Ex Parte Sims

Board of Patent Appeals and Interferences

Dec 6, 2007

10403340 (B.P.A.I. Dec. 6, 2007)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte PETER J. SIMS
____________

Appeal 2007-0547
Application 10/403,340
Technology Center 1600
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Decided: December 6, 2007
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Before DONALD E. ADAMS, ERIC GRIMES, and LORA M. GREEN,
Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL

This appeal under 35 U.S.C. § 134 involves claims 20-22 and 26; the
only other pending claims (23-25) were withdrawn from consideration (Br.
2). We have jurisdiction under 35 U.S.C. § 6(b).

INTRODUCTION
The claims are directed to a compound. Claim 20 is illustrative:
20. A compound that specifically promotes the formation of the
human C5b-9 complex selected from the group consisting of molecules
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Application 10/403,340

structurally mimicking C9 amino acid residues 359 to 384 when they are in
spatial orientation which promotes formation of the C5b-9 complex, wherein
the compound is not human C9.

The Examiner relies on the following prior art references to show
unpatentability:
Michael M. Frank et al., “Complement,” Second Edition Fundamental
Immunology, 679-701 (1989).

Dale L. Bodian et al., “Mutational Analysis of the Active Site and
Antibody Epitopes of the Complement – inhibitory Glycoprotein, CD59,”
185(3) J. Exp. Med., 507-516 (1997).

The rejection as presented by the Examiner is as follows:
Claims 20-22 and 26 stand rejected under 35 U.S.C. § 102(b) as being
anticipated by Bodian.
We affirm.

DISCUSSION
The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). Therefore, we limit our discussion to
representative claim 20. Claim 21, 22 and 26 will stand or fall with claim
20.
Claim 20 is drawn to a compound. On February 10, 2005 the
Examiner introduced a Restriction Requirement into the record. In addition
to requiring an election of a patentably distinct group of invention, the
Examiner required Appellant to elect a species of the claimed compound
(Restriction Requirement 3). On March 7, 2005, Appellant responded by
electing, without traverse, “[a]ntibody as the distinct species of the claimed
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invention” (Election 2). Accordingly, we interpret the term compound to
mean antibody.
According to claim 20, the antibody (1) specifically promotes the
formation of the human C5b-9 complex and (2) is selected from the group
consisting of molecules structurally mimicking C9 amino acid residues 359
to 384 when they are in a spatial orientation that promotes the formation of
the C5b-9 complex.1
Thus, claim 20 reads on an antibody that structurally mimics amino
acid residues 359 to 384 of C9 when these C9 amino acid residues are in a
spatial orientation that promotes the formation of C5b-9. As a result, the
claimed antibody will specifically promote the formation of the human C5b-
9 complex.
We direct attention to Appellant’s claim 21, which requires that the
antibody of claim 20 binds “specifically to amino acids 42 to 58 of human
CD59.” The Examiner reasons that “an antibody that binds specifically to
amino acids 42-58 of human CD59 structurally mimics [amino] acid
residues 359-384 of complement component C9 because they both
specifically bind to the same region of CD59” (Answer 3). Stated
differently, the Examiner construes claim 20 to read on, or encompass, an
antibody that specifically binds to amino acids 42 to 58 of human CD59.
In this regard, the Examiner finds that Bodian teaches three
monoclonal antibodies (HC2, 2/24, and A35) that specifically bind to the
region of amino acids 42-58 of human CD59 (Answer 3-4). The Examiner

1 Claim 20 also requires that the compound is not human C9, which in view
of the species election, is superfluous to our review of the claim as it reads
on an antibody.

