**BIOTECH AND PHARMA NEWS**

[Preciouslife1]

Drug Said To Shrink Tumors

New York Times Full Feed -

The drug Revlimid, made by the Celgene Corporation, can shrink tumors and slow down the spread of multiple myeloma, a deadly cancer of the bone marrow, according to two studies conducted in the United States and Europe.
Revlimid, a derivative of thalidomide, helped shrink tumors for about 60 percent of patients in combination with dexamethasone, a corticosteroid, and stopped the cancer from spreading for six months, according to two studies published in this week's New England Journal of Medicine.
The drug, known chemically as lenalidomide, won American approval for multiple myeloma in July 2006 based on the studies.

[Preciouslife1]

Race to mimic human embryonic stem cells
'Personalized' tissues come a step closer.


The donor cells used to create cloned primate embryos came from a monkey, Semos, named after the god in the science fiction work Planet of the Apes. Two much-anticipated scientific firsts announced this week bring the dream of regenerative medicine a step closer. The production of cloned primate embryonic stem cells and the reprogramming of adult human cells both represent important milestones in the quest to produce 'pluripotent' cells, which can develop into almost any of the body's roughly 200 cell types.

Human embryonic stem cells have this property, and those used in research are usually extracted from leftover embryos created during in vitro fertilization. But researchers want to create pluripotent cells that are genetically matched to individual patients. Such cells could then be transplanted to treat disorders such as Parkinson's disease and diabetes, or be used by researchers to model disease progression.

Cloning offers one way to create these cells. This week, a team led by Shoukhrat Mitalipov of Oregon Health & Science University in Beaverton report the first creation of embryonic stem cells from cloned monkey embryos (see page 497). Until now, cloned embryonic stem cells had been created only in mice. The accomplishment in primates is "like breaking the sound barrier", says Robert Lanza, of Los Angeles-based biotech company Advanced Cell Technology.

The creation in 1996 of the first cloned animal, Dolly the sheep, led to a rapid succession of clones. But continued failure to achieve cloned human or monkey embryos resulted in pessimism.

In 2003, primate-cloning researcher Gerald Schatten said: "With current approaches, NT [nuclear transfer, a cloning technique] to produce embryonic stem cells in nonhuman primates may prove difficult — and reproductive cloning unachievable1." This was after his study involving 716 monkey eggs failed to produce a single clone. Then, in February 2004, Woo Suk Hwang, then of Seoul National University in Korea, announced that he had created cloned human embryonic stem cells2. But, in January 2006, those results were shown to have been faked, and some suspected that Schatten was right.

Mitalipov's group had been trying for almost a decade to achieve reproductive cloning in monkeys, and used some 15,000 eggs in the process. After Hwang's results turned out to be fraudulent, the researchers decided to switch from reproductive cloning to trying to establish a cloned embryonic stem-cell line. They took skin cells from Semos, a nine-year-old rhesus macaque, and inserted the cells' nuclei into eggs that had had their own genetic material removed. By January 2007, they had a cell line that retained its embryonic pluripotency — and, a couple of months later, another.

Mitalipov credits their success to a US$19,000 imaging machine, named Oosight, which allows the structures in the egg that hold the DNA to be clearly seen, enabling easy extraction — the first step in nuclear transfer. Previously, researchers used a dye named Hoechst combined with ultraviolet light to locate and remove an egg's DNA. But Mitalipov's group found that this method damaged the egg.

Mitalipov says that his group's technique should work in human cells: "There's nothing specific here. But you must use this kind of imaging system," he says.

Reproductive cloning in monkeys, though, still looks to be a long way off. In April, after creating the two cell lines, Mitalipov's team tried transferring 77 embryos created into about a dozen surrogates. All failed to create pregnancies.

In the aftermath of the Hwang fraud, Nature has taken the unusual step of having these results independently verified by a team at Monash University in Melbourne, Australia3. "The scientific community has a need to have some certainty in the outcomes of nucleartransfer experiments given the recent unfortunate experience with human somatic-cell nuclear transfer. We have total confidence in these conclusions," says Alan Trounson, a member of the Monash team.

Many scientists are hesitant to apply the technique in humans because it requires women to undergo an uncomfortable procedure that involves significant health risks. Altogether, Mitalipov's team used 304 eggs to produce the two primate embryonic stemcell lines. The researchers still have little idea of what separates the majority failures from the rare successes, so a similar number of eggs would probably be required to establish human lines.

Avoiding controversy

"The basic science of this is important," says John Gearhart, director of the Stem Cell Program at Johns Hopkins Medicine in Baltimore, Maryland. "But the low frequency of success here is troubling — particularly when considering human work."


After reprogramming, cells taken from human skin became embryonic-like stem cells.But there is another promising route to creating pluripotent cells that does not require eggs or the controversial destruction of embryos. On Tuesday, Shinya Yamanaka of the University of Kyoto in Japan reported that his team had created pluripotent cells from human skin cells4 and, on the same day, a team of researchers led by James Thomson at the University of Wisconsin, Madison, reported the same5.

Yamanaka's work builds on his exciting discovery last year that introducing four transcription factors into mouse skin cells 'reprogrammed' the cells into an embryo-like state. Early this summer, Yamanaka and two other groups reported using the same four factors to create cells that seemed to be indistinguishable from embryonic stem cells6.

Because of the basic differences between human and mouse cells, Yamanaka was surprised to find that these four factors produced the same result in humans. The team generated 10 pluripotent lines from a culture of some 50,000 facial skin cells that had been subjected to the four factors. The skin sample, provided by a company in the United States, had been taken from a 36-year-old Caucasian woman. Yamanaka repeated the exercise with cells from synovial (joint) fluid from a 69-yearold man with similar results. During culture, the pluripotent cells take on the flat shape of embryonic stem cells.

Why so few cells successfully form such 'induced' pluripotent stem (iPS) cells is a mystery that Yamanaka is still trying to resolve. But because he uses such a cheap resource — cells that can be attained in their millions from a single skin biopsy — the low yield is not a problem, he says. In comparison to human embryonic stem cells — after much political wrangling and laborious effort, there are only three cell lines in Japan — his technique is prolific, Yamanaka says. "In a little dish you can get ten cell lines quickly. Practically speaking it's a very high success rate."

Like the mouse iPS cells, Yamanaka's human iPS cells passed all the basic tests for embryonic stem cells, including the ability to form tumours expressing the three primary germ layers when injected under the skin of a mouse engineered to have no immune system.

“Until now, cloned embryonic stem cells had been created only in mice.”

But are they truly pluripotent? The most stringent tests, carried out in mice, are to see whether a whole individual can be created from iPS cells or whether iPS cells mixed with an embryo's are expressed in all of the resulting chimaeric mouse's tissues. Neither test can be done with human cells.
"In humans, there's no answer to the question," says Yamanaka.

