Interference 102,728
the Brake 1 application does not disclose or suggest any screening conditions for
detecting an “n=0” construct. We point out, however, that screening for the appropriate
clones using a synthetic oligonucleotide is simply one of the steps in the well-known
oligonucleotide mutagenesis procedure. Dr. Tekamp-Olson’s Declaration 1, pp. 2-4,
paras. 4-5; Singh Declaration, SR 568, para. 58; Hitzeman Declaration, SR 168-169,
para. 9. Therefore, it reasonably follows that the screening aspect of the procedure
would have been well-known by one skilled in the art at the time the Brake 1 application
was filed. Accordingly, we again find Dr. Falkinham’s testimony to be inconsistent with
the testimony of three declarants of record, including Singh’s declarants, Drs. Singh and
Hitzeman.
Moreover, Dr. Falkinham has not explained how an oligonucleotide primer which
lacks the nucleotide sequence encoding the “glu-ala” portion of the " factor spacer
sequence can bind to a construct which has that sequence. An oligonucleotide probe
can only bind when the nucleotide sequence to which it is complementary is present.
An oligonucleotide probe without the sequence encoding the “glu-ala” residues can only
form a completely-matched duplex with an “n=0” construct. See, the Johnson
Declaration, p. 10, para. 10; Tekamp-Olson’s Declaration 2, pp. 6-7, para. 8. Since
only a portion of the probe (either the 5' end which is complementary to the sequence
encoding the “lys-arg” residues remaining in the spacer sequence or the 3' end which is
complementary to the nucleotide sequence encoding the initial amino acids of EGF
sequence) will bind to an “n$1” construct, only a partial duplex will be formed. Id.
Thus, we agree with Brake that those skilled in the art would have recognized that
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