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`IPR2021-00491
`
`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 IPR2021-00491
`
`Patent 8,197,807
`_______________
`
`PATENT OWNER RESPONSE
`
`
`
`

`

`IPR2021-00491
`Patent Owner Response
`
`2.
`
`3.
`
`TABLE OF CONTENTS
`
`I.
`INTRODUCTION ......................................................................................... 1
`BACKGROUND OF DR. BRENNER’S INVENTION ............................. 3
`II.
`III. PETITIONER HAS NOT MET ITS BURDEN OF SHOWING THAT
`EITHER THE CELL ARTICLE (GROUND 1) OR THE ’337 PCT
`PUBLICATION (GROUND 2) IS PRIOR ART ........................................ 6
`A.
`The Asserted Cell Article and ’337 PCT Publication Are Not “By
`Another” and Thus Not Prior Art Under 35 U.S.C. § 102(a) or
`§ 102(e) .................................................................................................. 7
`1.
`To Qualify as Prior Art Under § 102(a) or § 102(e), Relied-
`Upon Subject Matter in the Reference Must Be Invented “By
`Another,” i.e., by Dr. Bieganowski ............................................. 8
`The Invention of the ’807 Patent and Relied-Upon Subject
`Matter in the Cell Article and ’337 PCT Publication ............... 12
`The Relied-Upon Subject Matter in the Cell Article and ’337
`PCT Publication Was Invented Only by Dr. Brenner And Not
`Dr. Bieganowski ........................................................................ 14
`Patent Owner’s Evidence For the “By Another” Issue Is
`Corroborated and Sufficient ...................................................... 18
`The Board’s Institution Decision .............................................. 23
`5.
`The Asserted Cell Article Is Not Prior Art Under
`35 U.S.C. § 102(b)............................................................................... 26
`1.
`Petitioner’s Position on Priority Is Based on an Unsupported
`and Inapplicable Paris Convention Argument .......................... 27
`The ’807 Patent’s Priority Claim to the ’701 Application Meets
`the Requirements of 35 U.S.C. § 120 and the Cell Article Is
`Thus Not Prior Art Under § 102(b) .......................................... 35
`IV. CONCLUSION ............................................................................................ 38
`
`
`B.
`
`4.
`
`2.
`
`i
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`

`

`IPR2021-00491
`Patent Owner Response
`
`TABLE OF AUTHORITIES
`
`
`Page(s)
`
`Cases
`
`Actelion Pharm., Ltd. v. Matal,
`881 F.3d 1339 (Fed. Cir. 2018) .......................................................................... 29
`In re Costello,
`717 F.2d 1346 (Fed. Cir. 1983) ............................................................................ 8
`CSL Behring LLC v. Bioverativ Therapeutics Inc.,
`IPR2018-01313, Paper 10 (P.T.A.B. Jan. 9, 2019) ............................................ 11
`In re DeBaun,
`687 F.2d 459 (C.C.P.A. 1982) ............................................................................ 19
`Duncan Parking Techs., Inc. v. IPS Grp., Inc.,
`914 F.3d 1347 (Fed. Cir. 2019) .......................................................... 9, 11, 13, 15
`Dynamic Drinkware, LLC v. Nat’l Graphics, Inc.,
`800 F.3d 1375 (Fed. Cir. 2015) ............................................................................ 9
`EmeraChem Holdings, LLC v. Volkswagen Grp. of Am., Inc.,
`859 F.3d 1341 (Fed. Cir. 2017) ................................................................ 8, 20, 22
`Ethicon LLC v. Intuitive Surgical, Inc.,
`847 F. App’x 901 (Fed. Cir. 2021) ................................................................. 9, 13
`In re Gosteli,
`872 F.2d 1008 (Fed. Cir. 1989) .......................................................................... 31
`In re Katz,
`687 F.2d 450 (C.C.P.A. 1982) ............................................................ 8, 11, 18, 19
`In re Mathews,
`408 F.2d 1393 (C.C.P.A. 1969) .......................................................................... 20
`In re NTP, Inc.,
`654 F.3d 1268 (Fed. Cir. 2011) .......................................................................... 35
`In re Rath,
`402 F.3d 1207 (Fed. Cir. 2005) .......................................................................... 29
`
`ii
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`

