Trials@uspto.gov
`571.272.7822
`
`
`
`
` Paper No. 20
`
` Filed: April 20, 2018
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`COMPLETE GENOMICS, INC.,
`Petitioner,
`
`v.
`
`ILLUMINA CAMBRIDGE LTD.,
`Patent Owner.
`____________
`
`Case IPR2017-02174
`Patent 7,566,537 B2
`____________
`
`
`Before ERICA A. FRANKLIN, ZHENYU YANG, and
`TIMOTHY G. MAJORS, Administrative Patent Judges.
`
`MAJORS, Administrative Patent Judge.
`
`
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`
`Illumina Ex. 1083
`IPR Petition - USP 10,435,742
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`
`I. INTRODUCTION
`
`Complete Genomics, Inc. (“CGI” or “Petitioner”), on October 5,
`
`2017, filed a Petition to institute inter partes review of claims 1–6 and 8 of
`
`U.S. Patent No. 7,566,537 B2 (“the ’537 patent”). Paper 1 (“Pet.”).1
`
`Illumina Cambridge Ltd. (“Patent Owner”), on January 23, 2018, filed a
`
`Preliminary Response to the Petition. Paper 6 (“Prelim. Resp.”).
`
`Under 35 U.S.C. § 314(a), an inter partes review may not be instituted
`
`unless the Petition “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.” For the reasons stated below, we determine that Petitioner has
`
`not established a reasonable likelihood that it would prevail in showing the
`
`unpatentability of claims 1–6 and 8 of the ’537 patent.
`
`
`
`II. BACKGROUND
`
`A.
`
`Related Matters
`
`Petitioner identifies other proceedings related to the ’537 patent.
`
`Pet. 4–7. The identified proceedings include, inter alia, the following:
`
`1) IPR2013-00517 (petition for inter partes review by
`
`Intelligent Bio-Systems, Inc. (“IBS”));
`
`2) IPR2013-00518 (petition for inter partes review by IBS);
`
`3) Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd.,
`
`821 F.3d 1359 (Fed. Cir. 2016) (appeal of IPR2013-00517);
`
`4) Illumina, Inc. v. Qiagen, N.V., 207 F.Supp.3d 1081 (N.D.
`
`
`
`1 Petitioner identifies BGI Shenzhen Co., Ltd. (and other BGI companies) as
`a real party-in-interest to these proceedings. Pet. 4.
`
`2
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`Cal. 2016) (involving assertion of the ’537 patent against
`
`Qiagen and its subsidiary, IBS);
`
`5) The Trustees of Columbia University v. Illumina, Inc., 1:12-
`
`cv-00376-GMS (D. Del.) (involving assertion of patents
`
`against Illumina, and assertion of the ’537 patent against
`
`IBS, Columbia’s licensee of the accused technology); and
`
`6) IPR2017-02172 (petition for inter partes review by CGI,
`
`filed concurrent with the present Petition).
`
`Pet. 4–7. We describe these proceedings in more detail in Section II.E.
`
`below.
`
`B.
`
`Background Technology and the ’537 Patent
`
`The ’537 patent relates generally to labeled nucleotides and
`
`nucleosides, and to methods of using such molecules in, for example,
`
`nucleic acid sequencing reactions. Ex. 1501, 2:1–7.
`
`A “nucleotide” consists of a nitrogenous base, a sugar, and one or
`
`more phosphate groups. Id. at 4:48–49. An illustrative depiction of a
`
`deoxyribonucleotide triphosphate is provided below.
`
`Ex. 1601, ¶ 8. The depiction above shows, inter alia, the 3'-hydroxyl (3'-
`
`OH) group of the deoxyribose sugar; the sugar of a DNA nucleotide is a 2'
`
`
`
`3
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`deoxyribose, meaning the 2' carbon lacks a bond to an oxygen atom. Id.
`
`¶ 10 (depicting 2-deoxyribose and ribose); Ex. 1501, 4:49–51 (“In RNA, the
`
`sugar is a ribose, and in DNA is a deoxyribose, i.e., a sugar lacking a
`
`hydroxyl group that is present in ribose [at the 2' carbon]”).
