Trials@uspto.gov
`571-272-7822
`
`Paper No. 39
`Entered: January 16, 2019
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`ELYSIUM HEALTH INC.,
`Petitioner,
`
`v.
`
`TRUSTEES OF DARTMOUTH COLLEGE,
`Patent Owner.
`____________
`
`Case No. IPR2017-01795
`Patent 8,383,086 B2
`____________
`
`Before SUSAN L.C. MITCHELL, CHRISTOPHER G. PAULRAJ, and
`JOHN E. SCHNEIDER, Administrative Patent Judges.
`
`SCHNEIDER, Administrative Patent Judge.
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`THORNE - EXHIBIT 1018
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`I.
`
`INTRODUCTION
`
`A. Background
`Elysium Health Inc. (“Petitioner”) filed a Petition requesting inter
`partes review of claims 1–5 of U.S. Patent No. 8,383,086 B2 (“the ’086
`patent”). Paper 1 (“Pet.”). The Trustees of Dartmouth College (“Patent
`Owner”) filed a Preliminary Response contending that the Petition should be
`denied as to all the challenged claims. Paper 8 (“Prelim. Resp.”). We
`determined, based on the information presented in the Petition and
`Preliminary Response, that there was a reasonable likelihood that Petitioner
`would prevail in challenging claims 1 and 3–5 as unpatentable under
`35 U.S.C. § 102(a). Pursuant to 35 U.S.C. § 314, the Board instituted trial
`on January 29, 2018, as to those claims. Paper 9 (“Institution Decision,
`“Dec.”).
`On April 24, 2018, the Supreme Court of the United States held that a
`final written decision under 35 U.S.C. § 318(a) must decide the patentability
`of all claims challenged in the petition. SAS Inst., Inc. v. Iancu, 138 S. Ct.
`1348, 1359–60 (2018). On April 26, 2018, the Office issued Guidance on
`the Impact of SAS on AIA Trial Proceedings,1 which states that “if the
`PTAB institutes a trial, the PTAB will institute on all challenges raised in
`the petition.” The Guidance also states that, for pending trials, the panel
`may issue an order supplementing the institution decision to institute on all
`challenges raised in the petition. Id.
`On April 27, 2018, pursuant to the Supreme Court’s decision in SAS
`and the Guidance provided by the USPTO, we issued an Order Relating to
`
`1 See https://www.uspto.gov/patents-application-process/patent-trial-and-
`appeal-board/trials/guidance-impact-sas-aia-trial (“Guidance”).
`2
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`the Conduct of the Proceedings modifying our institution decision to
`institute on all of the challenged claims and all of the grounds in the petition.
`Paper 22 (“Modified Institution Decision”).
`Patent Owner, Trustees of Dartmouth College, filed a Motion for
`Rehearing of our modified Decision to Institute Inter Partes Review as set
`forth in our April 27, 2018, Order Relating to the Conduct of the Proceeding.
`Paper 24. On September 5, 2018, we denied Patent Owner’s Motion for
`Rehearing. Paper 36.
`Patent Owner filed its Response to the Petition on June 4, 2018, Paper
`28 (“Response”), and Petitioner filed its Reply to Patent Owner’s response
`on August 22, 2018, Paper 33 (“Reply”). An oral hearing was held on
`October 2, 2018. The transcript of the hearing has been entered into the
`record. Paper 38 (“Tr.”).
`We have jurisdiction under 35 U.S.C. § 6. Petitioner bears the burden
`of proving unpatentability of the challenged claims, and that burden of
`persuasion never shifts to Patent Owner. Dynamic Drinkware, LLC v. Nat’l
`Graphics, Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015). To prevail, Petitioner
`must prove unpatentability by a preponderance of the evidence. See
`35 U.S.C. § 316(e); 37 C.F.R. § 42.1(d). This Final Written Decision is
`issued pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73. For the
`reasons that follow, we determine that Petitioner has shown by a
`preponderance of the evidence that claims 1 and 3–5 of the ’086 patent are
`unpatentable, but has not shown that claim 2 of the ’086 patent is
`unpatentable. See 35 U.S.C. § 316(e).