But, he adds, if the cells are for use in therapy or research on a disease affecting a particular tissue, it doesn't matter. Yamanaka's cells, for example, were able to form neurons, and cardiac muscle cells that — after differentiating for 12 days — started beating. But iPS cells do have drawbacks. Introduction of the four 'Yamanaka factors' requires genetic manipulation using viral vectors that health agencies would be unlikely to approve for clinical use. And one of the factors, c-myc, is thought to be responsible for tumours in mice.

Thomson, who was the first to isolate and maintain human embryonic stem cells in culture, has gone part way towards solving these problems. He also used four factors, introduced by viral vectors, to reprogramme human foreskin cells. But only two of the four are the same, and he does not use c-myc. What is more, the discovery that a different recipe resulted in successful reprogramming suggests that scientists might have a greater degree of flexibility in finding clinically acceptable variations on Yamanaka's selection.

Onto the home strait
With researchers crowding into the field, Gearhart and others anticipate rapid advancement. "The iPS strategy is a major paradigm shift in reprogramming cells, and if proved effective and safe with human cells — most likely coming very very soon — it will diminish the role of somatic-cell nuclear transfer (SCNT) for deriving patient-specific pluripotent cells," says Gearhart.

The case for iPS-cell research and against using cloning was highlighted this weekend when the University of Edinburgh's Iam Wilmut, one of Dolly's creators, announced that he planned to turn his back on the field he pioneered in favour of research using Yamanaka's reprogramming technique.
Mitalipov maintains that the egg is the only "perfect reprogramming machine", and is confident that cloned cells will be the first to show therapeutic value. He says he has already more than doubled the efficiency of his cloning technique. And he is preparing for the clinic. Plans are underway to create cloned embryonic cell lines from Semos and some ten other monkeys, to induce diseases such as diabetes in them, and then see if the cloned embryonic stem cells can be used to treat them.

[Preciouslife1]

p53 regulates drug sensitivity

http://www.biotechnews.com.au/index.php/id;617534440;fp;4194304;fpid;1

‘Guardian of the genome’ predicts treatment outcomes for childhood cancer.

Australian researchers have identified a new role for a cancer-prevention gene in the response to drug treatment for childhood cancer.

In humans, the p53 tumour suppressor gene, also known as the 'guardian of the genome', is known for its role in the prevention of cancer.

Mutations in the gene are associated with a high incidence of cancer due to the uncontrolled division of cells which give rise to tumours.

In childhood cancers such as neuroblastoma, p53 mutations are rare at diagnosis, but they can emerge after chemotherapy.

In a study published in the international journal Cancer Research this month, researchers from the Children's Cancer Institute Australia for Medical Research (CCIA) and collaborators in the USA, describe a new role for p53 in childhood cancer.

The group showed that by inactivating p53 in neuroblastoma cells, the most common childhood cancer, the cancer cells became resistant to a number of chemotherapy drugs.

"Our results provide definitive evidence of a role for p53 as a gene which dictates drug sensitivity in neuroblastoma," lead author Dr Chengyuan Xue, of CCIA's molecular diagnostics program, said.

"These results highlight the importance of p53 status as an indicator of a patient's treatment response in neuroblastoma."

Further research has found that p53 does not have one defined function in cancer susceptibility to treatment, he said.

"In some cancer cell types it does not act as a drug sensitivity gene. It is therefore important to assess the clinical effect of p53 mutations in different cancers in a tissue context."

[Preciouslife1]

Clinicians May In Future Treat Diseases By Regulating The Immune Response

http://www.medicalnewstoday.com/articles/89630.php

Investigators at St. Jude Children's Research Hospital have discovered a new signaling molecule that prevents immune responses from running amok and damaging the body.
The finding could lead to the development of new treatments for cancer, using vaccines; for autoimmune diseases, such as Type 1 diabetes; and for inflammatory diseases, such as inflammatory bowel disease (IBD) and asthma.

The St. Jude team discovered that specialized immune lymphocytes called regulatory T cells release a protein complex composed of two proteins called Ebi3 and Il12a. This protein complex acts like a brake on the activity of the aggressive immune cells called effector T lymphocytes. A report on this discovery appears in the journal Nature Nov. 22, 2007.

The newly recognized protein complex is one of a large group of signaling molecules called cytokines that cells use to communicate with each other. Since the immune system cytokines are called interleukins, the St. Jude team named this protein interleukin-35 (IL-35). Most cytokines stimulate immune system cells by driving the immune attack or causing inflammation. However, IL-35 is one of the few signaling molecules known to inhibit immune system activity.

"The discovery of IL-35 is important because the manipulation of regulatory T cells is a key goal of immunotherapy," said Dario Vignali, Ph.D., associate member in the St. Jude Department of Immunology, and the paper's senior author. Immunotherapy is the treatment of infections, cancer or other diseases by manipulating the immune system to enhance or restrict its activity. Despite the fact that regulatory T cell-mediated immunotherapy holds promise for patients, the molecules responsible for the cells' ability to suppress immune system activity are largely unknown, a problem that has slowed progress in this field.

The St. Jude team showed that the genes that produce IL-35 (Ebi3 and II12a) are active in regulatory T cells but not in effector T cells and are critical to regulatory T cell function. In fact, regulatory T cells that lack the Ebi3 and II12a genes lose much of their ability to suppress effector T cells. In addition, these regulatory T cells are unable to cure mouse models of an inflammatory disease that closely resembles human IBD.

When the researchers added regulatory T cells to a culture dish with effector T cells, the regulatory T cells dramatically increased their production of the decoded forms (messenger RNA) of the Ebi3 and II12a genes. This suggests that effector T cells had released signals that stimulated the regulatory T cells to decode these genes and make IL-35, the researchers reported.

"The identification of IL-35 as a key cytokine released by regulatory T cells adds significantly to our understanding of how these cells prevent immune responses from running out of control and causing damage," Vignali said. "Regulatory T cells are seen as a major impediment to the development of effective anti-cancer vaccines and may prevent sterilizing immunity in certain chronic infections, such as hepatitis C and tuberculosis. As the maximal suppressive function of regulatory T cell is dependent on IL-35, blocking its activity may reduce regulatory T cell function and reduce their ability to block anti-tumor immune responses. Thus, treatments that block IL-35 activity may make anti-cancer vaccines more effective." Vaccines work by stimulating the immune system to recognize and attack specific targets, such as germs or cancer cells.

"Autoimmune diseases and inflammatory diseases are caused by a breakdown of the normal regulatory processes that control our immune system," Vignali said. "Novel treatments that add IL-35 or boost IL-35 activity may also provide new therapeutic opportunities for these diseases."

"The identification of IL-35 is especially exciting because, to date, it is the only known cytokine that is made specifically by regulatory T lymphocytes and can suppress the activity of effector T cells directly," said Lauren Collison, Ph.D., a postdoctoral fellow in Vignali's laboratory who contributed significantly to the project. "This suggests that controlling levels of IL-35 in patients might one day allow clinicians to dial the immune response up or down depending on the needs of the patient." Collison is the paper's first author.

