Trials@uspto.gov
`571-272-7822
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`Paper 49
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` Date: April 22, 2024
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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`BLUEBIRD BIO, INC.,
`Petitioner,
`v.
`SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH,
`Patent Owner.
`
`IPR2023-00070
`Patent 7,541,179 B2
`
`
`Before SHERIDAN K. SNEDDEN, JAMES A. WORTH and
`CYNTHIA M. HARDMAN, Administrative Patent Judges.
`
`
`SNEDDEN, Administrative Patent Judge.
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`
`
`
`DECISION
`Final Written Decision
`Determining No Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
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`571-272-7822
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`Paper 49
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` Date: April 22, 2024
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
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`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`BLUEBIRD BIO, INC.,
`Petitioner,
`v.
`SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH,
`Patent Owner.
`
`IPR2023-00070
`Patent 7,541,179 B2
`
`
`Before SHERIDAN K. SNEDDEN, JAMES A. WORTH and
`CYNTHIA M. HARDMAN, Administrative Patent Judges.
`
`
`SNEDDEN, Administrative Patent Judge.
`
`
`
`
`DECISION
`Final Written Decision
`Determining No Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
`
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`IPR2023-00070
`Patent 7,541,179 B2
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`
`I.
`
`INTRODUCTION
`
`We have jurisdiction under 35 U.S.C. § 6. We issue this Final Written
`Decision pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73 in an inter
`partes review involving bluebird bio, Inc. (“Petitioner”) and Sloan Kettering
`Institute for Cancer Research (“Patent Owner”). Based on the record before
`us, we conclude that Petitioner has not demonstrated, by a preponderance of
`the evidence, that claims 1, 10, 19, and 22 (“Challenged Claims”) of U.S.
`Patent No. 7,541,179 B2 (Ex. 1001, “the ’179 patent”) are unpatentable.
`A. Background
`Petitioner filed a Petition to institute inter partes review of claims 1,
`10, 19, and 22 of the ’179 patent. Paper 1 (“Pet.” or “Petition”). Patent
`Owner filed a Preliminary Response. Paper 5. We instituted an inter partes
`review of all claims and all grounds asserted in the Petition on April 24,
`2023. Paper 8. Following institution, Patent Owner filed a Response to the
`Petition (Paper 27, “PO Resp.”), Petitioner filed a Reply to Patent Owner’s
`Response (Paper 35, “Reply”), and Patent Owner filed a Sur-reply (Paper
`41, “Sur-reply”).
`On January 24, 2024, the parties presented arguments at an oral
`hearing. The transcript of the hearing has been entered into the record.
`Paper 47 (“Tr.”).
`B. Related Matters
`Petitioner and Patent Owner identify San Rocco Therapeutics, LLC v.
`bluebird bio, Inc., et al., No. 1-21-cv-01478 (D. Del.)1 as a related district
`
`
`1 Patent Owner captions this case “Errant Gene Therapeutics, LLC v.
`Bluebird Bio, Inc., 1-21-cv-01478, (D. Del. October 21, 2021).” Paper 4, 2.
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`court litigation. Pet. 2–3; Paper 4, 2–3. Patent Owner also identifies Errant
`Gene Therapeutics, LLC v. Memorial Sloan-Kettering Cancer Center and
`Sloan Kettering Institute of Cancer Research, 1-21-cv-08206 (S.D.N.Y.) as
`a related litigation involving the ’179 patent. Paper 4, 3.
`The parties further identify IPR2023-00074, challenging certain
`claims of U.S. Patent No. 8,058,061 B2 (“the ’061 patent”), as a related
`matter. Pet. 2–3; Paper 4, 2–3. The ’061 patent issued from a divisional
`application of U.S. application number 10/188,221 (“the ’221 application”),
`which issued as the ’179 patent. Ex. 1001, code (21).
`C. The ’179 Patent
`The ’179 patent is directed to a recombinant vector, e.g., a lentiviral
`vector, incorporating a functional globin gene and large portions of the β-
`globin locus control region (“LCR”). Ex. 1001, 1:47–51. The Specification
`defines a “recombinant lentiviral vector” as “an artificially created
`polynucleotide vector assembled from a lentiviral-vector and a plurality of
`additional segments as a result of human intervention and manipulation.” Id.
