Oxford Nanopore Technologies Ltd.v.University of Washington

Patent Trial and Appeal Board

Feb 26, 2016

13069187 (P.T.A.B. Feb. 26, 2016)

Trials@uspto.gov
571-272-7822
Paper No. 51
Date Entered: February 26, 2016

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

OXFORD NANOPORE TECHNOLOGIES LTD.,
Petitioner,
v.
UNIVERSITY OF WASHINGTON and
UAB RESEARCH FOUNDATION,
Patent Owners.
_______________

Case IPR2014-005131
Patent 8,673,550 B2
_______________

Before FRANCISCO C. PRATS, JACQUELINE WRIGHT BONILLA, and
SHERIDAN K. SNEDDEN, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

FINAL WRITTEN DECISION
35 U.S.C. § 318(a) and 37 C.F.R. § 42.73

1 Case IPR2015-00057 has been joined with this proceeding.
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I. INTRODUCTION
A. Statement of the Case
In this Final Written Decision, we address the patentability of three
claims, i.e., claims 10, 17, and 18, in U.S. Patent No. 8,673,550 B2 (Ex.
1001, “the ’550 patent”).
As background, Oxford Nanopore Technologies Ltd. (“Petitioner”)
filed a first Petition (Paper 1, “Pet.”) requesting inter partes review of claims
1, 5, 6, 10–13, 16, 17, 18, 19, 23, 24, 25, 29–31 and 34–41 of the ’550
patent. The University of Washington and UAB Research Foundation
(collectively, “Patent Owner”) filed a Preliminary Response. Paper 10
(“Prelim. Resp.”).
Upon review of those papers and cited information, we instituted trial
as to two anticipation grounds presented by Petitioner in relation to claims 1,
5, 6, 10–12, 16–19, 23, 25, 29, 30, 34, 37, and 41 of the ’550 patent. Paper
12, 29 (“Decision to Institute,” or “Dec.”).
After we instituted trial, Petitioner filed a second Petition for inter
partes review of the same claims subject to review in the first case.
IPR2015-00057, Paper 1 (“Supplemental Petition” or “Supp. Pet.”).2
Petitioner also timely filed a motion seeking joinder of IPR2015-00057 with
the instant proceeding. IPR2015-00057, Paper 3. In the second case, we
instituted trial as to one obviousness ground presented by Petitioner in
relation to claim 10 only, and joined IPR2015-00057 with the instant
proceeding. Paper 28, 28.

2 Petitioner entered the Supplemental Petition into the proceeding as Exhibit
1059.
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Thereafter, Patent Owner filed a Response (Paper 16; “PO Resp.”),
and Petitioner filed a Reply (Paper 26, “Reply”) in relation to instituted
grounds in the first proceeding. In addition to its Response, Patent Owner
filed a non-contingent Motion to Amend the ’550 patent, cancelling all
challenged claims except for claims 10, 17, and 18. Paper 17, 1–3.
In addition, after IPR2015-00057 was joined to the instant proceeding,
Patent Owner filed a Supplemental Response (Paper 32, “Supp. Resp.”), and
Petitioner filed a Supplemental Reply (Paper 35, “Supp. Reply”) in relation
to the instituted obviousness ground.
Patent Owner subsequently filed a Motion to Exclude Evidence
(Paper 39, “Mot. to Exclude”), Petitioner filed an Opposition to that Motion
(Paper 44, “Opp.”), and Patent Owner filed a Reply to that Motion (Paper
47, “Reply Opp.).
Patent Owner also filed a Motion for Observations on Cross
Examination (Paper 40, “Mot. Obs.”), and Petitioner filed an Opposition to
that Motion (Paper 46, “Opp. Mot. Obs.”).
Oral Hearing was held on December 3, 2015, in relation to the joined
proceedings and the Hearing Transcript has been entered in the record.
Paper 49 (“Tr.”).
In light of Patent Owner’s Motion to Amend, the joinder of IPR2015-
00057 to the instant proceeding, and the record developed during trial, the
following asserted grounds of unpatentability are before us for review:
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(1) Claim 10, under 35 U.S.C. § 102(b),3 for anticipation by Butler;4
(2) Claims 17 and 18, under 35 U.S.C. § 102(b), for anticipation by
the Wong Poster;5
(3) Claims 17 and 18, under 35 U.S.C. § 102(b), for anticipation by
the Wong Abstract;6 and
(4) Claim 10, under 35 U.S.C. § 103(a), for obviousness over the ’782
patent7 and Butler.
We have jurisdiction under 35 U.S.C. § 6(c). This Final Written
Decision is entered pursuant to 35 U.S.C. § 318(a). “In an inter partes
review instituted under this chapter, the petitioner shall have the burden of

3 The application which issued as the ’550 patent was filed on March 22,
2011. Ex. 1001, cover page. Accordingly, the versions of §§ 102 and 103 in
effect before the Leahy-Smith America Invents Act (“AIA”) apply to the
claims of the ’550 patent. See AIA, Public Law 112–29 § 3, 125 Stat. 288.
4 Thomas Butler, Nanopore Analysis of Nucleic Acids (2007) (Ph.D.
dissertation, University of Washington, Seattle, Washington) (Ex. 1003)
(“Butler”).
5 Risa Wong, Engineering Mycobacterium smegmatis Porin A (MspA) for
DNA Analysis, University of Washington Summer Research Poster Session,
pamphlet cover, program description, schedule of events, poster, and
abstract (August 16, 2007) (Ex.1008).
6 Although Petitioner presented the Wong Poster and the Wong Abstract in a
single Exhibit (Ex. 1008), which is designated collectively as “Wong” in our
first Institution Decision (Paper 12, 3), Patent Owner contends that the
Poster and Abstract “are in fact separate and distinct from each other.” PO
Resp. 10 (citing Ex. 2004 ¶ 6 (Declaration of Jennifer Harris; Declaration
executed Dec. 8, 2014) (“Harris Declaration” or “Harris Decl.”)). Petitioner
does not dispute Patent Owner’s contention. See Reply 7–15. We,
therefore, evaluate the Wong Poster and Wong Abstract separately.
7 George Church et al., U.S. Patent No. 5,795,782 (issued Aug. 18, 1998)
(Ex. 1024) (“ the ’782 patent”).
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proving a proposition of unpatentability by a preponderance of the
evidence.” 35 U.S.C. § 316(e).
We conclude that Petitioner has not proved by a preponderance of the
evidence that claim 10 of the ʼ550 patent is anticipated by Butler under 35
U.S.C. § 102(b).
We conclude that Petitioner has not proved by a preponderance of the
evidence that claims 17 and 18 are anticipated by the Wong Poster under 35
U.S.C. § 102(b).
We conclude that Petitioner has not proved by a preponderance of the
evidence that claims 17 and 18 are anticipated by the Wong Abstract under
35 U.S.C. § 102(b).
We conclude that Petitioner has proved by a preponderance of the
evidence that claim 10 is unpatentable for obviousness over the ’782 patent
and Butler under 35 U.S.C. § 103(a).
Patent Owner’s Motion to Amend is granted.
Patent Owner’s Motion to Exclude Evidence is denied.
B. Related Proceedings
Concurrently with the first Petition filed in the instant proceeding,
Petitioner filed another Petition advancing additional challenges to the
claims of the ’550 patent. Pet. 1; IPR2014-00512. No trial was instituted in
IPR2014-00512. IPR2014-00512, Paper 12.
C. The ’550 patent
The ’550 patent discloses using a “Mycobacterium smegmatis porin
(Msp)” to detect analytes in liquid media. Ex. 1001, 7:54–8:55. The ’550
patent explains that a porin is a tunnel-forming protein through which
nutrients pass in living mycobacteria. Id. at 7:53–55, 18:32–58. Wild-type
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M. smegmatis porins include “MspA,” “MspB,” “MspC”, and “MspD.” Id.
at 18:59–61. The ’550 patent discloses that the tunnel of an Msp porin has a
“goblet” shape, which includes two sections, a cone-shaped “vestibule,” and
a narrower “constriction zone.” Id. at 27:9–16; Fig. 1.
As to its analytical methods, the ’550 patent explains that, when an
Msp porin is placed in a lipid bilayer that separates first and second
conductive liquid media, application of an electrical field can cause an
analyte to be driven into, and/or through, the porin. Id. at 7:53–8:16. The
’550 patent explains:
The electric field moves an analyte such that it interacts with
the tunnel. By “interacts,” it is meant that the analyte moves
into and, optionally, through the tunnel, where “through the
Msp tunnel” (or “translocates”) means to enter one side of the
tunnel and move to and out of the other side of the tunnel.

Id. at 28:1–6.
The analyte may be detected by “measuring an ion current as the
analyte interacts with an Msp porin tunnel to provide a current pattern,
wherein the appearance of a blockade in the current pattern indicates the
presence of the analyte.” Id. at 8:13–16. A “‘blockade’ is evidenced by a
change in ion current that is clearly distinguishable from noise fluctuations
and is usually associated with the presence of an analyte molecule at the
pore’s central opening.” Id. at 33:38–41. “More particularly, a ‘blockade’
refers to an interval where the ionic current drops below a threshold of about
5–100% of the unblocked current level, remains there for at least 1.0 µs, and
returns spontaneously to the unblocked level.” Id. at 33:43–46.
The ’550 patent discloses that “an analyte may be a nucleotide, a
nucleic acid, an amino acid, a peptide, a protein, a polymer, a drug, an ion, a
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pollutant, a nanoscopic object, or a biological warfare agent. Optionally, an
analyte is a polymer, such as a protein, a peptide, or a nucleic acid.” Id. at
8:45–49.
The ’550 patent discloses that the negatively charged amino acids in
the tunnel of the wild-type MspA were thought to inhibit the entry of
negatively charged DNA into the porin. Id. at 42:15–19. Thus, the ’550
patent describes embodiments of mutant porins in which negative amino
acids in the constriction zone, vestibule, and around the entrance of wild-
type MspA, are replaced with positively charged residues, so as to allow
more optimal translocation of single-stranded DNA through the mutated
porin. Id. at 42:19–22, 45:45–46:13.
Claims 1, 10, 17, and 18, recite the subject matter under consideration
herein, and read as follows:

1. A method for detecting the presence of an
analyte, comprising:

applying an electric field sufficient to translocate
an analyte from a first conductive liquid
medium to a second conductive liquid
medium in liquid communication through a
Mycobacterium smegmatis porin (Msp)
having a vestibule and a constriction zone
that define a tunnel; and

measuring an ion current, wherein a 5% or more
reduction in the ion current for at least 1.0
µs compared to an ion current level for the
Msp without an analyte present indicates the
presence of the analyte in the first medium.

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10. The method of claim 1, wherein at least one of
the first or second conductive liquid media comprises a
plurality of different analytes.

17. A system comprising a Mycobacterium
smegmatis porin (Msp) having a vestibule and a
constriction zone that define a tunnel,

wherein the tunnel is positioned between a first
conductive liquid medium and a second
conductive liquid medium allowing liquid
communication between the first and second
conductive liquid media,

wherein at least one conductive liquid medium
comprises an analyte, and

wherein the system is operative to detect the
analyte when the system is subjected to an
electric field sufficient to translocate the
analyte from one conductive liquid medium
to the other.

