IPR2017-01795
`
`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 IPR2017-01795
`
`Patent 8,383,086
`_______________
`
`PATENT OWNER RESPONSE
`
`THORNE - EXHIBIT 1017
`
`

`

`I.
`II.
`
`TABLE OF CONTENTS
`
`SUMMARY OF ARGUMENT ....................................................................... 1
`THE ’086 PATENT ......................................................................................... 3
`A.
`The Nicotinamide Riboside-Containing Pharmaceutical Compositions
`of the ’086 Patent Increase NAD+ Biosynthesis Upon Oral
`Administration ....................................................................................... 3
`B. All of the ’086 Patent Claims Require an Oral Pharmaceutical
`Composition Wherein Nicotinamide Riboside is the Active Agent ..... 4
`Level of Ordinary Skill in the Art ......................................................... 6
`C.
`III. CLAIM CONSTRUCTION ............................................................................ 6
`A.
`“Pharmaceutical composition comprising nicotinamide riboside” ....... 8
`1.
`Patent Owner’s Proposed Construction is Consistent with the
`Specification ................................................................................ 9
`Patent Owner’s Proposed Construction is Consistent with the
`Express Claim Language .......................................................... 12
`Petitioner’s Proposed Interpretation of “pharmaceutical
`composition” Should Be Rejected ............................................ 13
`“is isolated from a natural or synthetic source” .................................. 17
`B.
`IV. PETITIONER HAS NOT MET ITS BURDEN OF SHOWING THAT
`ANY OF THE CLAIMS OF THE ’086 PATENT ARE UNPATENTABLE
`OVER EITHER GROUNDS 1 OR 2 ............................................................ 19
`A. Anticipation Standard .......................................................................... 19
`B. Goldberger et al. Does Not Anticipate the ’086 Patent Claims
`Because it Does Not Teach a Pharmaceutical Composition
`Containing Nicotinamide Riboside as the Active Agent .................... 20
`1.
`Goldberger et al. Does Not Anticipate Claim 1 of the ’086
`Patent ......................................................................................... 21
`i
`
`2.
`
`3.
`
`
`
`

`

`2.
`
`3.
`
`4.
`
`Goldberger et al. Does Not Anticipate Claim 3 of the ’086
`Patent ......................................................................................... 25
`Goldberger et al. Does Not Anticipate Claim 4 of the ’086
`Patent ......................................................................................... 27
`Goldberger et al. Does Not Anticipate Claim 5 of the ’086
`Patent ......................................................................................... 28
`THE MODIFIED INSTITUTION DECISION DOES NOT CHANGE
`THE RESULT THAT PETITIONER HAS FAILED TO ESTABLISH
`UNPATENTABILITY OF ANY CLAIM OF THE ’086 PATENT
`OVER GROUNDS 1 OR 2 ................................................................. 30
`1.
`Petitioner Has Failed to Establish Unpatentability
`of Claim 2 .................................................................................. 31
`Petitioner Has Failed to Establish Unpatentability
`of Any Claim over Ground 2 .................................................... 32
`CONCLUSION .............................................................................................. 35
`
`C.
`
`2.
`
`V.
`
`
`
`
`ii
`
`

