Real Estate Investor to Plead Guilty To Bid Rigging

   (DOJ) - 3/3/2014 - A Northern California real estate investor has agreed to plead guilty for his role in conspiracies to rig bids and commit mail fraud at public real estate foreclosure auctions in Northern California, the Department of Justice announced.
   Felony charges were filed recently in the U.S. District Court for the Northern District of California in Oakland against Charles Gonzales, of Alamo, Calif. Including Gonzales, a total of 44 individuals have pleaded guilty or agreed to plead guilty as a result of the department’s ongoing antitrust investigations into bid rigging and fraud at public real estate foreclosure auctions in Northern California.
   According to court documents, beginning as early as April 2009 until about October 2010, Gonzales conspired with others not to bid against one another, and instead to designate a winning bidder to obtain selected properties at public real estate foreclosure auctions in Alameda County, Calif. Gonzales was also charged with conspiring to commit mail fraud by fraudulently acquiring title to selected Alameda County properties sold at public auctions and making and receiving payoffs and diverting money to co-conspirators that would have gone to mortgage holders and others by holding second, private auctions open only to members of the conspiracy. The department said that the selected properties were then awarded to the conspirators who submitted the highest bids in the second, private auctions. The private auctions often took place at or near the courthouse steps where the public auctions were held.
   “The Antitrust Division’s ongoing investigation has resulted in charges against 44 individuals for their roles in schemes that defraud distressed homeowners and lenders,” said Bill Baer, assistant Attorney General in charge of the Department of Justice’s Antitrust Division. “The division will continue to work with its law enforcement partners to vigorously protect competition at the local level.”
    The department said that the primary purpose of the conspiracies was to suppress and restrain competition and to conceal payoffs in order to obtain selected real estate offered at Alameda County public foreclosure auctions at non-competitive prices. When real estate properties are sold at the auctions, the proceeds are used to pay off the mortgage and other debt attached to the property, with remaining proceeds, if any, paid to the homeowner. According to court documents, the conspirators paid and received money that otherwise would have gone to pay off the mortgage and other holders of debt secured by the properties, and, in some cases, the defaulting homeowner.
   “The symbolism of holding illegitimate and fraudulent private auctions near a courthouse is deplorable,” said David J. Johnson, FBI Special Agent in Charge of the San Francisco Field Office. “The justice system will continue to prevail in this ongoing investigation pursuing bid rigging and fraud at public foreclosure auctions.”
    A violation of the Sherman Act carries a maximum penalty of 10 years in prison and a $1 million fine for individuals. The maximum fine for the Sherman Act charges may be increased to twice the gain derived from the crime or twice the loss suffered by the victim if either amount is greater than $1 million. A count of conspiracy to commit mail fraud carries a maximum sentence of 30 years in prison and a $1 million fine. The government can also seek to forfeit the proceeds earned from participating in the conspiracy to commit mail fraud.
   The charges are the latest filed by the department in its ongoing investigation into bid rigging and fraud at public real estate foreclosure auctions in San Francisco, San Mateo, Contra Costa and Alameda counties, Calif. Investigations are being conducted by the Antitrust Division’s San Francisco Office and the FBI’s San Francisco Office. Anyone with information concerning bid rigging or fraud related to public real estate foreclosure auctions should contact the Antitrust Division’s San Francisco Office at 415-934-5300, or call the FBI tip line at 415-553-7400.
   Source: Financial Fraud Enforcement Task Force

