Trials@uspto.gov
`571-272-7822
`
` Paper 12
`
`Date: April 14, 2021
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`EVERGREEN THERAGNOSTICS, INC.,
`Petitioner,
`
`v.
`
`ADVANCED ACCELERATOR APPLICATIONS SA,
`Patent Owner.
`____________
`
`PGR2021-00001
`Patent 10,596,278 B2
`____________
`
`
`Before SHERIDAN K. SNEDDEN, ZHENYU YANG, and
`JAMIE T. WISZ, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Post-Grant Review
`35 U.S.C. § 324
`
`
`
`
`
`
`
`
`
`
`571-272-7822
`
` Paper 12
`
`Date: April 14, 2021
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`EVERGREEN THERAGNOSTICS, INC.,
`Petitioner,
`
`v.
`
`ADVANCED ACCELERATOR APPLICATIONS SA,
`Patent Owner.
`____________
`
`PGR2021-00001
`Patent 10,596,278 B2
`____________
`
`
`Before SHERIDAN K. SNEDDEN, ZHENYU YANG, and
`JAMIE T. WISZ, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Post-Grant Review
`35 U.S.C. § 324
`
`
`
`
`
`
`
`
`
`
`
`PGR2021-00001
`Patent 10,596,278 B2
`
`
`INTRODUCTION
`Evergreen Theragnostics, Inc. (“Petitioner”) filed a Petition (Paper 2
`(“Pet.”)), requesting a post-grant review of claims 1–25 of U.S. Patent
`No. 10,596,278 B2 (Ex. 1002, “the ’278 patent”). Advanced Accelerator
`Applications SA (“Patent Owner”) filed a Preliminary Response (Paper 7
`(“Prelim. Resp.”)). With our authorization, Petitioner filed a Reply
`(Paper 9), and Patent Owner filed a Sur-Reply (Paper 11).
`We review the Petition under 35 U.S.C. § 324, which provides that a
`post-grant review may not be instituted unless “it is more likely than not that
`at least 1 of the claims challenged in the petition is unpatentable.” 35 U.S.C.
`§ 324(a). For the reasons provided below, we deny institution of a post-grant
`review.
`
`Related Matters
`Petitioner also filed PGR2021-00002, challenging the same claims of
`the ’278 patent. 1 Pet. 76. Petitioner further filed PGR2021-00003,
`challenging the claims of U.S. Patent No. 10,596,276, a patent in the same
`family as the ’278 patent. Id.
`Background of the Technology and the ’278 Patent
`The ’278 patent relates to “radionuclide complex solutions of high
`concentration and of high chemical stability, [which] allows their use as
`drug product for diagnostic and/or therapeutic purposes.” Ex. 1002,
`Abstract.
`
`
`1 The parties filed separate papers, addressing the issue of parallel petitions.
`Papers 3, 8. Because we deny the instant Petition for different reasons, we
`do not discuss that issue.
`
`2
`
`
`
`PGR2021-00001
`Patent 10,596,278 B2
`
`
`The targeted drug delivery concept has been used in radiomedicine to
`deliver radionuclides selectively to the target cells for diagnostic or
`therapeutic purposes. Id. at 1:35–37. In a radiomedicine application, a target
`cell receptor binding moiety is linked to a chelating agent that is able to form
`a strong complex with the metal ions of a radionuclide. Id. at 1:38–41. When
`the radiopharmaceutical drug is delivered, the decay of the radionuclide
`affects only the target cells. Id. at 1:41–44.
`Specifically, peptide receptor radionuclide therapy (PRRT) was
`developed because “[n]early all cancers have overexpression of specific
`receptors on the tumor surface.” Ex. 1016, 2951. 2 “The most widely
`employed modality of PRRT uses somatostatin analogues for targeting
`somatostatin receptors, which are overexpressed in neuroendocrine cancer.”
`Id. 177Lu is a therapeutic radionuclide (id. at 2939), and DOTA is one of the
`most widely used chelating agent for Lu (id. at 2940). Thus, 177Lu-labeled-
`DOTA-somatostatin analogues, including 177Lu-DOTA-TATE and
`177Lu-DOTA-TOC have been used in PRRT. Id. at 2952.
