Court Opinion

ID: 2653917
Source: CourtListenerOpinion
Date Created: 2014-02-21 01:01:35.692219+00
Date Added: 2024-06-11T12:57:58.225289
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
                ______________________

   TAKEDA PHARMACEUTICAL COMPANY
LIMITED, TAKEDA PHARMACEUTICALS NORTH
 AMERICA, INC., TAKEDA PHARMACEUTICALS,
 LLC, TAKEDA PHARMACEUTICALS AMERICA,
         INC., AND ETHYPHARM, S.A.,
               Plaintiffs-Appellees,

                           v.

    ZYDUS PHARMACEUTICALS USA, INC. AND
       CADILA HEALTHCARE LIMITED,
             Defendants-Appellants.
             ______________________

                      2013-1406
                ______________________

    Appeal from the United States District Court for the
District of New Jersey in No. 10-CV-1723, Judge Joel A.
Pisano.
                 ______________________

              Decided: February 20, 2014
               ______________________

    ARLENE L. CHOW, Hogan Lovells US LLP, of New
York, New York, argued for plaintiffs-appellees. With her
on the brief were ERIC J. LOBENFELD of New York, New
York; CATHERINE E. STETSON and FREDERICK LIU, of
Washington, DC.      Of counsel was PHILIPPE YOLAND
RIESEN, of Tokyo, Japan.
2   TAKEDA PHARMACEUTICAL CO.    v. ZYDUS PHARMACEUTICALS
                                                        USA

   STEVEN J. MOORE, Kelley Drye & Warren, LLP, of
Stamford, Connecticut, argued for defendants-appellants.
With him on the brief was JAMES E. NEALON.
                ______________________

    Before PROST, PLAGER, and CHEN, Circuit Judges.
PROST, Circuit Judge.
     Zydus Pharmaceuticals USA, Inc. and Cadila
Healthcare Limited (“appellants” or “Zydus”) appeal from
a final judgment of the U.S. District Court for the District
of New Jersey finding that appellants had infringed claim
1 of U.S. Patent No. 6,328,994 (“’994 patent”) and had
failed to establish that it was invalid. For the reasons
stated below, we reverse the district court’s finding of
infringement, but affirm its ruling on invalidity.
                        BACKGROUND
    Takeda Pharmaceutical Company Limited, Takeda
Pharmaceuticals North America, Inc., Takeda Pharma-
ceuticals, LLC, Takeda Pharmaceuticals America, Inc.,
and Ethypharm, S.A. (“appellees” or “Takeda”) own
patents that claim the formulation for the brand-name
drug Prevacid® SoluTab™. Prevacid® SoluTab™ con-
tains the active ingredient lansoprazole, which is a proton
pump inhibitor used to treat gastroesophageal reflux
disease, or acid reflux. It is the only proton pump inhibi-
tor available as an orally disintegrable tablet. A patient
taking Prevacid® SoluTab™ simply allows the tablet to
disintegrate in his or her mouth, leaving behind thou-
sands of granules which the patient then swallows. The
stated objective of the ’994 patent is that the formulation
contains granules small enough to avoid a feeling of
roughness in the patient’s mouth upon disintegration.
    In 2010, Zydus filed an abbreviated new drug applica-
tion (“ANDA”) with the Food and Drug Administration,
seeking to manufacture a generic version of Prevacid®
TAKEDA PHARMACEUTICAL CO.   v. ZYDUS PHARMACEUTICALS      3
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SoluTab™. Takeda then filed suit, alleging that Zydus’s
ANDA product infringed multiple claims of several pa-
tents. Only claim 1 of the ’994 patent remains at issue.
Zydus counterclaimed, alleging that claim 1 was invalid
for failure to comply with the requirements of 35 U.S.C.
§ 112.
   Claim 1 recites:
   An orally disintegrable tablet which comprises (i)
   fine granules having an average particle diameter
   of 400 µm or less, which fine granules comprise a
   composition coated by an enteric coating layer
   comprising a first component which is an enteric
   coating agent and a second component which is a
   sustained-release agent, said composition having
   10 weight % or more of an acid-labile physiologi-
   cally active substrate that is lansoprazole and (ii)
   an additive wherein said tablet having a hardness
   strength of about 1 to about 20 kg, is orally disin-
   tegrable.
’994 patent col. 37 ll. 43-53. The district court held a
claim construction hearing, at which it construed the
claim term “fine granules having an average particle
diameter of 400 µm or less.” Takeda argued that the term
should be construed to include a deviation of ±10%, be-
cause it is “universally accepted” that there is a 10%
standard of error for particle size measurements. J.A.
154. Zydus, on the other hand, argued that the term
should be construed as “precisely 400 µm.” J.A. 496. The
district court agreed with Takeda, and construed the term
to mean “fine granules up to and including the enteric
coating layer having an average particle diameter of 400
µm (±10%) or less.” Takeda Pharm. Co. v. Zydus Pharms.
USA Inc., No. 10-1723, 2011 WL 4736306, at *3-4 (D.N.J.
Oct. 5, 2011).
   The issue of infringement turned on how particle size
was measured. During the manufacturing process, indi-
4   TAKEDA PHARMACEUTICAL CO.    v. ZYDUS PHARMACEUTICALS
                                                        USA