NIH, Others Work To Validate Disease Targets

   (NIH) - 2/16-2014 -The National Institutes of Health, 10 biopharmaceutical companies and several nonprofit organizations recently launched an unprecedented partnership to transform the current model for identifying and validating the most promising biological targets of disease for new diagnostics and drug development.
   The Accelerating Medicines Partnership (AMP) aims to distinguish biological targets of disease most likely to respond to new therapies and characterize biological indicators of disease, known as biomarkers. Through the Foundation for the NIH (FNIH), AMP partners will invest more than $230 million over five years in the first projects, which focus on Alzheimer’s disease, type 2 diabetes, and the autoimmune disorders rheumatoid arthritis and systemic lupus erythematosus (lupus).
   A critical and groundbreaking element of the partnership is the agreement that the data and analyses generated will be made publicly available to the broad biomedical community. The three- to five-year, milestone-driven pilot projects in these disease areas could set the stage for broadening AMP to other diseases and conditions.
   “Patients and their caregivers are relying on science to find better and faster ways to detect and treat disease and improve their quality of life,” NIH Director Francis S. Collins stated. “Currently, we are investing a great deal of money and time in avenues with high failure rates, while patients and their families wait. All sectors of the biomedical enterprise agree that new approaches are sorely needed.”
    As a result of technological revolutions in genomics, imaging, and more, researchers have been able to identify many changes in genes, proteins, and other molecules that predispose to disease and influence disease progression. While researchers have identified thousands of such biological changes that hold promise as biomarkers and drug targets, only a small number have been pursued. Choosing the wrong target can result in failures late in the development process, costing time, money, and ultimately, lives. Currently, developing a drug from early discovery through U.S. Food and Drug Administration approval takes well over a decade and has a failure rate of more than 95 percent. As a consequence, each success costs more than $1 billion.
   “The AMP rallies scientific key players of the innovation ecosystem in a more unified way to address one of the key challenges to Biopharma drug discovery and development,” said Mikael Dolsten, M.D., Ph.D., President of Worldwide Research and Development at Pfizer. “This type of novel collaboration will leverage the strengths of both industry and NIH to ensure we expedite translation of scientific knowledge into next generation therapies to address the urgent needs of Alzheimer’s, diabetes and RA/lupus patients.”
  AMP has been more than two years in the making, with intense interactions between scientists in the public and private sectors, progressive refinement of the goals, strategy development support from the Boston Consulting Group, and scientific project and partnership management by the FNIH. Through this effort, AMP partners have developed research plans and are sharing costs, expertise, and resources in an integrated governance structure that enables the best informed contributions to science from all participants.
   The research highlights for each disease area are:

Alzheimer’s disease

   Identify biomarkers that can predict clinical outcomes by incorporating an expanded set of biomarkers into four major NIH-funded clinical trials, which include industry support, designed to delay or prevent disease.
    Conduct large-scale, systems biology analyses of human patient brain tissue samples with Alzheimer’s disease to validate biological targets that play key roles in disease progression, and increase understanding of molecular networks involved in the disease, to identify new potential therapeutic targets.
  For more information about NIH Alzheimer’s disease research, see the 2012-2013 Alzheimer’s Disease Progress Report: Seeking the Earliest Interventions.

Type 2 diabetes

   Build a knowledge portal of DNA sequence, functional genomic and epigenomic information, and clinical data from studies on type 2 diabetes and its heart and kidney complications. The portal will include existing data and new data from studies involving 100,000–150,000 individuals. The rich collection of curated and collated information in this portal will provide an opportunity to identify the most promising therapeutic targets for diabetes from the growing mountain of potentially relevant data.
    Focus on DNA regions that might be critical for the development or progression of type 2 diabetes and search for natural variations in targeted populations that might predict the likelihood of success of drug development aimed at these targets.

Rheumatoid arthritis and lupus

    Collect and analyze tissue and blood samples from people with rheumatoid arthritis and lupus to pinpoint biological changes at the single cell level, to allow comparisons across the diseases and provide insights into key aspects of the disease process.
Identify differences between rheumatoid arthritis patients who respond to current therapies and those who do not, and provide a better systems-level understanding of disease mechanisms in RA and lupus.
   Highly collaborative steering committees with representation from public- and private-sector partners will be established for each disease area to oversee the research plans. The steering committees will be managed by FNIH under the direction of an AMP executive committee comprised of leaders from NIH, industry, the FDA, and patient advocacy organizations.
   More information about the program and the disease research plans can be found here: www.nih.gov/amp.
   Source: The National Institutes of Health

