Trials@uspto.gov
`571.272.7822
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`
`
`
` Paper No. 20
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` Filed: April 20, 2018
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`
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`COMPLETE GENOMICS, INC.,
`Petitioner,
`
`v.
`
`ILLUMINA CAMBRIDGE LTD.,
`Patent Owner.
`____________
`
`Case IPR2017-02172
`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. 1082
`IPR Petition - USP 10,435,742
`
`

`

`IPR2017-02172
`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
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`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
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`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.” Institution of inter partes review is, however, discretionary.
`
`See 35 U.S.C. § 314(a); 35 U.S.C. § 325(d); 37 C.F.R. § 42.108(a). Based
`
`on the particular circumstances of this case, as explained below, we exercise
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`our discretion under § 325(d) and deny the Petition.
`
`
`
`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.,
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`821 F.3d 1359 (Fed. Cir. 2016) (appeal of IPR2013-00517);
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`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
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`

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`IPR2017-02172
`Patent 7,566,537 B2
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`Cal. 2016) (involving assertion of the ’537 patent against
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`Qiagen and its subsidiary, IBS);
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`5) The Trustees of Columbia University v. Illumina, Inc., 1:12-
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`cv-00376-GMS (D. Del.) (involving assertion of patents
`
`against Illumina, and assertion of the ’537 patent against
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`IBS, Columbia’s licensee of the accused technology); and
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`6) IPR2017-02174 (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.
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`below.
`
`B.
`
`Background Technology and the ’537 Patent
`
`The ’537 patent relates generally to labeled nucleotides and
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`nucleosides, and to methods of using such molecules in, for example,
`
`nucleic acid sequencing reactions. Ex. 1001, 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. 1101, ¶ 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'
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`
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`3
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`IPR2017-02172
`Patent 7,566,537 B2
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`deoxyribose, meaning the 2' carbon lacks a bond to an oxygen atom. Id.
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`¶ 10 (depicting 2-deoxyribose and ribose); Ex. 1001, 4:49–51 (“In RNA, the
`
`sugar is a ribose, and in DNA is a deoxyribose, i.e., a sugar lacking a
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`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. 1101, ¶¶ 8–9. Natural DNA contains four
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`bases: the base may include a purine or pyrimidine, such as the purines
`
`adenosine (A) and guanidine (G), and the pyrimidines cytidine (C) and
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`thymidine (T). Ex. 1001, 4:51–54. The sequence of these bases in DNA
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`provides genetic information, and ultimately encodes the traits in living
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`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.
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`1101, ¶ 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
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`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.
`
`1001, 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. 1001, 2:23–24. The label may be, for example, a
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`4
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`IPR2017-02172
`Patent 7,566,537 B2
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`fluorophore that is detectable by fluorescence spectroscopy. Id. at 5:20–25.
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`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
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`the protecting group “can be removed to expose a 3'-OH.” Id. at 2:25–28.
`
`The ’537 patent depicts several exemplary labeled nucleotide
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`structures, such as shown below.
`
`
`
`Ex. 1001, 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
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`patent explains that “X” in this molecule can be, for example, a triphosphate,
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`and that R1 and R2 may be selected from H, OH, or any group that can be
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`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
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`azidomethyl protecting group is shown below.
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`
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`5
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`IPR2017-02172
`Patent 7,566,537 B2
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`Ex. 1101, ¶ 95. The representation above shows a 3'-O-azidomethyl
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`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
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`an enzyme is used to incorporate a labeled nucleotide into the nucleic acid
`
`molecule. Ex. 1001, 2:32–38. The ’537 patent also describes methods of
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`using labeled and blocked nucleotides to determine the sequence of a target
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`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
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`nucleotide at a time into the complementary strand, thus providing a
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`controlled sequencing reaction. Id. at 7:51–54. The detectable label
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`uniquely identifies the particular type of nucleotide (e.g., containing a base
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`“G”) that was incorporated into the growing complementary strand. Id. at
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`2:55–57, 5:20–24, 10:4–9. The label and protecting group are then removed,
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`thus exposing a 3'-OH on the previously added nucleotide, and the process
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`repeats with the addition of the next labeled and blocked nucleotide(s). Id.