18. The system of claim 17, wherein the Msp is a
mutant comprising at least a first mutant MspA
monomer.

II. ANALYSIS
A. Claim Construction
The Board interprets claims in an unexpired patent using the “broadest
reasonable construction in light of the specification of the patent in which
[they] appear[].” 37 C.F.R. § 42.100(b); In re Cuozzo Speed Tech., LLC,
793 F. 3d 1268, 1275 (Fed. Cir. 2015), cert. granted sub nom. Cuozzo Speed
Techs., LLC v. Lee, 84 U.S.L.W. 3218 (U.S. January 15, 2015) (No. 15-
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446). Under that standard, the Board applies to claim terms their ordinary
and customary meaning, as would be understood by one of ordinary skill in
the art in the context of the entire disclosure. In re Translogic Tech. Inc.,
504 F.3d 1249, 1257 (Fed. Cir. 2007).
1. “electric field sufficient to translocate an analyte”
Challenged claim 10 of the ’550 patent depends from now-canceled
claim 1, which requires “applying an electric field sufficient to translocate
an analyte from a first conductive liquid medium to a second conductive
liquid medium in liquid communication through a Mycobacterium
smegmatis porin (Msp) having a vestibule and a constriction zone that define
a tunnel.” Ex. 1001, 104:40, 103:35–39. Claim 17 includes similar
language. Id. at 105:22–23.
Petitioner contends that this language does not require the analyte to
be actually translocated from the first medium to the second medium. Pet.
17–19.
As we note in our Decision to Institute (Dec. 8–9), however, the
express language in claims 1 and 17 requires applying an electric field
sufficient to translocate an analyte from a first medium to a second medium,
and the Specification of the ’550 patent explains that translocate means to
move into and out of the other side of the tunnel. Ex. 1001, 28:4–6.
Accordingly, we construe claims 1 and 17 as requiring that an analyte, if
present, must translocate, that is, move, from the first medium through the
Msp porin to the second medium, when the electric field is applied.
2. “analytes”
Claim 10 recites that “at least one of the first or second conductive
liquid media comprises a plurality of different analytes.” Ex. 1001, 104:39–
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41. In our Decision to Institute, we concluded that, when giving claim 10 its
broadest reasonable construction consistent with the Specification of the
’550 patent, the term “analyte” or “analytes” encompasses any compound
detectable by the methods recited in the claims. Dec. 8–9.
Patent Owner contends that, viewing the plain language of claim 10
and its antecedent claim 1 in light of the Specification of the ’550 patent, the
term “analyte” does not reasonably encompass the ions that form the ion
current measured in the claimed analyte detection process, because those
ions are not detectable by the claimed methods. PO Resp. 2–7.
Petitioner contends that, because the Specification states that
detectable analytes can be ions, the term “analytes” in claim 10 encompasses
any ions present in either the first or second conductive media, including the
ions forming the measured ion current. Pet. 17; Reply 1–4. Petitioner
contends further that Patent Owner’s proffered construction improperly
limits the scope of claim 10 by importing limitations into the claim from the
Specification. Reply 2 (citing Phillips v. AWH Corp., 415 F.3d 1303, 1323
(Fed. Cir. 2005) (en banc)).
We agree with Patent Owner. In particular, we conclude that the term
“analytes” in claim 10 encompasses only those substances detectable by
measuring a reduction in ion current of 5% or more for at least 1.0
microsecond (as recited in independent claim 1), as compared to an ion
current level for the Msp without an analyte present. That is, the term
“analytes” does not encompass the ions forming the ion current that is
measured in the claimed analyte detection process.
We acknowledge, as noted above, the ’550 patent Specification’s
broad disclosure that detected analytes may include any of a variety of
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substances, including ions. Ex. 1001, 8:45–49. Nonetheless, to detect an
analyte, claim 1, from which claim 10 depends, requires its practitioner to
compare (1) a first measured ion current obtained from the first liquid
medium suspected of containing the analyte, with (2) a second measured ion
current, obtained “without an analyte present,” that is, a known control
containing no analyte. Id. at 103:42. As claim 1 states, the presence of the
analyte is indicated by a reduction in the first measured ion current of 5% or
more for at least 1.0 microsecond, as compared to the second measured ion
current level without an analyte present. Id. at 103:40–44.
Thus, as Patent Owner contends (PO Resp. 3–4), if the ions forming
the first and second measured ion currents were considered “analytes,” the
comparison required by claim 1, and its dependent claim 10, could not be
performed, because removing the current-forming ions to prepare a sample
“without an analyte present” (as recited in claim 1) would make it
impossible to measure the ion current necessary to perform the required
comparison. This conclusion is consistent with Examples 2, 3, and 6 of the
’550 patent, each of which is described as comparing ion current blockades
“with and without [a]nalyte” (Ex. 1001, 41:55, 42:27, 45:49), yet each of
which uses an ion-containing buffer including potassium and chloride ions
to generate the measured current (id. at 41:15–16 (describing all ion
conductance experiments as being performed in 1M KCl, 10 mM
Hepes/KOH buffered at pH 8)).
Accordingly, we conclude that, consistent with the Specification of
the ’550 patent, the broadest reasonable interpretation of the term “analytes”
in claim 10 encompasses only those substances detectable by measuring a
reduction in ion current of 5% or more for at least 1.0 microsecond, as
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compared to an ion current level for the Msp without an analyte present, and
does not encompass the ions forming the measured ion current, or other
buffer components present in the liquid media used in the analyte detection
process.
Because the ions forming the measured ion currents are necessary to
the comparison required by claim 10, and because the current-forming ions
and other buffer components are described in Examples 2, 3, and 6 as being
present in samples lacking analyte, we are not persuaded that our claim
construction improperly reads limitations into the claims, as Petitioner
argues. See Reply 2. Rather, by evaluating the functions of the various
claimed components in light of the examples in the Specification, our claim
construction ensures that the term “analytes” is interpreted in a manner
consistent with the ’550 patent’s disclosure of how the claimed process
actually works.
B. Anticipation of Claim 10 by Butler (Ex. 1003)
1. Overview of Butler
Butler discloses experiments that tested the capacity of a mutant Msp
porin (“SSN-MspA”) to detect DNA, using an apparatus that contained a
lipid bilayer that separated two pools of electrically-conductive liquid media
containing potassium chloride as a buffer, the porin being placed in the lipid
bilayer. Ex. 1003, 33 (Fig. 3.1), 95 (explaining that the system shown in
Figure 3.1 was used in the Msp porin experiments), 102 (disclosing
mutations in SSN-MspA).8 Butler discloses that when voltages of 160 mV,
180 mV, and 200 mV were applied to the apparatus, and the resulting

8 In citing to Butler, we cite to the page numbers inserted by Petitioner at the
bottom of each page.
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current was measured, single stranded DNA molecules (“ssDNA”) 50
nucleotides in length (“dA50”), caused “blockades,” that is, reductions in
current of 50 percent or more, lasting from 10 to 100 microseconds, as
compared to a control containing no ssDNA. Id. at 108, 109 (Fig. 6.8).
2. Analysis
Petitioner contends that Butler’s process has all of the steps and
features of claim 1, from which claim 10 depends. Pet. 22–23. As to claim
10, Petitioner contends that, “[b]ecause an ion qualifies as an analyte and
because potassium ions were present in the experiments Butler performed to
detect DNA, another analyte, the limitation of ‘a plurality of different
analytes’ is met by Butler.” Id. at 29.
Patent Owner contends that, because the potassium ions in Butler’s
experiments were used to generate the measured ion current indicative of the
presence of DNA in the same manner as Examples 2, 3, and 6 of the ’550
patent, the potassium ions are not “analytes” encompassed by claim 10 of
the ’550 patent. PO Resp. 7–9 (citing Ex. 2003 ¶¶ 14–18 (Benner Decl.)).9
Thus, according to Patent Owner, the liquid media used in Butler contained
only a single analyte, the DNA molecules Butler tested. Id. Accordingly,
Patent Owner contends, Butler fails to meet claim 10’s requirement that at
least the first or second liquid medium contains a plurality of different
analytes. Id. at 9.
As discussed above, we agree with Patent Owner that the term
“analytes” in claim 10 does not encompass the ions that produce the ion
current that is measured in the claimed process. Petitioner does not dispute

