The Problem:
The screening of candidate compounds as
potential drugs is time-consuming and uncertain.
The probability of a “hit” compound is dependent
upon the library size of compounds tested and
the effectiveness of the screening procedure.
Furthermore, a successful in vitro or in vivo
assay can not predict the effectiveness of the
drug candidate in humans. Absorption,
distribution, binding, metabolism, and excretion
of the drug are unknown at this level of the
drug development process. As a result, the
effectiveness of the candidate drug can only be
determined by testing it in animal models.
Unfortunately, the leap from an in vitro or in
vivo assay to that of an animal experiment
almost always requires modification of the
compound to improve the therapeutic profile.
However, these modifications to the original
drug chemistry may make the drug ineffective by
potentially reducing its biophysical properties
of affinity and specificity and potentially
increasing its cross-reactivity and side
effects, in effect, destroying the opportunity
of using the compound as an effective drug.
Because of all of
these issues involved in drug development, the
process is reduced to a trial and error approach
inevitably making it unpredictable—on average, only
one in a thousand drug candidates make it to
clinical trials in humans.
The cost and time associated with this
traditional method of drug development is
expensive and quite slow. From lab bench
to pharmacy shelves it takes anywhere from 7 to 15 years and
costs almost $1 Billion.
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The Solution: we undertake the drug
discovery process in vivo. Normally, a drug
candidate would be developed against a protein or target
known to be involved in the disease of interest. This
means that the target must be known in some form.
However, the development of aptabody™ drugs does not
necessitate such knowledge, and dramatically
reduces the
time and cost for drug development. This process of
aptabody™ drug development is known as aptagenesis™.
The
unique chemistry of aptabodies™, unlike other forms of
drugs currently used, permits the selection in whole
animal models. By using an animal model with the
disease state, specific knowledge of the cellular or
protein target is not needed.
Method of
AptagenesisTM:
A healthy animal
is challenged with a large library of aptabodies™(1012
to 1015 different molecules).
Unchanged aptabodies™ that are quickly cleared or
linger around in the bloodstream become
the first round of “suspects.” These suspects
are administered to an animal model exhibiting the
disease state of interest. Sacrifice of the animal and
recovery of the diseased tissue permits recovery of
aptabodies™ that concentrated at the disease site – the
“prospects.” Prospects are recovered and
amplified. Further rounds of challenge and recovery are
expected to reduce the number of prospects to
those with the highest affinity or
activity to the pathological marker of the
disease.
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Aptabodies™
are nucleic acid molecular scaffolds with
associated functional groups, which like
antibodies, can bind to targets with high
affinity and specificity. Amino acids,
fatty acids, carbohydrates, as well as small organics
comprise the chemical alphabet available to
aptabodies. Aptabodies™ can
circulate through the body and penetrate tumors
and other disease targets. |
The high
binding affinity of aptabodies™ results from the
functional group attachments and a very large
surface area available for the binding.
The synthetic production of aptabodies™ permits
a wide range of functionality to be
incorporated, and can be easily modified with cytotoxic and radioactive
materials to destroy tumors; moreover, the
functional group attachments provide sufficient
chemistry to allow for enzymatic activity and
processing of diseased targets.
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