`
`
`B. Related Proceedings
`
`
`
`3
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`
`Petitioner represents that the ’086 patent is at issue in ChromaDex,
`Inc., v Elysium Health, Inc., Case No. 16-cv-02277-KES (C.D. Cal.).
`Pet. 30. Petitioner also represents that a petition for inter partes review has
`been filed challenging related patent U.S. Patent No. 8,197,807 in IPR2017-
`01796. Id. We denied institution of inter partes review of the petition in
`IPR2017-01796. Elysium Health, Inc. v. Trustees of Dartmouth College,
`Case IPR 2017-01795 (PTAB Jan. 18, 2018) (Paper 9).
`
`C. The ’086 Patent
`The ’086 patent issued on February 26, 2013, with Charles M.
`Brenner listed as the inventor. Ex. 1001, (45) (75). The ’086 Patent issued
`from an application filed on April 12, 2012, and claims priority to an
`application filed April 20, 2006. Id. (63). The parties have not disputed the
`claimed priority date for the ’086 Patent. Pet. 8 (addressing qualification as
`prior art according to the “earliest possible priority date” of the ’086 patent),
`19 (same).
`The ’086 Patent relates generally to the production of nicotinamide
`riboside (“NR”) and compositions containing NR. Ex. 1001, col. 4, ll. 1–16.
`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 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. Ex.
`1001, col. 4, ll. 14–16, col. 29, ll. 43–46.
`D. Illustrative Claim
`Petitioner challenges claims 1–5 of the ’086 Patent. Independent
`claim 1 is illustrative, and is reproduced below:
`
`
`
`4
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`
`1. A pharmaceutical composition comprising nicotinamide
`riboside in admixture with a carrier, wherein said
`composition is formulated for oral administration.
`Ex. 1001, col. 53, ll. 38–40.
`E. The Alleged Grounds of Unpatentability
`Petitioner challenges the patentability of all of the claims of the ’086
`patent based on the following grounds:
`References
`Basis
`Goldberger et al.2
`35 U.S.C. § 102
`Goldberger and Tanner3 35 U.S.C. § 102
`
`
`Claims Challenged
`1–5
`1–5
`
`Petitioner further relies on the declaration of Joseph A. Baur, Ph.D.
`Ex. 1002. Patent Owner relies on the declaration of Zhaohui Sunny Zhou,
`Ph.D. Ex 2002.
`
`II. ANALYSIS
`
`A. Claim Construction
`For petitions filed prior to November 13, 2018,
` [a] claim in an unexpired patent that will not expire before a final
`written decision is issued shall be given its broadest reasonable construction
`in light of the specification of the patent in which it appears.” 37 C.F.R.
`
`
`2 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. HEATH REPORTS 1385 (1928) (“Goldberger et
`al.”). Ex. 1005.
`3 Goldberger and Tanner, A Study of the Treatment and Prevention of
`Pellagra, 39 PUB. HEALTH REPORTS 87 (1924) (“Goldberger and Tanner”).
`Ex. 1006.
`
`
`
`5
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`§ 42.100(b).4 When applying that standard, we interpret the claim language
`as it should be understood by one of ordinary skill in the art in light of the
`specification. In re Suitco Surface, Inc., 603 F.3d 1255, 1260 (Fed. Cir.
`2010). Under this standard, we interpret claim terms using “the broadest
`reasonable meaning of the words in their ordinary usage as they would be
`understood by one of ordinary skill in the art, taking into account whatever
`enlightenment by way of definitions or otherwise that may be afforded by
`the written description contained in the applicant’s specification.” In re
`Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997). “Under a broadest reasonable
`interpretation, words of the claim must be given their plain meaning, unless
`such meaning is inconsistent with the specification and prosecution history.”
`Trivascular, Inc. v. Samuels, 812 F.3d 1056, 1062 (Fed. Cir. 2016). Only
`terms that are in controversy need to be construed and only then to the extent
`necessary to resolve the controversy. Vivid Techs., Inc. v. Am. Sci. & Eng’g,
`Inc., 200 F.3d 795, 803 (Fed. Cir. 1999).
