Ex Parte Roos et al

Patent Trial and Appeal Board

Dec 29, 2016

13512924 (P.T.A.B. Dec. 29, 2016)

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.
13/512,924 08/03/2012 Fredrik Roos 20120051-05 3591
7590
Agilent Technologies, Inc. in care of:
CPA Global
P. O. Box 52050
Minneapolis, MN 55402
EXAMINER
SMITH, JONAH
ART UNIT PAPER NUMBER
1639
NOTIFICATION DATE DELIVERY MODE
01/03/2017 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 FREDRIK ROOS, HENRIK JOHANSSON,
MAGNUS ISAKSSON, MATS NILSSON,
OLLE (OLOF) ERICSSON, and SIMON FREDRIKSSON1
Appeal 2015-001193
Application 13/512,924
Technology Center 1600
Before ULRIKE W. JENKS, RYAN H. FLAX, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
JENKS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims directed
to amplifying nucleic acids. The Examiner rejects the claims on the grounds
of nonstatutory obviousness type double patenting and obviousness. We
have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
1 According to Appellants, the Real Party in Interest is Agilent
Technologies, Inc. (App. Br. 3.)
Appeal 2015-001193
Application 13/512,924
STATEMENT OF THE CASE
Claims 1, 2, 6—10, 12—14, 16, 17, 20, 22—25, 29, and 30 are on appeal,
and can be found in the Claims Appendix of the Appeal Brief. Claim 1, the
only independent claim, is representative of the claims on appeal, and reads
as follows:
1. A method for amplifying at least one target nucleic acid in a
nucleic acid sample, comprising:
(a) fragmenting the nucleic acid sample to create at least
one target fragment comprising said target nucleic acid and
comprising two probe-complementary portions, wherein at least
one of said two probe-complementary portions is located at an
end of the target fragment;
(b) contacting said fragmented nucleic acid sample with at
least one probe which is provided with an immobilization moiety
and optionally is immobilized on a solid phase by means of said
moiety, and which comprises two target fragment­
complementary portions which are complementary in sequence
to the probe-complementary portions of the target fragment,
wherein said portions of the probe may be adjacent, or separated
by an intervening non-target fragment-complementary portion;
(c) rendering the fragmented nucleic acid sample single-
stranded, wherein the step may occur before, contemporaneously
with or after step (b);
(d) allowing the probe-complementary portions of the
target fragment to hybridize with the target-fragment
complementary portions of the probe;
(e) if the probe provided in step (b) is not immobilized,
immobilizing the probe-target fragment hybrid on a solid phase
by means of said immobilization moiety;
(f) separating non-immobilized nucleic acid fragments
from the solid phase;
(g) contacting the solid phase with a ligase to ligate,
directly or indirectly, ligatable 5’ and 3’ ends of the target
fragment whereby the target fragment is circularized, wherein
where one of said probe-complementary portions of the target
fragment is not located at an end of the target fragment, the
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ligatable end, other than that at which a probe-complementary
portion is located, is created by the action of a flap endonuclease
or an exonuclease; and
(h) amplifying said circularized target fragment.
The Examiner rejects the claims as follows:
Claims 1, 2, 20, and 30 under 35 U.S.C. § 103(a) as unpatentable over
Dahl et al. (WO 2005/111236 A1 (“Dahl”)) in view of Albert (US
2008/0194413 Al, published Aug. 14, 2008).
Claims 1, 2, 6—10, 12—14, 16, 17, 20, 22—25, 29 and 30 are rejected on
the ground of nonstatutory obviousness-type double patenting as being
unpatentable over claims 1—22 of US 7,790,388 in view of Albert.
Obviousness over Dahl and Albert
The issue is: Does the preponderance of evidence of record support
the Examiner’s conclusion that the combination of Dahl and Albert renders
obvious step “(g) contacting the solid phase with a ligase to ligate, directly
or indirectly, ligatable 5 ’ and 3 ’ ends of the target fragment whereby the
target fragment is circularized, wherein where one of said probe­
complementary portions of the target fragment is not located at an end of the
target fragment, the ligatable end, other than that at which a probe­
complementary portion is located, is created by the action of a flap
endonuclease or an exonuclease” as claimed?
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Findings of Fact
FF1. Dahl teaches a method of amplifying a plurality of target sequences
with minimal amplification artifacts, i.e., false amplification products.
The method is depicted in Fig. 1 reproduced below.
DNA cleavage
1
Digested DNA with defined ends
Selector 1
Selector 2
Selectors
Mix digested DNA
and Selectors
Selector design
Common primer
motif
1
Short *
Long \ /
Target specific ends
Or
Common primer
motif
Short ^
Long ~r~----------
T
Target specific ends
FIG. 1 illustrates the first step of the procedure.
Digestion of genomic DNA with one or a pool of
restriction enzyme, results in fragments with defined
ends. The digested fragments are denaturated to single
stranded DNA and added together with the designed
selectors. Each of the selectors is composed of two
oligonucleotides, a long and a short, which are
hybridized to each other; one which contains one or two
target specific ends and at least one primer motif, and a
shorter one that contains at least one primer motif.
