Company 10-K part 1:
ITEM 1. BUSINESS
We design, produce and sell primarily to pharmaceutical and biotechnology
firms, infrastructure products and, to a lesser extent, services that accelerate
and enhance the process of discovering new drugs. Our proprietary integrated
technology platform is comprised of instrumentation and consumables (microplates
and fluorescence-based assay technologies) designed to provide flexible
solutions to the current and evolving high throughput requirements of drug
discovery laboratories. We intend to establish our products, marketed as
CRITERION-TM-, as the "gold standard" for addressing many of the key bottlenecks
in drug discovery. Further, we believe that, in the future, as more details of
the human genome become available, pharmaceutical and biotechnology firms will
begin utilizing high throughput screening in genomics during their search for
new drugs. In this regard, recently, we have demonstrated that certain products
from our CRITERION product line can be used to genotype or characterize single
nucleotide polymorphisms, or SNPs, and we have begun to commercialize these
products for genotyping applications.
DRUG DISCOVERY
The drug discovery process involves the synthesis and testing, or screening,
of compounds against a target. A compound is a molecule that might influence a
disease by its effect on a target. Targets are biological molecules, such as
enzymes, receptors, other proteins and nucleic acids that are believed to play a
role in the onset or progression of a disease. The stages of the drug discovery
process include:
- target identification,
- target validation (including genotyping of SNPs),
- assay development,
- primary screening,
- secondary and tertiary screening,
- lead compound optimization and
- clinical candidate selection.
DRUG DISCOVERY--SCREENING
Targets are identified based on their potential role in altering the
progression or prevention of a disease. Until recently, scientists using
conventional methods had identified only a few hundred targets, many of which
had not been comprehensively screened. Recent developments in molecular biology
and genomics have led to a dramatic increase in the number of targets available
for drug discovery.
After a target is validated, the researcher selects a library of compounds
to screen against this target. Compounds have historically been obtained from
natural sources or synthesized one at a time. Traditionally, pharmaceutical
companies, using conventional synthesis techniques, have compiled their compound
libraries over decades. However, recent technology advancements in parallel
synthesis combinatorial chemistry and other chemical synthesis techniques, as
well as licensing arrangements, have enabled industrial and academic groups to
greatly increase the supply and diversity of compounds available for screening
against targets. As a result, many researchers now have access to libraries of
hundreds of thousands of compounds.
Prior to high throughput screening of compounds against a target, a
biological test or assay must be developed. An assay is a combination of
reagents, which measures the effect of a compound on the activity of a target.
Assay development involves screening the assays to optimize performance against
the selected target and are broadly classified as either biochemical or
cellular. Following target and compound library selection and synthesis and
assay development, the compounds must be screened to determine their effect on
the target, if any. In the primary screening campaign, a compound that has an
effect on the target is defined as a hit. A greater number of compounds screened
against a given target result in a higher
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statistical probability that a hit will be identified, assuming that the library
is sufficiently diverse. Scientists use both cellular and biochemical assays in
their drug discovery efforts. Both types of assays use a variety of detection
methods, including:
- absorbence,
- radioisotopic,
- luminescence and
- a variety of fluorometric technologies, such as fluorescence intensity,
fluorescence polarization and time-resolved fluorescence.
Biochemical assays are usually performed with purified molecular targets and
generally have certain advantages, such as speed, convenience, simplicity and
specificity. Cellular assays are performed with living cells, which may
sacrifice speed and simplicity, but may deliver more biologically relevant
information. Once a compound is identified as a hit, and the data is validated
in a follow up screen, several secondary and tertiary screens are performed to
evaluate its potency and specificity for the intended target. This cycle of
repeated screening continues until a small number of lead compounds is selected.
Further screening, notably against pharmacokinetic and toxicological parameters,
optimizes these lead compounds. Optimized lead compounds with the greatest
therapeutic potential and window of selectivity may be selected as candidates
for clinical evaluation.
Due to the recent dramatic increase in the number of available compounds and
targets, a bottleneck has developed at the screening stage of the drug discovery
process. Historically, screening has been a manual, time-consuming process.
Screening significantly larger numbers of compounds against an increasing number
of targets requires a system that can operate with a high degree of automation
and analytical flexibility.
To address these bottlenecks, we have developed instrumentation and assays
to provide integrated high throughput solutions. We believe that our technology
platform addresses the major throughput limitations associated with current high
throughput systems and will allow our customers to accelerate the identification
and optimization of lead compounds for development into new medicines. |
