of the curriculum to become a Licensed Vocational Nurse which takes two years of training after obtaining basic education credits.
Bruce Hammock
"
More focus on making money than on improving health and environment
Daily Democrat
Article Created: 11/23/2007 06:18:25 AM PST
University bureaucracies stifle research when they focus more on generating revenue than in fulfilling a public obligation to improve human health and the environment.
"That's a growing viewpoint of many interested in the technology transfer field," said UC Davis entomologist Bruce Hammock, who served as one of the speakers at the recent National Institutes of Environmental Health Sciences conference at the Berry Hill Plantation, South Boston, Va.
The two-day conference addressed a deepening concern among the multiple National Institutes of Health and the National Research Council of the National Academy of Sciences:
How to translate basic research effectively to improve human health and the environment.
The academic culture is "wonderful for innovation and training, but university bureaucracies are incompatible with translation," said Hammock, a distinguished professor of entomology who directs the UCD Superfund Basic Research Program of NIEHS.
Speaking on "Universities' Focus on Revenue Generation in Licensing Stifles Innovation: The Case to Modify the Bayh-Doles Act," Hammock said that "We as a nation have developed the most powerful innovation factory in human history but universities are poor at moving public
Advertisement
Click Here!
sector innovation into the private sector for development and implementation."
The Bayh-Dole Act of 1980, co-authored by Sens. Birch Bayh (D-Indiana) and Sen. Robert Dole (R-Kansas), turned over the licenses for federally funded research projects to universities, but "an unintended consequence of this act was the generation of university technology transfer offices or TTOs," Hammock said.
The Kauffman Foundation, which Hammock described as "the largest entrepreunal 'think tank' in the United States," issued a report in April that said TTOs "have become gatekeepers" and "that in many cases, constrain the flow of inventions and frustrate faculty, entrepreneurs and industries."
The Kauffman Foundation report said the Bayh-Dole Act was intended "to speed up the process of moving technologies from the laboratory to the marketplace by clearing the way for universities to claim legal and, therefore, financial rights to federal government-funded innovations developed by their faculty. However, new layers of administration developed that centralized the process, narrowed the view of innovation as only patents, and emphasized revenue generation rather than volume of innovations the university commercializes."
Expanding on ideas expressed by the Kauffman Foundation and the American Chemical Society, Hammock told the scientific conference that "universities have great difficulty in determining the value of their own technologies due, in part, to the diversity of technologies developed. There is often a degree of arrogance among TTOs, resulting in hesitancy to solicit advice on establishing the value of a technology. As a result, they overlook important early state technology from young faculty while searching for 'home run' technologies from established investigators. Because TTOs are afraid of making bad decisions, the flow of the technology from the university is drastically delayed."
"Having failed to patent innovative technologies from young faculty, universities tend to spend far too much on the technology they do patent - trying to substitute very expensive language for research," Hammock said.
The UC Davis professor said a possible solution, suggested by the Kauffman Foundation, is for universities to move from the short-term profit model to a volume model where many technologies are patented at low cost and licensed rapidly.
The six-week clinical training is part of the curriculum to become a Licensed Vocational Nurse which takes two years of training after obtaining basic education credits.
Bruce Hammock
"
11.22.2007
Scientific American: Nothing Says "Early Earth Was Cool" Like World's Oldest Diamonds
Scientific American: Nothing Says "Early Earth Was Cool" Like World's Oldest Diamonds: " 
Are Aliens Among Us?
In pursuit of evidence that life arose on Earth more than once, scientists are searching for microbes that are radically different from all known organisms
By Paul Davies
The origin of life is one of the great unsolved problems of science. Nobody knows how, where or when life originated. About all that is known for certain is that microbial life had established itself on Earth by about three and a half billion years ago. In the absence of hard evidence of what came before, there is plenty of scope for disagreement.
Thirty years ago the prevailing view among biologists was that life resulted from a chemical fluke so improbable it would be unlikely to have happened twice in the observable universe. That conservative position was exemplified by Nobel Prize–winning French biologist Jacques Monod, who wrote in 1970: “Man at last knows that he is alone in the unfeeling immensity of the universe, out of which he emerged only by chance.” In recent years, however, the mood has shifted dramatically. In 1995 renowned Belgian biochemist Christian de Duve called life “a cosmic imperative” and declared “it is almost bound to arise” on any Earth-like planet. De Duve’s statement reinforced the belief among astrobiologists that the universe is teeming with life. Dubbed biological determinism by Robert Shapiro of New York University, this theory is sometimes expressed by saying that “life is written into the laws of nature.”
How can scientists determine which view is correct? The most direct way is to seek evidence for life on another planet, such as Mars. If life originated from scratch on two planets in a single solar system, it would decisively confirm the hypothesis of biological determinism. Unfortunately, it may be a long time before missions to the Red Planet are sophisticated enough to hunt for Martian life-forms and, if they indeed exist, to study such extraterrestrial biota in detail.
An easier test of biological determinism may be possible, however. No planet is more Earth-like than Earth itself, so if life does emerge readily under terrestrial conditions, then perhaps it formed many times on our home planet. To pursue this tantalizing possibility, scientists have begun searching deserts, lakes and caverns for evidence of “alien” life-forms—organisms that would differ fundamentally from all known living creatures because they arose independently. Most likely, such organisms would be microscopic, so researchers are devising tests to identify exotic microbes that could be living among us.
Scientists have yet to reach a consensus on a strict definition of life, but most would agree that two of its hallmarks are an ability to metabolize (to draw nutrients from the environment, convert those nutrients into energy and excrete waste products) and an ability to reproduce. The orthodox view of biogenesis holds that if life on Earth originated more than once, one form would have swiftly predominated and eliminated all the others. This extermination might have happened, for example, if one form quickly appropriated all the available resources or “ganged up” on a weaker form of life by swapping successful genes exclusively with its own kind. But this argument is weak. Bacteria and archaea, two very different types of microorganisms that descended from a common ancestor more than three billion years ago, have peacefully coexisted ever since, without one eliminating the other. Moreover, alternative forms of life might not have directly competed with known organisms, either because the aliens occupied extreme environments where familiar microbes could not survive or because the two forms of life required different resources.
