Filed on behalf of: Thorne Research, Inc.
`By: Michael T. Rosato (mrosato@wsgr.com)
`
`Lora M. Green (lgreen@wsgr.com)
`
`Tasha M. Thomas (tthomas@wsgr.com)
`WILSON SONSINI GOODRICH & ROSATI
`701 Fifth Avenue, Suite 5100
`Seattle, WA 98104-7036
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_____________________________
`
`
`THORNE RESEARCH, INC.,
`Petitioner,
`
`v.
`
`TRUSTEES OF DARTMOUTH COLLEGE,
`Patent Owner.
`
`_____________________________
`
`Case No. IPR2021-00491
`Patent No. 8,197,807
`_____________________________
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,197,807
`
`
`
`
`
`

`

`TABLE OF CONTENTS
`
`
`
`C. 
`
`D. 
`
`Page
`Introduction ...................................................................................................... 1 
`A. 
`Brief Overview of the ’807 Patent ........................................................ 2 
`B. 
`Brief Overview of the Prosecution History ........................................... 6 
`i. 
`Summary of the claims’ prosecution .......................................... 6 
`ii. 
`The earliest effective filing date of the claims is April 20,
`2006 ............................................................................................. 8 
`Brief Overview of Prior and Related IPR Proceedings ....................... 18 
`i. 
`The ’807 patent’s prior IPR proceeding ................................... 18 
`ii. 
`The ’086 patent’s prior IPR proceeding ................................... 21 
`The Board Should Not Exercise Its Discretion under Section
`325(d) to Deny Institution ................................................................... 23 
`i. 
`The asserted art is materially different ..................................... 24 
`ii. 
`The asserted art is not cumulative ............................................. 26 
`iii. 
`The asserted art was not materially evaluated during
`examination or during the previous IPR ................................... 26 
`The Board Should Not Exercise Its Discretion under Section
`314(a) to Deny Institution ................................................................... 27 
`i. 
`Factors 1 and 2 .......................................................................... 28 
`ii. 
`Factors 3-5 ................................................................................. 28 
`iii. 
`Factors 6 and 7 .......................................................................... 29 
`Brief Overview of the Scope and Content of the Prior Art ................. 29 
`i. 
`Bieganowski .............................................................................. 32 
`ii. 
`Rosenbloom .............................................................................. 34 
`i
`
`E. 
`
`F. 
`
`I. 
`
`
`
`

`

`iii.  Brenner ...................................................................................... 34 
`Brief Overview of the Level of Skill in the Art .................................. 35 
`G. 
`Grounds for Standing ..................................................................................... 36 
`II. 
`III.  Mandatory Notices under 37 C.F.R. § 42.8 ................................................... 36 
`IV.  Statement of the Precise Relief Requested .................................................... 37 
`V. 
`Claim Construction ........................................................................................ 38 
`A. 
`“carrier” ............................................................................................... 39 
`B. 
`“isolated” ............................................................................................. 39 
`VI.  Detailed Explanation Of Grounds For Unpatentability ................................. 40 
`A. 
`[Ground 1] Claims 1-3 Are Obvious over Bieganowski
`(EX1008) and Rosenbloom (EX1015) ................................................ 40 
`i. 
`Claim 1 ...................................................................................... 44 
`ii. 
`Claim 2 ...................................................................................... 48 
`iii.  Claim 3 ...................................................................................... 49 
`[Ground 2] Claims 1-3 Are Anticipated by Brenner (EX1007) ......... 51 
`i. 
`Claim 1 ...................................................................................... 52 
`ii. 
`Claim 2 ...................................................................................... 54 
`iii.  Claim 3 ...................................................................................... 55 
`VII.  Conclusion ..................................................................................................... 56 
`VIII.  Certificate of Compliance .............................................................................. 57 
`X. 
`Payment of Fees under 37 C.F.R. §§ 42.15(a) and 42.103 ........................... 58 
`XI.  Appendix – List of Exhibits ........................................................................... 59 
`
`B. 
`
`ii
`
`
`