`
`Nucleotides, such as depicted above, are building blocks of DNA and,
`
`through complementary base-pairing, form molecules of DNA that consist
`
`of two associated nucleic acid strands and a double-helical structure that
`
`resembles a twisting ladder. Ex. 1601, ¶¶ 8–9. Natural DNA contains four
`
`bases: the base may include a purine or pyrimidine, such as the purines
`
`adenosine (A) and guanidine (G), and the pyrimidines cytidine (C) and
`
`thymidine (T). Ex. 1501, 4:51–54. The sequence of these bases in DNA
`
`provides genetic information, and ultimately encodes the traits in living
`
`organisms. Intelligent Bio-Systems, 821 F.3d at 1362.
`
`A base of one DNA strand bonds with the complementary base on the
`
`opposing strand in a known pattern: A pairs with T, and G pairs with C. Ex.
`
`1601, ¶ 9. Because of this pattern of base pairing, if the sequence of one
`
`strand is known, the other strand’s sequence can be deduced. Id. In
`
`addition, enzymes (e.g., DNA polymerase) may cause the strand to be
`
`extended with the phosphate group on the 5' carbon of each additional
`
`nucleotide attaching to the 3'-OH of the last nucleotide in the strand via a
`
`new phosphodiester bond. Id. ¶ 11. The added nucleotide is one that, as
`
`explained above, bonds with its complementary base of the nucleotide at a
`
`corresponding position on the opposing nucleic acid strand. Id. ¶ 9; Ex.
`
`1501, 2:50–53.
`
`As described in the ’537 patent, “[t]he invention features a nucleotide
`
`or nucleoside molecule, having a base that is linked to a detectable label via
`
`a cleavable linker.” Ex. 1501, 2:23–24. The label may be, for example, a
`
`4
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`fluorophore that is detectable by fluorescence spectroscopy. Id. at 5:20–25.
`
`The nucleotide also includes a ribose or deoxyribose sugar, which “sugar
`
`can include a protecting group attached via the 2' or 3' oxygen atom,” and
`
`the protecting group “can be removed to expose a 3'-OH.” Id. at 2:25–28.
`
`The ’537 patent depicts several exemplary labeled nucleotide
`
`structures, such as shown below.
`
`
`
`Ex. 1501, Fig. 1 (partial). Figure 1 (partial) above shows a nucleotide
`
`having a base (here cytidine) attached to a label via a linker. Id. The ’537
`
`patent explains that “X” in this molecule can be, for example, a triphosphate,
`
`and that R1 and R2 may be selected from H, OH, or any group that can be
`
`transformed into an OH. Id. at 4:7–11. Among the “suitable hydroxyl
`
`protecting groups” that can be transformed into an OH, the ’537 patent
`
`identifies azidomethyl (CH2N3). Id. at Fig. 3. A further representation of an
`
`azidomethyl protecting group is shown below.
`
`
`
`5
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`Ex. 1601, ¶ 143. The representation above shows a 3'-O-azidomethyl
`
`deoxynucleotide triphosphate, where the azidomethyl group is attached to
`
`the 3' oxygen atom of the deoxyribose sugar moiety thereby protecting a
`
`nascent 3'-OH.
`
`The ’537 patent describes methods of labeling nucleic acids, in which
`
`an enzyme is used to incorporate a labeled nucleotide into the nucleic acid
`
`molecule. Ex. 1501, 2:32–38. The ’537 patent also describes methods of
`
`using labeled and blocked nucleotides to determine the sequence of a target
`
`single-stranded polynucleotide. Id. at 2:50–57. More specifically, the ’537
`
`patent explains that this method
`
`can be carried out by contacting the target polynucleotide
`separately with the different nucleotides to form the complement
`to that of the target polynucleotide, and detecting
`the
`incorporation of the nucleotides. Such a method makes use of
`polymerisation, whereby a polymerase enzyme extends the
`complementary strand by incorporating the correct nucleotide
`complementary to that on the target. The polymerisation reaction
`also requires a specific primer to initiate polymerisation.
`
`Id. at 8:50–58. Because the 3'-OH of the nucleotide(s) to be added is
`
`protected by a protecting group, the enzyme incorporates only one
`
`nucleotide at a time into the complementary strand, thus providing a
`
`controlled sequencing reaction. Id. at 7:51–54. The detectable label
`
`uniquely identifies the particular type of nucleotide (e.g., containing a base
`
`“G”) that was incorporated into the growing complementary strand. Id. at
`
`2:55–57, 5:20–24, 10:4–9. The label and protecting group are then removed,
`
`thus exposing a 3'-OH on the previously added nucleotide, and the process
`
`repeats with the addition of the next labeled and blocked nucleotide(s). Id.