`The ’278 patent explains that,
`One technical problem with those radiopharmaceutical drug
`products is that the decay of the radionuclide occurs constantly,
`e.g. also during the manufacturing and during storage of the drug
`product, and the released high energy emissions induce the
`cleavage of the chemical bonds of the molecules which form part
`of the drug product. This is often referred to as radiolysis or
`radiolytic degradation. The radiolytic degradation of the receptor
`
`
`2 Unless otherwise noted, we cite the original page numbers of the exhibits.
`3
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`PGR2021-00001
`Patent 10,596,278 B2
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`
`binding moiety of the drug may lead to a decrease in its efficacy
`to act as a diagnostic and/or therapeutic.
`Ex. 1002, 1:45–54.
`The ’278 patent states that, before its invention, the usage of
`radiopharmaceutical drugs was limited due to their poor stability and the
`lack of any significant shelf-life. Id. at 1:55–2:8. Although prior art taught
`various ways to reduce radiolysis and improve stability of
`radiopharmaceutical drugs, each of those strategies has its own drawbacks.
`Id. at 2:9–39.
`According to the ’278 patent,
`It remains therefore a challenge to design a ready-to-use
`radiopharmaceutical drug product which can be produced at
`commercial scale and delivered as a sufficiently stable and sterile
`solution in a high concentration which leads to a for patient
`convenient small infusion volume and which has a composition
`of high physiological tolerability (e.g. a composition which does
`not contain ethanol).
`Id. at 2:40–47.
`The ’278 patent states that its inventors “found a way to design and
`produce a highly concentrated radionuclide complex solution which is
`chemically and radiochemically very stable even if stored at ambient or short
`term elevated temperatures so that it can be produced on commercial scale
`and supplied as ready-to-use radiopharmaceutical product.” Id. at 2:50–55.
`
`
`
`4
`
`
`
`PGR2021-00001
`Patent 10,596,278 B2
`
`
`Illustrative Claim
`Independent claim 1 is illustrative of the challenged claims and
`is reproduced below:
`1. A pharmaceutical aqueous solution comprising:
`(a) a complex formed by
`(ai) the radionuclide 177Lu (Lutetium-177), and
`(aii) a somatostatin receptor binding peptide linked to the
`chelating agent DOTA; and
`(b) at least two different stabilizers against radiolytic degradation
`comprising
`(bi) gentisic acid or a salt thereof; and
`(bii) ascorbic acid or a salt thereof;
`wherein
`said radionuclide is present in a concentration that it provides
`a volumetric radioactivity of from 250 to 500 MBq/mL;
`said stabilizers are present in a total concentration of from 1.0
`to 5.0 mg/mL; and the pharmaceutical aqueous solution has
`less
`than 1% ethanol, and the radiochemical purity
`(determined by HPLC) of the solution is maintained at ≥95%
`for at least 72 h when stored at 25 ℃.
`
`
`
`
`5
`
`
`
`PGR2021-00001
`Patent 10,596,278 B2
`
`
`23
`
`8–10
`
`103
`
`103
`
`Asserted Grounds of Unpatentability
`Claim(s) Challenged 35 U.S.C. §
`Reference(s)/Basis
`1–5, 8–22, 24–25
`102(a)
`Protocol3
`1–5, 8–22, 24–254
`103
`Protocol, Maus, 5 SEC Statement6
`6, 7
`103
`Protocol, Maus, SEC Statement,
`De Leon-Rodriguez, 7 Banerjee8
`Protocol, Maus, SEC Statement,
`Filice9
`Protocol, Maus, SEC Statement,
`’536 patent10
`Protocol, ’536 patent, Maus
`Enablement
`Improper Dependency
`
`103
`11–14
`112
`1–25
`
`24
`
`3 Protocol associated with Strosberg et al., Phase 3 Trial of 177Lu-Dotatate
`for Midgut Neuroendocrine Tumors, 376 N. Engl. J. Med. 125–35 (2017)
`(Ex. 1012).