`

` Cases
`
`TABLE OF AUTHORITIES
`
`ACTV, Inc. v. Walt Disney Co.
`346 F.3d 1082 (Fed. Cir. 2003) ..................................................................... 12, 15
`Atofina v. Great Lakes Chem. Corp.
`441 F.3d 991 (Fed. Cir. 2006) .............................................................................. 19
`Continental Can Co. USA, Inc. v. Monsanto Co.
`948 F.2d 1264 (Fed. Cir. 1991) ............................................................................ 20
`Crown Operations Int’l, Ltd. v. Solutia Inc.
`289 F.3d 1367 (Fed. Cir. 2002) ............................................................................ 19
`Cuozzo Speed Techs., LLC v. Lee
`136 S. Ct. 2131 (2016) ........................................................................................... 6
`Electro Med. Sys., S.A. v. Cooper Life Scis., Inc.
`34 F.3d 1048, 32 U.S.P.Q.2d 1017 (Fed. Cir. 1994) .................................... 19, 30
`HTC Corp. v. Cellular Commc’ns Equip., LLC
`877 F.3d 1361 (Fed. Cir. 2017) ............................................................... 20, 23, 30
`In re Morris
`127 F.3d 1048 (Fed. Cir. 1997) .............................................................................. 7
`In re Smith Int’l, Inc.
`No. 2016-2303, 2017 WL 4247407 (Fed. Cir. 2017) ............................... 7, 11, 16
`In re Suitco Surface, Inc.
`603 F.3d 1255 (Fed. Cir. 2010) .............................................................................. 7
`In re Translogic Tech., Inc.
`504 F.3d 1249 (Fed. Cir. 2007) ............................................................................ 16
`Trivascular, Inc. v. Samuels
`812 F.3d 1056 (Fed. Cir. 2016) ....................................................................... 8, 15
`Verdegaal Bros. v. Union Oil Co. of California
`814 F.2d 628, 2 USPQ2d 1051 (Fed. Cir. 1987) ................................................... 2
`iii
`
`
`
`

`

`Statutes
`
`35 U.S.C. § 316(e) ..................................................................................................... 1
`Other Authorities
`
`M.P.E.P. § 2131 ......................................................................................................... 2
`Rules
`
`Office Patent Trial Practice Guide
`77 Fed. Reg. 48756 (Aug. 14, 2012) ...................................................................... 6
`Regulations
`
`37 C.F.R. § 42.100(b) ................................................................................................ 6
`
`
`
`
`iv
`
`

`

`EXHIBIT LIST
`
`Description
`Declaration of Zhaohui Sunny Zhou, PhD. (“Zhou Decl.”)
`Transcript of Joseph A. Baur deposition taken on April 26, 2018
`(“Baur Tx.”)
`Excerpt from McGraw-Hill Dictionary of Scientific and Technical
`Terms (2003) (“McGraw-Hill 2003”)
`Excerpt from New Oxford American Dictionary (2005) (“New
`Oxford American 2005”)
`Excerpt from Remington: The Science and Practice of Pharmacy,
`Alfonso R. Gennaro, editor, 20th ed. Lippingcott Williams &
`Wilkins: Philadelphia, Pa., 2000 (“Remington”)
`Raats, et al., Molecular analysis of bacterial communities in raw
`cow milk and the impact of refrigeration on its structure and
`dynamics, Food Microbiology, Vol. 28, pp. 465-71 (2011)
`Rasolofo, et al., Molecular analysis of bacterial population
`structure and dynamics during cold storage of untreated and treated
`milk, Int’l J. Food Microbiology, Vol. 138, pp. 108-18 (2010)
`Kurnasov, et al., Ribosylnicotinamide Kinase Domain of NadR
`Protein: Identification and Implications in NAD Biosynthesis, J.
`Bacteriology, Vol. 184, No. 24, pp. 6906-17 (Dec. 2002)
`Johnson, et al., Characterization of NAD salvage pathways and their
`role in virulence in Streptococcus pneumoniae, Microbiology, Vol.
`161, pp. 2127-36 (2015)
`Holsinger, et al., Milk pasteurisation and safety: a brief history and
`update, Rev. sci. tech. Off. int. Epiz, Vol. 16(2), pp. 441-51 (1997)
`
`v
`
`Exhibit No.
`2002
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`2010
`
`2011
`
`
`
`