`
`at 2:55–3:16, 7:43–8:14. By detecting, one-by-one, the type of nucleotides
`
`6
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`that are added to the complementary strand, the sequence of the entire target
`
`polynucleotide chain can be determined. Id. at 2:50–3:3.
`
`C.
`
`Illustrative Claims
`
`Petitioner challenges claims 1–6 and 8. Claim 1, the only challenged
`
`independent claim, and dependent claim 6 are reproduced below:
`
`1. A method of labeling a nucleic acid molecule, the method
`comprising incorporating into the nucleic acid molecule a
`nucleotide or nucleoside molecule, wherein the nucleotide or
`nucleoside molecule has a base that is linked to a detectable label
`via a cleavable linker and the nucleotide or nucleoside molecule
`has a ribose or deoxyribose sugar moiety, wherein the ribose or
`deoxyribose sugar moiety comprises a protecting group attached
`via the 2' or 3' oxygen atom, and said protecting group can be
`modified or removed to expose a 3' OH and the protecting group
`comprises an azido group.
`
`
`
`6. The method according to claim 1, wherein the protecting
`group is CH2N3 [i.e., azidomethyl].
`
`Ex. 1501, 19:48–59, 20:3–4.
`
`
`D.
`
`The Asserted Grounds of Unpatentability
`
`Petitioner contends claims 1–6 and 8 are unpatentable under
`
`35 U.S.C. § 103 based on the following grounds. Pet. 8–9.
`
`
`
`Ground References
`Dower,2 Church,3 and Zavgorodny4
`1
`
`
`Basis Claims
`§ 103 1, 2, 4–6,
`and 8
`
`
`
`2 Dower et al., US 5,547,839, issued Aug. 20, 1996. Ex. 1504.
`3 Church et al., WO 00/53812 A2, published Sept. 14, 2000. Ex. 1606.
`4 Sergey Zavgorodny et al., 1-Alkylthioalkylation of Nucleoside Hydroxyl
`Functions and Its Synthetic Applications: A New Versatile Method in
`Nucleoside Chemistry, 32 TETRAHEDRON LETTERS 7593–96 (1991). Ex.
`1508.
`
`7
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`2
`
`
`
`Dower, Church, Zavgorodny, and Prober5
`
`
`3
`
`§ 103
`
`
`Petitioner also relies on the Declaration of John D. Sutherland,
`
`D. Phil. (Ex. 1601), and several ancillary references.
`
`E. History of the ’537 Patent at the U.S. Patent Office and in Other
`Legal Proceedings
`
`i) Relevant Prosecution History
`
`The ’537 patent issued on July 28, 2009 from U.S. Application No.
`
`11/301,578, filed December 13, 2005. Ex. 1501.6 Claim 9 (which later
`
`issued as claim 1) did not recite a “protecting group” or a “protecting group
`
`[that] comprises an azido group” when that claim was originally filed. Ex.
`
`1502, 71. On October 30, 2007, the Examiner entered a rejection of claim 9
`
`as anticipated by Ju.7 Id. at 84. On February 1, 2008, the applicants
`
`amended claim 9, adding a limitation of a “protecting group [that] comprises
`
`an azido group.” Id. at 71 (underlining omitted). The applicants also added,
`
`inter alia, new claim 34, which was substantially the same as claim 9 except
`
`that it recited “the protecting group comprises an allyl moiety.” Id. at 72.
`
`The applicants responded to the Examiner’s rejection, explaining the
`
`addition of the azido group to claim 9, and argued the amended and newly
`
`presented claims were not taught or suggested by the prior art. Id. at 77–78.
`
`
`
`5 James M. Prober et al., A System for Rapid DNA Sequencing with
`Fluorescent Chain-Terminating Dideoxynucleotides, 238 SCIENCE 336–41
`(1987). Ex. 1507.
`6 This application is a divisional of US Application No. 10/227,131, filed on
`August 23, 2002 and which issued as US 7,057,026 B2 on June 6, 2006.
`7 Ju et al., US 6,664,079 B2, issued Dec. 16, 2003. Ex. 1538.
