Trials@uspto.gov
`Tel: 571-272-7822
`
`
`Paper 28
`Entered: April 27, 2015
`
`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 Owner.
`_______________
`
`Case IPR2015-00057
`Patent 8,673,550 B2
`_______________
`
`
`Before FRANCISCO C. PRATS, JACQUELINE WRIGHT BONILLA, and
`SHERIDAN K. SNEDDEN, Administrative Patent Judges.
`
`PRATS, Administrative Patent Judge.
`
`
`
`DECISION
`Granting Petitioner’s Motion for Joinder
`and Instituting Inter Partes Review
`37 C.F.R. §§ 42.108, 42.122
`
`
`
`
`
`Tel: 571-272-7822
`
`
`Paper 28
`Entered: April 27, 2015
`
`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 Owner.
`_______________
`
`Case IPR2015-00057
`Patent 8,673,550 B2
`_______________
`
`
`Before FRANCISCO C. PRATS, JACQUELINE WRIGHT BONILLA, and
`SHERIDAN K. SNEDDEN, Administrative Patent Judges.
`
`PRATS, Administrative Patent Judge.
`
`
`
`DECISION
`Granting Petitioner’s Motion for Joinder
`and Instituting Inter Partes Review
`37 C.F.R. §§ 42.108, 42.122
`
`
`
`
`
`
`Case IPR2015-00057
`Patent 8,673,550 B2
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`I. INTRODUCTION
`A. Statement of the Case
`On October 13, 2014, Oxford Nanopore Technologies Ltd.
`(“Petitioner”) filed a Petition (Paper 1, “Pet.”) requesting inter partes review
`of claims 1, 5, 6, 10–12, 16–19, 23, 25, 29, 30, 34, 37, and 41 of U.S. Patent
`No. 8,673,550 B2 (Ex. 1001, “the ’550 patent”). On the same day,
`Petitioner also filed a Motion for Joinder (Paper 3, “Joinder Motion”),
`requesting joinder of the Petition with another instituted proceeding, Oxford
`Nanopore Techs. v. University of Washington, Case IPR2014-00513 (“the
`’513 proceeding”), also involving challenges to claims of the ’550 patent.
`Petitioner filed its Joinder Motion within one month of the September 15,
`2014, institution date of the ’513 proceeding, as required by 37 C.F.R.
`§ 42.122(b).
`The University of Washington and UAB Research Foundation
`(collectively, “Patent Owner”) filed an Opposition to Petitioner’s Motion for
`Joinder (Paper 7, “Opp. to Joinder”), and Petitioner filed a Reply to the
`Opposition to Motion for Joinder (Paper 8, “Reply to Opp. to Joinder”).
`Thereafter, Patent Owner filed a Preliminary Response. Paper 9, “Prelim.
`Resp.”
`We have jurisdiction under 35 U.S.C. § 314, which provides that an
`inter partes review may be instituted only if “the information presented in
`the [Petition and Preliminary Response] . . . shows that there is a reasonable
`likelihood that the petitioner would prevail with respect to at least 1 of the
`claims challenged in the petition.” 35 U.S.C. § 314(a).
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`In its Preliminary Response, Patent Owner states that, in its Motion to
`Amend in the ’513 proceeding, it canceled all challenged claims in the ’550
`patent, except claims 10, 17, and 18, an action that took place after Petitioner
`filed its Petition in the current case. Prelim. Resp. 4. Therefore, Patent
`Owner contends, “the only claims left for consideration in the present
`proceeding are claims 10, 17, and 18.” Id. We agree and, accordingly,
`consider Petitioner’s challenges only as to claims 10, 17, and 18 in the
`instant case.
`Upon consideration of the instant Petition, we conclude that Petitioner
`has established a reasonable likelihood that it would prevail in its challenge
`to claim 10 of the ’550 patent, but not as to claims 17 and 18. We, therefore,
`institute an inter partes review as to claim 10. For the reasons discussed
`below, we also grant Petitioner’s Joinder Motion.