[Preciouslife1]

News From The Journal Of Clinical Investigation

http://www.medicalnewstoday.com/articles/89637.php

Location, location, location: gene determining body organ position identified

Primary ciliary diskinesia (PCD) is an inherited disease caused by mutations in any one of a number of genes, including the gene DNAH5. Individuals with PCD are highly susceptible to chronic recurrent respiratory infections and the left-right positioning of the organs of their body is completely mirror image reversed (i.e., instead of their heart being on the left side of their body it is on the right). Some individuals with PCD exhibit heterotaxy, a condition characterized by randomized left-right organ positioning. It had not been established previously whether the genetic defects that lead to PCD are also responsible for heterotaxy, but new research in mice by Cecelia Lo and colleagues at the National Institutes of Health, Bethesda, has now suggested that this is the case.

In the study, a substantial proportion of fetal mice with a mutation in both copies of their Dnahc5 gene (the mouse eq.uivalent of DNAH5) exhibited heterotaxy and, as observed in human heterotaxy syndromes, these embryos had variable combinations of complex structural heart defects. Further analysis confirmed that these mice were a robust model of PCD, indicating that a Dnahc5 mutation causing PCD-like disease in mice also can cause heterotaxy. These data led the authors to suggest individuals with PCD should be assessed for heterotaxy and associated congenital heart defects, and conversely, patients with heterotaxy should be evaluated for undiagnosed PCD. Such combined diagnoses would dictate very different clinical strategies that may improve outcome.

Title: Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia

Author Contact:
Cecilia W. Lo
National Institutes of Health, Bethesda, Maryland, USA.

New role for intestinal protein in blood clotting

An intestinal protein known as BSDL that helps the body breakdown and absorb cholesterol is also found circulating in our bloodstream, where its role has been an enigma. However, in a new study, Laurence Panicot-Dubois and his colleagues at the Université de la Méditerranée, France, have identified a role for blood-borne BSDL in blood clot formation.

In vitro analysis showed that BSDL enhances the activation of human platelets -- cells found in the blood that when activated are key to the formation of blood clots. In addition, in normal mice BSDL accumulated at sites of blood clot formation and in BSDL-deficient mice tail injury resulted in increased bleeding time. Further analysis revealed that BSDL mediated its effects on platelets in vitro and in vivo by binding a protein on the surface of platelets known as CXCR4. Indeed, inhibition of CXCR4 prevented BSDL-mediated human platelet activation, and eliminated BSDL accumulation and reduced blot clot size in mice. These data led the authors to conclude that the interaction between BSDL and CXCR4 might be a new target for therapies to treat conditions in which blood clots form inappropriately inside blood vessels, such as occurs in individuals with pancreatic cancer.

Title: Bile salt-dependent lipase interacts with platelet CXCR4 and modulates thrombus formation in mice and humans

Author Contact:
Laurence Panicot-Dubois
Université de la Méditerranée, Faculté de Médecine -- Timone, Marseille, France

Two hits are better than one for causing leukemia

The genetic abnormalities that cause acute myeloid leukemia (AML) are many and varied. Although mice engineered to mimic a single genetic abnormality eventually develop leukemia, it is thought that a second genetic defect occurring as the mice age is required for this to happen. Support for this "2-hit" hypothesis has now been generated by Pier Giuseppe Pelicci and colleagues from the European Institute of Oncology, Italy.

In this study, analysis of leukemic cells from individuals with AML indicated that disease associated with aberrant expression of the gene PRDM16 was accompanied by mutations in the gene that makes the p53 protein, which is known to suppress cancer development. Further analysis revealed that when one of the proteins made by the PRDM16 gene, sPRDM16, was overexpressed in the bone marrow of mice it could induce the development of leukemia, but the full extent of its leukemic potential required that the mice lack p53. These data led the authors to conclude that overexpression of sPRDM16 and disruption of the p53 tumor suppressor pathway cooperate in the development of leukemia, both in human patients with AML and in mice, and to suggest that inhibition of sPRDM16 is a potentially relevant antileukemogenic strategy.

Title: Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in mice

Author Contact:
Pier Giuseppe Pelicci
European Institute of Oncology, Milan, Italy.

Diabetic hearts feel the burn

A normal heart burns both fats and sugars for fuel. In contrast, diabetic hearts rely almost exclusively on fats for energy, leading to heart failure. PPAR-alpha and PPAR-beta/delta are proteins found in heart tissue. In the diabetic heart, enhanced activity of PPAR-alpha drives the use of fats as fuel, but the role of PPAR-beta/delta has been unknown. While seeking to understand the role of these proteins in diabetic heart failure, Daniel Kelly and his colleagues at Washington University School of Medicine, Missouri, have discovered that selective activation of PPAR-beta/delta in the heart improves cardiac function in mice.

The heart of mice in which PPAR-alpha is engineered to be overexpressed only in the heart (MHC-PPAR-alpha mice) has been shown to mimic the diabetic heart -- with increased fat and decreased sugar fuel usage, and subsequent cardiac arrest. In contrast, in this study, the hearts of mice engineered to overexpress PPAR-beta/delta only in the heart (MHC-PPAR-beta/delta mice) were shown to process sugars for energy and had function normally. Most strikingly, the degree of heart tissue death following heart attack was reduced in MHC-PPAR-beta/delta mice compared with both normal mice and MHC-PPAR-alpha mice. Researchers also uncovered a reason for these observed differences -- the two proteins have opposite effects on the genes responsible for sugar usage by the heart for fuel. The authors therefore suggested that heart-specific PPAR-beta/delta activation might be a useful therapy for reducing diabetes-induced heart disease in humans.

Title: Nuclear receptors PPAR-beta/delta and PPAR-alpha direct distinct me.tabolic regulatory programs in the mouse heart

Author Contact:
Daniel P. Kelly
Washington University School of Medicine, St. Louis, Missouri, USA

New understanding as to why individuals with an inherited disease don't see clearly

Williams-Beuren syndrome (WBS) is an inherited disease caused by the deletion of a segment of the genome that carries more than 20 genes. Several characteristics identify individuals with WBS, including a distinctive, elfin-like facial appearance; overly friendly personalitites; a love for music; and a lack of motion and depth perception. The latter are thought to be caused by defects in the region of the brain that deals with visual information. However, Miguel Castelo-Branco and colleagues at the IBILI, Portugal, have now determined that individuals with WBS also have a developmental defect in the retina (the thin layer of neural cells that lines the back of the eyeball) and that this causes additional visual deficits.

[Preciouslife1]

Rebuilding The Evolutionary History Of HIV 1 Unravels A Complex Loop
Main Category: HIV / AIDS News

http://www.medicalnewstoday.com/articles/89584.php

An essential component of the human immunodeficiency virus (HIV-1) molecular machinery responsible for infecting cells consists of functionally-specialized layers, according to a study by investigators at the University of California San Diego (UCSD) Antiviral Research Center (AVRC), published November 23 in PLoS Computational Biology.

