Trials@uspto.gov
`571-272-7822
`
`Paper 63
`Date: May 31, 2022
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`THORNE RESEARCH, INC.,
`Petitioner,
`v.
`TRUSTEES OF DARTMOUTH COLLEGE,
`Patent Owner.
`
`IPR2021-00268
`Patent 8,383,086 B2
`
`
`
`
`
`
`
`
`
`
`
`Before SUSAN L.C. MITCHELL, ROBERT A. POLLOCK, and
`JOHN E. SCHNEIDER, Administrative Patent Judges.
`SCHNEIDER, Administrative Patent Judge.
`
`
`
`
`
`JUDGMENT
`Final Written Decision
`Determining the Challenged Claim Unpatentable
`35 U.S.C. § 318 (a)
`Denying Petitioner’s Motion to Exclude
`Denying Patent Owner’s Motion to Exclude
`37C.F.R. § 42.64
`
`
`
`
`
`

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`IPR2021-00268
`Patent 8,383,086 B2
`
`INTRODUCTION
`I.
`A. Background and Summary
`Thorne Research, Inc. (“Petitioner”) filed a Petition requesting inter
`partes review of claim 2 of U.S. Patent No. 8,383,086 B2 (Ex. 1001, “the
`’086 patent”). Paper 2 (“Pet.”). The Trustees of Dartmouth College (“Patent
`Owner”) filed a Preliminary Response contending that the Petition should be
`denied. Paper 10 (“Prelim. Resp.”). During a telephone conference held on
`March 23, 2021, the panel authorized additional briefing on whether certain
`references were the works “by another” as the term is used in 35 U.S.C.
`§ 102(a).1 Ex. 1024, 23–24. In accordance with such authorization,
`Petitioner filed a Reply to Patent Owner’s Preliminary Response. Paper 15
`(“Pet. Reply”).We instituted inter partes review on June 10, 2021. Paper 21
`(“Dec.”)
`Patent Owner then filed a response on September 21, 2021. Paper 27
`(“PO Resp.”). Petitioner then filed a Reply. Paper 34 (“Reply”). Patent
`Owner filed a sur-reply. Paper 36 (“Sur-Reply”). An oral hearing was
`conducted on March 15, 2022. A copy of the transcript has been made of
`record. Paper 62. (“Tr.”)
`We have jurisdiction under 35 U.S.C. § 6. This is a Final Written
`Decision under 35 U.S.C. § 318(a) as to the patentability of the claim on
`which we instituted trail. Based on the complete record before us, we
`determine that Petitioner has shown, by a preponderance of the evidence,
`that claim 2 is unpatentable. In addition, for the reasons explained below, we
`
`
`1 35 U.S.C. §§ 102 and 103 was amended by the Leahy-Smith America
`Invents Act (“AIA”), Pub. L. No. 112-29, 125 Stat. 284, 287–88 (2011).
`Because the ’086 patent was filed before the effective date of the relevant
`amendment, the pre-AIA version of §§ 102 and 103 applies.
`
`2
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`IPR2021-00268
`Patent 8,383,086 B2
`deny both Petitioner’s Motion to Exclude Evidence and Patent Owner’s
`Motion to Exclude Evidence.
`B. Real Parties in Interest
`Thorne Research, Inc. identifies itself as the real party-in-interest.
`Pet. 33. The Trustees of Dartmouth College identifies itself as the real
`parties-in-interest. Paper 5, 2.
`C. Related Matters
`Petitioner represents that a petition for inter partes review was filed
`challenging all claims (1–5) of the ’086 patent in IPR2017-01795 (“the
`’1795 IPR”). Pet. 1, 33. We issued a final decision holding that all claims
`were unpatentable except claim 2. Ex. 1018. That decision was affirmed by
`the Federal Circuit on March 6, 2020. Ex. 1004 1–2.
` Petitioner also represents that a petition for inter partes review was
`filed by a third party challenging related patent U.S. Patent No. 8,197,807
`“the ’807 patent”) in IPR2017-01796. Pet. 34. We denied institution of inter
`partes review of the petition in IPR2017-01796. Elysium Health, Inc. v.
