Peptech / Domantis / Magic Bullets

Old news for some, but this article basically explains in simple terms that importance of Diversys, now called domantis, to Peptech, and why many of the big holders of the stock, see the investment in Domantis as a bag full of future value.

Magic bullets' finally on target - Biotechnology


The Weekend Australian Edition 1 SAT 02 MAR 2002 Page 031

By: Graeme O'Neill




WHEN Cesar Milstein and George Kohler invented monoclonal antibodies in
1975, medical science hailed them as ``magic bullets'' that would
revolutionise the diagnosis and treatment of disease.
The first generation of magic bullets misfired badly. Derived from the
immune-system genes of mice, monoclonal antibodies (MABs) caused
life-threatening allergic reactions in many human patients.
But a new wave of ``designer'' monoclonal antibodies (MABs) is now entering
clinical use. They are of human origin, and they are fulfilling the
technology's promise of providing a new source of potent therapeutic drugs
and uniquely sensitive diagnostic reagents.
Antibodies are Y-shaped protein molecules, secreted by specialised
immune-system cells called B-cells. They are a primary defence against
infectious microbes and parasites, toxins and the myriad alien substances
that the body encounters in a lifetime.
For almost any molecule found in nature, the immune system can generate an
antibody of complementary shape and affinity, using a complex gene-shuffling
mechanism.
The human immune system has a potential repertoire of 1 trillion antibodies.
From this vast library it selects a best-fit antibody, then refines its
genetic formula until it achieves a perfect match with an target antigen's
shape. It then makes billions of copies of the original B-cell to
mass-produce the antibody. The target antigen might be a protein on the
surface of the virus or bacterium, a receptor molecule on a cell, a fungal
toxin, or an allergenic protein on a pollen grain. Once the immune system
achieves a perfect match, B-cells swamp the interloper, coating it with
neutralising antibodies that mark its destruction.
To make a MAB, researchers select a target antigen, sift the immune system's
vast ``library'' for a perfect match, then copy its DNA formula. New
techniques have greatly simplified the process of identifying promising new
therapeutic or diagnostic MABs, and synthesising them in industrial
quantities.
MABs can be used to seek out and destroy viruses, bacteria, toxins or other
alien molecules, or to correct metabolic disorders. As diagnostics, they can
be used to confirm microbial infections, provide early warning of cancer,
identify metabolic errors, or outline solid tumours for precision surgery.
In the early 1990s, British molecular geneticist Dr Greg Winter of Cambridge
University devised a revolutionary technique for producing MABs in bulk by
splicing human antibody genes into specialised viruses called
bacteriophages.
Winter's advance has given researchers access to the vast library of a
trillion-plus human antibody formulae. Where it formerly took many months to
find the perfect antibody for a new therapeutic or diagnostic target,
researchers can now identify half a dozen candidates in an afternoon.
Biopharmaceutical companies and biomedical research agencies have scrambled
to exploit Winter's technique. Between 1998 and 2001, global revenues from
human-engineered antibodies soared from zero to around $A6 billion. Rival
MAB therapies for the crippling auto-immune disorder, rheumatoid arthritis,
account for half this figure.
US biopharma giant Genentech's new breast-cancer therapy, Herceptin, is
another major earner. It employs a MAB that blocks estrogen receptors,
starving breast tumors of the hormone that fuels their rampant growth.
The new rheumatoid-arthritis therapies, which are revolutionising the
treatment of the disorder, were developed by subsidiaries of biopharma
giants BASF and Johnson and Johnson.
They are generating a lucrative stream of royalty payments for Sydney-based
biopharma company Peptech Ltd, which owns a vital patent on the therapeutic
target -- a cell-signalling molecule called tumor necrosis factor-1 (TNF-1).
In the late 1980s, Peptech researchers were studying TNF-1, which initiates
the inflammatory response that causes the immune system to destroy the
cartilage cushioning the joints.
Peptech shelved the project because there was no way to create a human MAB
to block TNF-1, but the company presciently lodged a provisional patent on
any future MAB therapeutic that targeted TNF-1. Greg Winter has recently
developed a way of producing cut-down human MABs small enough to enter
recesses or cavities inaccessible to full-sized antibodies.
``Lite'' MABs can also be tailored for therapeutic uses requiring
short-lived activity, such as poisoning.
Peptech last year acquired 34 per cent of Winter's new company, sus, and
plans to develop its own ``lite'' MABs it has already identified several
potentially lucrative therapeutic targets.
Peptech founder Dr Geoff Grigg, now the company's scientific adviser, says
many Australian research laboratories are constantly identifying new
therapeutic targets for MABs.
The Diversus alliance gives the company -- and Australia -- a strong
strategic position in the emerging global market for MAB-based drugs and
diagnostics.
Brisbane-based biotech company AGEN is trialling a new MAB that detects and
highlights life-threatening blood clots in the lung, pulmonary embolisms and
deep vein thromboses in the legs, so-called ``economy-class syndrome'' in
long-distance airline travellers.