The Argument for Aliens
Even if alternative life does not exist now, it might have flourished in the distant past before dying out for some reason. In that case, scientists might still be able to find markers of their extinct biology in the geologic record. If alternative life had a distinctively different metabolism, say, it might have altered rocks or created mineral deposits in a way that cannot be explained by the activities of known organisms. Biomarkers in the form of distinctive organic molecules that could not have been created by familiar life might even be hiding in ancient microfossils, such as those found in rocks dating from the Archean era (more than 2.5 billion years ago).
A more exciting but also more speculative possibility is that alternative life-forms have survived and are still present in the environment, constituting a kind of shadow biosphere, a term coined by Carol Cleland and Shelley Copley of the University of Colorado at Boulder. At first this idea might seem preposterous; if alien organisms thrived right under our noses (or even in our noses), would not scientists have discovered them already? It turns out that the answer is no. The vast majority of organisms are microbes, and it is almost impossible to tell what they are simply by looking at them through a microscope. Microbiologists must analyze the genetic sequences of an organism to determine its location on the tree of life—the phylogenetic grouping of all known creatures—and researchers have classified only a tiny fraction of all observed microbes.
To be sure, all the organisms that have so far been studied in detail almost certainly descended from a common origin. Known organisms share a similar biochemistry and use an almost identical genetic code, which is why biologists can sequence their genes and position them on a single tree. But the procedures that researchers use to analyze newly discovered organisms are deliberately customized to detect life as we know it. These techniques would fail to respond correctly to a different biochemistry. If shadow life is confined to the microbial realm, it is entirely possible that scientists have overlooked it.
Ecologically Isolated Aliens
Where might investigators look for alien organisms on Earth today? Some scientists have focused on searching for organisms occupying a niche that is ecologically isolated, lying beyond the reach of ordinary known life. One of the surprising discoveries in recent years is the ability of known life to endure extraordinarily harsh conditions. Microbes have been found inhabiting extreme environments ranging from scalding volcanic vents to the dry valleys of Antarctica. Other so-called extremophiles can survive in salt-saturated lakes, highly acidic mine tailings contaminated with metals, and the waste pools of nuclear reactors.
Nevertheless, even the hardiest microorganisms have their limits. Life as we know it depends crucially on the availability of liquid water. In the Atacama Desert in northern Chile is a region that is so dry that all traces of familiar life are absent. Furthermore, although certain microbes can thrive in temperatures above the normal boiling point of water, scientists have not yet found anything living above about 130 degrees Celsius (266 degrees Fahrenheit). It is conceivable, though, that an exotic alternative form of life could exist under more extreme conditions of dryness or temperature.
Thus, scientists might find evidence for alternative life by discovering signs of biological activity, such as the cycling of carbon between the ground and the atmosphere, in an ecologically isolated region. The obvious places to look for such disconnected ecosystems are in the deep subsurface of Earth’s crust, in the upper atmosphere, in Antarctica, in salt mines, and in sites contaminated by metals and other pollutants. Alternatively, researchers could vary parameters such as temperature and moisture in a laboratory experiment until all known forms of life are extinguished; if some biological activity persists, it could be a sign of shadow life at work. Scientists used this technique to discover the radiation-resistant bacterium Deinococcus radiodurans, which can withstand gamma-ray doses that are 1,000 times as great as what would be lethal for humans. It turns out that D. radiodurans and all the other so-called radiophiles that researchers have identified are genetically linked to known life, so they are not candidate aliens, but that finding does not rule out the possibility of discovering alternative life-forms in this way.
Investigators have already pinpointed a handful of ecosystems that appear to be almost completely isolated from the rest of the biosphere. Located far underground, these microbial communities are cut off from light, oxygen and the organic products of other organisms. They are sustained by the ability of some microbes to use carbon dioxide and hydrogen released by chemical reactions or radioactivity to metabolize, grow and replicate. Although all the organisms found to date in these ecosystems are closely related to surface-dwelling microbes, the biological exploration of Earth’s deep subsurface is still in its infancy, and many surprises may lie in store. The Integrated Ocean Drilling Program has been sampling rocks from the seabed to a depth approaching one kilometer, in part to explore their microbial content. Boreholes on land have revealed signs of biological activity from even deeper locations. So far, however, the research community has not conducted a systematic, large-scale program to probe the deep subsurface of Earth’s crust for life.
Ecologically Integrated Aliens
One might suppose it would be easier to find alternative life-forms if they were not isolated but integrated into the known biosphere existing all around us. But if shadow life is restricted to alien microbes that are intermingled with familiar kinds, the exotic creatures would be very hard to spot on casual inspection. Microbial morphology is limited—most microorganisms are just little spheres or rods. Aliens might stand out biochemically, though. One way to search for them is to make a guess as to what alternative chemistry might be involved and then look for its distinctive signature.
A simple example involves chirality. Large biological molecules possess a definite handedness: although the atoms in a molecule can be configured into two mirror-image orientations—left-handed or right-handed—molecules must possess compatible chirality to assemble into more complex structures. In known life-forms, the amino acids—the building blocks of proteins—are left-handed, whereas the sugars are right-handed and DNA is a right-handed double helix. The laws of chemistry, however, are blind to left and right, so if life started again from scratch, there would be a 50–50 chance that its building blocks would be molecules of the opposite handedness. Shadow life could in principle be biochemically almost identical to known life but made of mirror-image molecules. Such mirror life would not compete directly with known life, nor could the two forms swap genes, because the relevant molecules would not be interchangeable.
Fortunately, researchers could identify mirror life using a very simple procedure. They could prepare a nutrient broth consisting entirely of the mirror images of the molecules usually included in a standard culture medium; a mirror organism might be able to consume the concoction with gusto, whereas a known life-form would find it unpalatable. Richard Hoover and Elena Pikuta of the NASA Marshall Space Flight Center recently performed a pilot experiment of this kind, putting a variety of newly discovered extremophiles into a mirror broth and then looking for biological activity. They found one microbe that grew in the broth, an organism dubbed Anaerovirgula multivorans that had been isolated from the sediments of an alkaline lake in California. Disappointingly, this organism did not turn out to be an example of mirror life; rather it was a bacterium with the surprising ability to chemically alter the amino acids and sugars of the wrong handedness so as to make them digestible. The study, however, looked at just a small fraction of the microbial realm.