`at 2:36–40. The Specification defines “functional globin gene” as “a
`nucleotide sequence the expression of which leads to a globin that does not
`produce a hemoglobinopathy phenotype, and which is effective to provide
`therapeutic benefits to an individual with a defective globin gene.” Id. at
`2:41–45. “The functional globin gene may encode a wild-type globin,” “a
`mutant form of globin,” “α-globin, β-globin, or γ-globin.” Id. at 2:45–53.
`The recombinant lentiviral vector is used as a gene therapy vector to provide
`“therapeutically meaningful levels of human globin for sustained periods of
`time.” Id. at 1:36–44.
`The Specification describes the recombinant vector as including
`“large portions of the locus control region (LCR) which include DNase I
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`hypersensitive sites HS2, HS3 and HS4.” Id. at 2:54–56. The Specification
`defines “large portions” as “portions of the locus control region which
`encompass larger portions of the hypersensitive sites as opposed to
`previously tested fragments including only the core elements.” Id. at 2:60–
`64. In a specific vector, designated TNS9, the LCR is 3.2 kilobases (“kb”)
`in size and “consists of an 840 [base pair (‘bp’)] HS2 fragment (SnaBI-
`BstXI), a 1308 bp HS3 fragment (HindIII-BamHI) and a 1069 bp HS4
`fragment (BamHI-BanII).” Id. at 3:24–26. Figure 1, reproduced below,
`illustrates the TNS9 vector.
`
`
`
`Figure 1 illustrates the TNS9 vector with exons represented by filled
`boxes and introns represented by open boxes. Id. at 3:14–16. The TNS9
`vector includes, from the 5ʹ end to the 3ʹ end, a splice donor (SD), packaging
`region (Ψ), rev-response element (RRE), splice acceptor (SA), 3'-β-globin
`enhancer (E), β-globin gene, human β-globin promoter (P), and LCR
`(including HS2, HS3, and HS4). Id. at 3:16–19. The 5ʹ and 3ʹ ends include
`long terminal repeat (LTR) sequences. See id. at Fig. 1.
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`D. Illustrative Claim
`Petitioner challenges claims 1, 10, 19, and 22 of the ’179 patent.
`Claim 1, set forth below, is the only independent claim and is illustrative of
`the claimed subject matter.
`1. A recombinant vector comprising
`a nucleic acid encoding a functional globin operably
`linked to a 3.2-kb nucleotide fragment which consists essentially
`of three contiguous nucleotide fragments obtainable from a
`human β-globin locus control region (LCR),
`the three fragments being
`a BstXI and SnaBI HS2-spanning nucleotide fragment of
`said LCR,
`a BamHI and HindIII HS3-spanning nucleotide fragment
`of said LCR and
`a BamHI and BanII HS4-spanning nucleotide fragment of
`said LCR, said vector providing expression of the globin in a
`mammal in vivo.
`Ex. 1001, 11:55–65. Dependent claim 19 recites that the functional globin is
`β-globin, and dependent claim 10 recites that the functional globin is human
`β-globin. Id. at 13:4–5, 14:6–7. Dependent claim 22 recites that the vector
`is a lentiviral vector. Id. at 14:12–13.
`E. Evidence
`Petitioner relies upon information that includes the following.
`May, Therapeutic Hemoglobin Synthesis in Beta-Thalassemic
`Mice Expressing Lentivirus-Encoded Human Beta-Globin,
`Cornell University (2001) (Ex. 1004, “May Thesis”).
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`in β-
`May, et al., Therapeutic Haemoglobin Synthesis
`Thalassaemic Mice Expressing Lentivirus-Encoded Human β-
`globin, 406 NATURE 82–86 (2000) (Ex. 1005, “May Article”).2
`May, et al., Lentiviral-Mediated Transfer of the Human β-Globin
`Gene and Large Locus Control Region Elements Permit
`Sustained Production of Therapeutic Levels of β-Globin in
`Long-Term Bone Marrow Chimeras, 1(5) MOL. THERAPY S248–
`49 (2000) (Ex. 1006, “May Abstract”).
`Petitioner also relies upon the Declarations of Jörg Bungert, Ph.D.
`(Ex. 1002) and Ingrid Hsieh-Yee, Ph.D.3 (Ex. 1036).