`IPR2021-00491
`Patent Owner Response
`
`Return Mail, Inc. v. U.S. Postal Serv.,
`139 S. Ct. 1853 (2019) ........................................................................................ 31
`Sandt Tech., Ltd. v. Resco Metal & Plastics Corp.,
`264 F.3d 1344 (Fed. Cir. 2001) .......................................................................... 21
`Sanofi-Aventis v. Immunex,
`IPR2017-01879, Paper 88 (P.T.A.B. Feb. 14, 2019) .......................................... 18
`Scimed Life Sys. v. Medtronic Vascular, Inc.,
`468 F. Supp. 2d 60 (D.D.C. 2006) ...................................................................... 30
`Tech. Licensing Corp. v. Videotek, Inc.,
`545 F.3d 1316 (Fed. Cir. 2008) .......................................................................... 32
`Thomson, S.A. v. Quixote Corp.,
`166 F.3d 1172 (Fed. Cir. 1999) .......................................................................... 25
`Thorne Research, Inc. v. Trustees of Dartmouth College,
`IPR2021-00268, Paper 21 (P.T.A.B. June 10, 2021) ..................................passim
`Trans Ova Genetics, LC v. XY, LLC,
`No. IPR2018-00250, Paper 35 (P.T.A.B. June 26, 2019) .................................. 25
`Varian Med. Sys. v. William Beaumont Hospital,
`IPR2016-00160, Paper 82 (P.T.A.B. May 4, 2017) ....................................... 9, 21
`Yasuko Kawai v. Metlestics,
`480 F.2d 880 (C.C.P.A. 1973) ............................................................................ 29
`Statutes
`35 U.S.C. § 102(a) ............................................................................................passim
`35 U.S.C. § 102(b) ............................................................................................passim
`35 U.S.C. § 119 .................................................................................................passim
`35 U.S.C. § 120 .................................................................................................passim
`35 U.S.C. § 316 ...................................................................................................... 1, 9
`35 U.S.C. § 363 .................................................................................................. 32, 37
`
`iii
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`

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`IPR2021-00491
`Patent Owner Response
`
`Other Authorities
`https://wipolex.wipo.int/en/text/287556 .................................................................. 28
`https://wipolex.wipo.int/en/text/288637 .................................................................. 28
`MPEP § 1893.03(c) .................................................................................................. 37
`
`iv
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`

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`IPR2021-00491
`
`Pursuant to 35 U.S.C. § 316(a)(8) and 37 C.F.R. § 42.120, Trustees of
`
`Dartmouth College (“Patent Owner”) respectfully submit this Response to the
`
`Petition filed by Thorne Research, Inc. (“Petitioner”) regarding U.S. Patent No.
`
`8,197,807 (Ex. 1001, “the ’807 patent”).
`
`I.
`
`INTRODUCTION
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`Petitioner bears “the burden of proving a proposition of unpatentability by a
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`preponderance of the evidence.” 35 U.S.C. § 316(e). Petitioner has failed to meet
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`that burden here.
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`The primary reference in each of Petitioner’s Grounds is not prior art. The
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`relied-upon portions of the ’337 PCT Publication1 and Cell article2 regarding
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`1 International Publication No. WO 2005/077091 A2 (“the ’337 PCT Publication”)
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`(Ex. 1007).
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`2 Bieganowski & Brenner, “Discoveries of Nicotinamide Riboside as a Nutrient
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`and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD+
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`in Fungi and Humans,” 117 Cell 495 (May 14, 2004) (“the Cell article”) (Ex.
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`1008).
`
`1
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`

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`IPR2021-00491
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`claims 1-3 of the ’807 patent are not “by another,” and thus these two references
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`are not prior art under either pre-AIA § 102(a) or § 102(e).3
`
`In addition, with respect to Petitioner’s assertion of the Cell article as pre-
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`AIA § 102(b) prior art, Petitioner’s priority argument is based entirely on an
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`unsupported theory that the ’807 patent priority claim is defective under the Paris
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`Convention treaty. Tellingly, Petitioner cites no U.S. law or statute in support of
`
`its theory. The ’807 patent makes a proper priority claim to earlier U.S. Patent
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`Application No. 11/113,701 (“the ’701 Application”) under 35 U.S.C. § 120, the
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`controlling U.S. statute, and Petitioner does not even argue otherwise. Indeed, the
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`Board correctly found in its Institution Decision in a related IPR that a continuation
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`of the ’807 patent properly claims priority back to the ’701 Application through the
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`’807 patent.4 Thus, the Cell article is not prior art under pre-AIA § 102(b).
`
`
`3 The Petition refers to the ’337 PCT Publication and Cell article as “Brenner” (Ex.
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`1007) and “Bieganowski” (Ex. 1008), respectively. See Pet. at 32-35, 59. Patent
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`Owner refers to the asserted references as the ’337 PCT Publication (Ex. 1007) and
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`Cell article (Ex. 1008) to avoid confusion with eponymous declarations in this IPR.
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`4 Thorne Research, Inc. v. Trustees of Dartmouth College, IPR2021-00268, Paper
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`21, 15-17 (P.T.A.B. June 10, 2021) (regarding U.S. Patent No. 8,383,086 (“the
`
`’086 patent”)).
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`2
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`