`

`
`
`I.
`
`INTRODUCTION
`
`Thorne Research, Inc., (“Thorne” or “Petitioner”) hereby requests review of
`
`U.S. Patent No. 8,197,807 to Charles M. Brenner (“the ’807 patent,” EX1001),
`
`which is currently assigned to the Trustees of Dartmouth College (“Dartmouth”).
`
`This is the second inter partes review filed against the ’807 patent. The first
`
`IPR, IPR2017-01796 (“the ’1796 IPR”), was filed by Elysium Health, Inc.
`
`(“Elysium”). Elysium challenged the claims of the ’807 patent in that proceeding
`
`on the basis of art that taught the use of milk, skim milk, or buttermilk for the
`
`treatment of black-tongue in dogs and pellagra in human subjects. See EX1025, 7-
`
`11, 18-21. In its Institution Decision (“DI”), the Board declined to institute on the
`
`grounds presented in the petition because the Board found that Elysium had not
`
`demonstrated that the active agent required by the claims, nicotinamide riboside
`
`(“NR”), was isolated as that term had been construed. See EX1027, 5-8, 10-11.
`
`This petition demonstrates that compositions of “isolated” NR were known,
`
`or would have been obvious, in view of the understanding of the art at the time of
`
`invention. And that is not surprising from a reading of the ’807 patent, which
`
`admits that NR was freely available. The ’807 patent specifically acknowledges
`
`that “[s]ynthetic 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.”
`
`
`
`1
`
`

`

`EX1001, 27:39-42. The patent acknowledges further that “[i]solated extracts of
`
`the natural sources can be prepared using standard methods,” or that NR “can be
`
`chemically synthesized using established methods.” Id., 27:45-46, 28:59-61. The
`
`’807 patent also acknowledges that supplements, such a NR, “can be prepared by
`
`methods and contain carriers that are well-known in the art.” Id., 29:29-31.
`
`Moreover, because Patent Owner failed to meet the requirements of Article
`
`4 of the Paris Convention, which governs priority claims made in applications filed
`
`under the Patent Cooperation Treaty (“PCT”), April 20, 2006, is the earliest
`
`priority date to which Patent Owner is entitled. Accordingly, Patent Owner’s
`
`published PCT application, WO 2005/077091 (EX1007, “Brenner”) published
`
`August 25, 2005, which has a different inventive entity and essentially the same
`
`disclosure of the ’807 patent, is prior art to the ’807 patent and anticipates the
`
`challenged claims.
`
`This petition thus demonstrates a reasonable likelihood that claims 1-3 are
`
`unpatentable, and Thorne respectfully requests institution of this proceeding.
`
`A. Brief Overview of the ’807 Patent
`
`The ’807 patent is entitled “Nicotinamide Riboside Kinase Compositions
`
`and Methods for Using the Same,” with Charles M. Brenner being the sole named
`
`inventor. The claims of the ’807 patent relate to compositions of isolated NR
`
`formulated for oral administration, wherein the isolated NR is in combination with
`
`2
`
`
`

`

`one or more of tryptophan, nicotinic acid, or nicotinamide in admixture with a
`
`carrier. See EX1002, ¶¶17-18, 34-36.
`
`One known pathway of biosynthetic synthesis of nicotinamide adenine
`
`dinucleotide (“NAD+”) uses tryptophan, and supplementation with niacins (i.e.,
`
`nicotinic acid and nicotinamide) prevents pellagra in populations with tryptophan-
`
`poor diets. EX1001, 1:23-30. The ’807 patent explains that nicotinic acid and
`
`nicotinamide are known vitamin forms of NAD+. Id., 1:23-25. That is, as
`
`acknowledged by the ’807 patent, “[i]t is well-established that nicotinic acid is
`
`phosphoribosylated to nicotinic acid mononucleotide (NaMN), which is then
`
`adenylated to form nicotinic acid adenine dinucleotide (NaAD), which in turn is
`
`amidated to form NAD+.” Id., 1:30-35 (citations omitted). The ’807 patent also
`
`discloses yeast and human nicotinamide riboside kinase enzymes (“Nrk”), which
`
`have specific functions in NAD+ metabolism. Id., 3:11-13; EX1002, ¶¶19-20.
`
`The ’807 patent also discloses “a dietary supplement composition containing
`
`nicotinamide riboside identified in accordance with the methods of the present
`
`invention and a carrier.” EX1001, 4:21-23; EX1002, ¶21. The ’807 patent
`
`generally states that the NR may be “administered in combination with tryptophan,
`
`nicotinic acid or nicotinamide.” EX1001, 4:34-36. The ’807 patent notes that NR
`
`was known to be a precursor for NAD+ in bacteria, but it was found that it is also a
`
`precursor to NAD+ in a eukaryotic biosynthetic pathway. EX1001, 3:3-5, 3:10-11;
`
`3
`
`
`

