  United States Court of Appeals
      for the Federal Circuit
                 ______________________

            ENZO LIFE SCIENCES, INC.,
                 Plaintiff-Appellant

                            v.

  ROCHE MOLECULAR SYSTEMS, INC., ROCHE
     DIAGNOSTICS CORPORATION, ROCHE
   DIAGNOSTICS OPERATIONS, INC., ROCHE
  NIMBLEGEN, INC., BECTON, DICKINSON AND
    COMPANY, AKA BECTON DICKSON AND
 COMPANY, BECTON DICKINSON DIAGNOSTICS
  INC., AKA BECTON DICKSON DIAGNOSTICS,
      GENEOHM SCIENCES INC., ABBOTT
  LABORATORIES, ABBOTT MOLECULAR, INC.,
              Defendants-Appellees
             ______________________

       2017-2498, 2017-2499, 2017-2545, 2017-2546
                ______________________

    Appeals from the United States District Court for the
District of Delaware in Nos. 1:12-cv-00106-LPS, 1:12-cv-
00274-LPS, 1:12-cv-00275-LPS, 1:13-cv-00225-LPS, Chief
Judge Leonard P. Stark.
                 ______________________

         SEALED OPINION ISSUED: June 20, 2019
          PUBLIC OPINION ISSUED: July 5, 2019 ∗


   ∗   This opinion was originally filed under seal and has
been unsealed in full.
2     ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,
                                                      INC.


                 ______________________

   JUSTIN P.D. WILCOX, Desmarais LLP, New York, NY,
argued for plaintiff-appellant. Also represented by JOHN
M. DESMARAIS; PETER CURTIS MAGIC, San Francisco, CA.

     MATTHEW WOLF, Arnold & Porter Kaye Scholer LLP,
Washington, DC, argued for defendants-appellees Roche
Molecular Systems, Inc., Roche Diagnostics Corporation,
Roche Diagnostics Operations, Inc., Roche NimbleGen,
Inc., Becton, Dickinson and Company, Becton Dickinson
Diagnostics Inc., GeneOhm Sciences Inc.

   JOHN C. O'QUINN, Kirkland & Ellis LLP, Washington,
DC, argued for defendants-appellees Abbott Laboratories,
Abbott Molecular, Inc. Also represented by MICHAEL
PEARSON, JASON M. WILCOX; JAMES F. HURST, AMANDA J.
HOLLIS, Chicago, IL; BENJAMIN ADAM LASKY, New York,
NY.

    OMAR KHAN, Wilmer Cutler Pickering Hale and Dorr
LLP, New York, NY, for defendants-appellees Roche Mo-
lecular Systems, Inc., Roche Diagnostics Corporation,
Roche Diagnostics Operations, Inc., Roche NimbleGen,
Inc., Becton Dickinson and Company, Becton Dickinson Di-
agnostics Inc., GeneOhm Sciences Inc. Also represented by
ROBERT J. GUNTHER, JR., CHRISTOPHER R. NOYES; WILLIAM
G. MCELWAIN, THOMAS SAUNDERS, Washington, DC.
                  ______________________

    Before PROST, Chief Judge, REYNA and WALLACH,
                    Circuit Judges.
PROST, Chief Judge.
    Enzo Life Sciences, Inc. (“Enzo”) appeals the decision
of the U.S. District Court for the District of Delaware
granting summary judgment against Enzo and holding
that the asserted claims are invalid for lack of enablement.
ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,          3
INC.