9 Declaration of Steven A. Benner, Ph.D. (Declaration executed Dec. 5,
2014) (Ex. 2003; “Benner Declaration” or “Benner Decl.”).
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Patent Owner’s contention that the potassium ions in Butler’s experiments
form the ion current that Butler measured. See Reply 1–6. Moreover, we
discern no error in Patent Owner’s assertion, and supporting testimony of its
witness, Dr. Benner, that Butler’s system is essentially identical to the
system described in Examples 2, 3, and 6 of the ’550 patent, all of which use
the potassium ions to generate the measured ion current.
Accordingly, we agree with Patent Owner that the term “analytes” in
claim 10 does not encompass the potassium ions in Butler’s experiments.
Because Petitioner relies on the potassium ions in Butler’s experiments,
along with the DNA in those experiments, as corresponding to the plurality
of different analytes required by claim 10 (see Pet. 29), we agree with Patent
Owner that Petitioner has not shown that Butler describes a process which
includes all of the features of claim 10. We conclude, therefore, that
Petitioner has not shown by a preponderance of the evidence that Butler
anticipates claim 10 of the ’550 patent.
Petitioner’s arguments do not persuade us to the contrary. Petitioner
contends that the potassium and chloride ions used in Butler’s experiments
could be detected in a system using sodium and bromide ions as the current-
forming ions. Reply 4, n.2. That a system using liquid media different than
the media used by Butler might be able to detect potassium and chloride
does not persuade us that the system actually described in Butler, which uses
potassium to form an ion current, can detect potassium ions based on a 5%
or more reduction in ion current for at least one microsecond, as claim 10
requires. Again, moreover, if Butler’s potassium ions were considered
analytes, their removal to perform the claim-required comparison “without
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an analyte” would render the system incapable generating the ion current
necessary to that comparison.
In its Reply, Petitioner also advances a theory of unpatentability
distinct from that presented in its Petition. Specifically, Petitioner contends
that, in addition to the potassium ions used to generate the current measured
in Butler, the liquid media used in Butler’s experiments inherently included
contaminants which would generate a reduction in ion current of 5% or more
for at least 1 microsecond. Reply 4–6. Accordingly, Petitioner contends,
beyond the potassium ions discussed above, Butler’s liquid media included,
in addition to the DNA Butler tested, substances encompassed by the term
“analytes,” thereby meeting claim 10’s requirement for a plurality of
different analytes. Id.
As provided in 37 C.F.R. § 42.23(b), a “reply may only respond to
arguments raised in the corresponding opposition or patent owner response.”
Thus, “a reply that raises a new issue or belatedly presents evidence will not
be considered and may be returned.” Office Patent Trial Practice Guide, 77
Fed. Reg. 48,756, 48,767 (Aug. 14, 2012). One indication that a new issue
has been raised in a reply is where a petitioner submits “new evidence
necessary to make out a prima facie case” of unpatentability of an original
claim. Id. In contrast, where evidence submitted in support of a reply
responded only to contentions presented in a Patent Owner response, and
was not relied upon or necessary to the prima facie case of unpatentability,
our reviewing court found no abuse of discretion by the Board in admitting
the reply evidence. Belden Inc. v Berk-Tek LLC, 805 F.3d 1064, 1077–79
(Fed. Cir. 2015).
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Here, Petitioner contends that, in advancing its new contentions, its
Reply merely responds to Patent Owner’s argument that the only substance
in Butler’s liquid media that would be considered an analyte is the single
stranded DNA tested by Butler. Reply 5, n.3; see also id. at 4 (citing Ex.
2003 ¶ 17 (Benner Decl.)).
It might be true that Patent Owner’s Response argued that the DNA
tested by Butler was the only analyte encompassed by claim 10. The basis
for that argument, however, was Patent Owner’s response to contentions and
evidence raised by Petitioner in its Petition. Specifically, Patent Owner
responded that the potassium ions identified in the Petition as the second
analyte were not reasonably considered “analytes” under the broadest
reasonable construction of claim 10 consistent with the Specification. See
PO Resp. 2–9. In its Reply, Petitioner now raises an entirely novel theory of
unpatentability, a theory Patent Owner would not have addressed in its
Response, as it was not raised in the Petition. We are not persuaded that
presenting this novel theory of unpatentability, distinct from that originally
presented in its Petition, truly responds to Patent Owner’s arguments about
the reasonableness of considering potassium ions “analytes” as that term is
used in claim 10. Rather, because the Reply presents new evidence in an
effort to raise a new theory of anticipation, we conclude that the Reply
exceeds its proper scope. See Office Patent Trial Practice Guide, 77 Fed.
Reg. 48,756, 48,767 (Aug. 14, 2012).
Nonetheless, even if we were to overlook the procedural infirmities in
Petitioner’s Reply arguments, which we do not, we would not find the
arguments persuasive.
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To show that Butler anticipates claim 10, Petitioner must show that
Butler discloses “every limitation of the claimed invention, either explicitly
or inherently.” In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997).
Petitioner contends that, in addition to the dA50 molecules Butler
tested, Butler also discloses two types of contaminants in its experiments
that would be considered “analytes”: (1) divalent and trivalent ions, and (2)
less than full-length oligonucleotides. Reply 5. Petitioner has not shown
sufficiently that Butler explicitly or inherently discloses that those
substances were present in the DNA experiments cited by Petitioner.
As to the alleged divalent and trivalent ion impurities, Butler states
only that “[i]f these hypothetical contaminant molecules are present in the
dA50 aliquots that we add to the cis compartment, then we would observe the
correlation between increased blockade rate and the presence of dA50.” Ex.
1003, 107 (emphasis added). Butler’s hypothetical guess at potential causes
of ion current blockades does not equate to an explicit disclosure of the
presence of those contaminants in its experiments. Moreover, because
Butler’s disclosure, at best, suggests that such contaminants might possibly
have been present, Butler does not inherently disclose the presence of those
contaminants. See Agilent Techs., Inc. v. Affymetrix, Inc., 567 F.3d 1366,
1383 (Fed. Cir. 2009) (“The very essence of inherency is that one of
ordinary skill in the art would recognize that a reference unavoidably teaches
the property in question.”) (emphasis added); In re Oelrich, 666 F.2d 578,
581 (CCPA 1981) (“Inherency, however, may not be established by
probabilities or possibilities. The mere fact that a certain thing may result
from a given set of circumstances is not sufficient.”).
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As to the alleged less than full length oligonucleotide contaminants,
we acknowledge Butler’s disclosure that oligonucleotide impurities were
present in the RNA samples used to test the capacity of a different pore
protein, α-hemolysin, to detect nucleic acids. See Ex. 1003, 69, 72.
Petitioner does not show sufficiently, however, that Butler’s disclosure of
RNA impurities in a different sample, used in experiments different from the
Msp porin experiments relied upon to show anticipation, equates to either an
explicit or inherent disclosure that the DNA used in Butler’s Msp porin
experiments contained the same impurities.
As to Butler’s Msp porin experiments, Butler discloses that the
“homogeneous” dA50 molecules it used “were synthesized by Integrated
DNA Technologies” (IDT). Ex. 1003, 38. As to those molecules, Butler
states that “[a]ll samples were PAGE purified by the suppliers,” thereby
indicating that the tested samples were pure, i.e., did not contain
contaminants. Id. Accordingly, we find that Butler does not explicitly
disclose that the DNA used in its Msp porin experiments contained
oligonucleotide contaminants that, along with the dA50 molecules, would be
considered “analytes,” as required by claim 10.
Petitioner contends, nonetheless, that literature from IDT, Butler’s
DNA supplier, establishes that less than full length oligonucleotide
contaminants were inherently present in the DNA samples Butler used in the
allegedly anticipating experiments. See Reply 6 (citing Exs. 1043,
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1051).10, 11 Thus, Petitioner contends, even if IDT were able to attain a
sample purity of 99%, the 1% of the sample representing incompletely
synthesized oligonucleotides, “in the context of the system described in
Butler would result in more than a trillion contaminating nucleic acid
molecules − in a system designed to detect single molecules.” Id. (citing Ex.
1004 ¶ 31).12
Petitioner does not explain with specificity which disclosures in
Exhibit 1051 it relies upon to show that IDT’s PAGE-purified products
necessarily contain impurities. Nonetheless, we acknowledge the disclosure
that, as to unmodified oligonucleotides, “purity of >90% is routinely
achieved” using PAGE purification. Ex. 1051, 1. We acknowledge also the
disclosure in Exhibit 1043 that, “[f]or the most demanding applications, IDT
offers Dual HPLC Purification and Dual PAGE and HPLC Purification.
These methods result in oligos of the highest possible purity.” Ex. 1043, 2.
Although these disclosures might show a degree of probability that the
IDT PAGE-purified products used in Butler contained less than full length
oligonucleotide contaminants, as noted above, a showing of inherency may
not be based on probability or possibility, but instead requires establishing
that the reference unavoidably teaches the limitation at issue. In re Oelrich,
666 F.2d at 581; Agilent, 567 F.3d at 1383.

10 IDT Webpage - IDT DNA PAGE and HPLC Purification
(http://www.idtdna.com/pages/products/dna-rna/hplc-page) (accessed Feb. 9,
2015) (Ex. 1043).
11 IDT Webpage - Purification of Oligonucleotides Quick Look (2009) (Ex.
1051).
12 Declaration of Daniel Branton, Ph.D. (Declaration executed Mar. 11,
2015) (Ex. 1044; “Branton Reply Declaration” or “Branton Reply Decl.”).

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To that end, we note that IDT’s disclosure of routinely achieving
greater than 90% purity encompasses the possibility of products having
100% purity. Indeed, Dr. Benner testified in his deposition that he had
tested IDT products of the type used by Butler, and found no detectable
contaminants:
We typically analyze all IDT-generated nucleotides. I
have not, of course, to my recollection, ever, I don’t believe I
have ever ordered a 50 specifically. We actually order things,
we run gels on them, we do mass specs on them. We are not
able to detect impurities in PAGE-purified oligos, and,
therefore, I would probably refer to the webpage, first sentence,
which is that “PAGE obtains extremely high purity,” where I
would refer to the greater than 90 percent as something that
their legal counsel introduced in to give the lowest possible
level of -- that is, the highest possible level of impurity that they
could conceivably have.
We have never seen an IDT oligo that has been PAGE-
purified delivered to us with less than 99-point-something, that
is, we’ve never been able to detect other things in that oligo as
it’s delivered.

Ex. 1042, 61:20–62:14 (Benner Deposition) (emphasis added); see also id. at
57:13–16 (“[W]hat we get from IDT -- and we pay them for it -- is
molecules for which there is no detectable impurity by any of a number of
standards that are common in the art to detect them.”).
Thus, given Dr. Benner’s testimony that the IDT-provided,
PAGE-purified oligonucleotides he has tested did not contain detectable
impurities, contrasted with the mere probabilistic implication from the IDT
webpages (Exs. 1043 and 1051) that IDT’s products might contain
impurities, Petitioner has not shown by a preponderance of the evidence that
the IDT-supplied dA50 molecules used in Butler’s experiments inherently
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contained contaminants detectable as “analytes,” as required by claim 10 of
the ’550 patent. Accordingly, in the contentions of unpatentability advanced
in its Reply, Petitioner has not shown by a preponderance of the evidence
that Butler, explicitly or inherently, describes a process that includes a
plurality of different analytes, as required by claim 10.
In sum, for the reasons discussed, Petitioner has not shown by a
preponderance of the evidence that Butler anticipates claim 10 of the ’550
patent.
C. Anticipation of Claims 17 and 18 by the Wong Poster (Ex. 1008, 2)
1. Overview of the Wong Poster
The Wong Poster and the Wong Abstract, which Petitioner filed as
separate pages in Exhibit 1008, were cited as a single item in an Information
Disclosure Statement submitted during prosecution of the ’550 patent. Pet.
12; PO Resp. 10. The Wong Poster was presented by an undergraduate
student, Risa Wong, at a poster session conducted at the University of
Washington on August 16, 2007. Pet. 12; PO Resp. 10.
Page 3 of Exhibit 1008 is a title page reading “UW Summer Research
Poster Session.” Ex. 1008, 3. The date, time, and location of the poster
session are indicated as August 16, 2007, 9:00 AM to noon, and Mary Gates
Hall Commons. Id.
Page 4 of Exhibit 1008 includes the following welcoming statement:
This poster session is a collaboration among several
summer programs hosting UW and non-UW undergraduates
from around the country, including the Amgen Scholars
Program, Biostatistics Summer REU, Clinical Research
Experience for Engineers, Genetically Engineered Materials
Science & Engineering Center, Hooked on Photonics STC-
MDITR, Intel Summer Research Experience, National
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Nanotechnology Infrastructure Network, and University of
Washington Engineered Biomaterials.

