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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`Ambry Genetics Corporation,
`Petitioner
`v.
`
`The Johns Hopkins University,
`Patent Owner
`
`
`
`Case No. IPR2017-02093
`
`Patent No. 7,824,889
`
`
`
`PATENT OWNER’S PRELIMINARY RESPONSE TO PETITION
`PURSUANT TO 37 C.F.R. § 42.107
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`Case No. IPR2017-02093
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`TABLE OF CONTENTS
`
`B.
`
`I.
`INTRODUCTION ........................................................................................... 1
`II. OVERVIEW .................................................................................................... 2
`A.
`The Petition ........................................................................................... 2
`B.
`Level of Skill in the Art ......................................................................... 2
`C.
`The Inventors Improved Upon Existing Mutation Detection
`Methods and Limiting Dilution PCR .................................................... 3
`III. PETITIONER’S CONSTRUCTION OF VARIOUS PHRASES AND
`TERMS IS UNREASONABLY BROAD AND NOT SUPPORTED
`BY THE RECORD .......................................................................................... 8
`A.
`Petitioner Ignores the Context of the Claim in Construing the
`Term “Plurality” in the Phrase “to Form a Set Comprising a
`Plurality of Assay Samples” ................................................................ 10
`Petitioner’s Proposed Construction of “Assay Samples of the
`Set” Is Also Unreasonably Broad........................................................ 11
`IV. PETITIONER’S EXPERT DECLARATION IS MERELY
`ATTORNEY ARGUMENT IN THE GUISE OF EXPERT
`TESTIMONY ................................................................................................ 12
`SYKES WAS ALREADY CONSIDERED BY THE PATENT
`OFFICE .......................................................................................................... 15
`VI. GROUNDS 1 AND 2 ARE REDUNDANT ................................................. 17
`VII. CLAIM 1 IS NOVEL OVER CHIANG ........................................................ 18
`A.
`Chiang Fails to Disclose the “Analyzing” Step .................................. 18
`B.
`Chiang Fails to Disclose the “Comparing” Step ................................. 22
`VIII. CLAIMS 1 AND 8 ARE NOVEL OVER SYKES ....................................... 24
`A.
`Sykes Fails to Disclose the “Analyzing” Step .................................... 25
`B.
`Sykes Fails to Disclose the “Comparing” Step ................................... 27
`
`V.
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`Case No. IPR2017-02093
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`IX. CHIANG AND SYKES FAIL TO DISCLOSE FEATURES OF
`CLAIMS 1 AND 8, AND A PERSON OF SKILL IN THE ART
`WOULD NOT HAVE A REASONABLE EXPECTATION OF
`SUCCESS IN THEIR COMBINATION OR HAVE BEEN
`MOTIVATED TO COMBINE THEM ......................................................... 30
`CONCLUSION .............................................................................................. 34
`
`
`X.