`1. Pharmaceutical Composition
`Claim 1 recites a “pharmaceutical composition comprising
`nicotinamide riboside . . . formulated for oral administration.” Ex. 1001,
`col. 53, ll. 38–40. Claim 3 reads “[t]he pharmaceutical composition of claim
`1, wherein the formulation comprises a tablet, troche, capsule, elixir,
`suspension, syrup, wafer, chewing gum, or food.” Ex. 1001, col. 53, ll. 44–
`
`4 The Final Rule changing the claim construction standard to the federal
`court claim construction standard that is used to construe a claim in a civil
`action under 35 U.S.C. § 282(b) does not apply here as the Petitioner was
`filed before the effective date of the Final Rule, November 13, 2018. See
`Changes to the Claim Construction Standard for Interpreting Claims in Trial
`Proceedings Before the Patent Trial and Appeal Board, 83 Fed. Reg. 51,340,
`51,340, 51,344 (Oct. 11, 2018).
`
`
`
`6
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`46.In our Institution Decision, we agreed with and adopted Petitioner’s
`proposal that the term “pharmaceutical composition” should include food
`products, as that construction is supported by the language of claim 3 and
`disclosure in the Specification of the ’086 patent. Dec. 5.
`a. Food as a “Pharmaceutical Composition”
`Patent Owner renews its argument that the term “pharmaceutical
`composition” should not be construed to include foods, and proposes its own
`construction of the term “pharmaceutical composition comprising
`nicotinamide riboside” as “a composition containing nicotinamide riboside
`as the active agent.” Resp. 8–16.
`As discussed in our Institution Decision, both the Specification and
`claims clearly teach that the claimed pharmaceutical composition can be a
`food. The Specification teaches:
`For oral therapeutic administration, the compound can be
`combined with one or more carriers and used in the form of
`ingestible tablets, buccal tablets, troches, capsules, elixirs,
`suspensions, syrups, wafers, chewing gums, foods and the like.
`
`Ex. 1001, col. 29, ll. 43–47 (emphasis added). Claim 3 recites “[t]he
`pharmaceutical composition of claim 1, wherein the formulation comprises a
`tablet, troche, capsule, elixir, suspension, syrup, wafer, chewing gum, or
`food.” Ex. 1001, col. 53, ll. 44–46 (emphasis added.). Thus, as used in the
`’086 patent, we find that the term “pharmaceutical composition”
`encompasses foods.
`
`b. Active Agent
`Patent Owner asks the Board to construe not just the term
`‘pharmaceutical composition” but the term “pharmaceutical composition
`comprising nicotinamide riboside.” Resp. 8. Patent Owner contends that
`7
`
`
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`the term should be construed to mean a pharmaceutical composition where
`NR is the active agent. Id. Patent Owner contends that this construction is
`consistent with the Specification, citing to several portions of the
`Specification teaching that NR is used to treat or prevent various conditions.
`Resp. 9–10. Patent Owner argues that these teachings in the Specification
`would lead one skilled in the art to understand that the pharmaceutical
`composition would include NR as an active agent as opposed to an inactive
`excipient. Id. at 10.
`Petitioner responds that Patent Owner’s proposed construction is
`improper. Reply 2. Petitioner contends that the use of the term
`“comprising” in the claims means that the claim includes, but is not limited
`to, NR as an active agent. Reply 3. Petitioner also argues that it is improper
`to read an active agent limitation into the claims. Reply 8. Petitioner
`contends that the Specification does not support construing the term
`“pharmaceutical composition” to require the presence of an active agent, nor
`does the Specification otherwise support a requirement that NR be the active
`agent in the claimed composition. Reply 6–8.
`We have considered the parties’ arguments, and find that the term
`“pharmaceutical agent” as used in the present claims calls for the presence
`of at least one active agent. As taught by the Specification, pharmaceutical
`composition is a composition which can be used to treat or prevent a disease
`or disorder. See, e.g., Ex. 1001, col. 4, ll. 19–24; col. 31, ll. 42–46. One
`skilled in the art would understand from these teachings in the Specification
`concerning treating or preventing a disease or disorder that a pharmaceutical
`composition is one where at least one component of the composition acts to
`treat or prevent the disease or disorder. Such a component can properly be
`
`
`
`8
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`described as an active agent regardless of whether it is purposefully added to
`the composition.