`4 Petitioner separately challenges claim 17 as obvious over the Protocol,
`Maus, SEC Statement, and the general knowledge of an ordinarily skilled
`artisan. Pet. 67–69. Because the general knowledge of an artisan is always
`part of the obviousness analysis, we do not list this ground separately.
`5 Maus et al., Aspects of Radiolabeling of 177Lu-DOTA-TATE: After C18
`Purification Re-Addition of Ascorbic Acid Is Required to Maintain
`Radiochemical Purity, 1 Int. J. Diagnostic Imaging 5–12 (2014) (Ex. 1009).
`6 United States Security and Exchange Commission Form F-1 for Advanced
`Accelerator Applications S.A. (2014) (Ex. 1018).
`7 De Leon-Rodroguez et al., The Synthesis and Chelation Chemistry of
`DOTA−Peptide Conjugates, 19 Bioconjugate Chem. 391–402 (2008)
`(Ex. 1014).
`8 Banerjee et al., Lutetium-177 Therapeutic Radiopharmaceuticals: Linking
`Chemistry, Radiochemistry, and Practical Applications, 115 Chem. Rev.
`2934−74 (2015) (Ex. 1016).
`9 Filice et al., Radiolabeled Somatostatin Analogues Therapy in Advanced
`Neuroendocrine Tumors: A Single Centre Experience, 2012 J. Oncology
`1–10 (2012) (Ex. 1028).
`10 Zamora et al., US 6,261,536 B1, issued Jul. 17, 2001 (Ex. 1013).
`6
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`PGR2021-00001
`Patent 10,596,278 B2
`
`
`In support of its positions, Petitioner relies on the declarations of
`Stephan Maus (Ex. 1006), Ingrid Hsieh-Yee, Ph.D. (Ex. 1008), and Paul E.
`Dietz, Ph.D., Esq. (Ex. 1037).
`
`ANALYSIS
`Preliminary Matters
`Before we discuss the substantive issues, we address a few
`preliminary matters.
`First, Patent Owner argues that we should exercise our discretion
`under 35 U.S.C. § 325(d) and deny institution because “Maus Was
`Overcome in Prosecution and [Petitioner] Presents Substantially the Same
`Arguments.” Prelim. Resp. 52. Because, as explained below, we deny
`institution for other reasons, we decline to consider whether institution
`should be denied under § 325(d).
`Second, Patent Owner contends that the Petition improperly multiplies
`the obviousness grounds. Prelim. Resp. 66. Patent Owner argues that,
`although the Petition asserts six enumerated challenges on the bases of
`obviousness, by linking prior art by numerous disjunctive and “and/or”
`connectors, it in fact proposes at least sixteen different combinations of art.
`Id. at 66–67. According to Patent Owner, this constitutes an “unduly
`burdensome number of combinations,” which justifies a denial of institution.
`Id. at 68. We agree with Patent Owner that excessive use of disjunctive and
`“and/or” connectors is improper. Although we decline to deny institution
`solely on this basis, we construe the problematic challenges as including all
`the prior art asserted. For example, the Petition states Challenge 3 as
`follows:
`
`7
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`PGR2021-00001
`Patent 10,596,278 B2
`
`
`Dependent claims 6–7 are rendered obvious under 35 U.S.C.
`§ 103 by (i) Protocol (Ex. 1012) in view of De León-Rodríguez
`(Ex. 1014) and/or Banerjee (Ex. 1016) or (ii) Protocol (Ex. 1012)
`in view of Maus (Ex. 1009) further in view of SEC Statement
`(Ex. 1018) further in view of De León-Rodríguez (Ex. 1014)
`and/or Banerjee (Ex. 1016).
`Pet. 10. We construe this ground as challenging claims 6 and 7 as obvious
`over the combined teachings of the Protocol, Maus, the SEC Statement, De
`León-Rodríguez, and Banerjee.
`Third, the parties dispute whether Petitioner has shown that the
`Protocol is prior art: Petitioner argues yes (see Pet. 14; Reply 1–3; Ex. 1008
`¶¶ 19–36; Ex. 1037 ¶¶ 6–14); Patent Owner contends no (see Prelim.
