Ex Parte Schenk

Board of Patent Appeals and Interferences

Aug 30, 2010

10777792 (B.P.A.I. Aug. 30, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/777,792 02/11/2004 Dale B. Schenk 057437-391790 3041
826 7590 08/30/2010
ALSTON & BIRD LLP
BANK OF AMERICA PLAZA
101 SOUTH TRYON STREET, SUITE 4000
CHARLOTTE, NC 28280-4000
EXAMINER
KOLKER, DANIEL E
ART UNIT PAPER NUMBER
1649
MAIL DATE DELIVERY MODE
08/30/2010 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte DALE B. SCHENK
__________

Appeal 2010-004495
Application 10/777,792
Technology Center 1600
__________

Before ERIC GRIMES, JEFFREY N. FREDMAN, and
STEPHEN WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
composition comprising a beta-amyloid peptide, Aβ1-7, linked to a toxoid
from a pathogenic bacterium to form a conjugate. The Patent Examiner

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.

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rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.

STATEMENT OF THE CASE
The invention concerns a composition comprising an Aβ1-7 peptide
linked to a toxoid from a pathogenic bacterium to form a conjugate. The
Specification states that “Aβ, also known as β-amyloid peptide … is a
peptide of 39-43 amino acids, which is the principal component of
characteristic plaques of Alzheimer’s disease.” (Spec. 15, [0071]). The
Specification also explains that Aβ generates “an immune response in excess
of that of other antigens.” (Id., [0072]). According to the Specification,
preferred immunogenic fragments for linking to a toxoid “include Aβ1-5, 1-
6, 1-7, 1-10, 3-7, 1-3, and 1-4.” (Id. at 16, [0077]). Some compositions of
the invention also comprise an adjuvant that “augment[s] the intrinsic
response to an immunogen without causing conformational changes in the
immunogen that affect the qualitative form of the response.” (Id. at 40,
[0156]). QS-21 is said to be a preferred adjuvant. (Id. at 41, [0157]).
Claims 119-143 are on appeal. Claims 119, 131 and 133 are
representative and read as follows:
119. A composition comprising an Aβ peptide linked to a carrier
which is a toxoid from a pathogenic bacterium to form a conjugate, wherein
the Aβ peptide is Aβ1-7.

131. A composition comprising (a) an Aβ peptide linked to a carrier
which is a toxoid from a pathogenic bacterium to form a conjugate, wherein
the Aβ peptide is Aβ1-7 and (b) an adjuvant.

133. The composition of claim 131, wherein the adjuvant comprises
QS-21.
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The Examiner rejected the claims as follows:
• claims 119, 121-125, and 131 under 35 U.S.C. § 103(a) as
unpatentable over Selkoe,2 Wong,3 and Penney;4
• claims 119-125 and 131-132 under 35 U.S.C. § 103(a) as
unpatentable over Selkoe, Wong, Penney, and Restifo;5
• claims 119, 121-125, 131 and 133-138 under 35 U.S.C. § 103(a) as
unpatentable over Selkoe, Wong, Penney, and Hancock;6 and
• claims 119, 121-131 and 133-143 under 35 U.S.C. § 103(a) as
unpatentable over Selkoe, Wong, Penney, Hancock, and Collier.7
Claims 120-132 and 139-143 have not been argued separately and
therefore stand or fall with claim 119; claims 134-138 stand or fall with
claim 133. 37 C.F.R. § 41.37(c)(1)(vii).

OBVIOUSNESS
The Issue
The Examiner’s position is that Wong disclosed a conjugate for
producing antibodies against Aβ, comprising Aβ1-10 linked to KLH, a
carrier protein and antigen that increases the immune system reaction to the