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`IPR2021-00491
`
`For at least the reasons set forth herein, Petitioner has failed to meet its
`
`burden to establish that claims 1-3 of the ’807 patent are unpatentable.
`
`II. BACKGROUND OF DR. BRENNER’S INVENTION
`
`Charles M. Brenner, Ph.D. (“Dr. Brenner”) is the sole inventor of the ’807
`
`patent. Ex. 2002 ¶¶ 6, 11-15; ’807 patent at (75). The claimed invention stemmed
`
`from a nicotinamide riboside (“NR”) research project (“NR research project”) that
`
`Dr. Brenner led in late 2003 and early 2004 at Dartmouth Medical School. See id.
`
`¶¶ 11-15; Ex. 2015 ¶¶ 6-14.
`
`For decades prior to Dr. Brenner’s invention, scientists knew about the
`
`importance of nicotinamide adenine dinucleotide (“NAD+”) to human health, see
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`Ex. 2017 at 83 (explaining that NAD+ is of “immeasurable importance in cellular
`
`metabolism”), and that increasing NAD+ levels could aid in treating numerous
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`diseases, see Ex. 2018 (filed 1988) at Abstract; Ex. 2019 (filed 1999) at 1:14-18.
`
`While scientists were aware that compounds such as nicotinic acid and
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`nicotinamide were capable of increasing NAD+ levels, see Ex. 2018 at 2:33-43,
`
`prior to the invention of Dr. Brenner, the role of NR in increasing NAD+ levels
`
`was not understood. Ex. 2015 ¶ 8.
`
`Dr. Brenner realized that there were unsolved problems in NAD+
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`metabolism and a potential opportunity for gene and pathway discovery related to
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`NAD+, which led him to focus on NR. Id. ¶ 8. As part of the NR research project,
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`3
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`

`

`IPR2021-00491
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`Dr. Brenner established that NR is an NAD+ precursor in a previously-unknown
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`pathway. Id. ¶ 9. Dr. Brenner’s research project also led to the identification of
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`“yeast nicotinamide riboside kinase, Nrk1, and both human Nrk enzymes and [the
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`demonstration of] their specific functions in NAD+ metabolism biochemically and
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`genetically.” Id. ¶ 10; Ex. 1008 at 495. Dr. Brenner’s research led him to
`
`conclude that NR is a useful compound for elevation of NAD+ and that
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`supplementation with NR may be beneficial. Ex. 2015 ¶ 10. It was Dr. Brenner
`
`alone who conceived of the invention of claims 1-3 of the ’807 patent. Id. ¶¶ 5, 10,
`
`12-13; Ex. 2002 ¶ 14.
`
`Dr. Brenner’s laboratory research team included a postdoctoral fellow
`
`named Pawel Bieganowski Ph.D. (“Dr. Bieganowski”), who performed, at Dr.
`
`Brenner’s direction, experiments and assays for identifying yeast and human genes
`
`that have Nrk activity. Ex. 2002 ¶ 13; Ex. 2003 ¶ 7; Ex. 2015 ¶ 11; Ex. 2004 at
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`16:18-17:3, 19:10-14, 21:22-22:14. Dr. Bieganowski did not have an inventive
`
`role in any aspect of Dr. Brenner’s inventions regarding therapeutic uses or
`
`compositions of NR. Ex. 2002 ¶ 14; Ex. 2003 ¶ 8; Ex. 2015 ¶ 12; see also Ex.
`
`2004 at 21:22-22:14, 26:14-23, 10:10-20.
`
`As a result of the NR research project, Dartmouth filed U.S. Provisional
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`Patent Application No. 60/543,347 (“the ’347 Provisional”) on February 10, 2004,
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`and International Application No. PCT/US2005/004337 (“the ’337 PCT
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`4
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`