`Trustees of Dartmouth College, IPR2017-01796, Paper 9 (PTAB Jan. 18,
`2018).
`Petitioner represents that it filed a petition for inter partes review of
`the related ’807 patent in IPR 2021-00491, filed February 1, 2021. Paper 18.
`We instituted trial in this proceeding on August 12, 2021 and the case is
`awaiting decision.
`Patent Owner states that the ’086 patent is the subject of an
`infringement action in the United States District Court for the District of
`Delaware in a case captioned ChromaDex, Inc., et al. v. Elysium Health,
`Inc., Case No. 18-cv-01434 (D. Del.). Paper 5, 3. Patent Owner further states
`the ‘086 patent is also subject to a patent misuse counterclaim in
`
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`IPR2021-00268
`Patent 8,383,086 B2
`ChromaDex, Inc. v. Elysium Health, Inc., Case No. 16-cv-02277-CJC (C.D.
`Cal.). Id. Patent Owner has also indicated that it has filed an action against
`Petitioner for infringement of the ’086 patent and the ’807 patent in
`ChromaDex, Inc., et al. v. Thorne Research, Inc., Case No. 1:21-cv-04241
`(S.D.N.Y.). (Paper 19).
`Petitioner represents that the district court in the Delaware action
`granted Elysium Health’s Motion for Summary Judgment of Invalidity of
`claim 2 of the ’086 patent and claims 1, 2, and 3 of the ’807 patent as invalid
`under 35 U.S.C. § 101 for claiming patent ineligible subject matter. Paper
`32, 2. Patent Owner has appealed the district court’s decision. Id.
`D. The ’086 Patent
`The ’086 patent issued on February 26, 2013, with Charles M.
`Brenner listed as the inventor. Ex. 1001, codes (45), (75). The ’086 patent
`issued from an application filed on April 12, 2012, and on its face, claims
`priority to an application filed April 20, 2006. Id. at code (63). The
`Specification of the ’807 patent includes the following claim of priority:
`This application is a continuation of U.S. patent
`application Ser. No. 11/912,400 filed Nov. 20, 2007 now U.S.
`Pat. No. 8,197,807, which is the National Stage of International
`Application No. PCT/US2006/015495 filed Apr. 20, 2006,
`which claims benefit of priority to U.S. patent application Ser.
`No. 11/113,701 filed Apr. 25, 2005, the teachings of which are
`incorporated herein by reference in their entireties.
`
`
`Ex. 1001 col. 1, ll. 7–13.
`
`
`As discussed in Section II.D, below, the parties disagree as to whether
`the ’086 patent is entitled to an earlier priority date of April 25, 2005.
`The ’086 Patent relates generally to the production of nicotinamide
`riboside (“NR”) and compositions containing NR. Ex. 1001, col. 4, ll. 1–16.
`
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`IPR2021-00268
`Patent 8,383,086 B2
`The ’086 patent also describes the use of compositions containing an
`effective amount of NR to treat various disorders stemming from a
`deficiency in NR. Id. at col. 4, ll. 17–29. The compositions can be in the
`form of a dietary supplement, such as ingestible tablets, buccal tablets,
`troches, capsules, elixirs, suspensions, syrups, wafers, chewing gums, and
`food. Id. at col. 4, ll. 14–16, col. 29, ll. 43–46.
`E. Illustrative Claims
`Claim 2 is the only challenged claim before us. Claim 2 depends from
`claim 1 and therefore incorporates all of the limitations of claim 1. 35 U.S.C.
`§ 112, fourth paragraph (2006). Claims 1 and 2 are reproduced below.
`1. A pharmaceutical composition comprising nicotinamide
`riboside in admixture with a carrier, wherein said
`composition is formulated for oral administration.
`2. The pharmaceutical composition of claim 1, wherein the
`nicotinamide riboside is isolated from a natural or synthetic
`source.