`

`Pursuant to 35 U.S.C. § 316(a)(8) and 37 C.F.R. § 42.120, Trustees of
`
`Dartmouth College (“Patent Owner”) responds to the Petition filed by Elysium
`
`Health, Inc. (“Petitioner”) regarding U.S. Patent No. 8,383,086 (Ex. 1001, “the
`
`’086 patent”).
`
`I.
`
`SUMMARY OF ARGUMENT
`
`Petitioner bears “the burden of proving a proposition of unpatentability by a
`
`preponderance of the evidence.” 35 U.S.C. § 316(e). Petitioner has failed to meet
`
`that burden here.
`
`The ’086 patent claims require a pharmaceutical composition containing
`
`nicotinamide riboside as the active agent. The asserted prior art, Goldberger et al.
`
`(Ground 1) and Goldberger and Tanner (Ground 2)1, discloses milk and buttermilk,
`
`respectively. Petitioner has not established that either milk or buttermilk is a
`
`
`1 The Board instituted review of claims 1, 3, 4 and 5 on Ground 1
`
`(anticipation), but did not institute review of claim 2, nor did the Board institute
`
`review on Ground 2 (anticipation). Paper 9, at 19. After the Board announced it
`
`would institute review on all claims and all grounds (see Paper 22, “Modified
`
`Institution Decision”), Patent Owner filed a Request for Rehearing (Paper 24),
`
`which is currently pending. The Board has indicated that the Patent Owner
`
`Response should address all grounds in the Petition. Paper 25.
`
`
`
`1
`
`

`

`pharmaceutical composition containing nicotinamide riboside as the active agent.
`
`Because all claims of the ’086 patent require the same pharmaceutical composition
`
`containing nicotinamide riboside as the active agent, Petitioner has failed to
`
`establish that the prior art anticipates any claim of the ’086 patent. See Verdegaal
`
`Bros. v. Union Oil Co. of California, 814 F.2d 628, 631, 2 USPQ2d 1051, 1053
`
`(Fed. Cir. 1987) (“A claim is anticipated only if each and every element as set forth
`
`in the claim is found, either expressly or inherently described, in a single prior art
`
`reference.”); see also M.P.E.P. § 2131 (“To anticipate a claim, the disclosure must
`
`teach every element of the claim.”).
`
`Additionally, claim 2 depends from claim 1 and further requires
`
`nicotinamide riboside “isolated from a natural or synthetic source,” which the
`
`Board has already properly concluded is not disclosed in either of Petitioner’s
`
`asserted prior art references. Specifically, with respect to claim 2, the asserted
`
`prior art references do not disclose nicotinamide riboside that is isolated from a
`
`natural or synthetic source. Paper 9, at 13-14.
`
`Finally, Petitioner has failed to establish that the prior art discloses
`
`dependent claim 5, which covers the pharmaceutical composition of claim 1
`
`“which increase[s] NAD+ biosynthesis upon oral administration.” In fact,
`
`Petitioner’s expert expressly admits there is no proof that milk leads to such an
`
`increase. Ex. 2003, Baur Tx., at 45:22-47:17.
`
`2
`
`
`
`

`

`For the reasons set forth herein, Petitioner has failed to meet its burden to
`
`establish by a preponderance of the evidence that any claim of the ’086 patent is
`
`anticipated by either Goldberger et al. or Goldberger and Tanner.
`
`II. THE ’086 PATENT
`
`A. The Nicotinamide Riboside-Containing Pharmaceutical
`Compositions of the ’086 Patent Increase NAD+ Biosynthesis
`Upon Oral Administration
`
`Prior to the ’086 patent invention, the gene products and pathways to
`
`nicotinamide adenine dinucleotide (NAD+), a co-enzyme found in cells, were
`
`understood to include de novo synthesis, nicotinic acid import, and nicotinamide
`
`salvage. ’086 patent, at 2:20-29, Scheme 1. The ’086 patent inventor, however,
`
`discovered that nicotinamide riboside is “an NAD+ precursor in a previously
`
`unknown but conserved eukaryotic NAD+ biosynthetic pathway,” and,
`
`importantly, that oral pharmaceutical formulations of nicotinamide riboside as the
`
`active agent could be used to treat conditions that are connected to NAD+
`
`biosynthesis. Id. at 2:62-3:3, 8:39-41. As described in the specification:
`
`the
`through
`that work
`[A]gents (e.g., nicotinamide riboside)
`discovered nicotinamide
`riboside kinase pathway of NAD+
`biosynthesis could have therapeutic value in improving plasma lipid
`profiles, preventing
`stroke, providing neuroprotection with
`chemotherapy treatment, treating fungal infections, preventing or
`reducing neurodegeneration, or in prolonging health and well-being.
`Thus, the present invention is further a method for preventing or
`3
`
`
`
`