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reaches this conclusion by finding that Bodian teaches that single
substitution mutations at amino acid positions within the region defined by
amino acids 42-58 of human CD59, reduced the ability of each antibody to
bind its target (id.). From this, the Examiner concludes that since each of the
three monoclonal antibodies bind to the region of amino acids 42-58 of
human CD59, each antibody structurally mimics amino acid residues 359-
384 of C9 and will promote the formation of the human C5b-9 complex
(Answer 4).2
In response Appellant argues that because Bodian does not state that
the antibodies are structural mimics of C9, the Examiner’s position which is
based on the doctrine of inherent anticipation must fall (Br. 4; Reply Br. 3).
Appellant develops his argument along two lines of reasoning:
1. The allosteric effect, wherein “mutations in a protein at one region
can affect binding of antibodies that recognize complete[ly] different
domains” (Br. 4); and
2. Even if Bodian’s antibodies “did bind to one or more residues with
the CD59 42-58 region, this fact alone does not mean that they must
constitute a structural mimic of C9 sequences” (id. (emphasis removed)).
Accordingly, the issue before us is whether the evidence relied upon
by the Examiner supports a finding that Bodian teaches an antibody that
blocks CD59’s ability to inhibit the formation of the C5b-9 complex; and if
so, would a person of ordinary skill in the art understand Bodain to teach
that such an antibody would mimic C9 amino acid residues 359 to 384 when

2 The Examiner relies on Frank to provide background information (Answer
5). Accordingly, we do not include it in our discussion.
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they are in a spatial orientation which promotes the formation of the C5b-9
complex?
Under the doctrine of inherency, if an element is not expressly
disclosed in a prior art reference, the reference will still be deemed to
anticipate a claim if the missing element “is necessarily present in the thing
described in the reference.” Cont'l Can Co. v. Monsanto Co., 948 F.2d
1264, 1268 (Fed. Cir. 1991). “Inherent anticipation requires that the missing
descriptive material is ‘necessarily present,’ not merely probably or possibly
present, in the prior art.” Trintec Indus., Inc. v. Top-U.S.A. Corp., 295 F.3d
1292, 1295 (Fed. Cir. 2002) (quoting In re Robertson, 169 F.3d 743, 745
(Fed. Cir. 1999)). Stated differently, “a bare suggestion or hope that
requires significant experimentation for implementation or verification is not
an invalidating ‘anticipation’ of that which is ultimately achieved.”
PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1372 (Fed.
Cir. 2007).
One aspect of Bodian’s study was to define the regions of the CD59
protein required for its complement-inhibitory activity (Bodian 508: col. 1,
ll. 44-47). The antibodies used in Bodian’s study were obtained by purchase
or gift (Bodian 508: bridging paragraph, cols. 1-2). The antibodies were
chosen due to their varying capacity to block the protective effects of CD59
(Bodian 511: col. 1, ll. 6-8). Specifically, Bodian teaches that HC2 and 2/24
have strong CD59-blocking activity3, whereas A35 exhibits a weak CD59-
blocking activity (Bodian 511: col. 1, ll. 10-12). Thus, the preponderance of

3 CD59-blocking activity refers to the ability of the antibody to block
CD59’s ability to inhibit complement-mediated lysis of host cells (see e.g.,
Bodian 510: col. 1, ll. 38-50).
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the evidence relied upon by the Examiner supports a finding that Bodian
teaches an antibody that blocks CD59’s ability to inhibit the formation of the
C5b-9 complex.
Therefore, the issue is whether a person of ordinary skill in the art
would understand Bodain to teach an antibody that mimics C9 amino acid
residues 359 to 384 when they are in a spatial orientation which promotes
the formation of the C5b-9 complex? In this regard, we find that Bodian
mapped the antibody epitopes by mutational analysis of CD59 (Bodian 511:
col. 2, ll. 1-6; Table 1; and Fig. 4). Bodian provides NMR based structural
diagrams of CD59 (Bodian 512: Figure 3). These diagrams identify the
amino acid mutations Bodian made to CD59 and illustrate the location of
these amino acids on CD59 (id.). Bodian teaches that a mutation of amino
acid 40 “eliminates the complement-inhibitory function of CD59 and
prevents the binding of all the function blocking anti-CD59 antibodies
tested” (Bodian 513: col. 2, ll. 4-6; cf. 512: Figure 3). In addition, Bodian
teaches that a mutation in amino acid 53, the amino acid adjacent to amino
acid residue 40 in CD59’s three-dimensional structure (Bodian: Figure 3A),
“inhibits the complement-inhibitory activity and reduces the binding of
four[ ]4 of the six CD59-blocking antibodies, implicating this residue as part
of the active site of CD59” (Bodian 514: col. 1, ll. 4-9). As the Examiner
points out, the ability of monoclonal antibodies HC2, 2/24, and A35 to bind
CD59 are all reduced by a mutation in amino acid 53 (Answer 3-4). Bodian
also explains that
[s]ites of protein-protein interaction are often defined by
regions of hydrophobic and irregular protein surface. In the