`
`
`Ex. 1001, col. 53, ll. 38–43.
`
`F. Evidence
`Petitioner relies on the following references:
`Stamler et al., WO 02/055018 A2, published July 18, 2002.
`(“Stamler”) (Ex. 1006).
`Brenner, et al., WO 2005/077091 A2, published August 25, 2005.
`(“Brenner”) (Ex. 1007).
`Bieganowski et al., Discoveries of Nicotinamide Riboside as a
`Nutrient and Conserved NRK Genes Establish a Preiss-Handler
`Independent Route to NAD+ in Fungi and Humans, 117 Cell 495 (May 14,
`2004) (“Bieganowski”) (Ex. 1008).
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`Patent 8,383,086 B2
`Petitioner also relies on the Declarations of Dr. Samie Jaffrey, M.D.,
`Ph.D. (Ex. 1002 and Ex. 1038). Patent Owner relies on the Declaration of
`Mansoor M. Amiji, Ph.D., R.PH. (Ex. 2014). Patent Owner also relies on the
`Declarations of Drs. Brenner and Bieganowski. (Exs. 2002, 2003, 2015,
`2021, and 2022).
`
`G. Prior Art and Asserted Grounds
`Petitioner asserts that claim 2 would have been unpatentable on the
`following grounds:
`Claim Challenged
`2
`2
`2
`2
`2
`
`
`
`35 U.S.C. §
`102(b)
`103(a)
`102(b)
`103(a)
`102(a) or (e)
`
`Reference(s)/Basis
`Stamler
`Stamler
`Bieganowski
`Bieganowski
`Brenner
`
`H. The Prior Proceeding
`As noted above, the ‘086 patent was the subject of a prior IPR
`proceeding, the ’1795 IPR, initiated by a third party, Elysium Health, Inc.,
`on July 17, 2017. Elysium requested review of original claims 1–5 of the
`‘086 patent on grounds that: (1) claims 1–5 were anticipated under 35 U.S.C.
`§ 102(b) by Goldberger et al., A Study of the Blacktongue-Preventive Action
`of 16 Foodstuffs, with Special Reference to the Identity of Blacktongue of
`Dogs and Pellagra of Man, 43 Pub. Health Reports 1385 (1928) (Ex. 1011,
`“Goldberger”); and (2) claims 1–5 were anticipated under § 102(b) by
`Goldberger and Tanner, A Study of the Treatment and Prevention of
`Pellagra, 39 Pub. Health Reports 87 (1924) (Ex. 1012,
`“Goldberger/Tanner”). See Ex. 1018, 5. We granted Elysium’s petition on
`January 29, 2018. Id. at 2.
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`IPR2021-00268
`Patent 8,383,086 B2
`In our Final Written Decision, we concluded that Elysium had
`demonstrated by a preponderance of the evidence that claims 1 and 3–5 were
`unpatentable as anticipated by both Goldberger and Goldberger/Tanner. Id.
`at 42. We also concluded that Elysium had not demonstrated that claim 2
`was unpatentable. Id. Central to our holding with respect to claim 2 was our
`finding that Elysium had not demonstrated that the compositions disclosed
`in Goldberger and Goldberger/ Tanner comprised “isolated” NR, as we
`construed that claim term. Id. at 12–14, 26–27; see also id. at 12–15
`(construing “isolated” NR to mean “that the nicotinamide riboside is
`separated or substantially free from at least some of the other components
`associated with the source of the molecule such that it constitutes at least
`25% (w/w) of the composition”).
`II. ANALYSIS
`A. Collateral Estoppel
`Before we proceed with our analysis of claim 2, we must address the
`issue of collateral estoppel. In our Decision to Institute, we concluded that
`collateral estoppel precluded the relitigation of the patentability of the
`independent claims, including independent claim 1 from which presently
`challenged claim 2 depends. Dec. 13. We found that the present proceeding
`is limited to the requirement in claim 2 that the NR be isolated. Id.