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`IPR2021-00491
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`Application”) on February 9, 2005, which claimed priority to the ’347 Provisional.
`
`See Ex. 1005; Ex. 1007; Ex. 2002 ¶¶ 7-8, 15; Ex. 2015 ¶ 13. On August 25, 2005,
`
`the ’337 PCT Application was published as the ’337 PCT Publication, which
`
`Petitioner asserts in Ground 2 as the “Brenner” reference. See Pet. at 34, 38; Ex.
`
`1007; Ex. 2002 ¶ 8. The ’347 Provisional and ’337 PCT Publication both name
`
`Dr. Brenner and Dr. Bieganowski as co-inventors, but the portions of the ’337 PCT
`
`Publication relied upon by the Petition are solely the invention of Dr. Brenner. See
`
`Ex. 1005 at 3; Ex. 1007 at (75); Pet. at 34-35, 51-56; Ex. 2002 ¶¶ 7-8, 16-17; Ex.
`
`2003 ¶¶ 6, 8; Ex. 2015 ¶¶ 14-28; see also Ex. 2004 at 19:10-14, 21:22-22:14,
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`26:14-23, 10:10-20.
`
`Certain aspects of the NR research project were also included in the Cell
`
`article, which was published on May 14, 2004, and which Petitioner asserts in
`
`Ground 1 of this IPR as the “Bieganowski” reference. See Pet. at 32, 38; Ex. 1008;
`
`Ex. 2002 ¶ 9; Ex. 2015 ¶ 13. The Cell article names Dr. Brenner and Dr.
`
`Bieganowski as co-authors, but the portions of the Cell article relied upon by the
`
`Petition are solely the invention of Dr. Brenner. See Ex. 1008 at 495; Pet. at 40-
`
`50; Ex. 2002 ¶¶ 9, 18-19; Ex. 2003 ¶¶ 6, 8; Ex. 2015 ¶¶ 14-15, 29-34; see also Ex.
`
`2004 at 19:10-14, 21:22-22:14, 26:14-23, 10:10-20.
`
`The ’807 patent is directed to compositions of isolated NR in combination
`
`with one or more of tryptophan, nicotinic acid, or nicotinamide, wherein the
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`5
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`

`

`IPR2021-00491
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`composition is in admixture with a carrier and is formulated for oral administration
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`and increases NAD+ biosynthesis upon oral administration. See ’807 patent at
`
`claims 1-3. The ’807 patent issued from U.S. Patent Application No. 11/912,400
`
`(“the ’400 Application”). The ’400 Application is a national stage entry of
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`International Application No. PCT/US2006/015495 (“the ’495 PCT”), which
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`claims priority to the ’701 Application. The ’807 patent thus claims priority at
`
`least back to the ’701 Application. See id. at 1:11-13.
`
`III. PETITIONER HAS NOT MET ITS BURDEN OF SHOWING THAT
`EITHER THE CELL ARTICLE (GROUND 1) OR THE ’337 PCT
`PUBLICATION (GROUND 2) IS PRIOR ART
`Petitioner asserts Ground 1 based on the Cell article and Ground 2 based on
`
`the ’337 PCT Publication, but neither of these references is prior art. First, the
`
`portions of the Cell article and ’337 PCT Publication that Petitioner relies upon for
`
`the alleged unpatentability of claims 1-3 were conceived by the named inventor of
`
`the ’807 patent (Dr. Brenner), not “by another” (Dr. Bieganowski), meaning that
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`the Cell article and ’337 PCT Publication are not prior art under 35 U.S.C. § 102(a)
`
`or § 102(e). Second, as the Board correctly found in its Institution Decision in a
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`related IPR with respect to a continuation of the ’807 patent,5 Petitioner’s
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`unsupported and inapplicable Paris Convention argument regarding the ’807
`
`
`5 Thorne Research, IPR2021-00268, Paper 21, 15-17.
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`6
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`

