IPR2017-01796
`
`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 IPR2017-01796
`
`Patent 8,197,807
`_______________
`
`PRELIMINARY RESPONSE TO PETITION FOR INTER PARTES
`REVIEW OF U.S. PATENT NO. 8,197,807
`
`THORNE - EXHIBIT 1026
`
`

`

`
`
`IPR2017-01796
`
`2.
`
`3.
`
`TABLE OF CONTENTS
`
`I.
`INTRODUCTION ........................................................................................... 1
`BACKGROUND ............................................................................................. 3
`II.
`III. CLAIM CONSTRUCTION ............................................................................ 5
`A.
`“isolated” Terms (Claims 1, 2) .............................................................. 6
`1.
`Patent Owner’s Proposed Constructions Are Consistent
`With The Specification ............................................................... 7
`Patent Owner’s Proposed Constructions Are Consistent
`With The Claims ....................................................................... 12
`Petitioner’s Proposed Constructions Should Not
`Be Adopted ............................................................................... 14
`IV. PETITIONER HAS NOT DEMONSTRATED “A REASONABLE
`LIKELIHOOD OF PREVAILING” AGAINST AT LEAST ONE CLAIM
`OF THE ’807 PATENT UNDER 35 U.S.C. § 314(a) .................................. 19
`A. Ground 1: Petitioner Has Not Demonstrated A “Reasonable
`Likelihood Of Prevailing” As To Claims 1-3 Over
`Goldberger et al. .................................................................................. 20
`1.
`Goldberger et al. Does Not Disclose “isolated nicotinamide
`riboside” .................................................................................... 20
`Goldberger et al. Does Not Disclose Isolated Nicotinamide
`Riboside “in admixture with a carrier” ..................................... 22
`Goldberger et al. Does Not Disclose A Composition That
`“increases NAD+ biosynthesis upon oral administration” ....... 24
`Goldberger et al. Does Not Disclose Nicotinamide Riboside
`“isolated from a natural or synthetic source” ............................ 26
`B. Ground 2: Petitioner Has Not Demonstrated A “Reasonable
`Likelihood Of Prevailing” As To Claims 1-3 Over Goldberger
`and Tanner ........................................................................................... 28
`
`2.
`
`3.
`
`4.
`
`

`

`1.
`
`IPR2017-01796
`
`Goldberger and Tanner Does Not Disclose “isolated
`nicotinamide riboside” .............................................................. 28
`Goldberger and Tanner Does Not Disclose Isolated
`Nicotinamide Riboside “in admixture with a carrier” .............. 30
`Goldberger and Tanner Does Not Disclose A
`Composition That “increases NAD+ biosynthesis
`upon oral administration” ......................................................... 32
`Goldberger and Tanner Does Not Disclose Nicotinamide
`Riboside “isolated from a natural or synthetic source” ............ 34
`CONCLUSION .............................................................................................. 37
`
`2.
`
`3.
`
`4.
`
`
`
`V.
`
`
`

`

`
`
`IPR2017-01796
`
`The Trustees of Dartmouth College (“Patent Owner”) respectfully submit
`
`this Preliminary Response to the Petition seeking inter partes review of U.S. Patent
`
`No. 8,197,807 (Ex. 1001, “the ’807 patent”) filed by Elysium Health, Inc.
`
`(“Petitioner”). This Response is timely under 35 U.S.C. § 313 and 37 C.F.R. §
`
`42.107 because it is within three months of the August 5, 2017 date of the Notice
`
`granting the Petition a filing date. Paper No. 3, Notice of Filing Date, at 1.
`
`I.
`
`INTRODUCTION
`
`Patent Owner respectfully submits that inter partes review of the ’807 patent
`
`should not be instituted because Petitioner has failed to demonstrate that it has a
`
`reasonable likelihood of prevailing with respect to any of the challenged claims of
`
`the ’807 patent.
`
`First, Petitioner has not provided any evidence that either of its prior art
`
`references of the proposed Grounds discloses the essential claim element of
`
`“isolated nicotinamide riboside” as claimed in independent claim 1 of the ’807
`
`patent. Petitioner instead relies on an improper claim construction and expert
`
`testimony for the inapposite conclusion that nicotinamide riboside present in milk
`
`or buttermilk is “isolated” when milk is removed from a cow. Because neither
`
`prior art reference of the proposed Grounds discloses isolated nicotinamide
`
`riboside like that claimed in the ’807 patent, Petitioner cannot establish that the
`
`references anticipate the claims of the ’807 patent.
`
`1
`
`