`In its Response, Patent Owner contends that we erred in finding that it
`was estopped from relitigating the limitations of claim 1. PO Resp. 34–38.
`Patent Owner contends that collateral estoppel is not applicable to the
`present proceeding because Petitioner has not made the requisite showing
`for collateral estoppel to apply. Id. at 35–36. Patent Owner argues that
`because the present proceeding involves different prior art, the identical
`issue was not litigated in the prior proceeding. Id. at 37. Thus, Patent Owner
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`IPR2021-00268
`Patent 8,383,086 B2
`contends that collateral estoppel does not apply as claim 2 presents a
`materially different issue of patentability than that addressed with respect to
`claim 1. Id. at 37–38. Patent Owner contends that collateral estoppel does
`not preclude Patent Owner from litigating whether Stamler teaches all the
`elements of claim 2, including those incorporated from claim 1. Id. at 38;
`Sur-Reply 15.
`Petitioner responds that while this proceeding does involve different
`art, collateral estoppel prevents Patent Owner from relitigating “issues,
`including issues of fact, that were previously before the board.” Reply 15
`(emphasis omitted).
`We have considered the arguments presented by the parties and find
`the issue of collateral estoppel moot because we find Petitioner has
`established by a preponderance of the evidence that Stamler teaches all of
`the elements of claim 2 including the limitations of claim 1.
`B. Legal Standards
`1. Burden of Proof
`At this stage of the proceeding, the burden rests on the petitioner to
`establish by a preponderance of the evidence that claim 2 is unpatentable.
`35 U.S.C. § 316(e) (2008).
`
`2. Anticipation2
`“Under 35 U.S.C. § 102, every limitation of a claim must identically
`appear in a single prior art reference for it to anticipate the claim.” Gechter
`v. Davidson, 116 F.3d 1454, 1457 (Fed. Cir. 1997). “[U]nless a reference
`discloses within the four corners of the document not only all of the
`
`
`2 As noted above, the pre-AIA provisions of 35 U.S.C. apply to the ’086
`patent.
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`IPR2021-00268
`Patent 8,383,086 B2
`limitations claimed but also all of the limitations arranged or combined in
`the same way as recited in the claim, it cannot be said to prove prior
`invention of the thing claimed and, thus, cannot anticipate under 35 U.S.C.
`§ 102.” Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed. Cir.
`2008).
`
`3. Obviousness
`The question of obviousness is resolved on the basis of underlying
`factual determinations including (1) the scope and content of the prior art,
`(2) any differences between the claimed subject matter and the prior art, (3)
`the level of skill in the art, and (4) where in evidence,3 so-called secondary
`considerations. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966). If the
`differences between the claimed subject matter and the prior art are such that
`the subject matter, as a whole, would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which said
`subject matter pertains, the claim is unpatentable under 35 U.S.C. § 103(a).
`KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007).
`A proper § 103 analysis requires “a searching comparison of the
`claimed invention—including all its limitations—with the teaching of the
`prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir. 1995).
`“Obviousness requires more than a mere showing that the prior art
`includes separate references covering each separate limitation in a claim
`under examination.” Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352,
`1360 (Fed. Cir. 2011). “Rather, obviousness requires the additional showing
`that a person of ordinary skill at the time of the invention would have
`
`
`3 Patent Owner does not present evidence of secondary considerations in this
`proceeding.
`
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`Patent 8,383,086 B2
`selected and combined those prior art elements in the normal course of
`research and development to yield the claimed invention.” Id.
`C. Effective filing date of the ’086 Patent
`Petitioner contends that the ’086 patent is not entitled to a priority date
`any earlier than April 20, 2006, the filing date of U.S. Application No.
`11/912,400 (“the ’400 application”), which is the national stage application
`of International Patent Application No. PCT/US2006/015495 (“the ’495
`PCT application”). Pet. 6. Petitioner contends that operation of both the
`Paris Convention and the Patent Cooperation Treaty (“PCT”) precludes any
`claim of priority earlier than that date. Petitioner contend that under the
`Paris Convention and the PCT, Patent Owner may not claim priority back to
`US Application No. 11/113,701 (“the ’701 application”) as the ’701
`application does not meet the requirements of the PCT or the Paris
`convention. Id. at 7–14.