Another possibility is that shadow life might share the same general biochemistry with familiar life but employ a different suite of amino acids or nucleotides (the building blocks of DNA). All known organisms use the same set of nucleotides—designated A, C, G and T for their distinguishing bases (adenine, cytosine, guanine and thymine)—to store information and, with rare exceptions, the same 20 amino acids to construct proteins, the workhorses of cells. The genetic code is based on triplets of nucleotides, with different triplets spelling out the names of different amino acids. The sequence of triplets in a gene dictates the sequence of amino acids that must be strung together to build a particular protein. But chemists can synthesize many other amino acids that are not present in known organisms. The Murchison meteorite, a cometary remnant that fell in Australia in 1969, contained many common amino acids but also some unusual ones, such as isovaline and pseudoleucine. (Scientists are not sure how the amino acids formed in the meteorite, but most researchers believe that the chemicals were not produced by biological activity.) Some of these unfamiliar amino acids might make suitable building blocks for alternative forms of life. To hunt for such aliens, investigators would need to identify an amino acid that is not used by any known organisms nor generated as a by-product of an organism’s metabolism or decay, and to look for its presence in the environment, either among living microbes or in the organic detritus that might be generated by a shadow biosphere.
To help focus the search, scientists can glean clues from the burgeoning field of synthetic, or artificial, life. Biochemists are currently attempting to engineer completely novel organisms by inserting additional amino acids into proteins. A pioneer of this research, Steve Benner of the Foundation for Applied Molecular Evolution in Gainesville, Fla., has pointed out that a class of molecules known as alpha-methyl amino acids look promising for artificial life because they can fold properly. These molecules, however, have not been found in any natural organism studied to date. As investigators identify new microbes, it would be a relatively simple matter to use standard tools for analyzing the composition of proteins, such as mass spectrometry, to learn which amino acids the organisms contain. Any glaring oddities in the inventory would signal that the microbe could be a candidate for shadow life.
If such a strategy were successful, researchers would face the difficulty of determining whether they were dealing with a genuine alternative form of life descended from a separate origin or with merely a new domain of known life, such as archaea, which were not identified until the late 1970s. In other words, how can scientists be sure that what seems like a new tree of life is not in fact an undiscovered branch of the known tree that split away a very long time ago and has so far escaped our attention? In all likelihood, the earliest life-forms were radically different from those that followed. For example, the sophisticated triplet DNA code for specifying particular amino acids shows evidence of being optimized in its efficiency by evolutionary selection. This observation suggests the existence of a more rudimentary precursor, such as a doublet code employing only 10, rather than 20, amino acids. It is conceivable that some primitive organisms are still using the old precursor code today. Such microbes would not be truly alien but more like living fossils. Nevertheless, their discovery would still be of immense scientific interest. Another possible holdover from an earlier biological epoch would be microbes that use RNA in place of DNA.
The chance of confusing a separate tree of life with an undiscovered branch of our own tree is diminished if one considers more radical alternatives to known biochemistry. Astrobiologists have speculated about forms of life in which some other solvent (such as ethane or methane) replaces water, although it is hard to identify environments on Earth that would support any of the suggested substances. (Ethane and methane are liquid only in very cold places such as the surface of Titan, Saturn’s largest moon.) Another popular conjecture concerns the basic chemical elements that make up the vital parts of known organisms: carbon, hydrogen, oxygen, nitrogen and phosphorus. Would life be possible if a different element were substituted for one of these five?
Phosphorus is problematic for life in some ways. It is relatively rare and would not have existed in abundance in readily accessible, soluble form under the conditions that prevailed during the early history of Earth. Felisa Wolfe-Simon, formerly at Arizona State University and now at Harvard University, has hypothesized that arsenic can successfully fill the role of phosphorus for living organisms and would have offered distinct chemical advantages in ancient environments. For example, in addition to doing all the things that phosphorus can do in the way of structural bonding and energy storage, arsenic could provide a source of energy to drive metabolism. (Arsenic is a poison for regular life precisely because it mimics phosphorus so well. Similarly, phosphorus would be poisonous to an arsenic-based organism.) Could it be that arseno-life still lingers in phosphorus-poor and arsenic-rich pockets, such as ocean vents and hot springs?
Another important variable is size. All known organisms manufacture proteins from amino acids using large molecular machines called ribosomes, which link the amino acids together. The need to accommodate ribosomes requires that all autonomous organisms on our tree of life must be at least a few hundred nanometers (billionths of a meter) across. Viruses are much smaller—as tiny as 20 nanometers wide—but these agents are not autonomous organisms because they cannot reproduce without the help of the cells they infect. Because of this dependence, viruses cannot be considered an alternative form of life, nor is there any evidence that they stem from an independent origin. But over the years several scientists have claimed that the biosphere is teeming with cells that are too small to accommodate ribosomes. In 1990 Robert Folk of the University of Texas at Austin drew attention to tiny spheroidal and ovoid objects in sedimentary rocks found in hot springs in Viterbo, Italy. Folk proposed that the objects were fossilized “nannobacteria” (a spelling he preferred), the calcified remains of organisms as small as 30 nanometers across. More recently, Philippa Uwins of the University of Queensland has discovered similar structures in rock samples from a deep-ocean borehole off the coast of Western Australia. If these structures indeed arise from biological processes—and many scientists hotly dispute this contention—they may be evidence of alternative life-forms that do not use ribosomes to assemble their proteins and that thus evade the lower size limit that applies to known life.
Perhaps the most intriguing possibility of all is that alien life-forms inhabit our own bodies. While observing mammalian cells with an electron microscope in 1988, Olavi Kajander and his colleagues at the University of Kuopio in Finland observed ultrasmall particles inside many of the cells. With dimensions as small as 50 nanometers, these particles were about one-tenth the size of conventional small bacteria. Ten years later Kajander and his co-workers proposed that the particles were living organisms that thrive in urine and induce the formation of kidney stones by precipitating calcium and other minerals around themselves. Although such claims remain controversial, it is conceivable that at least some of these Lilliputian forms are alien organisms employing a radically alternative biochemistry.
What Is Life, Anyway?