2 US Patent No. 5,262,332 issued to Dennis J. Selkoe, Nov. 16, 1993.
3 Caine W. Wong et al., Neuritic plaques and cerebrovascular amyloid in
Alzheimer disese are antigenically related, 40 PROC. NATL. ACAD. SCI.
8729-8732 (1985).
4 US Patent No. 5,773,007 issued to Christopher L. Penney et al., Jun. 30,
1998.
5 US Patent No. 5,733,548 issued to Nicholas P. Restifo et al., Mar. 31,
1998.
6 US Patent No. 5,723,130 issued to Gerald E. Hancock et al., Mar. 3, 1998.
7 US Patent No. 5,601,827 issued to R. John Collier et al., Feb. 11, 1997.
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molecule with which it is conjugated. (Ans. 3-4). The Examiner found that
Wong taught that antibodies raised against the conjugate are useful for
detecting Aβ and diagnosing Alzheimer’s disease. (Id. at 4).
The Examiner found that Selkoe also disclosed a method of detecting
and diagnosing Alzheimer’s disease using antibodies to Aβ. (Id. at 3). The
Examiner found that Selkoe taught a method of making the antibodies by
using fragments of about 8 or more amino acid residues of β-AP. (Id.).
According to the Examiner, Selkoe’s “about 8” includes 7 amino acids, as
recited in instant claim 119. (Id.). Turning to Penney, the Examiner found
that this reference taught that purified antigens (protein-conjugates) are not
optimally effective in eliciting an antibody response. (Id. at 4). However,
the Examiner found that Penney disclosed that if an immunostimulant such
as the diphtheria toxoid CRM 197 or KLH carrier molecule is included in
the composition, the antibody response will be boosted. (Id.).
According to the Examiner, it would have been obvious to a person of
ordinary skill in the art at the time the invention was made to make a
composition comprising Aβ1-7 covalently linked to CRM 197. The
Examiner reasoned that because Wong disclosed coupling residues 1-10 of
Aβ, i.e., Aβ1-10, to a heterologous protein to increase antigenicity, it would
have been obvious to select a shorter peptide for this purpose. In particular,
the Examiner reasoned that Selkoe suggested using 7 amino acids of Aβ by
disclosing the use “of about 8” amino acids of Aβ. (Id. at 3, 4). The
Examiner also reasoned that because Penney taught that CRM 197 and KLH
are both effective carriers that increase antigenicity, it would have been
obvious to simply substitute the toxoid CRM 197 for Wong’s KLH. (Id. at
4).
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Regarding claim 133, the Examiner found that Penney taught that
adjuvants can optionally be added to antibody-inducing compositions to
mitigate local hypersensitivity to the carrier or to increase immunogenicity.
(Id. at 4, 5). Additionally, the Examiner found that Hancock taught that
“QS-21 … is particularly suitable as an adjuvant as it increases the immune
response, resulting in more antibodies that tightly bind to the antigen
administered.” (Id. at 5-6). According to the Examiner, it would have been
obvious to a person of ordinary skill in the art at the time the invention was
made to select QS-21 as an adjuvant to be included with the conjugate
suggested by Selkoe, Wong and Penney because Hancock taught that QS-21
was known to be particularly effective in eliciting antibodies. (Id. at 6).
Appellant contends that the Examiner has not established a prima
facie case of obviousness, alleging that the prior art “provided no or
insufficient reason for the artisan to have used a fragment of Aβ of only
seven amino acids [nor] any reason that these seven amino acids should
correspond to Aβ1-7….” (Reply Br. 4). Appellant also asserts that the
“purported switch from a preferred carrier for use in animals to a carrier
suitable for use in humans without any proposal of human use represents
hindsight …..” (Id.). Additionally, Appellant asserts that it would not have
been obvious to include Hancock’s QS-21 adjuvant in the combination.
Further, Appellant contends that “the claimed conjugate is an unexpectedly
superior agent for human therapeutic administration” and “unexpectedly
advantageous for therapeutic use” relative to Wong’s conjugate. (Id.).
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The issues with respect to this rejection are:
whether it would have been obvious to a person of ordinary skill in
the art at the time the invention was made to combine the teachings of Wong
and Selkoe to make a conjugate comprising an Aβ1-7 fragment;
whether modifying the conjugate of Wong and Selkoe by exchanging
Wong’s KLH carrier protein for Penney’s CRM 197 carrier protein
amounted to a simple, predictable substitution of one known element for
another;
whether it would have been obvious to a person of ordinary skill in
the art at the time the invention was made to select QS-21 as the adjuvant for
the modified conjugate composition of Wong, Selkoe and Penney; and
whether Appellant has established that the claimed invention provided
unexpected results sufficient to rebut a prima facie case of obviousness.

Findings of Fact
1. We adopt the Examiner’s findings of facts. (See Ans. 3-7).
2. Selkoe stated that “smaller β-AP fragments of 8 or more amino acids[]
can be used as an immunogen to produce peptide antibodies that can be used
to detect β-AP deposits in [Alzheimer’s Disease] patients.” (Selkoe col. 21,
ll. 18-23).

Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
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ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
A showing of unexpected results must be commensurate in scope with
the breadth of the claims. In re Grasselli, 713 F.2d 731, 743 (Fed. Cir.
1983).

Analysis
A. The Rejection over Selkoe, Wong and Penney
The Examiner correctly found (Ans. 3-4) that Selkoe taught using a
fragment of about 8 amino acid residues of Aβ, which we agree includes a
fragment of 7 amino acid residues, to produce antibodies to Aβ. Similarly,
Wong disclosed using an Aβ fragment to produce antibodies to Aβ. Wong’s
peptide comprised the first 10 residues of Aβ and coupled the fragment to a
carrier protein to form a conjugate.
These combined disclosures would have suggested to a person of
ordinary skill in the art at the time the invention was made that Wong’s
peptide may be effectively synthesized using fewer than the first 10 residues
of Aβ, i.e., the first 7 residues of Aβ. The fact that Wong did not expressly
disclose an advantage “in clearing Aβ deposits” as asserted by Appellant
(App. Br. 11) does not establish that the Examiner’s combination was
impermissibly based upon hindsight. We conclude that the combination of
the known elements of Wong and Selkoe in a known manner amounted to a
predictable variation that could have been implemented by a person of
ordinary skill. KSR, 550 U.S. at 416.
Nor are we persuaded by Appellant’s assertion that an artisan would
not have had a reason to use select an antibody that binds within residues 1-
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10 of Aβ (Wong’s peptide) instead of the “numerous other antibodies to Aβ
[that were] subsequently described in the art for diagnosis,” such as C-
terminal antibodies. (App. Br. 11). This argument only suggests that
compositions comprising additional Aβ fragments may also have been
obvious at the time of the invention, but not that the claimed composition
was nonobvious over the combination of the cited prior art.
Appellant’s assertion that Selkoe “would have discouraged the use of
small synthetic fragments of Aβ for generating antibodies for purposes of
diagnosis” (App. Br. 11) is not supported by the evidence. As the Examiner
explained (Ans. 9), Selkoe specifically taught that synthetic Aβ fragments of
about 8 or more amino acids were immunogens to produce antibodies that
could be used to detect Aβ deposits in Alzheimer’s Disease patients. (See
FF-2). Nor do we find that Selkoe’s teaching to use a fragment of about 8 or
more residues suggested “that a fragment of 8 residues is about the
minimum size and that if a smaller fragment is used there is at least a risk of
failure,” as asserted by Appellant (App. Br. 12). We agreed above with the
Examiner that Selkoe’s teaching “of about 8” residues is correctly
interpreted to include the use of a fragment having 7 residues; to interpret it
otherwise would render “about” superfluous.
We are also unpersuaded by Appellant’s assertion that it would not
have been obvious to substitute Wong’s KLH carrier with CRM 197. (App.
Br. 10). Penney’s disclosure of KLH as a preferred carrier for animal use
was consistent with the broader teaching that both KLH and CRM 197 were
effective carrier molecules. (See Ans. 4). Thus, the Examiner’s proposed
modification merely requires “the simple substitution of one known element
for another” see KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 417 (2007),
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and is not the result of impermissible hindsight reconstruction, as Appellant
contends (see App. Br. 10).
Appellant further asserts that “[p]atentability is further evidenced by
two unexpected results of the claimed conjugate vis-à-vis the cited art.”
(App. Br. 12). Appellant asserts that the claimed conjugates are
unexpectedly superior to Wong’s conjugates for human therapeutic use, as
shown by “Table 16 . . .(p. 99),” said to show that “antibodies binding to an
epitope within residues 1-7 of Aβ are particularly advantageous.” (Id. at
11.) Table 16, entitled “Analysis of Epitope Specificity” appears at page 98.
According to Table 16, N-term mab 3D6 recognized epitope 1-5, mab 10D5
recognized epitope 3-6, and mab 22C8 recognized epitope 3-7. Appellant
has not pointed us to evidence that a conjugate of toxoid and Aβ1-7 was
used as the antigen to generate those antibodies. In our independent review
of the Specification, we have not found evidence that a toxoid conjugate of
Aβ1-7 was used to generate the data in Table 16. It appears, for example
that mab 10D5 was generated by using a conjugate of sheep-anti-mouse IgG
with Aβ1-12, not a claimed conjugate. (See Spec. 65-71, ¶¶ [0267], [0282],
[0285], and Tables 5 and 6.)
As Appellant referred to Table 16 as being on page 99, we have also
reviewed the table appearing on page 99, i.e, Table 17. Table 17 likewise
does not state that a conjugate of Aβ1-7 was used to generate any of the
antibodies whose properties are shown. Because Appellant did not provide
evidence that a claimed toxoid conjugate of Aβ1-7 was used to generate the
data said to show unexpected results, we agree with the Examiner that
“Appellant is arguing about the advantages of different products from those
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claimed.” (Ans. 8.) Such evidence is insufficient to overcome prima facie
obviousness. See Grasselli, 713 F.2d at 743.
B. The Rejection Over Selkoe, Wong, Penney and Restifo
Appellant contends that claims 119-125 and 131-132 would not have
been obvious over the combination of Selkoe, Wong, Penney and Restifo for
the same reasons argued with respect to the combination of Selkoe, Wong,
and Penney. (App. Br. 15). We are unpersuaded of Examiner error for the
reasons discussed in part A.
C. The Rejection Over Selkoe, Wong, Penney and Hancock
To the extent Appellant contends that claims 119, 121-125, 131 and
133-138 would not have been obvious over the combination of Selkoe,
Wong, Penney and Hancock for the same reasons argued with respect to the
combination of Selkoe, Wong, and Penney (App. Br. 15), we remain
unpersuaded for the reasons discussed in part A.
Regarding claims 133-138, Appellant additionally asserts that
“Hancock would not have motivated replacement of Freund’s adjuvant by
Wong in favor of QS-21.” (Id. at 15). According to Appellant, “QS-21 is
not indicated to improve or even be equally effective for stimulation of
antibodies relative to Freund’s adjuvant … [which is] restricted to animal
use.” (Id. at 15-16). We agree with the Examiner’s finding and explanation
that, while differences exist between QS-21 and Freund’s adjuvant, both
were known in the art at the time of the invention to be effective adjuvants
for increasing immune response. (Ans. 11-12.) The Examiner’s
combination involved “the simple substitution of one known element for
another.” See KSR Int’l Co., 550 U.S. at 417.
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Appellant’s assertion that this substitution “confers an unexpected
benefit for use in humans … because Aβ1-7 was not known to have any
therapeutic use in humans, as discussed previously” (App. Br. 16) is
misdirected and insufficient to overcome prima facie obviousness for the
reasons already discussed.
D. The Rejection Over Selkoe, Wong, Penney, Hancock, and Collier
Appellant contends that claims 119, 121-131 and 133-143 are not
obvious over the combination of Selkoe, Wong, Penney, Hancock and
Collier for the same reasons set forth above with respect to the combination
of Selkoe, Wong, Penney and Hancock. (App. Br. 17). Consequently, we
are unpersuaded for the reasons discussed in part C.