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`at 2:55–3:16, 7:43–8:14. By detecting, one-by-one, the type of nucleotides
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`6
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`IPR2017-02172
`Patent 7,566,537 B2
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`that are added to the complementary strand, the sequence of the entire target
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`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. 1001, 19:48–59, 20:3–4.
`
`
`D.
`
`The Asserted Grounds of Unpatentability
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`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
`Tsien,2 Greene & Wuts,3 and Zavgorodny4
`1
`
`
`Basis Claims
`§ 103 1, 2, 4–6,
`and 8
`
`
`
`2 Tsien, WO 91/06678 A1, published May 16, 1991. Ex. 1003.
`3 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. 1005.
`4 Sergey Zavgorodny et al., 1-Alkylthioalkylation of Nucleoside Hydroxyl
`Functions and Its Synthetic Applications: A New Versatile Method in
`
`7
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`IPR2017-02172
`Patent 7,566,537 B2
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`2
`
`
`
`Tsien, Greene & Wuts, Zavgorodny, and
`Prober5
`
`
`3
`
`§ 103
`
`
`Petitioner also relies on the Declaration of John D. Sutherland,
`
`D. Phil. (Ex. 1101), and cites to 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. 1001.6 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.
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`1002, 71. At the time the application was filed, the applicants disclosed
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`Zavgorodny ’007 in an Information Disclosure Statement (IDS) along with
`
`
`
`Nucleoside Chemistry, 32 TETRAHEDRON LETTERS 7593–96 (1991). Ex.
`1008.
`5 James M. Prober et al., A System for Rapid DNA Sequencing with
`Fluorescent Chain-Terminating Dideoxynucleotides, 238 SCIENCE 336–41
`(1987). Ex. 1007.
`6 This application is a divisional of U.S. Application No. 10/227,131, filed
`on August 23, 2002 and which issued as U.S. 7,057,026 B2 on June 6, 2006.
`7 S.G. Zavgorodny et al., S,X-Acetals In Nucleoside Chemistry. III. Synthesis
`of 2'- and 3'-O-Azidomethyl Derivatives of Ribonucleosides, 19
`NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS 1977–91 (2000)
`(“Zavgorodny ’00”). Ex. 1009. Zavgorodny ’00 was not expressly relied
`upon as part of the prior art combination in IPR2013-00517 or the prior art
`combinations proposed in the pending IPRs (IPR2017-02172 and IPR2017-
`02174). Zavgorodny ’00 includes similar disclosures related to azidomethyl
`blocking groups that are relied upon from Zavgorodny (Ex. 1008) in the
`presently pending Petition, and that were relied upon in IPR2013-00517.
`Compare Ex. 1009, 7494–95 with Ex. 1008, 1980–81 (disclosing an
`
`8
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`Patent 7,566,537 B2
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`roughly twenty other references. Id. at 197–99. On June 25, 2007, the
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`applicants filed an IDS disclosing Tsien, along with four other references.
`
`Id. at 115–16. Greene & Wuts and Prober are identified in the body of the
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`’537 patent’s specification. Ex. 1001, 5:30–31, 6:14–17.
`
`On October 30, 2007, the Examiner entered a rejection of claim 9 as
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`anticipated by Ju.8 Ex. 1002, 84. In response, on February 1, 2008, the
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`applicants amended claim 9, adding the limitation:
`
`and the nucleoside 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 atoms, and said protecting group can be modified or
`removed to expose a 3’ OH group and the protecting group
`comprises an azido group.
`
`Id. at 71 (underlining omitted and emphasis added). 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
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`addition of the azido group to claim 9, and arguing the amended and newly
`
`presented claims were not taught or suggested by the prior art. Id. at 77–78.
`
`
`
`The Examiner responded on May 16, 2008 with a rejection of claim
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`34 as obvious over Tsien and Greene & Wuts.9 Id. at 64. The Examiner
`
`
`
`azidomethyl group can be removed under specific and mild conditions
`(triphenylphosphine in aqueous pyridine at ~ 20°C)). Zavgorodny was
`disclosed and appears in the references cited portion of the ’537 patent. Ex.