If a biochemically weird microorganism should be discovered, its status as evidence for a second genesis, as opposed to a new branch on our own tree of life, will depend on how fundamentally it differs from known life. In the absence of an understanding of how life began, however, there are no hard-and-fast criteria for this distinction. For instance, some astrobiologists have speculated about the possibility of life arising from silicon compounds instead of carbon compounds. Because carbon is so central to our biochemistry, it is hard to imagine that silicon- and carbon-based organisms could have emerged from a common origin. On the other hand, an organism that employed the same suite of nucleotides and amino acids as known life-forms but merely used a different genetic code for specifying amino acids would not provide strong evidence for an independent origin, because the differences could probably be explained by evolutionary drift.
A converse problem also exists: dissimilar organisms subjected to similar environmental challenges will often gradually converge in their properties, which will become optimized for thriving under existing conditions. If this evolutionary convergence were strong enough, it could mask the evidence for independent biogenesis events. For example, the choice of amino acids may have been optimized by evolution. Alien life that began using a different set of amino acids might then have evolved over time to adopt the same set that familiar life-forms use.
The difficulty of determining whether a creature is alien is exacerbated by the fact that there are two competing theories of biogenesis. The first is that life begins with an abrupt and distinctive transformation, akin to a phase transition in physics, perhaps triggered when a system reaches a certain threshold of chemical complexity. The system need not be a single cell. Biologists have proposed that primitive life emerged from a community of cells that traded material and information and that cellular autonomy and species individuation came later. The alternative view is that there is a smooth, extended continuum from chemistry to biology, with no clear line of demarcation that can be identified as the genesis of life.
If life, so famously problematic to define, is said to be a system having a property—such as the ability to store and process certain kinds of information—that marks a well-defined transition from the nonliving to the living realm, it would be meaningful to talk about one or more origin-of-life events. If, however, life is weakly defined as something like organized complexity, the roots of life may meld seamlessly into the realm of general complex chemistry. It would then be a formidable task to demonstrate independent origins for different forms of life unless the two types of organisms were so widely separated that they could not have come into contact (for instance, if they were located on planets in different star systems).
It is clear that we have sampled only a tiny fraction of Earth’s microbial population. Each discovery has brought surprises and forced us to expand our notion of what is biologically possible. As more terrestrial environments are explored, it seems very likely that new and ever more exotic forms of life will be discovered. If this search were to uncover evidence for a second genesis, it would strongly support the theory that life is a cosmic phenomenon and lend credence to the belief that we are not alone in the universe.
"
Venture Capital Deals Total $7.1B In Q3 | socalTECH.com
Venture Capital Deals Total $7.1B In Q3 | socalTECH.com: " Monday, October 22, 2007
Venture Capital Deals Total $7.1B In Q3
PricewaterhouseCoopers and the National Venture Capital Association reported over the weekend that nationwide, venture capital deals totaled $7.1B in 887 deals for the third quarter. The firms, which released their PwC/NVC MoneyTree Report, based on data from Thomson Financial over the weekend, reported that Southern California saw nearly $784.4M in venture deals for the quarter.
San Diego County lead the region in deal totals, with $359.2M in deals; Los Angeles County saw $342.4M in investments; and Orange County saw $82.625M. The largest financing for the quarter was for Thousand Oaks-based Ceres, which scored $75M in a venture round; other large fundings included Santa Monica-based Agensys, with $41.3M; and Sorrento Mesa-based SmartDrive Systems, with $41.0M raised.
The most active industries for investment for Q2 were Biotechnology, with $294.6M invested in the region, followed by nearly $103M in telecommunications deals; software firms also saw a great deal of investment, with $70.58M in investments spread across the area.
For the first time in several quarters, Southern California trailed New England in venture funding totals, as New England reported $998.0M in investments over 119 deals; versus 93 deals in Southern California. Silicon Valley continued to lead the nation, with $2.48B in investments over 287 deals.
Nationally, investments were down for the third quarter, from $7.2B and 1000 deals for Q2; sectors seeing increases in investment were Clean Tech, Internet, and Media and Entertainment; Life Sciences and Software saw slight declines in investment.
"
Complete DNA sequencing commercially available - The Money Times
Complete DNA sequencing commercially available - The Money Times: "
Personal genome sequencing will be possible at the commercial level with DeCode Genetics and 23andMe announcing start of this service.
Companies will scan about a million and 600,000 sites across the genome and assess a person’s risk for common diseases, along with providing information about ancestry, physical traits, and the ability to compare genes with friends and family.
DeCode Genetics will start "DeCodeMe" service for $985 for the personal genotyping product a person. The second company 23andMe will charge $999 per genome.
"We will include all the common diseases, including Alzheimer's," said Kari Stefansson, DeCode chief executive. "If, as a competent adult, you choose to look at your risk of developing Alzheimer's, that is your prerogative. But no one will force you to look at your Alzheimer's risk if you do not want to."
Till now, complete genome was only sequenced for research purposes and to study the causes of various diseases. Among the few people who got their DNA sequenced was James Watson, who gave the double helix model for DNA along with Crick.
Personalized DNA sequence will give analysts specific data for predicting the reasons for various common diseases and in case there are any mutations, they will be detected easily. This can be useful in treating certain diseases like cancer, Alzheimer's disease etc as the defected gene sequence can be compared to that of healthy individual’s DNA.
The service will be provided in North America and Europe. The person who wants to have his DNA sequenced will send a cheek swab to DeCode. After a few weeks he can access his DNA sequence on the website. The information will be protected by a password.
Although this service offers a lot of benefits but at the same time there are many concerns over this. The main issue is that of privacy. If the information gets into the hands of some negative elements, they can use it as their own DNA and thus wrong person will be implicated.
"If you want to commit a crime, there is nothing we can do to stop you," Dr Stefansson said.
One main concern is that the technology is still not so well developed. This can lead to discrepancies in the tests by different companies. It will be very bad for the person if he/she get the wrong news. People might suffer mentally if for example they know that they have a gene which will finally lead to cancer.
Scientists also feel that the knowledge of the genetic variations leading to diseases is still limited. So, it won’t be of much use to go through such a process. Craig Venter, the DNA sequencing pioneer who has analysed his whole genome in great detail, said he had found little useful information about his own health.
