Ex Parte Ach et al

Patent Trial and Appeal Board

Jan 7, 2014

12325562 (P.T.A.B. Jan. 7, 2014)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE PATENT TRIAL AND APPEAL BOARD
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Ex parte ROBERT A. ACH and BRIAN J. PETER
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Appeal 2013-005568
Application 12/325,562
Technology Center 1600
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Before DONALD E. ADAMS, DEMETRA J. MILLS, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL1,2
This appeal under 35 U.S.C. § 134 involves claims 1-10, 12, 13, and
16-18 (June 18, 2012 Office Action, Summary).3 Examiner entered a
rejection under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C.
§ 6(b).
We affirm.

1 The Real Party in Interest is Agilent Technologies, Inc. (App. Br. 3.)
2 This Appeal is related to Appeal 2011-009447, decision reversing the
obviousness rejection entered October 31, 2011.
3 Pending claims 11, 14, and 15 stand withdrawn from consideration (June
18, 2012 Office Action, Summary).
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Application 12/325,562

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STATEMENT OF THE CASE
The claims are directed to a method of analyzing a test mammalian
genome. Claim 1 is representative and is reproduced in the Claims
Appendix of Appellants’ Brief.
Claims 1-10, 12, 13, and 16-18 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Berlin,4 Pljevaljčić,5 and
Chan.6
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Berlin suggests
A method . . . for distinguishing 5-position methylation changes
of cytosine bases and cytosine-to-thymine mutations and for the
detection of single nucleotide polymorphisms (SNPs) or point
mutations in genomic DNA, in which[, inter alia,] . . . a
genomic DNA sample is treated with sulfite or disultife in such
a way that all of the cytosine bases that are not methylated in
the 5-position of the base are changed in such a way that a base
is formed that is different in its base-pairing behavior, whereas
the cytosines methylated at the 5-position remain unchanged.
(Berlin, Abstract; see also id. at col. 3, ll. 53-63; see also App. Br. 5.)
FF 2. Examiner relies on Pljevaljčić to suggest “a method using
methyltransferase and a[n] AdoMet cofactor analog for quantitative labeling

4 Berlin, US 7,179,594 B2, issued February 20, 2007.
5 Goran Pljevaljčić, et al., Quantitative Labeling of Long Plasmid DNA with
Nanometer Precision, 8 ChemBioChem 1516-1519 (2007).
6 Eugene Y. Chan, DNA Mapping Using Microfluidic Stretching and Single-
Molecule Detection of Fluorescent Site-Specific Tags, 14 Genome Research
1137-1146 (2008).
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Application 12/325,562

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of DNA with nanometer precision,” wherein the AdoMet cofactor analog is
an aziridine cofactor with a Cy5 flourophor (June 18, 2012 Final Rej. 11-12;
see also Pljevaljčić 1519: col. 1, ll. 24-26; App. Br. 5 (Pljevaljčić “provides
a method by which DNA can be fluorescently labeled using a
methyltransferase”)).
FF 3. Examiner relies on Chan to suggest “a method of DNA mapping
using microfluidic stretching and single-molecule detection of fluorescent
site-specific tags” (June 18, 2012 Final Rej. 14).
ANALYSIS
Based on the combination of Berlin, Pljevaljčić, and Chan, Examiner
concludes that, at the time Appellants’ invention was made, “[o]ne of
ordinary skill in the art . . . would have had a reasonable expectation of
success in arriving at the Applicant’s invention as claimed” (June 18, 2012
Final Rej. 13). We find no error in Examiner’s conclusion.
Appellants content that while Pljevaljčić suggests “a method by which
DNA can be fluorescently labeled using a methyltransferase” the “use of
Pljevalj[č]i[ć]’s labeling method in Berlin’s [SNP detection] method would
require either performing a bisulf[i]te treatment on a fluorescently-labeled
nucleic acid, or removing the bisulfite treatment step form Berlin’s method.
Either way, it is not clear how Berlin’s method would work” and “the
proposed modification would result in a change in the principle of operation
of Berlin’s method, or . . . render it inoperable” (id. at 5-6). We are not
persuaded.
The combination of Berlin and Pljevaljčić does not require (1) the
removal of the bisulfite treatment step from Berlin’s method or (2) the
bisulfite to act upon Pljevaljčić’s labeled methyl group. To the contrary,
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Application 12/325,562

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consistent with the steps outlined by Appellants, the combination suggests
the use of Pljevaljčić’s labeled cofactor to methylate and label cytosine in a
nucleic acid sample using a methyltransferase (App. Br. 5; FF 1-2). The
nucleic acid sample is then treated with bisulfite, which acts not on the
methylated and labeled cytosine, but instead on non-methylated cytosines
(id. (“As is well known, bisulfite changes C’s to U’s . . ., but leaves methyl-
C alone”)). Accordingly, notwithstanding Appellants’ contention to the
contrary, the combination of Berlin and Pljevaljčić does not require a change
in the operation of, or “complete reconstruction of,” Berlin’s method (App.
Br. 7). Further, Appellants’ failed to provide persuasive argument or
evidence that supports a conclusion that a methylated and labeled cytosine
would somehow interfere with or inhibit the action of bisulfite, which does
not act on the methylated and labeled cytosine, or that bisulfite would
somehow negatively interact with the fluorescent label (see App. Br. 6 (“the
effect of the bisulfite treatment on the fluorescent group would be
unknown”)).
CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claim 1 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Berlin, Pljevaljčić, and
Chan is affirmed. Claims 2-10, 12, 13, and 16-18 fall with claim 1.

AFFIRMED
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