`1001, 3 (right col.).
`8 Ju et al., US 6,664,079 B2, issued Dec. 16, 2003. Ex. 1038.
`9 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 the present Petition and in IPR2013-00517. Ex. 1002, 64, 67. The 1999
`
`9
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`Patent 7,566,537 B2
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`determined 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 claim 28 (reciting
`
`an azidomethyl (CH2N3) protecting group), the Examiner, without further
`
`comment, noted those claims were allowed. Id. On August 21, 2008, the
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`applicants canceled claim 34 and its dependent claims, and requested
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`allowance of the other pending claims. Id. at 59. Claims 9 and 28 later
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`issued in the ’537 patent as claims 1 and 6, respectively. Id. at 25.
`
`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
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`request for adverse judgment. Pet. 6; Exs. 1088 and 1089.
`
`In IPR2013-00517, IBS challenged claims 1–6 and 8 of the ’537
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`patent on multiple obviousness grounds. Pet. 6; Ex. 1090, 6–7 (Rev.
`
`Petition dated Aug. 3, 2013, Paper 7). The specific grounds are below:
`
`
`
`Ground References
`1a
`Ju and Zavgorodny
`
`Ju and Greene & Wuts
`
`Tsien and Zavgorodny
`
`1b
`
`1c
`
`1d
`
`2a
`
`Tsien and Greene & Wuts
`
`Tsien, Zavgorodny, and Prober
`
`
`
`Basis
`§ 103
`
`§ 103
`
`§ 103
`
`§ 103
`
`§ 103
`
`
`Claims
`1–6 and 8
`
`1–6 and 8
`
`1–6 and 8
`
`1–6 and 8
`
`3
`
`third edition of Greene & Wuts (Ex. 1005) appears in the references cited
`portion of the ’537 patent. Ex. 1001, 3 (right col.).
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`10
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`2b
`
`Tsien, Greene & Wuts, and Prober
`
`§ 103
`
`
`3
`
`
`
`Ex. 1090, 7–8.
`
`Patent Owner waived the filing of a preliminary response and, on
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`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
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`1c in the table above). Ex. 1091, 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 that the challenges to claims 1–6 and
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`8 based on the combination of Tsien (or Ju) and Greene & Wuts were
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`“redundant” to the grounds for which institution was ordered. Id. at 5, 15.
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`On May 5, 2014, Illumina filed its Patent Owner Response. Ex. 1092. And,
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`on July 28, 2014, IBS filed its Reply. Ex. 1093.
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`The Board held a full trial and issued a Final Written Decision dated
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`February 11, 2015. Ex. 1094. The Board determined that the preponderance
`
`of the evidence did not support a conclusion that claims 1–6 and 8 were
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`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.
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`11
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`In reaching its conclusion, the Board also relied on Greene & Wuts
`
`and Loubinoux,10 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; Ex. 1005, 248. Thus, contrary to
`
`IBS’s contentions, the Board determined the ordinarily skilled person would
`
`not have been motivated to use an azidomethyl group to meet Tsien’s
`
`sequencing criteria — especially the requirement for quantitative
`
`deblocking. Id. at 7, 18.11 Although the Board also criticized IBS’s Reply
`
`as introducing new evidence and lines of reasoning to support the challenge,
`
`the Board nevertheless determined the Reply was unpersuasive. Id. at 16
`
`(“[E]ven if we were to overlook the procedural infirmities in Petitioner’s
`
`Reply arguments, we would not find them persuasive”).12
`
`
`
`10 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.
`1006. Greene & Wuts cites Loubinoux for the use of an azidomethyl group
`to protect phenols. Ex. 1005, 260.
`11 The Board made similar findings and reached a similar conclusion with
`respect to the challenge based on Ju and Zavgorodny. Ex. 1094, 18–22.
`12 For example, the Board considered but rejected IBS’s contention that it
`would have been obvious and a matter of ordinary creativity to use
`deblocking conditions other than those reported in Zavgorodny (e.g., using
`different removal agents and/or higher concentrations of reagents to drive
`the reaction rapidly to completion). Ex. 1094, 14–18.