Dr Stefansson still feels that there is benefit of doing this. He said there is a strong scientific foundation behind this, which people can use to alter their own lifestyle in response to genetic risks. This can be used for enjoyment also, he said. "You have the opportunity to engage in a fun and interesting exchange when you compare your results to those of your friends."
Still there is a lot of work to be done in this field. There should be proper attention given to the privacy of this data. Appropriate laws should be formulated and scientists have to link more and more genetic variations to diseases, so that the data can be effectively used for the benefit of humans.
"
C&EN: COVER STORY - Synthetic Receptors Pull Molecules Into Cells
C&EN: COVER STORY - Synthetic Receptors Pull Molecules Into Cells: "August 25, 2003
Volume 81, Number 34
CENEAR 81 34 p. 38
ISSN 0009-2347
Volume 81, Number 34
CENEAR 81 34 p. 38
ISSN 0009-2347
DO IT YOURSELF
If the cell you're targeting with a drug doesn't have a receptor for that drug, that's okay. Just add one yourself.
That's what Blake R. Peterson, an assistant chemistry professor at Pennsylvania State University, is doing with "synthetic receptor targeting" [Bioconjugate Chem.,14, 67 (2003)]. The team working on the synthetic receptors includes graduate students Stephen L. Hussey and Scott E. Martin.
"We've discovered over the past two years that it's possible to make synthetic molecules that stably associate with cellular plasma membranes," Peterson says. The compounds that he uses are derived from 3b-cholesterylamine.
"By linking protein-binding motifs to 3b-cholesterylamines, we're able to display from these nonnatural cell surface receptors protein-binding groups that can engage protein ligands," he says. When proteins bind to the receptors on the cell surface, the binding triggers endocytosis. The ligands are typically antibodies, but molecules such as streptavidin can also be used [J. Am. Chem. Soc.,124, 6265 (2002)].
"We think that we're organizing a piece of the cellular plasma membrane when the ligand binds the receptor. That organization is sensed by the cell, and the cell in turn internalizes the ligand," Peterson says. "We see enhancements of as much as 300-fold in terms of delivery. We can really deliver a tremendous amount of material into cells in this way."
Peterson believes that certain cell types are going to be more susceptible to delivery by this method than others. For example, cells with higher rates of endocytosis may be more susceptible. In addition, tumor cells need large amounts of cholesterol to grow, so they may be more likely to take up the cholesterol-mimicking receptors.
Peterson believes that the mechanism of uptake involves cross-linking the receptors. Therefore, molecules being delivered will probably have to form bivalent interactions with the receptors.
Peterson is working on the delivery of the anticancer drug methotrexate, which inhibits the enzyme dihydrofolate reductase. Methotrexate is not cell permeable. Instead, it's taken up by folate receptors on the cell surface. One way that cancer cells become resistant to methotrexate is by stopping production of the folate receptors.
Peterson is investigating whether these missing cell surface receptors can be replaced with synthetic ones. Methotrexate would be delivered by linking it to a protein that targeted the receptor. If Peterson's group can design a receptor that will dimerize when it interacts with methotrexate, the protein would be unnecessary.
In his original systems, both the receptor and the protein were internalized. Now, Peterson is working on a system in which the receptors are recycled.
"We have a new set of compounds that undergo recycling. They're even better mimics of naturally occurring receptors in the sense that the receptor goes into the cell via endocytosis, but it releases the protein and can return to the cell surface by plasma membrane recycling."
CYCLING In synthetic receptor targeting, the plasma membranes of living cells are loaded with synthetic compounds that function as nonnatural receptors. In this illustration, the light blue portion is the cell surface, which has been loaded with receptors that have protein-binding motifs. The darker blue portion is the intracellular region, and the boundary between them is the plasma membrane. A macromolecular ligand, in this case antifluorescein IgG, binds to the receptor, triggering the formation of lipid rafts and the uptake of the receptor-ligand complex via endocytosis. Nonnatural receptors capable of dissociating from the ligand are recycled to the cell surface.
COURTESY OF BLAKE PETERSON
RNAi: Nobel Prize-Winning Biotechnology
RNAi: Nobel Prize-Winning Biotechnology: " "
RNAi: Nobel Prize-Winning Biotechnology
2 Recommendations
The Nobel Prize in physiology or medicine was awarded earlier this week. It went to Andrew Fire of Stanford University and Craig Mello of the University of Massachusetts Medical School for their work in RNA interference (RNAi). This technology is relatively young by Nobel standards, with the acknowledged research being completed less than 10 years ago. RNAi works by targeting messenger RNA and preventing it from being translated into protein, thus "knocking down" specific gene products. It is similar to antisense technology developed a decade earlier, but has so far proven more robust and effective.
The biotechnology industry has been quick to recognize and adopt RNAi as a tool in drug development programs, and to explore its potential as a therapeutic entity itself. RNAi uses short double-stranded RNA (siRNA) to effect protein knockdown. Providers of synthetic RNA, the consumable product for this technology, have already been merged into larger industry suppliers over the last few years, with Dharmacon being merged with Fisher Scientific (NYSE: FSH) and Ambion with Applied Biosystems (NYSE: ABI).
Other companies are exploring the use of siRNAs as potential drugs themselves. These include publicly traded Alnylam Pharmaceuticals (Nasdaq: ALNY) and Sirna Therapeutics (Nasdaq: RNAI). The ability of RNAi to target and deplete specific gene products gives it potential as a drug against both infectious diseases and genetic disorders caused by over- or undesired protein production. Both Alnylam and Sirna have been able to line up collaborations with big pharmaceutical firms such as Merck (NYSE: MRK), Novartis (NYSE: NVS), and GlaxoSmithKline (NYSE: GSK). This speaks to the recognized therapeutic potential of RNAi.
There are still obstacles to be overcome before siRNA-based therapeutics reach the market -- in particular, systematic delivery of these inherently unstable drugs throughout the body -- but advances in product stability by chemical modification and drug delivery continue to be made.
While drugs based on RNAi knockdown technology may have the potential to become the next big thing in biotechnology, they are still a long, long way from becoming FDA-approved marketable entities. But it's never too soon to start keeping an eye on the future -- the Motley Fool Rule Breakers newsletter specializes in identifying promising emerging technology companies, and you can try it free for 30 days.
