  United States Court of Appeals
      for the Federal Circuit
               ______________________

  RICHARD STORER, GILLES GOSSELIN, JEAN-
    PIERRE SOMMADOSSI, PAOLA LACOLLA,
                Appellants

                          v.

                 JEREMY CLARK,
                     Appellee

                 UNITED STATES,
                     Intervenor
               ______________________

                     2015-1802
               ______________________

    Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. 105,981.
                  ______________________

               Decided: June 21, 2017
               ______________________

   GREGORY A. CASTANIAS, Jones Day, Washington, DC,
argued for appellants. Also represented by JENNIFER
LORAINE SWIZE; ANTHONY M. INSOGNA, JOHN DAVID
KINTON, San Diego, CA; THOMAS EUGENE FRIEBEL, New
York, NY; CALVIN GRIFFITH, Cleveland, OH.

    FRANK SCHERKENBACH, Fish & Richardson PC, Bos-
ton, MA argued for appellee. Also represented by
2                                           STORER   v. CLARK



JONATHAN ELLIOT SINGER, CRAIG E. COUNTRYMAN, W.
CHAD SHEAR, San Diego, CA.

    JOSEPH FORREST BUSA, Appellate Staff, Civil Division,
United States Department of Justice, Washington, DC,
argued for intervenor. Also represented BY MARK R.
FREEMAN, BENJAMIN C. MIZER; THOMAS W. KRAUSE, Office
of the Solicitor, United States Patent and Trademark
Office, Alexandria, VA.
                 ______________________

    Before PROST, Chief Judge, NEWMAN, and DYK, Circuit
                          Judges.
NEWMAN, Circuit Judge.
    This patent interference contest involves methods of
treating hepatitis C by administering compounds having
a specific chemical and stereochemical structure, based on
the following foundation formula of a five-membered ring
having the fluorine substituent in the 2´(down) position:




Storer Br. at 8. The priority decision was based on ena-
blement of this product. The interference was declared
between an issued patent (Storer et al.) and a pending
application (Clark), both of which were filed before the
effective date of the America Invents Act, the statute that
abolished the first-to-invent interference rule in favor of a
STORER   v. CLARK                                          3



first-to-file rule. By the terms of the Act, § 3(n)(2), the
prior, first-to-invent, law applies to this interference.
    To establish priority, Storer relied on the disclosure in
the provisional specification from which priority was
claimed for conception and constructive reduction to
practice. In its joint decision on Clark’s motion to deny
Storer the benefit of the provisional application and on
Clark’s motion to invalidate Storer’s claims on the
grounds of lack of enablement and written description, 1
the Patent Trial and Appeal Board (PTAB or “Board”)
held that Storer’s provisional application was not ena-
bling for the count of the interference, and on that ground
the PTAB entered judgment granting priority to Clark. 2
Storer appeals that judgment and the underlying decision
on Clark’s motions.
    We take note that Storer initially filed in the District
of Delaware, seeking review of the Board’s decision under
35 U.S.C. § 146. The district court dismissed the case,
Idenix Pharmaceuticals. LLC v. Gilead Pharmasset LLC,
2016 WL 6804915, at *1 (D. Del. Nov. 16, 2016), based on
this court’s ruling in Biogen MA, Inc. v. Japanese Founda-
tion for Cancer Research, 785 F.3d 648 (Fed. Cir. 2015),
that the America Invents Act eliminated the option of
district court review under Section 146 for interferences
declared after September 15, 2012. Although Storer says
that Biogen was incorrectly decided, that decision is
binding on this panel. Storer’s appeal of the district
court’s dismissal has been stayed pending the outcome of



    1   Decision on Motions – Bd.R. 125, Clark v. Storer,
Interference No. 105,981, (P.T.A.B. Jan. 16, 2015), Doc
No. 687 (“Bd. Op.”).
    2 Clark v. Storer, Interference No. 105,981, 2015
WL 1325503 (P.T.A.B. Mar. 23, 2015).
4                                          STORER   v. CLARK



