Akeson, Mark A. et al.

Patent Trials and Appeals Board

Apr 10, 2020

14300453 - (D) (P.T.A.B. Apr. 10, 2020)

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.
14/300,453 06/10/2014 Mark A. Akeson 482.32-4 6792
24353 7590 04/10/2020
BOZICEVIC, FIELD & FRANCIS LLP
BOZICEVIC, FIELD & FRANCIS
201 REDWOOD SHORES PARKWAY
SUITE 200
REDWOOD CITY, CA 94065
EXAMINER
WOOLWINE, SAMUEL C
ART UNIT PAPER NUMBER
1637
NOTIFICATION DATE DELIVERY MODE
04/10/2020 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):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte MARK A. AKESON,
DAVID W. DEAMER, WILLIAM B. DUNBAR,
ROGER JINTEH ARRIGO CHEN, and NOAH A. WILSON

__________

Appeal 2019-003508
Application 14/300,453
Technology Center 1600
__________

Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL

Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1–32 and 34. We have jurisdiction
under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies The Regents of the University of
California as the real party in interest. Appeal Br. 3.
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STATEMENT OF THE CASE
The following rejections are before us for review:
(1) Claims 1, 2, 6, 12–21, 27–32, and 34, under pre-AIA 35 U.S.C.
§ 102(e) as anticipated by Nair2 (Ans. 3–4);
(2) Claims 3 and 5, under pre-AIA 35 U.S.C. § 103(a) as being
unpatentable over Nair (Ans. 4–6);
(3) Claims 1, 2, 5, 6, 12–21, 27–32, and 34, under pre-AIA 35 U.S.C.
§ 103(a) as being unpatentable over Su3 and Folch4 (Ans. 6–9);
(4) Claims 3 and 4, under pre-AIA 35 U.S.C. § 103(a) as being
unpatentable over Su, Folch, and Thill5 (Ans. 9–10);
(5) Claims 1, 2, 6, 12–21, and 27–32 and under pre-AIA 35 U.S.C.
§ 103(a) as being unpatentable over Ling6 and Tom-Moy7 (Ans. 10–12);
(6) Claims 1–6, 12–21, 27–32, and 34, under 35 U.S.C. § 101 as
claiming the same invention as that of claims 1–6, 12–21, 27–32, and 34, of
Chen ’8548 (Ans. 12–13);
(7) Claims 7–9 and 22–24, on the ground of nonstatutory double
patenting as being unpatentable over claims 7–9 and 22–24 of Chen ’854
(Ans. 13–14);

2 US 2007/0099191 A1 (published May 3, 2007).
3 US 2006/0019247 A1 (published Jan. 26, 2006).
4 US 7,501,279 B2 (issued Mar. 10, 2009).
5 US 6,632,610 B2 (issued Oct. 14, 2003).
6 US 2005/0127035 A1 (published June 16, 2005).
7 US 2005/0136408 A1 (published June 23, 2005).
8 US 8,461,854 B2 (issued June 11, 2013).
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(8) Claims 10, 11, 25, and 26, on the ground of nonstatutory double
patenting as being unpatentable over claims 10, 11, 25, and 26 of Chen ’854
in view of Akeson ’5949 (Ans. 14–15);
(9) Claims 1–8, 10, 12–23, 25, 27–32, and 34, on the ground of
nonstatutory double patenting as being unpatentable over claims 1–8, 9, 10–
21, 22–28, and 30, of the ’315 Application10 (issued as Akeson ’688)11 (Ans.
15–16);
(10) Claims 9, 11, 24, and 26, on the ground of nonstatutory double
patenting as being unpatentable over claims 8, 9, 21, and 22 of Application
No. 14/919,315 (issued as Akeson ’688) in view of Su (Ans. 16); and
(11) Claims 1, 2, and 20, on the ground of nonstatutory double
patenting as being unpatentable over claims 3 and 8 of Chen ’43712 (Ans.
16–17).
Appellant’s claims 1 and 20 are the independent claims on appeal and
read as follows:
1. A method for nucleic acid sequencing, comprising:
(a) providing a chip comprising a plurality of
individually addressable nanopores, an
individually addressable nanopore of said plurality
of individually addressable nanopores containing
at least one nanopore formed in a membrane
disposed adjacent to an electrode, wherein each
individually addressable nanopore is adapted to
detect a nucleic acid molecule or a portion thereof;