4 Antibodies A35, HC2, 2/24, and MEM43 (Bodain 511: Table 1).
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NMR structures of human CD59 W40 lies at the base of a
hydrophobic groove, formed by residues F23, C39, W40, and
L54, which is lined on one side by a ridge of hydrophilic
residues (K41, H44, R53 and R55; Fig. 3 D).

(Bodian 514, col. 1, ll. 51-57.) As illustrated by Bodian’s figure 3A and
discussed above, amino acid residues 40, 53 and 54 fall within the active site
of CD59. The mutation of these amino acid residues directly affects the
ability of monoclonal antibodies HC2, 2/24, and A35 to bind CD59; and
block CD59’s activity. According to Bodian, “the present data strongly
suggest that there is a single active site [for C8 and C9] and that this site lies
in the vicinity of W40” (Bodian 513: col. 2, ll. 1-3). In sum, the
preponderance of the evidence on this record demonstrates that monoclonal
antibodies HC2, 2/24, and A35 bind in a region defined by amino acid
residues 42-58 of human CD59 and structurally mimic C9 amino acid
residues 359 to 384 when they are in a spatial orientation which promotes
the formation of the C5b-9 complex.
We recognize Appellant’s arguments concerning the allosteric effect
which “could be responsible for the loss of binding of Bodian’s antibodies
to” Bodian’s CD59 mutants (Br. 4). This argument is not supported by the
evidence of record; therefore we are not persuaded by this argument. If
Appellant’s argument had merit, then Bodian would not be able to map
antibody epitopes by mutational analysis of CD59 (see e.g., Bodian 511: col.
2, ll. 1-6; Table 1; and Fig. 4).
Further, while Bodian does not expressly teach that the HC2, 2/24,
and A35 monoclonal antibodies are structural mimics of the C9 sequence,
there is no evidence on this record that they are not. Instead, Bodian teaches
that the C9 binding site on CD59 is at the same location that the HC2, 2/24,
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and A35 antibodies recognize CD59 and inhibit its activity. Accordingly,
we find that the preponderance of the evidence on this record supports the
Examiner’s finding that monoclonal antibodies HC2, 2/24, and A35 are
structural mimics of C9 amino acid residues 359 to 384 when they are in
spatial orientation which promotes formation of the C5b-9 complex.
Accordingly, we are not persuaded by Appellant’s assertion that
while the Examiner may be correct that the antibodies shown
by Bodian do bind to the same regions of CD59 as C9, and may
even be further correct that, in so doing they act as structural
mimics of particular residues within C9, it is absolutely clear
that the Examiner might also be incorrect.

(Br. 5.) The evidence on this record provides more than a bare suggestion
that requires significant experimentation for implementation or verification.
To the contrary, the evidence on this record supports the Examiner’s
conclusion that the prior art monoclonal antibodies bind the same site as C9,
inhibit CD59 activity, and therefore would be expected to be a structural
mimics of C9 amino acid residues 359 to 384 when they are in spatial
orientation which promotes formation of the C5b-9 complex.
In our opinion the Examiner has provided the evidence necessary to
shift the burden to Appellant. However, for the foregoing reasons,
Appellant has failed to carry his burden. Accordingly, we affirm the
rejection of claim 20 under 35 U.S.C. § 102(b) as being anticipated by
Bodian. Claims 21, 22 and 26 fall together with claim 20.

CONCLUSION
In summary, we affirm the rejection of record.
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED

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