`Patent Owner relies upon the Declarations of James Riley, Ph.D.
`(Ex. 2002, Ex. 2056); Michel Sadelain, M.D., Ph.D. (Ex. 2006); Chad May,
`Ph.D. (Ex. 2007); Stefano Rivella, Ph.D. (Ex. 2008); and Lucio Luzzatto,
`M.D., Ph.D. (Ex. 2009).4
`F. Asserted Grounds of Unpatentability
`Petitioner asserts that claims 1, 10, 19, and 22 are unpatentable on the
`following four grounds:
`
`
`2 Patent Owner refers to Exhibit 1005 as the “Nature Article.” See, e.g.,
`PO Resp. 12.
`3 Petitioner relies on the declaration of Dr. Hsieh-Yee, a librarian, to address
`authenticity and public availability of the cited references. Ex. 1036 ¶ 16.
`4 Patent Owner relies on the declarations of Drs. Sadelain, May, Rivella, and
`Luzzatto to address inventorship and, in some instances, conception and
`reduction to practice allegations.
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`Claim(s) Challenged
`1, 19, 22
`1, 19, 22
`1, 19, 22
`1, 10, 19, 22
`
`35 U.S.C. §5
`102
`102
`103
`103
`
`Reference(s)/Basis
`May Thesis
`May Article
`May Article
`May Abstract
`
`II. ANALYSIS
`
`A. Person of Ordinary Skill in the Art
`The level of skill in the art is a factual determination that provides a
`primary guarantee of objectivity in an obviousness analysis. Al-Site Corp. v.
`VSI Int’l Inc., 174 F.3d 1308, 1324 (Fed. Cir. 1999) (citing Graham v. John
`Deere Co., 383 U.S. 1, 17–18 (1966); Ryko Mfg. Co. v. Nu-Star, Inc.,
`950 F.2d 714, 718 (Fed. Cir. 1991)).
`Petitioner asserts that a person of ordinary skill in the art (“POSA”)
`“at the time of the alleged invention would have had: (1) at least an
`advanced degree (e.g., a Master’s or Ph.D.) in biochemistry, biotechnology,
`protein chemistry, genetics, molecular and structural biology,
`bioengineering, or similar disciplines.” Pet. 17 (citing Ex. 1002 ¶¶ 14–15).
`Petitioner further asserts that a POSA would have had “(2) several years of
`post-graduate training or related experience in one or more of these areas”
`and “(3) an understanding of vector design and the effect of LCR fragments
`
`
`5 The Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 112–29, 125
`Stat. 284 (2011), amended 35 U.S.C. §§ 102 and 103, effective March 16,
`2013. Because the application from which the ’179 patent issued has an
`effective filing date before that date, the pre-AIA version of §§ 102 and 103
`apply.
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`on gene expression, including experience with how the LCR regulates gene
`expression.” Id.
`Patent Owner does not dispute Petitioner’s description of the level of
`ordinary skill in the art. See PO Resp. Because Petitioner’s uncontested
`definition of one of ordinary skill in the art is reasonable and consistent with
`the ’179 patent and the prior art of record, we adopt Petitioner’s definition
`for purposes of this Decision.
`B. Claim Construction
`The Board applies the same claim construction standard that would be
`used to construe the claim in a civil action under 35 U.S.C. § 282(b).
`37 C.F.R. § 100(b) (2019). Under that standard, claim terms “are generally
`given their ordinary and customary meaning” as understood by a person of
`ordinary skill in the art at the time of the invention. Phillips v. AWH Corp.,
`415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc) (quoting Vitronics Corp.
`v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996)). “In determining
`the meaning of the disputed claim limitation, we look principally to the
`intrinsic evidence of record, examining the claim language itself, the written
`description, and the prosecution history, if in evidence.” DePuy Spine, Inc.
`v. Medtronic Sofamor Danek, Inc., 469 F.3d 1005, 1014 (Fed. Cir. 2006)
`(citing Phillips, 415 F.3d at 1312–17).
`Petitioner states that “no term of the ’179 patent requires construction
`to resolve the challenges in this Petition.” Pet. 22 (citing Ex. 1002 ¶¶ 49–
`50). Patent Owner does not argue for any express claim constructions. See
`PO Resp.
