Business Potential for Agricultural Biotechnology - Asian Productivity ...

Business Potential for Agricultural Biotechnology Products
cult, once they have been produced and cloned, it will be possible to create herds of transgenic
animals giving pharmaceutical milk products of identical quality (Reichenstein et al., 2001).
However, production using milk has some disadvantages. Producing milk is time-consuming
(lactation has to occur) and sex-dependent (sexual maturation has to occur), and the target protein
is difficult to purify from numerous other milk proteins. Urine, on the other hand, is continuously
produced right after birth and relatively free of other proteins.
PPL in the UK produced “Tracy,” the first transgenic sheep, in 1991 using transgenic techniques
in order to produce human protein in its milk (AAT) (Wright et al., 1991). In 1997, PPL
announced that transfection of a human blood coagulation factor IX gene to a cell culture prior
to nuclear transfer had produced “Polly,” a genetically engineered lamb (Schnieke et al., 1997).
In 1997, a U.S. scientist in a Dutch laboratory reported the production of a biologically active
human blood coagulation factor VIII protein in the milk of a transgenic pig (Paleyanda et al.,
1997).
In 2003, GTC, a biotherapeutics company, announced completion of clinical trials for
Atryn, a recombinant human antithrombin for deep vein thromboses (DVTs) and thromboembolisms
in patients with a hereditary deficiency of antithrombin (GTC, 2004). GTC submitted a
marketing authorization application (MAA) to the European Medicines Evaluation Agency
(EMEA) for review in early 2004. The submission was accepted in late February 2004, and GTC
is planning the commercialization of Atryn. GTC stresses that Atryn is “the first therapeutic
protein produced using transgenic technology to be submitted to any regulatory agency anywhere
in the world” (GTC, 2004).
TRANSGENIC ANIMALS AS BIOREACTORS
Transgenic Pigs
hEPO Transgene Expression in Transgenic Pig (Saerome) (Source of information: 3 October
1998. National Livestock Research Institute [NLRI], Suwon, Korea. Patents: PCT WO 01/59074,
GB2376024 [2004.9.22])
NLRI has been a leader in Korean livestock research since 1906. The Institute has a wellorganized
research system covering almost every aspect of farm animal research. Although the
Animal Biotechnology Division is relatively new, it has focused on current technologies, including
the field of livestock cloning and transgenic animals.
Epoetin alfa is used to treat anemia patients and is produced by Amgen, the company dominating
virtually the entire EPO market; the drug had a market share of about USD6 billion in
2001. The market share of epoetin alfa has been increasing every year since 1989, the year the
USFDA approved its medical use (Datamonitor, 2002). In 1998, it was USD2 billion; by 2001, it
had grown to USD6 billion. Its market share is expected to increase further after the expiration
of the key patent enables the marketing of various generic drugs of a similar nature. Erythropoietin
is used to treat various symptoms of anemia, ranging from anemia associated with
chronic renal failure (CRF) to anemia in cancer chemotherapy patients (Tsakiris, 2000). Medicare
covers only anemia associated with CRF patients due to the high price of drugs and a supply
shortage caused by limited production capacity. In many countries, including the U.S., in
some cases where EPO is called for, it is either not covered by Medicare or not administered
(Greer, 1999). Listed in Table 1 are the world’s top ten biopharmaceutical products.
Using mouse whey acidic protein (WAP) promoter (Piletz et al., 1981) as expression controller,
NLRI scientists designed a human EPO transgenic expression vector and introduced it
into pig embryos via microinjection. The founder male was born in 1998. After the identification
and analysis of hEPO proteins in its milk, NLRI has been producing TG progeny. Although the
purification project is ongoing, a basic foundation has been established that included amino acid
sequences, expression level, and activity analysis. Erythropoietin (EPO), a ca. 34 kDa glycoprotein
that stimulates red blood cell formation, is produced primarily in adult kidneys (Fisher,
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