82 • Impacts of Applied Genetics — Micro-Organisms, Plants, and Animals 
term benefits were not established. Since then, clinical 
investigation of urokinase has been hampered by 
domestic regulatory problems, which have raised the 
cost of production and restricted its availability in the 
United States. 
In January 1978, Abbott Laboratories obtained a 
new drug application for urokinase and introduced the 
product Abbokinase; by that time, however, the sales 
of urokinase in Japan were already pushing $90 million 
per year. Recently, Sterling Drug has begun marketing 
a urokinase product (Breokinase) manufactured by 
Green Cross of Japan: "According to Japanese reports, 
urokinase is the first Japanese-made drug formulation 
to receive production and sales approval from FDA. 
Green Cross estimates that within 3 years of the start 
of Sterling’s marketing activities, the value of uro- 
kinase exports will reach Yen 500 million ($2.12 mil- 
lion) per month, and considers that its profits from ex- 
porting a finished product will probably be better than 
those from bulk drug sales or the licensing of technol- 
ogy.’’ The Green Cross product is made from human 
urine collected throughout Korea and Japan, and takes 
advantage of technology licensed from Sterling. Ab- 
bott’s product, on the other hand, is derived from 
kidney-cell culture. 
15. Intergeneric hybrids have extremely interesting pos- 
sibilities. For example, it would be beneficial to cepha- 
losporin-process technology to combine in one orga- 
nism the acyltransferase from Penicillium chrysogenum 
and the enzymes of C. acremonium, which does not in- 
corporate side chain precursors onto cephalosporin 
like P. chrysogenum does for penicillins. 
16. Another example of recombination between species is 
that reported for two species of fungi, Aspergillus nidu- 
lans and A. rugulosus, subsequent to protoplast fusion. 
The only report of a successful cross between 
genera using protoplast fusion technology has been be- 
tween the yeasts Candida tropicalis and Saccario- 
mycopsis fibuligera, which took place at low frequency 
and gave rise to types intermediate between the 
parents. 
17. An example of screening is provided by the new 
i8-lactam (penicillin-like) antibiotics. Using older 
screening methods, no new ;8-lactams were found 
from 1956 until 1972 when a new method was devised. 
A new series of these antibiotics was thus found. 
Within the past year, 6 new )3-lactams have been 
commercialized and at least 12 more are in clinical 
trials around the world. The sales forecasts for these 
new agents are estimated to he o\ er $1 billion. 