We affirm as to non-enablement and do not reach the other
issues presented on appeal.
                               I
     Deoxyribonucleic acid (“DNA”) and ribonucleic acid
(“RNA”) are nucleic acids. They are made of a series of
building blocks, called nucleotides, linked together in a
chain. A single nucleotide is made up of a sugar, a phos-
phate, and a nitrogenous base. DNA nucleotides have one
of four nitrogenous bases: adenine (A); guanine (G); cyto-
sine (C); and thymine (T). RNA has the same bases, except
it uses uracil (U) instead of thymine (T).
     A polynucleotide refers to multiple nucleotides linked
together in a chain. 1 The nucleotides located at each end
of a polynucleotide chain are referred to as terminal nucle-
otides. All other nucleotides in a polynucleotide chain are
referred to as internal nucleotides.
     Two strands of polynucleotides can pair with each
other, i.e., hybridize, through hydrogen bonding between
the bases on each polynucleotide strand. The bases T and
U pair with A, while G pairs with C. This is referred to as
complementary base pairing or “Watson-Crick base pair-
ing,” and this pairing is how the now-familiar double helix
shape is formed. Two polynucleotide strands will hybridize
if the arrangement of nucleotides in each strand is such
that enough bases can pair with each other. For example,
whether two strands will hybridize depends in part on the
number of complementary base pairs that exist between
the two polynucleotides.
    Hybridization techniques are used to detect the pres-
ence of certain nucleic acid sequences of interest, i.e., target
sequences, such as genetic alterations. In such procedures,



    1    An oligonucleotide is simply a shorter polynucleo-
tide (e.g., just a few nucleotides in length).
4     ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,
                                                      INC.


scientists use a hybridization “probe”—i.e., a labeled poly-
nucleotide that is hybridizable and remains detectable af-
ter    hybridization     occurs—that     is      sufficiently
complementary to the target sequence. The probe will hy-
bridize with the target sequence if the target sequence is
present, and the label on the probe then allows scientists
to detect the hybridized probe.
     Nucleic acid hybridization was well understood by
June 1982, which is the claimed priority date of the patents
at issue in this appeal. The prevailing method of labeling
probes at that time was via radioactive labeling. Radioac-
tive labeling generally involved replacing certain atoms in
the nucleotide sequence with corresponding radioactive
isotopes.
    Non-radioactive labeling was just developing at the
time of the claimed inventions. In 1981, Dr. David Ward
and others at Yale University successfully developed a non-
radioactive probe by attaching a label to a polynucleotide
via a chemical linker at a base position of a nucleotide. See
J.A. 4129–33 (publication by Dr. Ward and others titled
“Enzymatic synthesis of biotin-labeled polynucleotides:
Novel nucleic acid affinity probes”). Dr. Ward demon-
strated that attaching labels at certain positions of the nu-
cleotide (“the Ward positions”) would not disrupt the
polynucleotide’s ability to hybridize and be detected upon
hybridization.
    In December 1981, Enzo licensed the exclusive rights
to the patent portfolio covering Dr. Ward’s discovery. See
J.A. 4258–75. Shortly thereafter, in June 1982, Enzo filed
a patent application covering non-radioactive labeling at
additional positions on a nucleotide. The two patents in
this appeal issued from applications filed in 1995 that
claim priority from this 1982 application.
    Both patents in this appeal generally relate to the use
of non-radioactively labeled polynucleotides in nucleic acid
hybridization and detection applications. The patents
ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,       5
INC.


share the same specification in relevant part. See J.A. 90
n.6.
                             A
    U.S. Patent No. 6,992,180 (“the ʼ180 patent”) relates to
non-radioactive labeling of polynucleotides where the label
is attached at the phosphate position of a nucleotide. The
claims are not directed to any specific polynucleotide, nor
do they focus on the chemistry or linker used to attach a
label, the number of labels to attach to a polynucleotide, or
where within the polynucleotide to attach those labels. In-
stead, the claims encompass all polynucleotides with labels
attached to a phosphate, as long as the polynucleotide re-
mains hybridizable and detectable upon hybridization.
Claim 1 of the ʼ180 patent is representative:
    1. An oligo- or polynucleotide which is complemen-
    tary to a nucleic acid of interest or a portion
    thereof, said oligo- or polynucleotide comprising at
    least one modified nucleotide or modified nu-
    cleotide analog having the formula
        Sig-PM-SM-BASE
    wherein PM is a phosphate moiety, SM is a
    furanosyl moiety and BASE is a base moiety com-
    prising a pyrimidine, a pyrimidine analog, a pu-
    rine, a purine analog, a deazapurine or a
    deazapurine analog wherein said analog can be at-
    tached to or coupled to or incorporated into DNA or
    RNA wherein said analog does not substan-
    tially interfere with double helix formation or
    nucleic acid hybridization, said PM being at-
    tached to SM, said BASE being attached to SM,
    and said Sig being covalently attached to PM
    directly or through a non-nucleotidyl chemical link-
    age, and wherein said Sig comprises a non-polypep-
    tide, non-nucleotidyl, non-radioactive label
    moiety which can be directly or indirectly
6     ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,
                                                      INC.


