Tuesday December 7, 8:46 am Eastern Time
Company Press Release
SOURCE: Millennium Pharmaceuticals, Inc.
Millennium Issued Broad Patent Relating to the
Leptin Receptor and Body Weight Regulation
Accomplishments in Obesity Research Program Showcase Unique Disease-Specific Strategy for
Drug Discovery
CAMBRIDGE, Mass., Dec. 7 /PRNewswire/ -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM - news) today
announced it has received a United States patent for identifying compounds that modulate body weight using the OB receptor,
also called the leptin receptor. The award, issued as U.S. Patent No. 5,972,621, concludes several years of competition in the
U.S. Patent Office among pharmaceutical, biotechnology and academic organizations for the rights covered under this patent.
This is the first U.S. patent covering methods of using the leptin receptor to discover new drugs for weight regulation, and
Millennium's 13th U.S. patent in the area of weight regulation and obesity.
The claims of this patent relate to methods for discovering new weight- modulating therapeutics by identifying compounds that
bind to the leptin receptor or alter the activity of the leptin receptor. Agonists of the receptor may be useful in decreasing body
weight and antagonists may be useful for increasing body weight. Louis Tartaglia, Ph.D., vice president of metabolic diseases at
Millennium, and his colleagues previously published their research findings on the leptin receptor in the journal Cell (December
29, 1995), which became the foundation for applied uses of the receptor.
While it is widely understood that the leptin pathway is key to controlling body weight, extensive research confirms that it is the
leptin receptor, versus the leptin hormone, that holds great potential for obesity drug discovery and for discovering drugs that
increase body weight to treat cachexia and other wasting disorders. The leptin receptor is not only important as a drug target,
but its discovery may be key to unlocking other key targets in the leptin pathway. The leptin hormone, itself, is unlikely to be a
viable therapeutic because it cannot effectively cross the blood-brain barrier at therapeutic concentrations, and many obese
people have developed resistance to it. These issues may be surmountable with small molecule drugs that act on the receptor or
on downstream signaling molecules.
''These findings, in addition to the many related genes and targets discovered at Millennium, give us a tremendous
understanding of obesity,'' said Dr. Louis Tartaglia, a co-inventor on the patent. ''The cloned leptin receptor has allowed us to
identify and exploit the leptin pathway for the discovery of drugs that will modulate it,'' Dr. Tartaglia added.
''This patent further validates Millennium's leadership in obesity research and represents a clear message from the United States
Patent Office that Millennium scientists were the first to discover the role of the leptin receptor in body weight regulation,'' said
Mark Boshar, associate general counsel and chief patent counsel of Millennium. ''The broad scope of the patent presents very
significant impediments for competitors seeking to exploit the leptin receptor for the discovery of drugs that regulate body
weight.''
Millennium's preeminent six-year obesity and metabolic disease program has yielded the successful discovery of many genes
governing the various aspects of weight regulation and a portfolio of patents. These include patents covering the histamine H3
receptor, a hypothalamic G-protein-coupled receptor (GPCR) important in appetite control (U.S. Patent No. 5,882,893),
screening methods involving the MC4-receptor (U.S. Patent No. 5,908,609), the uncoupling protein homolog (UCPH) gene
(U.S. Patent No. 5,741,666), and the tub gene (U.S. Patent No. 5,646,040). These patents form the cornerstone of the most
comprehensive obesity research program in the world.
Millennium's Obesity Research Program
Three critical elements make up the core of Millennium's obesity research program. First, is the comprehensive identification
and validation of GPCRs expressed in regions of the hypothalamus, an area of the brain important in body weight regulation.
GPCRs span the cell membrane, providing key targets for therapeutic intervention by activating specific intracellular pathways.
GPCRs are also known to be key targets in obesity that may produce viable small molecule drugs. Using its genomics
technologies, Millennium has already identified over 60 GPCRs expressed in the hypothalamus and is systematically evaluating
which of these are most critical to body weight regulation using high-throughput validation technologies. Early successes from
this program are already being used for drug screening.