9 US 6,746,594 B2 (issued June 8, 2004).
10 Application No. 14/919,315.
11 US 10,196,688 B2 (issued Feb. 5, 2019).
12 US 9,377,437 B2 (issued June 28, 2016).
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(b) directing a plurality of nucleic acid molecules to
said individually addressable nanopores; and
(c) characterizing, with the aid of a processor coupled
to said chip, a nucleic acid sequence of each of
said nucleic acid molecules based on electrical
signals received from said plurality of individually
addressable nanopores.
20. A system for nucleic acid sequencing, comprising:
(a) a chip comprising a plurality of individually
addressable nanopores, an individually addressable
nanopore of said plurality of individually
addressable nanopores containing at least one
nanopore formed in a membrane disposed adjacent
to an electrode, wherein each individually
addressable nanopore is adapted to aid in the
detection of said nucleic acid molecule or a portion
thereof; and
(b) a processor coupled to said chip, wherein said
processor is programmed to aid in characterizing a
nucleic acid sequence of said nucleic acid
molecule based on electrical signals received from
said plurality of individually addressable
nanopores.
Appeal Br. 17, 19.
ANTICIPATION—NAIR
The Examiner’s Rejection
In rejecting claims 1, 2, 6, 12–21, 27–32, and 34 as anticipated by
Nair, the Examiner interpreted the “characterizing” step (c) of Appellant’s
claim 1 as encompassing Nair’s process, which determines the length of
nucleic acid sequences. See Ans. 4 (“[S]ince ‘characterizing’ a nucleic acid
sequence can be broadly interpreted to encompass determining the length (as
opposed to the base order) of a nucleic acid sequence, Nair meets this
limitation, see [Nair’s] paragraphs [0031]–[0032].”); see also Ans. 18 (citing
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Final Act.13 20–21 as providing “reasoning for such claim interpretation”);
Final Act. 21 (citing Hogan,14 Milne,15 Luo,16 and Zhang17 as evidence that a
skilled artisan would interpret characterizing a nucleic acid sequence to
encompass determining the length of the sequence).
Analysis
Appellant does not persuade us that the Examiner erred by
interpreting claim 1 as encompassing the process described in Nair.
Appellant’s claim 1 recites a process for nucleic acid sequencing.
Appeal Br. 17. Step (a) of claim 1 recites providing a chip that has a
plurality of individually addressable nanopores, with one nanopore of the
plurality being formed in a membrane adjacent to an electrode, and with
each nanopore being adapted to detect a nucleic acid molecule or a portion
thereof. See id. Step (b) of claim 1 recites directing a plurality of nucleic
acid molecules to the individually addressable nanopores. See id.
Step (c) of claim 1 recites “characterizing, with the aid of a processor
coupled to said chip, a nucleic acid sequence of each of said nucleic acid
molecules based on electrical signals received from said plurality of
individually addressable nanopores.” Appeal Br. 17.
Appellant does not dispute the Examiner’s finding that the process
described in Nair includes steps encompassed by steps (a) and (b) of claim 1.
See Appeal Br. 4–10; Reply Br. 2–5. Rather, Appellant contends that the
Examiner erred in determining that step (c) of claim 1 encompasses Nair’s

13 Final Office Action entered February 14, 2018.
14 US 6,376,186 B1 (issued Apr. 23, 2002).
15 US 2007/0248590 A1 (published Oct. 25, 2007).
16 US 2007/0048759 A1 (published Mar. 1, 2007).
17 US 2007/0015695 A1 (published Jan. 18, 2007).
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step of using its nanopore-containing chip to determine the length of
nucleotide sequences. See Appeal Br. 4–10; Reply Br. 2–5; see also Nair
¶ 31 (disclosing “a diagnostic process for high-speed sizing of elongated
elements by fabricated nanopores” in which “the elongated elements may
comprise . . . chain biomolecules mixtures like DNA [and] RNA”); Nair ¶ 33
(disclosing that apparatus may include “silicon chip[]containing an array of
individually addressable nanopores”); Nair ¶ 35 (describing use of
“processing unit” to characterize sequence length).
In particular, Appellant contends, “the only reasonable interpretation
of characterizing a nucleic acid sequence of individual nucleic acid
molecules is that an order of bases in individual nucleic acid molecules is
determined.” Appeal Br. 6 (citing 2017 Marziali Declaration 2).18
We are not persuaded. The language used by Appellant in step (c) is
does not require the claim interpretation Appellant advances. Step (c) of
claim 1 does not recite determining the order of the bases in the nucleic acid
molecules directed to the nanopores. See Appeal Br. 17. Rather, step (c)
only recites “characterizing . . . a nucleic acid sequence” of each of the
nucleotide molecules directed to the nanopores. Id. (emphasis added).
Because claim 1 does not recite determining the order of the bases in
the nucleic acid molecules directed to the nanopores, Appellant does not
persuade us that the language used in claim 1 only supports the claim
interpretation Appellant advances. See Appeal Br. 6 (“It bears emphasis that
the object of the characterization in claim 1 is not merely ‘each of said
nucleic acid molecules’ (which would include length determination, etc.),

18 Declaration of Andre Marziali, Ph.D., under 37 C.F.R. § 1.132
(declaration signed December 18, 2017).
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but rather a nucleic acid sequence of each of such nucleic acid molecules.”);
Reply Br. 3.19
We acknowledge, as Appellant contends (see Appeal Br. 5–6; Reply
Br. 2–3), that although the PTO is “required to give all claims their broadest
reasonable construction, . . . any such construction [must] be consistent with
the specification, and th[e] claim language should be read in light of the
specification as it would be interpreted by one of ordinary skill in the art.”
In re Abbott Diabetes Care Inc., 696 F.3d 1142, 1149 (Fed. Cir. 2012)
(citation omitted). “Indeed, the specification is always highly relevant to the
claim construction analysis. Usually it is dispositive; it is the single best
guide to the meaning of a disputed term.” Id. (internal quotes and citations
omitted).
In the present case, Appellant’s Specification is consistent with the
Examiner’s determination that the language at issue, “characterizing . . . a
nucleic acid sequence” of the nucleotide molecules directed to the nanopores
(Appeal Br. 17 (emphasis added)), encompasses determining the length of
the polynucleotide sequences. Specifically, the Specification discloses that
the “use of membrane channels to characterize polynucleotides as the
molecules pass through the small ion channels has been studied by
Kasianowicz . . . .” Spec. ¶ 7 (citation omitted; emphasis added).