    detected when attached to PM or when said
    modified nucleotide is incorporated into said
    oligo- or polynucleotide or when said oligo- or
    polynucleotide is hybridized to said comple-
    mentary nucleic acid of interest or a portion
    thereof, and wherein Sig comprises biotin, imino-
    biotin, an electron dense component, a magnetic
    component, a metal-containing component, a fluo-
    rescent component, a chemiluminescent compo-
    nent, a chromogenic component, a hapten or a
    combination of any of the foregoing.
ʼ180 patent claim 1 (emphases added).
    “Sig” represents a signaling moiety (i.e., a label); PM
represents a phosphate moiety; SM represents a sugar moi-
ety; and BASE represents a base moiety.
                              B
    The asserted claims of U.S. Patent No. 8,097,405 (“the
ʼ405 patent”) fall into two categories: (1) in situ hybridiza-
tion claims; and (2) liquid phase hybridization claims.
    The in situ hybridization claims (claims 63, 64, 65, 95,
103, 128, and 144) describe a process that uses a probe non-
radioactively labeled at any non-Ward position to identify
chromosomes. In situ hybridization is where probes are
hybridized to a target that is fixed, usually on a glass slide.
Claim 64 is exemplary.
    The liquid phase hybridization claims (claims 196 and
198) describe a process that uses a non-radioactively la-
beled probe to hybridize and detect a target sequence in a
liquid medium, rather than on a glass slide. These claims
cover using probes labeled non-radioactively at any posi-
tion on the nucleotide, including the three Ward positions.
The asserted liquid phase hybridization claims depend
from claim 189.
ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,       7
INC.


                             C
    This consolidated appeal involves four district court
cases. 2 The ʼ180 patent is at issue in all four cases, while
the ʼ405 patent is at issue only in the cases against Abbott.
     In January 2012, Enzo filed suit against Roche Molec-
ular Systems, Inc., Roche Diagnostics Corp., Roche Diag-
nostics Operations, Inc., and Roche Nimblegen, Inc.
(collectively, “Roche”) alleging infringement of the ʼ180 pa-
tent. J.A. 1212–16 (Compl.) (Case No. 1:12-cv-106). In
March 2012, Enzo filed separate suits against Becton,
Dickinson and Co., Becton Dickinson Diagnostics Inc., and
GeneOhm Sciences, Inc. (collectively, “BD”); and Abbott
Laboratories and Abbott Molecular, Inc. (collectively, “Ab-
bott”) alleging infringement of the ʼ180 patent. J.A. 2833–
36 (Compl.) (Case No. 1:12-cv-275 against BD); J.A. 1964–
67 (Compl.) (Case No. 1:12-cv-274 against Abbott). In Feb-
ruary 2013, Enzo filed a second suit against Abbott alleging
infringement of the ʼ405 patent. J.A. 3973–77 (Compl.)
(Case No. 1:13-cv-225).
    In June 2017, in the cases against Roche and BD, the
district court denied summary judgment with respect to
written description, but granted summary judgment in fa-
vor of the defendants, holding that all asserted claims of
the ʼ180 patent were invalid as not enabled. See J.A. 59–
77, 99–117. The district court entered partial final judg-
ment of invalidity pursuant to Federal Rule of Civil Proce-
dure 54(b) with respect to the claims of the ʼ180 patent in
the cases against BD and Roche. J.A. 14–18 (BD), 5–9
(Roche).
    In the two Abbott cases, Enzo agreed that the district
court’s earlier enablement ruling as to the ʼ180 patent
would be deemed to apply to the claims of that patent


    2  Appeal Nos. 17-2354 and 17-2355 were dismissed
by agreement of the parties in those appeals. ECF No. 98.
8     ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,
                                                      INC.