`
`
`
`8
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`The Examiner responded on May 16, 2008 with a rejection of claim
`
`34 as obvious over Tsien and Greene & Wuts.8 Id. at 64. The Examiner
`
`determined that the 3'-OH allyl protecting group was implicitly disclosed in
`
`Tsien and also obvious in view of Greene & Wuts and “the Patent Owner’s
`
`admission that all of the protecting groups are known in the prior art.” Id. at
`
`65. As to claim 9 (reciting an azido protecting group) and dependent claim
`
`28 (reciting an azidomethyl (CH2N3) protecting group), the Examiner,
`
`without further comment, noted those claims were allowed. Id. On August
`
`21, 2008, the applicants canceled claim 34 and its dependent claims, and
`
`requested allowance of the other pending claims. Id. at 59. Claims 9 and 28
`
`later issued in the ’537 patent as claims 1 and 6, respectively. Id. at 25.
`
`Dower, Church, and Zavgorodny appear in the references cited
`
`portion of the ’537 patent. Ex. 1501, 2 (left and right columns) and 3 (right
`
`column). The Examiner did not, however, specifically rely on these
`
`references or apply them to support a rejection during prosecution. Prober is
`
`referenced in the ’537 patent’s specification. Ex. 1501, 5:30–31.
`
`ii) Prior Petitions for Inter Partes Review
`
`In IPR2013-00518, IBS challenged claims 7 and 11–14 of the ’537
`
`patent, which claims were canceled based on Patent Owner’s disclaimer and
`
`request for adverse judgment. Pet. 6; Exs. 1588 and 1589.
`
`
`
`8 The Examiner appears to have relied on a prior edition of Greene & Wuts
`(Theodora W. Greene & Peter G.M. Wuts, PROTECTIVE GROUPS IN ORGANIC
`SYNTHESIS (John Wiley & Sons, Inc., 1991) to the third edition relied upon
`in IPR2017-02172 and in IPR2013-00517. Ex. 1502, 64, 67.
`
`9
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`In IPR2013-00517, IBS challenged claims 1–6 and 8 of the ’537
`
`patent on multiple obviousness grounds. Pet. 6; Ex. 1590, 6–7 (Rev.
`
`Petition dated Aug. 3, 2013, Paper 7). The specific grounds are below:
`
`
`
`Ground References
`1a
`Ju and Zavgorodny
`
`Ju and Greene & Wuts9
`
`Tsien10 and Zavgorodny
`
`1b
`
`1c
`
`1d
`
`2a
`
`2b
`
`Tsien and Greene & Wuts
`
`Tsien, Zavgorodny, and Prober
`
`Tsien, Greene & Wuts, and Prober
`
`
`
`Ex. 1590, 7–8.
`
`Basis Claims
`§ 103
`1–6 and 8
`
`§ 103
`
`§ 103
`
`§ 103
`
`§ 103
`
`§ 103
`
`
`1–6 and 8
`
`1–6 and 8
`
`1–6 and 8
`
`3
`
`3
`
`Patent Owner waived the filing of a preliminary response and, on
`
`February 13, 2014, the Board instituted inter partes review on claims 1–6
`
`and 8 over Tsien (or Ju) in combination with Zavgorodny (grounds 1a and
`
`1c in the table above). Ex. 1591, 2, 15. The Board further instituted review
`
`of claim 3 based on the combination of Tsien, Zavgorodny, and Prober
`
`(ground 2a). Id. The Board concluded the other grounds were redundant.
`
`Id. at 5, 15. On May 5, 2014, Illumina filed its Patent Owner Response. Ex.
`
`1592. And, on July 28, 2014, IBS filed its Reply. Ex. 1593.
`
`
`
`9 Theodora W. Greene & Peter G.M. Wuts, PROTECTIVE GROUPS IN
`ORGANIC SYNTHESIS 1–5, 14–23, 246–60 (John Wiley & Sons, Inc., 3rd ed.
`1999). Ex. 1505.
`10 Tsien, WO 91/06678 A1, published May 16, 1991. Ex. 1503.