The unprecedented genetic diversity and adaptability of HIV-1 has so far foiled the best efforts to eradicate the global HIV/AIDS epidemic. The surface of the HIV-1 particle is studded with protein spikes that allow the virus to enter human cells. This study examined an important component of the protein spike called the third variable loop (labeled "V3").

Protein components like V3 are problematic because they are so diverse; up to 35% of the amino acids can differ between strains of HIV-1. Exposed to human antibodies, V3 rapidly evolves to avoid the immune system. However, the V3 loop's critical function as a docking mechanism for HIV-1 to infect cells must impose limits on these evolutionary contortions.
By deciphering the hidden limits on HIV-1 evolution, scientists hope to facilitate the development of antiviral drugs and vaccines.

The investigators developed a new method combining techniques from molecular evolution and artificial intelligence. They reconstructed the evolutionary history underlying 1,145 genetic sequences encoding the V3 loop to discover groups of amino acids that were biologically dependent on each other. These "co-evolving" amino acids formed ties across the V3 loop like rungs on a ladder, corroborating models from structural studies of the same protein.

The investigators caution that this study was restricted to a small portion of the genome. Nevertheless, the study represents a significant advancement in our understanding of HIV-1 evolution and identifies important targets in the protein spike for future research.

PUBLIC LIBRARY OF SCIENCE
European Bioinformatics Institute
Wellcome Trust Genome Campus
CB10 1DS
http://www.plos.org

[Preciouslife1]

Key Nerve Navigation Pathway Identified

http://www.medicalnewstoday.com/articles/89631.php

Newly launched nerve cells in a growing embryo must chart their course to distant destinations, and many of the means they use to navigate have yet to surface. In a study published in the current issue of the journal Neuron, scientists at the Salk Institute for Biological Studies have recovered a key signal that guides motor neurons -- the nascent cells that extend from the spinal cord and must find their way down the length of limbs such as arms, wings and legs.

The Salk study, led by Samuel Pfaff, Ph.D, a professor in the Gene Expression Laboratory, identifies a mutation they christened Magellan, after the Portuguese mariner whose ship Victoria was first to circumnavigate the globe.
The Magellan mutation occurs in a gene that normally pilots motor neurons on the correct course employing a newly discovered mechanism, their results demonstrate.

In the mutants, growing neurons can be seen leaving the spinal cord normally but then appear to lose direction.
The elongating cells develop "kinks" and sometimes fold back on themselves or become entwined in a spiral, forming coils outside the spinal cord. "They appear to become lost in a traffic roundabout," described Pfaff, who observed the growing neurons with fluorescent technology.

Understanding how motor neurons reach the appropriate targets is necessary for the implementation of novel therapies, including embryonic stem cell replacement for the treatment of presently incurable disorders such as Lou Gehrig's disease, in which motor neurons undergo irreversible decay.

"Embryonic studies provide useful insights on how to replicate the system in an adult," said Pfaff. And, as he also pointed out, the mechanisms used by motor neurons are likely to be similar to those used in other parts of the central nervous system, such as the brain. The Magellan mutation discovered by Pfaff's group was found in mice, but the affected gene, called Phr1, has also been identified in other model systems, including fruit flies and the worm species C. elegans.

A growing nerve bears at its bow a structure called the growth cone, a region rich in the receptor molecules whose job is to receive cues from the environment, much as ancient mariners who observed the stars and set their course accordingly. During development, the growth cone continuously pushes forward, while the lengthening neuron behind it matures into the part of the cell called the axon. Once the growing cell "lands" at its target in a muscle cell, it is the axon that will relay the messages that allow an animal to control and move its limbs at will.

In Magellan mutants, Pfaff's team discovered that the growth cone becomes disordered. Rather than forming a distinct "cap" on the developing neuron, the cone is dispersed in pieces along both the forward end and the axon extending behind it.

"The defect is found in the structure of the neuron itself," said Pfaff, noting that the fundamental pieces, such as the receptors capable of reading cues, all seem to be present. Without the correct orientation of receptors, however, signals cannot be read accurately, resulting in growth going off course.

"A precise gradient normally exists across the cone," said Pfaff, "which is disrupted in the Magellan mutants." As a result, cells lose their polarity. They literally do not know the front end from the back end, according to Pfaff. This sense of polarity is a universal feature common to all growing neurons. Therefore, "Phr1 is likely to play a role in most growing neurons to ensure their structure is retained at the same time they are growing larger," he said.

Pfaff and his group identified Magellan using a novel system they had developed, in which individual motor neurons and axons can be visualized fluorescently. They were able to screen more than a quarter of a million mutations, and the mutations of interest were rapidly mapped to known genes as a result of the availability of the sequenced mouse genome -- a byproduct of the effort to sequence entire genomes such as that in the human.

The Magellan mutation is located in a gene known as Phr1, which is also active in other parts of the nervous system, indicating that it most likely functions to steer other types of neurons, such as those that enervate sensory organs or connect different regions of the brain. Studies of Magellan may therefore shed light on how a variety of neurological disorders might be treated with cell replacement strategies

[Preciouslife1]

Kyto Biopharma Inc. Confirms Definitive Isolation of the Human Vitamin B12 Receptor (TCblR)
TCblR Novel Target for Monoclonal Antibody Cancer Therapy

http://app.quotemedia.com/quotetools/popups/story.jsp

Kyto Biopharma Inc. (OTCBB:KBPH), (“Kyto”), a biotechnology company focused on developing monoclonal antibody based therapeutic agents for cancer treatment, announced today that for the first time it has conclusively isolated the protein and gene encoding the human Vitamin B12 receptor - TCblR for the cellular uptake of the transcobalamin-bound Vitamin B12. The over expression of TCblR in cancer cells provides the rationale for targeting the Vitamin B12 receptor in the treatment of various forms of cancer.

“The discovery of the TCblR gene and the expression of its encoded receptor protein represents a seminal milestone in the annals of cellular biology,” commented Dr. Uri Sagman, a founder and a director of Kyto. “Targeting TCblR in cancer cells with monoclonal antibodies holds a tremendous promise as a strategy to combat cancer,” added Dr. Sagman.

The isolation of the TCblR gene and the expression of the TCblR protein was achieved by Dr. Edward Quadros and his team at the State University of New York (SUNY) at Downstate Medical Center. In addition, the team at SUNY has successfully expressed the fragment of the receptor protein responsible for binding to the transcobalamin – B12 complex. Kyto has embarked on a program to develop targeted human monoclonal antibodies to TCblR as therapeutics for various forms of cancer.
In addition, Kyto intends to couple chemotherapeutic drugs and me.tabolic toxins to such therapeutic monoclonal antibodies and enhance their biological activity as powerful targeting agents.

