Appeal No. 2002-0091 Page 3
Application No. 08/479,884
exemplified variants have multiple substitutions. See, e.g., pages 46-47. For
some of the mutated positions, the specification provides a list of the amino acid
substitutions that are preferred. See, e.g., pages 52 and 56.
Some of the exemplified variants have substitutions in amino acids that are
not listed in claim 88. Among the exemplified embodiments that are within the
scope of the present claims, however, nearly all have a binding affinity that differs
from that of wild-type hGH. The relative binding affinity of the variants is shown in
the specification by the ratio Kd(variant)/Kd(wt). A higher Kd value corresponds to
lower binding affinity, so a variant that binds worse than wild-type hGH will have a
Kd(variant)/Kd(wt) value greater than 1, while a variant that binds better than wild-
type hGH will have a Kd(variant)/Kd(wt) of less than 1.
The specification discloses at least 41 single-substitution variants and at
least 13 multiple-substitution variants that fall within the scope of claim 88. Of the
single-position variants, 31 (about 75%) had a Kd(variant)/Kd(wt) value greater than
1; i.e., they bound the relevant target with less affinity than wild-type hGH. The
worst of the lot was variant I58A, which had a Kd(variant)/Kd(wt) value of 17. See
page 78. Of the multiple-position variants, 12 (about 92%) had a Kd(variant)/Kd(wt)
value greater than 1; the worst of them was a variant having 13 substitutions
including Q181K, which had a Kd(variant)/Kd(wt) value of greater than 100. See
page 47.
On the other hand, some of the exemplified variants encompassed by claim
88 had a Kd(variant)/Kd(wt) value of less than 1, meaning that they bound the
relevant target better than wild-type hGH. Eight of the single-position variants and
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