Appeal No. 1995-2723
Application 07/858,747
The examiner acknowledges that Schwartz does not teach (Answer, page 5):
[m]utating said instability/inhibitory sequences within said gene by making
multiple point mutations such that the amino acid sequence encoded by
mRNA is unchanged.
The examiner relies on Wisdom as teaching (Answer, page 6):
[i]nstability/inhibitory sequences coding for 4 amino acids of c-myc mRNA
and disruption of the initiation codon by a single point mutation effects
mRNA stability and rapid turnover of the mRNA . . . .
The examiner relies on Kunkel as teaching (Answer, page 6):
[a] method of producing several single base substitution mutations
introduced within a DNA template region as a way of generating a high
frequency of desired nucleotide changes of a genotype by using a uracil-
containing DNA template, prepared by standard procedures after growth on
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an Escherichia coli dut ung strain (see page 488, column 1). Kunkel also
teaches site specific misincorporation mutagenesis which is used to change
single codons from C to A and C to T (see page 490, column 2).
Finally, Hatfield is said to disclose (Answer, paragraph bridging pages 6-7):
[a]nalyzing the frequency of at least some codon pairs (encoding the same
amino acid) from organism to organism, this information is used to construct
and express altered or synthetic genes having greater translational efficiency
for highly expressed genes (see abstract). Hatfield et al. also discloses that
by replacing from 10% to 20% or more of the codons may be designed to
either increase or decrease the translational efficiency of the codon pairs
(see column 5, lines 34-40).
The examiner concludes (Answer page 7):
[I]t would have been prima facie obvious to one of ordinary skill in the art at
the time the invention was made to identify RNA sequences in the gag
region of HIV-1 which decrease RNA stability or inhibit expression as taught
by Schwartz et al, in view of other known instability/inhibitory sequences and
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