Interference No. 105,188
Short v. Punnonnen
chimeric molecule. This is a very efficient method of
combining useful mutations from many different parental
sequences through multiple crossovers. Sexual PCR’s high
recombination rate takes advantage of this by recombining a
5 large number of mutations in a minimum number of selection
cycles.
(Exh. 2052, p. 551, col. 2, first full para.); and
10 The advantage of sexual PCR is that it uses a very low
rate of random mutation . . . . The longer the sequence,
the lower the rate needs to be. Recombination and selection
quickly yield functional blocks containing combinations of
compatible point mutations. At a larger scale, these
15 functional building blocks are permutated and the best
combinations are selected. The low point mutation rate and
the homology requirement for recombination make it a process
that is mostly gentle and conservative, but also capable of
big sequence jumps.
20
(Exh. 2052, p. 551, col. 2, second to last full para.).
Regarding a promising alternative technique called exon
shuffling, Stemmer states (Exh. 2052, p. 552, cols. 1-2, bridging
25 para.):
Exon shuffling may also be used to obtain random
peptide libraries of very large effective sizes. Without
homologous introns, the degree of homology between peptides
selected from a random library would be insufficient for
30 recombination. . . . . Recombination inside the exon is
unlikely because of their random sequence origin and much
shorter length. The recombined exons are cloned back into
the phage, and a new library of 10 is obtained and8
screened. This process is repeated until no further
35 improvement occurs.
5. Prima facie obviousness
We have considered the combined teachings of the Freeman and
Short PCTs in light of Stemmer’s description of the knowledge and
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