The Dow Chemical Company and Plant Research International B.V. of
Wageningen, The Netherlands, have agreed to join forces to speed
development of therapeutic proteins with mammalian-like glycan structures in
transgenic plants. Through their collaboration, the companies will work to
expand the utility of plant-based production for pharmaceutical proteins.
"Dow is delighted to be working with Plant Research International, an
innovative leader in glycoprotein optimization in transgenic plants," said Kurt
Hoeprich, Director of Market Development for Dow Plant-Based
Biopharmaceuticals. "By optimizing glycoprotein production in plants, we can
greatly expand the applicability of this new production platform in the rapidly
growing biopharmaceutical marketplace."
According to industry research by a financial analyst from U.S. Bancorp Piper
Jaffray, Inc., approximately 100 therapeutic proteins are now in mid- to
late-stage clinical development. Potential manufacturing capacity shortages
are leading pharmaceutical companies to consider plant-based production
Dirk Bosch, group leader at Plant Research International explains: "We are very
pleased with this excellent match of Dow?s proprietary expression
technologies and biopharmaceutical protein processing expertise with Plant
Research International?s proven, integrated R&D capabilities for biosynthetic
pathway engineering and protein analysis. This agreement will accelerate
scientific developments at our institute and will place us in a position to help
generate additional technological breakthroughs relevant to therapeutic protein
production. Dow is a major player, with complementary skills and networks
which support our ambition to use our expertise to benefit the pharmaceutical
The agreement calls for Dow and Plant Research International to share their
intellectual property estates in the field of glycosylated protein production in
transgenic plants. Dow will lead commercialization of this exclusive technology
for the therapeutic protein contract manufacturing market. Earlier this year, Dow
secured patents on technology to enable glycan production in plants, which it
will make available under this agreement. The agreement also involves a
multi-year collaborative research program focused on further optimizing
protein glycosylation in transgenic plant systems.
Dow also has agreements in place with Epicyte Pharmaceutical Inc., a
biopharmaceutical company focused on the discovery and development of
therapeutics to treat inflammatory and infectious diseases, and Centocor, Inc.,
to produce monoclonal antibodies in transgenic plants. According to Hoeprich,
"This group of strategic agreements aligns key technology leaders toward
fulfilling the promise of plant-based approaches to drug substance supply.
Beyond overcoming the well-reported capacity limitations in the
biopharmaceutical industry, a plant-based approach also holds the potential to
lower capital and operating costs."
Glycans are a series of specific sugar units which are an integral part of many
complex proteins, including many life-saving, high-value therapeutic proteins
on the market today and in clinical development. The presence of glycans on
proteins is essential for full functionality in the body and, more specifically, in
the bloodstream. Many commercially important proteins must contain specific
glycans to be fully functional or efficacious and work safely in the human body.
Examples of glycosylated therapeutic proteins include Factor VIII, a protein
critical to the blood clotting process. Individuals with hemophilia are unable to
produce Factor VIII protein and must administer the glycan-containing version
of this protein on a regular basis. Further, 10 of the 11 monoclonal antibody
drugs on the market today contain glycan structures. The presence of a glycan
on an antibody therapeutic is critical for ensuring structural integrity is
maintained and for optimum efficacy.
There are differences between glycans placed on a protein produced in plants
and those placed on a protein produced by the dominant manufacturing
method, mammalian cell culture. Lessening or completely eliminating these
differences will greatly increase the acceptance level and viability of
plant-based production techniques.
Enabling glycan production via the plant-based approach can result in lower
capital costs and greater production efficiencies. In addition, a plant-based
approach can produce a faster route to production, simpler downstream
processing and provide nearly limitless capacity. Plant-based production
accommodates a wide range of protein types, including some not possible with
traditional production technologies.
Effective plant-based technology can also improve the efficacy of drug
substances by overcoming the problem of incomplete glycosylation, the
incomplete formation of human carbohydrate patterns. Incomplete
glycosylation can result in increased costs of production due to more
processing steps, reduced half-life of the protein in the body, increased
immunogenicity and reduced clinical effectiveness. Eliminating this problem can
result in improved drug properties, greater production efficiencies and, in some
cases, additional patent protection for drug developers.