`B. Related Proceedings
`Concurrently with the Petition filed in the ’513 proceeding, Petitioner
`filed another Petition (“the ’512 Petition”) advancing additional challenges
`to the claims of the ’550 patent. Oxford Nanopore Techs. v. University of
`Washington, Case IPR2014-00512, Paper 1 (“the ’512 proceeding”). The
`Board declined to institute trial on any of the grounds presented in the ’512
`Petition. Oxford Nanopore Techs. v. University of Washington, Case
`IPR2014-00512, slip op. 20–21 (PTAB Sept. 15, 2014).
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`C. Proposed Grounds of Unpatentability
`Petitioner contends that claims 10, 17, and 18 are unpatentable under
`35 U.S.C. § 103(a) based on the following specific grounds (Pet. 6)1:
`
` Reference[s]
`The ’782 patent2 in view of the
`Gundlach Grant Abstract3 or Butler4
`
`
`The ’782 patent in view of the
`Gundlach Grant Abstract
`
`Claim[s] challenged
`10
`
`17 and 18
`
`
`D. 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 multimeric protein through
`which nutrients pass in mycobacteria. Id. at 7:53–55, 18:32–57. Wild-type
`M. smegmatis porins include MspA, MspB, MspC, and MspD. Id. at 18:59–
`
`
`1 Petitioner supports its challenges with Declarations by James Willcocks,
`Ph.D. (“Willcocks Decl.”) (Ex. 1009), Daniel Branton, Ph.D. (“Branton
`Decl.”) (Ex. 1012), and Dr. Roland Benz (“Benz Decl.”) (Ex. 1013).
`2 George Church et al., U.S. Patent No. 5,795,782 (issued Aug. 18, 1998)
`(Ex. 1006).
`3 Abstract of Gundlach, J, Engineering MspA for Nanopore Sequencing,
`NHGRI Grant Application, No. 1R21HG004145-01, awarded September 25,
`2006 (Ex. 1005).
`4 Thomas Butler, Nanopore Analysis of Nucleic Acids (2007) (Ph.D.
`dissertation, Univ. of Washington, Seattle, Washington) (Ex. 1003).
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`61. The ’550 patent discloses that wild-type or mutant Msp porins may be
`used in its analytical methods. Id. at 7:60–64.
`The ’550 patent discloses that the tunnel of an Msp porin includes two
`sections, a “vestibule,” and a “constriction zone.” Id. at 27:15–16.
`The ’550 patent states that a “‘vestibule’ refers to the cone-shaped
`portion of the interior of an Msp porin whose diameter generally decreases
`from one end to the other along a central axis, where the narrowest portion
`of the vestibule is connected to the constriction zone. A vestibule may also
`be referred to as a ‘goblet.’” Id. at 27:9–14; see also id. at Fig. 1 (showing
`structure of wild-type MspA porin).
`A “‘constriction zone’ refers to the narrowest portion of the tunnel of
`an Msp porin, in terms of diameter, that is connected to the vestibule.” Id. at
`27:35–37.
`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 further:
`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
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`presence of the analyte.” Id. at 8:13–16. Thus, 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
`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 are thought to inhibit DNA entry into the
`porin. Id. at 42:15–19. Thus, the ’550 patent describes embodiments 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 porin. Id. at 42:19–22, 45:45–46:13.
`Claims 1, 10, 17, and 18, recite the challenged subject matter under
`consideration herein, and read as follows:
`
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`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.
`
`
`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
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`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 Techs., LLC,
`778 F.3d 1271, 1278–81 (Fed. Cir. 2015). Under that standard, claim terms
`are given 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).
`Petitioner “submits that no terms, other than those already construed
`by the Board in connection with IPR2014-00513, are in need of
`construction.” Pet. 20. Patent Owner does not contend otherwise, nor does
`Patent Owner proffer any specific construction of any claim terms.
`In the ’513 proceeding we noted that claim 1 of the ’550 patent
`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.” Oxford
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`Nanopore Techs. v. University of Washington, Case IPR2014-00513, slip
`op. 8 (PTAB Sept. 15, 2014) (citing Ex. 1001, 103:35–39, 105:22–23).
`Given its express language, we construed claim 1 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. Id. at 9. We apply that construction herein.