Kyto has entered into an arrangement with third party providers to manufacture murine antibodies that will be used in the development of humanized monoclonal antibodies to TCblR. Dr. Quadros, with the input of Dr. Michael Rosenblum of MD Anderson Cancer Center, and a director of Kyto, will oversee the development of the monoclonal antibody program on behalf of the Company.

ABOUT KYTO BIOPHARMA INC.

Kyto Biopharma Inc. is a Florida incorporated and a Toronto based biotechnology company that develops monoclonal antibody therapies for the treatment of various forms of cancer.
The Company intends to develop its Vitamin B12 receptor based technology and is looking for a suitable partner to assist with the development and commercialization of a marketable cancer therapeutic. Vitamin B12 regulates one of two major cellular pathways for the production of Folates, the cell’s primary source of carbon and the progenitor for the synthesis of DNA. The newly isolated vitamin B12 receptor is over expressed in a host of various forms of cancer cells and serves as a viable target for development of therapeutic monoclonal antibodies. Kyto holds an extensive portfolio of intellectual property including IP protection for the newly discovered TCblR gene and its product.

[Preciouslife1]

Thomson Scientific Publishes its Third Quarter Issue of the Ones to Watch Reviewing the Most Promising Drugs in the Pharmaceutical Pipeline
PR Newswire Europe (inc. UK Disclose) - Nov. 30, 2007

PHILADELPHIA, Nov. 30 /PRNewswire-FirstCall/
Thomson Scientific, part of The Thomson Corporation (NYSE: TOC; TSX: TOC) and leading provider of information solutions to the worldwide research and business communities, has issued its quarterly The Ones-to-Watch report. It provides expert insight into the five most promising drugs entering each new phase of clinical development between July and September 2007.
"Bookending this quarter's list are three potential treatments for Alzheimer's disease, two of which are just entering clinical trials and one that has already received FDA approval," said Peter Robins, editorial and *********************************** manager, Thomson Scientific. "This quarter's The Ones to Watch report showcases the ongoing drive to find therapies for diseases that impact on ageing and sedentary populations."

Which are the Ones-to-Watch this Quarter?

Topping this quarter's approval list is Exelon TDS, a new transdermal patch formulation of rivastigmine, which looks like a winner for Novartis. In the seven years since its launch, the oral formulation of rivastigmine has seen year-on-year US dollar growth as a treatment of Alzheimer's disease - and Parkinson's disease- associated dementia. The FDA approved Exelon TDS for mild to moderate dementia in July 2007. The EU approval followed two months later. The U.S. launch is expected imminently.
Second on the list is AZOR, which was developed by Daiichi Sankyofor the treatment of hypertension and includes a combination of two component drugs. In previous Phase III trials, all doses of the combination produced greater mean reductions in blood pressure than either drug alone.
This, along with its favorable side-effect profile, should make AZOR an attractive treatment option for patients whose blood pressure does not respond to either component drug in isolation. U.S. approval was granted in September 2007.
While the reason for menopause remains unknown, KV Pharmaceutical believes EvaMist, which takes the third spot on the list, may offer significant advantages to women experiencing menopause. This product is a small, easy-to- use hand-held applicator that delivers a pre-set metered dose via the skin, releasing estradoil into the bloodstream over 24 hours. EvaMist gained FDA approval in July 2007.

The first of two potential treatments for cancer on the list of notable drugs gaining approval this quarter is Yondelis, developed by PharmaMar for patients who have not responded to previous regimens in their treatment of soft tissue sarcoma. Yondelis is the first approved product from PharmaMar, a Spanish biotech specializing in cancer drugs derived from marine organisms and has Orphan Drug status in both the EU and U.S., securing extended protection against generic competition.
The second approval win for Novartis this quarter, Tasigna, is an orally available inhibitor of Bcr-Abl, c-Kit, PDGF-R and related receptor tyrosine kinases for the potential treatment of various types of leukemia. Though the drug has been approved only in Switzerland for chronic myeloid leukemia, it is awaiting approval in the U.S. and Japan and has been recommended for approval across the EU.

Following are the top five drugs in each category of phase changes:

The Five Most Promising Drugs Entering Phase III Trials * bevasiranib sodium, (Wet AMD), Opko * recombinant active glucocerebrosidase, (Gaucher's disease), Protalix * odanacatib, (osteoporosis), Merck & Co * laquinimod, (multiple sclerosis), Active Biotech/Teva * elesclomol, (solid tumors), Synta[/i]
[b]The Five Most Promising Drugs Entering Phase II Trials * CPP-109, (addiction to cocaine and methamphetamine), Catalyst
Pharmaceuticals * intranasal insulin formulation, (diabetes), Nastech * LCP-AtorFen, (cholesterol), Life Cycle * EC-145, (ovarian and lung cancer), Endocyte * TG-100801, (AMD, diabetic macular edemia, diabetic retinopathy),
TargeGen

The Five Most Promising Drugs Entering Phase I Trials *
affitope AD-01, (Alzheimer's disease), AFFiRiS * MEM-63908, (Alzheimer's disease, CNS disorders), Memory/Roche * TC-5619, (schizophrenia, depression), Targacept * RDEA-806, (HIV infection), Ardea Biosciences * APD-791, (arterial thrombosis), Arena Pharmaceuticals.

About This Quarterly Report:
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[Preciouslife1]

Mice tests trap 'old' gene and show key to youth

Irish Independent - Nov. 30, 2007

A single gene could hold the secret of eternal youth, scientists revealed yesterday.
By blocking its activity, researchers were able to rejuvenate the skin of two-year-old mice.
Not only did the animals appear more youthful, but at a biological level they resembled newborn mice.
The same gene, NF-kappa-B, is thought to play a role in numerous other aspects of ageing.

It acts as a regulator, causing a wide range of other genes to be more or less active in older people.

Dr Howard Chang, from the Stanford School of Medicine in California, who led the research, said: "We found a pretty striking reversal to that of the young skin. The implication is that the ageing process is plastic and potentially amenable to intervention.''

However, he cautioned against raising false hopes of a "fountain of youth'' that can turn back time.

Cancer

At present no-one knows how long the rejuvenating process lasts. Also, there is no telling what long-term harmful side effects might result from tinkering with NF-kappa-B.

The protein made by the gene has roles in a number of body functions including the immune system, and may help fight against cancer.

As a result, suppressing NF-kappa-B on a long-term basis could result in cancers or other diseases, said the researchers, whose findings are reported today in the journal 'Genes and Development'.

"You might get a longer life-span but at the expense of something else,'' Dr Chang warned.

However he thought the work might yield short-term treatments to improve wound healing or boost organ function during illness.

Older people could, for instance, be helped to recover more rapidly from injuries or surgery.

NF-kappa-B belongs to a gene family called transcription factors, which help control the transfer of protein-making instructions from other genes. In this way, they regulate gene activity.

Dr Chang's team searched existing data from earlier gene investigations to show that NF-kappa-B controlled genes involved in ageing.

