Ex Parte Allawi et al

Board of Patent Appeals and Interferences

May 2, 2011

11266723 (B.P.A.I. May. 2, 2011)

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.
11/266,723 11/03/2005 Hatim T. Allawi FORS-10324 9094
72960 7590 05/02/2011
Casimir Jones, S.C.
2275 DEMING WAY, SUITE 310
MIDDLETON, WI 53562
EXAMINER
WOOLWINE, SAMUEL C
ART UNIT PAPER NUMBER
1637
MAIL DATE DELIVERY MODE
05/02/2011 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 HATIM T. ALLAWI, VICTOR LYAMICHEV,
VECHESLAV A. ELAGIN, SCOTT M. LAW, and JEFF G. HALL
__________

Appeal 2010-009027
Application 11/266,723
Technology Center 1600
__________

Before DEMETRA J. MILLS, MELANIE L. McCOLLUM, and STEPHEN
WALSH, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a nucleic
acid detection or quantification method. The Examiner has rejected the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Claims 1-13, 20-23, and 28-30 are pending and on appeal (App. Br. 3-
5). The claims subject to each rejection have not been argued separately and
Appeal 2010-009027
Application 11/266,723

2
therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii). We will focus
on claims 1 and 20, which read as follows:
1. A method for detecting a target nucleic acid in a sample
comprising: exposing said sample to detection assay reagents under
conditions such that said target nucleic acid is detected, if present, in a single
step reaction, wherein said single step reaction comprises a reverse
transcription reaction, a target amplification reaction comprising a
polymerase chain reaction, and a signal amplification reaction comprising an
invasive cleavage assay reaction.
20. A method for multiplex detection of target nucleic acids,
comprising: a) providing reverse transcription, polymerase chain reaction,
and invasive cleavage assay reagents in a microfluidics card, wherein said
reagents are configured to reverse transcribe said target nucleic acid, amplify
said target nucleic acid, and amplify a signal in a cleavage reaction so as to
detect amplified target nucleic acids; b) exposing a sample suspected of
containing said target nucleic acids to said reagents using centrifugal force;
and c) detecting the presence or absence of said target nucleic acids.
Claims 1, 7, 8, 11, 12, and 28 stand rejected under 35 U.S.C. § 103(a)
as obvious over Sorge
1
in view of Hughes
2
(Ans. 3).
Claims 2 and 10 stand rejected under 35 U.S.C. § 103(a) as obvious
over Sorge in view of Hughes and Burckhardt
3
(Ans. 5).
Claims 3-5 stand rejected under 35 U.S.C. § 103(a) as obvious over
Sorge in view of Hughes, McLaughlin,
4
and Biswas
5
(Ans. 7).

1
Sorge, US 6,528,254 B1, Mar. 4, 2003.
2
Hughes, Jr., US 6,630,333 B1, Oct. 7, 2003.
3
Burckhardt, US 5,501,963, Mar. 26, 1996.
4
McLaughlin et al., US 2003/0104395 A1, Jun. 5, 2003.
5
Biswas et al., US 2003/0082614 A1, May 1, 2003.
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Application 11/266,723

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Claims 6 and 30 stand rejected under 35 U.S.C. § 103(a) as obvious
over Sorge in view of Hughes and Brzostowicz
6
(Ans. 8).
Claim 9 stands rejected under 35 U.S.C. § 103(a) as obvious over
Sorge in view of Hughes and Allen
7
(Ans. 9).
Claim 13 stands rejected under 35 U.S.C. § 103(a) as obvious over
Sorge in view of Hughes, Innis,
8
and Loehrlein
9
(Ans. 10).
Claim 29 stands rejected under 35 U.S.C. § 103(a) as obvious over
Sorge in view of Hughes and Eggert
10
(Ans. 12).
Claims 20, 22, and 23 stand rejected under 35 U.S.C. § 103(a) as
obvious over Sorge in view of Kellogg
11
(Ans. 13).
Claim 21 stands rejected under 35 U.S.C. § 103(a) as obvious over
Sorge in view of Kellogg, McLaughlin, and Biswas (Ans. 15).
I
In rejecting claims 1-13 and 28-30, the Examiner relies on Sorge and
Hughes, alone or in view of additional reference(s) (Ans. 3-13). The
Examiner relies on Sorge for teaching
a method for detecting a target nucleic acid in sample
comprising:
exposing said sample to detection assay reagents under
conditions such that said target nucleic acid is detected, if

6
Brzostowicz et al., US 2003/0113886 A1, Jun. 19, 2003.
7
Allen et al., US 2003/0204870 A1, Oct. 30, 2003.
8
Innis et al., US 5,075,216, Dec. 24, 1991.
9
Loehrlein et al., US 2003/0204322 A1, Oct. 30, 2003.
10
Eggert et al., Relative Quantitative RT-PCR Protocol for TrkB Expression
in Neuroblastoma Using GAPD as an Internal Control, 28 BIOTECHNIQUES
681-691 (2000).
11
Kellogg et al., US 6,063,589, May 16, 2000.
Appeal 2010-009027
Application 11/266,723