`

`
`
`IPR2017-01796
`
`Second, Petitioner has not provided any evidence that either of its prior art
`
`references of the proposed Grounds discloses the essential claim element of a
`
`composition of isolated nicotinamide riboside that “increases NAD+ biosynthesis
`
`upon oral administration,” as required by independent claim 1 of the ’807 patent.
`
`Petitioner instead relies on an argument regarding milk that was already considered
`
`by the Examiner and overcome during prosecution, which is a sufficient basis for
`
`the Board to exercise its discretion under 35 U.S.C. § 325(d) and deny institution.
`
`Third, Petitioner has not provided any evidence that either of its prior art
`
`references of the proposed Grounds discloses the essential claim element of the
`
`isolated nicotinamide riboside “in admixture with a carrier” as claimed in
`
`independent claim 1 of the ’807 patent. Because neither prior art reference of the
`
`proposed Grounds discloses nicotinamide riboside in admixture with a carrier like
`
`that claimed in the ’807 patent, Petitioner cannot establish that the references
`
`anticipate the claims of the ’807 patent.
`
`Fourth, Petitioner has not provided any evidence that either of its prior art
`
`references of
`
`the proposed Grounds discloses compositions comprising
`
`nicotinamide riboside that “is isolated from a natural or synthetic source,” as
`
`required by claim 2 of the ’807 patent. Petitioner again relies on an improper
`
`claim construction and questionable expert testimony for its argument that
`
`nicotinamide riboside present in milk or buttermilk is “isolated” from a natural
`
`2
`
`

`

`
`
`IPR2017-01796
`
`source when milk is removed from a cow. Because neither prior art reference
`
`discloses nicotinamide riboside isolated from a natural or synthetic source as in
`
`claim 2 of the ’807 patent, Petitioner cannot establish that the references anticipate
`
`claim 2 of the ’807 patent.
`
`For at least these reasons, the institution of an inter partes review of the ’807
`
`patent should be denied.
`
`II. BACKGROUND
`
`The ’807 patent is directed to compositions of isolated nicotinamide riboside
`
`formulated in admixture with a carrier that increase NAD+ biosynthesis upon oral
`
`administration. See ’807 patent, at claim 1. Increasing NAD+ levels can help to
`
`treat a range of diseases and conditions, including cancer. See, e.g., id. at 7:54-
`
`9:20. As disclosed in the ’807 patent, NAD+ was known to be formed through de
`
`novo synthesis, nicotinic acid import, and nicotinamide salvage. See id. at 2:25-35,
`
`Scheme 1. The ’807 patent inventor, however, discovered that nicotinamide
`
`riboside is an “NAD+ precursor in a previously unknown but conserved eukaryotic
`
`NAD+ biosynthetic pathway,” and that “supplementation with nicotinamide
`
`riboside as [a] third importable NAD+ precursor can be beneficial for certain
`
`conditions.” Id. at 3:3-11, 8:58-60.
`
`The ’807 patent achieves the desired supplementation by isolating
`
`nicotinamide riboside, whether through chemical synthesis or extraction from a
`
`3
`
`