19 The Examiner points out that, during prosecution of Akeson ’688, in
response to essentially the same rejection over Nair, Appellant’s claims
“were amended to recite ‘determining’ the nucleic acid sequence of each
nucleic acid molecule, rather than ‘characterizing’ (Appellant response of
09/30/2016), and those rejections were withdrawn (OA 01/18/2017).
Following additional amendments, the . . . application was ultimately
allowed.” Ans. 18.
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The Specification explains that Kasianowicz20 was “able to determine
experimentally lengths of polynucleotides by measuring changes in the ionic
current.” Spec. ¶ 7 (emphasis added). Thus, Appellant’s Specification uses
the same “characteriz[ing] polynucleotides” language (id.) as used in claim 1
in relation to determining the length of nucleic acid sequences. Appellant
does not persuade us, therefore, that the Examiner’s interpretation of claim 1
as encompassing Nair’s nucleic acid sequence length determination is
inconsistent with Appellant’s Specification, or unreasonable in light of the
Specification.
Indeed, Hogan’s disclosure, that a “polynucleotide sequence was
characterized by the criteria of length” (Hogan 14:65–66), is consistent with
the Specification’s use of characterizing polynucleotide sequences as
including determination of nucleic acid sequence length. Similarly, Milne’s
disclosure of “characterizing the size of nucleic acid sequences” (Milne
¶ 431) is consistent with the disclosure in Appellant’s Specification that
characterizing polynucleotide sequences encompasses determining a nucleic
acid sequence’s length.
That Hogan and Milne might ultimately be directed to applications
other than determining the order of bases in a polynucleotide does not
persuade us that Hogan and Milne fail to provide evidence that the
Examiner’s claim interpretation is not only consistent with the Specification,
but also reasonable in light of how skilled artisans use the language at issue
in Appellant’s claim 1. See Appeal Br. 7–8; Reply Br. 3–4.