CONCLUSIONS OF LAW
The evidence supports the Examiner’s conclusion that it would have
been obvious to a person of ordinary skill in the art at the time the invention
was made to combine the teachings of Wong and Selkoe to make a
conjugate comprising an Aβ1-7 fragment.
Modifying the conjugate of Wong and Selkoe by exchanging Wong’s
KLH carrier protein for Penney’s CRM 197 carrier protein would have been
a simple and predictable substitution of one known element for another.
It would have been obvious to a person of ordinary skill in the art at
the time the invention was made to select QS-21 as the adjuvant for the
modified conjugate composition of Wong, Selkoe and Penney.
Appellant has not established that the claimed invention provided
unexpected results sufficient to rebut the prima facie case of obviousness.

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12
SUMMARY
We affirm the rejection of claims 119, 121-125, and 131 under
35 U.S.C. § 103(a) over Selkoe, Wong, and Penney;
we affirm the rejection claims 119-125 and 131-132 under 35 U.S.C.
§ 103(a) over Selkoe, Wong, Penney, and Restifo;
we affirm the rejection of claims 119, 121-125, 131 and 133-138
under 35 U.S.C. § 103(a) over Selkoe, Wong, Penney, and Hancock; and
we affirm the rejection of claims 119, 121-131 and 133-143 under
35 U.S.C. § 103(a) over Selkoe, Wong, Penney, Hancock, and Collier.

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

lp

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