this appeal. Order, Idenix Pharm. LLC v. Gilead Phar-
masset LLC, No. 17-1369 (Fed. Cir. Feb. 16, 2017).
                      BACKGROUND
    Inventors Richard Storer et al. were issued U.S. Pa-
tent No. 7,608,600 (“the ‘600 Patent”), on a final applica-
tion filed on June 27, 2003. The patent is assigned to
Idenix Pharmaceuticals. In the interference proceeding,
Storer was initially declared the senior party based on the
June 28, 2002 filing date of provisional application No.
60/392,350 (called “the S1 application” by the Board).
Clark’s Application No. 11/854,218, assigned to Gilead
Pharmasset, was filed September 12, 2007, with priority
claimed to a provisional application filed on May 30, 2003.
    Clark moved to deny Storer the priority date of the S1
application and to invalidate Storer’s claims, arguing that
the S1 application did not enable compounds having the
2´F(down) substituent. Storer argued that these com-
pounds were generically disclosed in the S1 application,
and were readily obtained based on the disclosure in the
S1 provisional and the prior art. The Board did not agree,
and by withdrawing entitlement to the provisional’s filing
date, the Board awarded priority to Clark. Storer now
appeals that decision.
                       DISCUSSION
The Interfering Claims
    Storer and Clark were investigating the treatment of
hepatitis C using modified nucleoside compounds, includ-
ing certain heterocyclic compounds having a fluorine
substituent in the 2´ position. The PTAB identified the
interfering subject matter, and selected claims for purpos-
es of determining priority. From the Storer patent, the
Board selected claim 1:
    1. A method for the treatment of a host infected
    with a hepatitis C virus, comprising administer-
STORER   v. CLARK                                         5



   ing to the host infected with a hepatitis C virus an
   effective amount of a compound having the formu-
   la:




   or a pharmaceutically acceptable salt thereof,
   wherein:
   R1 is H; mono-, di- or triphosphate; acyl; an amino
   acid ester; a carbohydrate; a peptide;
   or a pharmaceutically acceptable leaving group
   which when administered in vivo provides a com-
   pound wherein R1 is H or phosphate;
   R2 is H; acyl; an amino acid ester; a carbohydrate;
   a peptide; or a pharmaceutically acceptable leav-
   ing group which when administered in vivo pro-
   vides a compound wherein R2 is H;
   Base* is selected from the group consisting of ad-
   enine,    N6-alkylpurine,     N6-acylpurine,   N6-
   benzylpurine, N6-halopurine, N6-vinylpurine, N6-
   acetylenic     purine,    N6-acyl    purine,   N6-
   hydroxyalkylpurine, N6-alkylamino-purine, N6-
   thioalkyl purine, N2-alkylpurine, N2-alkyl-6-
   thiopurine, thymine, cytosine, 5-fluorocytosine, 5-
   methylcytosine, 6-azapyrimidine, 6-azacytosine, 2-
   and/or 4-mercaptopyrimidine, uracil, 5-halouracil,
   5-fluorouracil,       C5-alkylpyrimidine,       C5-
   benzylpyrimidine,       C5-halopyrimidine,     C5-
   vinylpyrimidine, C -acetylenic pyrimidine, C -acyl
                       5                        5
6                                          STORER   v. CLARK



    pyrimidine,     C5-hydroxyalkyl     purine,     C5-
    amidopyrimidine,       C5-cyanopyrimidine,      C5-
    iodopyrimidine, C -iodo-pyrimidine, C -Br-vinyl
                       6                     5

    pyrimidine,       C6-Br-vinylpyrimidine,        C5-
    nitropyrimidine,     C -amino-pyrimidine,
                           6                       N2-
    alkylpurine, N2-alkyl-6-thiopurine, 5-azacytidinyl,
    5-azauracilyl, triazolopyridinyl, imidazolopyridi-
    nyl,   pyrrolopyrimidinyl,    pyrazolopyrimidinyl,
    guanine, hypoxanthine, 2,6-diaminopurine, and 6-
    choropurine;
    R12 is C(Y3)3; and
    Y3 is independently H or F.
From the Clark application, the Board selected claim 164:
    164. A method for the treatment of hepatitis C in-
    fection, which comprises:
    administering to a mammal in need thereof an an-
    tivirally effective amount of a (2ˊR)-2ˊ-deoxy-2ˊ-
    fluoro-2ˊ-C-methyl nucleoside (β-D or β-L) or its
    pharmaceutically acceptable salt of the structure:




    wherein R1 and R7 are independently H, a mono-
    phosphate, a diphosphate, a triphosphate, a H-
    phosphonate, an alkyl, an alkyl sulfonyl, or an ar-
    ylalkyl sulfonyl; and R4 is NH2 or OH.
STORER   v. CLARK                                         7