vidual cores of lansoprazole are enteric coated using a
fluid-bed coating process. Inevitably, that process results
in a certain portion of the coated cores becoming fused
together. These fused multi-cored granules are known as
“hard agglomerates.”
    Takeda argued that the average particle diameter
should be determined by measuring each individual core,
regardless of whether they had fused together into a hard
agglomerate. Taking that measurement requires “virtual
dissection” of hard agglomerates, meaning drawing an
artificial line between the two fused cores such that the
software will treat them separately for measurement
purposes.      Obviously, artificially dividing large hard
agglomerates into several smaller granules for measure-
ment purposes lowers the average particle size of a sam-
ple, making it more likely to infringe claim 1 of the ’994
patent. Zydus argued that, to the contrary, because the
specification describes measuring particle size after the
coating process and says nothing about deagglomeration,
it by definition includes hard agglomerates in the meas-
urement of average particle diameter. In support of its
position, Zydus pointed out that the actual size of the
fused particles is what is relevant to how the granules feel
in the patient’s mouth, regardless of the size of the small-
er fused cores that make up a hard agglomerate. Under
the district court’s claim construction, where the maxi-
mum average particle size is 440 µm, Zydus’s ANDA
product would infringe claim 1 of the ’994 patent if hard
agglomerates were virtually dissected prior to measure-
ment, but would not infringe if hard agglomerates were
included in the measurement.
    After a bench trial, the district court agreed with
Takeda and found that the ’994 patent requires measur-
ing the average diameter of each core, regardless of how
many cores are in a given hard agglomerate. Takeda
Pharm. Co., Ltd. v. Zydus Pharms. USA Inc., No. 10-1723,
slip op. at 12-13 (D.N.J. May 7, 2013) (“Opinion”). Based
TAKEDA PHARMACEUTICAL CO.    v. ZYDUS PHARMACEUTICALS      5
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on that finding, the district court determined that Zydus’s
ANDA product infringed claim 1 of the ’994 patent. Id. at
19-21. The district court further concluded that Zydus
had failed to establish by clear and convincing evidence
that claim 1 was invalid. Id. at 25-42. The court then
entered an injunction preventing Zydus from manufactur-
ing or selling its ANDA product until the expiration of
the ’994 patent. Id. at 43-46. Zydus appealed all of the
district court’s rulings.
    We have jurisdiction under 28 U.S.C. § 1295(a)(1).
                         ANALYSIS
                  I. Claim Construction
    Claim construction is a question of law that we review
without deference. Cybor Corp. v. FAS Techs., Inc., 138
F.3d 1448, 1455-56 (Fed. Cir. 1998) (en banc). Our start-
ing point in construing a claim term must be the words of
the claim itself. See Vitronics Corp. v. Conceptronic, Inc.,
90 F.3d 1576, 1582 (Fed. Cir. 1996); Phillips v. AWH
Corp., 415 F.3d 1303, 1314 (Fed. Cir. 2005) (en banc)
(“[T]he claims themselves provide substantial guidance as
to the meaning of particular claim terms.”). However, it
is axiomatic that the claims “must be read in view of the
specification, of which they are a part.” Phillips, 415 F.3d
at 1315 (quoting Markman v. Westview Instruments, Inc.,
52 F.3d 967, 979 (Fed. Cir. 1995) (en banc), aff’d 517 U.S.
370 (1996)). Additionally, a court “should also consider
the patent’s prosecution history, if it is in evidence.”
Markman, 52 F.3d at 980. Although courts are permitted
to consider extrinsic evidence, such as expert testimony,
dictionaries, and treatises, we have cautioned that such
evidence is generally of less significance than the intrinsic
record. Phillips, 415 F.3d at 1317 (citing C.R. Bard, Inc.
v. U.S. Surgical Corp., 388 F.3d 858, 862 (Fed. Cir. 2004)).
Ultimately, “[t]he construction that stays true to the
claim language and most naturally aligns with the pa-
tent’s description of the invention will be, in the end, the
6   TAKEDA PHARMACEUTICAL CO.    v. ZYDUS PHARMACEUTICALS
                                                       USA