`Patent Owner contends that the recited provisions of the Paris
`Convention and PCT are not applicable to the ’086 patent, as all of the ’086
`patent’s claim of priority, including the claim for priority to PCT
`applications, arise under 35 U.S.C. § 120 and not 35 U.S.C. § 119. Prelim.
`Resp. 17–20. Patent Owner contends the ’086 patent meets all of the
`requirements of 35 U.S.C. § 120, and as such, Patent Owner contends the
`’086 patent is also entitled to claim priority to the April 25, 2005 filing date
`of U.S. Application No. 11/113,701 (“the ’701 application”). Id. at 25.
`In our Decision to Institute, we agreed with Patent Owner that the
`’086 patent was entitled to a filing date of April 25, 2005. Dec. 17. We based
`our decision of the fact that the ’086 patent meets the requirements of
`35 U.S.C. § 120. We found that the prior application supported the
`limitations recited in claims 2; Dr. Brenner was listed on all the prior
`
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`IPR2021-00268
`Patent 8,383,086 B2
`applications; there was co-pendency for the applications; and the
`specification of the ’086 patent specifically identified the earlier
`applications. Dec. 16–17.
`In its Reply, Petitioner renews its contention that the ’086 patent is not
`entitled to a filing date earlier than April 20, 2006. Reply 1. In support of its
`contention, Petitioner points to the cover sheet of the ’086 patent, which
`does not state that the ’086 patent claims priority to the April 25, 2005 filing
`date of the ’701 application, but rather only recites a priority claim to the
`’495 PCT application, which was filed on April 26, 2006, and which, in turn,
`claims priority back to the ’701 application. Id. at 1–2. Petitioner contends
`that Patent Owner requested a corrected filing receipt for the ’086 patent that
`recites a claim of priority back to the April 25, 2005 filing date of the ’701
`application, but the request was denied. Id. at 2. Petitioner contends
`The priority grants by the USPTO for both the ’086 and
`’807 patents are consistent with Article 4 of the Paris
`Convention. PO was put on notice through the corrected filing
`receipts issued by the USPTO and has failed to take any
`corrective action. IPR2015-00414, Paper 34, 15 (noting, in
`denying priority, PO could have sought certificate of correction
`or reissue, but failed to do so); Braun v. Becton, Dickinson and
`Co., 1:16-cv-411-RGA, 7 (D. Del. June 9, 2017) (citing
`IPR2015-00414 for same proposition). PO’s arguments
`otherwise should be rejected.
`
`Id.
`
`In reply, Patent Owner contends that Petitioner is improperly raising a
`new argument. Sur-reply 1. Patent Owner contends the ’086 patent makes a
`proper claim of priority under 35 U.S.C. § 120, and the Board’s initial
`decision regarding the filing date of the ’086 patent was correct. Id at 2.
`We have considered the arguments presented by the parties and find
`that our initial decision on priority was correct. The ’086 patent claims
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`Patent 8,383,086 B2
`priority to domestic applications involving either US patent applications or a
`PCT application designating the United States. See Ex. 1001, col. 1, ll. 7–13.
`Under § 120, a patent is entitled to the priority date of an
`earlier filed application if (1) the written description of the
`earlier filed application discloses the invention claimed in the
`later filed application sufficient to satisfy the requirements of
`§ 112; (2) the applications have at least one common inventor;
`(3) the later application is filed before the issuance or
`abandonment of the earlier filed application; and (4) the later
`application contains a reference to the earlier filed application.
`In re NTP, Inc., 654 F.3d 1268, 1277 (Fed. Cir. 2011); see also 35 U.S.C.
`§ 120 . As discussed above and in our Decision to Institute, the ’086 patent
`meets this criterion.
