Ex Parte Umek et al

Board of Patent Appeals and Interferences

Aug 23, 2010

09626096 (B.P.A.I. Aug. 23, 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.
09/626,096 07/26/2000 Robert M Umek 067456-5030-US 8157
67374 7590 08/23/2010
MORGAN, LEWIS & BOCKIUS, LLP (SF)
ONE MARKET SPEAR STREET TOWER
SAN FRANCISCO, CA 94105
EXAMINER
CALAMITA, HEATHER
ART UNIT PAPER NUMBER
1637
MAIL DATE DELIVERY MODE
08/23/2010 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 ROBERT M. UMEK, GARY BLACKBURN,
BRUCE D. IRVINE, ROBERT H. TERBRUEGGEN,
CHANGJUN YU, and JOST G. VIELMETTER
__________

Appeal 2010-002918
Application 09/626,096
Technology Center 1600
__________

Before ERIC GRIMES, LORA M. GREEN, and JEFFREY N. FREDMAN,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of identifying nucleotides in a target sequence. The Examiner has rejected

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.
Appeal 2010-002918
Application 09/626,096

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the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We
reverse.
STATEMENT OF THE CASE
The Specification discloses methods “to electronically detect nucleic
acids, particularly alterations such as nucleotide substitutions (mismatches)
and single nucleotide polymorphisms (SNPs)” (Spec. 1: 8-10).
Claims 60-69 are on appeal. Claim 60 is the only independent claim
and reads as follows:
60. A method of determining the identification of
nucleotide(s) at a first detection position in a first domain of a
target sequence, said target sequence comprising said first
domain and a second domain, said method comprising:
a. providing an electrode with a covalently attached
capture probe, wherein said capture probe has a sequence
substantially complementary to said second domain of said
target sequence;
b. contacting said electrode with:
(i) said target sequence;
(ii) a first label probe substantially complementary to
said first domain, comprising a first nucleotide at an
interrogation position and a first electron transfer moiety
(ETM) with a first redox potential;
(iii) a second label probe substantially complementary to
said first domain, comprising a second nucleotide at said
interrogation position and a second ETM with a second redox
potential;
under conditions wherein if said nucleotide at said
interrogation position is perfectly complementary to said
detection position, hybridization of said probe(s) occurs; and
c. detecting the presence of said first and/or second ETM
to determine the nucleotide(s) at said detection position.

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Issue
The Examiner has rejected claims 60-69 under 35 U.S.C. § 103(a) as
being obvious in view of Kayyem2 and Shuber.3
The Examiner finds that Kayyem discloses the invention of claim 60
except for “using multiple ETM labeled probes for detecting the same
domain” (Ans. 3-4). The Examiner finds that Shuber discloses “multiple
oligonucleotide probes with labels for determining nucleotides at the
detection position” (id. at 4) and concludes that it would have been obvious
“to use the ETM labeled oligonucleotides, as taught by Kayyem et al. with
the multiple oligonucleotide probes for mutation detection, as taught by
Shuber” (id. at 5). The Examiner reasons that an “ordinary practitioner
would have been motivated to use ETM labeled oligonucleotides … with the
multiple oligonucleotide probes for mutation detection because Kayyem
states that no electron transfer occurs unless nucleotide base pairing exists in
the double stranded sequence between the electron donor and acceptor” (id.).
Appellants contend that the references do not suggest “contacting an
electrode with … a second label probe comprising a second ETM with a
second redox potential,” as required by the claims (Appeal Br. 14).
The issue presented is: Does the evidence of record support the
Examiner’s conclusion that Kayyem and Shuber would have suggested
contacting an electrode with two probes comprising different ETMs?