`

`treating a disease or condition associated with the nicotinamide
`riboside kinase pathway of NAD+ biosynthesis by administering an
`effective amount of nicotinamide riboside composition.
`
`Id. at 27:60-28:3.
`
`In light of the discovery that nicotinamide riboside is an effective active
`
`agent, the ’086 patent claims oral pharmaceutical compositions containing
`
`nicotinamide riboside. Contrary to Petitioner’s arguments, the ’086 patent does not
`
`cover any composition that happens to include nicotinamide riboside. Instead the
`
`’086 patent claims cover oral compositions specifically formulated with
`
`nicotinamide riboside as the active agent.
`
`B. All of the ’086 Patent Claims Require an Oral Pharmaceutical
`Composition Wherein Nicotinamide Riboside is the Active Agent
`
`Each of dependent claims 2 through 5 depend from independent claim 1,
`
`which claims pharmaceutical compositions comprising nicotinamide riboside as
`
`the active agent, wherein the nicotinamide riboside is in admixture with a
`
`pharmaceutically acceptable carrier, and the composition is formulated for oral
`
`administration. See ’086 patent, at claim 1.
`
`Dependent claim 2 further specifies that the nicotinamide riboside of the
`
`claimed pharmaceutical composition “is isolated from a natural or synthetic
`
`source.” See id. at claim 2. The ’086 patent specification includes examples of
`
`
`
`4
`
`

`

`such sources, and further describes methods for isolating nicotinamide riboside
`
`from a natural source such as cow’s milk. See id. at 26:64-27:12.
`
`Dependent claim 3 identifies a subset of forms that oral formulations of the
`
`nicotinamide riboside-containing pharmaceutical composition can take, including
`
`“a tablet, troche, capsule, elixir, suspension, syrup, wafer, chewing gum, or food.”
`
`Id. at claim 3. As explained in the ’086 specification, regardless of which of these
`
`oral dosage forms the composition takes, an amount of active agent (i.e.,
`
`nicotinamide riboside) is also present. See id. at 29:43-53.
`
`Dependent claim 4 recites pharmaceutically acceptable components that may
`
`be optionally added to the pharmaceutical composition, including “tryptophan,
`
`nicotinic acid, or nicotinamide.” Id. at claim 4. As described in the specification,
`
`these additional components may optimize NAD+ metabolism for certain
`
`conditions, but are in addition to the operative active agent, nicotinamide riboside.
`
`Id. at 28:36-48.
`
`Finally, dependent claim 5 claims the pharmaceutical composition of claim 1
`
`which further “increase[s] NAD+ biosynthesis upon oral administration.” Id. at
`
`claim 5. This claimed increase in NAD+ biosynthesis is based on the inclusion of
`
`nicotinamide riboside as the active agent and leads to the therapeutic result of
`
`preventing or treating a wide range of diseases and conditions due to an increase in
`
`NAD+ biosynthesis when administrated orally. See id. at 28:3-15.
`
`
`
`5
`
`