`While we agree with Petitioner that the face of the ’086 patent does
`not include a citation of the ‘701 application, the specification does contain a
`clear claim of priority back to the ’701 application. Ex. 1001, col. 1. ll. 7–13;
`Ex. 1004 1.
`Petitioner cites to Apple Inc. v. e-Watch, Inc., IPR2015-00414, Paper
`34 (PTAB June 22, 2016) to support its contention that Patent Owner’s
`failure to seek correction of the priority claim on the face of the ’086 patent
`is fatal to Patent Owner’s claim that the filing date should stretch back to
`April 25, 2005. See Reply. 2. The facts in Apple are different that the present
`case. In Apple, the priority claim in the specification misidentified the
`application as a divisional of a prior application when in fact it was not.
`Apple, Paper 35 7. The Board found this error in identifying the relationship
`of the applications was fatal to the patent owner’s priority claim. Id. at 17.
`This is in contrast to the present case where the specification properly
`identifies each of the prior applications and states the proper relationship.
`Ex, 1001, col. 1, ll. 7–13. As the Board in Apple pointed out, pre-AIA
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`35 U.S.C. § 120 stated an application is entitled to the benefit of the filing
`date of the first application “if filed before the patenting or abandonment of
`or termination of proceedings on the first application or on an application
`similarly entitled to the benefit of the filing date of the first application and
`if it contains or is amended to contain a specific reference to the earlier filed
`application.” Apple, Paper 34, 9 (quoting 35 U.S.C. § 120). In the present
`case, the specification contains a specific reference to the chain of
`applications extending back of the ’701 application with appropriate co-
`pendency of the applications in the chain.
`We are not persuaded by Petitioner’s argument that the Office’s
`refusal to grant Patent Owner’s request for a corrected filing receipt
`confirms Petitioner’s contention that the ’086 patent is limited to an April
`20, 2006 filing date. Reply 2. The Office did not unequivocally state that the
`’086 patent was not entitled to a priority date of April 26, 2005. Rather, in
`responding to Patent Owner’s request for a corrected filing receipt the office
`indicated that it could not comply with the request because Patent Owner
`failed to submit a new application data sheet with the desired benefit claims.
`Ex. 1004 130.
`Based on the foregoing, we confirm our earlier decision that the ’086
`patent is entitled to a filing date of April 25, 2005
`D. Level of Ordinary Skill in the Art
`The level of ordinary 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)).
`
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`Petitioner contends that the definition of a person of ordinary skill in
`the art offered by Patent Owner in the ’1795 IPR, which, as noted above,
`also involved the ’086 patent, should apply to this proceeding, namely
`“someone with a Ph.D. in biochemistry or similar field in the pharmaceutical
`sciences, with familiarity and experience with pharmacokinetics.” Pet. 33.
`Patent Owner does not dispute Petitioner’s definition and, indeed, Patent
`Owner’s expert, Dr. Amiji, used the same definition in his analysis. Ex. 2014
`¶ 21. For purposes of this Decision, therefore, we adopt Petitioner’s
`description.
`We also note that the applied prior art reflects the appropriate level of
`skill at the time of the claimed invention and supports Petitioner’s definition.
`See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001).
`E. Claim Construction
`We interpret a claim “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. § 42.100(b) (2020). Under this standard, we construe the
`claim “in accordance with the ordinary and customary meaning of such
`claim as understood by one of ordinary skill in the art and the prosecution
`history pertaining to the patent.” Id. Furthermore, we need only construe the
`claims to the extent necessary to determine the patentability of the
`challenged claims. See Nidec Motor Corp. v. Zhongshan Broad Ocean
`Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017) (“[W]e need only construe
`terms ‘that are in controversy, and only to the extent necessary to resolve the
`controversy . . . .’” (quoting Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200
`F.3d 795, 803 (Fed. Cir. 1999))).
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`The parties have proposed constructions for three terms:
`“pharmaceutical composition comprising nicotinamide riboside”; “carrier”;
`and “isolated.” We address each of these terms in turn.