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`Case No. IPR2017-02093
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`TABLE OF AUTHORITIES
`
`Cases
`Apotex Inc. v. Wyeth LLC,
`IPR2014-00115, Paper 94 (PTAB Apr. 20, 2015) ............................................... 31
`Cardiocom, LLC,
`IPR2013-00439, Paper 26 (PTAB Jan. 16, 2014) ................................................ 13
`
`Continental Can Co. v. Monsanto Co.,
`948 F.2d 1264 (Fed. Cir. 1991) ............................................................................ 19
`Cultec, Inc. v. Stormtech LLC,
`IPR2017-00777 (PTAB Aug. 22, 2017) ......................................................... 7, 15
`Cuozzo Speed Tech., LLC v. Lee,
`136 S. Ct. 2131 (2016) ........................................................................................... 8
`Dayco Prods., Inc. v. Total Containment, Inc.,
`258 F.3d 1317 (Fed. Cir. 2001) ............................................................................ 10
`Google, Inc. v. EveryMD.com LLC,
`IPR2014-00347, Paper 9 (PTAB May 22, 2014) ................................................. 31
`Graham v. John Deere Co. of Kansas City,
`383 U.S. 1 (1966) ................................................................................................. 30
`In re Cortright,
`165 F.3d 1353 (Fed. Cir. 1999) .............................................................................. 8
`In re Kahn,
`441 F.3d 977 (Fed. Cir. 2006) .............................................................................. 14
`In re NTP, Inc.,
`654 F.3d 1279, 1288 (Fed. Cir. 2011) .................................................................... 8
`
`In re Suitco Surface,
`603 F.3d 1255 (Fed. Circ. 2010) ................................................................. 8, 9, 10
`In re Vaeck,
`947 F.2d 488 (Fed. Cir. 1991) .............................................................................. 31
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`InfoBionic, Inc. v. Braemar Manufacturing, LLC,
`IPR2015-01704, Paper 11 (PTAB Feb. 16, 2016) ............................................... 14
`Kinetic Techs., Inc. v. Skyworks Solutions, Inc.,
`IPR2014-00529, Paper 8 (PTAB Sept. 23, 2014) ................................................ 13
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ............................................................................................. 31
`
`Lewmar Marine, Inc. v. Barient, Inc.,
`827 F.2d 744 (Fed. Cir. 1987) .............................................................................. 18
`Liberty Mutual Ins. Co. v. Progressive Casualty Ins. Co.,
`CBM2012-00003, Paper 7, 2 (PTAB Oct. 25, 2012) .......................................... 17
`
`Microsoft Corp. v. Proxyconn, Inc.,
`789 F.3d 1292 (Fed. Cir. 2015) ..........................................................................8, 9
`Organik Kimya AS v. Rohm & Haas Co.,
`Nos. 2015-1983 and 2015-2001 (Fed. Cir. Oct. 11, 2017) .................................... 9
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ............................................................................ 31
`Princeton Biochemicals, Inc. v. Beckman Coulter, Inc.,
`411 F.3d 1332 (Fed. Cir. 2005) ............................................................................ 30
`Procter & Gamble Co. v. Teva Pharms. USA, Inc.,
`566 F.3d 989 (Fed. Cir. 2009) .............................................................................. 31
`Schering Corp. v. Geneva Pharms., Inc.,
`339 F.3d 1373 (Fed. Cir. 2003) ..................................................................... 18, 25
`TRW Auto. US LLC v. Magna Elecs., Inc.,
`IPR2014-00258, Paper 18 (PTAB Aug. 27, 2014) .............................................. 14
`Unified Patents, Inc. v. Berman,
`IPR2016-01571 (PTAB Dec. 14, 2016) .......................................................... 7, 15
`W.L. Gore & Assoc., Inc. v. Garlock, Inc.,
`721 F.2d 1540 (Fed. Cir. 1983) ............................................................................ 32
`
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`Ziegman v.Stephens,
`IPR2015-01860 (PTAB Feb. 24, 2016) ............................................................... 15
`Statutes
`35 U.S.C. § 103 ........................................................................................................ 16
`35 U.S.C. § 313 .......................................................................................................... 2
`35 U.S.C. § 325(d) ........................................................................................ 7, 15, 17
`Rules
`37 C.F.R. § 42.107 ..................................................................................................... 2
`37 C.F.R. § 42.108(c) ............................................................................................... 14
`37 C.F.R. § 42.23(a) ................................................................................................. ix
`37 C.F.R. § 42.24(b) ................................................................................................ 36
`
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`LIST OF EXHIBITS
`
`Exhibit
`
`Description
`
`JHU2001 Declaration of Fred Kramer, Ph.D. dated December 26, 2017
`
`JHU2002 Curriculum Vitae of Fred Kramer, Ph.D.