Cancer Study Reveals Potential Drug Targets

   (NIH) - 1/31/2014 - Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bladder cancer — also known as urothelial carcinoma — resemble subtypes of breast, head and neck and lung cancers, suggesting similar routes of development.
   The researchers’ findings provide important insights into the mechanisms underlying bladder cancer, which is estimated to cause more than 15,000 deaths in the United States in 2014. TCGA is a collaboration jointly supported and managed by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both parts of the National Institutes of Health.
   “TCGA Research Network scientists continue to unravel the genomic intricacies of many common and often intractable cancers, and these findings are defining new research directions and accelerating the development of new cancer therapies,” NIH Director Francis Collins said.
   In this study, published online Jan. 29, 2014 in Nature, investigators examined bladder cancer that invades the muscle of the bladder, the deadliest form of the disease. The current standard treatments for muscle-invasive bladder cancer include surgery and radiation combined with chemotherapy. There are no recognized second-line therapies — second choices for treatments when the initial therapy does not work — and no approved targeted agents for this type of bladder cancer. Approximately 72,000 new cases of bladder cancer will be diagnosed in the United States in 2014.
   “This project has dramatically improved our understanding of the molecular basis of bladder cancers and their relationship to other cancer types,” said lead author John Weinstein, M.D., Ph.D., professor and chair of the Department of Bioinformatics and Computational Biology at The University of Texas M.D. Anderson Cancer Center in Houston. “In the long run, the potential molecular targets identified may help us to personalize therapy based on the characteristics of each patient’s tumor.”
   “The real excitement about this project is that we now have a menu of treatment and research directions to pursue,” said Seth Lerner, M.D., professor and chair in urologic oncology at Baylor College of Medicine in Houston, and one of the senior authors of the paper. “The field is poised to use this information to make new advances toward therapies for a very-difficult-to-treat form of bladder cancer.”   
   The research team analyzed DNA, RNA and protein data generated from the study of 131 muscle-invasive bladder cancer from patients who had not yet been treated with chemotherapy. The scientists found recurrent mutations in 32 genes, including nine that were not previously known to be significantly mutated. They discovered mutations in the TP53 gene in nearly half of the tumor samples, and mutations and other aberrations in the RTK/RAS pathway (which is commonly affected in cancers) in 44 percent of tumors. TP53 makes the p53 tumor suppressor protein, which helps regulate cell division. RTK/RAS is involved in regulating cell growth and development.
   The investigators also showed that genes that regulate chromatin — a combination of DNA and protein within a cell’s nucleus that determines how genes are expressed — were more frequently mutated in bladder cancer than in any other common cancer studied to date. These findings suggest the possibility of developing therapies to target alterations in chromatin remodeling.
   Overall, the researchers identified potential drug targets in 69 percent of the tumors evaluated. They found frequent mutations in the ERBB2, or HER2, gene. The researchers also identified recurring mutations as well as fusions involving other genes such as FGFR3 and in the PI3-kinase/AKT/mTOR pathway, which help control cell division and growth and for which targeted drugs already exist.
   Because the HER2 gene and its encoded protein, HER2 — which affects cell growth and development — are implicated in a significant portion of breast cancers, scientists would like to find out if new agents under development against breast cancer can also be effective in treating subsets of bladder cancer patients.
   “We’ve organized our medical care around the affected organ system,” Dr. Lerner said. “We have thought of each of these cancers as having its own characteristics unique to the affected organ. Increasingly, we are finding that cancers cross those lines at the molecular level, where some individual cancers affecting different organs look very similar. As targeted drug agents go through preclinical and clinical development, we hope that rather than treating 10 percent of breast cancers or 5 percent of bladder cancers, it eventually will make sense to treat multiple cancer types where the target is expressed.” The same theme runs through TCGA’s Pan-Cancer project, which is aimed at identifying genomic similarities across cancer types, with the goal of gaining a more global understanding of cancer behavior and development.
   “It is increasingly evident that there are genomic commonalities among cancers that we can take advantage of in the future,” NHGRI Director Eric Green said. “TCGA is providing us with a repertoire of possibilities for developing new cancer therapeutics.”
   The scientists also uncovered a potential viral connection to bladder cancer. It is known that animal papilloma viruses can cause bladder cancer. In a small number of cases, DNA from viruses — notably, from HPV16, a form of the virus responsible for cervical cancer — was found in bladder tumors. This suggests that viral infection can contribute to bladder cancer development.
   Tobacco is a major risk factor for bladder cancer; more than 70 percent of the cases analyzed in this study occurred in former or current smokers. However, the analysis did not identify major molecular differences between the tumors that developed in patients with or without a history of smoking.
   “The definitive molecular portrait of bladder cancer by the TCGA Network has uncovered a promising array of potential therapeutic targets that provides a blueprint for investigations into the activity of existing and novel therapeutic agents in this cancer,” said Louis Staudt, M.D., Ph.D., director, NCI Center for Cancer Genomics.

Reference

The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. Online January 29, 2014. DOI: 10.1038/nature12965.