`

`IPR2021-00491
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`patent’s priority fails to establish the Cell article as prior art under 35 U.S.C.
`
`§ 102(b).
`
`A. The Asserted Cell Article and ’337 PCT Publication Are Not “By
`Another” and Thus Not Prior Art Under 35 U.S.C. § 102(a) or
`§ 102(e)
`Both Grounds of the Petition are based on either the Cell article or ’337 PCT
`
`Publication. See Pet. at 38, 40-56. To qualify as § 102(a) or § 102(e) prior art,
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`these references must be “by another,” i.e., the relied-upon subject matter thereof
`
`must have been invented by someone other than the inventor of the challenged
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`’807 patent (Dr. Brenner). The relied-upon subject matter, however, was invented
`
`solely by Dr. Brenner, as confirmed by declaration testimony from Dr. Brenner,6
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`corroborating disclaimer testimony from Dr. Bieganowski’s declaration and
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`deposition, the superior-subordinate relationship between Drs. Brenner and
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`Bieganowski, and Dr. Brenner’s review of documentation. The Cell article and the
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`’337 PCT Publication are therefore not “by another” and not prior art under
`
`§ 102(a) or § 102(e).
`
`
`6 A first declaration of Dr. Brenner was submitted in connection with Patent
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`Owner’s Preliminary Response. Ex. 2002. Patent Owner also submits a second
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`declaration of Dr. Brenner in connection with this Patent Owner Response.
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`Ex. 2015.
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`7
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`

`

`IPR2021-00491
`
`
`1.
`
`To Qualify as Prior Art Under § 102(a) or § 102(e), Relied-
`Upon Subject Matter in the Reference Must Be Invented
`“By Another,” i.e., by Dr. Bieganowski
`Under Pre-AIA § 102, an inventor’s own work is prior art only if it
`
`constitutes a statutory bar under § 102(b). See In re Katz, 687 F.2d 450, 454
`
`(C.C.P.A. 1982). An inventor’s own work is thus not prior art under § 102(a) or
`
`§ 102(e). See id.; § 102(e).
`
`A patentee may “overcome a prior art reference under section 102(e)” by
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`“establish[ing] that the relevant disclosure describes their own invention.” In re
`
`Costello, 717 F.2d 1346, 1351 (Fed. Cir. 1983). For this, “the relevant question is
`
`… whether the portions of the reference relied on as prior art, and the subject
`
`matter of the claims in question, represent the work of a common inventive entity.”
`
`EmeraChem Holdings, LLC v. Volkswagen Grp. of Am., Inc., 859 F.3d 1341, 1345
`
`(Fed. Cir. 2017) (internal quotation omitted). A patentee may overcome a prior art
`
`reference under § 102(a) the same way, i.e., by establishing that the relied-upon
`
`portions of the reference describe their own invention. See Katz, 687 F.2d at 455.
`
`8
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`

`

`IPR2021-00491
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`The Federal Circuit set forth the following test “to decide whether a
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`reference … is ‘by another’”:
`
`[T]he Board must (1) determine what portions of the reference …
`were relied on as prior art to anticipate the claim limitations at issue,
`(2) evaluate the degree to which those portions were conceived “by
`another,” and (3) decide whether that other person’s contribution is
`significant enough, when measured against the full anticipating
`disclosure, to render him a joint inventor of the applied portions of the
`reference … .
`
`Duncan Parking Techs., Inc. v. IPS Grp., Inc., 914 F.3d 1347, 1358 (Fed. Cir.
`
`2019); see, e.g., Ethicon LLC v. Intuitive Surgical, Inc., 847 F. App’x 901, 908-09
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`(Fed. Cir. 2021) (applying the Duncan Parking test and reversing the Board).
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`Moreover, the burden of production and the ultimate burden of persuasion
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`are on Petitioner to establish that the Cell article and ’337 PCT Publication are “by
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`another” and therefore prior art. See Dynamic Drinkware, LLC v. Nat’l Graphics,
`
`Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015); 35 U.S.C. § 316(e); Varian Med. Sys.
`
`v. William Beaumont Hospital, IPR2016-00160, Paper 82, 21-22 (P.T.A.B. May 4,
`
`2017).
`
`Under the Duncan Parking test, for the Cell article or the ’337 PCT
`
`Publication to be prior art to claims 1-3, someone other than Dr. Brenner, the sole
`
`inventor of the ’807 patent, must have “conceived” some “significant” contribution
`
`to the relied-upon portions of the reference and thus be a “joint inventor” of the
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`relied-upon portions. Dr. Bieganowski is the only potential “other person[],” as he
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`9
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`