`
`JHU2003 Pohl and Shih (2004), Expert Rev. Mol. Diagn., 4:41-47
`
`JHU2004 Diehl and Diaz (2007), Curr. Opin. Oncol. 19: 36-42
`
`JHU2005 Vogelstein and Kinzler (1999), PNAS 96:9236-9241
`
`JHU2006
`
`Google ScholarTM for Digital PCR (1999, PNAS 96:9236-41)
`(Retrieved December 26, 2017 from
`https://scholar.google.com/scholar?hl=en&as_sdt=0%2C33&q=voge
`lstein+kinzler+digital+pcr&btnG )
`
`JHU2007 Parsons et al. (1995), Science 268:738-40
`
`JHU2008 Monckton & Jeffreys (1991), Genomics 11:465-67
`
`JHU2009 Navidi et al. (1991), Hum. Reprod. 6:836-49
`
`JHU2010
`
`Jeffreys et al. (1995), Electrophoresis 16:1577-85
`
`JHU2011 Sidransky et al. (1992), Nature 355:846-47
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`Description
`
`Merriam-Webster Dictionary. (2017) (Retrieved December 26, 2017
`from https://www.merriam-webster.com/dictionary/plurality and
`https://www.merriam-webster.com/dictionary/plural )
`
`Exhibit
`
`JHU2012
`
`JHU2013 Reserved
`
`JHU2014 Reserved
`
`JHU2015 Prosecution file history for U.S. Patent No. 6,440,706
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`Statement of Material Facts in Dispute
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`Petitioner, Ambry Genetics Corporation, did not submit a statement of
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`material facts in its Petition. Accordingly, no response is due pursuant to 37
`
`C.F.R. § 42.23(a), and no facts are admitted.
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`I.
`
`INTRODUCTION
`Ambry Genetics Corporation’s (“Petitioner’s”) challenges to two claims of
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`U.S. 7,824,889 (“the ’889 patent”) should be denied for at least three reasons. First,
`
`Petitioner’s claim constructions improperly stretch the claim terms far beyond their
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`broadest reasonable interpretation. Second, Petitioner recycles arguments that were
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`previously considered and rejected by the Examiner, and revisiting these
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`arguments would be a waste of the Board’s and Patent Owner’s time and
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`resources. Third, Petitioner’s prior art references fail to disclose every element of
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`the claims.
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`The challenged claims are directed to methods of determining an allelic
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`imbalance in a biological sample between a selected genetic sequence on a first
`
`chromosome and a reference genetic sequence on a second chromosome of the
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`sample using a digital amplification technique. Each of the methods recites
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`“analyzing the amplified molecules in the assay samples of the set to determine a
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`first number of assay samples which contain a selected genetic sequence on a first
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`chromosome and a second number of assay samples which contain a reference
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`genetic sequence on a second chromosome” and then “comparing the first number
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`of assay samples to the second number of assay samples to ascertain an allelic
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`imbalance in the biological sample.” Petitioner’s prior art references fail to
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`disclose both the “analyzing” and “comparing” steps. Thus, Petitioner has failed in
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`its burden of establishing a reasonable likelihood that at least one of the challenged
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`claims will be found unpatentable. Therefore, the Board should deny institution of
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`an inter partes review.
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`
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`II. OVERVIEW
`A. The Petition
`Petitioner filed a Petition for Inter Partes Review on September 11, 2017
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`(“the Petition”). The Petition challenges claims 1 and 8 of the ’889 patent
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`(“Challenged Claims”), alleging that claims 1 and 8 of the ’889 patent are
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`anticipated or obvious. The ’889 patent is assigned to Johns Hopkins University
`
`(“Patent Owner”). Patent Owner respectfully submits this Preliminary Response in
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`accordance with 35 U.S.C. § 313 and 37 C.F.R. § 42.107.
`
`B.
`Level of Skill in the Art
`Petitioner contends that, as of August 2, 1999, the person of ordinary skill in
`
`the art would typically have either (1) a Master’s degree in the biological sciences
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`or a related field, plus at least four years of laboratory experience, or (2) a Ph.D.