    The parties agree that the only question focuses on
whether the Storer S1 provisional together with the prior
art enabled compounds having a 2´F(down) substituent.
Enablement
    Enablement is relevant for validity and to the issue of
whether the provisional application is a constructive
reduction to practice. “Constructive reduction to practice
means a described and enabled anticipation under 35
U.S.C. 102(g)(1), in a patent application of the subject
matter of a count.” 37 C.F.R. § 41.201. “When a party to
an interference seeks the benefit of an earlier-filed United
States patent application, the earlier application must
meet the requirements of 35 U.S.C. § 120 and 35 U.S.C. §
112 ¶ 1 for the subject matter of the count.” Hyatt v.
Boone, 146 F.3d 1348, 1352 (Fed. Cir. 1998) (footnotes
omitted). Section 112 ¶ 1 requires:
   The specification shall contain a written descrip-
   tion of the invention, and of the manner and pro-
   cess of making and using it, in such full, clear,
   concise, and exact terms as to enable any person
   skilled in the art to which it pertains, or with
   which it is most nearly connected, to make and
   use the same, and shall set forth the best mode
   contemplated by the inventor of carrying out his
   invention.
35 U.S.C. § 112, para. 1. 3 Therefore, when the issue is
priority based on the content of the specification, “[t]he
earlier application must contain a written description of
the subject matter of the interference count, and must
meet the enablement requirement.” Hyatt, 146 F.3d at
1352.




   3     This section is now § 112(a).
8                                             STORER   v. CLARK



    Enablement is a matter of law, and is reviewed with-
out deference; however, the factual underpinnings of
enablement are reviewed for support by substantial
evidence on the entirety of the PTO record. Microsoft
Corp. v. Proxyconn, Inc., 789 F.3d 1292, 1297 (Fed. Cir.
2015). To establish enablement of a claim whereby new
chemical compounds are provided for use to treat disease,
the application must enable production or synthesis of the
new compounds. See In re Brebner, 455 F.2d 1402, 1404
(C.C.P.A. 1972) (“A method of making starting materials
not known in the art must be set forth in order to comply
with the enablement requirement.”).
    The Board held that the S1 provisional, taken togeth-
er with the prior art, did not enable the specific com-
pounds having the identified structure. Storer argued,
and repeats on appeal, that a person of ordinary skill
would have been able to make this class of compounds,
having the requisite stereochemistry, based on infor-
mation in the S1 provisional application and the prior art.
“The enablement requirement is met where one skilled in
the art, having read the specification, could practice the
invention without ‘undue experimentation.’” Streck, Inc.
v. Research & Diagnostic Sys., Inc., 665 F.3d 1269, 1288
(Fed. Cir. 2012) (quoting ALZA Corp. v. Andrx Pharm.,
LLC, 603 F.3d 935, 940 (Fed. Cir. 2010)).
    “Whether undue experimentation is required ‘is not a
single, simple factual determination, but rather is a
conclusion reached by weighing many factual considera-
tions.’” Id. As summarized in In re Wands, 858 F.2d 731,
737 (Fed. Cir. 1988), relevant factors may “include (1) the
quantity of experimentation necessary, (2) the amount of
direction or guidance presented, (3) the presence or ab-
sence of working examples, (4) the nature of the inven-
tion, (5) the state of the prior art, (6) the relative skill of
those in the art, (7) the predictability or unpredictability
of the art, and (8) the breadth of the claims.”
STORER   v. CLARK                                           9



    The Board determined that the claimed compounds
having a 2´F(down) substituent were not enabled in
Storer’s S1 provisional application, in that undue experi-
mentation would be required to produce this structure.
The Board analyzed the disclosure in terms of the eviden-
tiary factors set forth in Wands.
    Storer does not dispute the Board’s findings as to the
third, fourth, fifth, sixth, and eighth Wands factors, but
argues that these factors are not dispositive of enable-
ment. For the third Wands factor—the presence or ab-
sence of working examples—Storer does not dispute that
the S1 provisional contains no specific examples of syn-
thesis of compounds having the fluoro substituent in the
2´(down) position. Bd. Op. at 24.
    For the fourth Wands factor—the nature of the inven-
tion—the Board found that:
   Count 1 is best characterized as the administra-
   tion of a genus of nucleosides used in the treat-
   ment of viruses, particularly those of the family
   Flaviviridae (which includes HBV and HCV). We
   also find that, as of the time of filing of the S1 ap-
   plication, although organic fluoridation mecha-
   nisms were generally well-known in the art a 2ˊ-
   fluoro-2ˊ-methyl nucleoside with the fluoro sub-
   stituent in the “down” position had not yet been
   synthesized.
Id. at 25 (footnote omitted). Storer does not dispute this
finding.
   For the fifth Wands factor—the state of the prior
art—the Board found that:
   although DAST [N,N-diethylamino-sulfur trifluo-
   ride] was well-known in the prior art as fluoridat-
   ing agent for nucleosides and nucleoside analogs,
   the prior art did not teach, or explicitly suggest,
   the use of DAST in the fluoridation of a tertiary
10                                           STORER   v. CLARK



