Ex Parte Johansson et al

Patent Trial and Appeal Board

Sep 21, 2016

12664177 (P.T.A.B. Sep. 21, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/664,177 05/05/2010
22878 7590 09/23/2016
Agilent Technologies, Inc. in care of:
CPA Global
P. 0. Box 52050
Minneapolis, MN 55402
FIRST NAMED INVENTOR
Henrik Johansson
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.
FDEHN38.001APC 1609
EXAMINER
POHNERT, STEVEN C
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
09/23/2016 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
following e-mail address( es):
IPOPS.LEGAL@agilent.com
Agilentdocketing@cpaglobal.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HENRIK JOHANSSON and OLOF ERICSSON1
Appeal2014-002943
Application 12/664, 177
Technology Center 1600
Before DEMETRA J. MILLS, ULRIKE W. JENKS, and JOHN G. NEW
Administrative Patent Judges.
JENKS, Administrative Patent Judge.
uECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims directed
to a method of introducing target nucleic acid molecules into a DNA
sequence. The Examiner rejects the claims as obvious. We have
jurisdiction under 35 U.S.C. § 6(b ).
We AFFIRM.
1 According to Appellants, the real party in interest is Agilent Technologies,
Inc. (App. Br. 3.)
Appeal2014-002943
Application 12/664, 177
STATEMENT OF THE CASE
According to the Specification, the invention is directed to the field of
multiplex DNA analysis. (Spec. 1.) The invention provides
means to equip a target nucleic acid molecule population with
both common sequence elements and individual sequence
elements unique for single targets and or subpopulations within
the selected target sequences. The common elements can
subsequently be utilized for e.g. amplification of all selected
target sequences while the individual sequence elements can be
used for e.g. analysis, quantification or sorting of the respective
target molecules.
(Id. at 3.)
Claims 1-7 are on appeal, and can be found in the Claims Appendix
of the Appeal Brief. Claim 1 is representative of the claims on appeal, and
reads as follows (emphasis added):
1. A method for introducing common and/or individual
sequence elements in a target nucleic acid molecule in a sample
containing sample nucleic acid molecules, comprising the steps:
i) hybridizing a sample comprising single stranded nucleic acid
molecules with primary, secondary, and tertiary probe nucleic
acid molecules, wherein the 3 '-end of the tertiary probe
comprises a part complementary to the primary probe and the
5'-end of the tertiary probe comprises a part complementary to a
5'-part of the target nucleic acid molecule; the 3'-end of the
secondary probe is complementary to a 3'-part of the target
nucleic acid molecule and the 5'-end of the secondary probe is
not complementary to the target nucleic acid molecule; wherein
said primary, secondary and tertiary probes comprise said
common and/or individual sequence elements;
ii) ligating the 3'-end of the primary probe to the 5'-end of the
target nucleic acid molecule; and
iii) introducing said common and/or individual sequence
elements in said target nucleic acid molecule by elongating the
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Appeal2014-002943
Application 12/664,177
3'-end of the secondary probe or elongating the 3' end of the
nucleic acid molecule, using a nucleic acid polymerase.
(App. Br. 10, Claims Appendix.)
Appellants seek review of the Examiner's rejection of claims 1-7
under 35 U.S.C. § 103(a) as unpatentable over Weismann.2 Because the
claims are not separately argued, we focus our discussion on representative
claim 1. Claims 2-7 stand or fall with that claim. 37 C.F.R. § 41.37
( c )(1 )(iv).
Obviousness over Weissman
The issue is: Does the preponderance of evidence of record support
the Examiner's conclusion that Weissman teaches using single stranded
nucleic acids in the hybridization steps as required by the method claimed?
Findings of Fact
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art as set forth in the Examiner's Answer and
the Final Action dated April 4, 2013 ("Final Act."). For emphasis only we
highlight the following:
FPL The Examiner finds that Weissman's Fig lG (reproduced below FF2)
shows nucleic acids having "single stranded portions" (Ans. 8). The
Examiner's annotated Fig. 1 G is shown below:
FIG~ 1G
---s) ~----J•
b3~-~-------~
-------3'c
3~-------·-----------
2 Weissman et al., US 6,57 6,448 B2, issued June 10, 2003.
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Appeal2014-002943
Application 12/664,177
Fig. 1 G (Ans. 7) shows the Examiner's identified single stranded
nucleic acid regions as a, b, c, and d (Ans. 8).
FF2. With reference to Fig. lG-lI, reproduced below, Weissman discloses
probes and primers for the production of a rolling circle amplification
(RCA) template.
FIG. 1 G fi'_
~~· _________ _-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-__ ~'. ______________________ -~_:_-_ _-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_---------- 3'
f ~
.... ,,., ............ u ...................................................................................................... , ..... '1
3~ ... -.-.-.-.-.-.. -.. -.-.-... -.-...... -.-.. -.. -.... -... -.-.-.-.... -.... -.-.-.. -.-.. -.-.-.-.. -.-.-.-.. -.-.. -.-.-.. -.-.... -.-.-... -.. -........... -.......... -... -.-.-.. -............. -.
FIG. 1 H
FIG. 1 l
Fig. lH-lI show, the hybridization of primers and subsequent
circularization of the replication template.
A partially double-stranded adapter is used to circularize a
double stranded DNA fragment for use as an RCA template.
The adapter which has appropriate overhangs on its ends to
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Appeal2014-002943
Application 12/664, 177
allow ligation to both ends of the DNA fragment (FIG. lG) can
be used such that annealing of the ends results in a circularized
adapter-fragment construct (FIG. lH) and ligation seals the
nicks (FIG. II)
(Weissman 5: 51-58).
FF3. Weissman also teaches that "[t]he single-stranded DNA product of
rolling circle amplification can itself be replicated by annealing of
complementary primers which can be extended in conventional primer
