Ex Parte Liu

Board of Patent Appeals and Interferences

May 24, 2010

10870766 (B.P.A.I. May. 24, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte GEORGE DECAI LIU
__________

Appeal 2009-012189
Application 10/870,766
Technology Center 1600
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Decided: May 24, 2010
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Before DEMETRA J. MILLS, LORA M. GREEN, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s rejection of claims 10 and 21-26.1 We have jurisdiction under
35 U.S.C. § 6(b).

1 Claims 1-9 and 11-20 are also pending, but stand withdrawn from
consideration.
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Application 10/870,766

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STATEMENT OF THE CASE
Claim 10 is the only independent claim on appeal, and reads as
follows:
10. A system for detecting antigens captured on antibody arrays,
comprising:
an antibody array having at least two IgG antibodies, wherein each of
the at least two IgG antibodies on the antibody array can be induced to
present at least one shared conformational epitope when it is bound by its
antigen(s); and
a detecting agent that specifically binds to the at least two IgG
antibodies that have been induced by their antigens with the at least one
shared conformational epitope on the antibody array, thereby the antigens
captured by the antibody array can be detected independent of the structures
of the antigens.

We reverse.

ISSUE
Has the Examiner established that a preponderance of the evidence of
record supports the conclusion that the combination of Cull and
Stavrianopoulos renders the system of claim 10 obvious?

FINDINGS OF FACT
FF1 The Examiner rejects claims 10 and 21-26 under 35 U.S.C. § 103(a)
as being rendered obvious by the combination of Cull2 and Stavrianopoulos.3
(Ans.4 3.)

2 US 2005/0048545 A1, published Mar. 3, 2005.
3 US 4,868,103, issued Sep. 19, 1989.
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FF2 The Examiner finds that Cull teaches all of the limitations of
independent claim 10, except that Cull fails to teach that the antibody array
has at least two IgG antibodies. (Id. at 4.)
FF3 Cull relates to a “universal detection system for ligand binding, and
methods of use thereof.” (Cull, ¶2.)
FF4 Cull teaches:
Much of the literature describing the interaction of IgM
with its specific antigen and the resulting conformational
changes have used multivalent antigens (one molecule or
particle containing multiple antigenic sites that react with the
specific IgM under investigation). There is limited data
available for interaction with monovalent antigen or haptens.
Nevertheless, there are data that support a compelling argument
that 1) interaction of multimeric IgM with hapten or
monovalent antigen (the relevant configuration for most
proteomics applications, for example) is sufficient to induce an
IgM conformational change, as indicated by, e.g., Clq binding
or reaction with anti-J chain specific antibody, 2) “monomeric”
IgM (IgMs constituting a single IgG-like subunit described
above, composed of the two identical Ig mu heavy chains and
two identical Ig light chains, but lacking the J-chain and not
assembled into a multimer) also binds Clq in an antigen-
dependent fashion and so presumably also undergoes a
conformational change analogous to that of the multimer, 3)
little or no Clq binding or reaction with anti-J chain specific
antibody is detected with IgM or IgMs in the absence of antigen
(in contrast to unaggregated IgG).

(Id. at ¶9.)

4 As the pages of the Answer are not numbered, we number the page with
the heading “Examiner’s Answer” as page 1, and number the remaining
pages consecutively from there.
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FF5 Cull also described methods of making IgM binding reagents of IgG
antibody-producing hybridomas. (Id. at ¶38.)
FF6 The Examiner finds that that Stavrianopoulos teaches that “IgG or
IgM may be used as a binding site for C1q when bound to its corresponding
antigen.” (Ans. 4.)
FF7 Stavrianopoulos teaches that C1q is one of the complement proteins,
which consists of five subunits, “each with one binding site for the heavy
chains of those IgG classes (e.g., IgG-1, IgG-2, IgG-3, IgG-3, IgM) that can
trigger the entire C sequence.” (Stavrianopoulos, col. 16, ll. 46-64.)
FF8 Stavrianopoulos teaches further that “C1q does not bind either to
antigens or to antibodies individually,” but it is “following the complexing
of the antigen to the antibody does the C1q bind to the formed complex.”
(Id. at col. 17, ll. 3-7.) Stavrianopoulos describes an assay using C1q carried
out in solution. (Id. at col. 17, ll. 3-16.)
FF9 As to Kaul,5 the Examiner finds that Kaul teaches that the
immobilized antibodies of Kaul “are made to mimic an antigen-complexed
IgG.” (Ans. 9.) Thus, the Examiner finds, “the conformation of the
immobilized IgG of Kaul [ ] is the same as that of an IgG antibody that is
bound with an antigen and Kaul [ ] teach[es] that C1q binds with an IgG
antibody complexed with an antigen.” (Id.)
FF10 Kaul developed an assay in which wells were coated with IgG “to
mimic fixed/antigen-complexed IgG.” (Kaul 33235, first column.) Kaul