Id. at 4. As to authorship, the Wong Poster indicates “Risa Wong,
Junior, UW Amgen Scholars Program.” Id. at 2, center column.
As to its substantive disclosure, the Wong Poster describes an
apparatus in which an MspA mutant porin is placed in a lipid bilayer
between two containers (“wells”), each of which contains an electrically
conductive liquid medium, with liquid communication occurring between
the two wells through the porin. Ex. 1008, 2 (center column). Wong
describes one of the wells as containing single stranded DNA. Id. Wong
discloses that application of voltages of 140 mV and 180 mV allows
detection of the DNA because the ion current blockades occurring during
voltage application are consistent with DNA translocation through the porin.
Id. (right column); see also Ex. 1008, 2 (left column) (voltage potential
moves the DNA through the MspA mutant porin temporarily reducing ion
current).
2. The Parties’ Contentions
Petitioner contends that the poster session at which Ms. Wong
displayed the Wong Poster was “open to the public.” Pet. 12. Petitioner
contends also that the date of the poster session was more than one year
before the effective filing date of the ’550 patent. Id. Accordingly,
Petitioner contends, the Wong Poster qualifies as a “printed publication”
under 35 U.S.C. § 102(b). Id. (citing In re Klopfenstein, 380 F.3d 1345,
1348 (Fed. Cir. 2004)). Petitioner contends that the Wong Poster describes a
system having all of the features recited in claims 17 and 18. Pet. 41–43.
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Patent Owner does not dispute that the date of the poster session was
more than one year before the effective filing date of claimed subject matter
at issue. See PO Resp. 10–18, 20–21. Nor does Patent Owner dispute that
the Wong Poster describes a system having all of the features recited in
claims 17 and 18. Id. Rather, Patent Owner contends that, given the
circumstances of its display at the poster session, the Wong Poster is not a
printed publication under § 102(b). Id. Patent Owner relies primarily on the
testimony of Dr. Jennifer Harris, an employee of the University of
Washington, to explain the circumstances of the poster session. Id. at 10,
14–18 (citing Ex. 2004 (Harris Decl.)).13
Petitioner replies that the circumstances of the Wong Poster’s display
at the poster session support a conclusion that it qualifies as prior art under
§ 102(b). Reply 7–12. Petitioner also relies on testimony by Dr. Harris. Id.
at 8–12 (citing Ex. 1045 (Harris Deposition)).
3. Principles of Law
“The determination of whether a reference is a ‘printed publication’
under 35 U.S.C. § 102(b) involves a case-by-case inquiry into the facts and
circumstances surrounding the reference’s disclosure to members of the
public.” In re Klopfenstein, 380 F.3d at 1350. “The ‘printed publication’

13 Dr. Jennifer Harris was the Associate Director of the University of
Washington’s Undergraduate Research Program from September 2005
through March 2014. Ex. 2004 ¶ 1. Dr. Harris has been Director of the
Program since April 2014. Id.
Dr. Harris’s duties as both Director and Associate Director “include
developing and managing programs designed to educate undergraduate
students and prepare them for careers in research in all fields, including
science, technology, engineering and mathematics (‘STEM’), by giving
them the opportunity to conduct research under the supervision of faculty
members.” Id.
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bar is grounded on the principle that once an invention is in the public
domain, it is no longer patentable by anyone.” Id. at 1349 (quoting In re
Hall, 781 F.2d 897, 899 (Fed. Cir. 1986)) (internal brackets removed).
Thus, “public accessibility” is “the touchstone” in determining
whether a reference is a printed publication. In re Hall, 781 F.2d at 899. “A
given reference is ‘publicly accessible’ upon a satisfactory showing that
such document has been disseminated or otherwise made available to the
extent that persons interested and ordinarily skilled in the subject matter or
art exercising reasonable diligence, can locate it.” SRI Int’l, Inc. v. Internet
Sec. Sys., Inc., 511 F.3d 1186, 1194 (Fed. Cir. 2008) (quoting Bruckelmyer
v. Ground Heaters, Inc., 445 F.3d 1374, 1378 (Fed. Cir. 2006)). In other
words, “[a]ccessibility goes to the issue of whether interested members of
the relevant public could obtain the information if they wanted to.”
Constant v. Advanced Micro-Devices, Inc., 848 F.2d 1560, 1569 (Fed. Cir.
1988).
As to disclosures at communal events, in In re Klopfenstein the
Federal Circuit set out a list of “factors [to] aid in resolving whether or not a
temporarily displayed reference that was neither distributed nor indexed was
nonetheless made sufficiently publicly accessible to count as a ‘printed
publication’ under § 102(b).” In re Klopfenstein, 380 F.3d at 1350. The
court listed those factors as follows: “[1] the length of time the display was
exhibited, [2] the expertise of the target audience, [3] the existence (or lack
thereof) of reasonable expectations that the material displayed would not be
copied, and [4] the simplicity or ease with which the material displayed
could have been copied.” Id.
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Applying those factors, the court held that a fourteen-slide
presentation, printed and pasted onto poster boards and presented at two
professional conferences for a total of nearly three days, was a printed
publication, despite the fact that no copies of the presentation were
disseminated at either meeting, and the presentation was never catalogued or
indexed in any library or database. Id. at 1347–51. As to the target
audience, the court noted that the intended viewers at the first conference
were persons of ordinary skill in the pertinent art, and the intended viewers
at the second conference “most likely also possessed ordinary skill in the
art.” Id. at 1351.
The Federal Circuit’s holding in Massachusetts Institute of
Technology v. AB Fortia, 774 F.2d 1104 (Fed. Cir. 1985), underscores the
importance of the target audience at such communal events. There, the court
held that an oral presentation of a paper describing optimization of a
component used in cell culture media, made at a conference attended by 50
to 500 cell culturists having ordinary skill in the art, with copies of the paper
being distributed without restriction to the conference leader and at least six
persons of ordinary skill, was a printed publication under § 102(b). Id. at
1108–1109.
Addressing the issue in a summary judgment appeal, the Federal
Circuit similarly highlighted the importance of the target audience, noting
that, if proven, distribution of the document at issue at a “trade show . . .
would constitute a publication under 35 U.S.C. § 102(b).” TypeRight
Keyboard Corp. v. Microsoft Corp., 374 F.3d 1151, 1157–58 (Fed. Cir.
2004).
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In contrast, in vacating a summary judgment of anticipation, the
Federal Circuit in the SRI case, on that record, analogized the disclosure of
the document at issue to “placing posters at an unpublicized conference with
no attendees,” despite evidence that individuals with sufficient knowledge
and know-how regarding the document’s non-confidential posting on an
open server might have been able to access the document. SRI Int’l, 511
F.3d at 1197. Indeed, the SRI panel expressly contrasted the circumstances
of dissemination of the document at issue there from the events at which the
Klopfenstein poster was displayed. Id. at 1196 (“In Klopfenstein, two
professional conferences displayed posters. These posters were printed
publications because their entire purpose was public communication of the
relevant information.”) (citing Klopfenstein, 380 F.3d at 1347–50).
4. Discussion
Patent Owner persuades us that Petitioner has not shown by a
preponderance of the evidence that persons interested and ordinarily skilled
in the art pertinent to claims 17 and 18 of the ’550 patent, exercising
reasonable diligence, would have been able to locate the Wong Poster.
As Patent Owner contends, Dr. Harris testified that the poster session
at which Risa Wong displayed the Wong Poster was an event at which
approximately 80 undergraduate students presented posters and discussed
their summer research projects at the University of Washington’s 2007
Undergraduate Research Program. Ex. 2004 ¶¶ 2–4 (Harris Decl.); PO
Resp. 14–15. Dr. Harris testified that, in accordance with the Undergraduate
Research Program’s mission, “the purpose of the abstract and the poster
session was to educate the students by giving them presentation experience
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that would prepare them for graduate school and careers in science.” Ex.
2004 ¶ 4.
As Patent Owner contends, in the complete event program (Ex. 2002),
the full list of abstracts for which the students presented posters shows a
variety of technical subjects, including mutated enzymes, robots, coronary
artery disease, magnetic levitation, and power conversion in titanium oxide-
containing bilayer devices. PO Resp. 16 (citing Ex. 2002, 6, 7, 9, 11, 51).
As to the target audience, Dr. Harris testified that, before the poster
session, “the Undergraduate Research Program sent e-mail invitations to the
students and their mentors, faculty members, program staff, and campus
administrators, and encouraged the students to invite family and friends,”
and also “posted a brief announcement on the Undergraduate Research
Program’s home page shortly before the event listing the time, date, and
place of the poster session. Neither the invitations nor the announcement
specified the scientific subject matter of the student presentations.” Ex.
2004 ¶ 5.
Dr. Harris testified that she attended the poster session, and recalled
that the attendees “predominantly were connected to the individual student
presenters (e.g., mentors, friends, family members, and members of the
laboratories where the students worked over the summer) or to
undergraduate education at the University of Washington,” which is
“consistent with the fact that the primary purpose of the poster session was
to give the students presentation experience.” Id. ¶ 8. Dr. Harris testified
that, “[a]t the conclusion of the three-hour event, we immediately removed
the posters, including Risa Wong’s poster, from the room. After the posters
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were removed, neither I nor the Undergraduate Research Program took steps
to catalogue or index the posters.” Id. ¶ 9.
Thus, the poster session at issue plainly was not an unpublicized
conference with no attendees. Nonetheless, because invitation to the session
was based primarily on affiliation with a particular student, as opposed to
interest or skill in any particular technical subject matter, we agree with
Patent Owner that the poster session’s intended viewers were not
comparable to the technology-specific or industry-specific audiences
targeted in the professional conferences and trade show discussed in the
Klopfenstein, MIT, and TypeRight cases.
Petitioner’s rebuttal contentions do not persuade us that, despite the
poster session’s limited target audience, interested and ordinarily skilled
artisans exercising reasonable diligence would have been able to locate the
Wong Poster if they wished. To that end, Petitioner directs us to Dr.
Harris’s deposition testimony, which is asserted to “reveal[] that more than
50 Ph.D. level mentors and lab group members, all of whom were interested
in the field of molecular analysis, were either directly invited by
administrators or were expected to be invited to the event by students.
(Ex.1045 at 117-54 [Harris Deposition]; Ex. 2002).” Reply 8; see also id. at
11 (citing Ex 1045, 95:18–96:16). Petitioner also quotes a statement in an
email from Dr. Harris, apparently to participants in the Amgen Scholars
program, that “[t]he event is open to the public. Please INVITE YOUR
LAB GROUP, FRIENDS, FAMILY, ETC. The more the merrier.” Id.
(citing Ex. 1046, 2).
Petitioner does not explain specifically why the cited portions of Dr.
Harris’s deposition demonstrate that more than 50 of the invited attendees
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were interested or actively engaged in molecular analysis. See Reply 8. We
acknowledge, nonetheless, that Dr. Harris testified that the Undergraduate
Research Program would have invited all University of Washington faculty
members that were mentoring poster-presenting students in the Amgen
Scholars Program, and that those faculty mentors included practitioners in
biochemistry, chemistry, chemical engineering, immunology, electrical
engineering, genome sciences, neuropathology, medicinal chemistry,
bioengineering, and biology. Ex. 1045, 150–153.
Petitioner does not explain specifically, however, why the invited
faculty members would have been interested persons of ordinary skill in the
relevant art. Petitioner advances the following testimony of Dr. Branton
regarding the level of ordinary skill in the relevant art:
In my opinion, the level of ordinary skill in the art as of the
priority date of the ‘550 patent was high, at the Ph.D. level or at
least the masters level with several years of experience with
molecular analysis. The person of ordinary skill in this art area,
a cross-disciplinary field spanning biophysics and molecular
biology, would have training in both the physical and biological
sciences or training in one of those disciplines with access to
those with training in the other. The person of ordinary skill in
the art might have academic degrees in e.g., physics,
biophysics, molecular biology, biochemistry or various
bioengineering disciplines, but, more importantly, would have
knowledge or comprehension of the biological and physical
phenomena relevant to using nanopores to make highly precise
measurements at the molecular level.