     alcohol to convert a tertiary alcohol at a nucleo-
     side 2ˊ position to a tertiary fluorine at the nucle-
     oside 2ˊ “down” position. We further find that,
     although organic fluoridation techniques were
     well-known in the art at the time the S1 applica-
     tion was filed, fluoridation of tertiary alcohols to
     produce a 2ˊ “down” tertiary fluorine was not
     taught or suggested by the prior art.
Id. at 29. Storer does not dispute this finding.
    With respect to the sixth Wands factor, the Board par-
ticularly relied on Wands factors 1, 2, 3, 4, and 7 and
found that “the parties largely agree that the level of skill
in the art is very high” and that
     a person possessing the ordinary level of skill in
     this art, as of the time of the invention, would
     hold a doctoral degree in the field of organic, syn-
     thetic, or medicinal chemistry with at least a
     year’s experience in the field of nucleoside synthe-
     sis or relevant drug discovery.
Id. at 29–30. The Board also found that neither party
argued the eighth Wands factor regarding the breadth of
the claims. Id. at 34 n.64. These findings are not disput-
ed.
   The Board summarized the evidence and findings on
which it concluded that undue experimentation would be
needed to produce the designated molecule:
     (1) synthesis of a 2ˊ-fluoro-2ˊ-methyl nucleoside
     with the fluoro moiety in the “down” position re-
     quired at least two years of a high-priority exper-
     imentation by persons skilled in the art, including
     multiple consultations with experts at the top of
     their fields and additional formal training;
STORER   v. CLARK                                           11



   (2) the S1 application provides little in the way of
   direction or guidance as to how to synthesize such
   a compound;
   (3) the S1 application provides no explicit example
   of a 2ˊ-fluoro-2ˊ-methyl nucleoside, nor was an ex-
   ample provided by the relevant art as of the S1
   application’s filing date;
   (4) the invention is characterized as the admin-
   istration of a genus of nucleosides used in the
   treatment of viruses, particularly those of the
   family Flaviviridae (which includes HBV and
   HCV) and an embodiment of the count requires a
   2ˊ-fluoro(“down”) 2ˊ-methyl nucleoside;
   (5) although organic fluoridation techniques were
   well-known in the art at the time the S1 applica-
   tion was filed, fluoridation of tertiary alcohols to
   produce a 2ˊ “down” tertiary fluorine was not
   taught or suggested by the prior art;
   (6) the level of skill in the art was highly sophisti-
   cated: a person possessing the ordinary level of
   skill in this art, as of the time of invention, would
   hold a doctoral degree in the field of organic, syn-
   thetic, or medicinal chemistry with at least a
   year’s experience in the field of nucleoside synthe-
   sis or relevant drug discovery; and
   (7) the art, at least with respect to fluoridation of
   tertiary alcohols to produce a tertiary fluorine in
   the 2ˊ “down” position, was highly unpredictable.
   We therefore find that Wands factors 1, 2, 3, 5,
   and 7 strongly indicate that a person skilled in the
   art would not arrive at the claimed invention
   without undue experimentation.
Id. at 34–35.
12                                         STORER   v. CLARK