`

`EX1002, ¶20. The ’807 patent describes a method for identifying natural sources
`
`of NR using a mutant strain of yeast, where the yeast is only able to grow normally
`
`when supplied with a source containing NR. EX1001, 7:66-8:10. The ’807 patent
`
`also discloses that “milk is a source of nicotinamide riboside.” Id., 3:19-20; see
`
`also id., 7:66-8:1 (noting NR was identified in an acid whey preparation from
`
`cow’s milk); EX1002, ¶27. As demonstrated by the ’807 patent, NR found in the
`
`whey fraction of milk was sufficient to support the growth of a yeast strain that
`
`requires NR for growth. EX1001, 7:66-8:10, 27:7-9; EX1002, ¶27.
`
`As acknowledged by the ’807 patent, NR can be obtained commercially,
`
`isolated from natural sources using standard methods, or synthesized using
`
`established methods. EX1001, 27:39-42, 27:45-46, 28:58-61; EX1002, ¶23. For
`
`example, the ’807 patent discloses that “[s]ynthetic sources of nicotinamide
`
`riboside can include any library of chemicals commercially available from most
`
`large chemical companies including Merck, Glaxo, Bristol Myers Squibb,
`
`Monsanto/Searle, Eli Lilly and Pharmacia.” EX1001, 27:39-42; EX1002, ¶¶24-26.
`
`A wide variety of carriers are also disclosed by the ’807 patent, which notes that
`
`the compositions “can be prepared by methods and contain carriers which are well-
`
`known in the art.” EX1001, 29:43-58, 29:27-35; EX1002, ¶¶29-30.
`
`4
`
`
`

`

`The ’807 patent further discloses methods for preventing or treating a
`
`disease or condition associated with the NR pathway of NAD+ biosynthesis.
`
`EX1001, 4:24-26; EX1002, ¶22. The ’807 patent teaches:
`
`[A]gents (e.g., nicotinamide riboside) that work through the
`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.
`EX1001, 28:35-41; EX1002, ¶28.
`
`
`
`As for a therapeutically effective amount, the ’807 patent teaches that it is
`
`the amount of NR that “prevents, reduces, alleviates or eliminates the signs or
`
`symptoms of the disease or condition being prevented or treated.” EX1001, 29:11-
`
`14. The patent further states that the effective amount will vary with the disease or
`
`condition being addressed, and that the skilled clinician can evaluate the disease or
`
`condition after treatment and adjust the amount of NR as needed. Id., 29:14-18;
`
`EX1002, ¶31.
`
`
`
`The ’807 patent provides five examples, only one of which is relevant to the
`
`claimed composition. EX1002, ¶¶32-33. Specifically, Example 2 teaches
`
`preparation of a vitamin fraction from whey, as well as synthesis of NR from
`
`NMN. EX1001, 33:30-45; EX1002, ¶32.
`
`5
`
`
`

`

`Claim 1 of the ’807 patent recites:
`
`A composition comprising isolated nicotinamide riboside in combination
`
`with one or more of tryptophan, nicotinic acid, or nicotinamide, wherein said
`
`combination is in admixture with a carrier comprising a sugar, starch, cellulose,
`
`powdered tragacanth, malt, gelatin, talc, cocoa butter, suppository wax, oil, glycol,
`
`polyol, ester, agar, buffering agent, alginic acid, isotonic saline, Ringer’s solution,
`
`ethyl alcohol, polyester, polycarbonate, or polyanhydride, wherein said
`
`composition is formulated for oral administration and increases NAD+
`
`biosynthesis upon oral administration.
`
`Claim 2 is dependent from claim 1, and recites:
`
`The composition of claim 1, wherein the nicotinamide riboside is isolated
`
`from a natural or synthetic source.
`
`Claim 3 is also dependent from claim 1, and recites:
`
`The composition of claim 1, wherein the formulation comprises a tablet,
`
`troche, capsule, elixir, suspension, syrup, wafer, chewing gum, or food.
`
`See EX1002, ¶¶34-36.
`
`B.
`
`Brief Overview of the Prosecution History
`
`i. Summary of the claims’ prosecution
`
`The ’807 patent arose from U.S. Application No. 11/912,400 (“the ’400
`
`application”), filed on November 20, 2007. The original claims of the ’400
`
`6
`
`
`