`Resp. 20–38; Sur-Reply 1–3). We do not need to address this issue because
`even if Petitioner has shown that the Protocol is prior art, it has not shown it
`is more likely than not that the Protocol anticipates, or in combination with
`other prior art, renders obvious, the challenged claims.
`Eligibility for Post-Grant Review
`The post-grant review provisions apply only to a patent that contains a
`claim with an effective filing date on or after March 16, 2013. See Leahy-
`Smith America Invents Act (“AIA”), Pub. L. No. 112-29, 125 Stat. 284
`(2011), §§ 3(n)(1), 6(f)(2)(A).
`The ’278 patent issued on March 24, 2020, from an application filed
`on October 30, 2018. Ex. 1002, codes (22), (45). It also claims the benefit of
`two earlier applications filed on September 25, 2018 and July 25, 2018,
`respectively. Id., code (63). Because the ’278 patent issued from an
`application having claims with an effective filing date after March 16, 2013,
`it is available for post-grant review.
`
`8
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`PGR2021-00001
`Patent 10,596,278 B2
`
`
`The Petition was filed on October 2, 2020 (Paper 4, 1), within nine
`months of the grant of the ’278 patent. See 35 U.S.C. § 321(c). Petitioner
`further certifies that it has standing to seek a post-grant review of the
`’278 patent. Pet. 2.
`
`Claim Construction
`In a post-grant review, we construe a claim term “using 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. § 42.200(b) (2019).
`Under that standard, the words of a claim “are generally given their ordinary
`and customary meaning,” which is “the meaning that the term would have to
`a person of ordinary skill in the art in question at the time of the invention,
`i.e., as of the effective filing date of the patent application.” Phillips v. AWH
`Corp., 415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc).
`Petitioner points out that the ’278 patent defines the term “shelf life”
`as “the length of time that a pharmaceutical product may be stored while its
`product characteristics still comply with the product specification as defined
`during drug development and agreed by health authorities.” Pet. 13 (quoting
`Ex. 1002, 13:45–50). Patent Owner does not discuss the construction of this
`term. For purposes of this Decision, we adopt Petitioner’s proposed
`construction as it is set forth in the Specification with reasonable clarity,
`deliberateness, and precision. See In re Paulsen, 30 F.3d 1475, 1480 (Fed.
`Cir. 1994).
`Claim terms need only be construed to the extent necessary to resolve
`the controversy. Wellman, Inc. v. Eastman Chem. Co., 642 F.3d 1355, 1361
`
`9
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`PGR2021-00001
`Patent 10,596,278 B2
`
`(Fed. Cir. 2011). For purposes of this Decision, we see no need to expressly
`construe any other claim term.
`Disclosures of Relevant Prior Art
`The Protocol
`The Protocol reports “[a] multicentre, stratified, open, randomized,
`comparator-controlled, parallel-group phase III study comparing treatment
`with 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in patients with
`inoperable, progressive, somatostatin receptor positive, midgut carcinoid
`tumours.” Ex. 1012, 3.11
`According to the Protocol, 177Lu-DOTA0-Tyr3-Octreotate (trade name
`Lutathera) “is a radiopharmaceutical solution for infusion supplied as a
`ready-to-use product.” Id. at 43. “The product is manufactured and supplied
`to the clinical sites in monodose vials. One vial, for one administration,
`contains 7.4 GBq (200 mCi) of 177Lu-DOTA0-Tyr3-Octreotate at calibration
`time (the time of infusion) in a formulation solution of 22 to 25 mL.” Id. The
`Protocol discloses the infusion solution composition as having a
`radioconcentration of 370 MBq/mL and comprising 0.63 mg/mL gentisic
`acid and 2.80 mg/mL ascorbic acid. Id.
`The Protocol states Lutathera has a shelf life of 72 hours and “must be
`stored at a temperature below 25 ℃.” Id. at 164.
`Maus
`Maus presents a comparative study to investigate the effect of gentisic
`acid and ascorbic acid as stabilizers during and after the radiolabeling
`
`
`11 For Exhibit 1012, we cite the page numbers added by Petitioner.
