Abstracts from November 15, 2002 Issue
Biotechnology
researchers presented their latest findings on new gene therapy
techniques for the treatment of a number of human diseases at the
recent BIOPHEX conference, which was held at the Santa Clara Convention
Center in California. The meeting, organized by Genetic Engineering
News and Reed Exhibitions, also featured conference tracks on
bioprocessing and monoclonal antibodies. More than 185,000 individuals
develop brain and central nervous system (CNS) cancers annually,
resulting in 145,000 deaths each year in the U.S.
alone, according to David C. Ansardi, Ph.D., director of research and
pharmaceutical development at Replicon Neurotherapeutics (Danville, CA,
and Birmingham, AL). There
are no viable therapeutic alternatives for patients with neural tumors.
Meanwhile, there is an increasing incidence of metastases of the brain
and spine because of the prolonged survival of patients with lung,
breast, and melanoma cancers.
Ciphergen
Biosystems (Fremont, CA) last month released its new ProteinChip
AutoBiomarker system. The product adds fully automated ProteinChip
array handling, an array AutoLoader, new CiphergenExpress™ database
software, and high-throughput biomarker expression profiling kits to
the existing SELDI ProteinChip platform, according to the firm.
Researchers at the Virginia Prostate Center (VPC; Norfolk) were one of
the first users of the system. Notes Lisa Cazares, lab manager for the
VPC’s biomarker discovery laboratory, “In the past, a 100+ patient
clinical proteomics study would consume tremendous manpower, resources,
and time. Using the AutoBiomarker system, we just ran a 900-patient
study, running each sample in triplicate, in a little under three
weeks.”
PerkinElmer
(Boston) combined its life sciences and analytical instruments business
units into a new integrated business named Life and Analytical
Sciences. The new business will leverage the strengths of the
respective sales, service, and R&D organizations along with
operational scale to better serve customers, according to Peter B.
Coggins, Ph.D., formerly president of PerkinElmer Life Sciences, who
will now serve as president of the new organization. Life and
Analytical Sciences has approximately $1 billion in revenue, more than
2,000 sales, service, and applications-support personnel, and an annual
R&D budget of $65 million. “An integrated Life and Analytical
Sciences organization will enable PerkinElmer to provide a single,
unified face to our customers in the biopharmaceutical and clinical
diagnostics markets, as well as bring greater resources to our
analytical customers,” explains Gregory L. Summe, chairman and CEO of
PerkinElmer.
Today,
if a man is diagnosed with prostate cancer, most likely his prostate
will be removed. Even more unpleasant, he will probably need
chemotherapy to prevent a recurrence. In a few years, however, instead
of the chemotherapy, he might be able to get a simple vaccine with few
side effects. The vaccine will serve as a “drill sergeant” to ready the
body to fight future cancer cells in case the cancer metastasizes.
After the vaccine, the immune system should be ready to recognize cells
that present the cancer marker for which they were prepared by the
vaccine. Everyone is familiar with the traditional prophylactic use of
vaccines to immunize against common infectious diseases; however, the
past ten to fifteen years have witnessed the growth of new applications
of vaccines—prophylactic uses for cancer and HIV, as well as for
treating disease.
The
use of adenoviruses as vectors for gene therapy has been increasing in
recent years. As with other biological products, adenoviral vectors
must be tested for the presence of adventitious agents in order to
satisfy regulatory requirements. Viruses may contaminate biological
products from a number of sources including those present in the
individual from whom the producer cell line is derived; viruses of
animal origin, in media and tissue-culture reagents; and those from
operators or other sources that could have contaminated the cells
during handling in non-GMP conditions. For these reasons, all cell
lines, primary cells, or tissue products used for therapeutic purposes
require testing for the presence of a range of viruses (Figure 1). The
selection of viruses to be tested depends upon the origin of the cell
line and raw material used in manufacture.