`

`
`
`IPR2017-01796
`
`natural or synthetic source, and formulating the isolated product in admixture with
`
`a carrier for oral administration. As covered by claim 1, these compositions of
`
`isolated nicotinamide riboside “increase[] NAD+ biosynthesis upon oral
`
`administration.” See ’807 patent, at claim 1.
`
`The ’807 patent includes only three claims, and both dependent claims
`
`depend directly from independent claim 1. Specifically, dependent claim 2 covers
`
`the compositions of claim 1 wherein the nicotinamide riboside “is isolated from a
`
`natural or synthetic source.” See ’807 patent, at claim 2. The ’807 patent
`
`specification includes examples of such sources, and further describes methods for
`
`isolating nicotinamide riboside from a natural source such as cow’s milk. See id.
`
`at 27:39-54. Finally, dependent claim 3 covers specific types of oral formulations
`
`of the claim 1 compositions, including “a tablet, troche, capsule, elixir, suspension,
`
`syrup, wafer, chewing gum, or food.” See id. at claim 3.
`
`Contrary to Petitioner’s assertions, the ’807 patent does not claim any
`
`composition found in nature, nor does it claim any inherent properties of any
`
`naturally occurring composition. Instead, the claimed invention of the ’807 patent
`
`covers specific compositions of an isolated molecule (i.e., nicotinamide riboside)
`
`that can increase NAD+ biosynthesis when formulated in admixture with a carrier.
`
`4
`
`

`

`
`
`III. CLAIM CONSTRUCTION
`
`IPR2017-01796
`
`In an inter partes review, claim terms are interpreted according to their
`
`“broadest reasonable construction in light of the specification of the patent in
`
`which it appears.” Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2136
`
`(2016); see also id. at 2144-45; 37 C.F.R. § 42.100(b); Office Patent Trial Practice
`
`Guide, 77 Fed. Reg. 48756, 48764, 66 (Aug. 14, 2012). The broadest reasonable
`
`construction of the terms must be consistent with the patent specification. In re
`
`Suitco Surface, Inc., 603 F.3d 1255, 1259-60 (Fed. Cir. 2010) (“[C]laims should
`
`always be read in light of the specification and teachings in the underlying
`
`patent.”). As the Federal Circuit has explained:
`
`The correct inquiry in giving a claim term its broadest reasonable
`interpretation in light of the specification is not whether the
`specification proscribes or precludes some broad reading of the claim
`term adopted by the examiner. And it is not simply an interpretation
`that is not inconsistent with the specification. It is an interpretation
`that corresponds with what and how the inventor describes his
`invention in the specification, i.e., an interpretation that is “consistent
`with the specification.”
`
`In re Smith, Int’l, Inc., No. 2016-2303, 2017 WL 4247407, at *5 (Fed. Cir. 2017)
`
`(quoting In re Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997)).
`
`The specification should also be considered in light of the express language
`
`of the claims themselves. See Trivascular, Inc. v. Samuels, 812 F.3d 1056, 1062
`5
`
`

`

`
`
`IPR2017-01796
`
`(Fed. Cir. 2016) (“Construing individual words of a claim without considering the
`
`context in which those words appear is simply not ‘reasonable.’”).
`
`The patent prosecution history is also relevant for determining the correct
`
`construction of a disputed term in an inter partes review. See D’Agostino v.
`
`Mastercard Int’l Inc., 844 F.3d 945, 948 (Fed. Cir. 2016) (quoting Microsoft Corp.
`
`v. Proxyconn, Inc., 789 F.3d 1292, 1298 (Fed. Cir. 2015) (stating that “the Board
`
`‘should also consult the patent’s prosecution history in proceedings in which the
`
`patent has been brought back to the agency for a second review’”).
`
`In the absence of a reasonable claim construction, a petitioner cannot show a
`
`reasonable likelihood of success on its grounds for unpatentability. See Microsoft
`
`Corp. v. Proxyconn, Inc., IPR2012-00026, Paper 17 at p. 24 (PTAB Dec. 21, 2012)
`
`(explaining that “[a]s this argument is premised on Petitioner’s erroneous claim
`
`construction we are not persuaded of a reasonable likelihood of prevailing”).
`
`Because Petitioner has not offered a reasonable claim construction of the “isolated
`
`nicotinamide riboside” limitation of independent claim 1 of the ’807 patent,
`
`Petitioner has not demonstrated a reasonable likelihood that it will prevail on its
`
`assertion that the claims are unpatentable.
`
`A.
`
`“isolated” Terms (Claims 1, 2)
`
`Petitioner proposes constructions for “isolated” in independent claim 1 and
`
`“is isolated” in dependent claim 2 that are inconsistent with the claim language and
`
`6
`
`

