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Monoclonal
Antibodies: the medicine for the 21st century
Recent
developments in immunology are opening up a huge range of
potential new therapies. Other promising areas include vaccine
development, recombinant or modified growth factors and their
receptors, and the possibilities of therapy with whole cells.
However, the very diversity and exquisite specificity of these
new approaches pose huge new challenges to the pharmaceutical
industry and drug regulatory mechanisms. Exploitation which is
based mainly on market potential, intellectual property rights
and dividend forecasts will produce a few commercially
successful products.
Monoclonal
antibodies (mAbs) are nature’s biological warheads, able to
target and help eliminate foreign or abnormal agents from the
body. In theory, replicating this powerful defense system could
cure some of humanity’s most deadly diseases. It is able to
directly target and destroy cancer cells through use of the
immune system, reducing the debilitating side effects currently
experienced with radiation and chemotherapy, offering patients
an alternative and more effective therapy. An antibody is a
protein our own body makes to fight infections. For treatment of
diseases such as cancer these quantities are not enough, so one
needs to make antibodies outside the human body using modern
biotechnology methods and take those antibodies and give them
back to the human body in the form of injections.
In
1895 Hericourt and Richet described the first trials in which
cancer cells were injected into animals to raise an antiserum
for treating the patient. In 1975 Kohler and Milstein found the
key to aiming the "magic bullets" first envisaged 80
years earlier. For this discovery, they were awarded the 1984
Nobel Prize for medicine. The first generation of mAbs, derived
from the progeny of a single immune cell, was of the mouse
origin which showed only limited potential as therapeutics. The
human immune system recognized mouse mAbs as foreign material
producing human anti-mouse antibodies (HAMA) to clear them from
the body thereby limiting their therapeutic benefit. To make
mAbs successful in the clinic biotechnologists using the tools
of molecular biology needed to create non-immunogenic mAbs with
high binding affinities that could work effectively. Subsequent
efforts concentrated on using these techniques to produce human
or human like monoclonal antibody products such as chimeric and
humanized mAbs.
Monoclonal
antibodies represent one of the success stories of the biotech
industry. With a broad range of therapeutic and diagnostic
applications, this class of drug has a huge market potential. As
of early 2002, 18 monoclonal antibodies had been approved for
use in the US, 11 as human therapeutics and eight as
diagnostics. Close to 100 antibodies are in clinical trials and
hundreds more in preclinical development to treat diseases such
as cancer, inflammatory, autoimmune diseases, allergic
disorders, transplantation, cardiovascular and infectious
diseases. A conservative estimate points to about 1,100
biotherapeutic products currently in preclinical studies. MAbs
offer a glimmer of hope in the battle against cancers such as
breast and Non-Hodgkin's Lymphoma (NHL). As products begin to
emerge from phase III trials and approvals are seen across
Europe, the market place will develop and more confidence will
be instilled in the capabilities of these 'magic bullets'.
Quality of life is an area of ever increasing importance in
oncology and these novel therapies offer a vast improvement for
a patient already in emotional and physical suffering. The cost
of drug therapy accounts for a minority of the total cost of
cancer care, with patients requiring expensive supportive care
in order to manage the side effects of cytotoxic therapy. In
Europe in 2000, $291.4 million (U.S.) was spent on anti-emetic
therapy alone. Monoclonal Antibodies will eliminate the need for
support care and significantly improve the quality of life for
cancer patients. .
The
investment group, UBS Warburg has given projections in their
Sept 2001 Pharmaceutical and Biotechnology report that of mAb
market is forecast to grow to US$6 billion in 2005 and US$ 24
billion in 2010.
As
interest in the antibody field grows in both the biotechnology
and pharma sectors, primarily due to their versatility as
therapeutics, diagnostics, and as reagents in drug discovery
research, so grows the legal rambling about intellectual
property (IP) situations. While controversy regarding IP
position is nothing new to the antibody field, the court rulings
of these patent skirmishes will have far-reaching monetary and
product development repercussions for those companies involved
in the lawsuits that also have major alliances with first-tier
pharma companies.
Shantha
West has filed world wide patent for TB94 and also has been
granted the same. The company has filed PCT patent for RM-2 and
RM-4.
Shantha
Biotechnics is a leading Biotechnology company in India and has
the laurels of developing India’s first rDNA-based hepatitis B
vaccine. It has also developed and launched interferon alpha 2b.
A number of other recombinant therapeutic proteins are
undergoing toxicology studies and clinical trials. Shantha
Biotechnics is playing a leading role in the development of
therapeutic antibodies in India. Along with its US subsidiary
Shantha West based in San Diego, California the company is
utilizing the body’s own human immune system to produce
effective cancer specific antibodies. The company’s lead
pharmaceutical products are fully human monoclonal antibodies
designated TB94, RM2, RM3 and RM4. These unique monoclonal
antibodies have the potential to be used both as a diagnostic
tool as well as therapeutic reagent. The target diseases are
lung cancer, melanoma, pancreatic cancer, neuroblastoma, breast
and colon cancer. The company’s clinical approach is to use a
cocktail of antibodies to treat each target disease. The
estimated potential value for multi-mAb therapeutic products is
in excess of US$ 700 million.
Shantha
Biotechnics has recognized the need to keep the manufacturing
process in mind when developing biological products such as
monoclonal antibodies. Current manufacturing capacity for
biopharmaceuticals in general is fast becoming a rate-limiting
factor in the growth of the biotech sector. Antibody
therapeutics are likely to be the hardest hit by this shortage,
as they are required in much larger quantities than other
protein therapeutics. With the above in mind and also to make it
affordable in India the company has explored several potential
methods of large scale production and chosen transgenic plants
as the primary production method. Using this methodology we will
be able to produce in a cost effective manner and in
commercially viable quantities.
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