Ex. 1012 ¶ 34 (emphasis added).14

14 Declaration of Daniel Branton, Ph.D. (Declaration executed Mar. 18,
2014) (Ex. 1012; “Branton Declaration” or “Branton Decl.”).
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As to the requirement of a Ph.D. or master’s degree, we note that the
full event program to which Petitioner directs us (Reply 8 (citing Ex. 2002)),
does not indicate the degrees of the faculty mentors. See Ex. 2002, 6–54. A
number of the cited pages of Dr. Harris’ deposition, nonetheless, expressly
suggest that five of the discussed mentors had doctorates. Ex. 1045, 118
(“Dr. Klevit” (biochemistry)), 130 (“Professor Zhang” (material science and
engineering)), 131 (“Dr. Pun” (bioengineering)), 133 (“Professor Yager”
(bioengineering)), 143 (“Dr. Swanson” (genome sciences)).
Even assuming, however, that it is self-evident that those individuals,
or other faculty members in the subjects presented at the poster session, had
relevant doctoral degrees, as noted above, “more important[]” than the
practitioner’s degree or academic discipline, Petitioner’s definition of an
ordinarily skilled artisan requires “knowledge or comprehension of the
biological and physical phenomena relevant to using nanopores to make
highly precise measurements at the molecular level.” Ex. 1012 ¶ 34.
Petitioner does not direct us to clear or specific evidence showing that the
invited faculty mentors in the disciplines represented at the poster session, or
other invitees, would have had knowledge or comprehension relevant to
using nanopores to make highly precise measurements at the molecular
level, nor does Petitioner otherwise explain why that is the case. Nor does
Petitioner direct us to evidence showing that any of the invitees were
members of the public interested in the subject matter of the ’550 patent.
Petitioner does not, therefore, show sufficiently that the intended
audience of the poster session necessarily included interested persons of
ordinary skill in the art pertinent to claims 17 and 18 of the ’550 patent.
Indeed, the broad range of subjects included in the full event program to
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which Petitioner directs us (Ex. 2002) bolsters rather than undermines Patent
Owner’s assertion that the poster session’s intended audience was based on
affiliation with the presenting students, rather than being focused on a
particular technical discipline.
Petitioner also directs us to evidence that, before the poster session,
the Undergraduate Research Program’s publicly-available website included
information about Jens Gundlach and the nanopore-based work a student in
his laboratory would perform in connection with the Amgen Scholar’s
Program, as well as a biography of Ms. Wong describing the type of work
she was performing in Dr. Gundlach’s laboratory. Reply 9 (citing (Ex.
1045, 46:15–51:12, 54:16–56:10 (Harris Deposition)). Petitioner further
notes that the invitations (Ex. 1047) to the poster session included a link to
the Undergraduate Research Program website and the Program’s telephone
number. Reply 9. Accordingly, Petitioner contends, “given the content and
breadth of the invitations, including the website link, relevant persons
exercising reasonable diligence would have known about, and could easily
have accessed, the Wong Poster – and this alone qualifies the Poster as a
‘printed publication.’” Id. at 9–10.
As discussed above, however, Petitioner has not shown sufficiently
that the intended audience of the poster session, the invitees, included
interested persons of ordinary skill in the relevant art. Thus, that the poster
session’s invitees may have been able to access information about the
subject of Dr. Gundlach’s and Ms. Wong’s research through the
Undergraduate Research Program’s website does not persuade us that the
poster session itself was accessible to interested and ordinarily skilled
artisans exercising reasonable diligence. Nor has Petitioner explained
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convincingly why, aside from the invitations, the public accessibility of the
Undergraduate Research Program’s website, by itself, would have
adequately publicized the poster session at issue to the set of individuals
required to render the poster a printed publication under § 102(b).
We acknowledge that the Wong Poster is a single static poster that
was presented for three hours, as Petitioner contends. Reply 9. We
acknowledge, as Petitioner contends also, that Dr. Harris testified that Ms.
Wong was trained to convey the Wong Poster’s subject matter concisely,
and stood in front of the poster and interacted with people walking past the
poster during the three-hour session. Id. at 10 (citing Ex. 1045, 171:12–19,
193:10–194:6 (Harris Deposition)). We acknowledge, as Petitioner further
contends, that Dr. Harris testified that audience members were not restricted
from photographing the poster. Id. at 11–12 (citing Ex. 1045, 109:10–14).
As discussed above, nonetheless, although the poster session at issue
was open to the public, Petitioner has not shown sufficiently that the group
of people to whom the session was actually announced, the invitees,
included interested persons of ordinary skill in the relevant art. To the
contrary, the circumstances of the Wong Poster’s display—a three-hour
event whose target audience was based on affiliation with a group of
undergraduate students presenting posters of widely varying technical
subject matter, rather than focusing on a particular art or discipline—differ
significantly from a trade show or the multi-day, widely attended
professional conferences discussed in the Klopfenstein and MIT cases. Thus,
although the physical act of copying the Wong Poster might have been a
simple matter of taking a photograph, given the totality of the circumstances
of the poster’s display, the absence of restrictions or ease of copying does
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not persuade us that the Wong Poster would have been located by interested
and ordinarily skilled artisans exercising reasonable diligence.
In sum, for the reasons discussed, Petitioner has not shown, by a
preponderance of the evidence, that the facts and circumstances of the
display of the Wong Poster were such that the Wong Poster would have been
accessible to interested and ordinarily skilled artisans exercising reasonable
diligence. Because Petitioner has not shown that the Wong Poster is a
printed publication under 35 U.S.C. § 102(b), Petitioner has not shown by a
preponderance of the evidence that the Wong Poster anticipates claims 17
and 18 of the ’550 patent, under that statutory provision.
D. Anticipation of Claims 17 and 18 by the Wong Abstract (Ex. 1008, 1)
1. Overview of the Wong Abstract
The Wong Abstract appears in the printed program of the 2007 poster
session, discussed above, at which the Wong Poster was presented. Ex.
1008, 1; Ex. 2002, 52. As to its substantive disclosure, the Wong Abstract
outlines the technical concepts underlying the use of Msp porins in detecting
and analyzing DNA, and discloses that experiments were performed in
which certain mutant porins demonstrated current blockages in the presence
of single-stranded DNA. Ex. 1008, 1; Ex. 2002, 52.
2. Analysis
Petitioner contends that, because the Wong Abstract was presented in
the event program of the poster session at which the Wong Poster was
displayed, the Wong Abstract, like the Wong Poster, constitutes prior art
under § 102(b). Pet. 12.
Patent Owner concedes that the Wong Abstract “was included in the
event program (Ex. 2002) that was posted to the University of Washington
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Undergraduate Research Program’s website.” PO Resp. 19. Patent Owner
contends, nonetheless, that Petitioner has not advanced evidence showing
either that the abstract was posted on the website prior to the critical date for
claims 17 and 18, or that the posted document was accessible to the relevant
audience. Id. at 19–20. Patent Owner contends, moreover, that Petitioner
has not advanced evidence that either the event program or Wong Abstract
was meaningfully indexed or catalogued such that interested and ordinarily
skilled artisans would have been able to locate them. Id. at 20.
Petitioner replies that, because physical copies of the event program
were distributed “during and after” the 2007 poster session, the Wong
Abstract was accessible without restriction to ordinarily skilled artisans
exercising reasonable diligence. Reply 13.
Patent Owner persuades us that Petitioner has not shown that the
Wong Abstract is a printed publication under § 102(b).
We acknowledge Dr. Harris’s testimony that copies of the event
program, which included the Wong Abstract, were available at the entrance
to the room at which the poster session was held. Ex. 2004 ¶ 6 (Harris
Decl.); Ex. 1045, 61–62. We acknowledge also the following statements in
an email by Dr. Harris to “Summer REU Program Staff,” to which Petitioner
directs us (Reply 13): “I also want to let you know that we have plenty of
programs left over and I can send each of you a stack so that you can have
them for your use. Please let me know how many you would like.” Ex.
1049, 1.
As discussed above, however, we are not persuaded that Petitioner has
shown that the intended audience of the poster session, the invitees, included
interested persons of ordinary skill in the relevant art. Nor are we persuaded
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that Petitioner has explained convincingly why, other than invitation,
interested and ordinarily skilled artisans would have known about the
session. Accordingly, that copies of the Wong Abstract were available to
the target audience at the entrance to the poster session does not persuade us
that the Wong Abstract was accessible to interested persons of ordinary skill
in the relevant art. In addition, notwithstanding Dr. Harris’ email discussed
above, insufficient evidence exists to show that event programs were
distributed to anyone outside of the poster session. Petitioner, moreover,
does not direct us to clear or specific evidence explaining how distribution
of copies of the Wong Abstract to members of the Undergraduate Research
Program staff, even if done without restriction, would have made the
abstract accessible to interested and ordinarily skilled artisans exercising due
diligence. For example, the evidence presented by Petitioner does not
establish that the Wong Abstract was ever catalogued or indexed in any
library or database such that an interested and ordinarily artisan exercising
due diligence could have located the document.
Accordingly, Petitioner has not shown by a preponderance of the
evidence that the facts and circumstances of the distribution of the Wong
Abstract were such that the Wong Abstract would have been accessible to
interested and ordinarily skilled artisans exercising reasonable diligence.
Because Petitioner, therefore, has not shown that the Wong Abstract is a
printed publication under 35 U.S.C. § 102(b), we are not persuaded that
Petitioner has shown by a preponderance of the evidence that the Wong
Abstract anticipates claims 17 and 18 of the ’550 patent, under that statutory
provision.
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E. Obviousness of Claim 10 over the ’782 patent (Ex. 1024) and Butler (Ex.
1003)
1. Prior Art Evidence of Obviousness
We instituted trial based on Petitioner’s challenge to claim 10 of the
’550 patent for obviousness under 35 U.S.C. § 103(a) over the ’782 patent
and Butler. Paper 28, 28.
As the Supreme Court has stated, when evaluating claims for
obviousness, “the scope and content of the prior art are to be determined;
differences between the prior art and the claims at issue are to be
ascertained; and the level of ordinary skill in the pertinent art resolved.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007) (quoting Graham v.
John Deere Co., 383 U.S. 1, 17–18 (1966)). Secondary considerations, if
present, also must be considered. Id.
As to the level of ordinary skill, as discussed above, Petitioner
contends that the level in this art is high, at the Ph.D. level or at least
master’s level with several years of experience in molecular analysis, with
training in both the physical and biological sciences, or training in one of
those disciplines with access to those with training in the other, and with
“knowledge or comprehension of the biological and physical phenomena
relevant to using nanopores to make highly precise measurements at the
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molecular level.” Ex. 1056 ¶ 28 (Second Branton Decl.);15 Ex. 1057 ¶ 19
(Second Benz Decl.).16
Patent Owner does not assert error in the opinion of Petitioner’s
experts on this issue. See Supp. Resp., generally. Accordingly, we adopt
Petitioner’s definition for our obviousness analysis.
As to the scope of the prior art, and its differences from the challenged
claim, Petitioner contends that the ’782 patent describes a process having all
of the steps and features of claim 10, except that the ’782 patent does not
describe using an Msp porin as its tunnel-containing protein through which
its preferred analytes, nucleic acid molecules, are translocated. See Supp.
Pet. 24, 38–39 (Ex. 1059). Petitioner contends that an ordinary artisan
would have been motivated to modify the ’782 patent’s process and use
Butler’s mutant MspA porin as the tunnel-containing protein, given the
references’ expressed common goals of using a nanopore to effect rapid
nucleic acid analysis. Id. at 24–25. In particular, Petitioner contends that an
ordinary artisan would have considered the use of Butler’s MspA mutant
porin in the methods of the ’782 patent to be “nothing more than the
predictable use of a prior art element according to its established function.”
Id. at 29, 31.
Patent Owner does not assert error in Petitioner’s contention that the
’782 patent’s process differs from claim 10’s process only in that the ’782
patent’s process does not use the Msp porin required by claim 10. Rather,