`Based upon our review of the current record, we determine that no
`claim terms require express construction for purposes of this Decision. See
`Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co., 868 F.3d 1013,
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`1017 (Fed. Cir. 2017) (Only those terms that are in controversy need be
`construed, “and only to the extent necessary to resolve the controversy.”).
`C. Ground 1: Petitioner’s Assertion that Claims 1, 19, and 22 are
`Anticipated by the May Thesis
`Petitioner asserts that the May Thesis anticipates claims 1, 19, and 22.
`Pet. 23–26; see Reply 1. Patent Owner contends that the May thesis does
`not qualify as prior art and further that “Petitioner’s Reply makes clear that
`Petitioner has effectively conceded” this ground. PO Resp. 1; Sur-reply 1.
`Having considered the parties’ positions and evidence of record, we
`determine that Petitioner has not demonstrated by a preponderance of
`evidence that claims 1, 19, and 22 are anticipated by the May Thesis. Our
`analysis follows.
`We first summarize aspects of the May Thesis.
`Summary of the May Thesis
`1.
`The May Thesis describes therapeutic hemoglobin synthesis in β-
`thalassemic mice expressing lentivirus-encoded human beta-globin.
`Ex. 1004, 3. The May Thesis discloses recombinant lentivirus vector TNS9.
`Id. at 74. The TNS9 vector is illustrated in Figure 4.01(b), reproduced
`below:
`
`
`Figure 4.01(b) illustrates the TNS9 vector with exons represented by
`filled boxes and introns represented by open boxes. Id. The TNS9 vector
`includes, from the 5ʹ end to the 3ʹ end, a splice donor (SD), packaging region
`(Ψ), rev-response element (RRE), splice acceptor (SA), 3'-β-globin enhancer
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`(E), β-globin gene, human β-globin promoter (P), and LCR (including HS2,
`HS3, and HS4). Id. The 5ʹ and 3ʹ ends include long terminal repeat (LTR)
`sequences. See id. at Fig. 4.01(b). May Thesis discloses that the TNS9 LCR
`element (Fig. 4.01b) includes an 840 bp HS2 fragment (SnaBl-BstXI), a
`1308 bp HS3 fragment (HindUI-BamHI Banll), and a 1069 bp HS4 fragment
`(BamHI-Banll) to generate a 3.2 kb LCR element. Id. at 75.
`Discussion
`2.
`Petitioner asserts that the May Thesis, dated May 2001, was “publicly
`available on ProQuest by at least November 26, 2001.” Pet. 17 (citing
`Ex. 1004, cover; Ex. 1036 ¶¶ 1–26). The ’179 patent issued from the ’221
`application filed on July 1, 2002. Ex. 1001, code (22). The ’221 application
`claims priority to the ’861 provisional application, filed June 29, 2001, and
`the ’852 provisional application, filed on July 2, 2001. Id. at code (60).
`Petitioner asserts that “at least claims 1, 19, and 22 of the ’179 patent
`cannot claim priority to either provisional because [the provisional
`applications] do not satisfy at least the written description requirements of
`35 U.S.C. § 112 for these claims.” Pet. 13. As a result, Petitioner asserts
`that “the earliest date to which these claims of the ’179 patent may claim
`priority is July 1, 2002, the filing date of the [’221] application.” Id.
`Petitioner asserts that “[t]he May Thesis is prior art to the ’179 patent under
`35 U.S.C. §§ 102(a)[] and (b) based on the July 1, 2002 priority date” and
`“because it has a different inventive entity than the ’179 patent.” Id. at 17–
`18 & n.7.
`However, even assuming that claims 1, 19, and 22 are not entitled to
`receive benefit of an earlier filing date, we determine that Patent Owner has
`shown that the May Thesis represents the inventors’ own work, and thus the
`May Thesis is not prior art to the ’179 patent. PO Resp. 14–15.
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`The May Thesis is authored by Chad May, who is a listed inventor of
`the ’179 patent. Id.; Ex. 1004, 3; Ex. 1001, code (75). Thus, the May Thesis
`represents the work of one of the ’179 inventors and is therefore ineligible as
`prior art under 35 U.S.C. § 102(a) for challenged claims 1, 19, and 22. See,
`e.g., In re Katz, 687 F.2d 450, 454–455 (CCPA 1982) (a prior publication by
`inventors or a subset of the inventors does not qualify as prior art under
`102(a)).