Next the researchers blocked NF-kappa-B in the skin of two-year-old mice. After two weeks the mice had the same active genes in their skin cells as newborn animals.

Their skin was also thicker and more cells appeared to be dividing, as in the skin of younger mice.

[Preciouslife1]

In from the other Gates: Gates foundation funds stem cell program ; $5 million goes to CU, Children's pediatric research

Rocky Mountain News - Nov. 30, 2007

Children's Hospital has secured a $5 million gift to allow its new neighbor, the University of Colorado School of Medicine, to expand its stem cell research program to include pediatrics.

The effort is thought to be among the first programs to focus on stem cell research that targets child-related illnesses ranging from diabetes to heart problems.

The Gates Frontiers Fund - created by the children of the late Colorado rubber tycoon and philanthropist Charles C. Gates - provided the gift, which is set to be announced today.

To support the pediatric stem cell effort, Children's Hospital will recruit a physician-scientist who will hold a newly endowed chair.

"We're just beginning the search process," said Stephen Daniels, pediatrician in chief at Children's Hospital at the Anschutz Medical Campus in Aurora.

Daniels - also chairman of the pediatrics department at the CU School of Medicine - said stem cell-based therapies may provide future treatments for diabetes, neurological diseases, cardiac problems and cystic fibrosis, among other ailments.

He added that pediatric research "holds great promise for improving our ability to treat a wide variety of childhood illnesses" and deformities present at birth.

The new pediatric program also underscores the collaborative effort that CU researchers and physicians at the Anschutz campus hope to achieve.

In 2005, the Gates family made an initial $6 million donation that allowed CU's School of Medicine at the Anschutz campus to create a stem cell program.

Researchers there already target areas that include nerve- related diseases such as Parkinson's and Alzheimer's, heart disease, liver disease, vascular disease, juvenile diabetes, blood disease, skin disease and cancer.

The medical school's stem cell program is the only formal stem cell program in Colorado, although researchers elsewhere in the state are doing stem cell work. It's named the Charles C. Gates Regenerative Medicine and Stem Cell Biology Program.

Diane Gates Wallach, daughter of Charles Gates, said her father was deeply interested in the "medical potential" of stem cell research.

"He said, 'This is great science.' And he wanted to support great science," added Wallach, who previously chaired the Children's Hospital board and is a director of the Gates Frontiers Fund.

The Gates family contributions come amid tight federal funding as well as restrictions imposed by the Bush administration on embryonic stem cell research.

"Most of the interesting work right now is happening with private funding," said Denise Brown, executive director of the Colorado BioScience Association. "The feds are funding so little."

This month, however, researchers at Kyoto University and the University of Wisconsin announced they had made regular human cells match the healing potential of stem cells. The breakthrough sidesteps the ethical debate over harvesting stem cells from embryos.

[Preciouslife1]

Part #1
Beyond patents and royalties: the perception and reality of doing business with the NIH

http://www.nature.com/bioent/2005/051201/full/bioent895.html

GIL BEN-MENACHEM1, STEVEN M. FERGUSON2 & KRISHNA BALAKRISHNAN3

Gil Ben-Menachem is at Paramount Biosciences LLC, 124 Mount Auburn Street, Suite 200N, Cambridge, Massachusetts 02138, USA, e-mail: gilben@paramountbio.com

Steven M. Ferguson is at the US National Institutes of Health Office of Technology Transfer, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804, USA, e-mail: fergusos@mail.nih.gov

Krishna Balakrishnan is at the US National Institutes of Health Office of Technology Transfer, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804, USA, e-mail: balki@nih.gov

Young biotech startups can benefit hugely from the US National Institutes of Health (NIH), not least because of the agency's non-dilutive funding, guidance, and opportunities for collaboration. Increasingly, however, there is a fair bit of misunderstanding about what the NIH can and cannot do for a biotech entrepreneur.

Introduction

The NIH licensing landscape has changed significantly during recent years with increasing industry consolidation, large pharmaceutical firms are no longer looking to directly license early stage technologies for commercialization, and the number of NIH licenses signed with small and medium-sized biotech companies is on the rise. Unlike five to ten years ago, when all or most of the high revenue products based on NIH licenses came from large pharmaceutical firms, a majority of the latest success stories tend to be from biotech or other nonpharma companies. Some examples are Kepivance (palifermin) from Amgen, Velcade (bortezomib) from Millennium, Synagis (palivizumab) from Medimmune and Taxus Express (paclitaxel-eluting coronary stent system) from Angiotech1.

Several other products are being developed by younger firms with the help of the NIH. The new reality is that commercial partners, especially small, innovative ones, are essential to the NIH's role of helping to facilitate the formation of novel healthcare products for the public. From new or invigorated activities in technical assistance to technology licensing to financial considerations, the NIH has an extensive menu of options at NIH that bioentrepreneurs can use in their product development efforts.

Recent NIH licensing practices have been adapted and expanded to take advantage of these new realities. This is reflected in the sharp increase in corporate licensing activity from NIH over the past two years—now in excess of 300 transactions per year—with a particular focus on smaller firms.

Many groundbreaking technologies emanating from NIH laboratories are of a basic research nature and considered early stage, and they provide a wealth of untapped opportunities for bioentrepreneurs (see Box 1).
In this article we will try to provide a functional guide to bioentrepreneurs about the various access points for doing business with NIH. We'll review some of the unique features of the NIH licensing program, discuss financial issues like grants and contracts, and use examples of successful collaboration with industry to demonstrate how working with the NIH can help bioentrepreneurs in terms of finance, technology transfer, product development and validation, access to investigators and know-how. We'll also try to dispel some of the myths surrounding NIH's ethics policies (see Table 1).

Table 1: Top Five Myths of Doing Business with the NIH
Table available for viewing in the link provided...


Show me the money
As most entrepreneurs already know, the NIH can provide startups with nondilutive funding through the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs2. The NIH SBIR program is the most prolific funding source in the Federal Government for a bioentrepreneur, and as an added bonus, it comes with virtually no strings attached.

The SBIR program was established in 1982 by the Small Business Innovation Development Act to increase the participation of small, high technology firms in federal R&D activities. Under this program, departments and agencies with R&D budgets of $100 million or more are required to set aside 2.5 percent of their R&D budgets to sponsor research at small companies.

In 2005 NIH's combined SBIR and STTR grants will total $640 million. As a major mechanism in achieving the NIH roadmap goals of enhancing public-private partnership, the SBIR and STTR grants present an excellent funding source for small biotech companies. Recently a spirited debate is underway in the research and venture capital communities on whether it is appropriate for SBIR awards to be given to small companies in which venture capital has controlling interest (that is, more than 51% stake)3. The Small Business Administration (SBA) has yet to make a final ruling on this issue.