`
`12
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`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
`
`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
`
`
`
`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. 1094, 7.
`
`13
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`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 1087–88.14
`
`In its decision and order dated September 9, 2016, the district court
`
`found “Qiagen’s obviousness argument [was] unpersuasive” and “weak,”
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`and held that Patent Owner “has shown it is likely to defeat Qiagen’s
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`invalidity arguments.” Id. at 1088–90. The court determined, among other
`
`things, that “Greene & Wuts is an extensive treatise covering thousands of
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`protecting groups for various purposes,” and that, while “Greene & Wuts
`
`does teach the use of azidomethyl . . . [,] that reference is in a chapter
`
`
`
`14 As the Federal Circuit explains, on a motion for preliminary injunction,
`the district court should “weigh the evidence both for and against validity”
`then assess whether a “substantial question” exists related to the patent’s
`validity, “meaning that the alleged infringer has presented an invalidity
`defense that the patentee has not shown lacks substantial merit.” Titan Tire
`Corp., v. Case New Holland, Inc., 566 F.3d 1372, 1379 (Fed. Cir. 2009).
`
`14
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`directed at phenols, which are hydroxyl groups [] of a different type than the
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`hydroxyl group that appears in nucleotides or nucleosides.” Id. at 1089.
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`Also, the court found, “Greene & Wuts offers an entirely separate chapter on
`
`aliphatic alcohols, which include the types of hydroxyl groups that appear in
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`nucleotides and nucleosides . . . [but] makes no mention of azido groups” in
`
`that chapter. Id. The court pointed to testimony from Qiagen’s expert,
`
`acknowledging 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
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`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.
`
`After analyzing Qiagen’s invalidity defenses, the district court
`
`addressed other factors relevant to the request for a preliminary injunction
`
`(e.g., irreparable harm, etc.) and ultimately granted the injunction in Patent
`
`Owner’s favor. Id. at 1093–94. According to Patent Owner, after the
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`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
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`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
`
`15
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`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)).
`
`CGI filed the present petitions for inter partes review (IPR2017-
`
`02172 and IPR2017-02174) on October 5, 2017.
`
`
`
`III. ANALYSIS
`
`A. Discretionary Non-Institution
`
`i) Discretionary Non-Institution under § 314(a)
`
`Patent Owner argues we should exercise our discretion and deny the
`
`Petition under 35 U.S.C. § 314(a). See, e.g., Prelim. Resp. 21, 30. We are,
`
`as explained below, denying institution based on the Board’s discretion
`
`under § 325(d). See Section III.A.ii. Accordingly, we decline to reach
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`Patent Owner’s arguments related to whether discretionary denial under
`
`§ 314(a) is appropriate based on the circumstances presented here.
`
`ii) Discretionary Non-Institution under 35 U.S.C. § 325(d)
`
`Patent Owner argues the Board should deny institution under § 325(d)
`
`because “Tsien, Greene & Wuts, and Zavgorodny were previously presented
`
`to, and considered by, the Board . . . and the Federal Circuit.” Prelim. Resp.
`
`31. According to Patent Owner, “Section 325(d) ‘does not contain any
`
`recitation regarding the identity of the party that previously presented the
`
`prior art. . . . Thus, § 325(d) is not limited to instances where the petitioner
`
`is the party who previously brought the prior art to the Office’s attention.’”
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`Id. (quoting TCL Corp. v. Lexington Luminance LLC, IPR2017-01780, slip
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`op. at 8 (PTAB Jan. 2, 2018) (Paper 8)).
`
`16
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`The Petition does not address § 325(d) directly but, in supplemental
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`briefing authorized by the Board, Petitioner asserts that it is offering new
`
`arguments and evidence in support of the combination of Tsien, Greene
`
`& Wuts, and Zavgorodny. Paper 14, 7. Thus, Petitioner argues, the Board
`
`should not deny the Petition under § 325(d). Id.