5 Kaul, “Dissection of C1q Capability of Interacting with IgG: Time-
Dependent Formation of a Tight and Only Partly Reversible Association,”
272 J. BIOL. CHEM. 33234-244 (1997).
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found that C1q bound specifically to immobilized IgG in the absence of
antigen. (Id. at 33236, second column.)
FF11 The Examiner concludes that it would have obvious to the ordinary
artisan at the time of the invention to use IgG antibodies as taught by
Stavrianopoulos for the IgM in the assay of Cull as the use of the IgG
antibody is “a mere alternative and functionally equivalent labeling
technique and since the same labeling method would have been obtained.”
(Ans. 4.)

PRINCIPLES OF LAW
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
While the analysis under 35 U.S.C. § 103 allows flexibility in
determining whether a claimed invention would have been obvious, KSR
Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007), it still requires showing
that “there was an apparent reason to combine the known elements in the
fashion claimed by the patent at issue.” Id. Moreover, one of the inquiries
in the obvious analysis is “whether the improvement is more than the
predictable use of prior art elements according to their established
functions.” Id. at 417.

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ANALYSIS
Appellant argues that Cull teaches that with IgM there is little or no
C1q binding in the absence of antigen, which Cull contrasts to unaggregated
IgG. (App. Br. 10.) Thus, Appellant asserts, Cull is in fact teaching that
IgG will bind to C1q in the absence of antigen, which is substantiated by the
teaching of Kaul. (Id.) Kaul, Appellants assert, teaches an assay in which
the binding of C1q to immobilized IgG is assayed, in which the C1q can
bind to the immobilized IgG in the absence of bound antigen. (Id. at 13.)
We conclude that the Examiner has not established that there is a
reasonable expectation of success of substituting IgG as taught by
Stavrianopoulos for the IgM in the assay of Cull. Claim 10 is drawn to an
antibody array having at least two IgG antibodies, that is, it is drawn to at
least two IgG antibodies immobilized on a solid support, wherein the
antibodies “can be induced to present at least one shared conformational
epitope when it is bound by its antigen(s).”
We agree with Appellant that Cull at the very least implies that IgG
will bind to C1q in the absence of antigen. While Stavrianopoulos teaches
that IgG or IgM may be used as a binding site for C1q when bound to its
corresponding antigen, Stavrianopoulos discusses a solution phase assay,
and the Examiner does not point out where Stavrianopoulos teaches that
immobilized IgG only binds to C1q when bound to its antigen. We find that
Kaul is more relevant to the issue, as Kaul teaches that IgG may be
immobilized on a solid support to mimic a fixed/antigen-complexed IgG.
Kaul also demonstrates that C1q specifically binds to immobilized IgG in
the absence of antigen. The preponderance of evidence of record therefore
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supports Appellant’s position that the ordinary artisan would have expected
that IgG could bind to C1q in the absence of antigen, and thus using it in the
assay of Cull to assay for binding of antigen to immobilized antibody
through the use of C1q would have been unpredictable. Thus, the Examiner
has not established that substitution of IgG for IgM is a predictable use of
prior art elements according to their established functions, and we are
compelled to reverse the rejection.

CONCLUSION OF LAW
We conclude that the Examiner has not established that a
preponderance of the evidence of record supports the conclusion that the
combination of Cull and Stavrianopoulos renders the system of claim 10
obvious.
We are thus compelled to reverse the rejection of claims 10 and 21-26
under 35 U.S.C. § 103(a) as being rendered obvious by the combination of
Cull and Stavrianopoulos.

REVERSED

clj

DR. GEORGE DACAI LIU
1029 BRASSINGTON DRIVE
COLLEGEVILLE PA 19426