`10
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`PGR2021-00001
`Patent 10,596,278 B2
`
`177Lu-DOTA-TATE procedures. Ex. 1009, 6. When reporting the
`radiochemical purity [RCP] of 177Lu-DOTA-TATE, Maus states “95% RCP
`. . . is taken as [the] lowest level suitable for patient administration.” Id. at 9,
`caption to Figure 2.
`
`Kwekkeboom
`Kwekkeboom12 is the reference Maus followed for the manual
`radiolabeling procedure. Ex. 1009, 7 (Section 2.2, citing reference 13), 12
`(showing reference 13 is Kwekkeboom). Kwekkeboom reports that
`177Lu-DOTA-TATE “potentially represents an important improvement” over
`then available radionuclide-coupled somatostatin analogues for somatostatin
`receptor-mediated radiotherapy. Ex. 1010, 1319. When conducting the
`comparison, Kwekkeboom injected into six patients 177Lu-DOTA-TATE
`with radiochemical purity of “higher than 88%,” as determined by HPLC.
`Id. at 1320.
`
`The SEC Statement
`According to the SEC Statement, Lutathera was formulated with a
`three-day shelf life. Ex. 1018, 2, 90.
`Anticipation by the Protocol
`Petitioner argues that claims 1–5, 8–22, 24, and 25 of the ’278 patent
`are anticipated by the Protocol. Pet. 21–35. Based on this record, we
`determine Petitioner has not shown it is more likely than not that any of
`claims 1–5, 8–22, 24, and 25 is anticipated by the Protocol.
`
`
`12 Kwekkeboom et al., [177Lu-DOTA0,Tyr3]octreotate: Comparison with
`[111In-DTPA0]octreotide in Patients, 28 Eur. J. Nucl. Med. 1319–25 (2001)
`(Ex. 1010).
`
`11
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`PGR2021-00001
`Patent 10,596,278 B2
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`
`Petitioner argues that the Protocol discloses each limitation of claim 1.
`Pet. 21–26. Claim 1 recites, among others, that “the radiochemical purity
`(determined by HPLC) of the solution is maintained at ≥95% for at least
`72 h when stored at 25 ℃” (“the stability limitation”). Patent Owner
`contends that the Protocol does not disclose, explicitly or inherently, this
`limitation. Prelim. Resp. 39–45. On this record, we agree with Patent Owner.
`Petitioner argues the “Protocol disclosed that the pharmaceutical
`aqueous solution disclosed therein had an initial ‘radiochemical purity
`≥97%.’” Pet. 24 (citing Ex. 1012, 44, caption to Table 3) (emphasis added).
`Petitioner also relies on the Protocol for disclosing that Lutathera should be
`stored at less than 25 ℃ and has a shelf life of 72 hours. Id. (citing Ex. 1012,
`160, 164). According to Petitioner, “[a] POSA would have understood that,
`for a product to be stable at 72 hours, the radiochemical purity would have to
`be greater than 95% at the 72 hour timepoint.” Id. As support, Petitioner
`refers to the caption to Figure 2 in Maus for stating that, for 177Lu-DOTA-
`TATE, “95% RCP . . . is taken as [the] lowest level suitable for patient
`administration.” Id. (citing Ex. 1009, 9).
`Petitioner acknowledges that claim 1 recites that the radiochemical
`purity is maintained at ≥ 95% for at least 72 h when stored at 25 ℃, whereas
`the Protocol discloses “Lutathera must be stored at a temperature below
`25 ℃.” Id. at 25. Nonetheless, Petitioner argues that “[a] POSA would have
`understood that a pharmaceutical aqueous solution that has a shelf-life of 72
`hours when stored below 25° C (including, for example, 24.9° C), as
`disclosed in Protocol, would also have a shelf life of 72 hours when stored at
`
`12
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`PGR2021-00001
`Patent 10,596,278 B2
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`25° C.” Id. (citing Ex. 1006 ¶ 117). We are not persuaded by Petitioner’s
`arguments.