`
`10
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`The Board held a full trial and issued a Final Written Decision dated
`
`February 11, 2015. Ex. 1594. The Board determined the preponderance of
`
`the evidence did not support a conclusion that claims 1–6 and 8 were
`
`unpatentable. Id. at 3–4. Among other things, the Board “agree[d] with
`
`Patent Owner that Petitioner [had] not shown . . . that an ordinary artisan
`
`would have considered it obvious to use Zavgorodny’s azidomethyl group as
`
`the 3' hydroxyl protecting group in Tsien’s processes.” Id. at 9. The Board
`
`further found that “the prior art suggests that an ordinary artisan would not
`
`have expected Zavgorodny’s azidomethyl group to be removed
`
`quantitatively, as Tsien requires.” Id. at 14. As explained by the Board,
`
`Tsien’s requirement for quantitative deblocking “mean[s] essentially 100%
`
`removal of the protecting group.” Id. at 12.
`
`In reaching its conclusion, the Board also relied on Greene & Wuts
`
`and Loubinoux,11 which together disclose removal of an azidomethyl
`
`protecting group from phenols (as distinct from simple aliphatic alcohols
`
`like the 3' hydroxyl of a deoxyribonucleotide). Id. at 13. Based on the
`
`reported yields (60–80%) of deprotected phenols in Loubinoux, and Greene
`
`& Wuts’ teaching that a phenol is a better leaving group (i.e., is more easily
`
`cleaved) than a simple alcohol, the Board found that the ordinary artisan
`
`would have expected inefficient removal/deblocking of an azidomethyl
`
`moiety in Tsien’s methods. Id. at 13–14. Thus, the Board determined the
`
`ordinarily skilled person would not have been motivated to use an
`
`
`
`11 Bernard Loubinoux et al., PROTECTION OF PHENOLS BY THE
`AZIDOMETHYLENE GROUP APPLICATION TO THE SYNTHESIS OF
`UNSTABLE PHENOLS, 44 TETRAHEDRON 6055–64 (1988) (as translated).
`Ex. 1506. Greene & Wuts cites Loubinoux for the use of an azidomethyl
`group to protect phenols. Ex. 1505, 260.
`
`11
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`azidomethyl group to meet Tsien’s sequencing criteria — especially the
`
`requirement for quantitative deblocking. Id. at 7, 18.12
`
`iii) Proceedings Before the Federal Circuit
`
`On May 9, 2016, the Federal Circuit affirmed the Board’s
`
`determination in IPR2013-00517 that claims 1–6 and 8 had not been shown
`
`to be obvious. Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd., 821
`
`F.3d 1359 (Fed. Cir. 2016). The court analyzed the prior art combination of
`
`Tsien and Zavgorodny. Id. at 1363–64. And, like the Board, the court
`
`accepted that Tsien required quantitative deblocking for successful use of 3'
`
`blocking groups in Tsien’s DNA sequencing methods and that, “for the
`
`deblocking (i.e., the removal of the protecting group) to be quantitative, it
`
`must take place at 100% or near-100% efficiency.” Id. at 1364.
`
`According to the Federal Circuit, although the challenged claims of
`
`the ’537 patent do not require quantitative deblocking, the expectation (or
`
`lack thereof) of high efficiency deblocking “is central to a finding of no
`
`motivation to combine.” Id. at 1368. That is so, the court explained,
`
`because the petitioner argued the skilled artisan would have been motivated
`
`to use Zavgorodny’s azidomethyl group with Tsien’s SBS (sequencing-by-
`
`synthesis) method to meet Tsien’s criteria. Id.13 Analyzing Greene & Wuts
`
`and Loubinoux, the court further concluded there was “substantial evidence
`
`
`
`12 The Board reached a similar conclusion with respect to the challenge
`based on Ju and Zavgorodny. Ex. 1594, 18–22.
`13 As noted by the Federal Circuit, “IBS argued that an ordinary artisan, to
`improve the efficiency, reliability, and robustness of the sequencing by
`synthesis method taught by Tsien, would have been motivated to use other
`protecting groups that meet the criteria of Tsien, such as the azidomethyl
`group taught by Zavgorodny.” Intelligent Bio-Systems, 821 F.3d at 1364
`(internal quotation marks and citation omitted); see also Ex. 1594, 7.
`
`12
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`to support a finding that a person of ordinary skill would not have had a
`
`reason to combine Tsien or Ju with Zavgorodny to achieve the claimed
`
`invention.” Id. at 1368–69 (“These references [Greene & Wuts and
`
`Loubinoux] support a conclusion that the claimed efficiency that allegedly
`
`motivated the combination would not be achieved.”). Indeed, as the court
`
`held, “[t]his is so because the azidomethyl group would have been expected
`
`to perform inefficiently in that role [as a protecting group that can be
`
`removed to expose a 3'-OH group of a nucleotide].” Id. at 1369.