`
`In addition to § 314(a), the Board also has discretion to deny a petition
`
`under § 325(d). Section 325(d) provides, in pertinent part:
`
`In determining whether to institute or order a proceeding under
`this chapter, chapter 30, or chapter 31 [related to petitions for
`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. § 325(d). Section 325(d) is not specifically limited based on the
`
`identity of the party that advanced the prior art or arguments. Hence,
`
`§ 325(d) applies, for example, to a follow-on petition advancing the same or
`
`substantially the same prior art even if filed by a different petitioner. See,
`
`e.g., Unified Patents, Inc. v. PersonalWeb Techs., LLC, IPR2014-00702
`
`(PTAB July 24, 2014) (Paper 13) (informative); Google LLC v. Uniloc
`
`Luxembourg S.A., IPR2017-02067 (PTAB Mar. 29, 2018).
`
`
`
`As explained above, the Board already considered whether claims 1–6
`
`and 8 would have been unpatentable as obvious based on the teachings of
`
`Tsien, Greene & Wuts, Zavgorodny, and Prober. See supra Section II.E.ii.15
`
`
`
`15 Although not the focus of Patent Owner’s arguments, we observe that
`Tsien, Greene & Wuts, and Zavgorodny were before the Examiner during
`prosecution. See supra Section II.E.i. The Examiner, citing Tsien and
`Greene & Wuts and an admission (from Patent Owner) that all the protecting
`groups were known in the art, rejected as obvious certain claims reciting an
`allyl protecting group while expressly allowing the amended claims that
`
`17
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`There is no reasonable dispute that the same prior art that Petitioner is now
`
`asserting should be combined was already presented to the Board, and a full
`
`trial held. Indeed, the Board issued a Final Written Decision on this matter,
`
`and the Federal Circuit affirmed that decision.
`
`Petitioner’s attempt to overcome these facts by invoking allegedly
`
`new evidence and argument does not persuade us that another review of the
`
`same claims over Tsien, Greene & Wuts, and Zavgorodny is warranted. The
`
`fact remains, Petitioner is using Tsien, Greene & Wuts, and Zavgorodny in
`
`substantially the same way as those references were used in the prior
`
`challenge (and relying on substantially the same teachings in those
`
`references as well). That is, Tsien is relied upon for the basic nucleotide
`
`incorporation and sequencing methods, and Greene & Wuts and Zavgorodny
`
`are relied upon as teaching an azidomethyl protecting group that is allegedly
`
`a suitable protecting group for Tsien’s processes. Compare Ex. 1090, 31–37
`
`(claim chart in IPR2013-00517) with Ex. 1101, 36–44 (claim chart here).16
`
`Although the Board did not institute trial on any ground where Greene &
`
`Wuts was expressly used in an obviousness combination, finding those
`
`grounds redundant, the Board (and the Federal Circuit), nevertheless
`
`examined the same relevant teachings in Greene & Wuts that Petitioner cites
`
`here. Ex. 1094, 13; Intelligent Bio-Systems, 821 F.3d at 1368–69; Pet. 25,
`
`
`
`recited an azido or azidomethyl protecting group. Id. The Examiner’s
`allowance of the azido/azidomethyl claims under these circumstances,
`especially when paired with the Board’s thorough consideration of Tsien,
`Greene & Wuts, and Zavgorodny in IPR2013-00517 reinforces the
`appropriateness of exercising § 325(d) discretion here.
`16 Petitioner’s reliance on Prober is limited to dependent claim 3 and
`Prober’s teaching of the limitation in that claim of “wherein the base is a
`deazapurine.” Pet. 55–57.
`
`18
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`43–44. Both the Board and Federal Circuit determined and made clear, in
`
`their respective opinions, that those teachings reinforced that the challenged
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`claims had not been shown to be obvious over Tsien and Zavgorodny. See
`
`supra, Section II.E.ii–iii.17
`
`As to Petitioner’s “new” reasons for combining the references, those
`
`too are insufficient to avoid discretionary denial here. Pet. 31–32; see also
`
`Prelim. Resp. 31–32; Paper 17, 5. We are not persuaded Petitioner’s
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`“simple substitution” theory departs materially from arguments advanced in
`
`earlier proceedings. Pet. 53–54. Medtronic, Inc. v. Nuvasive, Inc.,
`
`IPR2014-00487, (PTAB Sept. 11, 2014) (Paper 8) (informative) (exercising
`
`discretionary denial under §