asserted against Abbott. J.A. 23, 14950–51. As to the ʼ405
patent, in August 2017, the district court denied Abbott’s
motion as to written description but granted summary
judgment in favor of Abbott, holding the claims invalid for
lack of enablement. J.A. 78–98. The district court entered
final judgment of invalidity of all asserted claims of the
ʼ180 and ʼ405 patents on September 1, 2017. J.A. 10–13,
23–26.
    Enzo timely appealed each judgment. This court con-
solidated the appeals. We have jurisdiction under 28
U.S.C. § 1295(a)(1).
                              II
    In reviewing a grant of summary judgment, we apply
the law of the regional circuit. Vasudevan Software, Inc. v.
MicroStrategy, Inc., 782 F.3d 671, 676 (Fed. Cir. 2015). The
Third Circuit reviews a district court’s grant of summary
judgment de novo. Melrose, Inc. v. City of Pittsburgh, 613
F.3d 380, 387 (3d Cir. 2010). “Summary judgment is ap-
propriate only where, drawing all reasonable inferences in
favor of the nonmoving party, there is no genuine issue as
to any material fact and . . . the moving party is entitled to
judgment as a matter of law.” Id. (quoting Ruehl v. Viacom,
Inc., 500 F.3d 375, 380 n.6 (3d Cir. 2007)). “[U]nless there
is sufficient evidence favoring the nonmoving party for a
jury to return a verdict for that party,” there is no need for
a trial, and summary judgment is appropriate. Anderson
v. Liberty Lobby, Inc., 477 U.S. 242, 249 (1986).
                             III
     The enablement requirement asks whether “the speci-
fication teach[es] those in the art to make and use the in-
vention without undue experimentation.” In re Wands, 858
F.2d 731, 737 (Fed. Cir. 1988). To satisfy this requirement,
“[t]he specification must contain sufficient disclosure to en-
able an ordinarily skilled artisan to make and use the en-
tire scope of the claimed invention at the time of filing.”
ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,            9
INC.


MagSil Corp. v. Hitachi Glob. Storage Techs., Inc., 687 F.3d
1377, 1381 (Fed. Cir. 2012). “Enablement is a question of
law based on underlying factual findings.” Id. at 1380.
     “To prove that a claim is invalid for lack of enablement,
a challenger must show by clear and convincing evidence
that a person of ordinary skill in the art would not be able
to practice the claimed invention without ‘undue experi-
mentation.’” Alcon Research Ltd. v. Barr Labs., Inc., 745
F.3d 1180, 1188 (Fed. Cir. 2014) (quoting In re Wands, 858
F.2d at 736–37). 3 In analyzing undue experimentation, we
consider factors such as: “(1) the quantity of experimenta-
tion necessary, (2) the amount of direction or guidance pre-
sented, (3) the presence or absence of working examples,
(4) the nature of the invention, (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.” In re Wands, 858 F.2d at 737.
     In our view, the issue in this appeal is not simply
whether the specification enables labeling; the question is
whether it enables creation of a labeled probe that is both
hybridizable and detectable upon hybridization. Many of
the alleged factual disputes raised by Enzo and many of the
arguments raised by Appellees relate to the details of cre-
ating the labeled polynucleotide. For example, Roche and
BD contend that the specification fails to sufficiently dis-
close internal phosphate labeling. But even if we assume
that the specification teaches one of skill in the art how to
create the broad range of labeled polynucleotides covered
by the claims, as explained below, the specification still
fails to teach one of skill in the art which combinations will


    3    In this case, the parties agree that the relevant per-
son of ordinary skill in the art is a scientist with a doctorate
in chemistry, biochemistry, biophysics, molecular biology,
or a similar field. Appellant’s Br. 30 (noting the parties’
agreement).
10    ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,
                                                      INC.