(Dahl 6:5-12.)
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FF2. Dahl teaches that the ligation products differ based on the selector
design. The variation in the ligation products are shown below in
Figure 2:
Digested ssDNA with defined ends Selectors
or
A Specific hybridization
ligation
0 Specific hybridization Ligation
“FIG. 2 the selectors are ligated to respective end[s] of the selected
digested single stranded DNA-targets (ssDNA). This process can be
performed in different ways” denoted A, B, and C in the figure (Dahl
6:14-16). The “ligation of selectors to targets can be performed in
parallel and amplified in a multiplex PCR with a common primer-
pair” (Dahl 6:26-27).
FF3. Dahl teaches that “[ajfter the amplification reaction, the products can
be analyzed using methods for nucleic acid analysis known in the art,
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such as DNA microarrays, gel-electrophoresis, or mass-spectrometry”
(Dahl 5:16-18).
FF4. The Examiner finds that Dahl teaches step “(e) immobilizing the
target-probe complex on a solid phase with the immobilization moiety
(see p. 5, Ln. 16-18)” (Ans. 6—7).
FF5. The Examiner finds that “[cjircularization on a solid support is an
obvious variant of circularization in solution” (Ans. 11).
FF6. Albert teaches a method of processing genomic DNA to reduce the
complexity of the genomic sample (see Albert Abstract).
The method uses pre-selected immobilized nucleic acid
probes to capture target nucleic acid sequences from a
genomic sample by hybridizing the sample to the probes
on a substrate. The captured target genomic nucleic
acids are washed and then eluted off of the substrate.
The eluted genomic sequences are more amenable to
detailed genetic analysis than a genomic sample that has
not been subjected to this procedure.
(Albert 17).
FF7. Albert teaches that “[ajfter hybridization, target nucleic acid
sequences present in the sample may be enriched by washing the array
and eluting the hybridized genomic nucleic acids from the array”
(Albert | 8). “The target nucleic acid molecules can be amplified
using for example, non-specific ligation mediated PCR through
multiple rounds of thermal cycling. Optionally, the amplified
products can be further enriched by a second selection against the
probes” (Albert 118).
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Principle of Law
“An examiner bears the initial burden of presenting a prima facie case
of obviousness.” In re Huai-Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir.
2011).
Analysis
The Examiner finds that Dahl teaches steps (a)-(f) as claimed (see
Ans. 5—7). The Examiner finds that “Albert also discloses steps (e)
immobilizing the target-probe complex on a solid phase with the
immobilization moiety . . . and (f) separating non-immobilized nucleic acid
fragments from the solid phase ... as part of a method for reducing the
complexity of a genomic sample [] so that it may be more efficiently further
analyzed” (Ans. 6—7). Based on the combination of references the Examiner
concludes that “[o]ne of ordinary skill would have been motivated to
combine Dahl’s method for amplifying nucleic acids with Albert’s use of a
microarray with immobilized probes and removal of unbound target to
increase specificity/reduce complexity of genomic DNA because the
references suggest/motivate as much” (Ans. 8).
Appellants contend that “Dahl does not explicitly state that the
circularized step can be done on a solid support” and “Albert [also] does not
teach the solid phase ligation step that is missing from Dahl” (App. Br. 5).
In other words, “none of the cited reference teaches solid phase ligation”
(Reply Br. 2). Furthermore, Appellants contend that the Examiner provides
no evidence to support the statement that “‘[cjircularization on a solid
support is an obvious variant of circularization in solution” (Reply Br. 2; see
also App. Br. 6 (“Examiner’s rebuttal indicates that he is basing this
rejection on the idea that because in solution circularization and solid
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supports are both known in the art, then it would obvious to circularize on a
solid support”)).
Based on the totality of the evidence, we find that Appellants have the
better position. Dahl teaches the steps of fragmenting the nucleic acid
sample (FF1), contacting the sample with a probe (FF1), creating single
stranded fragment (FF2), and allowing interaction between probe and
fragment followed by an amplification reaction (FF1, see FF2). Dahl also
discloses the use of a DNA microarray as a way of analyzing the amplified
reaction product (FF3).
We agree with the Examiner that Dahl teaches circularization of
fragments as well as amplification of fragments (see Final Act 10—11; Dahl
14: 26 to 15:21). However, we do not find evidence that Dahl carries out the
circularization step on a solid support, or at least the ligation step (g) on the
solid support. At best Dahl discloses contacting the previously amplified
probe-target product with the DNA microarray (FF3), but we do not agree
with the Examiner’s finding that this is achieved using an immobilization
moiety (FF4). Albert teaches a method of capturing target nucleic acid
molecules onto a solid support from a fragmented genomic nucleic acid
sample and amplifying those molecules (FF6—FF7). However, we find no
evidence that Albert teaches ligation reactions in the amplification process
that are performed while the samples are attached to the solid support.
Albert’s technique allows for the capture of a nucleic acid target from a
fragmented genomic sample and removal of any nucleic acid that is not
interacting with the probes.