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`degree in in the biological sciences or a related field, plus at least two years of
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`molecular biology laboratory experience. Petition, 8-9. Patent Owner disagrees.
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`One of ordinary skill in the art would have been a person with training and
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`education in molecular biology techniques, such as PCR and related laboratory
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`procedures, having either a Bachelor’s degree in biological or chemical sciences
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`and at least three years of experience in a laboratory, or a Master’s degree in
`
`biochemical sciences and at least one year of laboratory experience. Declaration of
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`Fred Kramer, Ph.D. (JHU2001), ¶ 12.
`
`C. The Inventors Improved Upon Existing Mutation Detection
`Methods and Limiting Dilution PCR
`At the time of the invention, the inventors recognized a need for molecular
`
`diagnostic methods sensitive enough to detect a mutant nucleic acid sequence
`
`among a background of normal nucleic acid sequences or a subtle allelic
`
`imbalance, for example, for use in the detection of mutations present during the
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`early stages of cancer in patient samples. See, e.g., AMB1001, 1:29-34; Vogelstein
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`and Kinzler (1999), PNAS 96:9236-41 (JHU2005); JHU2001, ¶¶ 27-28; Pohl and
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`Shih, 2004, Expert Rev. Mol. Diagn., 4:41-47 (JHU2003); Diehl and Diaz, 2007,
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`Curr. Opin. Oncol. 19:36-42 (JHU2004) (discussing the need for quantitative
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`digital analysis). As of August 1999 (the earliest priority date of the ’889 patent),
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`DNA sequencing was the preferred technique for the detection of mutations, but
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`DNA sequencing had substantial shortcomings. AMB1001, 1:49-51; JHU2001, ¶
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`27. For example, it was useful only when the fraction of mutated molecules was
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`greater than approximately twenty percent of the total. Id. Other techniques, such
`
`as the use of mutant-specific oligonucleotides or the digestion of polymerase chain
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`reaction (PCR) products created with specific restriction endonucleases, were also
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`problematic. AMB1001, 1:51-60; JHU2001, ¶ 27. For instance, the signal-to-noise
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`ratio distinguishing mutant and wild-type templates was widely variable in some
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`techniques. Id. Others, while being sensitive, presented problems with
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`quantification of the fraction of mutant molecules in the starting population. Id.
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`To overcome these and other limitations of the existing methods, Drs.
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`Vogelstein and Kinzler developed a novel method for accurately and quantitatively
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`detecting genetic sequences in mixed populations of sequences – digital
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`amplification or digital PCR. AMB1001, 1:65-67 and 4:42-43; JHU2001, ¶¶ 28-30.
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`The name of the method refers to its ability to convert the intrinsically exponential
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`nature of PCR to a linear one. AMB1001, 6:1-3; JHU2001, ¶ 31.1 Digital PCR
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`solved the need for a molecular diagnostic assay that was sensitive and specific
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`enough to identify mutations among a large background of normal cells. JHU2001,
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`¶ 32. When introduced, the power of this new method was immediately and
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`consistently appreciated by those of skill in the art. Id. By way of example, Drs.
`
`
`1 Notably, the term digital PCR has been used more broadly by different research
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`groups than the original use of the term, which has created confusion in the field.
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`JHU2001, ¶ 29. As accurately used, digital PCR includes all four of the claimed
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`steps as discussed further below. See, e.g., Shih Declaration from Reexamination
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`(AMB1004, 1100-1101).
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`Vogelstein and Kinzler’s scientific publication of digital PCR (PNAS (1999)
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`96:9236-41) (JHU2005) has been cited over 1,000 times. JHU2006. Had the
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`references relied upon by Petitioner disclosed this powerful method in 1992 or
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`1996, then scientists worldwide would have been using digital PCR to determine
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`the relative proportions of two sequences in a biological sample long before 1999.
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`JHU2001, ¶¶ 32-33.