`

`C. Level of Ordinary Skill in the Art
`
`Patent Owner contends that a person of ordinary skill in the art with respect
`
`to the ’086 patent would be someone with a Ph.D. in biochemistry or similar field
`
`in
`
`the pharmaceutical sciences, with
`
`familiarity and experience with
`
`pharmacokinetics. Ex. 2002, Zhou Decl., at ¶ 17. Although Petitioner’s proposed
`
`level of ordinary skill in the art does not specify any particular experience in the
`
`pharmaceutical sciences or pharmacokinetics, Petitioner’s proposal
`
`is not
`
`materially different for purposes of this review. See Pet. at 6. Patent Owner’s
`
`analysis and conclusions presented here would not change based on any
`
`differences between Patent Owner’s and Petitioner’s proposed level of ordinary
`
`skill in the art. Ex. 2002, Zhou Decl., at ¶ 18.
`
`III. CLAIM CONSTRUCTION
`
`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).2 The broadest reasonable
`
`2 The Patent Office issued a Notice of Proposed Rulemaking on May 9,
`
`2018, which proposes replacing this “broadest reasonable construction” standard
`
`with the standard applied in federal district courts, “including construing the claim
`
`
`
`6
`
`

`

`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)).
`
`
`in accordance with the ordinary and customary meaning of such claim as
`
`understood by one of ordinary skill in the art.” Changes to the Claim Construction
`
`Standard for Interpreting Claims in Trial Proceedings Before the Patent Trial and
`
`Appeal Board, 83 Fed. Reg. 21221, at 21223 (proposed May 9, 2018) (to be
`
`codified at 37 C.F.R. pt. 42). Petitioner’s analyses and conclusions presented
`
`herein would remain the same under either claim construction standard.
`
`
`
`7
`
`

`

`Terms should also be construed in light of the express language of the claims
`
`in which they appear. See Trivascular, Inc. v. Samuels, 812 F.3d 1056, 1062 (Fed.
`
`Cir. 2016) (“Construing individual words of a claim without considering the
`
`context in which those words appear is simply not ‘reasonable.’”).
`
`A.
`
` “Pharmaceutical composition comprising nicotinamide riboside”
`
`A person of ordinary skill in the art would understand that the ’086 patent is
`
`directed to nicotinamide riboside, and specifically, to its use as an active agent in
`
`the claimed pharmaceutical compositions. Petitioner’s proposed interpretation of
`
`the “pharmaceutical composition” term should be rejected because it does not
`
`provide any meaningful definition for the term and instead focuses only on the
`
`physical forms the claimed composition may take based on the language of
`
`dependent claim 3. Pet. at 7. In doing so, Petitioner ignores the disclosure of the
`
`’086 patent itself and the specification’s focus on nicotinamide riboside
`
`compositions. Patent Owner proposes that the Board construe the phrase
`
`“pharmaceutical composition comprising nicotinamide riboside” consistent with
`
`the way a person of ordinary skill in the art would understand that phrase, namely
`
`as “a composition containing nicotinamide riboside as the active agent.”
`
`
`
`8
`
`

`

`1.
`
`Patent Owner’s Proposed Construction is Consistent with
`the Specification
`
`The ’086 patent consistently and repeatedly emphasizes nicotinamide
`
`riboside and its use as an active agent in the claimed pharmaceutical compositions.
`
`For example, the specification discloses, among other things:
`• Methods of treating diseases or conditions with “an effective amount
`
`of a nicotinamide riboside composition so that the signs or symptoms
`
`of the disease or condition are prevented or reduced.” ’086 patent, at
`
`4:22-24 (emphasis added).
`• The diseases and conditions that “can be prevented or treated by
`
`supplementing a diet or a therapeutic treatment regime with a
`
`nicotinamide riboside composition.” ’086 patent, at 27:60-28:15
`
`(emphasis added); see also 8:57-59 (improve lipid profiles), 8:61-62
`
`(stroke), 27:32-36 (Alzheimer’s Disease, Parkinson’s Disease and
`
`Multiple Sclerosis), 27:45-47 (neurotoxicity before, during or after
`
`cytotoxic chemotherapy), 27:57-59 (fungal infections), and 28:12
`
`(aging).
`• A definition for the “effective amount of nicotinamide riboside,”
`
`which can be adjusted based on clinical evaluation “before and after
`
`treatment with the nicotinamide riboside.” ’086 patent, at 28:36-43
`
`(emphasis added).
`
`9
`
`
`
`