15 Declaration of Daniel Branton, Ph.D. (Declaration executed Oct. 11,
2014) (Ex. 1056; “Second Branton Declaration” or “Second Branton
Decl.”).
16 Declaration of Roland Benz, Prof., Dr., Dr. h.c. (Declaration executed Oct.
13, 2014) (Ex. 1057; “Second Benz Declaration” or “Second Benz Decl.”).
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Patent Owner contends that an ordinary artisan would not have considered it
obvious to use Butler’s Msp porin in the ’782 patent’s process because of the
poor understanding of the interactions between nucleic acids and tunnel-
forming proteins, and because an ordinary artisan, for a number of reasons,
would not have had a reasonable expectation that Butler’s Msp porin would
be able to translocate nucleic acids. Supp. Resp. 12–39. Patent Owner
contends also that an ordinary artisan would not have had a reasonable
expectation that Butler’s Msp porin would be able to characterize a
heterogeneous mixture as taught in the ’782 patent. Id. at 39–42.
Having reviewed Petitioner’s analysis and supporting evidence in
light of Patent Owner’s arguments and evidence, we find that a
preponderance of the evidence supports Petitioner’s position that an ordinary
artisan would have been prompted to use Butler’s MspA mutant porin in the
’782 patent’s process of analyzing a heterogeneous mixture containing a
plurality of different DNA molecules, thereby performing a process having
all of the steps and features required by claim 10 of the ’550 patent.
The ’782 patent, like the ’550 patent, discloses processes for
evaluating polymeric molecules, such as DNA or RNA, in which two
separate pools of electrically conductive media are separated by an ion
permeable passage, and an electrical potential between the two pools is
created, such that ionic current can flow through the ion permeable passage.
Ex. 1024, 2:35–42. The ’782 patent explains that “[w]hen the polymer
interacts sequentially with the interface at the ion permeable passage, the
ionic conductance of the passage will change (e.g., decrease or increase) as
each monomer interacts, thus indicating characteristics of the monomers
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(e.g., size, identity) and/or the polymer as a whole (e.g., size).” Id. at 2:42–
47. Thus, as to DNA or RNA, the method of the ’782 patent involves
measurements of ionic current modulation as the monomers
(e.g., nucleotides) of a linear polymer (e.g., nucleic acid
molecule) pass through or across a channel in an artificial
membrane. During polymer passage through or across the
channel, ionic currents are reduced in a manner that reflects the
properties of the polymer (length, concentration of polymers in
solution, etc.) and the identities of the monomers.

Id. at 6:52–59.
The ’782 patent explains further that “[s]everal individual polymers,
e.g., in a heterogenous [sic] mixture, can be characterized or evaluated in
rapid succession, one polymer at a time, leading to characterization of the
polymers in the mixture.” Id. at 1:51–54; see also id. at 4:51–56 (“The
mixture of polymers used in the invention does not need to be
homogenous. Even when the mixture is heterogenous [sic], only one
molecule interacts with a passage at a time, yielding a size distribution of
molecules in the mixture, and/or sequence data for multiple polymer
molecules in the mixture.”).
Example 6 of the ’782 patent discloses measurement of current
blockades of shorter and longer RNA molecules of known length, thereby
showing the “[r]elationship between polymer length and channel blockade
duration,” and “lending credibility to the accuracy of the methods of the
invention for measuring polymer length by measuring signal duration.” Id.
at 20:11–46.
As to ion permeable passages, rather than the Msp porin required by
claim 10, the ’782 patent discloses that “[p]referred channels for use in the
invention include the α-hemolysin toxin from S. aureus and maltoporin
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channels.” Id. at 4:65–67. As Petitioner discusses (Supp. Pet. 26), however,
the ’782 patent discloses that “[a]ny channel protein which has the
characteristics useful in the invention (e.g., minimum pore size around 2 Å,
maximum around 9 nm; conducts current) may be employed.” Ex. 1024,
10:13–15.
As Petitioner discusses (Supp. Pet. 26–27), Butler discloses that, in
general, the MspA porin “has many advantageous characteristics for nucleic
acid analysis including a short, narrow inner constriction, remarkable
robustness, ease of use, and the retention of pore-forming activity despite the
introduction of multiple amino-acid substitutions.” Id. Ex. 1003, 88.
As Petitioner further discusses (Supp. Pet. 29), Butler discloses that an
MspA mutant porin with excess negatively charged amino acids removed,
“SSN-MspA,” exhibited properties consistent with the translocation of
single stranded DNA through the protein’s pore, using essentially the same
system as that described in the ’782 patent. Ex. 1003, 107 (“The data in Fig.
6.8 are consistent with the scenario where dA50 molecules are
electrophoretically driven into the SSN-MspA pore and cause transient
blockades of the ionic current. Perhaps . . . the increase in the rate of Short
Deep events represents translocation of dA50 through SSN-MspA.”); see
also id at 88 (“We are presently working to verify the exciting possibility
that these blockades are a result of interaction between ssDNA and the
MspA mutant.”).
Given Butler’s disclosure that its SSN-MspA mutant porin exhibited
properties consistent with the DNA translocation required in the methods of
the ’782 patent, and given also the advantageous properties of the MspA
porins disclosed by Butler for use in nucleic acid analysis, the same pursuit
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as the ’782 patent, Petitioner persuades us that an ordinary artisan would
have been prompted to use Butler’s SSN-MspA mutant porin in the ’782
patent’s nanopore-based nucleic acid analysis processes. In addition, given
the reference’s teachings, an ordinary artisan would have had a reasonable
expectation that Butler’s porin would work in the ’782 patent’s processes.
Patent Owner’s arguments do not persuade us to the contrary. Patent
Owner contends that, despite the assertion that any channel protein with
suitable properties might be employed in analyzing nucleic acids, the ’782
patent discloses limited experiments with only its two preferred proteins,
α-hemolysin and maltoporin, and of the two, only α-hemolysin was able to
demonstrate a relationship between current blockade duration and nucleic
acid length. Supp. Resp. 15–16. Patent Owner contends that, because
α-hemolysin was the only pore-forming protein that had been used
effectively in prior art nucleic acid analyses, and because its mechanism of
action was not well understood, the state of the art was not such that an
ordinary artisan would have viewed substituting other pore-forming proteins
for the ’782 patent’s α-hemolysin a matter of simple substitution with a
reasonable expectation of success. Id. at 16–19.
We are not persuaded. We acknowledge the testimony of Drs. Benner
and Branton that, as of 2007, only α-hemolysin had been used in nucleic
acid analyses in published papers. Ex. 2018 ¶ 15 (Second Benner Decl.);17
Ex. 2036, 36:19–21 (Branton Deposition) (“But published papers, I have not
seen using other protein pores that have been identified.”). As discussed
above, however, the Butler reference, a 2007 doctoral thesis that neither

17 Declaration of Steven A. Benner, Ph.D. (Declaration executed June 26,
2015) (Ex. 2018; “Second Benner Declaration” or “Second Benner Decl.”).
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party disputes is prior art, describes the use of the SSN-MspA mutant in
experiments with results consistent with DNA translocation through the pore
protein. Ex. 1003, 107. Butler, moreover, presents a side-by-side
comparison of the structures of MspA and α-hemolysin, illustrating the
similar sizes of the pores, including their constriction zones, see id. at 94
(Fig. 6.2), leading Butler to state that “MspA structure is promising for
nanopore analysis.” Id. at 91 (italics removed). Thus, while prior art other
than the Butler reference might not have provided a reasonable expectation
of using porins other than α-hemolysin in nucleic acid analyses, that fact
does not explain why an ordinary artisan, presented with the teachings in
Butler about the similarities between SSN-MspA and α-hemolysin, lacked a
reasonable expectation that, like α-hemolysin, Butler’s SSN-MspA would be
useful in the nucleic acid analyses of the ’782 patent.
To that end, Patent Owner contends that the properties of the current
blockade events, which Butler characterized as potentially showing
translocation of DNA through the SSN-MspA porin, would not have led an
ordinary artisan to conclude that DNA actually had translocated through the
porin, in a manner that would have provided an ordinary artisan with a
reasonable expectation that the SSN-MspA could be successfully substituted
for the α-hemolysin taught in the ’782 patent. Supp. Resp. 19–21.
Moreover, Patent Owner contends, although Butler was hopeful that the
results obtained demonstrated translocation, Butler nonetheless recognized
that phenomena other than translocation may have been responsible for the
observed data. Id. at 22–23. Further, Patent Owner contends, the
disclosures in Butler, upon which Petitioner relies to show translocation, at
best show that DNA was driven into, rather than through, Butler’s SSN-
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MspA porin, as evidenced by Petitioner’s own witness, Dr. Branton. Id. at
23–27.
We acknowledge Patent Owner’s evidence that, when observing
current blockades in α-hemolysin, long and deep current blockades were
generally considered indicative of translocation of DNA through the protein,
whereas shorter duration blockades were not. See Supp. Resp. 19–21, 27
(citing Ex. 1003 (Butler), Ex. 2018 (Second Benner Decl.), Ex. 1022
(Kasianowicz),18 Ex. 2015 (Nakane),19 Ex. 1024 (the ’782 patent)),20 Ex.
2036 (Branton Deposition)).
As Petitioner notes (Reply 14), however, when evaluating the data
obtained using α-hemolysin, Butler states that it is “clear from the dC50
panel that many translocation-associated states were shorter than our 30 µs
cutoff time. Events demonstrating these short translocation signals were
classified as ‘Other’, and we hypothesize that fast translocation accounts for
a significant fraction of dC50 ‘Other’ type events listed in Table 4.1.” Ex.
1003, 44 (emphasis added). Accordingly, Butler does not teach that short
duration current blockades cannot be indicative of translocation.
As Patent Owner itself notes, moreover (Supp. Resp. 21), when
testing SSN-MspA, Butler observed that long and deep current blockades
occurred independently of whether single stranded DNA (dA50) was added