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`Contrary to the assertions of the Petitioner, digital PCR as described and
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`claimed by Drs. Vogelstein and Kinzler was not disclosed by others prior to
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`August 2, 1999. JHU2001, ¶¶ 28-29. Rather, traditional PCR followed by known
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`detection methods was disclosed. JHU2001, ¶ 28. Such disclosures are noted in the
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`background section of the ’889 patent. See ’889 patent (AMB1001), 1:46-63;
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`JHU2001, ¶ 28. Similarly, “single molecule PCR,” “limiting dilution analysis,” or
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`“limiting dilution PCR (LDPCR)” also had been described at that time. JHU2001,
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`¶ 29. While digital PCR certainly includes steps of limiting dilution and PCR, the
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`process does not end there. Rather, digital PCR requires additional steps and
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`features (e.g., the third and fourth steps of claim 1 of the ’889 patent, as well as
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`including a sufficient number of assay samples in the set so as to ascertain an
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`allelic imbalance). These additional steps and features are neither disclosed nor
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`suggested by the art cited in the Petition. JHU2001, ¶¶ 30-33. It is these additional
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`steps that distinguish the claimed digital PCR invention as a whole from prior art
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`limiting dilution PCR. JHU2001, ¶ 33.
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`The method claimed in the ’889 patent includes determining an allelic
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`imbalance between a first genetic sequence on a first chromosome and a second
`
`genetic sequence on a second chromosome. AMB1003, 1:22-43. The claimed
`
`method comprises distributing isolated nucleic acid template molecules isolated
`
`from a biological sample to form a set comprising a plurality of assay samples. Id.
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`The method also comprises amplifying the template molecules within the set to
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`form a population of amplified molecules in the assay samples of the set and
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`analyzing the amplified molecules in the assay samples of the set to determine a
`
`first number of assay samples that contain a selected genetic sequence on a first
`
`chromosome and a second number of assay samples that contain a reference
`
`genetic sequence on a second chromosome. Id. Finally, the method comprises
`
`comparing the first number of assay samples to the second number of assay
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`samples to ascertain an allelic imbalance in the biological sample. Id. The final few
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`steps of the claims are critical to digital PCR, as the ratio will reflect an allelic
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`imbalance of the sequences only if the dilution, amplification, and analysis steps
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`are properly performed. JHU2001, ¶ 33.
`
`The U.S. Patent and Trademark Office (“Patent Office”) twice
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`acknowledged the patentability of the Challenged Claims, first during original
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`prosecution and again in an ex parte reexamination of the ’889 patent
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`(Reexamination No. 90/012,895). Drs. Vogelstein and Kinzler were aware of
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`methods related to limiting dilution PCR (JHU2001, ¶ 41), citing, for example,
`
`Ruano et al. (1990, PNAS 87:6296-6300) (AMB1022) and Parsons et al. (1995,
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`Science 268:738-40) (JHU2007) in their publication. These references and others
`
`using limiting dilution PCR, including one of the primary references upon which
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`Petitioner relies (Sykes et al., 1992, BioTechniques 13(3):444-449; “Sykes”
`
`(AMB1011)), were disclosed to the Patent Office during prosecution. Petition, 4-5;
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`JHU2001, ¶ 41. The Board should not waste its resources analyzing these claims
`
`for yet a third time but instead should exercise its discretion under 35 U.S.C. §
`
`325(d) and not institute an inter partes review. See Unified Patents, Inc. v.
`
`Berman, IPR2016-01571, Paper 10 (PTAB Dec. 14, 2016) (denying institution
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`based on a combination of references that included a reference the examiner
`
`considered during prosecution and a second reference that was deemed
`
`cumulative); Cultec, Inc. v. Stormtech LLC, IPR2017-00777, Paper 7 (PTAB Aug.
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`22, 2017) (denying institution where the petitioner relied on art that the examiner
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`either previously considered or that was cumulative of that art).