`

`IPR2021-00491
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`is the only other individual named in the Cell article and ’337 PCT Publication
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`besides Dr. Brenner. See Ex. 1007 at (75); Ex. 1008 at 495. Therefore, Petitioner
`
`has the burden of establishing that Dr. Bieganowski conceived of—and thus
`
`invented—some significant contribution to the relied-upon portions of those two
`
`references.
`
`Petitioner’s Reply to Patent Owner’s Preliminary Response argues that a
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`reference may alternatively be “by another” if the “[relied-upon] portions do not
`
`represent the inventive work of Dr. Brenner, but instead represent the work of those
`
`in the prior art.” Paper 17 at 8-10 (emphasis in original). That is, Petitioner argues
`
`that the references are “by another” because certain relied-upon portions were
`
`allegedly in the prior art and thus not invented by either Dr. Brenner or Dr.
`
`Bieganowski. But Petitioner is wrong on multiple levels.7
`
`
`7 This argument in Petitioner’s Reply to Patent Owner’s Preliminary Response is
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`premised specifically on the limitation in claim 2 of the ’086 patent—i.e., “the
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`nicotinamide riboside is isolated from a natural or synthetic source”—which
`
`appears in the ’807 patent in only claim 2, not claims 1 or 3. See Paper 17 at 10
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`(relying on the fact that “the Board previously found … the subject matter recited
`
`in claim 1 of the ’086 patent” to be unpatentable); ’807 patent at claims 1-3.
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`10
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`

`

`IPR2021-00491
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`Foundationally, if the relied-upon portions were already in the prior art, then
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`Petitioner could just assert the underlying prior art reference. But instead,
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`Petitioner attempts to obfuscate and back-door a way around the proper “by
`
`another” analysis. The law is clear that the “by another” analysis asks who
`
`invented the relied-upon portions and does not, as Petitioner argues, ask whether
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`the relied-upon portions constitute an invention as opposed to merely “the work of
`
`those in the prior art.”
`
`Indeed, the “by another” test in Duncan Parking presumes that the relied-
`
`upon portions are inventive by asking whether those applied portions were
`
`“conceived” and “joint[ly] invent[ed]” by some other person. 914 F.3d at 1358;
`
`see also CSL Behring LLC v. Bioverativ Therapeutics Inc., IPR2018-01313, Paper
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`10, 11 (P.T.A.B. Jan. 9, 2019) (“As to what inquiry is relevant, in Katz the Federal
`
`Circuit determined that a reference by an inventor co-authored with non-inventors
`
`was not § 102(a) prior art on the basis that the co-authors contribution fails to rise
`
`to joint inventorship … .” (citing 687 F.2d at 455-56)). Moreover, the Duncan
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`Parking test requires an identifiable “other person[]” in order for a reference to be
`
`“by another,” and does not contemplate, as Petitioner suggests, that relied-upon
`
`portions of a reference can be contributed generally by “those in the prior art.”
`
`Compare 914 F.3d at 1358 with Paper 17 at 8-10.
`
`11
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`

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`IPR2021-00491
`
`
`2.
`
`The Invention of the ’807 Patent and Relied-Upon Subject
`Matter in the Cell Article and ’337 PCT Publication
`Dr. Brenner worked from 2003 to 2009 as a professor and researcher at
`
`Dartmouth Medical School, where he was the project leader and principal
`
`investigator of the NR research project. Ex. 2002 ¶ 11. As a part of that project, in
`
`late 2003, Dr. Brenner directed experiments and assays related to NR, and as a
`
`result, Dr. Brenner discovered that NR is an NAD+ precursor in a previously-
`
`unknown pathway, identified and named an Nrk gene and discovered sequences of
`
`the Nrk1 and Nrk2 genes in humans, and ultimately conceived of therapeutic uses
`
`and compositions of NR. Id. ¶ 12; Ex. 2015 ¶¶ 9-10, 12. One member of Dr.
`
`Brenner’s research team was Dr. Bieganowski, a postdoctoral fellow in molecular
`
`biology who performed, at Dr. Brenner’s direction, experiments and assays for
`
`identifying yeast and human genes that have Nrk activity. Ex. 2002 ¶ 13; Ex. 2003
`
`¶ 7; Ex. 2015 ¶¶ 11-12; Ex. 2004 at 16:18-17:3, 19:10-23, 21:22-22:14.
`
`Certain aspects of the NR research project were disclosed in the ’347
`
`Provisional, which Dartmouth filed on February 20, 2004. Ex. 2002 ¶ 15; see Ex.
`
`1005 at 2. Dartmouth later claimed priority to the ’347 Provisional in the ’337
`
`PCT Application, which was published as the ’337 PCT Publication. See Ex.
`
`1007; Pet. at 34; Ex. 2002 ¶¶ 7-8, 16; Ex. 2003 ¶¶ 6, 8. Certain results from the
`
`NR research project were also published in the Cell article. See Ex. 1008; Pet. at
`
`32; Ex. 2002 ¶¶ 9, 15, 18; Ex. 2003 ¶¶ 6, 8.
`
`12
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`