2 Kayyem et al., WO 98/20162, May 14, 1998
3 Shuber, U.S. Patent 5,633,134, May 27, 1997
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Findings of Fact
1. Kayyem discloses “nucleic acids covalently coupled to electrodes
via conductive oligomers.… [T]he invention is directed to the site-selective
modification of nucleic acids with electron transfer moieties and electrodes
to produce a new class of biomaterials.” (Kayyem, abstract.)
2. Kayyem discloses
compositions comprising electrodes with conductive oligomers
attached to probe nucleic acids, without second electron transfer
moieties, and soluble second probe sequences with second
electron transfer moieties. Upon binding of the target sequence,
which contains a first target domain for the first probe sequence
and a second target domain for the second probe sequence,
which preferably are adjacent, electron transfer may occur.
(Id. at 36: 10-14.)
3. Shuber discloses “a process for analyzing a DNA sample for the
presence of multiple mutations simultaneously using allele specific
oligonucleotide probes (ASOs)” (Shuber, col. 1, ll. 54-57).
4. Shuber discloses that “[t]raditionally, ASOs have been
radioactively end-labelled (e.g using 32P or 35S). However, ASOs can also
be labelled by non-isotopic methods (e.g. via direct or indirect attachment of
fluorochromes or enzymes, or by various chemical modifications of the
nucleic acid fragments that render them detectable …).” (Id. at col. 3, ll.
6-12.)
5. Shuber discloses that “hybridization can be detected using a means
which is appropriate for the particular label used. For example, if ASOs are
labelled radioactively, hybridization can be detected using autoradiography.”
(Id. at col. 4, ll. 8-11.)
Appeal 2010-002918
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Analysis
Claim 60 is directed to a method of determining the identification of a
nucleotide at a detection position in a target sequence, and requires using
two probes that each comprise a nucleotide at the position of interest and an
electron transfer moiety (ETM). The claim does not expressly state that the
probes differ in the nucleotide at the interrogation position and the attached
ETM, but those limitations are implicit in the claim language: if the two
probes were identical in sequence, they would not be “first” and “second”
probes, and if each of the probes was attached to the same ETM, binding of
the two probes could not be distinguished and therefore the method would
not allow “identification of nucleotide(s) at a first detection position,” as
stated in the preamble.
Appellants argue that the cited references do not disclose “contacting
an electrode with at least a second label probe comprising a second ETM
with a second redox potential, and thus do not teach each and every
limitation of the claims” (Appeal Br. 14). Appellants further argue that
although Shuber discloses a method that uses multiple probes, “the multiple
ASO probes in Shuber all have the same label” (id. at 13).
The Examiner responded to Appellant’s argument by stating that
“Shuber is not relied on to teach a second label probe comprising a second
ETM” (Ans. 6) and that a “skilled artisan having read the disclosure of
Kayeem [sic] et al. would recognize that ETMs as labels are distinguishable
one from another and having read Shuber would also recognize the
advantage of using such labels on probes when probing a single domain”
(id.).
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We agree with Appellants that the Examiner has not adequately
explained how the references would have suggested modifying Kayyem’s
method to include multiple probes comprising different ETMs. The
Examiner has not pointed to any disclosure in Kayyem or Shuber that shows
the use of two differently labeled probes, for separate detection, in the same
hybridization assay. Although the Examiner concludes that this limitation
would have been obvious based on Kayyem, she has not pointed out any part
of Kayyem that would have suggested to one of skill in the art using
different ETMs having detectably different redox potentials in Kayyem’s
method.
It is the Examiner’s burden to provide evidence that the claimed
invention would have been obvious. In this situation, without any evidence
on record that teaches or suggests differently labeled probes in a single
assay, much less differentially detectable ETMs, we are constrained to
reverse the obviousness rejection.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that Kayyem and Shuber would have suggested contacting an electrode with
a two probes comprising different ETMs.
SUMMARY
We reverse the rejection of claims 60-69 under 35 U.S.C. § 103(a).

REVERSED

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Application 09/626,096

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MORGAN, LEWIS & BOCKIUS, LLP (SF)
ONE MARKET SPEAR STREET TOWER
SAN FRANCISCO CA 94105