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`III. PETITIONER’S CONSTRUCTION OF VARIOUS PHRASES AND
`TERMS IS UNREASONABLY BROAD AND NOT SUPPORTED BY
`THE RECORD
`Petitioner defines certain claim terms so as to read steps of the claimed
`
`method completely out of the claims. The Board must construe claim terms
`
`according to their broadest reasonable interpretation (BRI) consistent with the
`
`specification. Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144-46 (2016);
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`see also Microsoft Corp. v. Proxyconn, Inc., 789 F.3d 1292, 1298 (Fed. Cir.
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`2015), overruled on other grounds by Aqua Prods., Inc. v. Matal, 872 F.3d 1290
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`(Fed. Cir. 2017), quoting In re Suitco Surface, Inc., 603 F.3d 1255, 1260 (Fed.
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`Circ. 2010) (“[C]laims should always be read in light of the specification and
`
`teachings in the underlying patent.”). Here, Petitioner’s proposed constructions are
`
`unreasonable. In fact, several are so broad as to contradict the patent’s disclosure
`
`and even capture the very prior art methods distinguished in the patent’s
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`specification. Such an overly broad construction is improper. “Even under the
`
`broadest reasonable interpretation, the Board’s construction ‘cannot be divorced
`
`from the specification and the record evidence’ and ‘must be consistent with the
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`one that those skilled in the art would reach.’” Microsoft, 789 F.3d at 1298
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`(internal citations omitted) (quoting In re NTP, Inc., 654 F.3d 1279, 1288 (Fed.
`
`Cir. 2011) and In re Cortright, 165 F.3d 1353, 1358 (Fed. Cir. 1999)); see also
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`Organik Kimya AS v. Rohm & Haas Co., Nos. 2015-1983 and 2015-2001, 8 (Fed.
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`Cir. Oct. 11, 2017) (quoting Microsoft, 789 F.3d at 1298).
`
`In an attempt to support its unreasonable positions, Petitioner
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`mischaracterizes Patent Owner’s position in related litigation regarding the proper
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`construction of various terms. Petition, 6-7, 9-11. Petitioner’s assertion that these
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`characterizations accurately reflect Patent Owner’s position is belied by the fact
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`that Petitioner provides no citation to the record in either the pending litigation or
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`the prosecution history of the challenged patent. This is so because Patent Owner
`
`has never taken those positions.
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`Petitioner’s constructions are contrary to how those skilled in the art would
`
`understand the terms in light of the specification. “A construction that is
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`‘unreasonably broad’ and which does not ‘reasonably reflect the plain language
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`and disclosure’ will not pass muster.” Microsoft, 789 F.3d at 1298 (quoting In re
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`Suitco Surface, Inc., 603 F.3d at 1260). Thus, Petitioner’s proposed constructions
`
`for the phrases “to form a set comprising a plurality of assay samples,” “assay
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`samples of the set,” and “comparing the first number of assay samples to the
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`second number of assay samples to ascertain a ratio which reflects the composition
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`of the biological sample” should be rejected.
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`A.
`
`Petitioner Ignores the Context of the Claim in Construing the
`Term “Plurality” in the Phrase “to Form a Set Comprising a
`Plurality of Assay Samples”
`Claim 1 requires that the nucleic acid template molecules be distributed from
`
`a biological sample “to form a set comprising a plurality of assay samples.”
`
`AMB1003, 1:22-43. Patent Owner proposed that “plurality” be construed to mean
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`two or more (the plurality of assay samples may be “a group of two or more
`
`portions of the set for analysis”) within the context of the claim. Petitioner,
`
`however, suggests that the construction of “plurality” somehow overrides the
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`context in which the term and associated phrase appear in the claim. But claim
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`terms and phrases are not read in a vacuum. The plain and ordinary meaning of the
`
`term “plurality” is “two or more.” See, e.g., Dayco Prods., Inc. v. Total
`
`Containment, Inc., 258 F.3d 1317, 1328 (Fed. Cir. 2001)(“‘[P]lurality,’ when used
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`in a claim, refers to two or more items, absent some indication to the contrary.”).