`
`iv) Proceedings Before the District Courts
`
`After the Federal Circuit’s decision, Patent Owner sued Qiagen N.V.
`
`and several of its subsidiaries (including IBS) in the Northern District of
`
`California, alleging infringement of the ’537 patent. Illumina, 207
`
`F.Supp.3d at 1083, 1086. Patent Owner also moved for a preliminary
`
`injunction against Qiagen. Id. Qiagen did not deny that its accused DNA
`
`sequencing products were covered by claims 1–6 and 8 of the ’537 patent,
`
`and instead argued the claims would have been obvious over Tsien, Ju, and
`
`Greene & Wuts. Id. at 1087–88.
`
`In its decision and order dated September 9, 2016, the district court
`
`found “Qiagen’s obviousness argument [was] unpersuasive” and “weak,”
`
`and held that Patent Owner “has shown it is likely to defeat Qiagen’s
`
`invalidity arguments.” Id. at 1088–90. The court determined, among other
`
`things, that “Greene & Wuts is an extensive treatise covering thousands of
`
`protecting groups for various purposes,” and that, while “Greene & Wuts
`
`does teach the use of azidomethyl . . . [,] that reference is in a chapter
`
`directed at phenols, which are hydroxyl groups [] of a different type than the
`
`hydroxyl group that appears in nucleotides or nucleosides.” Id. at 1098.
`
`13
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`Also, the court found, “Greene & Wuts offers an entirely separate chapter on
`
`aliphatic alcohols, which include the types of hydroxyl groups that appear in
`
`nucleotides and nucleosides . . . [but] makes no mention of azido groups” in
`
`that chapter. Id. The court pointed to testimony from Qiagen’s expert
`
`admitting that the removal conditions for azidomethyl disclosed in Greene &
`
`Wuts would be inappropriate for use with nucleotides and would alter DNA
`
`structures. Id. And, the court cited to the earlier decisions by the Board and
`
`Federal Circuit related to IPR2013-00517 and their analysis of Tsien and
`
`Greene & Wuts. Id. at 1090 n.2. In so doing, the court agreed that Greene
`
`& Wuts “would have indicated a low likelihood of success in using
`
`azidomethyl in the process taught by Tsien.” Id. at 1090. The court
`
`ultimately granted the preliminary injunction. Id. at 1093–94. According to
`
`Patent Owner, after the injunction was granted Qiagen agreed to a consent
`
`judgment and the case ended. Prelim. Resp. 2, 17–18; Paper 17, 4.
`
`In other, earlier-filed district court proceedings in Delaware, IBS sued
`
`Patent Owner for infringement of five DNA sequencing-by-synthesis related
`
`patents, and Patent Owner responded by asserting the ’537 patent (and two
`
`other patents) against IBS. Pet. 5. The Trustees of Columbia University v.
`
`Illumina, Inc., 1:12-cv-00376-GMS (D. Del.). This litigation was stayed
`
`based on eight requests for inter partes review (including IPR2013-00517).
`
`Pet. 5. According to Petitioner, although all the challenged claims in seven
`
`of the eight IPRs were canceled, “certain claims of the ’537 patent
`
`survived.” Pet. 5–6. The Delaware litigation ended via order of dismissal
`
`dated August 2, 2017, apparently based on the parties’ “negotiated
`
`settlement.” See The Trustees of Columbia University, 1:12-cv-00376-GMS
`
`(document 132 (Stipulation and Order of Dismissal)).
`
`14
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`CGI filed the present petitions for inter partes review (IPR2017-
`
`02172 and IPR2017-02174) on October 5, 2017. The petition in IPR2017-
`
`02172 challenges claims 1, 2, 4–6, and 8 as obvious over Tsien, Greene &
`
`Wuts, and Zavgorodny, and challenges claim 3 as obvious over Tsien,
`
`Greene & Wuts, Zavgorodny, and Prober.
`
`
`
`III. ANALYSIS
`
`A. Declining Discretionary Non-Institution under 35 U.S.C. § 314(a)
`
`Institution of inter partes review is discretionary. See 35 U.S.C.