    Based on these findings, the Board concluded that the
interference subject matter was not enabled by Storer’s
S1 provisional application.
Argument on Appeal
    Storer argues that the S1 provisional application “per-
formed the substantial step of disclosing the precise
chemical structure of the target compound.” Storer Br. at
47. Storer does not, however, identify any specific struc-
ture having the 2´F(down) substituent. The pages of the
S1 provisional cited by Storer include generic structures,
and Clark does not dispute that the “target compounds,”
as the Board calls the 2´F(down) compounds, are generi-
cally included in the S1 provisional application’s generic
formulas.
    Storer states that the prior art contains “a well-known
precursor compound that is only one step away from the
target compound.” Id. at 8. Storer states that this pre-
cursor is “Matsuda Compound 17,” citing Akira Matsuda
et al., Alkyl Addition Reaction of Pyrimidine 2´-
Ketonucleosides: Synthesis of 2´-Branched-Chain Sugar
Pyrimidine Nucleosides (Nucleosides and Nucleotides
LXXXI), 36 CHEMICAL & PHARMACEUTICAL BULL., no. 3,
Mar. 1988, at 945.
     Matsuda Compound 17 is presented in Storer’s brief
as
STORER   v. CLARK                                     13




Storer Br. at 12. Matsuda Compound 17 contains a
methyl group in the 2´(down) position, and Storer states
that Matsuda Compound 17 is readily converted into the
target compound by known methods to produce the de-
sired stereochemistry. Matsuda Compound 17 is not
mentioned in the S1 provisional, but Storer argues that
the precursor to Matsuda Compound 17 is in the S1
provisional, “as is that precursor’s conversion to the
Matsuda compound,” Id. at 48 n.16. Storer states that the
precursor “is only two steps away from the desired 2´-
methyl ‘up’, 2´-fluoro ‘down’ configuration,” and “each
scheme discloses how to modify the 2´-keto precursor to
obtain” Matsuda Compound 17. Id. at 9.
    Thus Storer argues that the Matsuda reference, to-
gether with the information in the S1 provisional, enable
synthesis of 2´F(down) compounds. Storer states that
Schemes 3, 4 and 8 in the S1 provisional each describes a
“2´-keto precursor, i.e., a compound with ‘=O’ at the 2´
position,” and that this is the path to the 2´F(down)
molecule. Id. at 9. The three schemes from the S1 provi-
sional are:
14                           STORER   v. CLARK




Storer Prov. Appl. at 119.
STORER   v. CLARK                                           15



Id. at 120.




Id. at 1948.
    These three schemes indeed show a compound with
=O at the 2´ position, but none shows conversion to
Matsuda Compound 17 or further conversion to the
2´F(down) analog. Clark points out that each scheme
produces compounds with the opposite spatial arrange-
ment from Matsuda Compound 17, for in Matsuda Com-
pound 17 the 2´-OH is “up,” whereas in Scheme 4 the 2´-
OH is “down.” Clark Br. at 5.
    Storer does not dispute the chemical facts, but argues
that the difference between Matsuda 17 and the provi-
sional synthesis schemes does not negate enablement
because
    if the alkylation reagent is methyl lithium (MeLi)
    or methyl Grignard (MeMgBr) for methylation as
    taught by the specification, one of ordinary skill in
    the art will obtain products with the orientation
    (i.e., “stereochemistry”) of the OH and methyl
    groups needed to synthesize the target compound
    using DAST or Deoxo-Fluor. Furthermore, the
    prior art teaches how to control the stereochemis-
    try of these groups.
16                                          STORER   v. CLARK



Storer Br. at 9-10 n.5. Although the S1 provisional
schemes show products with the opposite stereochemistry,
Storer argues that a person of ordinary skill could make
Matsuda Compound 17 employing these schemes. Storer
argues that “a skilled artisan would have recognized that
Matsuda Compound 17 was a viable precursor,” id. at 48,
and that: “With knowledge of those structures, the hypo-
thetical person would have known to use a common, one-
step synthesis to modify the well-known precursor to
obtain the target compound.” Id. Storer states that
“simply by looking at the chemical structure of the target
compound disclosed by Idenix, a person of ordinary skill
would know to use a fluorination reagent,” id., and “DAST
and Deoxo-Fluor were the most well-known fluorinating
reagents at the time for one-step fluorination reactions.”
Id. at 49. Storer argues that Matsuda provides any
necessary information not in the S1 provisional.
    Clark responds that these are overstatements, for nei-
ther Matsuda Compound 17 nor any compound with the
2´F(down) structure is mentioned in the Storer S1 provi-
sional. Clark points out that none of the several synthetic
schemes in Storer’s provisional application shows conver-
sion of any precursor into Matsuda Compound 17. Clark
states that Storer’s synthetic schemes only disclose com-
pounds with the “wrong stereochemistry.” Clark Br. at
37.
    The Board agreed with Clark’s position, and held that
the S1 provisional’s description of the 2´-keto precursor, in
combination with the Matsuda reference, was insufficient
to enable and thereby to establish possession of the
2´F(down) methyl(up) compound of claim 1 before Clark’s
priority date. The Board stated, correctly, that for new
chemical compounds the specification must provide suffi-
cient guidance that undue experimentation is not re-
quired to obtain the new compounds.
STORER   v. CLARK                                            17