`
`When taken in the context of the rest of the claim, however, a POSITA would
`
`understand that the number of assay samples is not simply two. Rather, the
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`plurality of samples that would be sufficient in given circumstances would depend
`
`on a number of factors, such as the frequency of the selected sequence or mutation
`
`in the biological sample or the degree of allelic imbalance and the size of the
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`sample. JHU2001, ¶¶ 37-38. Claims must “always be read in light of the
`
`specification and teachings in the underlying patent.” In re Suitco Surface, Inc.,
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`603 F.3d 1255, 1260 (Fed. Cir. 2010). Here, the claims and specification
`
`consistently refer to analyzing the assay samples of the set and comparing the
`
`numbers from this analysis to ascertain an allelic imbalance in the biological
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`sample. AMB1001, 2:16-22; JHU2001, ¶¶ 37-38. Therefore, depending on the
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`particular amount and composition of the nucleic acid template molecules isolated
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`from a biological sample, a POSITA would understand that the number of assay
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`samples required for the method, especially for relatively rare mutations or subtle
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`allelic imbalances, may necessarily be much higher than two in order to ascertain a
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`ratio that reflects the composition of the biological sample. JHU2001, ¶ 38;
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`AMB1001, 6:24-25. Thus, Petitioner’s singular focus on the term “plurality” to
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`mean as few as two is misleading. Whereas a “plurality” can be two or more, the
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`plurality of assay samples in the set, when considered in the full context of the
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`claims, varies based on a number of factors, such as the nature of the biological
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`sample and the frequency of the nucleic acids to be detected.
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`B.
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`Petitioner’s Proposed Construction of “Assay Samples of the Set”
`Is Also Unreasonably Broad
`Petitioner also misconstrues Patent Owner’s proposed construction of the
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`phrase “assay samples of the set.” Patent Owner proposed that the phrase
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`“amplified molecules in the assay samples of the set” (in the amplification step)
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`means “amplified molecules included, located, or positioned within the assay
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`samples associated with the set.” Petition, 10. Petitioner asserts that, under Patent
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`Case No. IPR2017-02093
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`Owner’s proposed construction, the amplified molecules need not even be part of
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`the set and that they may simply be “associated” with the set. Petition, 10. This is
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`incorrect.
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`Patent Owner’s proposed construction merely clarifies that the assay
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`samples are distinguishable as a set throughout the assay (i.e., including through
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`the amplifying, analyzing, and comparing steps). JHU2001, ¶ 39. They remain part
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`of the set, regardless of the physical location or characteristics of the assay
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`samples. Id. Inclusion in the set is necessary in order to ascertain an allelic
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`imbalance (an unequal ratio) in the biological sample. Id. Petitioner’s unreasonably
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`broad interpretation of the construction of this phrase is contrary to the
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`specification and should be rejected.
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`
`
`IV. PETITIONER’S EXPERT DECLARATION IS MERELY
`ATTORNEY ARGUMENT IN THE GUISE OF EXPERT
`TESTIMONY
`Petitioner relies on a declaration from its expert Dr. Buck (AMB1007).
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`However, Dr. Buck merely regurgitates the arguments that Petitioner sets out in its
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`Petition, and his declaration lacks sufficient facts and data to support his positions.
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`His superficial treatment of the prior art references is evident, for example, in his
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`discussion of Chiang (1996, Genome Research 6:1013-26; “Chiang”) (AMB1031).
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`Dr. Buck relies on Petitioner’s misstatements of Patent Owner’s proposed
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`constructions. See, e.g., AMB1007, ¶ 43. However, he provides no reason why he
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`believes one of ordinary skill in the art would arrive at such constructions. Rather,
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`he simply parrots the Petition. For example, in relation to the fourth step of the
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`Challenged Claims, he states that simply “examining two sequences (such as after
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`sequencing) without any comparison” or “simply attempting to discover an allelic
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`imbalance” would meet the claim limitation. AMB1007, ¶ 43. Dr. Buck notes that
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`Chiang discloses ascertaining an allelic imbalance in a biological sample.