`

`application were subject to a restriction requirement. See EX1004, 209-16. In
`
`response, applicant submitted a new set of claims directed to “[a] composition
`
`comprising isolated nicotinamide riboside in admixture with a carrier.” Id., 198-
`
`204.
`
`The examiner rejected the claims as anticipated by either Saunders (EX1028
`
`(Saunders 1), EX1029 (Saunders 2)) or Tanimori (EX1024). See EX1004, 182-84.
`
`Saunders prepared NR by enzymatic degradation of NAD+ or NMN, while
`
`Tanimori synthesized NR from nicotinamide and β-D-ribofuranose 1,2,3,5-
`
`tetraacetate. Id. The examiner additionally cited Tanimori for teaching “that
`
`nicotinamide riboside is a precursor of nicotinamide mononucleotide (β-NMN)
`
`which is a component used for chemical or enzymatic preparation of NAD+.” Id.
`
`at 184. Applicant amended the claims to further recite specific options for the
`
`carrier and that the isolated NR was in combination with one or more of
`
`tryptophan, nicotinic acid, or nicotinamide. Id., 128. The examiner applied the
`
`same references, rejecting the claims as obvious. See id., 115-18 (further applying
`
`Cuny (EX1016) as disclosing well-known carrier materials). Applicant again
`
`amended the claims to additionally recite that the composition is formulated for
`
`oral administration and increases NAD+ biosynthesis upon oral administration.
`
`See 1004, 57, 75. With regard to the former limitation, the examiner considered
`
`the claims obvious over the same references, but allowed the claims in view of the
`
`7
`
`
`

`

`latter limitation. See id., 50-51, 71-72. During prosecution, applicant pointed to
`
`Bieganowski (EX1008) as evidence establishing that NR was an NAD+ precursor
`
`in humans. Id., 103-04.
`
`ii. The earliest effective filing date of the claims is April 20, 2006
`
`On its face, the ’807 patent purports to be the national-stage entry of
`
`International Patent Application No. PCT/US2006/015495 (“the ’495 PCT
`
`application”) filed on April 20, 2006. EX1001, (22), (86). The ’807 patent further
`
`states that the ’495 PCT application claims the benefit of priority to U.S.
`
`Application No. 11/113,701 (“the ’701 application”), filed April 25, 2005, which,
`
`in turn, is a continuation-in-part of International Patent Application No.
`
`PCT/US2005/004337 (“the ’337 PCT application,” published as WO
`
`2005/077091), filed February 9, 2005. EX1001, 1:11-15. The ’337 PCT
`
`application claims the benefit of priority to U.S. Provisional Application
`
`60/534,347 (“the ’347 provisional”). EX1001, 1:15-19. As explained below, per
`
`the rules governing priority claims under the Paris Convention for the Protection of
`
`Industrial Property (“the Paris Convention”), the ’807 patent is, at best, only
`
`8
`
`
`

`

`entitled to the filing date of the ’495 PCT application, which is April 20, 2006, and
`
`not the filing dates of any of its earlier-claimed applications.1
`
`Article 4 of the Paris Convention governs priority claims made in
`
`applications filed under the Patent Cooperation Treaty (PCT). See PCT, Art. 8,
`
`sec. 2(a) (“[T]he conditions for, and the effect of, any priority claim…shall be as
`
`provided in Article 4…of the Paris Convention….”). Sections (C)(1)-(2) and C(4)
`
`of Article 4 state:
`
`(C)(1) The periods of priority…shall be twelve months for patents and
`utility models, and six months for industrial designs and trademarks.
`(C)(2) These periods shall start from the date of filing of the first
`application; the day of filing shall not be included in the period.
`***
`(C)(4) A subsequent application concerning the same subject as a
`previous first application within the meaning of paragraph (2), above,
`filed in the same country of the Union, shall be considered as the first
`application, of which the filing date shall be the starting point of the
`period of priority, if, at the time of filing the subsequent application,
`the said previous application has been withdrawn, abandoned, or
`refused, without having been laid open to public inspection and
`
`
`1 Because Bieganowski (EX1008) was published more than one year before the
`
`April 20, 2006 priority date Dartmouth is only able to claim under the Paris
`
`Convention, Dartmouth is unable to remove Bieganowski as a prior-art reference.
`
`9
`
`
`

