Appeal No. 2001-0288 Page 6
Application No. 08/277,031
According to the examiner (Answer, page 12) Yasumori ‘89 teaches “that
expression of the human cytochrome P450 IIC9 plays … ‘a substantial role in
xenobiotic and carcinogen metabolisms in human liver’, where its expression is
constitutive, i.e., continuous, and that it can, and should, be recombinantly
expressed in yeast.”
In view of these teachings, the examiner finds (Answer, pages 6 and 7):
It would have been obvious to one of ordinary skill in the art
at the time the invention was made to supplant the multiple
cytochrome P450-expressing transformed human cell of
Crespi et al. with the less expensive, more easily-
maintained, and specifically regulated yeast transformants
which recombinantly express the cytochrome P450/yeast
NADPH-cytochrome P450 reductase fusion of Sakaki et al.,
replacing a bovine cytochrome P450-encoding region of
Sakaki et al. in the fusion gene construct with each of the
human cytochrome P450 IA2-, IIE1- and IIIA4-encoding
DNAs used by Crespi et al. as well as the human
cytochrome P450 IIC9-encoding cDNA of Yasumori et al.
(‘89). This is because Crespi et al. and Yasumori et al. (‘89)
teach that the human IA2, IIE1, IIA4 and IIC9 cytochromes
P450 are all important components in the metabolism of
carcinogenic compounds and because Yasumori et al. (‘87)
teach that the IIC9 species is constitutively expressed – thus
is continuously present – in human liver cells. Use of a
yeast expression system is further obvious because Sakaki
et al. had already provided such a system, with appropriate
expression vectors, for recombinant expression of active
cytochromes P450 in yeast transformants. One of ordinary
skill in the art at the time the invention was made would have
experienced motivation to transform yeast cells with
expression vectors for the recombinant production of
mammalian cytochromes P450 because Wolf et al. had
suggested that a system using yeast transformants would be
useful.
In response appellants argue (Brief, page 9) that Yasumori ‘89 “refers to a
‘human-2’ protein and cDNA … at the time the present invention was made,
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