Ex Parte OZINSKY et al

Patent Trial and Appeal Board

Oct 22, 2018

13769195 (P.T.A.B. Oct. 22, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/769, 195 02/15/2013
25225 7590 10/24/2018
MORRISON & FOERSTER LLP
12531 HIGH BLUFF DRIVE
SUITE 100
SAN DIEGO, CA 92130-2040
FIRST NAMED INVENTOR
Adrian OZINSKY
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
655652004000 3413
EXAMINER
LEITH, NANCY J
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
10/24/2018 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ADRIAN OZINSKY, ROLF KUESTNER, and
GREGORY ZORNETZER1
Appeal2017-001038
Application 13/7 69,195
Technology Center 1600
Before DONALD E. ADAMS, ULRIKE W. JENKS, and
TA WEN CHANG, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method to determine the presence or absence of, quantify and/or identify at
least one RNA species in a sample, which have been rejected as obvious.
We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
STATEMENT OF THE CASE
RNases Hare enzymes that are able to bind a single-stranded RNA
hybridized to a complementary single-stranded DNA and then degrade the
1 Appellants identify the Real Party in Interest as Institute for Systems
Biology. (Appeal Br. 1.)
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Application 13/769,195
RNA portion of the RNA:DNA hybrid. (Carter2 1:45-50.) The
Specification states that "[t]he present invention takes advantage of the
reversible nuclease activity of RNase H due to the presence or absence of
magnesium ion to utilize DNA probes in a prepared oligomer library as
indices for the presence and/or amount of RNA complementary to them."
(Spec. ,r 5.) According to the Specification, the invention provides an easily
multiplexed and miniaturized method for detecting, quantitating, and
identifying RNA species in a sample. (Id. ,r 6.)
Claims 1, 4--16, 21, and 22 are on appeal. Claim 1 is illustrative and
reproduced below:
1. A method to determine the presence or absence of
and/or to quantify and/or to identify at least one RNA species in
a sample, comprising the steps of:
a) exposing the sample to at least one DNA probe
comprising a sequence complementary to said at least one RNA
species of interest to form DNA:RNA hybrids with any said
RNA species of interest in the sample;
b) incubating the DNA:RNA hybrids formed in a)
with RNase H under conditions that inhibit the nuclease activity
of the RNase H but do not inhibit its DNA:RNA binding
activity thereby forming a complex whereby said RNase His
bound to said hybrids designated RNase H-bound DNA:RNA;
c) separating RNase H-bound DNA:RNA from
unbound DNA and RNA;
d) incubating the RNase H-bound DNA:RNA under
conditions wherein the nuclease activity is restored so as to
hydrolyze the RNA of the DNA:RNA hybrids and release the
DNA probe; and
e) determining the presence or absence and/ or
amount and/or identity of the released DNA probe, thereby
determining the presence or absence and/ or quantity and/ or
identity of said at least one RNA species in the sample;
2 Carter et al., US 7,560,232 B2, issued July 14, 2009.
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Application 13/769,195
wherein multiple RNA species of interest are detected
and/or quantified and/or identified in a multiplexed assay and
wherein step a) employs DNA probes complementary to each
said multiple RNA species of interest and wherein in step e) the
presence and/or quantity and/or identity of DNA probe
complementary to each of said multiple RNA species of interest
is determined.
(Appeal Br. 10 (Claims App.).)
The Examiner rejects claims 1, 6, 8, and 11-14 under pre-AIA 35
U.S.C. § I03(a) as being unpatentable over Carter. (Ans. 3.)
The Examiner rejects claims 4, 5, and 9 under pre-AIA 35 U.S.C.
§ I03(a) as being unpatentable over Carter and Galas. 3 (Ans. 6.)
The Examiner rejects claim 10 under pre-AIA 35 U.S.C. § I03(a) as
being unpatentable over Carter and Shachar. 4 (Ans. 7-8.)
The Examiner rejects claims 15 and 16 under pre-AIA 35 U.S.C.
§ I03(a) as being unpatentable over Carter, Cheung, 5 and Ohtani. 6 (Ans. 8-
9.)
The Examiner rejects claims 7, 21, and 22 under pre-AIA 35 U.S.C.
§ I03(a) as being unpatentable over Carter, Bibikova,7 and Park. 8 (Ans. 10.)
3 Galas et al., WO 2011/097528 Al, published Aug. 11, 2011.
4 Shachar et al., US 2010/0262375 Al, published Oct. 14, 2010.
5 Cheung et al., US 2011/0294674 Al, published Dec. 1, 2011.
6 Naoto Ohtani et al., Heat Labile Ribonuclease HI from a Psychrotrophic
Bacterium: Gene Cloning, Characterization and Site-Directed Mutagenesis,
14 PROTEIN ENGINEERING 97 5 (2001 ).
7 Marina Bibikova et al., Technical Brief, Gene Expression Profile in
Formalin-Fixed, Paraffin-Embedded Tissues Obtained with a Novel Assay
for Microarray Analysis, 50 CLINICAL CHEMISTRY 2384 (2004).
8 Young Nyun Park et al., Technical Advance, Detection of Hepatitis C
Virus RNA Using Ligation-Dependent Polymerase Chain Reaction in
Formalin-Fixed, Paraffin-Embedded Liver Tissues, 149 AM. J. PATHOLOGY
1485 (1996).
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Application 13/769,195
DISCUSSION
Issue
The Examiner finds that Carter discloses all of the steps of claim 1,
which is the only independent claim, except that Carter does not suggest
"incubating the RNase H bound DNA:RNA under conditions where the
nuclease activity of the RNase His restored, so that the RNA is hydrolyzed,
and the DNA probe released." (Ans. 4, 5.) The Examiner concludes that it
would have been obvious to a skilled artisan to
manipulate the RNase Hin the reaction to first inhibit the
nuclease activity so that the RNA:DNA hybrid can be
formed, and then to allow an increase in the nucleolytic
activity of the RNase H through manipulation of the
reaction conditions, so as to degrade the RNA, which will