The
concept behind the FDA’s electronic records and signatures submissions
regulation, 21 CFR Part 11, is simple. It’s the implementation that’s
the problem. One reason, according to Tom Moran, vp, pharmaceutical
practice, NCS Technologies (Piscataway, NJ), is that the “industry
doesn’t completely believe they have hard and fast regulations.” The
fact of the matter, however, is that technology has evolved to the
point that automating the paper trail makes more sense than keeping the
same documents on paper. Rather than consulting on an individual basis
or selling a specific software program that brings part of an operation
into compliance, The Hollis Group (Paoli,
PA) has designed a template for every system in biotech and
pharmaceutical companies so that they can determine what they need to
do to bring existing computer and network infrastructures into
compliance.
New for the
custom oligos market from Invitrogen (Carlsbad,
CA) is the LUX™ (Light Upon eXtension) fluorogenic primer for
quantitative, real-time PCR. Compared to other types of primer systems
on the market, including dual-labeled probes, such as molecular beacons
or TaqMan® and SYBR® Green DNA-binding dye, LUX primers are
relatively
inexpensive to produce and easy to design; in addition, they offer high
sensitivity and sequence specificity, according to Frances Bai, product
manager for quantitative PCR at Invitrogen. Many companies are
jockeying for a piece of the attractive quantitative RT-PCR market,
which has been estimated at $100 million and growing at a rate of
25–30%. Primers for RT-PCR are one of Invitrogen’s fastest growing
product lines, says Bai, and she expects market demand to continue to
increase as quantitative RT-PCR is “one of the most powerful tools for
comparative gene-expression analysis.”
Streamlining
the drug development process is leading a number of companies to turn
their focus toward rational drug design. BSI Proteomics Corp.
(Gaithersburg, MD) signed a services
agreement with ArQule (Woburn,
MA) for BSI to utilize its Dynamically Controlled Crystallization
Systems™ (DCCS™) to determine protein structures for ArQule. DCCS
initiates, controls, and simultaneously monitors the entire protein
crystallization process. “The fundamental core of the system is its
ability to rationally control this process,” says Mark W. Sawicki,
Ph.D., director of structural biology. The BSI Automated Robotics DCCS
(ARD™), the latest addition to the DCCS family, screens 100 independent
precipitant conditions in parallel, optimizing each condition
individually during protein crystallization trials.
ChemBridge
Research Laboratories (CRL; San Diego) reports that it has identified
druglike small molecule leads against G-protein coupled receptors
(GPCRs), after applying its combinatorial chemistry approach and
library to create a GPCR-Targeted Library. Thomas R. Webb, Ph.D., vp of
R&D at CRL and ChemBridge Corp. (San Diego), explains that the
company’s “targeted library design approach” resulted in “the direct
confirmation of agonist activity against a peptide-ligand–binding GPCR.
Such activity is rarely found in standard screening collections of
small molecules,” he adds. “We found agonist activity in every compound
in a small and tightly focused set of compounds that were designed
using our template and building block approach.” The company is now
optimizing the lead series further, with the aim of enhancing
drug-relevant properties in parallel.
With
the current industry need to be able to make sense of the vast amount
of data being generated by 2-D protein gels and arrays, firms
developing software for these applications are finding their products
increasingly sought after. One such company, Nonlinear Dynamics
(Newcastle, U.K.), is in the favorable position of having been in the
market and concentrating specifically on this application for over ten
years. “In the late 80s, I was working on developing software for a
company making image analyzers,” Will Dracup, CEO and founder, says,
“when it occurred to me that it should be possible to make 2-D gel
analysis software run on a 32-bit, Windows-based PC. At that time,
companies developing this type of software were running it on Unix
platforms or were producing customized systems. These products were
generating high profit margins for the companies involved, and they
hoped it would be impossible to produce Windows-based software for such
complex applications.”