20 Kasianowicz, Characterization of individual polynucleotide molecules
using a membrane channel, 93 Proc. Natl. Acad. Sci. USA 13770–73
(1996).
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We acknowledge Dr. Marziali’s statement, based on the dictionary
definitions of sequence, characterize, and character, that “[a]s a person of
skill in the art, I believe the reasonable interpretation of characterizing a
nucleic acid sequence of individual nucleic acid molecules is that the order
of bases in individual nucleic acid molecules is determined.” 2017 Marziali
Declaration 2.
However, that a skilled artisan, based on dictionary definitions, would
interpret claim 1’s characterizing step as encompassing a determination of
the order of bases in a nucleic acid sequence does not persuade us that the
broadest reasonable interpretation of claim 1, consistent with the
Specification, also encompasses determining the length of a nucleic acid
sequence, as discussed above, and as determined by the Examiner. See In re
Abbott Diabetes Care Inc., 696 F.3d at 1149 (“[T]he specification . . . is the
single best guide to the meaning of a disputed term.”) (internal quotes and
citations omitted).
In sum, for the reasons discussed, Appellant does not persuade us that
the Examiner erred in determining that claim 1, including step (c), recites a
process that encompasses the process described in Nair. We therefore affirm
the Examiner’s rejection of claim 1 as anticipated by Nair.
Turning to Appellant’s other independent claim, Appellant contends
that Nair fails to anticipate claim 20, “at least for the reasons set forth above
with respect to claim 1.” Appeal Br. 6. We are not persuaded.
Appellant’s claim 20 recites a system for nucleic acid sequencing.
Appeal Br. 19. Claim 20’s system has a first component (a), a chip that has
a plurality of individually addressable nanopores, with one nanopore of the
plurality being formed in a membrane adjacent to an electrode, and with
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each nanopore being adapted to aid in detecting a nucleic acid molecule or a
portion thereof. Id. As noted above, Appellant does not dispute that Nair
describes a chip having the features required by Appellant’s claims.
Claim 20’s system has a second component (b), “a processor coupled
to said chip, wherein said processor is programmed to aid in characterizing
a nucleic acid sequence of said nucleic acid molecule based on electrical
signals received from said plurality of individually addressable nanopores.”
Appeal Br. 19 (emphasis added).
Appellant’s claim 20, unlike claim 1 discussed above, does not require
its chip to characterize a nucleic acid sequence of a nucleic acid molecule, as
is evident. Rather, the chip of claim 20 need only “aid in characterizing a
nucleic acid sequence of said nucleic acid molecule.” Appeal Br. 19
(emphasis added).
Nair discloses that determining the length of a nucleic acid sequence
aids in determining the order of bases in that nucleic acid sequence:
[C]urrent DNA sequencing methods involve electrophoretic
separation of DNA strands of varying sizes, generated by the
well-established polymerase chain reaction (PCR) process. The
PCR process generates DNA strands of varying lengths from
the original sample, such that the length of a generated strand
reflects the identity (e.g. A, C, G or T) of the base at the
fluorescently labeled termination position. The sequencing
problem is thus reduced to size-separating (or sizing) DNA
strands.
Nair ¶ 4 (emphasis added).
Thus, determining the length of a nucleic acid sequence as described
in Nair (see Nair ¶ 31) aids in determining the order of bases in that nucleic
acid sequence, which is all that claim 20 requires of its processor.
Accordingly, even if we were to adopt Appellant’s interpretation of claim 1
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(which we do not for the reasons discussed above), Appellant does not
persuade us that the Examiner erred in finding that Nair describes a system
having all of the features required by claim 20. We therefore affirm the
Examiner’s rejection of claim 20 as anticipated by Nair. Claims 2, 6, 12–19,
21, 27–32, and 34, fall with claims 1 and 20.
OBVIOUSNESS—NAIR
The Examiner’s Rejection
In rejecting claims 3 and 5 for obviousness over Nair, the Examiner
noted the teachings in paragraphs 4 and 6 of Nair that determining a nucleic
acid sequence’s length aids in determining the order of bases in the
sequence, and reasoned as follows:
It would have been prima facie obvious to one of
ordinary skill in the art at the time the invention was made to
apply Nair’s technology to the determination of sizes of PCR
generated sequencing fragments (thus arriving at the method of
claim 3) and thereby ultimately deduce the sequence of the
original nucleic acid sample (thus arriving at the invention of
claim 5), since Nair specifically introduced his invention by
discussing this very problem (i.e. a faster way to size nucleic
acid sequencing reaction products generated by PCR), thereby
implicitly suggesting his method as a solution.
Ans. 5–6.
Analysis
In traversing the Examiner’s obviousness rejection of claims 3 and 5
over Nair, Appellant contends that “Nair fails to teach or suggest
‘characterizing ... a nucleic acid sequence of each of said nucleic acid
molecules’ - which according to its broadest reasonable interpretation -
requires determining an order of bases in such individual nucleic acid
molecules.” Appeal Br. 10.
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For the reasons discussed above, we do not find this argument
persuasive. We therefore affirm the Examiner’s rejection of claims 3 and 5
for obviousness over Nair.
OBVIOUSNESS—SU, FOLCH, AND THILL
The Examiner’s Rejections
In rejecting claims 1, 2, 5, 6, 12–21, 27–32, and 34 for obviousness
over Su and Folch, the Examiner found that Su described processes and
systems having nearly all of the features of the rejected claims, except that
[w]hile Su taught the use of multiple “chambers” (paragraph
[0019]) or “sub-devices” (paragraph [0009]), indicating that the
“apparatus” could comprise “one or more sub-devices”
(paragraph [0020]), Su did not expressly teach that the multiple
sub-devices (which make up the claimed plurality of
individually addressable nanopores) were fabricated onto a
single substrate (i.e. “chip”, as recited in claims 1 and 20).
Ans. 8.
The Examiner cited Folch as evidence that the claimed subject matter
would have been obvious, despite the difference between the rejected claims
and Su. See Ans. 8–9. In particular, the Examiner reasoned, it would have
been obvious to
fabricate the multiple “sub-devices” of Su on a single substrate
(“chip”) as de[s]cribed by Folch, since Folch taught such a
device was “cheaper and more scalable than the conventional
devices and has much higher throughput ... [i]n addition, it
requires much less expertise and operator time” (column 1,
lines 48+).
Id. at 9.
In rejecting dependent claims 3 and 4 over Su, Folch, and Thill, the
Examiner cited Thill as evidence that, when analyzing polynucleotide
sequences as taught in Su and Folch, a skilled artisan would have considered
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it obvious to cut the polynucleotide sequence into smaller fragments. Ans.
9–10.
Analysis
Appellant does not persuade us that the Examiner erred in determining
that the processes and systems recited in independent rejected claims 1 and
20 would have been obvious over Su and Folch.
As to claim 1, the Examiner found that Su’s disclosure of determining
the distance between two labeled nucleotides on a single polynucleotide
molecule was encompassed by claim 1’s “characterizing” step (c). See Ans.
7 (“The labeled nucleic acids are passed through a nanopore in [a] chamber,
and the distances between labeled nucleotides are measured to compile a
distance map (hence, characterizing a nucleic acid sequence of the
molecules).”).
As explained in Su, to determine the order of bases in a template
nucleic acid sequence, copies of the template sequence are placed into four
different chambers containing a different labeled nucleotide, A, G, C, and T
or U. Su ¶ 19. Labeled nucleic acid strands complementary to the template
are then generated, and the labeled strands are then passed through
nanopores which can optically or electrically detect the labeled nucleotides,
thereby determining the distance between the labeled nucleotides on the
individual strands. See id. ¶¶ 19–21. The compiled “distance maps”
generated by characterizing the individual nucleic acid sequences “are used
to identify . . . or sequence . . . the template nucleic acid.” Id. ¶ 19; see also
id. ¶ 22 (“Signals detected by the electrical detector 345 may be processed
and/or stored by a computer 340. Distance maps 140 between labeled
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nucleotides 315 may be compiled and the nucleic acid 310 sequenced 150
and/or identified 160.”)
Appellant contends that, because Su requires reconstruction of
distance maps from multiple molecules labeled at different bases to arrive at
a consensus sequence, “Su does not describe determining an order of bases
of individual nucleic acid molecules, such that Su fails to teach or suggest
this feature of claims 1 and 20.” Appeal Br. 11.
As discussed above, however, Appellant does not persuade us that the
broadest reasonable interpretation of claim 1, consistent with Appellant’s
Specification, requires a determination of the order of the bases in the
analyzed nucleic acid sequence. We are not persuaded, therefore, that claim
1’s characterizing step (c) fails to encompass Su’s characterization of the
distance between labeled nucleotides in a nucleic acid sequence. See Su
¶ 19.
As to Appellant’s claim 20, as also discussed above, claim 20 does not
recite characterizing a nucleic acid sequence, but instead only requires a
processor programmed to aid in characterizing a nucleic acid sequence. See
Appeal Br. 19. Because Su’s processor-assisted determination of the
distance between labeled nucleotides aids in determining the order of bases
in a nucleic acid molecule (see Su ¶ 22), we are not persuaded that Su fails
to describe a processor having the features of step (b) of Appellant’s claim
20.
Appellant also contends that Folch does not describe determining the
order of bases in a nucleic acid molecule. See Appeal Br. 11 (citing 2016
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Marziali Declaration).21 As noted above, however, the Examiner relies on
Su, not Folch, as describing characterizing step (c) of Appellant’s claim 1
and the processor (b) of claim 20. See Ans. 7.
Appellant contends that a skilled artisan lacked motivation for
combining Su and Folch because making the combination would have
resulted in an inoperable device. Appeal Br. 11–12. In particular, Appellant
contends,
given the geometries disclosed by Su and Folch - it would not
be possible to combine the disclosures therein to arrive at an
operable device. Any parallelization of Su would require
completely different devices to allow the photon detection
and/or the electrodes to address and measure the nanopores
individually. Fabricating multiple elements of Su “on a single
substrate” would lead to electrical dependence of all the pores,
or of mixing of multiple pore optical signals, depending on the
method used.
Appeal Br. 11–12 (citing the 2016 Marziali Declaration).
We are not persuaded. Appellant’s conclusory assertions and Dr.
Marziali’s supporting statements do not include any specific evidence-based
explanation as to why the geometries of Su’s nucleic acid analyses and
Folch’s chip are incompatible, nor does Appellant explain specifically why
performing Su’s four nanopore analyses (see Su ¶ 19) on Folch’s chip would
necessarily lead to unacceptable electrical dependence and signal mixing
between the pores. Indeed, contrary to Appellant’s contentions and Dr.
Marziali’s statements, Folch states expressly that its chips may be used to
perform multiple parallel analyses, including nucleic acid sequence analysis:

