Interference No. 105,188
Short v. Punnonnen
well-known in the pertinent art for creating polynucleotide
variants encoding polypeptides eliciting an optimized immune
response in an expression host as compared to the immune
response elicited by the polypeptides encoded by the library of
5 polynucleotides from which the novel polynucleotide variants were
recombined. This finding is consistent with the prior art
teaching of the publication of Punnonen’s co-inventor Stemmer of
record. Willem P. C. Stemmer (Stemmer), “Searching Sequence
Space,” Biotechnology, Vol. 13, pp. 549-553 (June 1995)
10 (Exh. 2052), teaches that recursive sequence recombination is a
procedure well-known for rapidly creating the best polynucleotide
sequences for a specific task (Paper No. 60, p. 6, para. 12).
The 1995 Stemmer publication teaches:
Experiments conducted to date suggest that benchtop
15 in vitro evolution techniques are capable of creating
libraries as large as molecules. Researchers can mimic
natural evolution by searching these libraries for the best
candidates for a specific task: Repeated round[s] . . . of
selection and amplification of candidates has already been
20 shown to produce novel molecules capable of binding with
equal or higher affinity than their natural counterpart.
(Exh. 2052, p. 549, col. 1, third para.);
25 The problem with point mutagenesis strategies can be traced
to the fact that they introduce random “noise” into a
message at every cycle. If the noise level is too high
–relative to the library size and the selection stringency-
the message will gradually become nonsensical. This problem
30 has generated a great deal of speculation about how to
create “biased” libraries that attempt to use similar,
rather than random, amino acid substitutions. The optimum
-19-
Page: Previous 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 Next
Last modified: November 3, 2007