allow the labeled DNA probe to be detected without the
interference from RNA molecules. One of ordinary skill
in the art knowing that the RNase H activities can be
manipulated through the reaction conditions, such as the
magnesium ion levels, would have a reasonable
expectation of success in doing so.
(Id. at 5-6.)
Appellants contend among other things that Carter does not suggest
restoring the RNase H activity, as required by step d) of claim 1. (Appeal
Br. 3.)
The issue with respect to the rejections on appeal is whether Carter
suggests a method to determine the presence or absence of and/or to quantify
and/or to identify at least one RNA species in a sample comprising the steps
of "incubating RNase H-bound DNA:RNA under conditions wherein the
nuclease activity is restored so as to hydrolyze the RNA of the DNA:RNA
hybrids and release the DNA probe" and then "determining the presence or
absence and/or amount and/or identity of the released DNA probe, thereby
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Application 13/769,195
determining the presence or absence and/or quantity and/or identity of said
at least one RNA species in the sample."
Analysis
On balance, we find Appellants have the better position.
The Examiner acknowledges that "Carter fails to disclose or suggest
incubating the RNase H bound DNA:RNA under conditions where the
nuclease activity of the RNase His restored, so that the RNA is hydrolyzed,
and the DNA probe released." (Ans. 5.) However, the Examiner finds that
"Carter discloses that the presence or absence of magnesium ions in the
RNase H buffer can be used to manipulate whether the nucleolytic activity
of the RNase His present" and also teaches that "an active RNase H can be
added to degrade the RNA:DNA hybrids to liberate ribonucleotides." (Id. at
4.)
In light of the above and given Carter's teaching of a method for
detecting and/or quantifying an RNA of interest in a sample comprising a
step of "incubating ... DNA:RNA hybrids with an RNase H under
conditions that inhibit the nuclease activity of the RNase H," the Examiner
concludes that it would have been obvious to a skilled artisan to first inhibit
and then allow an increase in the nucleolytic activity of the RNase H by
varying reaction conditions, such as magnesium ion levels, in order to
degrade RNA and allow labeled DNA probe to be detected without
interference from RNA molecules. (Id. at 5---6.) The Examiner also finds
that a skilled artisan would have a reasonable expectation of success in
arriving at the claimed invention in view of Carter's disclosure that "RNase
H activities can be manipulated through the reaction conditions, such as ...
magnesium ion levels." (Id. at 6.)
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While we understand the Examiner's position, we are not persuaded.
We agree with the Examiner that Carter teaches that RNase H nucleolytic
activity is dependent on access to divalent cations such as magnesium ions.
(Carter 8:21-24, 10:61-11 :7.) However, this teaching is provided in the
context of the desirability of suppressing RNase H nucleolytic activity.
Likewise, while Carter teaches a preferred embodiment in which a protein
having RNase H activity is added to degrade RNA:DNA hybrids, the
embodiment does not involve incubating DNA:RNA hybrids with RNase H
under conditions that first inhibit and then restore RNase H nucleolytic
activity, nor does the embodiment involve determining the presence,
quantity, and/or identity of RNA in the sample using DNA probes released
through RNase H nucleolytic activity. Instead, in that embodiment Carter
teaches hybridizing RNA in the sample with immobilized DNA probes,
degrading the hybrids using RN ase H to release mono- and
oligoribonucleotides, generating ATP from liberated AMP nucleotides, and
then detecting the presence of the RNA sequence of interest through an ATP
detection reaction. (Id. at 4:51---65.)
We are cognizant that the rejection of claim 1 is one of obviousness
rather than anticipation; thus, "picking and choosing" disclosures in Carter
that are not directly related to each other for combination may be proper. In
reArkley, 455 F.2d 586,587, 172 USPQ 524,526 (CCPA 1972). In this
case, however, we find that the Examiner has not sufficiently articulated a
reason that a skilled artisan would have combined the disclosures in Carter
to supply the limitation not explicitly disclosed to arrive at the claimed
invention. For instance, the Examiner cites no evidentiary support for the
conclusion that, based on Carter's disclosures, a skilled artisan would have
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first inhibited and then allowed an increase in the nucleolytic activity of the
RNase H "in order to ... allow labeled DNA probe to be detected without
the interference from RNA molecules." (Ans. 5---6.) Neither has the
Examiner argued or shown that claim 1 is merely the combination of
familiar elements according to known methods to yield predictable results,
or may be arrived at by a simple substitution of known equivalents.
"[R ]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,418 (2007)
(quoting In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). Accordingly, we
reverse the Examiner's rejection of claim 1 as obvious over Carter. We also
reverse the rejection of claims 4--16, 21, and 22, which depend directly or
indirectly from claim 1, for the same reasons. In re Fine, 837 F .2d 1071,
107 6 (Fed. Cir. 198 8) ("Dependent claims are nonobvious under section 103
if the independent claims from which they depend are nonobvious. ").
SUMMARY
For the reasons above, we reverse the Examiner's decision rejecting
claims 1, 4--16, 21, and 22.
REVERSED
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