21 Declaration of Dr. Andre Marziali under 37 C.F.R. § 1.132 (declaration
signed December 20, 2016).
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The lab-on-a-chip device described here is a new
generation cell culture tool that allows the interrogation of large
number of single cells simultaneously. The device enables
parallel electrophysiological measurements, such as measuring
ion currents through ion channels residing in the plasma
membrane, as well as delivery of key biochemical factors to
multiple cells with a very high precision. To achieve this, an
array of very small holes is created on a thin transparent
membrane of silicon nitride or silicon oxide that is suspended
on an array of wells through a silicon wafer. . . . The device is
useful for a number of other applications, such as high-
throughput screening for drug discovery, immunoisolation of
cells, cell filtration and separation, biomolecular separation, and
protein and DNA sequencing.
Folch 1:62–2:21 (emphasis added).
And, as the Examiner found, Folch discloses specific advantages to
using its chip to perform parallel analyses as required in the methods of Su,
including the fact that it is “cheaper and more scalable than the conventional
devices and has much higher throughput. It can be automated and do
parallel analysis on multiple cells simultaneously. In addition, it requires
much less expertise . . . .” Folch 1:49–52.
Given the teachings in Folch, Appellant does not persuade us that the
Examiner erred in finding that a skilled artisan had motivation for
performing Su’s assays in a parallel manner on Folch’s chip. Accordingly,
for the reasons discussed above, Appellant does not persuade us that the
Examiner erred in concluding that a skilled artisan would have considered
the process of Appellant’s claim 1, and the system of Appellant’s claim 20,
obvious in view of Su and Folch. We therefore affirm the Examiner’s
rejection of claims 1 and 20 over Folch. Claims 2, 5, 6, 12–19, 21, 27–32,
and 34 fall with claims 1 and 20.
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In traversing the Examiner’s rejection of claims 3 and 4 over Su,
Folch, and Thill, Appellant relies on its arguments against the combination
of Su and Folch, discussed above. See Appeal Br. 12. As discussed above,
we do not find those arguments persuasive. We therefore affirm the
Examiner’s rejection of claims 3 and 4 over Su, Folch, and Thill.
OBVIOUSNESS—LING AND TOM-MOY
The Examiner’s Rejection
In rejecting claims 1, 2, 6, 12–21, and 27–32 for obviousness over
Ling and Tom-Moy, the Examiner found that Ling described chip-based
processes and systems for nucleic acid sequence analysis having nearly all of
the features of the rejected claims, except that “Ling did not teach using a
processor coupled to the chip.” Ans. 11.
The Examiner cited Tom-Moy as evidence that the claimed subject
matter would have been obvious, despite the difference between the rejected
claims and Ling. See Ans. 11–12. In particular, the Examiner concluded
that it would have been obvious to
modify the method of Ling by coupling a processor to the chip
since Tom-Moy demonstrates it was known in the art at the
time to couple a processor to a nanopore via a detector in order
to directly receive the signal resulting from passage of a nucleic
acid through the nanopore in order to analyze the data.
Id. at 12.
In particular, the Examiner reasoned that modifying Ling in the
posited manner would have
conferred an advantage over a process wherein the signals were
recorded and/or analyzed by (or transferred to a processor by),
say, a human being, since it would have been faster for a
processor to directly receive the data, and would have allowed
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said human being to do other work. In addition, the possibility
of human error would have been avoided.
Id.
Analysis
Appellant does not persuade us that the Examiner erred in determining
that the processes and systems recited in Appellant’s claims 1, 2, 6, 12–21,
and 27–32 would have been obvious over Ling and Tom-Moy.
Ling discloses “nanopore and micropore devices used for detecting,
and characterizing biomolecules, as well as sequencing nucleic acids, and
new methods for fabrication and application thereof.” Ling ¶ 2.
Paragraphs 46–47 of Ling describe the construction and operation of
the embodiment of the device shown in Ling’s Figure 4, which the Examiner
cited as having the features of the chip recited in Appellant’s claims. See id.
¶¶ 46–47; see also Ans. 10 (citing “overall device 400 of [F]igure 4”).
In relation to the device shown in Figure 4, Ling discloses that
“[w]hen a voltage is applied between 406 and 408, DNA or RNA molecules
can flow through the nanopore defined by two crossing V-grooves, and their
movement is recorded as reduction of the ionic current in the corresponding
nanopore as known in the art.” Ling ¶ 47 (emphasis added).
Contrary to Appellant’s contentions (see Appeal Br. 12) and the
statements in the 2016 Marziali Declaration (see 2016 Marziali Declaration
17) that Ling “nowhere” describes how to characterize nucleic acid
sequences using its device, Ling describes two specific prior art methods by
which its nanopores may be used to characterize nucleic acids:
For the applications of DNA sequencing, two prior art
methods have been proposed using nanopores. U.S. Pat. No.
5,795,782, issued to Church et al. discloses a method of reading
DNA sequence by detecting the ionic current variations as a
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single-stranded DNA molecule moving through the nanopore
under a bias voltage.
Another method for DNA sequencing using nanopores
was discussed in U.S. Pat. No. 6,537,755, issued to Drmanac.
Drmanac proposes to use nanopores to detect the DNA
hybridization probes (oligonucleotides) on a DNA molecule
and recover the DNA sequence information using the method of
Sequencing-By-Hybridization (SBH).
Ling ¶¶ 4–5.
Given Ling’s disclosure of specific prior art methods of using
nanopores to characterize nucleic acid sequences, Appellant does not
persuade us that Ling “nowhere” describes how to characterize nucleic acid
sequences using its device. Appeal Br. 12.
We are also unpersuaded by Appellant’s contention that Tom-Moy
“fails to recognize the challenges, let alone provide any guidance as to how,
e.g., translocation rate could be sufficiently controlled to enable
characterization of nucleic acid sequences of individual nucleic acid
molecules.” Appeal Br. 13. Absent some discussion of the particular
disclosures in Tom-Moy identified by the Examiner as describing the use of
a processor in nanopore-based nucleic acid sequence analysis, and a specific
explanation based on evidence or scientific reasoning as to why Tom-Moy
lacks enablement as to those disclosures, Appellant’s conclusory assertion of
lack of enablement is unpersuasive of Examiner error. See e.g., Amgen, Inc.
v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1354 (Fed. Cir. 2003)
(holding that a patent cited as prior art is presumed enabling); In re Morsa,
713 F.3d 104, 110 (Fed. Cir. 2013) (noting the presumption in Amgen
applies to publications as well, and explaining that to rebut the presumption,
an applicant “must generally do more than state an unsupported belief that a
