Appeal No. 1999-1215
Application No. 08/401,192
Modifications made to the structure of the ends of antisense
oligonucleotides can protect them, block the activities of the
exonucleases, and increase the stabilization of the
oligonucleotides.
The invention described here is based on the novel idea that
closed oligonucleotides, without free ends, would thus be … by
definition, resistant to this type of degradation. Closed
oligonucleotides, for example, circular oligonucleotides, do not
present a substrate which is accessible to 3’ or 5’ exonucleases,
and they are thus stabilized.
Thus, as suggested by appellants (Brief, page 5) “[t]he Blumenfeld
authors … were not motivated to linearize their oligonucleotides notwithstanding
that they clearly possessed knowledge of the facts alleged to motivate such a
modification. As argued by appellants (Brief, page 6) “[t]hroughout the
Blumenfeld reference, its authors describe the advantages of using closed
oligonucleotides.”
Therefore, we cannot agree with the examiner’s contention (Answer, page
6) “that the skilled artisan, being thoroughly familiar with the synthesis and use of
linear oligos, would read Blumenfeld et al. and recognize a good idea – using
two mechanisms of inhibition at once – which would be equally applicable to
standard linear oligos as to closed oligos.” Just as one of ordinary skill in this art
would recognize in Blumenfeld the advantage of using two mechanisms of
inhibition at once, this artisan would also recognize the advantage of using
closed oligos instead of linear oligos. We remind the examiner that as stated in
Panduit Corporation v. Dennison Manufacturing Co., 774 F.2d 1082, 1093, 227
USPQ 337, 344 (Fed. Cir. 1985) “[t]he well established rule of law is that each
prior art reference must be evaluated as an entirety, and that all of the prior art
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