`

`
`
`IPR2017-01796
`
`patent specification. Petitioner offers essentially the same construction for both
`
`terms based on a single phrase in the specification, but the proposed constructions
`
`ignore the language of the claims and the teachings of the specification. The
`
`“isolated” terms are more properly read in the context of the claims in which they
`
`appear because they are part of broader phrases that provide critical context for the
`
`meaning of each “isolated” term. See Trivascular, Inc., 812 F.3d at 1062
`
`(“Construing individual words of a claim without considering the context in which
`
`those words appear is simply not ‘reasonable.’”).
`
`Accordingly, Patent Owner requests that the Board construe the full phrases
`
`as shown below:
`
`Claim Term
`
`Proposed Construction
`
`“isolated nicotinamide riboside”
`
`nicotinamide riboside that is
`
`substantially free from other molecules
`
`“is isolated from a natural or synthetic
`
`fractionated from other cellular
`
`source”
`
`
`
`components
`
`1.
`
`Patent Owner’s Proposed Constructions Are Consistent
`With The Specification
`
`The specification is replete with discussions of the term “isolated,” including
`
`almost fifty instances of the term in the specification, eleven of which appear in the
`
`7
`
`

`

`
`
`IPR2017-01796
`
`Background of the Invention. All of the descriptions of isolated molecules and the
`
`process of isolating molecules from natural or synthetic sources support Patent
`
`Owner’s constructions of the “isolated” terms.
`
`The first appearance of the word “isolated” in the Detailed Description is in
`
`a discussion of isolated nucleic acids and polypeptides:
`
`The present invention is an isolated nucleic acid containing a
`eukaryotic nucleotide sequence encoding a nicotinamide riboside
`kinase polypeptide. As used herein, an isolated molecule (e.g., an
`isolated nucleic acid such as genomic DNA, RNA or cDNA or an
`isolated polypeptide) means a molecule separated or substantially free
`from at least some of the other components of the naturally occurring
`organism, such as for example, the cell structural components or other
`polypeptides or nucleic acids commonly found associated with the
`molecule. When the isolated molecule is a polypeptide, said
`polypeptide is at least about 25%, 50%, 60%, 70%, 75%, 80%, 85%,
`90%, 95%, 97%, 98%, 99% or more pure (w/w).
`
`’807 patent at 9:21-33 (emphasis added). Although this passage does not refer to
`
`“isolated nicotinamide riboside,” it does confirm that the patent uses “isolated” in
`
`the way a person of ordinary skill in the art would understand the term.
`
`Specifically, “isolated” molecules are those that are purified or otherwise separated
`
`to be substantially free from other molecules. Accordingly, the claimed “isolated
`
`nicotinamide riboside” is nicotinamide riboside that is substantially free from other
`
`8
`
`