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`AMB1007, ¶ 44. But he provides no other analysis or any explanation as to how
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`the disclosure in Chiang satisfies the “comparing” claim element, which requires
`
`determining numbers representing assay samples in the set containing a “selected
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`genetic sequence on a first chromosome” and assay samples in the set containing a
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`“reference genetic sequence on a second chromosome” and comparing the first and
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`second numbers to ascertain an allelic imbalance.
`
`Such conclusory and superficial attorney argument in the guise of expert
`
`testimony cannot serve as sufficient support for Petitioner’s arguments. See, e.g.,
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`Cardiocom, LLC, IPR2013-00439, Paper 26, 15-16 (PTAB Jan. 16, 2014); see also
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`Kinetic Techs., Inc. v. Skyworks Solutions, Inc., IPR2014-00529, Paper 8, 15-16
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`(PTAB Sept. 23, 2014) (“Merely repeating an argument from the Petition in the
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`declaration of a proposed expert does not give that argument enhanced probative
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`value,” and a petitioner cannot move forward to trial based upon such “mere
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`conclusory statements.”) (citing In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006));
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`TRW Auto. US LLC v. Magna Elecs., Inc., IPR2014-00258, Paper 18, 10-11
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`(PTAB Aug. 27, 2014) (giving little to no weight to expert testimony that “did not
`
`elaborate on [Petitioner’s] position because it simply repeated [Petitioner’s]
`
`conclusory statements verbatim”); see also InfoBionic, Inc. v. Braemar
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`Manufacturing, LLC, IPR2015-01704, Paper 11, 6 (PTAB Feb. 16, 2016) (denying
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`institution because expert merely repeated the argument in the Petition about what
`
`a reference meant without explaining why the expert believed that meaning to be
`
`correct). Therefore, little weight should be given to Dr. Buck’s testimony. Absent
`
`his conclusory testimony, the Petition has no evidentiary support, and institution
`
`should be denied.
`
`Patent Owner provides detailed expert testimony of Dr. Fred Kramer
`
`supporting the patentability of the Challenged Claims (JHU2001). And contrary to
`
`Dr. Buck’s testimony, Dr. Kramer’s testimony is supported with sufficient facts
`
`and data. Dr. Kramer’s testimony refutes the legal arguments set forth by the
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`Petitioner and repeated by Dr. Buck. Thus, even when the evidence is viewed in
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`the light most favorable to Petitioner (37 C.F.R. § 42.108(c)), Petitioner’s
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`unsupported arguments must fail.
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`V.
`
`SYKES WAS ALREADY CONSIDERED BY THE PATENT OFFICE
`“In determining whether to institute or order a proceeding under . . . chapter
`
`30 . . . or chapter 31 [i.e., inter partes review], 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. §
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`325(d); see also Cultec, Inc. v. Stormtech LLC, IPR2017-00777, Paper 7 (PTAB
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`Aug. 22, 2017) (denying institution where the petitioner relied on art that the
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`examiner either previously considered or that was cumulative of that art); Unified
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`Patents, Inc. v. Berman, IPR2016-01571, Paper 10 (PTAB Dec. 14, 2016)
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`(denying institution based on a combination of references that included a reference
`
`the examiner considered during prosecution and a second reference that was
`
`deemed cumulative); Ziegman v. Stephens, IPR2015-01860, Paper 11 (PTAB Feb.
`
`24, 2016) (denying institution based on a combination of references that included a
`
`primary reference that was considered by the Patent Office during prosecution).
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`Here, the Board should exercise its discretion to not institute the IPR, or, at a
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`minimum not institute with respect to Ground 2 and 3 because these grounds
`
`present the same prior art previously considered by the Patent Office during
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`original prosecution and reexamination of the ’889 patent.
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`Sykes de