`With respect to 35 U.S.C. § 102(b), we find that the May Thesis is
`ineligible as prior art, even assuming that claims 1, 19, and 22 are not
`entitled to receive benefit of an earlier filing date. Petitioner provides
`evidence that the May Thesis was publicly available as of November 26,
`2001. Pet. 17 (citing Ex. 1036 ¶¶ 1–26; Ex. 1002 ¶ 60). Patent Owner does
`not dispute that evidence. Based on the undisputed November 26, 2001
`public availability date, the May Thesis represents a disclosure less than one
`year before the asserted effective filing date, i.e., the July 1, 2002, for claims
`1, 19, and 22 challenged with this reference. Based on that timing and
`because the disclosure was made by the inventor, the May Thesis is not
`available as prior art to challenged claims 1, 19, and 22 under 35 U.S.C.
`§102(b).
`Petitioner has not established that the May Thesis is prior art to claims
`1, 19, and 22. Consequently, Petitioner has not demonstrated by a
`preponderance of evidence that claims 1, 19, and 22 are anticipated by the
`May Thesis.
`D. Ground 2: Petitioner’s Assertion that Claims 1, 19, and 22 are
`Anticipated by the May Article
`Petitioner asserts that claims 1, 19, and 22 are anticipated by the May
`Article. Pet. 26–33. Petitioner begins with its analysis of independent claim
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`1 (id. at 26–32), and then addresses the limitations added by dependent
`claims 19 and 22 (id. at 32–33). Patent Owner raises multiple
`counterarguments. PO Resp. 37–40. Having considered the parties’
`positions and evidence of record, we determine that Petitioner has not
`demonstrated by a preponderance of evidence that claims 1, 19, and 22 are
`anticipated by the May Article. Our analysis follows.
`We first summarize aspects of the May Article, also referred to by
`Patent Owner as “the Nature Article.” Id.
`1. May Article
`The May Article describes therapeutic hemoglobin synthesis in β-
`thalassemic mice expressing lentivirus-encoded human β-globin. Ex. 1005,
`82. The May Article describes constructing two recombinant lentiviruses
`carrying β-globin transcription units. Id. The lentiviruses including RNS1
`containing “a minimal LCR comprising previously tested core elements of
`HS2, HS3 and HS4,” and TNS9 containing “large fragments encompassing
`HS2, HS3 and HS4 were introduced instead of the corresponding core
`elements.” Id. The TNS9 vector is shown in Figure 1b, reproduced below:
`
`
`Figure 1b illustrates the TNS9 vector with the exons represented by
`filled boxes and the introns represented by open boxes. Id. The TNS9
`vector includes, from the 5ʹ end to the 3ʹ end, a splice donor (SD), packaging
`region (Ψ), rev-response element (RRE), splice acceptor (SA), 3'-β-globin
`enhancer (E), β-globin gene, human β-globin promoter (P), and LCR
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`(including HS2, HS3, and HS4). Id. The 5ʹ and 3ʹ ends include long
`terminal repeat (LTR) sequences. See id. at Fig. 4.01(b).
`Figure 1a of the May Article, reproduced below, depicts the TNS9
`LCR, comparing it to a vector referred to as “RNS1.”
`
`
`Id. at 82, Fig. 1a. With reference to Figure 1a, the May Article discloses that
`the “TNS9 was generated by replacing the core HS2 element of RNS1 with
`an 840-bp HS2 fragment, the core HS3 element with a 1,308-bp HS3
`fragment, and the core HS4 element with a 1,069-bp HS4 fragment,” where
`“[b]oxes represent HS fragments drawn to scale.” Id.
`Petitioner’s Contentions
`2.