`First, we observe that, as Patent Owner correctly points out, the
`Protocol does not actually measure the radiochemical purity of the Lutathera
`solution. See Prelim. Resp. 40. Instead, the Protocol merely “describes
`assumptions that the authors made concerning a clinical trial formulation:
`‘Values calculated assuming 177Lu specific activity of 740 GBq/mg at
`labelling time and a mean synthesis yield of 80% and radiochemical purity
`≥97%.’” Id. (quoting Ex. 1012, 44, caption to Table 3, emphasis added). We
`agree with Patent Owner “[t]hese assumptions do not provide any evidence
`of what the experimentally measured radiochemical purity of a formulation
`made with this composition actually was at any point in time, or at any
`temperature.” Id.
`Second, Petitioner has not pointed to persuasive evidence to show that
`an ordinarily skilled artisan would have understood a pharmaceutical
`aqueous solution having a shelf life of 72 hours when stored below 25 °C as
`also having a shelf life of 72 hours when stored at 25 °C. Indeed, besides
`Mr. Maus’s unsupported testimony stating the same, Petitioner relies on
`challenged claim 15, which depends from claim 1 and further recites that the
`pharmaceutical aqueous solution “has a shelf life of at least 72 h when stored
`at ≤25° C.” According to Petitioner, “[f]or such a claim to be properly
`dependent, the term in claim 1 ‘at 25° C’ must include at least storage at
`some temperatures below 25° C.” Pet. 26. We disagree.
`The ’278 patent, in one embodiment, defines its invention as “[t]he
`pharmaceutical aqueous solution according to any one of the preceding E
`
`13
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`PGR2021-00001
`Patent 10,596,278 B2
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`embodiments, which has a shelf life of at least 72 h when stored at ≤25 °C,
`in particular at least at least 72 h when stored at 25 °C.” Ex. 1002, 13:41–44.
`In other words, “≤25 °C” is broader than “at 25 °C.” Thus, we are not
`persuaded that temperature is the narrowing limitation for claim 15 to be
`properly dependent from claim 1. Instead, we agree with Patent Owner that,
`under the doctrine of claim differentiation, “‘[s]helf life’ [recited in
`claim 15] must mean something different than radiochemical purity [recited
`in claim 1] for claim 15 to have any different scope than” claim 1. See
`Prelim. Resp. 42.
`Third, putting the temperature limitation aside, we are not persuaded
`by Petitioner’s argument that having a shelf life of 72 hours is the same as
`maintaining the radiochemical purity of ≥95% for 72 hours. This, of course,
`is because, as explained above in relation to claim 15, the shelf-life
`limitation is separate and distinct from the stability limitation. In addition,
`Mr. Maus testifies, and Petitioner argues, “[a] POSA would have . . .
`understood that meeting the specification for radiochemical purity was
`typically what limited the shelf life of a 177Lu DOTA-TATE composition.”
`Ex. 1006 ¶ 115; Pet. 24–25 (emphasis added). In other words, other factors
`may also affect the shelf life of the composition.
`Moreover, Patent Owner has pointed to sufficient evidence to show
`that the prior art as a whole does not support Petitioner’s assertion. Petitioner
`relies on the caption to Figure 2 in Maus for stating that, for 177Lu-DOTA-
`TATE, “95% RCP . . . is taken as [the] lowest level suitable for patient
`administration.” Pet. 24 (citing Ex. 1009, 9). Patent Owner argues that
`“[n]owhere does the article cite any support for that assessment. Maus does
`
`14
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`PGR2021-00001
`Patent 10,596,278 B2
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`not even disclose the clinical use of the formulations produced.” Prelim.
`Resp. 44. More importantly, Patent Owner refers to other prior art
`references, including those Petitioner relies on, for teaching administering
`177Lu-DOTA-TATE with RCP lower than 95%. Id. at 44–45 (citing
`Exs. 1010, 1023, 2003). For example, Kwekkeboom injected into six
`patients 177Lu-DOTA-TATE with radiochemical purity of “higher than
`88%,” as determined by HPLC. Ex. 1010, 1320.
`Thus, under the totality of the circumstances, including the prior art as
`a whole, as well as the Specification and claim 15 of the ’278 patent, we are
`not persuaded that the Protocol explicitly discloses the stability limitation
`recited in claim 1.
`Petitioner further advances an inherency argument. A reference may
`anticipate without expressly disclosing a limitation of the claimed invention,
`if that limitation is necessarily present, or inherent, in the reference.