`1. Pharmaceutical Composition
`Both Petitioner and Patent Owner argue that we should adopt the
`same construction for this term as we did in the ’1795 IPR. Pet. 35–36;
`Prelim. Resp. 28. Absent any argument or evidence to the contrary, we apply
`the same construction in this proceeding that we applied in the ’1795 IPR for
`the reasons set forth in that proceeding: “a composition, including a food
`composition, which contains NR as an active agent in an amount effective
`for the treatment or prevention of a disease or condition associated with the
`nicotinamide riboside kinase pathway of NAD+ biosynthesis.” Ex. 1018,
`10–11.
`
`2. Carrier
`Both Petitioner and Patent Owner argue that we should adopt the
`same construction for this term as we did in the ’1795 IPR. Pet. 36; Prelim.
`Resp. 29. Absent any argument or evidence to the contrary, we apply the
`same construction in this proceeding that we applied in the ’1795 IPR for the
`reasons set forth in that proceeding: “[A] liquid or solid filler, diluent,
`excipient, or solvent encapsulating material, [that] is involved in carrying or
`transporting the subject compound from one organ, or portion of the body, to
`another organ, or portion of the body. Each carrier must be acceptable in the
`sense of being compatible with the other ingredients of the formulation and
`not injurious to the patient.” Ex. 1018, 14–15.
`3. Isolated
`Initially, both Petitioner and Patent Owner argued that we should
`adopt the same construction for the term “isolated” NR as we did in the
`
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`IPR2021-00268
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`’1795 IPR. Pet. 36–38; Prelim. Resp. 30–31. In our Decision to Institute, we
`adopted the construction we applied in the ’1795 IPR proceeding “the
`nicotinamide riboside is separated or substantially free from at least some of
`the other components associated with the source of the molecule such that it
`constitutes at least 25% (w/w) of the composition.” Dec. 19.
`In its Response, however, Patent Owner contends we need to construe
`the entire phrase “is isolated from a natural or synthetic source” and that the
`term should be given its plain and ordinary meaning. PO Resp. 32–33.
`Patent Owner contends that the ordinary meaning is that the NR is isolated
`from the source. Id. at 33. Patent Owner contends that this term requires an
`isolation or separation step that is distinct from an isolation step used as part
`of the manufacture of the synthetic product. See Sur-Reply 17–18; Ex. 1027
`55.
`
`Petitioner responds that the term does not require a separate isolation
`step after manufacture of the synthetic product and that the limitation is met
`if the NR is 25% pure. Reply 14–15.
`We have considered the arguments presented by the parties, and find
`that our initial construction is proper for the reasons set forth in the ’1795
`proceeding. Ex. 1018 12–14. We decline to adopt Patent Owner’s
`construction that calls for an isolation step separate from the process used to
`manufacture synthetic NR.
`The Specification of the ’086 patent teaches the following relating to
`the isolation of NR:
`Synthetic sources of nicotinamide riboside can include
`any library of chemicals commercially available from most
`large chemical companies including Merck, Glaxo, Bristol
`Meyers Squibb, Monsanto-Searle, Eli Lilly and Pharmacia.
`Natural sources which can be treated for the presence of a
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`nicotinamide riboside include, but are not limited to, cow’s
`milk, serum, meats, eggs, fruit and cereals. Isolated extracts of
`the natural sources can be prepared using standard methods. For
`example, the natural source can be ground or homogenized in a
`buffered solution, centrifuged to remove cellular debris, and
`fractionated to remove salts, carbohydrates, polypeptides,
`nucleic acids, fats and the like before being tested on the
`mutant[] strains of the invention. Any source of nicotinamide
`riboside that scores positively in the assay of the invention can
`be further fractionated and confirmed by standard methods of
`HPLC and mass spectrometry.