`Turning to the language of claim 1, the inclusion of “pharmaceutical”
`in the claim phrase “a pharmaceutical composition comprising nicotinamide
`riboside” supports Patent Owner’s argument that the claim phrase refers to a
`composition where NR is an active agent. This interpretation is consistent
`with the Specification as well as the wording of the claim itself. For
`example, the Specification states
`[T]he present invention is a method for preventing or
`treating a disease or condition associated with the nicotinamide
`riboside kinase pathway of NAD+ biosynthesis. The method
`involves administering to a patient having a disease or
`condition associated with the nicotinamide riboside kinase
`pathway of NAD+ biosynthesis an effective amount of a
`nicotinamide riboside composition so that the signs or
`symptoms of the disease or condition are prevented or reduced.
`Ex. 1001, col. 4, ll. 17–24 (emphasis added).
`The Specification also teaches, however, that NR is not the sole active
`agent that may be administered as part of such a composition. The
`Specification teaches that NR can be administered with additional NAD+
`precursors such as tryptophan, nicotinic acid, and nicotinamide. See, e.g.,
`Ex. 1001, col. 4, ll. 27–29; col. 24, ll. 40–48. As Petitioner points out, the
`claims use the open transitional term “comprising” that allows for
`components other than NR for a pharmaceutical composition encompassed
`by the claims. See Pet. 2–4. Thus, we conclude that, when read in light of
`the Specification, the claims do not call for NR to be the sole active agent
`present in the composition, but must be at least one active agent in the
`claimed pharmaceutical compositions.
`
`
`
`9
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`
`Petitioner contends that Patent Owner’s proposed construction would
`render the claims indefinite. Reply 12. Petitioner argues that the
`Specification is silent as to the amount of NR that is needed to effectively
`treat or prevent any disease or disorder and that it would require an undue
`amount of experimentation to determine if NR were acting as an active
`agent. Reply 13–15.
`We find this argument unpersuasive. Although the Specification and
`claims do not recite any specific amount of NR that constitutes an effective
`amount, the Specification does teach
`A physician or veterinarian having ordinary skill in the
`art can readily determine and prescribe the effective amount of
`the pharmaceutical composition required for prevention or
`treatment in an animal subject such as a human, agriculturally-
`important animal, pet or zoological animal.
`
`Ex. 1001, col. 31, ll. 42–46. In addition, the Specification teaches that an
`effective amount of NR is an amount sufficient to treat or prevent a disease
`or condition. See, e.g., Ex. 1001, col. 4, ll. 19–24, col. 27, l. 66 – col. 28, l.
`3. We agree with Patent Owner that, based on these teachings of the
`Specification, one skilled in the art would have been able to identify an
`effective amount of NR for use in a composition. Tr. 62–63. Thus, based on
`the full trial record, we do not find that Patent Owner’s proposed
`construction renders the claim indefinite or otherwise invalid under 35
`U.S.C. § 112.
`Based on the foregoing analysis, we construe the term
`“pharmaceutical composition” to be a composition, including a food
`composition, which contains NR as an active agent in an amount effective
`
`
`
`10
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`for the treatment or prevention of a disease or condition associated with the
`nicotinamide riboside kinase pathway of NAD+ biosynthesis.
`
`
`
`11
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`
`2. Is Isolated
`Claim 2 recites the limitation that the NR “is isolated from a natural or
`synthetic source.” Ex. 1001, col. 53, ll. 41–44. In our Institution Decision,
`we construed the term 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.” Dec. 9. We determined that the term “isolated,” as used
`in the Specification, embraces compositions containing NR where only some
`of the other components of the naturally occurring organism are removed.