`

`without leaving any rights outstanding, and if it has not yet served
`as a basis for claiming a right of priority. The previous application
`may not thereafter serve as a basis for claiming a right of priority.
`
`Emphasis added.
`
`
`
`Thus, under Paris Convention rules, to make a proper claim of priority for
`
`subject matter contained in a PCT application, the PCT application must have been
`
`filed within twelve months of the filing of the first application containing that
`
`subject matter. A subsequently-filed application containing the same subject
`
`matter may qualify as a “first” application only if the previous application has been
`
`withdrawn, abandoned, or refused and has not yet served as a basis for claiming a
`
`right of priority at the time of the subsequently-filed application’s filing.
`
`The ’347 provisional, filed on February 10, 2004, was the first application
`
`filed containing the subject matter of the claims of the challenged ’807 patent.
`
`This is demonstrated by the table below, which compares the limitations of claims
`
`1-3 to the disclosure of the ’347 provisional.
`
`Claim 1
`
`The ’347 provisional (EX1005)2
`
`[1.Preamble] A composition
`comprising isolated
`
`“Another aspect of the present invention is a
`dietary supplement composition containing
`
`
`2 As cited in the Table, the disclosure presented herein also appears in the ’807
`
`patent’s specification.
`
`10
`
`
`

`

`nicotinamide riboside
`
`nicotinamide riboside identified in accordance
`with the methods of the present invention and a
`carrier.” EX1005, 6:27-30; cf. EX1001, 4:21-23.
`
`“A still further aspect of the 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…an effective amount of a nicotinamide
`riboside composition….” EX1005, 6:31-7:6; cf.
`EX1001, 4:23-31.
`
`“As described herein, nicotinamide riboside
`isolated from deproteinized whey fraction of
`cow’s milk was sufficient to support NRK1-
`dependent growth in a qns1 mutant.
`Accordingly, mutant strains generated herein
`will be useful in identifying other natural or
`synthetic sources for nicotinamide riboside for
`use in dietary supplements.” EX1005, 53:17-24;
`cf. EX1001, 27:7-12.
`
`“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.
`
`11
`
`
`

`

`Natural sources which can be tested 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.” EX1005, 54:19-55:2; see also id.,
`64:29-65:9 (Example 2 describing preparation of
`isolated NR with a whey vitamin fraction); cf.
`EX1001, 27:39-46, 33:30-45.
`
`“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 or other polypeptides
`or nucleic acids commonly found 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).”
`EX1005, 16:13-24; cf., EX1001, 9:23-33.
`
`[1.1] in combination with one
`or more of tryptophan,
`
`“The method involves administering to a patient
`having a disease or condition associated with the
`nicotinamide riboside kinase pathway of NAD+
`
`12
`
`
`

`

`nicotinic acid, or
`nicotinamide,
`
`[1.2] wherein said
`combination is in admixture
`with a carrier comprising a
`sugar, starch, cellulose,
`powdered tragacanth, malt,
`gelatin, talc, cocoa butter,
`suppository wax, oil, glycol,
`polyol, ester, agar, buffering
`agent, alginic acid, isotonic
`saline, Ringer’s solution,
`ethyl alcohol, polyester,
`polycarbonate, or
`polyanhydride,
`
`biosynthesis an effective amount of a
`nicotinamide riboside composition so that the
`signs or symptoms of the disease or condition
`are prevented or reduced…. In another
`embodiment, the nicotinamide riboside is further
`administered in combination with tryptophan,
`nicotinic acid or nicotinamide.” EX1005, 7:1-
`10; cf. EX1001, 4:23-36.
`
`“Another aspect of the present invention is a
`dietary supplement composition containing
`nicotinamide riboside…and a carrier.” EX1005,
`6:27-30; cf. EX1001, 4:21-23.
`
`“Polypeptides, nucleic acids, vectors, dietary
`supplements (i.e. nicotinamide riboside), and
`nicotinamide riboside-related prodrugs…can be
`conveniently used or administered in a
`composition containing the active agent in
`combination with a carrier. Such compositions
`can be prepared by methods and contain carriers
`which are well-known in the art.” EX1005,
`56:16-57:2; see also id., 57:3-24 (listing
`exemplary carriers); cf. EX1001, 29:24-62.
`
`[1.3] wherein said
`composition is formulated for
`oral administration and
`
`“Polypeptides, nucleic acids, vectors, dietary
`supplements, and nicotinamide riboside-related
`prodrugs…can be administered via any route
`
`13
`
`
`