As an aside, hats off to Stanford University. Along with a share of the aforementioned prize in medicine or physiology, the faculty also scored in chemistry, as the Nobel committee recognized the work of Dr. Roger Kornberg "for his studies on the molecular basis of eukaryotic transcription."
For further Foolishness:
GlaxoSmithKline is a Motley Fool Income Investor selection, while Merck is a former selection of that service.
Fool contributor Ralph Casale spent more than two years of research on a project that RNAi made all but irrelevant. He owns shares in GlaxoSmithKline but holds no financial position in any other firm mentioned. He was at one time an employee of Applied Biosystems.The Motley Fool has adisclosure policy.
Foreign Invasion of the Biochip Market
Foreign Invasion of the Biochip Market: " "
Foreign Invasion of the Biochip Market
0 Recommendations
A market dominated by American companies is about to get a little tighter. A consortium of Japanese companies including Toshiba, and Canon (NYSE: CAJ) are planning on jointly developing biochips for research and diagnostic purposes.
The consortium, which will be set up in the middle of next month, will also bring in synthetic fiber maker Toray Industries, medical consulting firm MediBic, and 30 to 40 more companies. The group will be aided in the endeavor by the government-affiliated Kazusa DNA Research Institute.
There wasn't much more information in the announcement about it, but I'd guess it will be years before the consortium could have a marketable product. There's also no word on how the companies will sidestep Affymetrix' (Nasdaq: AFFX) and Agilent Technologies' (NYSE: A) patents on attaching RNA or DNA molecules to the silicone-based chips. Illumina (Nasdaq: ILMN) certainly hasn't been able to get around Affymatrix' patents.
While increased competition is not usually a good thing for companies, it shouldn't be too debilitating for American ones. The biochip market, which has essentially been limited to research laboratories, is expanding greatly.
For instance, chips are being developed for clinical diagnostics to determine the genetic makeup of patients and their tumors. They're also being developed to identify species quickly -- for example, with pests in food products or potential illegal imports. With the expected dramatic increase in the coming years, and the American companies' big head start in it, the biochip market still has a way to go before becoming the next automobile market.
For further biochip Foolishness:
Free Trip to South America!
The Value of Myriad's Genes
The Value of Myriad's Genes: " "
The Value of Myriad's Genes
13 Recommendations
Myriad Genetics (Nasdaq: MYGN) is unique in the biotech industry because it has a wildly profitable diagnostics business to support its drug research and development efforts.
The company has a lot of financial flexibility and does not need to rely on partnering the way other development-stage biotechs do, including Exelixis (Nasdaq: EXEL), Medarex (Nasdaq: MEDX), or Seattle Genetics (Nasdaq: SGEN).
And because Myriad's diagnostics products are booming, we can value the company based on hard cash -- and not need to cross our fingers that a drug will one day make it out of the Myriad pipeline and be a commercial success.
Scanning your genes
If your family has a history of cancer, you have higher risk of cancer yourself. Myriad sells five diagnostic products that assess whether a person has a high risk of cancer because of their genetic code. Myriad looks for the specific genes known to be involved in the development of cancer.
Being forewarned of a genetic disposition toward cancer enables health practitioners to keep cancer in check, by screening for it regularly and treating it at its earliest appearance. I expect that Myriad's products will become increasingly mainstream and sales should exhibit strong growth for years to come.
Myriad just launched a new product, TheraGuide 5-FU, and will introduce another test next year. The continued rollout of new products indicates a positive growth spurt.
For the quarter ended Sept. 30, Myriad's diagnostic revenues grew at a blistering 49% pace to reach $46 million. The company believes these revenues should be near $200 million for its fiscal year, and it has the manufacturing capacity to support $400 million in sales.
These products have eye-poppingly large margins. Gross margin came in at 84% last quarter, with operating margin of 40%. In other words, from sales of $46 million, the company came away with $18.5 million to reinvest. This cash generated from the diagnostics operations is the basis for my valuation.
Breaking it down
If Myriad maintains 40% operating margins on the expected $200 million in diagnostic product sales this fiscal year, that portion of the business would generate $80 million pre-tax. What is a business worth that generates this kind of cash?
I started with $80 million, then applied a 35% tax rate to the $80 million operating income, equaling $52 million in profit. Myriad had $12 million capital expenditures over the last 12 months, and I backed out a portion of that to arrive at a hypothetical $45 million free cash flow generated from diagnostic product revenue.
To keep things simple, I assumed that the cash flows from diagnostics would grow at 25% for 10 years, and then I applied a 3% terminal growth rate. While that sharp dropoff after 10 years isn't likely to reflect reality, the assumption keeps the exercise simple.
Using a discount rate of 12%, the value of the diagnostics business under these conditions is $2.4 billion. Note that the current market cap of the company is $2.1 billion, meaning that all of the company's pipeline drugs like Flurizan and Azixa are coming along for free. You could even draw the conclusion that Myriad's drug R&D is viewed as a drag on the company's diagnostic business.
Foolish take home
There is tremendous value in Myriad's diagnostic products. This segment of the business could be worth more than $2.4 billion -- I think it could exceed 25% growth over the next few years, and I expect robust growth to continue for well more than 10 years.
Myriad will report data from its first phase 3 trial with Flurizan in the treatment of Alzheimer's disease in the middle of next year. As owners of Atherogenics (Nasdaq: AGIX) and Neurochem (Nasdaq: NRMX) can attest, the release of phase 3 trial data is a dangerous time for biotech investors. But with the value of Myriad's diagnostic products now supporting the entire market cap of the company, shares probably won't come crashing down if Flurizan fails.
As with any other high-growth company this is not a risk-free investment, but it's certainly got attractive prospects and shares that are available at a good price.
Free Trip to South America!
Genetic Tests: Future or Fad?
Genetic Tests: Future or Fad?: "
Genetic Tests: Future or Fad?
2 Recommendations
They may take away my bachelor's in genetics for this, but I have to admit, I'm not interested in having a genomewide test run on my DNA. More specifically, I'm not interested in shelling out a thousand bucks to find out minute details about my genes.