                         ANALYSIS
    The boundary between a teaching sufficient to enable
a person of ordinary skill in the field, and the need for
undue experimentation, varies with the complexity of the
science. Knowledge of the prior art is presumed, as well
as skill in the field of the invention. The specification
need not recite textbook science, but it must be more than
an invitation for further research. Genentech, Inc. v. Novo
Nordisk A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997).
    In Genentech the patentee argued that the prior art
taught a method that could be used to produce a claimed
human growth hormone product, compensating for lack of
detail in the specification. The patentee argued that it
did not need to include information in the prior art. This
court agreed, but stressed the need to assure enablement
of the novel aspects of the invention:
   It is true . . . that a specification need not disclose
   what is well known in the art. See, e.g., Hybritech
   Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367,
   1385 (Fed. Cir. 1986). However, . . . . [i]t is the
   specification, not the knowledge of one skilled in
   the art, that must supply the novel aspects of an
   invention in order to constitute adequate enable-
   ment.
Genentech, 108 F.3d at 1366.
    The Storer provisional specification does not describe
synthesis of the 2´F(down) target compounds. The ques-
tion devolves to the adequacy of the disclosure in the
provisional of general schemes for synthesizing these
general classes of modified nucleosides, taken with the
knowledge of the art. The S1 provisional discloses two
general approaches. Provisional schemes 3 and 8 modify
the sugar portion of the target compound and then add
the base portion, as the provisional application calls the
18                                           STORER   v. CLARK



“Glycosylation of the nucleobase with an appropriately
modified sugar.” Storer Prov. Appl. at 117.
    Provisional scheme 4 shows modifying a compound
with the base already attached, to achieve the desired
structure. The provisional calls this “Modification of a
pre-formed nucleoside.” Id. at 119. The Board observed
that none of the approaches in the provisional proceeds
through a compound like Matsuda Compound 17, or
suggests how Matsuda 17 may be converted into the
target 2´F(down) compounds. The Board found that the
Storer provisional does not exemplify such a reaction, or
lead a person of ordinary skill to perform it. The Board
also observed that the S1 provisional schemes produce
compounds with opposite spatial arrangement from
Matsuda Compound 17.
    On review, we conclude that substantial evidence
supports the Board’s findings that the synthetic schemes
in Storer’s provisional application do not teach or suggest
conversion of any precursor into the 2´F(down) structure,
and that the Matsuda synthesis of a corresponding 2´-
methyl (down), 2´-hydroxyl (up) structure does not enable
a person of ordinary skill to produce the target compounds
without undue experimentation.
    Wands factor 7, the predictability or unpredictability
of the art, appears to be particularly relevant. Although
Storer states that this is predictable chemistry, and
therefore that detailed specific examples are not neces-
sary, the Board’s findings are in accord with the record.
The Board found:
     Having reviewed the parties’ arguments, and the
     proffered evidence, we find that the art, with re-
     spect to fluoridation of tertiary alcohols, was high-
     ly unpredictable, as evidenced by Idenix’s
     repeatedly unsuccessful attempts to synthesize its
     high-priority target nucleoside, and as further
STORER   v. CLARK                                        19



   evinced by the statements of Dr. Coe and Dr.
   Storer.
Bd. Op. at 33–34. Regarding Dr. Coe’s and Dr. Storer’s
statements, the Board stated:
   Dr. Paul Coe, an expert in organofluorines, ex-
   pressed skepticism regarding the use of DAST;
   and Dr. Richard Storer stated that “[a] lot of
   things which look simple on paper in related sys-
   tems have been tried and don’t work in this series.
   Having to make the tertiary fluoride is very dif-
   ferent to [sic] having to make secondary.”
Id. at 31 (quoting from the record). The Board also re-
ferred to evidence presented on behalf of Clark that
“attempted fluorination reactions (including those involv-
ing DAST) could fail, resulting in unfluorinated elimina-
tion and/or rearrangement products, or products with
incorrect stereochemistry.” Id. at 30.
    Even on Storer’s position that a person skilled in this
science would have started with Matsuda Compound 17,
Storer has not shown that the critical stereochemical
result would predictably ensue, although the reaction had
never been performed. The Board received evidence of
side reactions and the skepticism of experts. The Board
received evidence that Storer and his team had difficulty
and failures in synthesizing the target compound, as well
as evidence that Clark and his team were more readily
successful using apparently the same method.           The
Board’s finding that the chemistry was unpredictable is in
accord with the evidence.
    The first Wands factor is concerned with “undue” ex-
perimentation, and recognizes that what is “undue” of
itself depends on the subject matter and skill. The Board
discussed the amount of experimentation needed to
produce the claimed compounds, and found that:
20                                           STORER   v. CLARK