produce a polynucleotide that is hybridizable and detecta-
ble upon hybridization, as required by the claim language.
    With this focus on the functionality required by the
claims, we agree with Appellees that our decision in Wyeth
and Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380
(Fed. Cir. 2013), controls this case. In Wyeth, we affirmed
a grant of summary judgment and held the asserted claims
invalid for lack of enablement because it would have re-
quired undue experimentation to determine which com-
pounds in the claimed class would have the required
functionality. Id. at 1385–86. The claims in Wyeth were
construed to require a compound having certain function-
ality (e.g., immunosuppressive effects). Id. at 1383. The
claims covered a class of compounds that met those func-
tional requirements. Id. at 1385. The patentee’s witnesses
testified that minor alterations to the molecule disclosed in
the specification could impact the required functionality.
Id. The patent challengers in that case thus argued that a
person of ordinary skill in the art would need to screen each
compound to determine what candidates would have the
claimed functionality. Id. We agreed. Id. We noted the
breadth of the claims, the limited guidance provided in the
specification, the large number of possible candidates fall-
ing within the claimed genus (tens of thousands), and the
fact that it would be necessary to first synthesize and then
screen each of those candidates to determine whether it
had the required functionality. Id. We further noted that
one of the patentee’s scientists had confirmed the unpre-
dictability in the art by testifying that one would need to
test each compound to understand whether it would have
the desired functionality. Id. We thus concluded that there
was no genuine dispute that practicing the full scope of the
claims would require undue experimentation. Id.
    The facts in this appeal largely mirror those in Wyeth.
As in Wyeth, the asserted claims here require not just a
particular structure, but a particular functionality (i.e., the
labeled polynucleotides must be hybridizable and
ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,        11
INC.


detectable upon hybridization). As explained below, the
specification fails to teach one of skill in the art whether
the many embodiments of the broad claims would exhibit
that required functionality.
    The scope of the claims is quite broad. Claim 1 of the
ʼ180 patent encompasses all phosphate-labeled polynucle-
otides that are hybridizable and detectable. The claim
places almost no limitations on the structure of the claimed
polynucleotide, other than the fact that the label is at-
tached to the phosphate portion of the nucleotide. It does
not restrict the chemistry used to attach the label, the
chemical linker used, the number of labels within a probe,
or the location of the labels on the probe (i.e., whether they
are terminal or internal). As to the type of non-radioactive
label used, the claim provides broad categories, such as any
“electron dense component” or “magnetic component.”
     The specification’s guidance as to how such variables
would or would not impact the functionality of the claimed
probes is sparse. For example, Enzo directs our attention
to a sentence in the specification that states that “[a] par-
ticularly important and useful aspect of the special nucleo-
tides of this invention is the use of such nucleotides in the
preparation of DNA or RNA probes.” ʼ180 patent col. 54
ll. 18–20; see also id. col. 54 ll. 18–33 (describing generally
how a probe works). Enzo’s expert, Dr. Backman, ex-
plained that a skilled artisan would have understood this
reference to using the polynucleotide as a “probe” as mean-
ing a polynucleotide that is capable of hybridizing and be-
ing detected upon hybridization.            J.A. 5840–41 ¶ 57
(Backman Decl.). But at the time of the invention, the art
was highly unpredictable. As Enzo’s expert explained:
    At the time of the inventions of the ʼ180 patent, it
    was commonly thought that the addition of a non-
    radioactive label to a nucleic acid sequence at posi-
    tions other than a few known as ‘non-disruptive po-
    sitions’ . . . would interfere with or disrupt the
12     ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,
                                                       INC.