`Dec. 8; Ex. 1001, col. 9, ll. 3–10. We also determined that the Specification
`provides guidance as to how pure a molecule needed to be to be deemed
`“isolated,” and that one skilled in the art would have understood that in the
`context of the ’086 patent, “isolated” refers to a molecule that is at least 25%
`pure (w/w). Dec. 8. Although the Specification discusses this level of
`purity with respect to proteins, we determined that one skilled in the art
`would have understood that this level of purity extends to other types of
`“isolated” molecules referenced in the Specification, including NR. Id.
`In its Reply, Petitioner urges us to reconsider our construction of the
`term “is isolated.” Reply 17. Petitioner contends our construction is based
`on a misreading of the Specification. Id. Petitioner argues that the teaching
`of 25% purity only applies to peptides and not to other molecules such as
`NR. Reply 17. Petitioner urges us to adopt its broader proposed
`construction–“separated or substantially free from at least some of the other
`components of the naturally occurring organism.” Reply 18.
`Patent Owner contends that Petitioner’s proposed construction is
`unreasonably broad in that it would encompass milk when simply removed
`
`
`
`12
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`from a cow. Resp. 18. Patent Owner agrees with the Board’s analysis set
`forth in our Decision on Institution that Petitioner’s proposed construction
`would encompass compositions where even an insignificant amount of
`additional components have been removed. Id (citing Dec. 8–9).
`We have considered Petitioner’s and Patent Owner’s arguments and
`we see no need to alter our previous construction in light the full trial record.
`As we noted in our Institution Decision, construing the term “is isolated” as
`suggested by Petitioner would render the term unreasonably broad in that it
`would encompass separation of even an insignificant amount of other
`components. Dec. 8–9. The teachings in the Specification of the ’086
`patent counsel against such a broad construction when defining the term
`“isolated” with respect to 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
`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.
`
`
`
`13
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`Ex. 1001, 26:64–27:12. This teaching suggests that isolating NR is more
`than simply separating or rendering it substantially free from any amount of
`the other components of the naturally occurring organism. 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, the percentage
`of purity upon which we rely for the definition of “is isolated”—at least 25%
`(w/w) of the composition—in light of the complete disclosure of the
`Specification of the ’086 patent we find in light of the complete disclosure of
`the Specification of the ’086 patent 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.
`For the reasons set forth above and in our Institution Decision, we
`construe the term “is isolated” as used in the ’086 patent 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.”
`
`3. Carrier
`In our Institution Decision we construed the term “carrier” to mean
`
` 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.
`
`
`
`
`14
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`Dec. 6–7. The parties have not challenged this construction during trial.
`Response 6–19; Reply 2–18. We find no reason in view of the full trial
`record before us to revise this construction and apply it in our analysis in this
`final decision.
`
`B. Anticipation
`“Anticipation requires that all of the claim elements and their
`limitations are shown in a single prior art reference.” In re Skvorecz, 580
`F.3d 1262, 1266 (Fed. Cir. 2009). “A single prior art reference may
`anticipate without disclosing a feature of the claimed invention if such
`feature is necessarily present, or inherent, in that reference.” Allergan, Inc.
`v. Apotex Inc., 754 F.3d 952, 958 (Fed. Cir. 2014).
`“Inherency may not be established by probabilities or possibilities.
`The mere fact that a certain thing may result from a given set of
`circumstances is not sufficient to establish inherency.” Scaltech Inc. v.
`Retec/Tetra L.L.C., 178 F.3d 1378, 1384 (Fed. Cir. 1999) (citations omitted).
`A product is inherently anticipated where it is the natural result of the
`prior art process, even though it would be possible to prevent the formation
`of the product through extraordinary measures. See Allergan, 754 F.3d at
`961.
`
`1. Goldberger et al.
`Goldberger et al. discloses a study of foodstuffs for the prevention of
`blacktongue in dogs. Ex. 1005, 1385. Blacktongue is a canine condition
`similar to pellagra in humans. Id. at 1385–86. Like pellagra, blacktongue is
`caused by a deficiency of NAD+. Ex. 1010, 2. In the study, dogs were fed a
`blacktongue producing diet along with several candidates for preventing
`blacktongue. Ex. 1005, 1387–88. Among the candidates evaluated by
`15
`
`
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`Goldberger et al. was milk, including skim milk. Id. at 1402–05.