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reference is not enabling, and may proffer affidavits or declarations in
support of his position” unless the “reference appears to not be enabling on
its face”).
Appellant contends that the 2016 Marziali Declaration provides
“[f]urther details” showing that Ling and Tom-Moy do not enable
characterization of nucleic acid sequences. Appeal Br. 13. As explained in
37 C.F.R. § 41.37(c)(1)(iv), however, except in certain circumstances not
applicable here, “any arguments or authorities not included in the appeal
brief will be refused consideration by the Board for purposes of the present
appeal.” Thus, to the extent that the 2016 Marziali Declaration might
provide arguments and evidence not included in Appellant’s briefs, we do
not consider such arguments.
In sum, for the reasons discussed, Appellant does not persuade us that
the Examiner erred in determining that the processes and systems recited in
Appellant’s claims 1, 2, 6, 12–21, and 27–32 would have been obvious over
Ling and Tom-Moy. We therefore affirm the Examiner’s rejection of those
claims over those references.
DOUBLE PATENTING—CHEN ’854
The Examiner’s Rejections
The Examiner rejected claims 1–6, 12–21, 27–32, and 34 under 35
U.S.C. § 101 as claiming the same invention as that of claims 1–6, 12–21,
27–32, and 34, of Chen ’854. Ans. 12–13. The Examiner explained that
“[t]his is a statutory double patenting rejection. This rejection is based on a
common inventor between the instant application and the [Chen] ’854
patent.” Id. at 13.
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The Examiner rejected claims 7–9 and 22–24 on the ground of
nonstatutory obviousness-type double patenting as being unpatentable over
claims 7–9 and 22–24 of Chen ’854. Ans. 13–14. The Examiner explained
that the ranges of the parameters recited in the rejected claims overlap the
ranges of the same parameters recited in the conflicting claims of the ’854
patent, thereby rendering the subject matter of the rejected claims obvious in
view of the conflicting claims of the ’854 patent. Id.
The Examiner rejected claims 10, 11, 25, and 26 on the ground of
nonstatutory obviousness-type double patenting as being unpatentable over
claims 10, 11, 25, and 26 of Chen ’854 in view of Akeson ’594. Ans. 14–
15. The Examiner determined that, based on teachings in Akeson ’594, the
subject matter recited in rejected claims 10, 11, 25, and 26 would have been
obvious variations of the subject matter recited in the conflicting claims in
Chen ’854. See id.
Analysis
Appellant does not assert error in, or contest the merits of, any of the
double patenting rejections based on Chen ’854. Rather, Appellant contends
that it timely copied the claims of Chen ’854, and therefore that “the
appropriate action to be taken by the Board is to reverse the double patenting
rejections based on the [Chen] ’854 patent and declare an interference
between the instant application and the [Chen] ’854 patent.” Appeal Br. 15.
We are not persuaded. As seen in the discussions above and below,
none of the claims rejected for double patenting over Chen ’854 have been
held to be otherwise patentable. An interference, therefore, would not be
proper. See Manual of Patent Examining Procedure (MPEP) § 2303 (9th
ed., Rev. 08.2017, Jan. 2018); 37 C.F.R. § 41.102. Accordingly, because
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Appellant does not identify, nor do we discern error in, the Examiner’s
determinations that Appellant’s claims are unpatentable for either same-
invention statutory double patenting or obviousness-type double patenting
over Chen ’854, we affirm each of the Examiner’s double patenting
rejections based on Chen ’854.
DOUBLE PATENTING—
THE ’315 APPLICATION (NOW AKESON ’688)
The Examiner’s Rejections
The Examiner rejected claims 1–8, 10, 12–23, 25, 27–32, and 34 on
the ground of obviousness-type nonstatutory double patenting over claims
1–8, 9, 10–21, 22, 23–28, and 30, of the ’315 Application. Ans. 15–16.
The Examiner reasoned that, although the conflicting claims of the
’315 Application were not identical to the rejected claims, the conflicting
claims of the ’315 Application are species of the rejected claims, and
therefore anticipate the rejected claims. See Ans. 15. Therefore, the
Examiner reasoned,
per MPEP 806.04(i), if a generic claim is presented in a
separate application after the issuance of a patent claiming one
or more species within the scope of the generic claim, the
Office may reject the generic claim on the grounds of
nonstatutory double patenting when the patent and application
have at least one common inventor.
Id. at 15–16.
The Examiner also rejected claims 9, 11, 24, and 26 for obviousness-
type double patenting as being unpatentable over claims 8, 9, 21, and 22 of
the ’315 Application in view of Su. Ans. 16. The Examiner determined
that, based on the teachings in Su, the subject matter recited in rejected
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claims 9, 11, 24, and 26 would have been obvious variations of the subject
matter recited in the conflicting claims in the ’315 Application. See id.
Analysis
As noted above, the ’315 Application issued as Akeson ’688. See
Akeson ’688 front page. The Examiner finds that the issued claims of
Akeson ’688 render obvious the conflicting claims of the present application
for the same reasons as the claims of the ’315 Application on which the
double patenting rejection was originally based. See Ans. 22 (“The claims
of the allowed ’315 application [Akeson ’688] meet the limitations of the
instant claims (being more specific than the generic limitations of the instant
claims), and thus render the instant claims obvious. It is immaterial that the
’315 claims have been allowed.”).
Appellant contends that, because the claims of the ’315 Application
were amended before allowance to recite a number of additional features not
present in the claims of the present application, the Examiner erred in
rejecting the claims of the present application over Akeson ’688. Appeal Br.
13–14. Appellant contends:
In allowing the claims of the ’315 application, the Examiner
acknowledged that the pending claims of the ’315 application
and the pending claims of the instant application are patentably
distinct. Reversal of the present rejection is respectfully
requested at least for the reasons that prompted the Examiner to
withdraw the corresponding rejection in the ’315 application.
Id.; see also Reply Br. 6 (contending that the “double patenting rejections
should be reversed at least for the reasons set forth in the Appeal Brief” but
“nonetheless not[ing] willingness to file a terminal disclaimer over the
[Akeson] ’688 patent”).
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Appellant does not persuade us that the Examiner erred in determining
that claims 1–8, 10, 12–23, 25, 27–32, and 34 are unpatentable for
obviousness-type double patenting over claims 1–8, 9, 10–21, 22, 23–28,
and 30 of Akeson ’688. Nor does Appellant persuade us that the Examiner
erred in determining that claims 9, 11, 24, and 26 are unpatentable for
obviousness-type double patenting over claims 8, 9, 21, and 22 of Akeson
’688 in view of Su.
Claim 1 of the present application is representative of the claims
subject to the first double patenting rejection based on Akeson ’688.