     hybridization process, rendering the nucleotide in-
     effective for diagnostic purposes.
J.A. 4728 ¶ 74 (Backman Opening Report).
    Given the unpredictability of the art at the time and
the serious doubts held by those of skill in the art regarding
whether labels could be attached to non-Ward positions
without disrupting hybridization, merely stating that a la-
beled polynucleotide will work as a probe is not sufficient
to enable one of skill in the art to know that it would indeed
function as a probe—i.e., be hybridizable and detectable
upon hybridization.
    Enzo also presents Example V as an example of an in-
ternal phosphate-labeled polynucleotide that is hybridiza-
ble and detectable. Appellant’s Br. 32–33. Example V
states in full:
     Biotin and polybiotinylated poly-L-lysine were cou-
     pled to oligoribonucleotides using a carbodiimide
     coupling procedure described by Halbran and Par-
     ker, J. Immunol., 96 373 (1966). As an example,
     DNA (1 ug/ml), 1 ml) in tris buffer pH 8.2, sheared
     with 0.1 N sodium hydroxide was denatured by
     boiling for 10 minutes and quick cooling in an ice
     bath. Biotinyl-1,6-diaminohexane amide (2 mg, 6
     umol) or polybiotinylated poly-L-lysine (2 mg) and
     l-ethyl-3-diisopropylaminocarboimide HCl (10 mg,
     64 umol) were added, and the pH readjusted to 8.2.
     After 24 hours at room temperature in the dark,
     the mixture was dialyzed against 10 mM tris buff-
     ered saline. DNA was precipitated ethanol.
ʼ180 patent col. 33 ll. 33–44.
    Appellees contend that Example V is not a working ex-
ample. During prosecution, Enzo admitted that Example
V is a “‘paper’, rather than [a] ‘working example[].’”
J.A. 4703 (stating in an amendment made during prosecu-
tion that “Applicants have determined that the examples
ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,         13
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set forth . . . [except certain examples other than Example
V] are ‘paper’, rather than ‘working examples’”); J.A. 6657
(same). Additionally, Enzo’s expert testified that he was
not aware of Enzo having ever tested a phosphate-labeled
probe for hybridizability and detectability. J.A. 8547–48
p. 84 l. 5–p. 85 l. 16 (Backman deposition); J.A. 8551–52
p. 124 l. 10–p. 125 l. 11 (Backman deposition); see also
J.A. 6441 p. 133 ll. 6–15 (Backman deposition) (“Q: . . . is
there any bench experiment disclosed in the ʼ180 patent in
which the ʼ180 inventors attempted to determine whether
the product of Example V, that is, the Sig moiety attached
to an oligo- or polynucleotide could be detected after it had
hybridized to a compl[e]mentary nucleic acid of interest?
A. . . . no, they did not do an actual bench experiment to
that effect.”); id. p. 131 ll. 7–19. Regardless, even viewing
Example V as a working example, Example V is insuffi-
cient to enable the breadth of the claims here, especially in
light of the unpredictability in the art. 4
    The deficiencies in the description as to enablement
cannot be cured in this case by looking to the knowledge of
those skilled in the art at the time of the invention. Alt-
hough “a specification need not disclose what is well known
in the art,” that rule is “not a substitute for a basic enabling
disclosure.” Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d
1361, 1366 (Fed. Cir. 1997). As we have said before, a pa-
tentee “cannot simply rely on the knowledge of a person of
ordinary skill to serve as a substitute for the missing infor-
mation in the specification.” ALZA Corp. v. Andrx Pharm.,



    4   Nothing stated herein would necessarily disallow
proper constructive examples, which are intended to fulfill
both written description and enablement requirements.
Atlas Powder Co. v. E.I. du Pont De Nemours & Co., 750
F.2d 1569, 1577 (Fed. Cir. 1984) (“Use of prophetic exam-
ples, however, does not automatically make a patent non-
enabling.”).
14    ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,
                                                      INC.


