Appeal 2007-2400
Application 10/418,182
the unique aspects of the antigen binding site (Fv region), can be
mutagenized simultaneously, or separately within the VH or VL chains, to
study the three dimensional interrelationship of selected amino acids in this
site” (id. at col. 11, ll. 10-15.)
Crea provides an “Illustration[ ] of Walk-through Mutagenesis” (col.
12, l. 55) in which “five out of six CDRs of the MCPC 603 Fv molecule is
performed . . . . VL CDR2 was not targeted for mutagenesis because
structural studies indicated that this region contributes little to the binding
site in MCPC 603” (id. at col. 19, ll. 29-40).
We agree with the Examiner that Crea’s teachings would have
suggested the claimed library to those of ordinary skill in the art. Crea
teaches walk-through mutagenesis of immunoglobulin CDRs. Crea also
teaches that “the same or different” amino acid can be walked-through each
region and that the CDRs “can be mutagenized simultaneously, or separately
within the VH or VL chains.” Thus, Crea would have suggested, to the
skilled artisan, making a library containing the starting immunoglobulin and
all of the possible CDR walk-through mutants of that immunoglobulin; i.e.,
mutants created by carrying out walk-through mutagenesis of (a) each CDR
individually, (b) each of the possible pairs, trios, quartets, and quintets of
CDRs mutagenized simultaneously, and (c) all six CDRs mutagenized
simultaneously – in other words, the library defined by instant claim 1.
Crea teaches that walk-through mutagenesis
can be used to generate libraries of mutant proteins which are of
a practical size for screening. The method can be used to study
the role of specific amino acids in protein structure and function
and to develop new or improved proteins and polypeptides such
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