`

`
`
`IPR2017-01796
`
`molecules. The teachings in the specification regarding identification and isolation
`
`of nicotinamide riboside also support this construction.
`
`The specification explains that the source of nicotinamide riboside “can be
`
`from a natural or synthetic source identified by the method of the instant invention,
`
`or 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).” ’807 patent, at 28:58-63. As an initial matter, this teaching
`
`confirms that the claimed nicotinamide riboside can be (1) chemically synthesized,
`
`(2) isolated from a natural source, or (3) isolated from a synthetic source. While
`
`the specification points to the cited “established methods” for chemical synthesis
`
`of nicotinamide riboside, the specification provides several details on isolating the
`
`compound from a natural or synthetic source.
`
`First, the specification describes a method for identifying natural or synthetic
`
`sources of nicotinamide riboside:
`
`Thus, the present invention also encompasses [] a method for
`identifying such natural or synthetic sources. As a first step of the
`method, a first cell lacking a functional glutamine-dependent NAD+
`synthetase is contacted with an isolated extract from a natural or
`synthetic source. . . .
`
`As a second step of the method, a second cell lacking a functional
`glutamine-dependent NAD+ synthetase and a functional nicotinamide
`
`9
`
`

`

`
`
`IPR2017-01796
`
`riboside kinase is contacted with the same isolated extract from the
`natural or synthetic source of the prior step. . . .
`
`As a subsequent step of the method, the growth of the first cell and
`second cell are compared. If the isolated extract contains a
`nicotinamide riboside, the first cell will grow and the second cell will
`not.
`
`’807 patent, at 27:7-38. Although the claims do not recite any of these
`
`identification steps, they provide background and context for how a person of
`
`ordinary skill in the art would obtain isolated nicotinamide riboside that is not
`
`chemically synthesized.
`
`Second, the specification identifies various synthetic and natural sources
`
`from which nicotinamide riboside can be isolated:
`
`Synthetic sources of nicotinamide riboside can include any library of
`chemicals commercially available
`from most
`large chemical
`companies. . . .
`
`Natural sources which can be tested for the presence of []
`nicotinamide riboside include, but are not limited to, cow’s milk,
`serum, meats, eggs, fruit and cereals.
`
`’807 patent, at 27:39-45.
`
`Finally, the specification includes a description of standard methods for
`
`isolating extracts from natural sources:
`
`10
`
`

`

`
`
`IPR2017-01796
`
`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.
`
`’807 patent, at 27:45-54; see also id. at Example 2, 33:30-45 (describing
`
`“Nicotinamide Riboside and Whey Preparations”); 19:44-67 (describing common
`
`purification
`
`techniques,
`
`including
`
`fractionation,
`
`in
`
`the context of Nrk
`
`polypeptides).
`
`These teachings for identification and isolation of nicotinamide riboside for
`
`use in the claimed compositions are consistent with the way a person of ordinary
`
`skill in the art would understand the claimed phrase “is isolated from a natural or
`
`synthetic source.” Contrary to Petitioner’s arguments, the claims do not cover
`
`natural sources of nicotinamide riboside. Instead, the patent specification
`
`identifies various natural and synthetic sources for the compound and then teaches
`
`a person of ordinary skill in the art how to isolate nicotinamide riboside from those
`
`sources, including from cow’s milk. See ’807 patent, at 27:39-45. Specifically,
`
`the specification teaches the use of fractionation techniques to remove the other
`
`11
`
`

`

`
`
`IPR2017-01796
`
`cellular components of cow’s milk so that the nicotinamide riboside can be isolated
`
`suitably for use in the claimed compositions. See ’807 patent, at 27:45-54, 33:30-
`
`45. Accordingly, the specification supports Patent Owner’s proposed construction
`
`of the phrase “is isolated from a natural or synthetic source” as “fractionated from
`
`other cellular components.”
`
`2.
`
`Patent Owner’s Proposed Constructions Are Consistent
`With The Claims
`
`In light of the teachings in the specification, the ’807 patent claim language
`
`also supports Patent Owner’s claim construction proposals for the “isolated” terms,
`
`including that the Board should construe the broader phrases in which the
`
`“isolated” terms appear.
`
` Although the word “isolated” appears in both
`
`independent claim 1 and dependent claim 2, the context in which the terms appear
`
`is critical for defining the terms in the manner dictated by the specification.
`
`The phrase “isolated nicotinamide riboside” appears in claim 1, the only
`
`independent claim. Claim 1 specifically claims compositions of the isolated
`
`nicotinamide riboside in combination with other components, the specific type of
`
`formulation, and the effect of those compositions:
`
`isolated nicotinamide riboside
`in
`A composition comprising
`combination with one or more of tryptophan, nicotinic acid, or
`nicotinamide, wherein said combination is in admixture with a
`carrier . . . wherein
`said composition
`is
`formulated
`for oral
`
`12
`
`