`Petitioner asserts that the May Article discloses each element of
`claims 1, 19, and 22. See Pet. 26–36. Specifically, Petitioner asserts that the
`May Article discloses a recombinant vector, TNS9, including a nucleic acid
`encoding a β-globin gene, e.g., a human β-globin gene, operably linked to an
`LCR consisting of large segments, which are composed of three fragments
`(HS2, HS3, and HS4) that are adjacent, i.e., contiguous to each other. Id. at
`26–27, 32 (citing Ex. 1005, 82–84). Petitioner asserts further that the May
`Article explains that the three fragments were “generated by replacing the
`core HS2 element . . . with an 840-bp HS2 fragment, the core HS3 element
`. . . with a 1,308-bp HS3 fragment, and the core HS4 element . . . with a
`1,069-bp HS4 fragment.” Id. at 27–28 (citing Ex. 1005, 82) (emphasis
`omitted, alterations in original). Additionally, Petitioner asserts that the May
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`Article discloses that the HS2, HS3, and HS4 fragments “sum up to 3217 bp,
`or roughly 3.2 kb.” Id. at 28 (citing Ex. 1002 ¶ 101). Petitioner also asserts
`that the May Article discloses that the vector “increased globin expression in
`vivo.” Id. at 32.
`Petitioner contends that the May Article “teaches the restriction sites
`bounding the HS2, HS3, and HS4 fragments as recited in claim 1” by:
`(a) disclosing the lengths of those fragments in the TNS9 vector as 840 bp,
`1308 bp, and 1069 bp; and (b) depicting the fragments on a “drawn to scale”
`map of the LCR with a comparison, in size and placement, to previously
`published fragments for the core elements of HS2, HS3, and HS4 in a RNS1
`vector. Id. at 28 (citing Ex. 1005, 82, Fig. 1(a); Ex. 1002 ¶¶ 103–118).
`Petitioner asserts that “[b]y July 1, 2002, the entire map of the LCR region
`was available to a POSA in the GenBank database under accession numbers
`‘HUMHBB,’ ‘U01317,’ and ‘NG_000007.1.’” Id. at 28–29 (citing
`Ex. 1016, 14903–05, Fig. 2; Ex. 1002 ¶¶ 104–105). Petitioner notes that
`Patent Owner recognized the knowledge in the art at the time of the
`invention during prosecution. Id. at 29 (citing Ex. 1032, 301) (explaining
`that the sequences provided by the GenBank Accession numbers “are the
`reference sequences for the human β-globin region and are well known to
`those of skill in the art”).
`Additionally, Petitioner asserts that “by July 1, 2002, a finite number
`of restriction enzymes, including BstX1, SnaBI, BamHI, HindIII, and BanII,
`were available for sale through commercial sources.” Id. at 30 (citing Ex.
`1002 ¶ 106).6 Petitioner asserts that the specific sequences that these
`
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`6 We recognize that the ’179 patent issued from the ’221 application filed on
`July 1, 2002, and thus Petitioner’s analysis is predicated on the ’179 patent
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`restriction enzymes recognized were also known at the time of the invention.
`Id. According to Petitioner, a skilled artisan would “have been able to map
`all of the possible restriction sites in the regions flanking the cores of HS2,
`HS3, and HS4.” Id. (citing Ex. 1002 ¶¶ 107–110). Petitioner contends that,
`based on the disclosures in the May Article regarding the size and location
`of TNS9’s HS2, HS3, and HS4 fragments, “a POSA would have placed
`these fragments onto the restriction-site map of the LCR they would have
`had available at the time.” Id. at 30–31 (Ex. 1002 ¶¶ 110–112). Petitioner
`asserts that “[i]n doing so, a POSA would have identified only six possible
`combinations of restriction enzyme fragments, one of which is recited in
`claim 1.” Id. at 31 (citing Ex. 1002 ¶¶ 112–117). Thus, Petitioner contends
`that, based on the May Article disclosures, a POSA would have “‘at once
`envisage[d]’ a limited class of restriction fragments.” Id. (citing
`Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381–83
`(Fed. Cir. 2015) (“Thus, substantial evidence supports the Board’s
`conclusion that [the prior-art reference] effectively teaches 15 combinations,
`of which one anticipates pending claim 1.”)) (alteration in original).
`Petitioner supports its contentions with the declaration of Dr. Bungert.
`Ex. 1002.
`
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`not being entitled to its priority claims. Because we determine that the May
`Article would not have rendered obvious any of the Challenge Claims even
`assuming a July 1, 2002 effective filing date, we need not address the issue
`of whether the ’221 application is entitled to claim priority to the ’861
`provisional application, filed June 29, 2001, and the ’852 provisional
`application, filed on July 2, 2001. For the purposes of this discussion, we
`assume that May Article, published July 6, 2000, is prior art to the ’179
`patent under 35 U.S.C. § 102(b) based on the July 1, 2002 filing date.