`
`§ 314(a) (authorizing institution of an inter partes review under particular
`
`circumstances, but not requiring institution under any circumstances);
`
`37 C.F.R. § 42.108(a) (stating “the Board may authorize the review to
`
`proceed”) (emphasis added); Harmonic Inc. v. Avid Tech., Inc., 815 F.3d
`
`1356, 1367 (Fed. Cir. 2016) (“[T]he PTO is permitted, but never compelled,
`
`to institute an IPR proceeding” under § 314(a).).
`
`Patent Owner argues the Board should exercise its discretion under
`
`§ 314(a) and deny the Petition pursuant to General Plastic Indus. Co. Ltd. v.
`
`Canon Kabushiki Kaisha, Case IPR2016-01357 (PTAB Sept. 6, 2017)
`
`(Paper 19) (precedential) (hereinafter “General Plastic”).14 Prelim. Resp.
`
`19–27.
`
`Patent Owner acknowledges that Petitioner is not and was not a party
`
`to any prior petition or litigation challenging the validity of the ’537 patent’s
`
`claims. Paper 17, 1–2; see also Paper 14, 1–4. Petitioner asserts that it
`
`
`
`14 Patent Owner did not, in its Preliminary Response, argue for discretionary
`denial under 35 U.S.C. § 325(d), unlike in IPR2017-02172.
`
`
`15
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`neither cooperated nor coordinated with any earlier challenge to the ’537
`
`patent. Paper 14, 4.
`
`Notwithstanding the above, Patent Owner, relying primarily on the
`
`prior and unsuccessful challenges to the ’537 patent by different parties,
`
`urges that we should deny the Petition. Paper 17, passim. However, we
`
`decline to extend General Plastic and discretionary denial under § 314(a) to
`
`the facts here. See, e.g., Pfizer, Inc. v. Genentech, Inc., IPR2017-01923 slip
`
`op. 23–25 (PTAB Apr. 4, 2018) (declining to expand General Plastic to a
`
`new petitioner advancing new art and arguments).
`
`B. Overview of the Asserted References
`
`i) Dower (Ex. 1504)
`
`Dower is a U.S. patent that issued in 1996. Dower “provides a
`
`method and apparatus for sequencing many nucleic acid sequences
`
`immobilized at distinct locations on a matrix surface.” Ex. 1504, 1:21–25.
`
`Dower describes the use of labeled and blocked 3'-OH deoxynucleotides in a
`
`cycle that includes elongating a primer by a single nucleotide, removing the
`
`blocking group and label, and repeating the process for subsequent labeled
`
`and blocked nucleotides. Id. at Abstract, Fig. 8, 4:44–5:2, 15:35–40; see
`
`also Ex. 1601, ¶ 25. With respect to this DNA sequencing method, Dower
`
`further discloses:
`
`DNA polymerase, or a similar polymerase, is used to extend the
`chains by one base by incubation in the presence of dNTP
`analogs which function as both chain terminators and fluorescent
`labels. . . . When each cluster incorporates the proper one of the
`four bases and the fluorescence scanning is complete, the matrix
`is stripped of the label and chain terminators are deblocked for a
`next round of base addition. Because the base addition is
`directed by the template strand, the complementary sequence of
`the fragments at each address of the matrix is deduced.
`
`
`16
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`Ex. 1504, 23:15–32.
`
`
`
`Dower teaches a detectable label may be attached to the nucleobase or
`
`elsewhere on the molecule provided the position is compatible with
`
`appropriate polymerization. Id. at 15:54–59, Fig. 9. According to Dower,
`
`when different structures are used as the detectable label and the chain
`
`terminator/blocking group (i.e., the label and blocking group are different
`
`moieties and/or are located at different locations on the molecule), it is
`
`preferable to simultaneously deprotect the 3'-position and cleave the label
`
`using the same conditions. Id. at 25:23–40. Dower teaches “[t]he
`
`appropriate reaction conditions are those used for conventional sequencing
`
`reactions with the respective polymerases” and “[t]he conditions are then
`
`modified in the usual ways to obtain the optimal conditions . . . .” Id. at
`
`17:25–29. Dower further teaches that “[t]he removal reaction will
`
`preferably be achieved using mild conditions.” Id. at 15:52–54.
`
`
`
`Dower identifies useful blocking groups, but does not disclose an
`
`azido or azidomethyl group. Id. at 10:50–53, 18:16–20, 18:52–63, Fig. 6.
`
`Dower also does not teach the use of a linker when the label is attached to
`
`the nucleobase. Pet. 26.