The Examiner takes the position that because Albert “includes a
discussion of the benefits of adopting such a technique to facilitate
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subsequent analyses, including sequencing and amplification. . . . Therefore,
the instant improvement was already known to have the effect as the instant
claim” (Ans. 9). We are not persuaded by the Examiner’s rationale. Albert
hybridizes the genomic sample with probes attached to a solid support, and
even suggests using the solid support for additional purification at a later
point in their processing (see FF6 and FF7). However, the ligation steps
disclosed throughout the Albert reference, the samples are detached from the
support before the ligation protocol is performed (see FF6 and FF7).
Therefore, we agree with Appellants that “[t]he examiner has provided no
reason to perform a ligation while [] Dahl’s products are hybridized to
Albert’s array and, as such, this combination of references would not
provide the method being claimed” (App. Br. 5).
We conclude that the preponderance of the evidence of record does
not support the Examiner’s conclusion that the combination of Dahl and
Albert discloses a method having all limitations of independent claim 1 and
dependent claims thereto. We thus reverse the rejections under 35 U.S.C.
§ 103(a) that rely on the teachings of Dahl and Albert.
Nonstatutory Obviousness-type Double Patenting
The Examiner finds that “the claims of the’3 88 patent are directed to a
method for amplifying at least one target nucleic acid comprising
fragmenting, hybridizing, circularizing, amplifying and the use of adaptor
probes” (Final Act. 3—4). The Examiner acknowledges that “[t]he ‘388
patent does not explicitly disclose immobilizing adaptor probes” (Final Act.
4). The Examiner looks to Albert for teaching solid phase immobilization
and “separating non-immobilized nucleic acid fragments” (Final Act. 4).
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The Examiner finds that “[cjircularization on a solid support is an obvious
variant of circularization in solution” (FF5). The Examiner also looks to the
Specification of the ’388 patent to determine that amplification on the solid
support is valuable (Final Act. 10).
We agree with Appellants that the Examiner has not identified where
in the claims of the ’388 patent or Albert’s disclosure there is a suggestion to
ligate captured nucleic acid samples on a solid support in order to arrive at a
circularized nucleic acid product. Thus, we consider whether the Examiner
properly relies on “official notice” with respect to these elements.
As noted by Appellants, the Examiner does not provide evidence to
support the statement that “[cjircularization on a solid support is an obvious
variant of circularization in solution” (Reply Br. 2). MPEP 2144.03, citing
In re Ahlert, 424 F.2d 1088, 1091 (CCPA 1970), states that “notice of facts
beyond the record which may be taken by the examiner must be ‘capable of
such instant and unquestionable demonstration as to defy dispute’ (citing In
re Knapp Monarch Co., 296 F.2d 230 (CCPA 1961)).” Here, the Examiner
has not shown that circularization on a solid support was unquestionably
well known in the art.
We find that Appellants adequately traverse the Examiner’s finding
that “[cjircularization on a solid support is an obvious variant of
circularization in solution” in noting that it has no evidentiary support in the
applied references (Reply Br. 2; see also App. Br. 6 (“the Examiner’s
rebuttal indicates that he is basing this rejection on the idea that because in
solution circularization and solid supports are both known in the art, then it
would obvious to circularize on a solid support”)). “If applicant adequately
traverses the examiner’s assertion of official notice, the examiner must
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provide documentary evidence” (MPEP § 2144.03(C)). As also explained
by the Federal Circuit:
With respect to core factual findings in a determination of
patentability, [the Examiner] cannot simply reach conclusions
based on its own understanding or experience—or on [his]
assessment of what would be basic knowledge or common sense.
Rather, the [Examiner] must point to some concrete evidence in
the record in support of these findings.
In re Zurko, 258 F.3d 1379, 1385 (Fed. Cir. 2001). Reliance on common
knowledge or common sense in an obviousness rejection is applicable to “to
provide a known motivation to combine, [but] not to supply a missing claim
limitation” Arendi S.A.R.L. v. Apple Inc., 832 F.3d 1355, 1361
(2016)(“[W]hile ‘common sense’ can be invoked, even potentially to supply
a limitation missing from the prior art, it must still be supported by evidence
and a reasoned explanation”)). Here, the Examiner relies on common
knowledge without supporting evidence in the record showing that solid
phase ligation, let alone solid phase circularization, and solution phase
ligation are obvious variants that are well known in the context of ligation
procedures generally to arrive at the claimed limitation of “contacting the
solid phase with a ligase to ligate ... the target fragment whereby the target
fragment is circularized” as recited in claim 1.
Thus, the preponderance of evidence on this record fails to support the
Examiner’s conclusion that the combination of ’388 claims with Albert
renders the present claims obvious. Accordingly, we reverse the rejection
nonstatutory obviousness-type double patenting rejection.
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SUMMARY
We reverse the rejection of claims 1, 2, 20, and 30 under 35 U.S.C.
§ 103(a) over Dahl and Albert.
We reverse the rejection of claims 1, 2, 6—10, 12—14, 16, 17, 20, 22—
25, 29 and 30 on the ground of nonstatutory obviousness-type double
patenting as being unpatentable over claims 1—22 of US 7,790,388 in view
of Albert.
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).
REVERSED
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