`Schering Corp. v. Geneva Pharm., 339 F.3d 1373, 1377 (Fed. Cir. 2003).
`Petitioner’s inherency contention, in its entirety, reads as follows:
`Furthermore, the pharmaceutical aqueous solution disclosed in
`Protocol included each and every structural limitation recited in
`claim 1. Therefore, the pharmaceutical aqueous solution
`disclosed in Protocol necessarily would have maintained
`radiochemical purity, determined by HPLC, at ≥ 95% for at least
`72 hours when stored at 25° C, i.e., the radiochemical purity
`would have been the “natural result flowing from” the prior art
`disclosure. See Perricone v. Medicis Pharm. Corp., 432 F.3d
`1368, 1377 (Fed. Cir. 2005) (citing Eli Lilly & Co. v. Barr Labs.,
`Inc., 251 F.3d 955, 970 (Fed. Cir. 2001)).
`Pet. 26.
`
`15
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`PGR2021-00001
`Patent 10,596,278 B2
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`
`We are not persuaded by this argument because Petitioner has not
`sufficiently explained the premise of this argument. In other words,
`Petitioner has not sufficient explained why the recited radiochemical purity
`is the “natural result flowing from,” and thus, an inherent property of, a
`composition, instead of an additional requirement of the composition.
`In sum, Petitioner has not sufficiently demonstrated that the Protocol
`explicitly or inherently discloses the stability limitation recited in claim 1.
`Each of claims 2–5, 8–22, 24, and 25 also recites, either explicitly or through
`dependency, the same stability limitation. Thus, Petitioner has not shown it
`is more likely than not that any of claims 1–5, 8–22, 24, and 25 is
`anticipated by the Protocol.
`Obviousness over the Protocol, Maus, and the SEC Statement
`Petitioner argues that claims 1–5, 8–22, 24, and 25 of the ’278 patent
`would have been obvious over the Protocol, Maus, and the SEC Statement.
`Pet. 35–49. Based on this record, we determine Petitioner has not met its
`burden for institution under this ground.
`For the stability limitation, Petitioner relies on the same evidence and
`argument as presented in the anticipation ground. Pet. 37–38. Specifically,
`Petitioner relies on the teachings of the Protocol, including the assumption
`of ≥97% initial radiochemical purity of 177Lu-DOTA-TATE, and the shelf
`life of 72 hours when the solution is stored below 25 °C. Id. at 37. Petitioner
`also relies on the caption to Figure 2 in Maus for stating that, for 177Lu-
`DOTA-TATE, “95% RCP . . . is taken as [the] lowest level suitable for
`patient administration.” Id. at 38 (citing Ex. 1009, 9). Petitioner argues that
`“[a] POSA would have understood that for a product to have a shelf life of
`
`16
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`PGR2021-00001
`Patent 10,596,278 B2
`
`72 hours[,] the radiochemical purity would have to be greater than 95% at
`the 72 hour time point.” Id. According to Petitioner, an ordinarily skilled
`artisan, thus, would have been motivated to optimize the 177Lu-DOTA-
`TATE solution to meet the stability limitation, and would have had a
`reasonable expectation of success in doing so. Id. at 38–39.
`For the same reason explained above, we are not persuaded that a
`product having a shelf life of 72 hours would have a radiochemical purity
`greater than 95% at the 72-hour time point. See supra at 12–14. Because we
`disagree with Petitioner’s premise for its obviousness argument, we
`determine that Petitioner has not met its burden regarding the obviousness of
`the challenged claims to warrant instituting a trial.
`Other Obviousness Grounds
`Petitioner argues that dependent claims 6–14 and 23 of the ’278 patent
`would have been obvious over the Protocol, Maus, the SEC Statement, and
`several additional prior-art references. Pet. 50–69. Each of these challenged
`claims, through dependency, recites the stability limitation. Petitioner relies
`on, the same evidence and argument as discussed above, not the additional
`prior art, for teaching this limitation. For the same reasons explained above,
`we are not persuaded. See supra at 12–14, 16. Thus, we determine that
`Petitioner has not met its burden regarding these additional obviousness
`grounds.