It
is estimated that current drug therapy is based on less than 500
molecular targets. However, it is now thought that around 10,000 of the
40,000 genes in the human genome could provide a range of new
therapeutic targets. Novel mammalian-, cell-, and chip-based methods of
identifying and validating which diseases are associated with
these
important targets was the subject of discussion at the recent “8th
Annual Society for Biomolecular Screening (SBS) Conference,” held in
The Hague. Russell Phillips, Ph.D., a scientist at Deltagen (Redwood
City, CA) and Achim Plum, Ph.D., a senior scientist at Ingenium
Pharmaceuticals (Martinsried, Germany) presented counterpoint views on
how to find functions for different genes using mouse models. Both
stated the rationale for using this model is that the mouse genome has
around 95% homology with the human genome so it is thought to be a good
model on which to base human therapeutics.
The
European Parliament (EP) took its first vote on European Commission
(EC) proposals for widespread reform of European legislation on
pharmaceutical products. The proposals include measures designed to
boost innovation within the European pharmaceutical industry, bolster
competition in the generics field, streamline the approvals process,
and ensure patients get swift access to safe new medicines. Through its
first vote on the proposals, the EP supported plans to introduce a
central authorization procedure for all new medicines, but rejected EC
calls to allow patients suffering from AIDS, asthma, or diabetes to
obtain information on relevant drugs directly from pharmaceutical
companies. The EC maintains fears that such a move would lead to
unsolicited advertising by the pharma companies are unfounded, however.
In a statement, Erkki Liikanen, EC Commissioner for Enterprise, claimed
allowing patients suffering from these diseases to have direct access
to drug data “would simply enable patients to get good, appropriate,
and officially authorized information if they so request.” More
information on the scope and nature of the reform proposals are
available at: pharmacos.eudra. org/F2.home.html.
IDgene
Pharmaceuticals (Jerusalem) says it has discovered an association
between the COMT (catechol-O-methyltransferase) gene and schizophrenia.
The details of this finding will be published in next month’s issue of
The American Journal of Human Genetics and are now available online at www.journals.uchicago.edu/AJHG/home.html.
“The genetic basis of schizophrenia is poorly understood and the data
presented to date has been mostly inconclusive. IDgene has successfully
produced the most statistically significant results ever reported in
schizophrenia or in any other common polygenic disease. The study shows
that the COMT gene may account for more than 20% of all schizophrenia
patients. In the near future, we expect several additional discoveries
of novel disease susceptibility genes, as well as genes responsible for
variation in drug response,” notes IDgene’s CEO, Ariel Darvasi.
Ibex Technologies
(Montreal)
reports that it has discovered a novel therapeutic peptide target for
the treatment of arthritis that showed evidence of activating the
production of collagenase. The goal of the study that led to the
discovery was to determine whether a specific peptide, a collagen
fragment, upregulated gene expression and protein production of
collagenases in isolated normal human chondrocytes, and to determine
which receptor and signaling pathways were involved in this
upregulation. The study demonstrated that a synthetic peptide of type
II collagen can induce the cleavage of type II collagen by collagenase
in human-cartilage explants. This occurs when the peptide “docks” with
a receptor on the surface of a cartilage cell, which in turn signals
the collagenase gene to start producing additional destructive enzymes.
The data was presented by A. Robin Poole, Ph.D., and colleagues from
the Shriners Hospitals for Children (Montreal), at the recent “66th
Annual Scientific Meeting of the American College of Rheumatology” in New Orleans.
Applied
Biosystems (AB; Foster City, CA) is perhaps best known for providing
instruments for DNA analysis. However, the company’s portfolio of
technologies, reagents, and service offerings has expanded its market
presence throughout basic life science research, as well as the drug
discovery and drug development markets. Most recently, the business has
expanded its focus to create new proteomics technologies and
knowledge-based products that integrate life science data with tools
and technology for the analysis of the growing amounts of sequence and
other biological information. Since it was founded in 1981 and after a
$22-million IPO in 1983 and a series of mergers and acquisitions over
the years, AB has grown into a business with customers in approximately
150 countries. AB is an Applera Corporation business, traded on the New
York Stock Exchange under the symbol ABI.