18 John J. Kasianowicz et al., Characterization of individual polynucleotide
molecules using a membrane channel, 93 PNAS 13770-13773 (1996) (Ex.
1022). In citing to Kasianowicz, Patent Owner uses an incorrect exhibit
number. See Supp. Resp. (citing Ex. 1011).
19 Jonathan J Nakane et al., Nanopore sensors for nucleic acid analysis, 15 J.
PHYS.: CONDENS. MATTER R1365–R1393 (2003) (Ex. 2015).
20 In citing to the ’782 patent, Patent Owner uses an incorrect exhibit
number. See Supp. Resp. 21, 27 (citing Ex. 2006).
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to the liquid media. Ex. 1003, 107 (“The rates of Short Mid, Short Deep and
Long Mid events always increase by at least a factor of 10 in the presence of
dA50, while the rate of Long Deep events seems independent of the presence
of dA50.”). Given the apparent differences between α-hemolysin and
SSN-MspA as to the measured characteristics of their current blockades in
the presence of DNA, we are not persuaded that Patent Owner has explained
convincingly why an ordinary artisan necessarily would have considered
results obtained using α-hemolysin predictive of whether SSN-MspA
translocated DNA.
Moreover, rather than suggesting only that DNA entered the
SSN-MspA molecule, but did not translocate through, Butler states expressly
that, “[p]erhaps . . . the increase in the rate of Short Deep events represents
translocation of dA50 through SSN-MspA.” Ex. 1003, 107; see also id. at
110 (“It will be necessary to obtain direct proof of translocation by directly
detecting single-stranded DNA molecules on the trans side of the bilayer
after an experiment.”) (citations omitted); id. at 111 (“The first critical
milestone for this project will be verification of ssDNA translocation
through a mutant MspA pore.”). Thus, while an ordinary artisan viewing
Butler’s statements regarding interaction of SSN-MspA with DNA might not
have understood translocation necessarily to have been proved, Patent
Owner does not persuade us that, reading the reference as a whole, a
preponderance of the evidence fails to support Petitioner’s contention that
there was a reasonable expectation that Butler’s protein would be suitable in
the methods of the ’782 patent.
We acknowledge the speculative nature of Butler’s disclosures
regarding translocation. It is well-settled, however, that “[o]bviousness does
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not require absolute predictability of success. . . . For obviousness under
§ 103, all that is required is a reasonable expectation of success.” In re
Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (quoting In re O’Farrell, 853
F.2d 894, 903–04 (Fed. Cir. 1988)) (emphasis removed).
In the instant case, as discussed above, Butler presents a side-by-side
comparison of the structures of α-hemolysin, used in the methods of the ’782
patent, and the MspA porin, illustrating the similar sizes of the pores,
including their constriction zones. Ex. 1003, 94 (Fig. 6.2). Summarizing its
structural attributes, Butler states that “MspA structure is promising for
nanopore analysis.” Id. at 91 (italics removed). Butler also explains that the
MspA porin “has many advantageous characteristics for nucleic acid
analysis including a short, narrow inner constriction, remarkable robustness,
ease of use, and the retention of pore-forming activity despite the
introduction of multiple amino-acid substitutions.” Id. at 88. Butler then
describes a single specific mutant version of that protein, SSN-MspA, which
exhibited properties causing Butler to opine that it was capable of
translocating DNA, though that property had not yet been verified. Id. at
107, 111.
Thus, rather than requiring the ordinary artisan to vary numerous
parameters, select from numerous choices, or apply a promising but
unguided general approach (In re O’Farrell, 853 F.2d at 903), Butler
provided a single specific protein, and identified a number of properties
explaining why that protein reasonably would have been expected to be
equivalently useful to α-hemolysin in methods of nucleic acid analysis. An
ordinary artisan, therefore, need only have substituted Butler’s SSN-MspA
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porin for the α-hemolysin in the ’782 patent’s nucleic acid analysis methods
to verify the usefulness of the SSN-MspA in those methods.
Indeed, the facts in the instant case are similar to those in In re
O’Farrell, where the court found that a reasonable expectation of success
had been established. In O’Farrell, the claims were directed to expressing a
hybrid protein in bacteria. 853 F.2d at 895. As here, the cited prior art
reference did not conclusively establish that those proteins would be
produced using the methods the reference described. Id. at 900. Instead, as
here, the cited reference only speculated at success, and explained how
success might be verified. Id. at 901 (“It would be interesting to examine the
expression of a normally translated eukaryotic sequence in pBGP120. If an
inserted sequence contains a ribosome binding site that can be utilized in
bacteria, production of high levels of a readthrough transcript might allow
for extensive translation of a functional eukaryotic polypeptide.”) (quoting
cited reference; emphases added).
In summarizing its conclusion in O’Farrell, the court pointed to facts
similar to those presented in the instant case, stating that “the prior art
explicitly suggested the substitution that is the difference between the
claimed invention and the prior art, and presented preliminary evidence
suggesting that the method could be used to make proteins.” Id. Thus,
given the overall teachings in Butler, discussed above, the speculative nature
of Butler’s disclosure regarding translocation does not persuade us that an
ordinary artisan lacked a reasonable expectation that Butler’s SSN-MspA
protein, like α-hemolysin, would be capable of translocating nucleic acids,
and, therefore, would be useful the ’782 patent’s nucleic acid analysis
methods.
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Patent Owner seeks to discredit Dr. Branton’s obviousness testimony
by pointing out that, when reviewing a draft paper that included the
experimental results reported in the Butler thesis, as well as additional
results, Dr. Branton questioned whether translocation had occurred. Supp.
Resp. 27–29. Patent Owner directs us to evidence purporting to show that,
before recommending the paper for publication, the group reviewing the
draft, which included Dr. Branton, required the authors to perform additional
experiments to conclusively prove that nucleic acid had been translocated
through the MspA porins. Id. at 30–34. Patent Owner contends that the
instant facts are, therefore, consistent with those in In re Carroll, 601 F.2d
1184, 1186–87 (CCPA 1979), in which an ordinarily skilled reviewer’s
negative assessment of a master’s thesis, made prior to filing the application
at issue, was held to demonstrate that the thesis did not establish the
obviousness of the subject matter disclosed therein. Supp. Resp. 34–35.
We do not find these arguments persuasive. As to the alleged
inconsistencies in Dr. Branton’s testimony, as discussed above, we find that
the teachings in the references themselves support finding that an ordinary
artisan would have been motivated to substitute Butler’s SSN-MspA for the
’782 patent’s α-hemolysin, and would have had a reasonable expectation
that Butler’s protein would work in the ’782 patent’s nucleic acid analysis
methods. As to the proposition that ordinary artisans would not have viewed
Butler’s data as conclusively proving that DNA had translocated through the
porin, as discussed above, O’Farrell makes it clear that conclusive proof is
not required to show a reasonable expectation of success. Thus, even
assuming evidence indicates that a group reviewing a relevant scientific
manuscript for publication requested additional experiments to “prove”
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translocation of nucleic acid, such evidence does not dictate that we find no
reasonable expectation of success here.
Patent Owner also contends that the testimony of Petitioner’s expert
witnesses, submitted with the first Petition in this proceeding to show that
the ’550 patent’s claims are not entitled to priority to the earlier filed
provisional application (Ex. 1016), demonstrates the absence of a reasonable
expectation of translocation, because the relevant disclosures in Butler and
the provisional application are similar. Supp. Resp. 36–39. We are not
persuaded.
We first note that the standards for obviousness and written
description support differ. As noted above, absolute certainty is not required
to show a reasonable expectation of success in obviousness determinations.
O’Farrell, 853 F.2d at 903–04. In contrast, when evaluating disclosures for
descriptive support, “[o]ne shows that one is ‘in possession’ of the invention
by describing the invention, with all its claimed limitations, not that which
makes it obvious.” Lockwood v. American Airlines, Inc., 107 F.3d 1565,
1572 (Fed. Cir. 1997).
We are not persuaded, moreover, that the current blockade events
described in the provisional application are similar to those described in
Butler. Specifically, the provisional application describes the events as “too
brief to . . . estimate the depth of the blockade.” Ex. 1016, 14. In contrast,
Butler was able to ascertain the depths of the blockades posited as
representing translocation, with accuracy sufficient to allow their
presentation in a graph. Ex. 1003, 109 (Fig. 6.8). Butler also expressly
characterized the events posited as representing translation as “Short Deep
events.” Id. at 107. Accordingly, the testimony of Petitioner’s expert
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witnesses regarding the disclosure in the provisional application does not
undermine Butler’s suggestion of a reasonable expectation of success.
Patent Owner contends that analysis of multiple analytes, as taught in
the ’782 patent, requires discriminating between different polymers based on
their constituent monomers, a capacity that an ordinary artisan would not
have reasonably expected Butler’s SSN-MspA to have. Supp. Resp. 39–42
(citing Ex. 2015 (Nakane), Ex. 1026 (Deamer), Ex. 2018 (Second Benner
Decl.)). We are not persuaded, however, that the ’782 patent’s disclosure of
characterizing heterogeneous mixtures is limited to monomer-dependent
analysis.
As noted above, and as Patent Owner recognizes (Supp. Resp. 16),
Example 6 of the ’782 patent uses α-hemolysin to establish that there is a
“[r]elationship between polymer length and channel blockade duration.”
Ex. 1024, 20:11–12. Because of this relationship between polymer length
and channel blockade duration, the ’782 patent explains that a
heterogeneous sample containing a plurality of analytes (as required by
claim 10) can be analyzed, “yielding a size distribution of molecules in the
mixture.” Id. at 4:54–55.
As discussed above, Butler’s SSN-MspA and the ’782 patent’s
α-hemolysin are closely similar as to pore size and structure. Ex. 1003, 94
(Fig. 6.2). Accordingly, even assuming that an ordinary artisan did not
reasonably expect Butler’s SSN-MspA to be able to distinguish between
different polymers in a mixed sample based on the polymers’ constituent
monomers, that fact does not persuade us that an ordinary artisan lacked a
reasonable expectation that SSN-MspA would have been able to provide a
size distribution in a mixed sample containing a plurality of different
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analytes, as taught in the ’782 patent, in a fashion similar to α-hemolysin.
To the contrary, given the structural and size similarities between Butler’s
SSN-MspA and the ’782 patent’s α-hemolysin, an ordinary artisan would
have reasonably expected SSN-MspA to be useful in the ’782 patent’s
processes of providing a size distribution in a mixed sample containing a
plurality of different analytes, encompassed by claim 10.
In sum, for the reasons discussed, having considered the prior art
advanced by Petitioner in light of Patent Owner’s arguments and evidence
regarding the cited references’ teachings, we find, based on the teachings in
those references, that an ordinary artisan would have been prompted to
substitute Butler’s SSN-MspA for the α-hemolysin used in the processes of
analyzing nucleic acid taught in the ’782 patent, and would have had a
reasonable expectation that the SSN-MspA would work in those processes.
Accordingly, an ordinary artisan would have had reason to perform, and
would have had a reasonable expectation of successfully performing, a
process having all of the steps and features required by claim 10 of the ’550
patent.
2. Secondary Considerations/Objective Indicia
When assessing obviousness, in addition to the teachings in the prior
art, the objective indicia of nonobviousness must be considered “as part of
all the evidence, not just when the decision maker remains in doubt after
reviewing the art.” Eurand, Inc. v. Mylan Pharm. Inc. (In re
Cyclobenzaprine Hydrochloride Extended–Release Capsule Patent Litig.),
676 F.3d 1063, 1076–77 (Fed. Cir. 2012) (citation omitted).
Although Petitioner bears the ultimate burden of persuasion under
35 U.S.C. § 316(e), as Petitioner contends (Supp. Reply 22), Patent Owner
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must establish a nexus between the objective evidence of nonobviousness
and the claimed subject matter. See In re GPAC Inc., 57 F.3d 1573, 1580
(Fed. Cir. 1995) (“For objective evidence to be accorded substantial weight,
its proponent must establish a nexus between the evidence and the merits of
the claimed invention.”).
In particular, the objective indicia “must be tied to the novel elements
of the claim at issue” and must “‘be reasonably commensurate with the
scope of the claims.’” Institut Pasteur & Universite Pierre Et Marie Curie
v. Focarino, 738 F.3d 1337, 1347 (Fed. Cir. 2013) (quoting Rambus Inc. v.
Rea, 731 F.3d 1248, 1257 (Fed. Cir. 2013)).
Patent Owner contends that objective evidence of nonobviousness
shows that that “(1) the claimed method performed unexpectedly better than
the methods using α-HL (the nanopore of choice prior to the inventors’
discovery); (2) Illumina, the world leader in DNA sequencing, licensed the
‘550 patent; and (3) the claimed method garnered industry-wide praise,
including from Petitioner itself.” Supp. Resp. 43.
We agree with Petitioner that Patent Owner’s objective evidence of
nonobviousness is not sufficiently commensurate in scope with the subject
matter encompassed by claim 10. See Supp. Reply 23–24.
Claim 1, from which claim 10 depends, recites a process of using an
Msp porin to detect an “analyte” in a first liquid medium. Ex. 1001, 103:33–
43. Claim 10 requires either the first liquid medium, or a second liquid
medium, to contain a plurality of different analytes. Id. at 104:39–41. As
noted above, the ’550 patent states that the term “analyte” encompasses a
wide variety of different substances, having widely varying properties,
including “a nucleotide, a nucleic acid, an amino acid, a peptide, a protein, a
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polymer, a drug, an ion, a pollutant, a nanoscopic object, or a biological
warfare agent.” Id. at 8:45–48.
In contrast, the evidence to which Patent Owner directs us to show
that Msp porins function unexpectedly better than α-hemolysin only relates
to DNA. See Ex. 2014, 16060 (“Passing DNA with a series of double-
stranded sections through MspA provides proof of principle of a simple
DNA sequencing method using a nanopore.”);21 Ex. 2031, 56 (“We have
combined Phi29 DNA polymerase (DNAP) as a molecular motor with a
mutant MspA nanopore to allow controlled movement of a DNA strand
through the pore.”);22 id. at 61, 62 (“using [a] Phi29 DNA polymerase to
control the movement of intact DNA strands through a nanopore”);
Ex. 2023, 1 (“DNA passed through the protein nanopore”);23 Ex. 2037, 1
(sequencing bacteriophage genome).24 Patent Owner does not direct us to
any clear or specific evidence suggesting that the alleged superiority of the
claimed Msp porin over α-hemolysin as to DNA analysis would extend to
any other analytes encompassed by claim 10. Accordingly, we agree with