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`Patent Owner’s Response
`3.
`Patent Owner contends that Petitioner has not met its burden to show
`that claims 1, 19, and 22 are anticipated by the May Article. PO Resp. 37–
`40. Patent Owner asserts that the May Article does not expressly or
`inherently disclose all of the elements of the challenged claims. Id. In
`particular, Patent Owner asserts that the May Article does not disclose the
`claimed restriction sites surrounding the hypersensitive sites—the “BstXI
`and SnaBI HS2-,” “BamHI and HindIII HS3-,” or “BamHI and BanII HS4-”
`spanning nucleotide fragments. Id. at 37–38. Patent Owner asserts that “the
`[May] Article does not even disclose the use of restriction enzymes at all,”
`and therefore “it cannot inherently disclose every possible restriction site
`surrounding the hyper-specific sites.” Id. at 39 (citing Ex. 2002 ¶¶ 105–117;
`Ex. 1005).
`
`Discussion
`4.
`Having considered the parties’ positions and evidence of record,
`summarized above, we determine that the May Article fails to disclose the
`restriction sites surrounding the BstXI and SnaBI HS2-, BamHI and HindIII
`HS3-, or BamHI and BanII HS4-spanning nucleotide fragments, as required
`by the challenged claims. According to Petitioner, that limitation is
`inherently disclosed by the May Article’s description of the lengths of the
`HS2, HS3, and HS4 fragments in the TNS9 vector and its depiction of those
`fragments on a map of the LCR. Pet. 28. To support its inherency
`argument, Petitioner relies on knowledge in the art, i.e., the availability of
`the entire map of the LCR region, and the availability of restriction enzymes,
`including BstX1, SnaBI, BamHI, HindIII, and BanII. Id. at 30–31 (citing
`Kennametal, 780 F.3d at 1381–83). Based on that combined information,
`Petitioner contends that a POSA would “have been able to map all of the
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`possible restriction sites in the regions flanking the cores of HS2, HS3, and
`HS4.” Id. Petitioner asserts further that “[g]iven the May Article’s
`disclosure regarding the size and location of [TNS9’s] HS2, HS3, and HS4
`fragments, a POSA would have placed these fragments onto the restriction-
`site map of the LCR” that was available at the time, and would have
`identified only six possible combinations of restriction enzyme fragments,
`including the one recited in claim 1. Id. Upon closer inspection, however,
`we appreciate from the testimony of Petitioner’s declarant, Dr. Bungert, that
`the process involved in arriving at those six possible combinations is
`predicated on numerous assumptions guiding a number of exacting steps to
`be performed in order to achieve the claimed LCR fragment. According to
`Dr. Bungert, the process for making the claimed LCR fragment would have
`involved the steps of (a) placing fragments that are the disclosed size of the
`HS2, HS3, and HS4 fragments from the TNS9 vector in the May Article
`onto the known restriction-site map of the LCR; (b) comparing those
`fragments to the “‘drawn to scale’ map” in the May Article; and then (c)
`identifying various fragments and determining which ones are consistent
`with the May Article’s description and match up with the fragments on the
`May Article’s drawn to scale map. Ex. 1002 ¶¶ 112–117. To identify the
`fragments consistent with the May Article’s description, it was necessary for
`Dr. Bungert to use certain assumptions that exclude unfavorable enzymes
`such as using a range of ± 20 bp in order to identify fragments with lengths
`that are within 20 bp of the fragments reported in the May Article. Id. In
`view of the number of assumptions and steps required to get from what is
`disclosed in the May Article to arrive at the alleged “six possible LCRs (i.e.,
`combination of HS2, HS3, and HS4 fragments based on the TNS9 LCR
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`disclosed in the May Article)—including the LCR recited in claim 1,”
`Ex. 1002 ¶ 117, we do not find that Petitioner has demonstrated that
`fragments having the restriction sites recited in claim 1 would have been “at
`once envisage[d]” by a skilled artisan as argued by Petitioner. Pet. 30–31.