     a high amount of experimentation is necessary to
     synthesize a 2´-fluoro-2´-methyl nucleoside with
     the fluoro moiety in the “down” position, requiring
     at least two years of a high priority experimenta-
     tion by persons skilled in the art, including multi-
     ple consultations with experts at the top of the
     fields and additional formal training.
Id. at 19. The Board discussed the evidence showing
Storer’s continuing research after the S1 provisional was
filed, including the following findings:
     •   “Idenix’s research team in Montpellier,
         France, repeatedly attempted without success
         to    synthesize   a    2´-methyl(“up”)   2´-
         fluoro(“down”) nucleoside during the interval
         between December 2002 and September
         2004.” Id. at 14.
     •   “Idenix scientists also corresponded with con-
         sultants Dr. George Fleet and Dr. Paul Coe in
         an attempt to effect a synthesis of the desired
         compound.” Id. at 14.
     •   “Idenix personnel also attended a ‘Scientific
         Update Course’ entitled ‘Making and Using
         Fluoroorganic Molecules’ in April, 2003, and
         submitted a report summarizing the course
         content.” Id. at 15.
     •   “Dr. Jean-François Griffon, leader of the
         Montpellier group, testified that he attempted
         at least seven different synthetic schemes, in-
         cluding several suggested by Dr. Coe, and in
         some cases employing DAST, without suc-
         cess.” Id. at 15.
     •   “[A]ttempts by the Montpellier team to use
         DAST in the synthesis of a 2´-fluoro-2´-methyl
         nucleoside produced similar failures.” Id. at
         16.
STORER   v. CLARK                                           21



   •     “With respect to the testimony of Jingyang
         Wang who allegedly synthesized the desired
         compound in a single attempt in January,
         2015, at Idenix’s research facility in Cam-
         bridge, Massachusetts, we note that, prior to
         beginning her synthesis, Ms. Wang had re-
         ceived the reports from the Montpellier group
         as well as intermediate compositions synthe-
         sized at Montpellier. Consequently, Ms. Wang
         was not, as Storer seems to suggest, attempt-
         ing synthesis of a 2´-fluoro-2´methyl nucleo-
         side ab initio, but rather had the hindsight
         benefit of the Montpellier group’s efforts.” Id.
         at 17 (citations to the record omitted).
Storer argues that the Board failed to address the fact
that Clark readily synthesized a target compound in a
single step from Matsuda Compound 17. The Board
acknowledged Storer’s argument that it was “informative
that Clark, a chemist without a Ph.D., was allegedly able
to make a 2ˊ-methyl (up) 2ˊ-fluoro (down) nucleoside in
just a few months using DAST.” Id. at 13. Storer states
that “Clark’s experiments directly contradict the Board’s
reliance on the allegedly failed attempts of Griffon.”
Storer Br. at 55. There was evidence that Clark used a
method similar to that attempted by Griffon on the Storer
team, and that Clark succeeded where Griffon apparently
failed. Storer stated to the Board that Griffon actually
produced the target compound, but was not able to purify
it from the reaction mixture.
    The Board found, on consideration of the entire rec-
ord, that a person of ordinary skill, with the disclosure in
the provisional application and knowledge of the prior art,
would not have been led to make the target compound,
and could not do so without undue experimentation. The
Board received evidence that successful fluorination
reactions of the desired stereochemistry had not been
reported for structurally similar compounds.
22                                         STORER   v. CLARK



    We conclude that substantial evidence supports the
Board’s finding that “a high amount of experimentation is
necessary to synthesize” the target compound. The record
before the Board showed sufficient variability and unpre-
dictability to support the Board’s conclusion that Storer’s
provisional application did not enable the interference
subject matter. The Board’s decision is affirmed.
                      AFFIRMED