`

`• Optional combinations, including other NAD+ precursors, with the
`
`“nicotinamide riboside treatments.”
`
` ’086 patent, at 28:44-48
`
`(emphasis added).
`
`These are but a few examples of portions of the specification that confirm to a
`
`person of ordinary skill in the art that the claimed ’086 patent invention is a
`
`pharmaceutical composition in which nicotinamide riboside is the active agent,
`
`rather than just an inactive excipient. Ex. 2002, Zhou Decl., at ¶¶ 23-28.
`
`These disclosures also reflect the understanding of a person of ordinary skill
`
`in the art that a pharmaceutical, at its most basic level, contains an active
`
`ingredient. Ex. 2002, Zhou Decl., at ¶ 31. Even the compendium identified in the
`
`’086 patent specification (’086 patent, at 28:56-60) repeatedly refers to the
`
`inclusion of an active agent in a pharmaceutical. Ex. 2002, Zhou Decl., at ¶¶ 30-
`
`31; Ex. 2006, Remington, at 700-01, 858, 860; see also Ex. 2004, McGraw-Hill
`
`2003, at 1571 (defining “pharmaceutical” as “[a] chemical produced industrially
`
`(medicinal drug), which is useful in preventive or therapeutic treatment of a
`
`physical, mental, or behavioral condition”); Ex. 2005, New Oxford American
`
`2005, at 1275 (defining “pharmaceutical” as “a compound manufactured for use as
`
`a medicinal drug”).
`
`Accordingly, the construction for this phrase should be consistent with the
`
`patentee’s clear intent to identify nicotinamide riboside as the active agent of the
`
`
`
`10
`
`

`

`claimed compositions. See In re Smith Int’l, 2017 WL 4247407, at *5 (broadest
`
`reasonable interpretation must be the one that “corresponds with what and how the
`
`inventor describes his invention in the specification, i.e., an interpretation that is
`
`consistent with the specification”) (internal quotations omitted).
`
`Moreover, the specification describes the claimed compositions in terms of
`
`“the active agent,” and specifically identifies the active agent of the invention to be
`
`nicotinamide riboside. For example, in the context of describing pharmaceutically
`
`acceptable carriers, the specification states:
`
`“Polypeptides, nucleic acids, vectors, dietary supplements (i.e.
`nicotinamide riboside), and nicotinamide riboside-related prodrugs
`produced or identified in accordance with the methods of the
`invention can be conveniently used or administered in a composition
`containing the active agent in combination with a pharmaceutically
`acceptable carrier.”
`
`’086 patent, at 28:49-54 (emphasis added). Similarly, in the claimed compositions,
`
`a pharmaceutically acceptable carrier “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.” ’086 patent, at 28:62-64 (emphasis added); see also id. at
`
`29:43-53 (disclosure of the “active compound” in oral forms), 30:4-7 (disclosure of
`
`“active compound” in syrups or elixirs), 30:9-12 (disclosure of “active compound”
`
`in sustained-release preparations). In light of the specification, a person of
`
`
`
`11
`
`