Phase I grant support, also known as a feasibility study, is normally funded at $100,000 for 6 months (SBIR) or $100,000 for 12 months (STTR). Phase II support is available to Phase I recipients and provides two-year awards of $750,000 (SBIR) or $500,000 (STTR). To foster the best quality applicants, the NIH SBIR program provides prospective applicants with a wealth of information, including advice documents4, free workshops and conferences5, and easy access to the program officials who can answer more in-depth questions6. Those who hope to receive an SBIR grant from the NIH must convince the agency that the proposed research is unique, creates value for the general public at large through advancements in knowledge and treatment of disease, and is relevant to the overall goals of NIH. It is important to contact the program officials ahead of time within the particular component of NIH from which funding is sought to determine whether the proposed research plan fits these criteria.

[Preciouslife1]

Part #2

Applications are evaluated by a peer group of researchers drawn from industry and academia. It is, therefore, important that applicants do not include proprietary information. The success rate for well-written SBIR grants is 25–30%. More than the mere funding, SBIR-funded projects have earned the seal of approval from a panel of expert peer reviewers, which will facilitate further fund-raising efforts. Unlike private financiers who evaluate a business plan for its economic returns, NIH reviewers determine whether an SBIR grant application to NIH is significantly aligned with the agency's public health mission. However, like any other attempt by a biotech startup that seeks funds, an SBIR proposal should describe a sound and innovative approach to solving an unmet medical need, and applicants must prove that a committed R&D team that can successfully achieve its objectives is in place.

Early market intelligence
Another valuable NIH resource for bioentrepreneurs is the CRISP7 (Computer Retrieval of Information on Scientific Projects). This is a searchable database of federally funded biomedical research projects conducted at universities, hospitals and other research institutions. CRISP can be queried to find prospective collaborators or scientific advisors from a universe of prequalified, NIH-funded group of researchers.

For a small company with limited scientific depth, this list can provide the comfort of NIH-reviewed investigators, and provide insight into funded research plans and strategies that are being contemplated for the next three to five years. The database can be queried based on institutions, disease indications, names of primary investigators, type of grants and state. Thus, when properly used, it can provide a wealth of information regarding NIH-funded projects in a specific area.

CRISP provides a heads-up about promising new areas of research, and indicates the scientists whose work should be monitored. It can also be used by biotechs to identify potential customers or key contacts.

Flexible IP licensing terms
Contrary to the perception that the NIH is only interested in working with academics, the NIH affords favorable treatment to small businesses and creates an attractive playing field for them to get into new areas of product development. For example, startups can negotiate to have patent prosecution of licensed technologies managed by the NIH. This is particularly useful for small firms that may not yet have internal counsel or the resources to retain a top intellectual property (IP) law firm.

Another feature of the NIH licensing program is that unlike many university-based license agreements, the NIH licenses do not require sponsored research agreements. Typically, this requirement may add significant costs to R&D programs which can impose a burden on cash-strapped small companies.

When licensing technologies from the NIH, entrepreneurs should also be aware that equity dilution will not be part of the negotiations. This feature becomes important as companies try to raise capital through additional rounds of financing. Likewise, biotech startups entering license agreements with NIH do not give up any co-marketing rights, nor do they forsake any downstream developmental rights. Research tool licenses negotiated through the NIH carry no grant-backs or reach-through rights. For instance, when a research tool technology is licensed to a company by NIH, the licensee is not required to grant back any usage rights to the improvements that it may develop subsequent to the license agreement. Also the licensee is not required to share with NIH any future profits that may be made as a result of improvements to the original discovery. In other words, IP derived from new discoveries made with NIH-licensed tools will remain clear and unencumbered.

The overlooked role of OTT
The NIH licensing program represents one of the largest and most successful technology transfer efforts in the US biomedical field, having entered into almost 2,500 license agreements in the previous 18 years (FY 1988 to FY 2004), and having generated more than $500 million in royalty revenues8. Recently we undertook a market research study to better understand the profile and needs of NIH licensees. The main focus areas of that study were an examination of the different ways by which potential licensees became aware of the NIH technologies that were available for licensing, and whether there were any particular mechanisms of interaction that were preferred by different customer segments.

One interesting observation that came out of this study related to how small companies scout for new licensing opportunities from NIH. Although large companies (with bigger resources) were found to rely more on their familiarity with inventors' publications and their personal contact with the inventor community, small businesses relied more on the marketing messages that originated from the NIH Office of Technology Transfer (OTT)9.

The marketing messages from NIH that were found most useful by potential licensees consisted of brief one-page summaries of the new NIH inventions available for licensing. The NIH disseminates this information in a timely fashion through our website10,11 and our electronic Listserv12. In addition to getting up-to date information from these sources about the NIH licensing opportunities, biotech startups can also get in touch with individual licensing specialists in our office whose areas of licensing practice may be most closely related to the company's focus areas13. Indeed the role of OTT in technology transfer ranges from invention disclosure, patenting, and technology marketing to license negotiations and postlicensing communications with licensee companies. Bioentrepreneurs have many points of access to NIH licensing professionals at several of these stages of technology transfer.

Free advice and training
Outreach to prospective bioentrepreneurs is important to the NIH. Many postdoctoral fellows, who are concluding their scientific training at the NIH may have the passion to start a biotech company, but usually lack the required business expertise. Scientists can exploit some of the NIH programs that target prospective bioentrepreneurs.

These programs include training in technology transfer through internships and fellowships offered at the Office of Technology Transfer14, graduate-level courses in technology transfer and in business development, where scientists can develop their business plans based on NIH technologies, and discussion groups such as the Bioscience Business Interest Group that help entrepreneurs with career development and networking15.

The NIH could be your first customer
Among the little known facts about doing business with the NIH, few are more overlooked than the commercial role that NIH plays as customer to a vast and growing number of biotech firms. With an intramural staff of about 17,000 employees, laboratories spread across the nation (with the Bethesda campus housing a majority of the labs), and an annual intramural budget of about $2.7 billion (FY 04), the NIH is perhaps the largest US consumer of bioscience research reagents and instruments. A variety of mechanisms for selling products and services to the NIH are possible, including stocking in government storerooms.

Selling to NIH can be seen as a daunting task for biotechs because of the US Government's complex acquisition process. However, there are a few simple steps that companies can take, such as establishing a blanket purchase agreement with NIH and getting their goods and services into the NIH stockroom. Once these steps are completed, it is much easier for NIH scientists to buy from such companies, and if the quality of goods and services provided by a particular biotech company is superior, an NIH scientist can justify buying from that source.

Companies that provide products and services to NIHlaboratories can not only generate cash flow and revenues to fuel R&D, but also begin to demonstrate their commercial acumen to would-be partners and investors (see Box 2).

The annual NIH Research Festival is an excellent starting point for companies hoping to sell products to the NIH16. This event is held every fall at the Bethesda campus and during spring on the Ft. Detrick campus. Part scientific, part social, part informational and part inspirational, this three-day event draws a variety of small-to-medium-sized bioscience companies. These events attract almost 6,000 NIH PhDs, many of whom come to these gatherings to buy the latest research tools.