`Goldberger et al. concluded that skim milk exercised a blacktongue
`preventative action. Id. at 1404.
`Subsequent research has shown that one of the components in milk is
`nicotinamide riboside, a precursor of NAD+. Ex. 1007, 3 (Table 1), 5
`(Table 3); Ex. 1008, 2 (milk a source of NR); Ex 1018, 838 (NR is found in
`milk); Ex. 1023, 22 (humans exposed to NR via dietary sources such as
`milk). Later studies also show that nicotinamide riboside increases the
`biosynthesis of NAD+. Ex. 1008, 6; Ex. 1018, 840.
`Petitioner contends that all of the limitations of the claims of the ’086
`patent are disclosed by Goldberger et al. Pet. 8–18. Patent Owner contends
`that Goldberger et al. does not anticipate any of the claims of the ‘086
`patent. Resp. 20–30.
`Based on the full trial record before us, we conclude that Petitioner
`has established by a preponderance of the evidence that claims 1 and 3–5 are
`anticipated by Goldberger et al. A preponderance of the evidence, however,
`does not support the conclusion that claim 2 is anticipated by Goldberger et
`al.
`
`a. Claim 1
`Claim 1 is directed to a pharmaceutical composition comprising
`nicotinamide riboside in admixture with a carrier and formulated for oral
`administration. We consider each of these claim limitations in turn.
`
`
`
`16
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`
`i.
`
` Pharmaceutical Composition comprising nicotinamide
`riboside
`We have construed the term pharmaceutical composition comprising
`nicotinamide riboside to mean a composition, including food, which
`contains NR as an active agent. See supra Section II.A.1.
`Petitioner contends that Goldberger et al. established that skim milk
`can be used to treat blacktongue, which is associated with a deficiency of
`NAD+. Pet. 11–12. Petitioner points to evidence in the record that NR is
`present in milk and is bioavailable. Pet. 12 (citing Ex. 1005, 1402–03;
`Ex. 1002 ¶ 31); Reply 19–23. Petitioner contends that the skim milk used by
`Goldberger et al. meets the claim limitations of a “pharmaceutical
`composition comprising [NR].” Pet. 12; Reply 20–23.
`Patent Owner contends that Petitioner has not established that the
`skim milk used by Goldberger et al. constitutes a pharmaceutical
`composition containing NR as an active agent. Resp. 20. Patent Owner
`contends that Goldberger et al. is silent as to the presence of NR in the skim
`milk used and argues that Petitioner has not put forward any evidence that
`the milk used by Goldberger et al. contained NR. Resp. 23.
`Patent Owner also argues that there is no evidence that the NR present
`in milk is active. Resp. 23. Patent Owner points to the teachings of
`Trammell I where it states that the NR in milk is bound to other molecules in
`milk to support its contention that the NR in milk is not active. Resp. 23;
`Ex. 1007, 2; see Ex 2002 ¶ 32. Patent Owner contends that Petitioner has
`not shown that the skim milk used by Goldberger et al. was not degraded by
`naturally occurring bacteria such that any NR present was eliminated or
`reduced to a level where it was ineffective. Resp. 23.
`
`
`
`17
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`
`Patent Owner also contends that the skim milk used by Goldberger et
`al. is not a pharmaceutical composition. Resp. 21–22. Patent Owner
`contends that not all food qualifies as a pharmaceutical composition since a
`pharmaceutical composition must contain an active agent. Resp. 22. Patent
`Owner argues that since there is no evidence that the NR in milk is active,
`Petitioner has not shown that the skim milk of Goldberger et al. is a
`pharmaceutical composition under the proper claim construction. Resp. 22.
`We have considered the parties’ arguments as well as the evidence of
`record and conclude Petitioner has established by a preponderance of the
`evidence that the skim milk administered by Goldberger et al. is a
`“pharmaceutical composition” as we have construed that term.