4
present, in a single step reaction, wherein said single step
reaction comprises a target amplification comprising a
polymerase chain reaction and a signal amplification
comprising an invasive cleavage reaction.
(Id. at 3.) The Examiner notes “that Sorge teaches that a sample may be
genomic DNA, RNA or cDNA” (id. at 4).
“[T]o the extent that Sorge does not teach a single-step reaction
including reverse transcription,” the Examiner relies on Hughes for teaching
that “one-step RT-PCR type reactions may be accomplished in one tube
thereby lowering the possibility of contamination” (id. at 5). The Examiner
concludes that it would have been obvious “to include a reverse
transcription[] reaction in the single step process taught by Sorge in order to
detect or quantify RNA” (id.).
Issue
With regard to the rejections over Sorge and Hughes, alone or in view
of additional reference(s), the issue is: Does the evidence support the
Examiner‟s conclusion that Sorge and Hughes suggest a single step reaction
comprising a reverse transcription reaction, a target amplification reaction,
and a signal amplification reaction?
Findings of Fact
1. The Specification discloses:
In some embodiments, the INVADER assay provides
detection[] assays in which the target nucleic acid is reused or
recycled during multiple rounds of hybridization with
oligonucleotide probes and cleavage of the probes. . . . When a
cleavage reaction is run under conditions in which the probes
are continuously replaced on the target strand . . . , multiple
probes can hybridize to the same target, allowing multiple
cleavages, and the generation of multiple cleavage products.
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(Spec. 55.)
2. The Specification also discloses:
Figure 1 shows a schematic diagram of an embodiment of the
INVADER assay. In the primary reaction, the target molecule
(hatched rectangle) forms the overlap-flap structure with the
invasive probe (open rectangle) and the primary probe which
includes the target-specific region (open rectangle) and the 5'
flap (filled rectangle). The overlap-flap is cleaved by the
structure-specific 5' nuclease. . . . In the secondary reaction, the
cleaved 5' flap forms the overlap-flap structure with FRET
cassette (gray line) labeled with a dye (D) and quencher (Q).
Cleavage of the FRET cassette by the 5' nuclease releases the
unquenched dye. The semicircular arrows indicate the
oligonucleotide turnover process essential for signal
amplification.
(Id. at 13-14 (emphasis added).)
3. In addition, the Specification discloses that “the INVADER
assay provides from 10
6
to 10
7
fold amplification of signal” (id. at 42).
4. Sorge discloses
a method of generating a signal indicative of the presence of a
target nucleic acid sequence in a sample comprising forming a
cleavage structure by incubating a sample comprising a target
nucleic acid sequence with a nucleic acid polymerase, and
cleaving the cleavage structure with a FEN nuclease to generate
a signal, wherein generation of the signal is indicative of the
presence of a target nucleic acid sequence in the sample.
(Sorge, col. 4, ll. 15-23.)
5. Sorge states that the “term „sample‟ . . . includes a sample of
nucleic acid (genomic DNA, cDNA, RNA)” (id. at col. 7, ll. 5-6).
6. Sorge also discloses that its “invention provides for a
polymerase chain reaction process wherein amplification and detection of a
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target nucleic acid sequence occur concurrently” (id. at col. 10, l. 66, to
col. 11, l. 1).
7. In Sorge‟s Example 6, the detection assay utilizes a Single-
Tube RT-PCR Core Reagent Kit (id. at col. 48, l. 63, to col. 49, l. 63,
especially at col. 49, l. 41).
8. Hughes discloses one-step RT-PCR (Hughes, col. 11, l. 49).
Analysis
“[D]uring examination proceedings, claims are given their broadest
reasonable interpretation consistent with the specification.” In re Hyatt, 211
F.3d 1367, 1372 (Fed. Cir. 2000). In discussing the INVADER assay, the
Specification states that “the oligonucleotide turnover process [is] essential
for signal amplification” (Finding of Fact (FF) 2). However, we do not
agree with Appellants that the Specification requires the term “signal
amplification” to refer “to the generation of multiple signals from each
target nucleic acid” (App. Br. 7 (emphasis added)), which would presumably
require at least a 2:1 ratio of signal to target, as Appellants provide no
specific definition of “signal amplification” in the Specification. Instead, we
interpret the term “signal amplification reaction” as would be understood by
one of ordinary skill in the art to additionally include reactions that result in
a ratio of signal to target between 1:1 and 2:1.
In the Examiner‟s Answer, at pages 19-21, the Examiner sets forth
what appears to be sound scientific reasoning supporting his position that
Sorge‟s method would result in some signal amplification. Appellants have
not adequately explained why this reasoning is incorrect.
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With regard to including a reverse transcription reaction, Appellants
argue “that neither Sorge nor Hughes provide any teaching whatsoever
regarding the compatibility of an invasive cleavage reaction and reverse
transcription” (App. Br. 10). However, Appellants have not adequately
explained why there would not have been a reasonable expectation of
success, particularly in view of Sorge‟s Example 6, which includes RT-PCR
(FF 7).
Conclusion
The evidence supports the Examiner‟s conclusion that Sorge and
Hughes suggest a single step reaction comprising a reverse transcription
reaction, a target amplification reaction, and a signal amplification reaction.
We therefore affirm the obviousness rejections of claims 1-13 and 28-30
over Sorge and Hughes, alone or in view of additional reference(s).
II
In rejecting claims 20-23, the Examiner relies on Sorge and Kellogg,
alone or in view of additional references (Ans. 13-16). The Examiner relies
on Sorge for teaching “a method wherein a sample is exposed to reverse
transcription, polymerase chain reaction and invasive cleavage assay
reagents configured to reverse transcribe, amplify and detect target nucleic
acids” (id. at 13). The Examiner also relies on Sorge for teaching
multiplexing (id. at 14). The Examiner relies on Kellogg for teaching a
microfluidics card (id.). The Examiner concludes that it would have been
obvious “to carry out the method taught by Sorge in a microfluidics card
taught by Kellogg” (id.).
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Application 11/266,723

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Appellants argue that “Sorge does not teach or suggest a signal
amplification reaction, either alone or used in conjunction with both a
reverse transcription and a target amplification reaction” (App. Br. 13).
However, we are not persuaded by this argument for the reasons discussed
above. We therefore affirm the obviousness rejections of claims 20-23 over
Sorge and Kellogg, alone or in view of additional references.

TIME PERIOD FOR RESPONSE
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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