`

`
`
`IPR2017-01796
`
`administration and
`administration.
`
`increases NAD+ biosynthesis upon oral
`
`’807 patent, at 53:59-54:58 (emphasis added). As supported by the specification,
`
`the “isolated nicotinamide riboside” recited in claim 1 refers to the nicotinamide
`
`riboside molecule itself. In other words, as used in claim 1, “isolated nicotinamide
`
`riboside” is nicotinamide riboside that is substantially free from other molecules.
`
`In contrast, claim 2 recites that “the nicotinamide riboside is isolated from a
`
`natural or synthetic source.” ’807 patent, at 54:60-61. As disclosed in the
`
`specification and confirmed by the words of the claim itself, “isolated” in claim 2
`
`refers to the process of isolating the nicotinamide riboside for use in the claimed
`
`compositions. Claim 2 is narrower than claim 1 because it further specifies that the
`
`nicotinamide riboside “is isolated from a natural or synthetic source,” to the
`
`exclusion of chemically synthesizing the compound. See ’807 patent, at 28:58-63.
`
`The correct definition of the phrase in which “isolated” appears in claim 2 will
`
`therefore be the one that is consistent with the scope of the claim itself.
`
`Specifically, the construction should be consistent with the disclosure of standard
`
`methods for isolating extracts from natural sources, such as fractionating
`
`nicotinamide riboside from other cellular components. See ’807 patent, at 27:45-
`
`54.
`
`13
`
`

`

`
`
`IPR2017-01796
`
`Accordingly, the claim language of dependent claim 2 confirms that the
`
`Board should construe the phrase “is isolated from a natural or synthetic source.”
`
`Because claim 1 must necessarily be broader than claim 2, and in light of the
`
`teachings of the specification, nicotinamide riboside that “is isolated from a natural
`
`or synthetic source” must be distinguished from nicotinamide riboside that is
`
`chemically synthesized. In other words, nicotinamide riboside that “is isolated
`
`from a natural or synthetic source” is nicotinamide riboside that is fractionated
`
`from other cellular components.
`
`3.
`
`Petitioner’s Proposed Constructions Should Not Be
`Adopted
`
`a.
`
`Petitioner’s Proposed Constructions Are Inconsistent
`With the Specification and Claims
`
`Petitioner’s proposed constructions ignore the teachings of the specification
`
`in favor of a single, incomplete, phrase pulled out of context. Although Petitioner
`
`quotes the majority of the passage discussing “isolated” nucleic acids, Petitioner
`
`concludes that any molecule in the patent is “isolated” if it is “separate or
`
`substantially free from at least some of the other components of the naturally
`
`occurring organism.” Pet. at 6. Although Petitioner claims its proposed
`
`constructions for the “isolated” terms are pulled from the specification, Petitioner’s
`
`proposals are incomplete because they ignore the language of the claims
`
`themselves and the teachings in the specification regarding nicotinamide riboside.
`
`14
`
`