`

`ordinary skill in the art would understand the subject compound (i.e., the active
`
`agent) of the ’086 patent to be nicotinamide riboside. Ex. 2002, Zhou Decl., at
`
`¶¶ 29, 33.
`
`2.
`
`Patent Owner’s Proposed Construction is Consistent with
`the Express Claim Language
`
`Indeed, the above passages from the ’086 patent specification are the same
`
`as those the Board relied on to define the “carrier” term in the Institution Decision.
`
`Paper 9, at 6-7 (quoting ’086 patent, at 28:61-67). As defined by the Board, the
`
`claimed carrier must carry or transport “the subject compound.” Id. In the first
`
`sentence of the paragraph the Board relied upon for its definition, the specification
`
`also refers to this compound as “the active agent.” ’086 patent, at 28:49-54. In
`
`both cases, “the subject compound” and “the active agent” refer to the compound
`
`that is transported by the carrier. That compound is indisputably the active agent,
`
`i.e. nicotinamide riboside. The Board’s construction of the “carrier” limitation,
`
`which also appears in claim 1, further confirms that the “pharmaceutical
`
`composition” phrase must be construed consistently to reflect the requirement for
`
`an active agent, that agent being nicotinamide riboside. See ACTV, Inc. v. Walt
`
`Disney Co., 346 F.3d 1082, 1088 (Fed. Cir. 2003) (“While certain terms may be at
`
`the center of the claim construction debate, the context of the surrounding words of
`
`the claims also must be considered in determining the ordinary and customary
`
`meaning of those terms”).
`
`12
`
`
`
`

`

`The remaining dependent claims also confirm that the active agent of the
`
`pharmaceutical composition of claim 1 is nicotinamide riboside. Claim 2
`
`specifically recites nicotinamide riboside and its isolation from a natural or
`
`synthetic source. See ’086 patent, at claim 2, 26:64-27:12. Claim 3 recites the
`
`different oral dosage forms the composition can take, all of which must also
`
`include an amount of active agent (i.e., nicotinamide riboside). See id. at claim 3,
`
`29:43-53. Claim 4 recites additional NAD+ precursors that may be added to the
`
`composition to optimize NAD+ metabolism for certain conditions, but those are in
`
`addition to the active agent nicotinamide riboside. See id. at claim 4, 28:36-48.
`
`Finally, claim 5 recites a therapeutic effect (i.e., increasing NAD+ biosynthesis)
`
`resulting from the inclusion of nicotinamide riboside as the active agent. See id. at
`
`claim 5, 28:3-15.
`
`Accordingly, consistent with the express claim language, including the
`
`Board’s definition of carrier, “pharmaceutical composition comprising
`
`nicotinamide riboside” should be construed as a “composition containing
`
`nicotinamide riboside as the active agent.” Ex. 2002, Zhou Decl., at ¶¶ 32-33.
`
`3.
`
`Petitioner’s Proposed Interpretation of “pharmaceutical
`composition” Should Be Rejected
`
`Petitioner does not offer an explicit construction of “pharmaceutical
`
`composition” and instead relies only on claim 3 to propose that the term “should be
`
`understood to include at least a tablet, troche, capsule, elixir, suspension, syrup,
`13
`
`
`
`

`

`wafer, chewing gum, or food.” Pet. at 6-7. However, as expressed in the
`
`specification, this phrase from claim 3 does not define the composition, but rather
`
`identifies some of the specific forms the composition of claim 1 (i.e., containing
`
`nicotinamide riboside as the active agent) can take when used for oral therapeutic
`
`administration:
`
`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.
`
`’086 patent, at 29:43-47. The very next sentence in the specification confirms that
`
`such compositions must include the “active compound” and that “[t]he amount of
`
`active compound in such compositions is such that an effective dosage level will
`
`be obtained.” Id. at 29:47-53. In other words, even if a composition takes the
`
`form of food, such food would not be necessarily considered a “pharmaceutical
`
`composition” of the ’086 patent unless the composition also included the active
`
`compound nicotinamide riboside.
`
`Contrary to this teaching, Petitioner’s proposed interpretation would lead to
`
`the absurd result that any food would qualify as a “pharmaceutical composition”
`
`under the ’086 patent. Petitioner’s expert, Dr. Baur, confirmed that under
`
`Petitioner’s
`
`interpretation “any food would qualify” as a pharmaceutical
`
`composition of the ’086 patent, without exception. Ex. 2003, Baur Tx., at 21:10-
`14
`
`
`
`