`

`increases NAD+ biosynthesis
`upon oral administration.
`
`includ[ing], but not limited to, oral….” EX1005,
`57:25-58:9; cf. EX1001, 29:63-30:12.
`
`“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.” EX1005, 58:15-19; see also
`id., 58:26-59:20 (describing various means for
`oral administration); cf. EX1001, 30:19-56.
`
`“It has now been shown that nicotinamide
`riboside, which was known to be an NAD+
`precursor in bacteria such as Haemophilus
`influenza…is an NAD+ precursor in a
`previously unknown but conserved eukaryotic
`NAD+ biosynthetic pathway.” EX1005, 4:2-10;
`see also id., 6:27-7:6, 15:32-16:5 (“nicotinamide
`riboside supplementation could be one route to
`improve lipid profiles in humans” and “could be
`an important supplement for acute conditions
`such as stroke”); cf. EX1001, 3:3-11, 4:21-33,
`9:9-14.
`
`“Thus, another aspect of the present invention is
`a method for preventing or treating a disease or
`condition…by administering an effective
`
`14
`
`
`

`

`amount of a nicotinamide riboside composition.”
`EX1005, 55:20-56:10; cf. EX1001, 28:41-45.
`
`Claim 2
`
`The ’347 provisional (EX1005)
`
`The composition of claim 1,
`wherein the nicotinamide
`riboside is isolated from a
`natural or synthetic source.
`
`“A still further aspect of the present invention is
`a method for identifying a natural or synthetic
`source for nicotinamide riboside.” EX1005,
`6:13-15; cf. EX1001, 4:8-9.
`
`“Another aspect of the present invention is a
`dietary supplement composition containing
`nicotinamide riboside identified in accordance
`with the present invention and a carrier.”
`EX1005, 6:27-30; cf. EX1001, 4:21-23.
`
`“As described herein, nicotinamide riboside
`isolated from deproteinized whey fraction of
`cow’s milk was sufficient to support NRK1-
`dependent growth in a qns1 mutant.
`Accordingly, mutant strains generated herein
`will be useful in identifying other natural or
`synthetic sources for nicotinamide riboside for
`use in dietary supplements.” EX1005, 53:17-24;
`cf. EX1001, 27:7-12.
`
`“Synthetic sources of nicotinamide riboside can
`include any library of chemicals commercially
`available from most large chemical companies
`including Merck, Glaxo, Bristol Meyers Squibb,
`
`15
`
`
`

`

`Monsanto/Searle, Eli Lilly and Pharmacia.
`Natural sources which can be tested 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.” EX1005, 54:19-55:2; see also id.,
`64:29-65:9 (Example 2 describing preparation of
`isolated NR with a whey vitamin fraction); cf.
`EX1001, 27:39-46, 33:30-45.
`
`Claim 3
`
`The ’347 provisional (EX1005)
`
`The composition of claim 1,
`wherein the formulation
`comprises a tablet, troche,
`capsule, elixir, suspension,
`syrup, wafer, chewing gum,
`or food.
`
`“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.” EX1005, 58:15-19; cf.
`EX1001, 30:19-23.
`
`
`
`
`
`As noted above, the ’495 PCT application was filed on April 20, 2006, more
`
`than twelve months after the filing of the ’347 provisional. EX1001, (87).
`
`Therefore, the ’495 PCT application cannot claim priority back to the ’347
`
`provisional with respect to the subject matter of claims 1-3, nor can it claim
`
`priority to the subsequently-filed ’337 PCT application, which was filed February
`
`16
`
`
`

`

`9, 2005. Moreover, because the Paris Convention rules have not been followed,
`
`any earlier claim of priority to subsequently-filed applications (i.e., the ’701
`
`application, filed April 25, 2005) containing the same subject matter as the ’347
`
`provisional is defective and has been lost.3
`
`As a result, the earliest possible priority date for claims 1-3 of the ’807
`
`patent is April 20, 2006, the filing date of the ’495 PCT application, because the
`
`’495 PCT application does not meet the requirements of Section 4 of the Paris
`
`Convention as it was filed more than twelve months after the filing of the first
`
`application containing the subject matter of the claims (i.e., the ’347 provisional).4
`
`
`3 At the time of the ’701 application’s filing, the ’347 provisional had not been
`
`“withdrawn, abandoned, or refused” as the ’701 application itself claimed a benefit
`
`of priority to the ’347 provisional. See EX1019, 241. The ’347 provisional also
`
`served as a basis for priority in the ’337 PCT application. See EX1007, (30).
`
`Thus, the ’701 application as a subsequent application to the same subject matter
`
`cannot qualify as a “first” application under Paris Convention rules.
`
`4 The ’807 patent also cannot directly claim priority to the ’701 application
`
`because the ’701 application had been abandoned before the filing date of the ’807
`
`patent (November 20, 2007). See EX1019, 1-4 (notice of abandonment mailed
`
`December 28, 2006).
`
`17
`
`
`