`

`
`
`IPR2017-01796
`
`Petitioner fails to even disclose that the passage to which it cites discusses
`
`nucleic acids rather than the claimed nicotinamide riboside. Moreover, Petitioner
`
`fails to account for the portion of its cited passage that explains that “isolated”
`
`nucleic acids must be substantially free from at least some of “the cell structural
`
`components or other polypeptides or nucleic acids commonly found associated
`
`with the molecule.” See ’807 patent, at 9:23-30. As a result, Petitioner’s proposed
`
`construction is incomplete with respect to both nicotinamide riboside and the very
`
`compound discussed in the portion of the specification from which Petitioner
`
`extracted the construction.
`
`In addition to the disclosure regarding nucleic acids, the specification
`
`includes disclosures regarding, inter alia, expression vectors, polypeptides,
`
`prodrugs, and cultured cells. The claims themselves are directed only to
`
`nicotinamide riboside compounds, so the construction of both “isolated” terms
`
`should be informed by the patent disclosures regarding nicotinamide riboside. The
`
`specification includes numerous teachings regarding the meaning of “isolated” in
`
`the context of nicotinamide riboside that Petitioner never mentions. As discussed
`
`above, those teachings support Patent Owner’s proposal to construe the broader
`
`phrase of “isolated nicotinamide riboside” in claim 1 and are consistent with the
`
`way a person of ordinary skill in the art would understand the “isolated
`
`nicotinamide riboside” phrase.
`
`15
`
`

`

`
`
`IPR2017-01796
`
`For the “is isolated” phrase in claim 2, Petitioner proposes only that the
`
`word “is” be added to its “isolated” construction. See Pet. at 7. Petitioner’s
`
`proposed construction is improper at least because it attempts to “constru[e]
`
`individual words of a claim without considering the context in which those words
`
`appear.” Trivascular, 812 F.3d at 1062; see also ACTV, 346 F.3d at 1088 (“While
`
`certain terms may be at the center of the claim construction debate, the context of
`
`the surrounding words of the claim also must be considered in determining the
`
`ordinary and customary meaning of those terms.”). For example, if Petitioner’s
`
`proposed construction were inserted into the language of claim 2, the claim would
`
`become nonsensical because it would read as “[t]he composition of claim 1,
`
`wherein the nicotinamide riboside [is separated or substantially free from at least
`
`some of the other components of the naturally occurring organism] from a natural
`
`or synthetic source.” See Pet. at 6-7. Even if the claim could be understood using
`
`Petitioner’s proposed construction, the virtual identity between Petitioner’s
`
`proposed constructions for the two “isolated” terms would improperly render claim
`
`2 redundant to claim 1.
`
`Because claim 2 recites nicotinamide riboside that “is isolated from a natural
`
`or synthetic source” and the specification includes detailed explanations of
`
`methods for isolating nicotinamide riboside from the claimed sources, it is more
`
`appropriate to construe the broader phrase consistently with those teachings. See
`
`16
`
`

`

`
`
`IPR2017-01796
`
`Trivascular, 812 F.3d at 1062 (criticizing constructions that “interpret the words in
`
`a claim without regard for the full claim language and the written description”).
`
`Specifically, and as discussed above, the specification describes common
`
`purification and fractionation techniques that are consistent with Patent Owner’s
`
`proposed construction. On the other hand, Petitioner ignores those teachings, even
`
`while its expert purports to understand “purified precursors [of NAD+],” including
`
`purified nicotinamide. See Ex. 1002 at 10, ¶15 (discussing precursor molecules,
`
`including nicotinamide riboside, that can be used to synthesize NAD+, and stating
`
`that modern cases of pellagra in humans “would be treated with purified
`
`precursors”). Accordingly, Petitioner’s proposed constructions for the “isolated”
`
`terms should be rejected.
`
`b.
`
`Petitioner’s Proposed Constructions Are Unreasonably
`Broad
`
`Petitioner’s proposed constructions are unreasonably broad because they
`
`would read on milk that has been removed from a cow. Petitioner asserts that
`
`“[t]he nicotinamide riboside naturally present in the skim milk Goldberger et al.
`
`administered to dogs is isolated … from the cow.” Pet. at 12. In other words,
`
`under Petitioner’s proposed construction, the nicotinamide riboside in milk is
`
`“isolated” only after it is evacuated from a cow, but not before. Such a result
`
`defies common sense. Moreover, Petitioner’s unreasonably broad construction
`
`makes no sense in light of the specification, which teaches that cow’s milk is a
`17
`
`