`

`IPR2021-00491
`
`The ’347 Provisional and the ’337 PCT Publication name both Dr. Brenner
`
`and Dr. Bieganowski as co-inventors. See Ex. 1005 at 3; Ex. 1007 at (75); Ex.
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`2002 ¶¶ 7-8; Ex. 2003 ¶ 6. Likewise, the Cell article names both Dr. Brenner and
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`Dr. Bieganowski as co-authors. See Ex. 1008 at 495; Ex. 2002 ¶ 9; Ex. 2003 ¶ 6.
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`Petitioner’s initial assertion of these references as prior art under § 102(a) and
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`§ 102(e) is based merely on the fact that these references name both Dr. Brenner
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`and Dr. Bieganowski. Pet. at 34 n.12.
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`However, under Duncan Parking, to determine whether these two references
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`are actually “by another,” the Board must determine specifically “what portions of
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`the reference … [are] relied on as prior art to [invalidate] the claim limitations at
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`issue.” 914 F.3d at 1358; see Ethicon, 847 F. App’x at 908-09 (reversing the
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`Board because it “did not correctly identify the portions of [the reference] relied
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`on”).
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`Here, the invention that is recited in claims 1-3 of the ’807 patent is a
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`composition of NR formulated for therapeutic use, with certain additional
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`attributes.8 Thus, while some relied-upon portions of the Cell article and ’337 PCT
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`8 The certain additional attributes include, for example, that the NR is isolated and
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`in combination with certain other components, that the composition is in admixture
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`with a certain carrier, that the composition is formulated for and increases NAD+
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`biosynthesis upon oral administration, that the NR is isolated from a natural or
`
`13
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`IPR2021-00491
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`Publication mention isolation techniques and other routine or previously-known
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`methods and technologies as background, all are specifically applied to, and relied
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`upon in the context of, therapeutic uses and compositions of NR. Ex. 2015 ¶¶ 15-
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`34; see also Ex. 2016 at 83:3-13, 84:23-86:8, 87:1-7, 87:23-88:25 (acknowledging
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`that cited portions of the Cell article and ’337 PCT Publication are relied upon by
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`Petitioner for a therapeutic “composition” as claimed).
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`3.
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`The Relied-Upon Subject Matter in the Cell Article and
`’337 PCT Publication Was Invented Only by Dr. Brenner
`And Not Dr. Bieganowski
`Dr. Brenner is the sole named inventor of the challenged ’807 patent. ’807
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`patent at (75); Ex. 2002 ¶¶ 1-4, 6. Dr. Brenner is also the sole inventor of the
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`subject matter of the Cell article and ’337 PCT Publication upon which Petitioner
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`relies, and therefore neither of those references is “by another.”
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`The relied-upon portions of the Cell article and ’337 PCT Publication are
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`relied upon by Petitioner in relation to therapeutic oral compositions of NR, which
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`is the subject of challenged claims 1-3. And Dr. Brenner was solely responsible
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`for all aspects of the NR research project related to therapeutic uses and
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`compositions of NR and all inventions regarding the same. Ex. 2002 ¶ 14; Ex.
`
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`synthetic source (claim 2), and/or that the composition is formulated into a certain
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`form (claim 3). See ’087 patent at claims 1-3.
`
`14
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`IPR2021-00491
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`2015 ¶¶ 12, 15-34; see also Ex. 2003 ¶ 8. Dr. Bieganowski did not contribute to or
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`conceive of any aspect of the NR research project regarding therapeutic uses or
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`compositions of NR, much less make a contribution “significant enough, when
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`measured against the full anticipating disclosure, to render him a joint inventor”
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`under Duncan Parking. 914 F.3d at 1358; Ex. 2002 ¶ 14; Ex. 2003 ¶ 8; Ex. 2015
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`¶¶ 4, 11-12; see also Ex. 2004 at 19:10-14, 21:22-22:14, 26:14-23, 10:10-20.
`
`a.
`
`Dr. Brenner Invented the Relied-Upon Subject Matter in