21 Ian M. Derrington et al., Nanopore DNA sequencing with MspA, 107
PNAS 16060-16065 (2010) (Ex. 2014).
22 James Clarke et al., WO 2012/107778 A2 (published Aug. 16, 2012) (Ex.
2031).
23 Monica Heger, Proof-of-Principle Study Shows MspA Is Superior to
Alpha-Hemolysin for Protein Nanopore Sequencing,
http://www.genomeweb.com/print/948013 (2010) (Ex. 2023).
24 Monica Heger, Pre-print Study Demonstrates Nanopore Sequencing of
Bacteriophage Genome with MspA Pore,
http://www.genomeweb.com/print/1407801?utm_source=SilverpopMailing
&utm_medium=email&utm_campaign=In%20Sequence%3A%20MspA%2
0Nanopore%… (2014) (Ex. 2037).
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Petitioner that the evidence advanced by Patent Owner to show
unexpectedness is not reasonably commensurate in scope with the subject
matter recited in claim 10.
Similarly, the evidence Patent Owner advances regarding the
company Illumina licensing the claimed technology all relates to DNA
sequencing. See Supp. Resp. 47–48; Ex. 1014 (“Illumina Inc. has licensed
the rights to a DNA sequencing technology . . . .”);25 Ex. 2026, 2 (“nanopore
DNA sequencing”).26 The evidence of industry praise all relates to DNA
sequencing also. See Supp. Resp. 48–50 (citing Exs. 2013, 2030, 2026,
2021, 2027–2029, 2031, 2038–42).
As with the evidence of unexpected results, Patent Owner does not
direct us to clear or specific evidence suggesting that the asserted licensing
activity or industry praise extends to the detection of any of the many and
varied analytes, other than DNA, encompassed by claim 10. Accordingly,
we agree with Petitioner that the evidence advanced by Patent Owner to
show licensing activity and industry praise is not reasonably commensurate
in scope with the subject matter recited in claim 10.
3. Ultimate Conclusion of Obviousness
As discussed above, having considered the prior art advanced by
Petitioner in light of Patent Owner’s arguments and evidence regarding the
cited references’ teachings, we find, based on the teachings in the ’782
patent and Butler, that an ordinary artisan would have had reason to perform,

25 UAB News, Licensing deal marks coming of age for UAB-UW nanopore
sequencing technology, http://www.uab.edu/news/innovation/item/3847-
licensing-deal-marks-coming-of-age-for-u... (accessed 2014) (Ex. 1014).
26 Hagan Bayley, Nanopore sequencing: from imagination to reality, Clin.
Chem. Author manuscript; available in PMC 2015 April 21 (Ex. 2026).
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and would have had a reasonable expectation of successfully performing, a
process having all of the steps and features required by claim 10 of the ’550
patent. As also discussed above, having considered Patent Owner’s
evidence and arguments regarding objective indicia of nonobviousness, we
find that Patent Owner’s evidence is not sufficiently commensurate in scope
with the subject matter recited in claim 10. Considering the record before
us, Patent Owner’s evidence and argument do not outweight Petitioner’s
showing of obviousness here.
Accordingly, under these circumstances, taking into consideration the
record as a whole, we conclude that Petitioner has shown by a
preponderance of the evidence that an ordinary artisan would have
considered the process of claim 10 obvious in view of the ’782 patent and
Butler.
F. Patent Owner’s Motion to Exclude Evidence
Patent Owner moves to exclude lines 21–25 of page 136 of Dr.
Benner’s Deposition (Ex. 1058), cited on page 15 of Petitioner’s Reply, and
lines 15–19 of page 153 of Dr. Benner’s Deposition, cited on pages 3 and 10
of Petitioner’s Reply. Mot. to Exclude 1.
We deny Patent Owner’s motion to exclude the disputed testimony.
Patent Owner contends that Petitioner uses the testimony on page 136
of Dr. Benner’s deposition in a misleading fashion, and that Petitioner cites
it out of context, and, therefore, the testimony should be excluded under
Federal Rule of Evidence (“FRE”) 403. Mot. to Exclude 2–6. For
essentially the same reasons, Patent Owner contends that the disputed
testimony on page 153 of Dr. Benner’s Deposition also should be excluded
under Rule 403. Id. at 6–7.
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The Board “may exclude relevant evidence if its probative value is
substantially outweighed by a danger of one or more of the following: unfair
prejudice, confusing the issues, misleading the jury, undue delay, wasting
time, or needlessly presenting cumulative evidence.” FRE 403. That
Petitioner may have cited the disputed testimony out of context, or used it to
support positions contrary to positions taken elsewhere in the proceeding,
does not persuade us that the disputed testimony itself should be excluded
under FRE 403. The Board, unlike a lay jury, has significant experience in
evaluating expert testimony. Accordingly, the danger of prejudice in this
proceeding is considerably lower than in a conventional district court trial.
We are not persuaded, moreover, that the issue of whether a party’s
argument cites testimony in proper context relates to the admissibility of that
testimony. The Board is capable of determining for itself whether a party’s
argument cites testimony in its proper context.
As to relevance, Patent Owner does not contend that the disputed
testimony on page 136 of Dr. Benner’s Deposition fails to meet any of the
broad criteria expressly set out in FRE 401. See Mot. to Exclude 2–4.
Rather, Patent Owner contends that the disputed testimony is irrelevant
because it is improper hindsight evidence, and is evidence of the inventor’s
viewpoint, rather than that of an ordinary artisan. Id.
We are not persuaded. The issue of whether Dr. Benner’s disputed
testimony should be viewed as improper hindsight goes to its weight, rather
than its admissibility. Similarly, the issue of whether Dr. Benner testified as
to the perspective of an inventor, rather than an ordinary artisan, also goes to
the testimony’s weight, rather than its admissibility. Indeed, none of the
cases Patent Owner cites stands for the proposition that, in an obviousness
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determination, testimony or other evidence is inadmissible under FRE 402
because it relates to improper hindsight, or the perspective of an inventor
rather than an ordinary artisan. See Ortho-McNeil Pharm., Inc. v. Mylan
Labs., Inc., 520 F.3d 1358, 1364–65 (Fed. Cir. 2008); Apple Inc. v.
ContentGuard Holdings, Inc., IPR2015-00453, 2015 WL 4467403, at *8
(PTAB July 13, 2015)); Amgen, Inc. v. F. Hoffmann- La Roche, Ltd., 580
F.3d 1340, 1363 (Fed. Cir. 2009).
In sum, for the reasons discussed, we deny Patent Owner’s motion to
exclude lines 21–25 of page 136 of Dr. Benner’s Deposition (Ex. 1058), and
lines 15–19 of page 153 of Dr. Benner’s Deposition.
III. CONCLUSION
For the foregoing reasons, Petitioner has not proved by a
preponderance of the evidence that claim 10 of the ʼ550 patent is anticipated
by Butler under 35 U.S.C. § 102(b).
For the foregoing reasons, Petitioner has not proved by a
preponderance of the evidence that claims 17 and 18 are anticipated by the
Wong Poster under 35 U.S.C. § 102(b).
For the foregoing reasons, Petitioner has not proved by a
preponderance of the evidence that claims 17 and 18 are anticipated by the
Wong Abstract under 35 U.S.C. § 102(b).
For the foregoing reasons, Petitioner has proved by a preponderance
of the evidence that claim 10 is unpatentable for obviousness over the ’782
patent and Butler under 35 U.S.C. § 103(a).
IV. ORDER
It is ORDERED that claim 10 of the ’550 patent has been shown by a
preponderance of the evidence to be unpatentable;
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FURTHER ORDERED that Patent Owner’s Motion to Amend is
granted;
FURTHER ORDERED that Patent Owner’s Motion to Exclude is
denied; and
FURTHER ORDERED that, because this is a final written decision,
parties to this proceeding seeking judicial review of our Decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.
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PETITIONER:

Steven Lendaris
Robert Scheinfeld
BAKER BOTTS LLP
steven.lendaris@bakerbotts.com
robert.scheinfeld@bakerbotts.com

PATENT OWNER:

Dorothy P. Whelan
Sean P. Daley
Michael Kane
FISH & RICHARDSON P.C.
Whelan@fr.com
Daley@fr.com
IPR39211-0004IP3@fr.com