`B. Obviousness of claim 10 over the’782 patent and Butler
`1. The ’782 patent (Ex. 1006)
`The ’782 patent discloses a method for evaluating polymer molecules,
`such as DNA or RNA, in which “[t]wo separate pools of liquid-containing
`medium and an interface between the pools are provided. The interface
`between the pools is capable of interacting sequentially with the individual
`monomer residues of a single polymer present in one of the pools.”
`Ex. 1006, 1:42–47. The ’782 patent discloses that the pools may contain
`electrically conductive media which are “separated by an impermeable
`barrier containing an ion permeable passage, and measurements of the
`interface characteristics include establishing an electrical potential between
`the two pools such that ionic current can flow across the ion permeable
`passage.” Id. at 2:37–42.
`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 (e.g.,
`size, identity) and/or the polymer as a whole (e.g., size).” Id. at 2:42–47.
`The ’782 patent explains further that “[s]everal individual polymers, e.g., in
`a heterogenous [sic] mixture, can be characterized or evaluated in rapid
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`succession, one polymer at a time, leading to characterization of the
`polymers in the mixture.” Id. at 1:51–54.
`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 that sequential determination of the
`identities of the individual nucleotides in the nucleic acid molecules offers a
`number of advantages in nucleic acid sequencing, including “reduction in
`the number of sequencing steps, and increasing the speed of sequencing and
`the length of molecule capable of being sequenced.” Id. at 5:38–40.
`The ’782 patent discloses that ion permeable passages useful in its
`invention include “naturally occurring, recombinant, or mutant proteins
`which permit the passage of ions under conditions where ions are present in
`the medium contacting the channel or pore. Synthetic pores are also
`included in the definition.” Id. at 3:15–18. “Preferred channels for use in
`the invention include the α-hemolysin toxin from S. aureus and maltoporin
`channels.” Id. at 4:65–67. The ’782 patent discloses, however, 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.” Id. at 10:13–16.
`In Example 5 of the ’782 patent, α-hemolysin from S. aureus was
`used to form a current-conducting channel in a lipid bilayer separating two
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`pools of electrically conductive media. Id. at 19:12–25. When a voltage
`was applied across the membrane, poly A, poly C, and poly U molecules in
`the media caused transient measurable current blockades consisting of “85–
`90% reductions of current amplitude [which] lasted up to several
`milliseconds.” Id. at 19:44–46.
`
`2. Butler (Ex. 1003)
`Butler discloses that nanopore analysis of nucleic acids “has the
`potential to be a central component of a fundamentally new DNA
`sequencing methodology.” Ex. 1003, 5.5 Like the ’782 patent, Butler
`explains that nanopore nucleic acid analysis involves placing a current-
`conducting channel, such as the α-hemolysin protein from S. aureus, in a
`lipid bilayer separating two pools of electrically conductive media, and
`applying a voltage across the membrane. Id. at 15–17. Also, like the ’782
`patent, Butler explains that the voltage drives the negatively charged DNA
`through the channel, which is observed as a transient blockade of the ionic
`current of the system, the measured reduction in current allowing detection
`of the DNA. Id.
`Butler discloses results from a “collaborative research effort . . . to
`engineer a porin (‘MspA’) found in the outer membrane of Mycobacterium
`smegmatis for application in nanopore analysis of nucleic acids.” Id. at 88.
`Butler discloses that the MspA porin “has many advantageous characteristics
`for nucleic acid analysis including a short, narrow inner constriction,
`
`
`5 In citing to Butler, we cite to the page numbers inserted at the bottom right
`corner of each of the pages of Exhibit 1003.
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`remarkable robustness, ease of use, and the retention of pore-forming
`activity despite the introduction of multiple amino-acid substitutions.” Id.
`Butler found initially, however, that the wild-type MspA porin did not
`interact with single-stranded DNA molecules (ssDNA). Id. Nonetheless, “a
`mutant with all of the excess negative charge removed has recently
`demonstrated frequent transient current blockades in the presence of ssDNA.
`We are presently working to verify the exciting possibility that these
`blockades are a result of interaction between ssDNA and the MspA mutant.”
`Id.
`
`In particular, Butler describes experiments in which the MspA triple
`mutant D90S/D91S/D93N (“SSNMspA”) provided data “consistent with the
`scenario where dA50 [ssDNA] molecules are electrophoretically driven into
`the SSN-MspA pore and cause transient blockades of the ionic current.” Id.
`at 107. Despite these results, Butler discloses:
`While this dA50-induced blockade explanation is both
`plausible and encouraging, we can identify at least two other
`candidate mechanisms for the observed blockade rate increase.
`First, it is possible and even likely that MspA gating can be
`induced by molecules other than single-stranded nucleic acids.
`For example, gating in α-HL can be induced by a variety of
`divalent and trivalent cations. Such molecules would be
`contaminants in our DNA experiments. . . . A second
`possibility is that the moderate rate of transient blockades
`observed in the DNA-free control experiments results from
`intrinsic conformational
`fluctuations of
`the SSN-MspA
`structure.
`
`Id. (citation omitted).
`Accordingly, Butler discloses, “[i]t will be necessary to obtain direct
`proof of translocation by directly detecting single-stranded DNA molecules
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`on the trans side of the bilayer after an experiment.” Id. at 110 (citations
`omitted). Butler discloses, moreover, that even if the blockades exhibited by
`the SSN-MspA mutant “are not caused by translocation of dA50, there are
`still a number of reasonable mutation strategies to pursue in our effort to
`engineer another protein pore that allows DNA translocation.” Id. at 111.
`Butler discloses, that if the “milestone” of DNA translocation is achieved,
`then we will begin a series of comparative experiments with a
`variety of mutants with the dual goals of optimizing MspA for
`nucleic acid analysis and understanding
`the nanoscale
`mechanisms that govern electrophoretic translocation of ssDNA
`and RNA through MspA. Results from these experiments will
`give significant insight into the physics underlying nanopore
`analysis and will hopefully lead to new MspA-based nanopore
`biosensors with improved analytical capabilities.
`
`
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`Id.
`
`3. Analysis
`Petitioner presents a claim chart to show where the features required
`by claim 1, from which claim 10 depends, may be found in the ’782 patent
`and Butler. Pet. 32–37. As to claim 10’s requirement that at least one of the
`two conductive media comprises a plurality of different analytes, Petitioner
`directs us (id. at 38) to column 1, lines 50–54, of the ’782 patent, which, as
`noted above, states 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.” Ex. 1006, 1:51–54.
`Petitioner contends that the ’782 patent describes methods having all
`of the steps and features of claim 10, except the use of an Msp porin. See
`Pet. 24, 38–39. Petitioner contends that an ordinary artisan would have been
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`motivated to modify the ’782 patent’s methods to incorporate Butler’s
`mutant MspA porin, 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.
`Petitioner persuades us, on the current record, that an ordinary artisan
`would have been prompted to use Butler’s mutant MspA porin as the
`channel protein in the nucleic acid analysis methods described in the ’782
`patent.
`As Petitioner discusses (Pet. 26), and as noted above, the ’782 patent
`discloses that any channel protein having appropriate properties may be used
`in its methods. Ex. 1006, 10:13–15. As Petitioner discusses (Pet. 29), and
`as noted above, Butler discloses that its “SSN-MspA” mutant exhibited
`properties consistent with the translocation of ssDNA through the protein’s
`pore, using essentially the same system as that described in the ’782 patent.
`Ex. 1003, 107. As Petitioner discusses (Pet. 26–27), and as noted above,
`Butler discloses that the MspA porin, in general, has a number of
`advantageous properties, including a short, narrow inner constriction,
`significant robustness, and ease of use. Ex. 1003, 88.
`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 MspA porins
`disclosed by Butler, Petitioner persuades us, on the current record, that an
`ordinary artisan would have been prompted to use Butler’s SSN-MspA
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`mutant porin in the ’782 patent’s nanopore-based nucleic acid analysis
`methods. On the current record, Patent Owner’s arguments do not persuade
`us to the contrary.
`Patent Owner contends that Butler expressed skepticism as to whether
`its results involved DNA translocation, and that Butler cautioned that
`mechanisms other than translocation may have been responsible for the
`results of its experiments. Prelim. Resp. 23–25. Thus, Patent Owner
`contends, an ordinary artisan “reading Butler’s cautionary statements
`regarding the inconclusiveness of his single-analyte experiments with
`respect to translocation would have had no reasonable expectation that the
`method could successfully be used with multiple analytes, as claim 10
`requires.” Id. at 25. Patent Owner contends that Petitioner offered no
`evidence to the contrary, and failed to address this issue entirely. Id.
`On this record, Patent Owner’s arguments do not persuade us that
`Petitioner has failed to provide a necessary showing for us to institute a trial
`on this ground.
`We acknowledge Butler’s recognition that the experimental results
`suggesting ssDNA translocation by the SSN-MspA protein may have been
`due to factors unrelated to translocation, and that translocation therefore
`required further verification. See Ex. 1003, 88, 107, 110–11. It is
`well-settled, however, that “[o]bviousness does 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).
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`As the Federal Circuit explained in Kubin, one circumstance in which
`the prior art fails to provide a reasonable expectation of success is where the
`art suggests “vary[ing] all parameters or try[ing] each of numerous possible
`choices until one possibly arrived at a successful result, where the prior art
`gave either no indication of which parameters were critical or no direction as
`to which of many possible choices is likely to be successful.” Id. at 1359
`(quoting O’Farrell, 853 F.2d at 903).
`Another circumstance in which the prior art fails to provide a
`reasonable expectation of success is where the art suggests exploring a
`“general approach that seemed to be a promising field of experimentation,
`where the prior art gave only general guidance as to the particular form of
`the claimed invention or how to achieve it.” Id.
`In the instant case, as noted above, Butler describes a single specific
`protein, SSN-MspA, with a specific amino acid sequence, that exhibits
`properties consistent with those required by the ’782 patent in its nanopore-
`based nucleic acid analytical methods. Thus, rather than requiring the
`ordinary artisan to vary numerous parameters, select from numerous choices,
`or apply a promising but unguided general approach, the artisan need only
`have substituted the SSN-MspA porin for the nanopores described in the
`’782 patent. That is, on the current record, given the teachings in the prior
`art advanced by Petitioner, an ordinary artisan need only have used Butler’s
`protein in the ’782 patent’s methods to verify its suitability in those methods.
`Accordingly, on the current record, Petitioner persuades us that ’550 patent
`simply confirmed the suitability, already suggested by Butler, of SSN-MspA
`in nanopore-based nucleic acid analysis.
`
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`16
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`Case IPR2015-00057
`Patent 8,673,550 B2
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`We, therefore, determine that, on this record, Petitioner has shown a
`reasonable likelihood of prevailing in its obviousness challenge to claim 10
`of the ’550 patent, based on the ’782 patent and Butler.
`C. Obviousness of claims 10, 17, and 18 over the’782 patent and
`the Gundlach Grant Abstract
`1. Gundlach Grant Abstract (Ex. 1005)
`The Gundlach Grant Abstract discloses that the “electrophoretic
`passage of single-strand DNA through a nanopore has the potential to
`become an inexpensive, ultrafast DNA sequencing technique.” Ex. 1005, 1.
`The Gundlach Grant Abstract states that its investigation “propose[s] to
`develop the Mycobacterium smegmatis porin A (MspA) into a new pore for
`nanopore sequencing.” Id. The Gundlach Grant Abstract discloses:
`MspA is a promising platform for engineering a nanopore
`sequencing device for a number of reasons: (i) Its short, narrow
`constriction zone may give it higher sequencing sensitivity and
`resolution. (ii) MspA is extremely robust (iii) Formation of
`stable MspA pores is easy and reliable. (iv) A wide range of
`stable MspA mutants can be readily engineered.
`
`
`Id.
`
`The Gundlach Grant Abstract discloses, however, that
`[i]n preliminary studies neither wild-type MspA nor MspA with
`a mutation in its constriction zone allowed translocation of
`DNA. Therefore, our goal is to tailor MspA for efficient
`translocation of DNA. We will remove excess negative charges
`from the rim and vestibule of the pore by site-directed
`mutagenesis, stabilize the loops near the constriction zone, and
`optimize the constriction zone for DNA passage. Translocation
`will be tested with a variety of ssDNA constructs in conditions
`designed to facilitate translocation. Once translocation is
`realized, further experiments will inform subsequent mutations
`to optimize MspA for nanopore sequencing.
`
`17
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`Id.
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`Analysis
`Petitioner cites the ’782 patent as describing systems and methods
`having all of the features of claims 10, 17, and 18 of the ’550 patent, except
`the use of the Mycobacterium smegmatis porin required by the challenged
`claims. Pet. 24, 45. Petitioner contends that an ordinary artisan would have
`been motivated to modify the ’782 patent’s methods to incorporate a mutant
`MspA porin, such as that disclosed in the Gundlach Grant Abstract, 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 the Gundlach Grant
`Abstract’s MspA mutant porin in the methods of the ’782 patent “nothing
`more than the predictable use of a prior art element according to its
`established function.” Id. at 29, 31, 46, 47.
`We agree with Patent Owner (see Prelim. Resp. 20–23) that Petitioner
`has not established a reasonable likelihood of prevailing in its obviousness
`challenge to claims 10, 17, and 18 of the ’550 patent, based on the ’782
`patent and the Gundlach Grant Abstract.
`We acknowledge the teachings in the Gundlach Grant Abstract, noted
`above, that MspA porins have qualities that would have made them desirable
`for use in nanopore-based methods of nucleic acid analysis. Ex. 1005, 1. As
`noted above, and as Patent Owner points out, however (Prelim. Resp. 20–
`21), wild-type and mutant MspA porins had not achieved the DNA
`translocation capacity required in the methods of the ’782 patent. See Ex.
`1005, 1 (“In preliminary studies neither wild-type MspA nor MspA with a
`
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`18
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`mutation in its constriction zone allowed translocation of DNA.”). Indeed,
`the Gundlach Grant Abstract merely proposes strategies by which a
`potentially useful porin might be obtained by modifying existing wild-type
`or mutant MspA porins. Id.
`Thus, contrary to Petitioner’s assertions (Pet. 29, 31, 46, 47), rather
`than disclosing a specific protein like Butler, discussed above, the Gundlach
`Grant Abstract does not describe a prior art element having an established
`function which an ordinary artisan would have simply substituted for the
`pores used in the ’782 patent. To the contrary, the Gundlach Grant
`Abstract’s hopeful disclosure that a porin useful in nucleic acid analysis
`potentially might be obtained after pursuing different mutation strategies is
`the type of teaching discussed in Kubin as failing to provide a reasonable
`expectation of success. Kubin, 561 F.3d at 1359 (insufficient showing of
`reasonable expectation of success where prior art suggests exploring a
`“general approach that seemed to be a promising field of experimentation,
`where the prior art gave only general guidance as to the particular form of
`the claimed invention or how to achieve it”).
`In sum, Petitioner does not persuade us that the Gundlach Grant
`Abstract describes a prior art element having an established function that an
`ordinary artisan would have substituted for the pores used in the ’782 patent.
`Accordingly, Petitioner does not persuade us that it has established a
`reasonable likelihood of prevailing in its obviousness challenge to claims 10,
`17, and 18 of the ’550 patent, based on the ’782 patent and the Gundlach
`Grant Abstract.
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`D. Arguments under 35 U.S.C. § 325(d)
`Section 325(d) states that, “[i]n determining whether to institute or
`order a proceeding under this chapter, chapter 30, or chapter 31, the Director
`may take into account whether, and reject the petition or request because, the
`same or substantially the same prior art or arguments previously were
`presented to the Office.” 35 U.S.C. § 325(d)
`Patent Owner argues that we should exercise our discretion under
`§ 325(d) and deny the Petition, because granting it effectively provides
`Petitioner with an improper “second bite at the apple” which attempts to
`correct the deficiencies in the ’512 Petition, but which presents substantially
`the same references and arguments rejected in the Institution Decision in the
`’512 proceeding. Prelim. Resp. 1. Patent Owner contends that Petitioner is
`“not entitled to multiple attempts to ‘get it right,’ with each successive
`attempt guided by the Board.” Id. at 2.
`We acknowledge that the Board has, in certain instances, denied
`second or “follow-on” petitions for inter partes review (“IPR”) where those
`second petitions presented substantially the same prior art and arguments
`presented previously, or presented art and arguments which could have been
`presented previously, and merely addressed deficiencies in the fir
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