Appeal No. 1999-2634
Application No. 08/108,606
twenty four hours and treating the E. coli with 0.2 to 0.4% formalin to prepare a killed
E. coli vaccine.
The examiner summarizes (Paper No. 16, pages 5-7)
It would have been obvious to one of ordinary skill in the art to substitute
formalin treatment for the colicin E2 taught by Evans et al because a
formalin-killed vaccine causes complete killing of bacteria without
significant loss of the antigenicity of the different CFAs and O antigens
and would be an alternative vaccine to the colicin E2 treated cells as
taught by Svennerholm et al. In addition the use of formalin to produce
killed E. coli vaccines is a common technique in the art as exemplified by
the preparations taught by Soderlind et al and Gregory et al. It would
have been obvious to use 0.2 M formaldehyde because this concentration
is equivalent to 0.2% formalin which is used to kill E. coli for use as a
vaccine as taught by Myers. ... It would have been obvious to resuspend
the harvested strain in saline instead of water prior to formalin treatment
because saline is a more physiologically compatible solution. It would
have been obvious to optimize the timing of the treatment of the cells with
formalin because such optimization would constitute routine
experimentation and be within the skill of the ordinary artisan. It would
also have been obvious to further incubate the formalin-treated
bacterial strains at 4EC in order to prevent contamination of the
culture or denaturation of the bacterial antigens prior to collecting
them for use in the vaccine. It would have been obvious to grow E. coli
with vigorous shaking because this is a routine condition for growing E.
coli and may be successfully used for preparing a killed vaccine in which
the E. coli contain colonization fimbrial antigens as taught by Myers et al.
Optimization of the density of the E. coli in the culture medium prior to
harvesting would be considered routine in the art and would be withing the
skill of the ordinary artisan. It would have been obvious to orally
administered an appropriate among of the formalin-inactivated vaccine
having CFA=s with antigenic and hemagglutinating properties and CTB to
prevent an enteric infection caused by enterotoxigenic E. coli bacteria in
humans because an orally administered inactivated vaccine expressing
CFA/I provided protection in humans as taught by Evans et al, and
Svennerholm et al specifically teach the advantages of adding CTB to an
orally administered ETEC vaccine. Therefore, one of skill in the art would
expect that a formalin-inactivated E. coli strain expressing CFA=s
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