Last week, deCODE genetics (Nasdaq: DCGN) announced that it's accepting subscriptions for its DNA testing service, deCODEme, which will test 1 million DNA variants using biochips from Illumina (Nasdaq: ILMN). That's a lot of variants, but it skips the rare -- but more definitive -- traits such as mutations in BRCA1, which drastically increases the risk of developing breast cancer. Instead, the test will concentrate on genes that lead to "obvious and potentially quirky traits."
The service will compete against the recently launched service from 23andMe, which has backing from Google (Nasdaq: GOOG) and Genentech (NYSE: DNA). Both companies have a Web 2.0 aspect in that you can share your genetic information among family and friends on the companies' websites. Learning about one's ancestry may be the potential driver of new customers for the foreseeable future, and the late-November launches were probably an effort to get rich Aunt Mildred to buy genetic tests for everyone for Christmas.
While I think this information is interesting, I'm just not sure these tests will become wildly popular until their prices come down. Investors looking to invest in genetic tests would be better off investing in companies -- like Rule Breakers pick Myriad Genetics (Nasdaq: MYGN), Genzyme (Nasdaq: GENZ), or even deCODE -- that offer tests for specific diseases that might run in an individual's family. As medicine gets more personal, specific genetic tests will have a lot more value to patients than genomewide tests.
More Foolishness about DNA:
"
11.21.2007
Chromophore - Wikipedia, the free encyclopedia
Chromophore - Wikipedia, the free encyclopedia: "
Chromophore
From Wikipedia, the free encyclopedia
A chromophore is part (or moiety) of a molecule responsible for its color.
When a molecule absorbs certain wavelengths of visible light and transmits or reflects others, the molecule has a color. A chromophore is a region in a molecule where the energy difference between two different molecular orbitals falls within the range of the visible spectrum. Visible light that hits the chromophore can thus be absorbed by exciting an electron from its ground state into an excited state.
In biological molecules that serve to capture or detect light energy, the chromophore is the moiety that causes a conformational change of the molecule when hit by light.
Chromophores almost always arise in one of two forms: conjugated pi systems and metal complexes.
In the former, the energy levels that the electrons jump between are extended pi orbitals created by a series of alternating single and double bonds, often in aromatic systems. Common examples include retinal (used in the eye to detect light), various food colorings, fabric dyes (azo compounds), lycopene, β-carotene, and anthocyanins.
The metal complex chromophores arise from the splitting of d-orbitals by binding of a transition metal to ligands. Examples of such chromophores can be seen in chlorophyll (used by plants for photosynthesis), hemoglobin, hemocyanin, and colorful minerals such as malachite and amethyst.
A common motif in biochemistry is chromophores consisting of four pyrrole rings. These come in two types:
- the pyrroles form an open chain, no metal: phytochrome, phycobilin, bilirubin
- the pyrroles form a ring (porphyrin), with a metal in the center: hemoglobin, chlorophyll
Complete DNA sequencing commercially available - The Money Times
Complete DNA sequencing commercially available - The Money Times: "
Personal genome sequencing will be possible at the commercial level with DeCode Genetics and 23andMe announcing start of this service.
Companies will scan about a million and 600,000 sites across the genome and assess a person’s risk for common diseases, along with providing information about ancestry, physical traits, and the ability to compare genes with friends and family.
DeCode Genetics will start "DeCodeMe" service for $985 for the personal genotyping product a person. The second company 23andMe will charge $999 per genome.
"We will include all the common diseases, including Alzheimer's," said Kari Stefansson, DeCode chief executive. "If, as a competent adult, you choose to look at your risk of developing Alzheimer's, that is your prerogative. But no one will force you to look at your Alzheimer's risk if you do not want to."
Till now, complete genome was only sequenced for research purposes and to study the causes of various diseases. Among the few people who got their DNA sequenced was James Watson, who gave the double helix model for DNA along with Crick.
Personalized DNA sequence will give analysts specific data for predicting the reasons for various common diseases and in case there are any mutations, they will be detected easily. This can be useful in treating certain diseases like cancer, Alzheimer's disease etc as the defected gene sequence can be compared to that of healthy individual’s DNA.
The service will be provided in North America and Europe. The person who wants to have his DNA sequenced will send a cheek swab to DeCode. After a few weeks he can access his DNA sequence on the website. The information will be protected by a password.
Although this service offers a lot of benefits but at the same time there are many concerns over this. The main issue is that of privacy. If the information gets into the hands of some negative elements, they can use it as their own DNA and thus wrong person will be implicated.
"If you want to commit a crime, there is nothing we can do to stop you," Dr Stefansson said.
One main concern is that the technology is still not so well developed. This can lead to discrepancies in the tests by different companies. It will be very bad for the person if he/she get the wrong news. People might suffer mentally if for example they know that they have a gene which will finally lead to cancer.
Scientists also feel that the knowledge of the genetic variations leading to diseases is still limited. So, it won’t be of much use to go through such a process. Craig Venter, the DNA sequencing pioneer who has analysed his whole genome in great detail, said he had found little useful information about his own health.
Dr Stefansson still feels that there is benefit of doing this. He said there is a strong scientific foundation behind this, which people can use to alter their own lifestyle in response to genetic risks. This can be used for enjoyment also, he said. "You have the opportunity to engage in a fun and interesting exchange when you compare your results to those of your friends."
Still there is a lot of work to be done in this field. There should be proper attention given to the privacy of this data. Appropriate laws should be formulated and scientists have to link more and more genetic variations to diseases, so that the data can be effectively used for the benefit of humans.
"
11.20.2007
ISN Newsletter - July 1999 - section 2
ISN Newsletter - July 1999 - section 2: "
DIETRICH LOTHAR MEYER
Dietrich Lothar Meyer, neuroethologist, neurophysiologist, neuroanatomist, died on June 8, 1999. There must be more stories about Dietrich than any other person in comparative neurobiology. It was impossible to resist his vibrant energy and mesmerizing personality. Who was this man?
Drawn into neuroscience after medical school and a thesis on the gait of schizophrenics, he studied vestibular mechanisms of compensation with Klaus Peter Schaefer in Goettingen, Germany, and Ted Bullock in La Jolla, California. His curiosity led him to compare species and exploit biodiversity. Ear nystagmus in deer? Tonus function in sense organs? The more exotic, dangerous, and difficult the specimen was to obtain, the better. For Dietrich, science was the thrill of traveling, hunting, having fun. A grant application without a trip to Africa, the Amazon, Australia or Alaska? Too boring!