Second, Millennium scientists make use of genomics technologies, such as transcriptional profiling, mouse models and database
mining, to uncover peripheral drug targets important to obesity. Published successes of this approach include Millennium's
identification of the UCPH gene and the MC4- receptor, and Millennium's and the Whitehead Institute's collaboration and joint
discovery of the protein, FATP4, which plays a role in transporting fatty acid molecules from the intestine into the body. This
discovery was recently published in the journal Molecular Cell (September 23, 1999). Inhibition of the protein's function may
provide new approaches to treating obesity, potentially more efficacious and with fewer side effects than those associated with
the most widely prescribed obesity drug on the market today.
Third, Millennium continues to use its leptin receptor to identify key leptin signaling molecules that may be superior therapeutic
intervention points. One such molecule, which Millennium identified through transcriptional profiling of leptin receptor-induced
genes in the hypothalamus, is now in drug screening.
The research which led to the discovery of the leptin receptor and its role in weight regulation was carried out under
Millennium's strategic research alliance with Hoffmann-La Roche Inc. (''Roche'') which began in 1994. This productive
five-year collaboration generated a pipeline of targets in the area of obesity and ended earlier this year with Millennium retaining
the rights to proceed with certain targets. Millennium will also continue to work on its proprietary pipeline of gene targets. The
Company's targets include genes involved in eating behavior, the enhancement of leptin sensitivity, and a novel anti-absorptive
target. Roche has rights under the new patent for the use of the OB receptor for identification of compounds that induce weight
loss. Millennium has retained the right to use the receptor for the discovery of compounds that induce weight gain. Such
compounds may be useful for the treatment of cachexia and other wasting disorders.
Millennium's Disease-focused Research Strategy
Millennium's strategy includes exploring the central and peripheral mechanisms involved in a given disease and applying the
Company's integrated technology platform to these mechanisms for the discovery of novel therapeutics. In addition to obesity,
Millennium is implementing this strategy in its other key therapeutic discovery programs, inflammation and oncology.
''Millennium is the first company to bring a comprehensive survey of the human genome toward understanding and combating a
human disease. Our obesity program sets a precedent for tackling other complex diseases, such as inflammation and cancer,''
said Robert Tepper, M.D., chief scientific officer of Millennium. ''While others may be codifying the human genome,
Millennium's objective is to aggressively identify targets and pathways for a particular disease, with the goal of ultimately
pinpointing and treating its underlying molecular causes and improving human health,'' Dr. Tepper added.
The Disease of Obesity
Obesity, a condition defined as being 20 percent over one's ideal body weight, is a serious public health concern. According to
the National Institutes of Health, more than one half of adults in the United States, or approximately 97 million people, are
overweight or obese. Obesity predisposes individuals to potentially life-threatening conditions such as hypertension, stroke,
heart disease and diabetes. Scientists also suspect that the disease is linked to certain types of cancer.
Millennium, a leading drug discovery and development company, employs large-scale genetics, genomics, high throughput
screening and informatics in an integrated science and technology platform. This innovative drug discovery platform is applied
across the entire healthcare sector, from gene identification through patient management, to accelerate and transform the
discovery and development of proprietary therapeutic and Diagnomics(TM) products and services. Headquartered in
Cambridge, Massachusetts, Millennium and its affiliates currently employ more than 850 people.
This press release contains forward-looking statements that involve a number of risks and uncertainties. Among the factors that
could cause actual results to differ materially from those indicated in such forward looking statements include uncertainties
relating to gene identification, drug discovery and clinical development processes; Millennium's ability to successfully integrate
the operations of LeukoSite, Inc.; changes in relationships with strategic partners and dependence upon strategic partners for
the performance of critical activities under collaborative agreements; the impact of competitive products and technological
changes; uncertainties relating to patent protection and regulatory approval; and uncertainties relating to the ability of Millennium
and its affiliates to obtain the substantial additional funds required for progress in drug discovery and development. The factors
that could affect the performance of Millennium are more fully described in filings by Millennium with the Securities and
Exchange Commission including but not limited to the factors set forth under the heading ''Business - Factors That May Affect
Results'' in the Annual Report on Form 10-K of Millennium for the year ended December 31, 1998 as filed on March 24,
1999.
Editor's Note: This release is available on Millennium's home page at: mlnm.com.
SOURCE: Millennium Pharmaceuticals, Inc. |