`Ex. 1001, 26:64–27:12. This teaching suggests that isolating NR is nothing
`more than simply separating or rendering it substantially free from any
`amount of the other components of the naturally occurring source. Although
`we recognize that the Specification only expressly indicates the percentage
`of purity upon which we rely for the definition of “is isolated”—at least 25%
`(w/w) of the composition—as being applied to polypeptides, Ex. 100 col. 9,
`ll. 10–12, we find that the same minimum percentage is also appropriate for
`the measure of isolation of NR. In the context of the ’086 patent, we find no
`reason why one skilled in the art would have viewed the term “isolated”
`differently for nucleic acids than for polypeptides.
`We do not discern any teaching in the ’086 patent of an isolation step
`that is separate from the manufacture of synthetic NR as suggested by Patent
`Owner and its expert Dr. Amiji. See PO Resp. 43–44; Ex. 2014 ¶ 65. The
`’086 patent teaches that the NR can be chemically synthesized using
`established methods (Tanimori (2002) Bioorg. Med. Chem. Lett. 12:1135-
`1137; Franchetti (2004) Bioorg. Med. Chem. Lett. 14:4655-4658).” Ex. 1001
`col. 28, ll. 18–21. These two references cited in the ’086 patent both teach an
`isolation step to separate the synthetically manufactured NR from residual
`starting materials and reaction by products. Ex. 1010, 4656; Ex. 1014, 1136.
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`Patent Owner argues that the isolation step of Franchetti does not
`meet the requirement of claim 2 in that the synthetically manufactured NR is
`not isolated from a “source.” See PO Resp. 43–45. We do not agree with
`Patent Owner’s interpretation. The ’086 patent states “[a]ny source of
`nicotinamide riboside that scores positively in the assay of the invention can
`be further fractionated and confirmed by standard methods of HPLC and
`mass spectrometry.” Ex. 1001, col. 27, ll. 9–12. Thus, a “source” of NR is
`something that has detectable amounts of NR that can be further
`fractionated.
`The reaction scheme taught by Franchetti produces a reaction mixture
`that produces NR, along with remaining starting materials and reaction by-
`products, components associated with the synthesis of NR. See Ex. 1010,
`4656. We find the reaction mixture of Franchetti to be a source of NR as the
`term is used in claim 2. This is consistent with the position taken by Patent
`Owner in the Elysium litigation, where Patent Owner argued that “a
`compound produced by a synthetic reaction, from which NR can be isolated,
`is, by definition, a ‘synthetic source’ of NR. The NR that is subsequently
`isolated from the result of that synthetic reaction would be both ‘chemically
`synthesized’ and ‘isolated from a natural or synthetic source.’” Ex. 2008,
`45–46.
`Patent Owner’s contention that a separate isolation step is
`subsequently required post manufacture of synthetic NR appears
`inappropriately redundant and not in keeping with the plain and ordinary
`meaning of “is isolated from a natural or synthetic source.” Such a
`subsequent isolation step would require one attempting to practice the
`invention recited in claim 2 to run NR though a purification step even if the
`NR were purchased from a manufacturer of NR who certified the NR to be
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`99% pure. See Tr. 60–61. This cannot be the result of the plain and ordinary
`meaning of “is isolated from a natural or synthetic source.” See Eon Corp.
`IP Holdings v. Silver Springs Networks, 815 F.3d 1314, 1321 (Fed. Cir.
`2016) (Court rejected construction “untethered to the contest of the
`invention.”).
`Based on the foregoing, we decline to adopt Patent Owner’s
`construction and apply the construction recited in our Decision to Institute.
`F. Ground 1 – Anticipation by Stamler
`Petitioner contends that claim 2 is anticipated by Stamler. Pet. 38.
`Patent Owner disagrees. PO Resp. 39.
`1. Stamler
`Stamler discloses a method for modulating nitric oxide bioactivity in a
`patient by inhibiting the enzyme glutathione-dependent formaldehyde
`dehydrogenase. Ex. 1006, 1–2; Ex. 1002 ¶ 48. Stamler discloses that
`inhibiting glutathione-dependent formaldehyde dehydrogenase benefits
`patients with breathing disorders (e.g., asthma, cystic fibrosis, and ARDS),
`heart disease, hypertension, ischemic coronary syndromes, atherosclerosis