`
`ii) Church (Ex. 1606)
`
`Church is an international patent application that published in 2000.
`
`Like Dower, it also relates to DNA sequencing-by-synthesis methods. Ex.
`
`1606, Abstract; id. at 6:9–25. Church teaches, inter alia, the use of a
`
`detectable label, such as a fluorophore, that is attached to the base by a
`
`cleavable disulfide linker. Id. at 17:10–11, Fig. 5. Church also teaches the
`
`use of thiol compounds, such as DTT (dithiothreitol) to reduce/cleave the
`
`disulfide linkage. Id. at 68:12–13. Church does not disclose a reversible
`
`blocking group that protects the 3'-OH of a nucleotide’s deoxyribose ring.
`
`17
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`iii) Zavgorodny (Ex. 1508)
`
`Zavgorodny is a synthetic organic chemistry paper published in 1991,
`
`and it relates to the chemical synthesis of nucleosides.15 Ex. 1508, 7593.
`
`Zavgorodny discloses over 100 compounds that are described as “useful
`
`specifically blocked synthons.” Ex. 1508, 7595. Zavgorodny does not,
`
`however, disclose any specific use for these compounds and, specifically,
`
`does not disclose their use in DNA sequencing methods. See Ex. 2023,
`
`104:10–14, 105:23–106:3.
`
`Zavgorodny identifies 21 potential protecting groups for the 2'- and 3'-
`
`OH groups of a deoxyribose sugar. Ex. 1508, 7594. One of those groups is
`
`an azidomethyl (CH2N3). Id. Zavgorodny discloses the “[a]zidomethyl
`
`group is of special interest, since it can be removed under very specific and
`
`mild conditions, viz. with triphenylphosphine in aqueous pyridine at 20 °C.”
`
`Id. at 7595.
`
`C.
`
`A Person of Ordinary Skill in the Art
`
`Petitioner proposes the following definition for the person of ordinary
`
`skill in the art:
`
`a member of a team of scientists working on the research and
`development of DNA analysis and sequencing techniques. Such
`a person would have held a doctoral degree related to bioorganic
`chemistry, biological chemistry or a closely related discipline,
`and had at least five years of practical academic or industrial
`laboratory experience directed toward the research and
`development of DNA analysis and sequencing technologies.
`
`
`
`
`15 As described in the ’537 patent, a “nucleoside” is similar to a nucleotide
`but lacks phosphate moieties. Ex. 1501, 4:59–63 (“A ‘nucleoside’ is
`structurally similar to a nucleotide, but are missing the phosphate
`moieties.”); see also Ex. 1601, ¶ 158 n.6.
`
`18
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`Pet. 13. Petitioner acknowledges (Pet. 14, n. 1) that its proposed definition
`
`is substantially similar to Patent Owner’s proposed definition, which reads:
`
`a member of a team of scientists addressing SBS product
`development. Such a person would have held a doctoral degree
`in chemistry, molecular biology, or a closely related discipline,
`and had at least five years of practical academic or industrial
`laboratory experience. Thus, a person of ordinary skill includes
`a person having a doctoral degree in a field related to chemistry,
`and at least five years of laboratory experience directed toward
`the research and development of DNA sequencing technologies.
`
`
`
`Prelim. Resp. 26; see also Ex. 1592, 9–10.
`
`
`
`We do not, for purposes of this Decision, discern a material difference
`
`between the parties’ definitions, which are not inconsistent with the prior art
`
`of record. As Petitioner bears the burden, we rely on Petitioner’s definition,
`
`but our analysis would be the same under either proposal. 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)
`
`(internal quotation marks and citation omitted).
`
`D. Claim Construction
`
`In an inter partes review, we interpret claim terms in an unexpired
`
`patent based on the broadest reasonable construction in light of the
`
`specification of the patent in which they appear. 37 C.F.R. § 42.100(b);
`
`Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2142 (2016) (affirming
`
`the broadest reasonable construction standard in inter partes review
`
`proceedings). Under that standard, we presume a claim term carries its
`
`“ordinary and customary meaning,” which “is the meaning the term would
`
`have to a person of ordinary skill in the art in question” at the time of the
`
`19
`
`

`

`IPR2017-02174
`Patent 7,566,537 B2
`
`invention. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir.
`
`2007). We need only construe terms in