Although not worded precisely identically, claim 1 of Akeson ’688
recites a step (a) of providing a chip with a plurality of nanopores having the
same features as recited in step (a) of claim 1 of the present application.
Compare Akeson ’688, 63:61–67 to Appeal Br. 17.
Step (b) of claim 1 of the present application recites “directing a
plurality of nucleic acid molecules to said individually addressable
nanopores.” Appeal Br. 17.
Corresponding step (b) of claim 1 of Akeson ’688 recites “providing a
plurality of processive enzyme-nucleic acid molecule complexes to
nanopores of said individually addressable elements.” Akeson ’688, 64:1–3.
Thus, although step (b) of claim 1 of Akeson ’688 recites directing a specific
type of nucleic acid molecule to its nanopores, step (b) of claim 1 of Akeson
’688 nonetheless has all of the features required by step (b) of claim 2 of the
present application.
Step (c) of claim 1 of the present application recites “characterizing,
with the aid of a processor coupled to said chip, a nucleic acid sequence of
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each of said nucleic acid molecules based on electrical signals received from
said plurality of individually addressable nanopores.” Appeal Br. 17.
Corresponding step (d) of Akeson ’688 recites, in relevant part
“determining, with the aid of a processor coupled to said chip, a nucleic acid
sequence of nucleic acid molecules of said processive enzyme-nucleic acid
molecule complexes based on current signals received from individually
addressable elements of said plurality of individually addressable elements.”
Akeson ’688, 64:6–11. Thus, as required by step (c) of claim 1 of the
present application, step (d) of Akeson ’688 recites a processor-aided
characterization of nucleic acid molecules based on electrical signals from
the nanopores.
Because claim 1 of Akeson ’688, thus, recites a process that includes
all of the steps and features of claim 1 of the present application, we discern
no error in the Examiner’s determination that claim 1 of Akeson ’688
anticipates claim 1 of the present application, despite the fact that claim 1 of
Akeson ’688 contains additional elements, and despite the fact that claim 1
of Akeson ’688 recites a number of the shared elements more specifically
than recited in claim 1 of the present application.
Because claim 1 of Akeson ’688, therefore, is a species that
anticipates the genus recited in claim 1 of the present application, we agree
with the Examiner that claim 1 of the present application is unpatentable for
obviousness-type double patenting over claim 1 of Akeson ’688. See In re
Hubbell, 709 F.3d 1140, 1145 (Fed. Cir. 2013) (The doctrine of
obviousness-type double patenting “prohibits the issuance of claims in a
second patent that are not patentably distinct from the claims of the first
patent. A later patent claim is not patentably distinct from an earlier claim if
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the later claim is obvious over, or anticipated by, the earlier claim.”)
(emphasis added; internal quotations and citations removed).
The fact that the Examiner determined that claim 1 of Akeson ’688 is
unobvious over the claims of the present application (see Appeal Br. 13–14)
does not negate the fact that claim 1 of the present application is anticipated
by, and therefore unpatentably obvious over, claim 1 of Akeson ’688. See In
re Hubbell, 709 F.3d at 1145; see also MPEP § 806.04(i) (generic claim in
application may be rejected for nonstatutory double patenting over patented
species claim when patent and application have at least one common
inventor).
In sum, for the reasons discussed, we affirm the Examiner’s rejection
of claim 1 of the present application for obviousness-type double patenting
over claim 1 of Akeson ’688. Claims 2–8, 10, 12–23, 25, 27–32, and 34 fall
with claim 1.
Appellant does not assert, nor do we discern, error in the Examiner’s
determination that claims 9, 11, 24, and 26 of the present application are
obvious variations of claims 8, 9, 21, and 22 of Akeson ’688 in view of Su.
We therefore affirm the Examiner’s rejection of claims 9, 11, 24, and 26 of
the present application for obviousness-type double patenting over claims 8,
9, 21, and 22 of Akeson ’688 in view of Su.
DOUBLE PATENTING—CHEN ’437
The Examiner’s Rejection
In rejecting claims 1, 2, and 20, for obviousness-type double patenting
over claims 3 and 8 of Chen ’437, the Examiner determined that claims 3
and 8 of Chen ’437 “recite all the limitations of instant claims 1 and 20,
respectively, other than ‘characterizing a nucleic acid sequence’ (rather, the
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’437 claims recite ‘analyzing’ nucleic acid molecules. Note that with regard
to instant claim 2, nucleic acid molecules would inherently derive from a
‘nucleic acid sample.’” Ans. 17.
The Examiner reasoned that, “[i]n order to understand what
‘analyzing’ nucleic acid molecules means in the ‘437 patent, the
specification of the ’437 patent clearly indicates sequencing. Since
‘sequencing’ is one way of ‘characterizing’ a nucleic acid sequence,
‘characterizing’ is obvious over ‘analyzing.’” Ans. 17.
Analysis
Appellant does not persuade us that the Examiner erred in determining
that claims 1, 2, and 20, are unpatentable for obviousness-type double
patenting over claims 3 and 8 of Chen ’437.
Appellant argues that the Office has conceded that claims 1, 2, and 20
of the present application are patentably distinct from the claims of Chen
’437 because no obviousness-type double patenting rejection was made over
Chen ’854 (which has claims identical to the presently rejected claims)
during prosecution of Chen ’437, and because, in prosecuting Chen ’437, the
Examiner withdrew an obviousness-type double patenting rejection over the
claims of the present application. See Appeal Br. 14–15 (“As such, the
Office has already twice made the determination that the claims of the ’437
patent and the claims of the instant application (which were copied from the
’854 patent) are patentably distinct.”). Appellant, however, identifies no
authority mandating that withdrawing or failing to make an obviousness-
type double patenting rejection over a conflicting previous or copending
application prohibits entering an obviousness-type double patenting rejection
after the conflicting application issues as a patent.
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Appellant, moreover, does not dispute or assert error in the
Examiner’s determination that claims 1, 2, and 20 of the present application
would have been obvious over claims 3 and 8 of Chen ’437. Because claims
1, 2, and 20 of the present application undisputedly would have been
obvious over claims 3 and 8 of Chen ’437, we affirm the Examiner’s
obviousness-type double patenting rejection of claims 1, 2, and 20 of the
present application over claims 3 and 8 of Chen ’437. See In re Hubbell,
709 F.3d at 1145 (The doctrine of obviousness-type double patenting
“prohibits the issuance of claims in a second patent that are not patentably
distinct from the claims of the first patent. A later patent claim is not
patentably distinct from an earlier claim if the later claim is obvious over, or
anticipated by, the earlier claim.”) (emphasis added; internal quotations and
citations removed).