`

`
`
`IPR2017-01796
`
`natural source from which nicotinamide riboside may be isolated, not a source of
`
`isolated nicotinamide riboside. See In re Smith Int’l, Inc., No. 2016-2303, 2017
`
`WL 4247407, at *5 (Fed. Cir. 2017) (concluding that giving a disputed term “such
`
`a strained breadth in the face of the otherwise different description in the
`
`specification was unreasonable”).
`
`For example, the specification discloses “a method for identifying a natural
`
`or synthetic source for nicotinamide riboside” and further specifies that “[i]n one
`
`embodiment, the natural source is cow’s milk.” ’807 patent, at 4:8-20. The
`
`specification further discloses that “nicotinamide riboside [was] isolated from
`
`deproteinized whey fraction of cow’s milk” and further explains those procedures
`
`in Example 2. See id. at 27:7-9, 33:30-45. Finally, the specification identifies
`
`cow’s milk as a source of nicotinamide riboside and explains that the nicotinamide
`
`riboside can be isolated from the cow’s milk using standard methods, such as
`
`centrifugation and fractionation. See id. at 27:42-54. The Federal Circuit has
`
`made clear that the broadest reasonable construction does not include those that are
`
`“unreasonable under general claim construction principles.” In Re Smith, 2017 WL
`
`4247407, at *5. Unreasonable constructions include those that are divorced from
`
`the specification and record evidence.” Id. Petitioner’s unreasonably broad
`
`constructions covering milk are divorced from the patent specification, and make
`
`no sense in the context of the inventions described therein.
`
`18
`
`

`

`
`
`IPR2017-01796
`
`IV. PETITIONER HAS NOT DEMONSTRATED “A REASONABLE
`LIKELIHOOD OF PREVAILING” AGAINST AT LEAST ONE
`CLAIM OF THE ’807 PATENT UNDER 35 U.S.C. § 314(a)
`Under 35 U.S.C. § 314(a), an inter partes review may only be instituted
`
`where “the information presented in the petition . . . and any response . . . shows
`
`that there is a reasonable likelihood that the petitioner would prevail with respect to
`
`at least one of the claims challenged in the petition.” See also 37 C.F.R. §
`
`42.108(c). The burden of showing that this statutory threshold has been met
`
`belongs to Petitioner. See, e.g., Office Patent Trial Practice Guide, 77 Fed. Reg.
`
`48756, 48756 (Aug. 14, 2012) (“The Board . . . may institute a trial where the
`
`petitioner establishes that the standards for instituting the requested trial are met . .
`
`. .”).
`
`Petitioner asserts two anticipation grounds in its challenge of the ’807
`
`patent. However, Petitioner has not shown that either of its prior art references of
`
`the proposed Grounds disclose elements required by independent claim 1 of the
`
`’807 patent. Specifically, Petitioner fails to establish that the prior art references of
`
`the proposed Grounds disclose (1) a composition comprising nicotinamide riboside
`
`that is substantially free from other molecules, and (2) isolated nicotinamide
`
`riboside in admixture with a carrier. Petitioner also fails to establish that the
`
`references of the proposed Grounds disclose a composition that “increases NAD+
`
`biosynthesis upon oral administration,” as required by claim 1. Petitioner’s
`
`19
`
`

`

`
`
`IPR2017-01796
`
`arguments on this essential limitation are the same as arguments raised and
`
`overcome during prosecution, so the petition can be denied on this basis alone
`
`under 35 U.S.C. § 325(d). See Prism Pharma Co. v. Choongwae Pharma Corp.,
`
`IPR2014-00315, Paper No. 14, at 12-13 (exercising discretion to deny institution
`
`under 35 U.S.C. § 325(d) because “substantially the same arguments were
`
`presented to the Office previously”).
`
`Because the other two challenged claims depend directly from claim 1,
`
`Petitioner has failed to establish that the asserted prior art references antic