`
`Enablement and Improper Dependency
`Petitioner contends that “if the stability limitations recited in the
`claims of the ’278 patent are not anticipated by or obvious over the Protocol
`formulation, the claims of the ’278 patent are unpatentable because they are
`
`17
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`PGR2021-00001
`Patent 10,596,278 B2
`
`not enabled for their full scope.” Pet. 70. Petitioner also argues that claim 24
`is invalid for improper dependency. Id. at 74–75.
`Institution of post-grant review is discretionary. See 35 U.S.C.
`§ 324(a); see also SAS Inst. Inc. v. Iancu, 138 S. Ct. 1348, 1356 (2018)
`(“[Section] 314(a) invests the Director with discretion on the question
`whether to institute review . . . .” (emphasis omitted)); Harmonic Inc. v. Avid
`Tech, Inc., 815 F.3d 1356, 1367 (Fed. Cir. 2016) (explaining that under
`§ 314(a), “the PTO is permitted, but never compelled, to institute an IPR
`proceeding”). 13
`In exercising that discretion, we are guided by the statutory
`requirement, in promulgating regulations for post-grant review, to consider
`the effect of any regulations on “the efficient administration of the Office
`[and] the ability of the Office to timely complete proceedings,” 35 U.S.C.
`§ 326(b), as well as the requirement to construe our rules to “secure the just,
`speedy, and inexpensive resolution of every proceeding,” 37 C.F.R.
`§ 42.1(b).
`Under the Office Guidance, “if the PTAB institutes a trial, the PTAB
`will institute on all challenges raised in the petition.” Guidance on the
`Impact of SAS on AIA Trial Proceedings (April 26, 2018). 14 Here, Petitioner
`advances nine challenges against the claims of the ’278 patent. Pet. 10–11.
`As discussed above, we determine that, on this record, Petitioner has not met
`
`
`13 Even though SAS and Harmonic address inter partes reviews, we see no
`reason to interpret the statute governing post-grant reviews differently.
`14 Available at https://www.uspto.gov/patents/ptab/trials/guidance-impact-
`sas-aia-trial.
`
`18
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`PGR2021-00001
`Patent 10,596,278 B2
`
`its burden for institution under seven art-based grounds. Supra at 11–17.
`Based on the particular facts of this proceeding, instituting a trial with
`respect to all grounds based on evidence and arguments directed only to
`these two non-art based grounds, one of which only concerns a single
`dependent claim, would not be an efficient use of the Board’s time and
`resources. 15 Cf. Chevron Oronite Co. LLC v. Infineum USA L.P.,
`IPR2018-00923, Paper 9, 10–11 (PTAB Nov. 7, 2018) (informative);
`Deeper, UAB v. Vexilar, Inc., IPR2018-01310, Paper 7 (PTAB Jan. 24,
`2019) (informative). Thus, we do not institute a post-grant review.
`ORDER
`In consideration of the foregoing, it is hereby:
`ORDERED that the Petition is denied and no post-grant review is
`instituted.
`
`
`
`
`
`
`15 We also note that Petitioner asserts its enablement challenge if the stability
`limitation is “not an inherent property of (or obvious over) the prior art
`taught compositions.” Pet. 72. In this Decision, however, we do not reach
`the conclusion on anticipation or obviousness. Instead, we only determine
`that Petitioner has not met its burden in showing the inherency or
`obviousness for institution purpose.
`
`19
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`PGR2021-00001
`Patent 10,596,278 B2
`
`FOR PETITIONER:
`
`C. Kyle Musgrove
`Paul Dietze
`Scott Cunning
`Elizabeth Crompton
`PARKER POE ADAMS & BERNSTEIN LLP
`kylemusgrove@parkerpoe.com
`pauldietze@parkerpoe.com
`scottcunning@parkerpoe.com
`elizabethcrompton@parkerpoe.com
`
`
`
`
`FOR PATENT OWNER:
`
`Jane Love
`Kyanna Sabanoglu
`GIBSON, DUNN & CRUTCHER LLP
`jlove@gibsondunn.com
`ksabanoglu@gibsondunn.com
`
`20
`
`
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