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 2, 6,
12–21,
27–32, 34
102(e) Nair 1, 2, 6, 12–
21, 27–32, 34

3, 5 103(a) Nair 3, 5
1, 2, 5, 6,
12–21,
27–32, 34
103(a) Su, Folch 1, 2, 5, 6, 12–
21, 27–32, 34

3, 4 103(a) Su, Folch, Thill 3,4
1, 2, 6,
12–21,
27–32
103(a) Ling, Tom-Moy 1, 2, 6, 12–
21, 27–32

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1–6, 12–
21, 27–
32, 34
101
(Statutory
Double
Patenting)
Chen ’854 1–6, 12–21,
27–32, 34

7–9, 22–
24
Obviousness-
Type Double
Patenting
Chen ’854

7–9, 22–24
10, 11,
25, 26
Obviousness-
Type Double
Patenting
Chen ’854,
Akeson ’594
10, 11, 25, 26
1–8, 10,
12–23,
25, 27–
32, 34
Obviousness-
Type Double
Patenting
Akeson ’688 1–8, 10, 12–
23, 25, 27–
32, 34

9, 11, 24,
26
Obviousness-
Type Double
Patenting
Akeson ’688, Su 9, 11, 24, 26
1, 2, 20 Obviousness-
Type Double
Patenting
Chen ’437 1, 2, 20
Overall
Outcome
1–32, 34

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED