`571-272-7822 Entered: March 26, 2019
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`
`OXFORD NANOPORE TECHNOLOGIES, INC.,
`Petitioner,
`v.
`
`PACIFIC BIOSCIENCES OF CALIFORNIA, INC.,
`Patent Owner.
`____________
`
`Case IPR 2018-01792
`Patent 9,738,929 B2
`____________
`
`
`
`Before ULRIKE W. JENKS, ZHENYU YANG, and JAMES A. WORTH
`Administrative Patent Judges.
`
`JENKS, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a)
`
`
`
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`IPR2018-01792
`Patent 9,738,929 B2
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`I. INTRODUCTION
`
`A.
`
`Background
`Oxford Nanopore Technologies, Inc. (“Petitioner”), filed a Petition
`requesting an inter partes review of claims 1–17 (“the challenged claim”) of
`U.S. Patent No. 9,738,929 B2 (Ex. 1001, “the ’929 patent”). Paper 1
`(“Pet.”). Pacific Biosciences of California, Inc. (“Patent Owner”) filed a
`Preliminary Response to the Petition. Paper 6 (“Prelim. Resp.”).
`We have authority under 35 U.S.C. § 314, which provides that an
`inter partes review may not be instituted “unless . . . 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). Upon consideration
`of the arguments and evidence presented in the Petition and the Preliminary
`Response, we are not persuaded that Petitioner has established a reasonable
`likelihood that it would prevail in its challenges of any of the claims in the
`’929 patent. Accordingly, we decline to institute an inter partes review of
`claims 1–17.
`B.
`Related Proceedings
`Petitioner identifies district-court litigation involving the ’929 patent
`in Pacific Biosciences of California, Inc., v. Oxford Nanopore Technologies,
`Inc., which was consolidated into actions 1:17-cv-00275-LPS, 1:17-cv-
`01353-LPS (D. Del.). Pet. 2. Petitioner also identifies IPR2018-017851 as
`relating to the ’929 patent. Id.
`
`
`1 The proceeding in IPR2018-01785 was terminated. See IPR 2018-01785
`(Paper 8).
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`C.
`
`Real Party in Interest
`Petitioner identifies itself, Oxford Nanopore Technologies, Inc. and
`“Oxford Nanopore Technologies, Ltd., the parent company of Oxford
`Nanopore Technologies, Inc., and Metrichor Ltd., a corporate affiliate of
`Oxford Nanopore Technologies, Inc., as the real parties in interest.” Pet. 2.
`Patent Owner identifies itself, “Pacific Biosciences of California, Inc.,” as
`the real party in interest. Paper 4, 2.
`C.
`The ’929 Patent (Ex. 1001)
`The ’929 patent is titled “Nucleic Acid Sequence Analysis.” Ex.
`1001, [54]. The ’929 patent issued from Application No. 15/383,965 (“the
`’965 application”), filed Dec. 19, 2016, which ultimately claims benefit of
`U.S. Provisional Application No. 61/099,696, filed Sept. 24, 2008, and
`U.S. Provisional Application No. 61/139,402, filed Dec. 19, 2008 Id. at
`[60].
`
`The ’929 patent concerns obtaining sequence data from discontiguous
`portions of single nucleic acid templates. Ex. 1001, 3:7–10. The ’929 patent
`teaches that “the sequencing reaction comprises passage of the single nucleic
`acid template through a nanopore.” Id. at 4:40–42. The ’929 patent teaches
`that the analytical reaction further “comprises at least one component
`comprising a detectable label, e.g., a fluorescently labeled nucleotide,” and
`an optical detection system to collect the data. Id. at 4:59–61. The ’929
`patent describes numerous templates for use in the sequencing reactions.
`[U]sing templates that allow repeated sequencing (e.g., circular
`templates, SMRTBELL™ templates, etc.) in a single reaction
`can increase the percent of a nucleic acid template for which
`nucleotide sequence data is generated and/or increase the fold-
`coverage of the sequence reads for one or more regions of
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`interest in the template, thereby providing more complete data
`for further analysis, e.g., construction of sequence scaffolds
`and/or consensus sequences for the nucleic acid template. For
`example, in certain preferred embodiments, templates sequenced
`by the methods described herein are templates comprising a
`double-stranded segment, e.g., greater than 75%, or even greater
`than 90% of the target segment will be double-stranded or
`otherwise internally complementary. Such templates may, for
`example, comprise a double stranded portion comprised of two
`complementary sequences and two single-stranded linking
`portions (e.g., oligos or “hairpins”) joining the 3' end of each
`strand of the double-stranded region to the 5' end of the other
`strand (sometimes referred to as “SMRTBELL™” templates).
`Id. at 66:8–27.
`The ’929 patent describes sequencing a contiguous template in order
`to obtain information about the sense and antisense strand of a double-
`stranded template.
`[A] sequencing process that begins, e.g., is primed, at the open
`end of the partially contiguous template, proceeds along the first
`or sense strand, providing the nucleotide sequence (A) of that
`strand, as represented in the schematic sequence readout
`provided. The process then proceeds around the linking
`oligonucleotide of the template, providing the nucleotide
`sequence (B) of that segment. The process then continues along
`the antisense strand to the A sequence, and provides the
`nucleotide sequence (A'), which provides consensus data for the
`sense strand as its antisense counterpart.
`Id. at 38:1–11.
`The ’929 patent teaches that “template nucleic acids comprising the
`same nucleotide sequence are analyzed in a plurality of reactions sufficient
`to provide adequate redundant nucleotide sequence data to determine a
`consensus sequence for the template nucleic acids.” Id. at 31:50–54. The
`’929 patent teaches a process for “transforming nucleotide sequence read
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`D.
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`data into consensus sequence data, wherein the nucleotide sequence read
`data is generated by sequencing a target region of a template nucleic acid
`multiple times, and the consensus sequence data is representative of a most
`likely actual sequence of the template nucleic acid.” Id. at 12:7–12.
`
`Illustrative Claim
`Claims 1–17 of the ’929 patent are challenged. Claim 1, the sole
`independent claim of the ’929 patent is illustrative and reproduced below:
`1. A method of determining a nucleotide sequence of a region
`of interest in a polynucleotide, the method comprising:
`[a] introducing a polynucleotide comprising a region of interest
`to a sequence analysis system comprising a nanopore in a
`membrane, [b] wherein the polynucleotide comprises a double-
`stranded portion comprising complementary strands of the
`region of interest;
`[c] applying a voltage across the membrane;
`[d] monitoring variations in ionic current through the nanopore
`of the sequence analysis system [e] during enzyme chaperone-
`regulated passage of the polynucleotide through the nanopore;
`[f] analyzing the monitored variations in ionic current to obtain
`nucleotide sequence information for the polynucleotide, [g]
`wherein the nucleotide sequence information comprises
`redundant sequence information for the region of interest,
`wherein the redundant sequence information comprises the
`nucleotide sequence of the complementary strands; and
`[h] determining a consensus sequence for the region of interest
`based on the redundant sequence information.
`Ex. 1001, 82:36–57 (labels [a]–[h] are added to distinguish the subparts for
`discussion purposes).
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`E.
`
`Prior art
`Petitioner relies upon the following prior art references (Pet. 1, 13–
`
`23):
`References
`Akeson
`
`Miner
`
`O’Dea
`
`Sanger
`
`Exhibits
`Ex. 1004
`
`Ex. 1007
`
`Ex. 1008
`
`Ex. 1009
`
`Ex. 1012
`
`Ex. 1014
`
`Patent / Publication
`Akeson et al., US 2006/0063171 Al, published
`Mar. 23, 2006.
`Gupte et al., US 6,087,099, issued July 11, 2000. Ex. 1005
`Gupte
`Makrigiorgos Makrigiorgos, US 2005/0142559 Al, published
`Ex. 1006
`June 30, 2005.
`Miner et al., Molecular barcodes detect
`redundancy and contamination in hairpin-
`bisulfite PCR, 32 NUCLEIC ACIDS RESEARCH
`e135 (2004).
`O’Dea and McLaughlin, Engineering Specific
`Cross-Links in Nucleic Acids Using Glycol
`Linkers, CURRENT PROTOCOLS IN NUCLEIC ACID
`CHEMISTRY 5.3.1–5.3.8 (2000).
`Sambrook Sambrook et al., Molecular Cloning: A
`Laboratory Manual, 2nd ed. Cold Springs Harbor
`Laboratory Press (1989)
`Sanger, Determination of Nucleotide
`Sequences in DNA
`Akeson ’433 Akeson et al., US 6,936,433 B2, issued Aug. 30,
`2005.
`
`
`Asserted Grounds of Unpatentability
`Petitioner challenges the patentability of claims 1–17 of the ’929
`patent on the following grounds (Pet. 24–67):
`Ground Claim(s)
`Basis2
`Reference(s)
`Challenged
`1–8, 10, 11,
`and 16
`
`F.
`
`1
`
`§ 103(a) Akeson and Gupte
`
`
`2 We apply pre-AIA 35 U.S.C. § 103 because the effective filing date of the
`
`6
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`Ground Claim(s)
`Challenged
`12
`17
`1–8, 10, 11
`and 13
`9
`12
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`2
`3
`4
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`Basis2
`
`Reference(s)
`
`§ 103(a) Akeson, Gupte, and Miner
`§ 103(a) Akeson, Gupte, and Akeson ’433
`§ 103(a) Akeson, Sanger, and Makrigiorgos
`
`§ 103(a) Akeson, Gupte, and Makrigiorgos
`§ 103(a) Akeson, Sanger, Makrigiorgos, and
`Miner
`§ 103(a) Akeson, Sanger, Makrigiorgos, and
`O’Dea
`Petitioner also relies on the Declaration of Dr. Patrick Hrdlicka
`(Ex. 1002) to support its assertions.
`G.
`Person of Ordinary Skill in the Art
`Petitioner asserts that a person of ordinary skill in the art would have
`had at least a Ph.D. or an equivalent amount of experience in molecular
`biology, genetics, biochemistry or a related field. Pet. 9 (citing Ex. 1002,
`¶¶ 31–32). Patent Owner does not dispute this characterization. We,
`therefore, adopt Petitioner’s definition for purposes of this Decision. We
`further note that the prior art itself demonstrates the level of skill in the art at
`the time of the invention. See Okajima v. Bourdeau, 261 F.3d 1350, 1355
`(Fed. Cir. 2001) (explaining that specific findings regarding ordinary skill
`level are not required “where the prior art itself reflects an appropriate level
`and a need for testimony is not shown”) (quoting Litton Indus. Prods., Inc. v.
`Solid State Sys. Corp., 755 F.2d 158, 163 (Fed. Cir. 1985)).
`
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`14 and 15
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`
`ʼ929 patent precedes the March 16, 2013, effective date for changes to
`35 U.S.C. § 103. See MPEP § 2159 (Rev. 08.2017).
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`II. CLAIM CONSTRUCTION
`Petitioner does not present any claim construction issues to be
`resolved in this proceeding. Prelim. Resp. 9. Patent Owner’s Preliminary
`Response also does not present any construction issues. We likewise
`determine that it is unnecessary to construe any term for purposes of this
`Decision. See Wellman, Inc. v. Eastman Chem. Co., 642 F.3d 1355, 1361
`(Fed. Cir. 2011) (“[C]laim terms need only be construed ‘to the extent
`necessary to resolve the controversy.’”) (quoting Vivid Techs., Inc. v. Am.
`Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)).
`III. ANALYSIS OF PETITIONER’S PRIOR ART CHALLENGES
`A patent claim is unpatentable under 35 U.S.C. § 103(a) if the
`differences between the claimed subject matter and the prior art are such that
`the subject matter, as a whole, would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which the
`subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
`(2007). The question of obviousness is resolved on the basis of underlying
`factual determinations, including: (1) the scope and content of the prior art;
`(2) any differences between the claimed subject matter and the prior art;
`(3) the level of skill in the art; and (4) objective evidence of nonobviousness.
`Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
`In determining whether there would have been a motivation to
`combine prior art references to arrive at the claimed invention, it is
`insufficient to simply conclude the combination would have been obvious
`without identifying any reason why a person of skill in the art would have
`made the combination. Metalcraft of Mayville, Inc. v. The Toro Co., 848
`F.3d 1358, 1366 (Fed. Cir. 2017).
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`A. Ground 1: Obviousness over Akeson and Gupte
`Petitioner argues that claims 1–8, 10, 11, and 16 would have been
`unpatentable as obvious over the combined teachings of Akeson and Gupte.
`Pet. 24–41.
`Akeson
`1.
`Akeson is a United States Patent Publication titled “Methods and
`Apparatus for Characterizing Polynucleotides.” Ex. 1004. Petitioner asserts
`that Akeson was not of record, and thereby not considered by the Examiner
`during the prosecution of the ’929 patent. Pet. 13.
`Akeson is directed at methods of analyzing polynucleotide structures
`using a nanopore analysis system. Ex. 1004 ¶ 9. Figures 1 and 2,
`reproduced below, show embodiments of the nanopore analysis system.
`
`
`Figures 2A through 2D are diagrams of representative nanopore devices that
`can be used in the nanopore analysis system of Figure 1. Id. ¶ 22. The
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`molecular motor 26 can be located on either the cis or trans side of the
`aperture 24 in the nanopore system. Id. ¶¶ 11, 52, 86, 87. The typical
`nanopore detection system 14 includes electronic equipment to measure the
`interaction of the polynucleotide with the nanopore aperture. Id. ¶ 39. The
`apparatus contains a structure 22 that separates two independent and
`adjacent pools of medium. Id. ¶ 41. This separating structure 22 includes
`“at least one nanopore aperture 24, e.g., so dimensioned as to allow
`sequential monomer-by-monomer translocation (i.e., passage) from one pool
`to another of only one polynucleotide at a time, and detection components
`that can be used to measure transport properties.” Id. The structure 22 is
`dimensioned in such a way that either single or double-stranded
`polynucleotide can be analyzed. Id. ¶ 43. Molecular motor 26 is located
`adjacent to the nanopore aperture 24 and determines whether a single or
`double-stranded polynucleotide is analyzed. Id. “A molecular motor 26
`includes, e.g., polymerases (i.e., DNA and RNA), helicases, ribosomes, and
`exonucleases.” Id. ¶ 47. When the molecular motor 26 is a DNA
`polymerase and is located on the cis side of the nanopore device, the
`polynucleotide requires incorporation of a nick or a primer that can serve as
`a template for the DNA polymerase. Id. ¶ 63.
`Figure 10, reproduced below, shows a nanopore device with
`molecular motor disposed on the cis side of the nanopore aperture. Id. ¶ 90.
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`The nanopore device as shown in Figure 10, above, applies a voltage, which
`draws the polynucleotide toward the aperture of the device. Id. In the
`schematic, the cis solution activates the helicase to separate the DNA and
`assists in pushing one of the strands of the DNA through the pore 24. Id.
`Each nucleotide monomer in the strand may be analyzed as it traverses the
`nanopore. Id.
`The polynucleotide sequence is determined by measuring transport
`properties of each monomer as it interacts with the nanopore aperture.
`“[T]ransport properties of the nanopore aperture may be measured by any
`suitable technique. . . . [and can] include current, conductance, resistance,
`capacitance, charge, concentration, optical properties (e.g., fluorescence and
`Raman scattering), and chemical structure.” Id. ¶ 76. “The monomer-
`dependent characterization achieved by nanopore sequencing may include
`identifying characteristics such as, but not limited to, the number and
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`composition of monomers that make up each individual polynucleotide, in
`sequential order.” Id. ¶ 79.
`2.
`Gupte
`Gupte is a United States Patent titled “Method for Sequencing Both
`Strands of a Double Stranded DNA in a Single Sequence Reaction.”
`Ex. 1005 [54]. Petitioner asserts that Gupte was not of record, and thereby
`not considered by the Examiner during the prosecution of the ’929 patent.
`Pet. 17.
`Gupte teaches opposite strand joining PCR to form a single stranded
`DNA product, which contains both strands of the original DNA. Ex. 1005,
`1:56–60. Figure 2, reproduced below, shows the steps to create such a
`single stranded product.
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`Figures 2A–2F illustrate the opposite strand joining strategy. Id. 2:61–62.
`Figure 2A shows genomic DNA; Figure 2B shows the product obtained
`when the DNA shown in is subjected to PCR; Figure 2C shows that
`intrastrand binding occurs forming a loop with the C tail hybridizing to the
`C' portion of the strand; Figure 2D shows a product, which upon
`denaturation is a single-stranded molecule, that contains both strands of exon
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`19, i.e., it contains both exon 19 and exon 19' in a tandem arrangement
`(separated by C, G1' and C'); Figure 2E and Figure 2F show products formed
`when the DNA illustrated in prior figures undergoes another round of PCR
`with various primers. Id. 2:50–3:37. “The original double-stranded DNA is
`amplified and the newly formed DNA undergoes steps to yield a single-
`stranded DNA which includes the same sequences as found in the two
`strands of a portion of the amplified region of the double-stranded DNA.”
`Id. 6:6–10.
`Analysis
`3.
`Claim 1 includes a preamble and eight subparts, designated as
`elements [a] through [h] (see above I.D.). Ex. 1001, 82:36–57; see Pet. 25–
`31; see Prelim Resp. 22–23. Petitioner asserts that the combination of
`Akeson and Gupte teaches the limitations of the preamble as well as
`elements 1[a] – [g]. Pet. 24–30. Patent Owner does not meaningfully
`dispute these assertions. See Prelim Resp. 32.
`Petitioner relies on Akeson’s use of a nanopore apparatus to determine
`the sequence of a polynucleotide. Pet. 25–30. “Nanopore sequencing is one
`method of rapidly determining the sequence of nucleic acid molecules.
`Nanopore sequencing is based on the property of physically sensing the
`individual nucleotides (or physical changes in the environment of the
`nucleotides (i.e., electric current)) within an individual polynucleotide (e.g.,
`DNA and RNA) as it traverses through a nanopore aperture.” Ex. 1004, ¶ 5.
`Claim element 1[h] requires “determining a consensus sequence for
`the region of interest based on the redundant sequence information.”
`Ex. 1001; Pet. 30–31. Petitioner asserts that this limitation is taught by
`Gupte. Id. at 30. Gupte teaches a method of amplifying double-stranded
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`DNA in such a way that yields “a single-stranded DNA which includes the
`same sequences as found in the two strands of a portion of the amplified
`region of the double-stranded DNA.” Ex. 1005, 6:6–10. “This method is
`referred to as opposite strand joining PCR. When denatured[,] this product
`forms a single-stranded DNA which contains both strands of the original
`DNA. When this resulting single-stranded DNA is sequenced it yields the
`sequence of both strands of the original double-stranded DNA.” Id. at 1:56–
`60.
`
`Petitioner relies on Gupte’s teaching of “sequencing of both strands of
`a polynucleotide” to conclude that “[o]ne of ordinary skill in the art would
`understand that comparing the sequences of both strands to identify any
`errors and to confirm the correct sequence results in the generation of a
`consensus sequence.” Pet. 30–31. Specifically, Petitioner asserts that
`a POSA would understand that one could compare the sequences
`of the two complementary strands obtained by the sequencing of
`the double-stranded polynucleotide of Gupte using the nanopore
`system of Akeson to identify any differences in the two
`sequences to determine a consensus sequence.
`Id. at 30 (citing Ex. 1002, ¶ 78).
`Patent Owner contends that Gupte fails to teach “generating a
`consensus sequence of any sort.” Prelim. Resp. 32, see also id. 37 (“the
`technique disclosed in Gupte does not allow for the sequences of the
`complementary strands from the same molecule to be used for determining
`the consensus sequence of the double-stranded nucleic acid template.”
`(emphasis added)). Sequencing both strands of a DNA molecule is not a
`teaching of determining consensus sequence based on redundant sequence
`information but rather “an observation that researchers had used sequence
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`data from complementary strands of DNA as a corroborative tool to confirm
`accuracy.” Id. at 33. Furthermore, Patent Owner contends that Petitioner’s
`expert “has confirmed that Gupte does not disclose determination of a
`consensus sequence.” Id. Patent Owner contends that “Gupte provides no
`teaching regarding how to resolve the inconsistencies so as to provide a
`consensus sequence corresponding to the most likely DNA sequence.” Id.
`Patent Owner contends that Petitioner’s expert acknowledges that more is
`required than just sequencing sense and antisense strands of a DNA
`molecule to establish a consensus sequence. Id. at 34 (citing Ex. 2008 at
`121:19–122:12 (“I would be very uncomfortable with having, let’s say, one
`data point only for each of a – each of the positions in a base pair. That
`would be scientifically unsound. That’s why I think a person of skill in the
`art would record many times – many sequence reads, strive to record as
`many as possible.”).
`We do not find Petitioner’s position persuasive. Petitioner relies on
`Gupte’s teaching of “sequencing of both strands of a polynucleotide” to
`arrive at “a consensus sequence.” Pet. 30–31. We are not persuaded that
`Petitioner has shown with sufficient particularity that Gupte’s disclosure of
`constructing a PCR product that contains both sense and antisense sequence
`information is the same as a consensus sequence as claimed and understood
`in light of the ’929 patent specification. See Ex. 1001, 12:7–12
`(“transforming nucleotide sequence read data into consensus sequence data,
`wherein the nucleotide sequence read data is generated by sequencing a
`target region of a template nucleic acid multiple times, and the consensus
`sequence data is representative of a most likely actual sequence of the
`template nucleic acid.”). The ’929 patent teaches that the nucleotide
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`sequence of sense and antisense strand is consensus data (i.e. the nucleotide
`sequence of complementary strands). See id. at 38:1–11. Consensus data is
`not the same as a “consensus sequence” which according to the ’929 patent
`is a collection of data that “is representative of a most likely actual sequence
`of the template nucleic acid.” Id. at 12:7–12. And, consensus data is also
`not the same as redundant sequence information, which is obtained by
`collecting data from a plurality of sequencing reactions for template nucleic
`acids. See id. at 31:50–54. Although the “consensus sequence” and the
`“redundant sequence information” limitations are both related to “the
`nucleotide sequence of complementary strands” limitation, the disclosure of
`the ’929 patent demonstrates that they are not the same.
`Petitioner’s expert attests that “[a] person of ordinary skill in the art
`would understand that the polynucleotides of Gupte could be sequenced by
`the method of Akeson” and that sequence of the polynucleotide of Gupte
`“would result in the nucleotide sequence of both complementary strands.”
`Ex. 1002, ¶ 77. Petitioner’s expert then concludes that “one of ordinary skill
`in the art would understand that comparing the sequences of both strands to
`identify any errors and to confirm the correct sequence results in the
`generation of a consensus sequence.” Id. ¶ 78. Here, Petitioner’s expert is
`relying on Gupte’s polynucleotide sequence to meet claim element 1[h] of
`the ’929 patent, specifically, the “the redundant sequence information” and
`the “consensus sequence” limitation. The issue is that Petitioner’s expert is
`also relying on that same polynucleotide sequence of Gupte to establish the
`limitation of “nucleotide sequence of complementary strands” in claim 1.
`See Ex, 1002, ¶ 69, see also id. ¶¶ 77–79. Thus, Petitioner relies on Gupte’s
`polynucleotide sequence containing a sense and antisense sequence to meet
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`three different positively recited claim limitations. Reliance on the same
`structure to meet three different claim limitations is unreasonable because
`the use of different language to describe each limitation suggests that they
`have different meaning. See, e.g., CAE Screenplates Inc. v. Heinrich Fiedler
`GmbH & Co. KG, 224 F.3d 1308, 1317 (Fed. Cir. 2000) (presumption that
`use of different terms in claims connotes different meanings). Here, the
`different terms are found in the same claim further supporting the position
`that the limitations are not the same.
`“In an [inter partes review], the petitioner has the burden from the
`onset to show with particularity why the patent it challenges is
`unpatentable.” Harmonic Inc. v. Avid Tech., Inc., 815 F.3d 1356, 1363 (Fed.
`Cir. 2016). The burden of persuasion never shifts to Patent Owner.
`Dynamic Drinkware, LLC v. Nat’l Graphics, Inc., 800 F.3d 1375, 1378
`(Fed. Cir. 2015). The ’929 patent explains that a “censuses sequence” is
`analyzed based on a plurality of reactions using the same templet. See Ex.
`1001, 31:50–54, see id. at 12:7–12 (“nucleotide sequence read data is
`generated by sequencing a target region of a template nucleic acid multiple
`times, and the consensus sequence data is representative of a most likely
`actual sequence of the template nucleic acid.”) The Petition fails to identify
`what disclosure in Gupta meets the limitation of element 1[h] directed to a
`“consensus sequence . . . based on the redundant sequence information”
`because the disclosure of a sequence that contains both sense and antisense
`information by itself is not a consensus sequence as understood in light of
`the ’929 patent specification. Petitioner has not provided a sufficient
`evidentiary basis from which to conclude that the Gupte’s single stranded
`molecule without more provides a “consensus sequence” as claimed. See
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`Pet. 30 (citing Ex. 1002, 78 (“[o]ne of ordinary skill in the art would
`understand that comparing the sequences of both strands to identify any
`errors and to confirm the correct sequence results in the generation of a
`consensus sequence”). Simply saying that a POSA would understand this to
`be a consensus sequence is not a sufficient basis to establish obviousness,
`this requires an explanation of how or why the skilled artisan would process
`information in a particular way to arrive at a consensus sequence as claimed.
`See InTouch Techs., Inc. v. VGO Comms., Inc., 751 F.3d 1327, 1352 (2014)
`(“Dr. Yanco’s testimony primarily consisted of conclusory references to her
`belief that one of ordinary skill in the art could combine these references, not
`that they would have been motivated to do so.”))
`Accordingly, we determine that Petitioner has not shown that there is
`a reasonable likelihood that it would prevail with regard to establishing that
`claim 1 would have been unpatentable as obvious over the combined
`teachings of Akeson and Gupte or that claims 2–9 and 12–15, which
`ultimately depend from claim 1 would have been unpatentable as obvious
`over the combined teachings of Akeson and Gupte. Any other issues raised
`in the Preliminary Response, such as for example whether the Board should
`exercise its discretion to deny institution under 35 U.S.C. §§ 314(a) and
`324(a) (see Prelim. Resp. 5–13), are moot.
`B. Ground 2, 3, and 5: Obviousness over Akeson and Gupte in
`combination with either Miner, Akeson ’433, or Makrigiorgos
`For its second asserted ground of unpatentability, Petitioner asserts
`that claim 12 is obvious over the combined teachings of Akeson, Gupte, and
`Miner. Pet. 41–42. For its third asserted ground of unpatentability,
`Petitioner asserts that claim 17 is obvious over the combined teachings of
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`Akeson, Gupte, and Akeson ’433. Id. at 43–44. For its fifth asserted ground
`of unpatentability, Petitioner asserts that claim 9 is obvious over the
`combined teachings of Akeson, Gupte, and Makrigiorgos.
`Each of these claims depends directly or indirectly from claim 1 and,
`therefore, includes the requirements of element 1[h]. For each of Grounds 2,
`3, and 5, Petitioner relies upon the combined teachings of Akeson and
`Gupte, as described above to teach element 1[h]. As we have found
`Petitioner’s arguments not persuasive in this regard, we determine that
`Petitioner has not shown that there is a reasonable likelihood that it would
`prevail with regard to the asserted obviousness of the challenged claims in
`grounds 2, 3, and 5.
`C. Ground 4: Obviousness over Akeson, Sanger, and Makrigiorgos
`Petitioner argues that claims 1–8, 10, 11, and 13 would have been
`unpatentable as obvious over the combined teachings of Akeson, Sanger,
`and Makrigiorgos. Pet. 45–67.
`1.
`Sanger
`Sanger is publication titled “Determination of Nucleotide Sequences
`in DNA.” Ex. 1012. Petitioner asserts that Sanger was not of record, and
`thereby not considered by the Examiner during the prosecution of the ’929
`patent. Pet. 16.
`Sanger teaches that by sequencing both strands of a DNA molecule
`sequencing errors are reduced.
`In most studies on DNA one is concerned with identifying the
`reading frames for protein genes, and to do this the sequence
`must be correct. Errors can readily occur in such extensive
`sequences and confirmation is always necessary. We usually
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`consider it necessary to determine the sequence of each region
`on both strands of the DNA.
`Ex. 1012, 3–4.
`2. Makrigiorgos
`Makrigiorgos is United Stated Patent Publication titled “Amplification
`of DNA in a Hairpin Structure, and Applications.” Ex. 1006. Petitioner
`asserts that Makrigiorgos was not of record, and thereby not considered by
`the Examiner during the prosecution of the ’929 patent. Pet. 20.
`Makrigiorgos teaches conversion of a DNA sequence to a hairpin
`structure and PCR amplification of the hairpin structure. Id. ¶ 23. The
`procedure converts a native DNA sequence into a hairpin using
`oligonucleotides Cap1 and Cap2. Id. (citing Figure 3A–C (not shown),
`¶¶ 71–72.
`Cap1 is sometimes referred to as a ‘joining structure,’ because
`once it is ligated to the nucleic acid sequence of interest it joins
`the upper strand of the nucleic acid sequence of interest to the
`lower strand of the same nucleic acid molecule. . . . Cap2 is
`sometimes referred to as a priming structure, because it contains
`regions of single-stranded nucleic acid to which primers can bind
`to initiate the polymerization reaction.
`Id. ¶ 28.
`Analysis
`3.
`Claim 1 includes a preamble and eight subparts, designated as
`elements [a] through [h]. Ex. 1001, 82:36–57; see Pet. 46–54; see Prelim
`Resp. 46–54. Petitioner asserts that the combination of Akeson, Sanger, and
`Makrigiorgos teach the preamble as well as elements 1[a] – [g]. Pet. 45–52.
`Patent Owner does not meaningfully dispute these assertions. See Prelim
`Resp. 46.
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`Claim element 1[h] requires “determining a consensus sequence for
`the region of interest based on the redundant sequence information.”
`Ex. 1001; Pet. 45–52. Petitioner relies on “Makrigiorgos [to] disclose[]
`methods for generating double-stranded polynucleotides that include both
`complementary structures.” Pet. at 45. Petitioner argues that confirmation
`of the sequence is necessary. Id. at 51 (citing Ex. 1012, 3–4 (“Errors can
`readily occur in such extensive sequences and confirmation is always
`necessary.”)). Petitioner argues that a “POSA would understand that one
`could compare the sequences of the two complementary strands . . . to
`determine a consensus sequence.” Id. (citing Ex. 1002, ¶ 121).
`Patent Ow