`Goldberger et al. report an experiment to determine if skim milk is
`effective in preventing blacktongue. Ex. 1005, 1404. Black tongue is
`caused by a deficiency of NAD+. Ex 1010, 2. Dr. Baur interprets the
`results of the experiment as establishing that milk alone improves the course
`of or prevents blacktongue. Ex. 1002 ¶ 21. Thus, the skim milk used by
`Goldberger et al. was administered to dogs “having a disease or condition
`associated with the nicotinamide riboside kinase pathway of NAD+
`biosynthesis . . . such that the signs or symptoms of the disease are
`prevented or reduced” by the Goldberger’s administration of the skim milk.
`Ex. 1001, col. 4, ll. 20–24.
`As we previously addressed, Patent Owner’s contention that foods are
`not pharmaceutical compositions is unpersuasive. Although we agree with
`Patent Owner that not all foods are necessarily pharmaceutical compositions,
`the Specification of the ’086 patent expressly teaches that the
`pharmaceutical composition of the present invention can include food. Ex.
`
`
`
`18
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`1001, col. 28, ll. 43–47, col. 53, ll. 44–46 (claim 3). In particular, where the
`food contains an active agent useful in treating or preventing a disease or
`condition associated with the nicotinamide riboside kinase pathway of
`NAD+ biosynthesis, we find it meets the definition of a pharmaceutical
`composition as that term is used in the challenged claims. See Tr.; 48; Ex.
`1018, 1 (NR is found in milk constituting a dietary source or NAD+
`production) and Ex. 1008 2 (NR improves wellness and treats diseases).
`Given that a food, such as the skim milk used by Goldberger et al. can
`be a pharmaceutical agent, there remains the questions of whether NR was
`necessarily present in Goldberger’s skim milk and whether such NR was
`necessarily active in the manner required by our claim construction.
`Patent Owner contends that while some of the references of record
`show that NR is present in milk, those references are all dated well after the
`Goldberger et al. study was published. Tr. 69. Patent Owner argues that
`there is nothing in the present record that shows that NR was present in the
`milk used by Goldberger et al or that it was active. Resp. 22–23.
`We have considered Patent Owner’s arguments and find that there is
`sufficient evidence in the present record to establish that NR was necessarily
`present in the skim milk used by Goldberger et al.
`Trammell I reports a study on the concentration of NR in milk.
`Ex. 1007, 1. In the study, both conventional milk and organic milk were
`studied. Id. The researchers in Trammell I reported that both conventional
`milk and organic milk contained NR. Id. The researchers concluded that
`“NR is a major NAD+ precursor in cow milk.” Id.
`
`
`
`19
`
`

`

`IPR2017-01795
`Patent 8,383,086 B2
`
`
`Trammell II reports a study of the bioavailability of NR taken orally.
`Ex. 1008, 1. In the background discussion, the researchers report that milk
`is a source of such NR. Id. at 2.
`Canto reports a study using NR to enhance oxidative metabolism and
`protect against high fat induced obesity. Ex. 1018, 838. In the introduction,
`Canto states that “NR is found in milk . . . constituting a dietary source for
`NAD+ production.” Id.
`Bogan, a literature review of NAD+ precursors, teaches that “NR is a
`newly discovered salvageable precursor of NAD+ that occurs in cow’s
`milk.” Ex. 1025, 119. Bogan also teaches that milk is a source of NR in
`vertebrates. Id. at 120. Bogan goes on to teach that milk, a natural source of
`NR, was shown to be effective in treating pellagra-like symptoms in
`animals. Id. at 121–122 (citing Ex. 1005)
`A filing with the Food and Drug Administration relating to the safety
`of an NR supplement Niagen teaches that “[h]umans are exposed to NR via
`dietary sources such as milk.” Ex. 1023, 22.
`Dr. Baur states in his declaration:
`As it is now known that blacktongue in dogs is a disease
`caused by NAD+ deficiency, it follows that the resolution or
`prevention of blacktongue by milk supplementation, as shown
`in Goldberger et al., is direct evidence that the milk stimulated
`greater NAD+ biosynthesis upon oral administration. (Ex.
`1005, Goldberger et al., at 1404.) This conclusion is confirmed
`by later studies, discussed above in