`

`24. This result is particularly nonsensical given that Petitioner’s expert also
`
`understands that pharmaceutical compositions generally should “be interpreted to
`
`always mean something that doesn’t harm the molecule being administered.” Id.
`
`at 19:21-20:6. Moreover, Petitioner’s expert repeatedly confirmed that, in the
`
`context of the ’086 patent, the molecule being administered is the active agent
`
`nicotinamide riboside. See id. at 19:21-20:16 (“Q: And in this case, that active
`
`agent would be nicotinamide riboside, correct? A: Yes.”), 23:4-23 (“Q: And the
`
`formulation that you’re referring to there, in paragraph 30, is the pharmaceutical
`
`composition of claim 1, where nicotinamide riboside is the active agent, correct?
`
`A: Yes.”), 25:11-14 (“Q: You’re referring to the nicotinamide riboside because
`
`that’s the active agent in the ’086 patent, correct? A: That’s correct.”).
`
`Petitioner’s proposed interpretation ignores and is inconsistent with the
`
`surrounding claim language of claim 1 and the language of the dependent claims,
`
`all of which confirms that the pharmaceutical composition must include
`
`nicotinamide riboside as the active agent. See supra Section II.B. Petitioner’s
`
`proposed construction can be rejected on this basis alone because it unreasonably
`
`seeks 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 (“the context of the surrounding words of the claims also must be
`
`considered in determining the ordinary and customary meaning of those terms”).
`
`
`
`15
`
`

`

`Petitioner’s proposal would also result in the claims being construed to cover
`
`milk. However, milk was explicitly disclosed as a prior art “source” of the active
`
`agent nicotinamide riboside. See ’086 patent, at 4:8-20 (describing an embodiment
`
`where cow’s milk is a natural source of nicotinamide riboside). This disclosure
`
`makes clear that the inventor did not intend the invention to cover milk as it occurs
`
`naturally, so adopting Petitioner’s proposal would not be a reasonable construction.
`
`See In re Smith, 2017 WL 4247407, at *6 (reversing the Board’s anticipation
`
`findings for lack of substantial evidence because giving a disputed term “such a
`
`strained breadth in the face of the otherwise different description in the
`
`specification was unreasonable”).
`
` Accordingly, Petitioner’s proposed
`
`interpretation of
`
`the claimed
`
`pharmaceutical compositions should be rejected because it does not account for the
`
`understanding that first and foremost, the pharmaceutical composition must
`
`contain the specified active agent, which in the ’086 patent is nicotinamide
`
`riboside. See Ex. 2003, Baur Tx., at 19:21-20:16, 23:4-23, 25:11-14. This
`
`understanding, which is reflected in Patent Owner’s proposed construction, is
`
`consistent with the interpretation of a person of ordinary skill in art in light of the
`
`entire disclosure of the ’086 patent. See In re Translogic Tech., Inc., 504 F.3d
`
`1249, 1257 (Fed. Cir. 2007); Ex. 2002, Zhou Decl., at ¶¶ 29-33.
`
`
`
`16
`
`

`

`Accordingly,
`
`the phrase
`
`“pharmaceutical
`
`composition
`
`comprising
`
`nicotinamide riboside” should be construed as a “pharmaceutical composition
`
`containing nicotinamide riboside as the active agent.”
`
`B.
`
`“is isolated from a natural or synthetic source”
`
`Claim 2 covers “[t]he pharmaceutical composition of claim 1, wherein the
`
`nicotinamide riboside is isolated from a natural or synthetic source.” ’086 patent,
`
`at claim 2. Petitioner proposed a construction only for the term “isolated” and
`
`proposed that the term be construed to mean “is separated or substantially free
`
`from at least some of the other components of the naturally occurring organism.”
`
`Pet. at 7. Petitioner relied on a single, incomplete, phrase from the specification in
`
`support of its proposed construction. Id. (citing ’086 patent, at 9:3-10).
`
`Patent Owner requested that the Board construe the complete phrase “is
`
`isolated from a natural or synthetic source” to mean “fractionated from other
`
`cellular components.” Pa