elongation reactions or in hyberbranching reactions in which
exponential amplification occurs" (Weissmann 3: 49-54).
FF4. The Specification provides that "depending on the source of nucleic
acids, the sample may have to be prepared to some extent. If genomic
DNA is used as source DNA it will advantageously be fragmented to
achieve complete denaturation of the double stranded DNA into single
stranded DNA available to probe hybridization" (Spec. 10 (emphasis
added)).
FF5. The Specification provides that the method step includes "denaturing
the sample nucleic acid molecules, if the sample nucleic acid
molecules are double-stranded, to obtain single stranded sample
nucleic acid molecules" (Spec. 3 (emphasis added)).
Analysis
We have reviewed Appellants' contentions that the Examiner erred in
rejecting claims 1-7 as obvious over the cited art. (App. Br. 4--9.) We
disagree with Appellants' contentions and adopt the findings concerning the
scope and content of the prior art and conclusions set forth in the Examiner's
Answer and the Final Act. For emphasis, we highlight and address the
following:
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Appeal2014-002943
Application 12/664, 177
Appellants contend that "Weisman's own disclosure makes it quite
clear that his sample is denatured and then renatured to produce double
strand molecules prior to hybridization with the oligonucleotides" (Reply Br.
3--4). Thus, "Weismann's suggestion to use molecules that are 'denatured
and re-annealed' is not a suggestion to use single stranded nucleic acid
molecules" as suggested by the Examiner (App. Br. 7). "[D]ouble stranded
nucleic acid molecules are required in Weissman's method because only
double stranded nucleic acid molecules ... [are] capable of being amplified
by rolling circle amplification" (id. at 6).
We are not persuaded. "[D]uring examination proceedings, claims are
given their broadest reasonable interpretation consistent with the
specification." In re Hyatt, 211F.3d1367, 1372 (Fed. Cir. 2000). The
Examiner interprets that "[t]he claims require 'single stranded nucleic acids'
however the claims do not specifically require the single stranded nucleic
acids are completely single stranded or merely a portion is single stranded"
(Ans. 8; see also Advisory Action3 ("the claim can be broadly interpreted as
having nucleic acid molecules which are partially or completely single
stranded")). This interpretation is consistent with the Specification. The
Specification clarifies that the need to be single stranded is to achieve
hybridization with a probe (FF4 and FF5). Thus, the Specification makes it
clear that the purpose of being "single stranded" is to achieve hybridization
with the probes and primers. In light of the teaching of the Specification we
find no error with the Examiner's claim interpretation that the nucleic acid
sequence needs to be single stranded only so far and for so long that it
3 Office Action dated June 14, 2013.
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Appeal2014-002943
Application 12/664, 177
allows hybridization with the requisite probes and the nucleic acid that is the
target for amplification.
The Examiner finds, and Appellants do not contest (see Reply Br. 3),
that "denaturing of nucleic acids followed by re-annealing (or hybridization)
to form heterohybrids inherently requires double stranded nucleic acids to
denature forming single stranded nucleic acids so as to allow them to
hybridize to another strand to form a heterohybrid" (Ans. 1 O; see also
Advisory Action ("the claims as presented inherently require conditions that
allow for the target nucleic acid and probe to be single stranded prior to the
hybridization and annealing, which would include 're-annealing,' to provide
conditions in which the complex of step i) is formed to allow for subsequent
hybridization step"); see FFl and FF2). Additionally, although not relied on
by the Examiner in making the rejection, we note that Weissman teaches that
the product of the rolling circle amplification is a single-stranded DNA that
can be further processed using complementary primers in conventional
reactions (FF3).
Appellants also contend that the Examiner's reliance on the language
of claim 7 is in error because the claim "does not imply or suggest that the
sample recited in claim 1 can be denatured and then reannealed to make
double strands prior to starting the method of claim 1" (App. Br. 9).
We are not persuaded, as explained by the Examiner, the claimed
method is not limited solely to the use of single stranded DNA, in other
words, DNA that is single stranded for the entire length of the nucleic acid
string. If double stranded DNA is used, then the additional step of preparing
the sample to obtain single stranded DNA for the purpose of hybridizing
probes to the DNA is needed as explained by the Specification (see FF4 and
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Application 12/664, 177
FF5). The Examiner's point is that the claim language of claim 1 is open
and can include additional steps (see Ans. 8), such as a denaturing step. See
Invitrogen Corp. v. Biocrest Mfg., L.P., 327 F.3d 1364, 1368 (Fed. Cir.
2003) ("The transition 'comprising' in a method claim indicates that the
claim is open-ended and allows for additional steps."). We agree with the
Examiner's interpretation that the inclusion of an additional step is
encompassed by the method as set out in claim 1.
Based on the preponderance of the evidence of record, we conclude
that the evidence cited by the Examiner supports a prima facie case of
obviousness with respect to claim 1, and Appellants have not provided
sufficient rebuttal evidence or evidence of secondary considerations that
outweighs the evidence supporting the prima facie case. Arguments not
made are waived. See 37 C.F.R. § 41.37(c) (1) (iv).
SUMMARY
We affirm the rejection of claim 1under35 U.S.C. § 103(a) as
unpatentable over W eismann. Claims 2-7 were not separately argued and
fall with claim 1. 37 C.F.R. § 41.37 (c)(l)(iv).
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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