Biodefense in your future?
Firms capable of developing products and services that focus on medical countermeasures to chemical, biological or radiological threats can receive grant or contract money through Project Bioshield. This project, which was signed into law on July 21, 2004, aims to protect the American public from various weapons of bioterrorism. Over the next 10 years, $6 billion will be committed to these efforts.

Awards granted through project Bioshield are not limited to academia. In fact, out of the ten grants and two contracts recently awarded by the National Institute of Allergy and Infectious Diseases (NIAID), totaling $27 million, five grants and two contracts were awarded to private companies.

These first grants and contracts, which range in duration from 12 to 18 months, respond to a key objective of the NIAID biodefense research agenda that emphasizes the development of new and improved medical products against 'Category A' agents—those biological agents considered by the Centers for Disease Control and Prevention to pose the greatest threat to national security.

[Preciouslife1]

PART #3

Can NIH scientists work with biotechs?
There is a perception among many industry professionals that the implementation of new ethics rules at NIH means that NIH researchers can no longer interact with the private sector.

Although it is true that NIH investigators cannot engage in outside consulting with biotech and pharmaceutical companies in their personal capacity, without prior approval, the fact is that technology transfer activities are actually among the official duties in which NIH scientists are encouraged or required to participate. These activities may include the reporting of new inventions from the lab, and assisting technology transfer staff with patenting, marketing and licensing interactions with companies. NIH scientists can also officially collaborate with industry scientists through Cooperative Research and Development Agreements (CRADAs), Clinical Trial Agreements (CTAs), and Material Transfer Agreements (MTAs).

In a CRADA arrangement, which could last for several years, NIH scientists and company scientists can engage in mutually beneficial joint research where each party provides unique resources, skills and funding, and where either partner may not be able to solely provide all the resources for successful completion of the project. In such an arrangement, the scope of the research work to be carried out and the license options granted to discoveries emanating from the joint research are clearly spelled out.

A CTA would typically involve a compound or therapeutic modality, which is proprietary to a company that desires the clinical trial infrastructure that NIH possesses. NIH generally enters into these agreements only in cases where such trials would be difficult or impossible to run in other places. The NIH is also particularly interested in clinical trials involving orphan diseases that affect 50,000 or fewer people each year. An MTA is a popular mechanism for exchanging proprietary research reagents, which is used by scientists worldwide. NIH scientists actively use this mechanism to share reagents with scientists in other nonprofit organizations.

Of the three collaborative mechanisms described above, a CRADA is perhaps the most comprehensive and far-reaching. Such agreements can facilitate financial support for an NIH lab, while providing the collaborating company with preferential access to the NIH scientist's future work and expertise during the research or clinical collaboration. The easiest way for a bioentrepreneur to begin to access this expertise is to simply approach the agency officially through the various technology development coordinator offices located in the individual institutes within NIH17.

Working with the NIH from abroad
Although a US-based government agency, the NIH's technology-licensing activities increasingly have a worldwide scope. Patent protection is sought in major non-US markets for discoveries made in NIH laboratories with license agreements to non-US firms now representing more than one out of every six licenses signed. Of particular note is the emerging biotech industry and entrepreneurial culture in countries such as India and China, which has also led to the growth of licensing activity in those areas by NIH for such products as vaccines that substantially serve those regional needs and markets (see Box 3).

To facilitate this effort, the NIH has added international technology transfer professionals, who focus their outreach and training efforts on non-US biotech and R&D organizations.

Conclusion
The NIH realizes that for its work to have full impact, the research findings generated in its laboratories must be translated into goods and services that benefit society by improving public health and by reducing the burdens of disease. Clearly this cannot be done without active partnerships with private industry.

Simultaneously there is a growing realization on the part of industry about the unique attributes of NIH research—attributes such as high-quality science, cutting edge discoveries in areas of research that may not be pursued in other laboratories and the agency's single-minded dedication to improving public health. Savvy bioentrepreneurs can come to NIH not only for money in the form of SBIR grants, but also for product development leads through various partnership mechanisms.

In addition, the NIH laboratories can be seen as an early adaptor customer that embraces new biomedical research products, and as a source of expertise and resources that may not be available in other places. At the same time there have been a number of myths that may have prevented some bioentrepreneurs from fully realizing the value of their interactions with NIH. Academics the world over already comprehend and appreciate the full value that NIH brings to their own work and to public health. But the full value of the NIH can only be realized if its utility is fully understood and engaged not only by academia, but also by the private sector.

References
http://ott.od.nih.gov/techdev.html
http://grants.nih.gov/grants/funding/sbir.htm
http://www.house.gov/science/hearings/ets05/june28/charter.pdf
http://grants.nih.gov/grants/funding/sbirsttr_tidbits_april2004.doc
http://grants.nih.gov/grants/funding/conferences.htm
http://grants.nih.gov/grants/funding/sbirsttr1/SBIR_STTR_ContactInfo.pdf
http://crisp.cit.nih.gov/
http://www.ott.nih.gov/pdfs/TTstats04.pdf
Ramakrishnan, V., Chen, J. & Balakrishnan, K. Effective Strategies for Marketing Biomedical Inventions: Lessons Learnt From NIH License Leads. J. Med. Mark. 5, 342–352 (2005).
http://www.ott.nih.gov/db/newtech.asp
http://www.ott.nih.gov/techabs.html
http://www.ott.nih.gov/join_ott.html
http://www.ott.nih.gov/resper_ott.html
http://ott.od.nih.gov/intern.html
http://www3.nci.nih.gov/bbig/
http://researchfestival.nih.gov/
http://ott.od.nih.gov/tdc.html

[Preciouslife1]

Scientists form new Seattle biotech, backed by $12MPuget Sound Business Journal (Seattle)

http://seattle.bizjournals.com/seattle/stories/2007/11/26/daily23.html?jst=b_ln_hl

A group of scientists who specialize in stem cell biology have formed a new biotech company backed by $12 million in original venture capital.

Fate Therapeutics will be based in Seattle and consists of leading scientists including Randall Moon of the University of Washington, who's director of the Institute for Stem Cell and Regenerative Medicine. Other scientists come from Stanford University, Harvard University and Scripps Research Institute.

The scientists say Fate will "harness the healing power of adult stem cells by using small molecule drugs to modulate cells in the body and by reprogramming mature adult cells into stem cells."

"Fate's timing is excellent. The science is now mature enough. Clear therapeutic modalities have emerged, and the cloud of political and ethical debate surrounding embryonic stem cells is now a thing of the past," said Fate's Executive Vice President Tom St. John, in a statement. St. John was previously the vice president of therapeutic development at Icos Corp. of Bothell, which was bought late last year by Eli Lilly & Co. (NYSE: LLY) for $2.3 billion.

The $12 million in funding came from venture capital firms Arch Venture Partners, Polaris Venture Partners, Venrock and OVP.