Sources and upstream processing - Pharmaceutical Biotechnology: Concepts and Aapplications - page 113

Table 5.5 Recombinant therapeutic proteins approved for general medical use that are
produced in S. cerevisiae. All are subsequently discussed in the chapter indicated

Trade name Description Use Chapter

Novolog Engineered short-acting

insulin

Diabetes mellitus 11

Leukine Granulocyte

macrophage CSF
(GM-CSF)

Bone marrow
transplantation

10

Recombivax, Comvax,
Engerix B, Tritanrix-
HB, Infanrmix,
Twinrix, Primavax,
Hexavax

All vaccine preparations
containing rHBsAg as
one component

Vacci nat ion 13

Revasc, Refl udan Hirudin Anticoagulant 12

Fasturtec Urate oxidase Hyperuricaemia 12

Regranex PDGF Diabetic ulcers 10

type glycosylation patterns generally trigger their rapid clearance from the blood stream. Such
products, therefore, would be expected to display a short half-life when parenterally administered
to humans, and some yeast sugar motifs can be immunogenic in humans.

5.2.3.2 Fungal production systems

Fungi have elicited interest as heterologous protein producers, as many have a long history of use
in the production of various industrial enzymes such as α-amylase and glucoamylase. Suitable fer-
mentation technology, therefore, already exists. In general, fungi are capable of high-level expres-
sion of various proteins, many of which they secrete into their extracellular media. The extracel-
lular production of a biopharmaceutical would be distinctly advantageous in terms of subsequent
downstream processing. Fungi also possess the ability to carry out post-translational modifi ca-
tions. Patterns of glycosylation achieved can, however, differ from typical patterns obtained when
a glycoprotein is expressed in a mammalian cell line. Again, this can trigger a reduction is serum
half-life or immunological complications in humans.
Most fungal host strains also naturally produce signifi cant quantities of extracellular proteases,
which can potentially degrade the recombinant product. This diffi culty can be partially overcome
by using mutant fungal strains secreting greatly reduced levels of proteases. Although researchers
have produced a number of potential therapeutic proteins in recombinant fungal systems, no biop-
harmaceutical produced by such means has thus far sought/gained marketing approval.

5.2.3.3 Transgenic animals

The production of heterologous proteins in transgenic animals has gained much attention in the re-
cent past. The generation of transgenic animals is most often undertaken by directly microinject-
ing exogenous DNA into an egg cell. In some instances, this DNA will be stably integrated into