LLC, 603 F.3d 935, 941 (Fed. Cir. 2010). And, more im-
portantly, all parties acknowledge that serious doubts ex-
isted in the art as to whether the use of non-radioactive
probes at non-Ward positions would be useful as probes.
For example, an inventor of the ʼ180 patent who is also
Enzo’s CEO explained that, at the time, it was thought “ag-
gressive chemical modification of nucleic acid would lead to
destruction of his [sic] content.” J.A. 6470 p. 1265 l. 5–
p. 1266 l. 15 (Dr. Rabbani deposition); see also J.A. 6465
p. 31 l. 12–p. 33 l. 13 (Dr. Rabbani explaining how more ag-
gressive modification of the nucleic acid was considered
“breaking the dogma”). Enzo’s expert, Dr. Backman, also
pointed out the view of the art at the time, stating that “[a]t
the time of the inventions of the ’180 patent, it was com-
monly thought that the addition of a nonradioactive label
to a nucleic acid sequence at positions other than [the Ward
positions at the base] would interfere with or disrupt the
hybridization process.” J.A. 4728 ¶ 74 (Backman’s Opening
Report); J.A. 4184 ll. 10–24 (Dr. Rabbani deposition). In-
deed, Enzo’s expert explained that for one of skill in the art
to be comfortable that a particular polynucleotide would
work as a probe, “they would need to actually make the
compound and test it in a hybridization experiment, which
they would have been dissuaded from doing because of
Ward.” J.A. 8454 p. 150 ll. 8–15 (Sherman deposition) (dis-
cussing a polynucleotide labeled at the terminal phosphate
and using carbodiimide chemistry and biotin); see also
J.A. 8456 ll. 3–11 (Sherman deposition) (“Q: . . . But if they
had been motivated to make this probe, non-Ward labeled
probe, your view is that they would have to make it and
test it in order to predict whether it would actually hybrid-
ize as of June 1982, right? A: Well, they would have to
make it and assure against the prevailing wisdom that it
could work.”); J.A. 8454–55 p. 150 l. 17–p. 151 l. 18 (Sher-
man deposition).
   Given such unpredictability in the art, and considering
the testimony of Enzo’s expert that each labeled
ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,       15
INC.


polynucleotide would need to be tested to determine
whether it is hybridizable and detectable upon hybridiza-
tion, the breadth of the claims here is particularly concern-
ing in the enablement inquiry. See In re Fisher, 427 F.2d
833, 839 (CCPA 1970) (“In cases involving unpredictable
factors, such as most chemical reactions and physiological
activity, the scope of enablement obviously varies inversely
with the degree of unpredictability of the factors in-
volved.”). Appellees contend that millions of embodiments
of the claims exist based on the many variables involved in
creating one of the claimed labeled polynucleotides. Enzo
disputes this number, arguing it is improperly inflated be-
cause it counts every possible polynucleotide sequence that
could exist as a separate embodiment. Even assuming
Enzo is correct that the length and sequence of the polynu-
cleotide do not give rise to separate embodiments, the other
variables (such as the type of label, the type of linker used
to attach the label, and the location of the labels within the
polynucleotide) still result in an extremely large number of
possible embodiments. Indeed, Enzo’s expert explained
that the number of possible polynucleotides that would fit
within the limitations of claim 1 would be at least “tens of
thousands.” J.A. 6438 p. 120 l. 20–p. 121 l. 11 (Backman
deposition).
    In sum, even if Example V describes one working em-
bodiment with the claimed functionality, undue experi-
mentation would still be required with regard to the many
other embodiments of the claims based on the number of
possible embodiments and the unpredictability in the art.
See Genentech, 108 F.3d at 1366 (“Patent protection is
granted in return for an enabling disclosure of an inven-
tion, not for vague intimations of general ideas that may or
may not be workable.”).
    We conclude by briefly addressing the asserted claims
of the ʼ405 patent. Those claims are broader than the as-
serted claims of the ʼ180 patent; rather than covering only
phosphate-labeled polynucleotides, they also cover labeling
16    ENZO LIFE SCIENCES, INC. V. ROCHE MOLECULAR SYSTEMS,
                                                      INC.


at other locations on a nucleotide. Like the claims of the
ʼ180 patent, the asserted claims of the ʼ405 patent require
the claimed polynucleotides to be hybridizable and detect-
able upon hybridization. Because the specification does not
enable the narrower scope of polynucleotides claimed in the
ʼ180 patent, it also cannot enable the broader scope of pol-
ynucleotides claimed in the ʼ405 patent. As such, even
though the asserted claims of the ʼ405 patent pertain to
certain processes, the claims are still not enabled for the
reasons described with respect to the ʼ180 patent.
    In sum, viewing the evidence in the light most favora-
ble to Enzo, we agree with the district court’s grant of sum-
mary judgment.
                             IV
    For the foregoing reasons, we affirm the district court’s
grant of summary judgment that the asserted claims of the
ʼ180 patent and the ʼ405 patent are invalid for lack of ena-
blement.
                       AFFIRMED