`Moreover, as is further discussed below in the context of Petitioner’s
`obviousness challenge over the May Article, we find merit in Patent
`Owner’s argument that “a POSA at the time would understand such
`fragments could be made in multiple different ways, including through
`amplification by polymerase chain reactions (‘PCRs’), cutting from genomic
`DNAs using restriction enzymes, or otherwise.” PO Resp. 38 (citing Ex.
`2002 ¶¶ 89, 106–115). Thus, Petitioner’s assertion that a skilled artisan
`would have immediately envisaged fragments having the restriction sites in
`claim 1 is further undermined because there would have been more than one
`method of making the fragments disclosed in the May Article, one of which
`did not involve using restriction enzymes.
`Accordingly, for at least the foregoing reasons, we determine that
`Petitioner has not established by a preponderance of the evidence that claims
`1, 19, and 22 are anticipated by the May Article.
`E. Ground 3: Petitioner’s Assertion that Claims 1, 19, and 22 would
`have been Obvious over the May Article
`As an alternative to Ground 2, Petitioner asserts that claims 1, 19, and
`22 would have been obvious in view of the May Article. Pet. 33–36.
`Specifically, Petitioner contends that the May Article discloses all of the
`limitations of claims 1, 19, and 22, “[h]owever, to the extent that the May
`Article is found not to disclose [the BstXI and SnaBI HS2-, BamHI and
`HindIII HS3-, or BamHI and BanII HS4- spanning nucleotide fragments
`limitation], that limitation nonetheless would have been obvious in view of
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`the teachings of May Article and the knowledge of a POSA at the time of the
`alleged invention.” Id. at 33. Patent Owner raises multiple
`counterarguments, which we find credible and supported by the evidence of
`record. PO Resp. 40–52. Thus, having considered the parties’ positions and
`evidence of record, we determine that Petitioner has not demonstrated by a
`preponderance of evidence that claims 1, 19, and 22 would have been
`obvious over the May Article. Our analysis follows.
`Petitioner’s Contentions
`1.
`Petitioner asserts that, to the extent the May Article is not considered
`to disclose “the three fragments being a BstXI and SnaBI HS2-spanning
`nucleotide fragment of said LCR, a BamHI and HindIII HS3-spanning
`nucleotide fragment of said LCR and a BamHI and BanII HS4-spanning
`nucleotide fragment of said LCR,” as recited by claim 1, “that limitation
`nonetheless would have been obvious in view of the teachings of the May
`Article and the knowledge of a POSA at the time of the alleged invention.”
`Pet. 33. Specifically, Petitioner contends that a skilled artisan would have
`known that the entire map of the LCR region was available at the time of the
`invention. Id. at 30, 33.
`Petitioner relies on the same disclosures discussed for the anticipation
`challenge and asserts that a POSA would have similarly “used the
`disclosures in the May Article regarding TNS9’s LCR, especially given the
`general knowledge of the map of the LCR to identify the claimed restriction
`sites, and narrowed the options to a finite list of possibilities for HS2, HS3,
`and HS4.” Id. at 34 (footnote omitted). Petitioner also contends that the
`skilled artisan would have known that certain restriction enzymes, including
`BstX1, SnaBI, BamHI, HindIII, and Banll, were commercially available. Id.
`at 30, 33. Based on that combined information, Petitioner contends, as
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`discussed for the anticipation ground, that “a POSA would have identified
`only six possible combinations of restriction enzyme fragments, one of
`which is recited in claim 1.” Id. at 34.
`Petitioner contends that “a POSA would have had a good reason to
`make the TNS9 vector identified in the May Article given the authors’
`disclosures that ‘[t]hese findings established that the larger LCR fragments
`. . . increased globin expression in vivo and, furthermore, suggested that
`TNS9 is more resistant to transcriptional silencing . . . than [the core
`elements].’” Id. at 35 (quoting Ex. 1005, 84; citing Ex. 1002 ¶ 132)
`(alteration in original). Additionally, Petitioner contends that a skilled
`artisan would have understood how to create the vector described in the May
`Article with the recited HS2, HS3, and HS4 fragments, with a reasonable
`expectation of success, as it “involved merely combining known elements in
`the field (i.e., the disclosed TNS9 vector fragments, as in the May Article,
`and a POSA’s knowledge of the restriction-site map of the LCR) to yield a
`predictable result (i
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