`the Cell Article
`The relied-upon portions of the Cell article represent the invention of Dr.
`
`Brenner alone, as Dr. Bieganowski did not invent any subject matter in these
`
`relied-upon portions of the Cell article. See Pet. at 40-50; Ex. 2002 ¶¶ 18-19; Ex.
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`2003 ¶ 8; Ex. 2015 ¶¶ 15, 29-34. In his declarations, Dr. Brenner identifies each
`
`portion of the Cell article cited by Petitioner, identifies specifically the subject
`
`matter that Petitioner relies upon in each of these cited portions, and then explains
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`how the relied-upon subject matter of each individual cited portion constitutes his
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`invention alone. Ex. 2002 ¶¶ 18-19; Ex. 2015 ¶¶ 15, 29-34. More specifically, Dr.
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`Brenner’s second declaration (Ex. 2015) explains that the relied-upon portions of
`
`the ’337 PCT Publication relate to aspects of his invention of a therapeutic
`
`composition of NR such as discovery that NR is an NAD+ precursor in a
`
`previously-unknown pathway (¶¶ 30, 33-34), identification of sources of NR for
`
`use in therapeutic compositions (¶¶ 30-31, 33), and use of NR as a therapeutic (¶¶
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`15
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`IPR2021-00491
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`30-34). Dr. Brenner also explains that he alone designed the experiments and
`
`assays described in the Cell article and that Dr. Bieganowski’s role was to perform
`
`the assays and experiments at his direction. Id. ¶¶ 30-31, 33.
`
`b.
`
`Dr. Brenner Invented the Relied-Upon Subject Matter in
`the’337 PCT Publication
`The relied-upon portions of the ’337 PCT Publication represent the
`
`invention of Dr. Brenner alone, as Dr. Bieganowski did not invent any subject
`
`matter in these relied-upon portions of the ’337 PCT Publication. See Pet. at 34-
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`35, 51-56; Ex. 2002 ¶¶ 16-17; Ex. 2003 ¶ 8; Ex. 2015 ¶¶ 15-28. In his
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`declarations, Dr. Brenner identifies each portion of the ’337 PCT Publication cited
`
`by Petitioner, identifies specifically the subject matter that Petitioner relies upon in
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`each of these cited portions, and then explains how the relied-upon subject matter
`
`of each individual cited portion constitutes his invention alone. Ex. 2002 ¶¶ 16-17;
`
`Ex. 2015 ¶¶ 15-28. More specifically, Dr. Brenner’s second declaration (Ex. 2015)
`
`explains that the relied-upon portions of the ’337 PCT Publication relate to aspects
`
`of his invention of a therapeutic composition of NR such as discovery that NR is
`
`an NAD+ precursor in a previously-unknown pathway (¶¶ 18, 24), identification of
`
`sources of NR for use in therapeutics (¶¶ 19, 24-26, 28), use of NR as a therapeutic
`
`(¶¶ 20-24), and carriers, forms of administration, and other components for a
`
`therapeutic composition of NR (¶¶ 22, 27). Again, Dr. Brenner also explains that
`
`he alone designed the experiments and assays described in the ’337 PCT
`
`16
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`IPR2021-00491
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`Publication and that Dr. Bieganowski’s role was to perform the assays and
`
`experiments at his direction. Id. ¶¶ 17, 19, 25-26, 28.
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`c.
`
`Dr. Bieganowski Disclaimed Any Inventive Contribution
`to the Relied-Upon Subject Matter
`Dr. Bieganowski, in his sworn declaration, disclaims any inventive
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`contribution to the relied-upon portions of the Cell article and ’337 PCT
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`Publication. Ex. 2003 ¶ 8. He also confirms that Dr. Brenner designed the
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`experiments related to the NR research project, and that his role was to perform the
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`experiments at Dr. Brenner’s direction. Id. ¶ 7.
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`In IPR2021-00268, where Petitioner challenges the related ’086 patent by
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`relying upon essentially the same portions of the Cell article and ’337 PCT
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`Publication as relied upon here, Petitioner was afforded the opportunity to depose
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`Dr. Bieganowski regarding whether those relied-upon portions are “by another.”9
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`See IPR2021-00268, Paper 2 at 42-50; IPR2021-00268, Ex. 1024 at 21:22-22:5,
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`23:20-25; see generally Ex. 2004. Despite having the opportunity to depose Dr.
`
`9 Given Petitioner’s deposition of Dr. Bieganowski in IPR2021-00268, and due to
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`the substantial similarity of Dr. Bieganowski’s declarations in the two proceedings,
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`Petitioner elected to forgo a separate comparable deposition in the present IPR,
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`thus acknowledging that Dr. Bieganowski’s deposition testimony in IPR2021-
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`00268 is also relevant to the “by another” issue in the present IPR. Ex. 2012.
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`17
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`IPR2021-00491
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`Bieganowski regard