Interference 103,781
involved U.S. Patent 5,380,831 requires modification of Bt DNA
sequences encoding insecticidal protein to “more closely resemble
the frequency of codon usage of the plant in which it is to be
expressed.” Even though Drs. Adang and Murray appeared to have
“agreed that the way to modify . . . [the Bt gene] was to change
the codon usage and balance the ratio of AT to GC, to being more
like that of a plant, and to retain the amino acid sequence of
the Bt gene and change it to the codons preferred by the plant”
(AR 4155), they spent a considerable amount of time doing things
“somewhat distinct” from that concept (AR 4156-4157; AR 6885).
Additionally, even though Drs. Adang and Murray suspected
that premature termination of transcription and inefficient
production of toxin in plants which had been transformed by
native Bt genes encoding insecticidal protein were related to
differences in codon usage and codons preferred by Bt and plant
genes, their suspicions were based on incomplete codon usage,
preference, and frequency data. They considered any conclusions
drawn therefrom, or inventive concepts based thereon, to be risky
(AR 0096, l. 21, to AR 0097, l. 2). Therefore, Dr. Murray, with
Dr. Adang acceding (AR 0116), expended a considerable amount of
time between December 12, 1986, and September 9, 1988, not only
looking for regions of the Bt gene which caused RNA instability
(AR 0107-0108; AR 4156-4156; AR 0111-0112; AR 0114-0115;
-133-
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