`

`This understanding is consistent with the Office’s Corrected Filing Receipt issued
`
`for the ’807 patent, which corrected the patent’s priority claim to include only the
`
`benefit of the ’495 PCT application’s filing date. Compare EX1004, 42 (corrected
`
`filing receipt) with id., 225 (original filing receipt).
`
`C. Brief Overview of Prior and Related IPR Proceedings
`
`As noted above, the ’807 patent was the subject of a prior IPR proceeding,
`
`the ’1796 IPR, initiated by Petitioner Elysium on July 17, 2017, but denied
`
`institution by the Board on January 18, 2018. Also relevant, a child patent to the
`
`’807 patent, U.S. Patent No. 8,383,086 (“the ’086 patent”), was the subject of
`
`another IPR proceeding, IPR2017-01795 (“the ’1795 IPR”), brought by Petitioner
`
`Elysium. The ’1795 IPR was instituted and received a Final Written Decision
`
`(“FWD”) determining all claims, except a dependent claim directed to a
`
`pharmaceutical composition containing isolated NR, were unpatentable.5
`
`i. The ’807 patent’s prior IPR proceeding
`
`The Elysium petition requested review of claims 1-3 of the ’807 patent and
`
`advanced two grounds: (1) claims 1-3 as anticipated under 35 U.S.C. § 102(b) by
`
`Goldberger et al., A Study of the Blacktongue-Preventive Action of 16 Foodstuffs,
`
`
`5 The current Petitioner, Thorne, is not an entity related to Elysium, nor was
`
`Thorne involved in the Elysium IPRs.
`
`18
`
`
`

`

`with Special Reference to the Identity of Blacktongue of Dogs and Pellagra of
`
`Man, 43 Pub. Health Reports 1385 (1928) (EX1011, “Goldberger”); and (2) claims
`
`1-3 as anticipated under § 102(b) by Goldberger and Tanner, A Study of the
`
`Treatment and Prevention of Pellagra, 39 Pub. Health Reports 87 (1924)
`
`(EX1012, “Goldberger and Tanner”). See EX1025, 5.
`
`The grounds advanced by Elysium relied in large part on inherency. The
`
`primary references described studies on the oral consumption of cow skim milk
`
`and buttermilk to prevent the onset of “black-tongue” in dogs and pellagra in
`
`human subjects, respectively. See id., 8-10, 18-19. Although not known to the
`
`researchers at the time, later research had established that NR, in addition to
`
`tryptophan and nicotinamide, was naturally present in milk, and thus, the milk
`
`orally administered in the references necessarily contained NR in combination with
`
`tryptophan and nicotinamide. See id., 11-13, 20, 24-25. Later research also
`
`established that NR prevented the diseases studied in the references and was more
`
`orally bioavailable than nicotinamide, making it a more potent booster of NAD+
`
`biosynthesis. See id., 10-11, 15, 21, 26.
`
`In its petition, Elysium advanced a construction for the term “isolated”
`
`recited in the claims as meaning “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
`
`19
`
`
`

`

`commonly found associated with the molecule.” EX1025, 6-7 (citing EX1001,
`
`9:23-30). With this construction, Elysium argued that the claims were anticipated
`
`by Goldberger because “[s]kim milk is the product that remains when almost all of
`
`the cream is removed from whole milk,” making the NR naturally present in the
`
`skim milk “isolated during the process of converting whole milk to skim milk
`
`because, during that process, the non-fat elements of whole milk (including
`
`nicotinamide riboside present in skim milk) are separated from the fat.” EX1025,
`
`14-16. Elysium advanced similar arguments in its second ground, reasoning the
`
`buttermilk orally administered in Goldberger and Tanner also contained “isolated”
`
`NR due to the process of converting whole milk or cream to buttermilk. Id., 23.
`
`In its DI, the Board construed the term “isolated” to mean “the nicotinamide
`
`riboside is separated or substantially free from at least some of the other
`
`compo