Dietrich had a keen instinct for the species with an unusual behavior. Geckos in a Brazilian bar show a 180o vestibulo-ocular reflex when tied to a beer coaster and tilted 360 degrees consternating other patrons. Flatfish could be manipulated to remain upright, fish with a ventral substrate response, upside down catfish, one eyed or four eyed fish -- whatever could tell us about underlying principles. Dietrich moved from the vestibular to the visual system, determining sources of CNS input to the eye, and explored long forgotten chemosensory systems (what do you know about the nervus terminalis?), always combining evolutionary, behavioral, physiological and anatomical perspectives.
Appointed full professor and head of the department of neuroanatomy in Goettingen at the age of 37, his many students included Werner Graf, Eberhard Fiebig, Christopher von Bartheld, Mario Wullimann, Michael Hofmann, Cordula Malz, Andreas Schober, Carmen Pinuela, and Arun Jadhao. Dietrich collaborated with bigwigs in comparative neurobiology, Ted Bullock, Walter Heiligenberg, Henning Scheich, Sven Ebbesson, Glenn Northcutt, Jack Pettigrew. Detailed scholarly work and formal presentations were not his style. He preferred eye to eye discussions in the bar next door and brief publications then off to the next expedition. There was no lack of ideas, only time ran out on this man whose life was burning like a candle lit at both ends. Dietrich was 51 years old.
Chris von Bartheld
"
NevadaNews - University of Nevada, Reno
NevadaNews - University of Nevada, Reno: "
Professor organizes first-of-its-kind international symposium on brain molecules
1/26/2006
Recently, University of Nevada, Reno Professor Christopher von Bartheld organized a first-of-its-kind symposium on the evolution of neurotrophic factors in the brain.
Neurotrophic factors are molecules contributing to the survival (nourishment) of nerve cells in the brain, and therefore the development of an organism as a whole.
“There must be communication between nerve cells and target organs,” von Bartheld said. “Trophic factors help to provide feedback and survival signals, assuring proper development and function of the brain.”
Von Bartheld organized his symposium in order to foster a dialogue on the role of neurotrophic factors in organisms throughout their evolutionary development.
The symposium, which took place in conjunction with the Annual Meeting of the Society for Neuroscience in Washington, D.C., featured a wide range of speakers representing six countries and three continents. Von Bartheld called it the most internationally varied panel ever seen at this annual gathering of comparative and evolutionary neurobiologists.
“There have been literally thousands of papers written on trophic factors during brain development,” said von Bartheld. “But this was the first symposium to explore what role trophic factors play in evolution in an organized and systematic way.”
The study of trophic factors has the potential to play a key role in research and breakthroughs concerning debilitative ailments such as Alzheimer’s and Parkinson’s diseases.
In addition to being the first of its kind, the symposium is affiliated with the publishers and editorial board of the journal "Brain, Behavior & Evolution." Dr. von Bartheld was granted the position of guest editor on a special issue of the journal focusing specifically on neurotrophic factors, and their evolution.
"
11.19.2007
Patent Law Blog (Patently-O): Obviousness: Motivation to Combine References Found in Expert Testimony
Patent Law Blog (Patently-O): Obviousness: Motivation to Combine References Found in Expert Testimony: "
Obviousness: Motivation to Combine References Found in Expert Testimony
Alza holds the patent on a once-daily controlled release oxybutynin formulation used to treat urinary incontinence. (U.S. Patent No. 6,124,355). Alza’s formulation is sold as Ditropan XL®. Mylan wants to sell a generic version and challenged the patent, and the district court obliged by finding the patent invalid as obvious.
In affirming the obviousness finding, a unanimous decision penned by Judge Gajarsa presents its defense of the much criticized teaching/suggestion/motivation test (TSM Test) for obviousness that is currently on review before the Supreme Court in the Teleflex case.
The meat of the opinion begins with a reminder that the motivation test did not arise with Federal Circuit, but rather that the making of the CCPA. The 1943 case of Fridolph, for instance, instructs that when “considering more than one reference, the question always is: does such art suggest doing the thing the [inventor] did."
Next, the opinion explains that the TSM test “has been developed consistent with the Supreme Court’s obviousness jurisprudence as expressed in Graham and the text of [Section 103(a)].” The court explains that the purpose of the proof portion of the TSM test test is to avoid the problem associated with hindsight. The theory is that obviousness “should be based on evidence rather than on mere speculation or conjecture.”
Many of the briefs in Teleflex argue that the TSM test is “rigid.” In Alza, the court disagreed, arguing that the test is flexible “because a motivation may be found implicitly in the prior art.” (emphasis in original).
We do not have a rigid test that requires an actual teaching to combine before concluding that one of ordinary skill in the art would know to combine references. This approach, moreover, does not exist merely in theory but in practice, as well. Our recent decisions in Kahn and in Cross Medical Products amply illustrate the current state of this court’s views.
In Kahn, the court emphasized the availability of implicit proof of a motivation to combine references, and in Cross Medical, the court found that motivation could come from “general knowledge.”
In this case, the patent holder Alza argued that back in 1995, there was no suggestion to try (or likelihood of success of) using controlled release pills because nobody thought that the formulation could be absorbed in the colon. Defendant Mylan relied on an expert witness who testified that back in 1995 there would have been a reasonable likelihood that a controlled release pill would work – and thus that there was a motivation to try it. Alza presented some references that suggested that controlled-release pills might not work, but those did not specifically discuss absorption of the type of molecule contained in Ditropan.
Based on the expert testimony, the lower court agreed that the TSM test had been satisfied and that the patent was invalid as obvious. The appellate panel affirmed on a clear error standard, finding that:
we cannot perceive clear error in the district court’s factual findings that while colonic absorption was not guaranteed, the evidence, viewed as a whole, is clear and convincing that a person of ordinary skill in the art would nonetheless have perceived a reasonable likelihood of success and that she would have been motivated to combine prior art references to make the claimed invention.
Obviousness affirmed.
"
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