correct construction.” Renishaw PLC v. Marposs Societa’
per Azioni, 158 F.3d 1243, 1250 (Fed. Cir. 1998).
    With these principles in mind, we turn to the disputed
claim language. Zydus challenges the district court’s
construction of the claim term “fine granules having an
average particle diameter of 400 µm or less.” The district
court construed that term to include a ±10% deviation.
Zydus argues that it should be construed to require an
average particle diameter of “precisely 400 µm or less.”
We agree with Zydus that the district court erred in
reading a margin of error into the disputed claim term.
    Beginning with the claim language itself—as we
must—there is no indication in the claim that 400 µm was
intended to mean anything other than exactly 400 µm. To
the contrary, the phrase “400 µm or less” is not qualified
by the word “about” or any other indicator of imprecision.
    Moreover, the specification confirms that the inven-
tors did not intend to deviate from that clear and unam-
biguous plain meaning. First, the specification contrasts
the “fine granules” of the claimed invention with larger
“conventional” granules, which it defines as “400 µm or
more of average particle diameter.” ’994 patent col. 2 ll.
17-18.    The specification explains that conventional
granules of that size “produce a feeling of roughness in
the mouth”—one of the very problems the claimed inven-
tion purports to solve. Id. col. 2 ll. 16-17. That clear
dividing line between the “fine” granules of 400 µm or less
(which avoid a feeling of roughness in the mouth) and
“conventional” granules of 400 µm or more (which do not)
disappears if the “fine granules” are construed as incorpo-
rating a 10% deviation. Thus, there can be little doubt
that the narrower construction “most naturally aligns
with the patent’s description of the invention.” Renishaw,
158 F.3d at 1250.
   Second, the specification goes on to explain that the
maximum particle size is “practically 425 µm or less,”
TAKEDA PHARMACEUTICAL CO.   v. ZYDUS PHARMACEUTICALS      7
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where “practically” means that “the particles may include
a small quantity (about 5 weight % or less) of particles
whose particle diameter is out of above described
range.” ’994 patent col. 5 l. 65–col. 6 l. 8. Elsewhere, the
patent defines “average particle diameter” to mean the
median particle diameter. See id. col. 5 ll. 43-46. It would
be impossible for a tablet to comply with the specifica-
tion’s maximum particle diameter of practically 425 µm
(meaning that only 5% of particles have diameters larger
than 425 µm) if it had a median particle diameter of 440
µm (meaning that 50% of the particles are larger than 440
µm), as the district court’s claim construction would
permit. This tension suggests that the inventors did not
intend to incorporate a ±10% deviation into the average
particle diameter of claim 1.
    Takeda argues that the inventors effectively acted as
their own lexicographers and modified the plain meaning
of the term “fine granules” in the specification. The
specification states:
   In the present invention, “fine granules having an
   average particle diameter of 400 µm or less, which
   fine granules comprise a composition coated by an
   enteric coating layer, said composition having 10
   weight % or more of an acid-labile physiologically
   active substance” have an average particle diame-
   ter of about 400 µm or less, in order that rough-
   ness is not felt in the mouth. Preferably, the
   average particle diameter of the fine granules is
   300 to 400 µm.
’994 patent col. 5 ll. 57-64 (emphasis added). Takeda
maintains that the inventors therefore expressly defined
400 µm as an approximate figure, and that a skilled
artisan would know that a standard deviation for particle-
size measurements is ±10%. We disagree.
   The word “about” is used to modify the phrase “400
µm or less” only three times in the specification. In
8    TAKEDA PHARMACEUTICAL CO.      v. ZYDUS PHARMACEUTICALS
                                                         USA

addition to the passage quoted above, the specification
states:
    [T]he average particle a [sic] diameter of the in-
    cluded granules must be about 400 µm or less,
    preferably about 350 µm.
Id. col. 2 ll. 20-22. And later, it reiterates:
    The “fine granules” have an average particle di-
    ameter of about 400 µm or less, preferably 350 µm
    or less. Preferably; the average particle diameter
    of the fine granules is 300 to 400 µm.
Id. col. 12 ll. 58-61. In every one of these instances, the
word “about” is immediately followed by a preference for
an average particle size lower than 400 µm. Nowhere
does the specification suggest that an average particle
size greater than 400 µm (even within 10% of that figure)
could achieve the inventive result of avoiding a feeling of
roughness in the mouth. Thus, we are not persuaded that
the mere presence of the word “about” at three points in
the specification can justify a 10% expansion of claim
scope.
    Indeed, the remainder of claim 1 demonstrates that
the inventors knew how to express ambiguity in claim
language when they so desired; it provides that the tablet
must have a hardness strength of “about 1 to about 20
kg.” ’994 patent col. 37 l. 52 (emphasis added). Plainly,
then, had the inventors desired the average particle
diameter to include a margin of error, they could easily
have included the word “about” in the claim language. In
the absence of their decision to do so, however, we will not
take it upon ourselves to rewrite the claim in that way.
    This reading of the specification is confirmed by the
prosecution history. There, the inventors distinguished
the claimed invention over a potentially invalidating prior
art reference because the reference failed to disclose an
average particle diameter of 400 µm or less. J.A. 7228.
TAKEDA PHARMACEUTICAL CO.   v. ZYDUS PHARMACEUTICALS      9
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The inventors explained that “[b]y having the average
particle diameter of the granules within 400 µm, the
feeling of roughness in a mouth can be prevented.” J.A.
7228 (emphasis added). In other words, the inventors
have consistently relied on 400 µm as the dividing line
between granules that would avoid roughness in the
mouth and those that would not—meaning those that
were within the scope of the invention, and those that
were not. We long ago established that “[w]here there is
an equal choice between a broader and a narrower mean-
ing of a claim, and there is an enabling disclosure that
indicates that the applicant is at least entitled to a claim
having the narrower meaning, we consider the notice
function of the claim to be best served by adopting the
narrower meaning.” Athletic Alternatives, Inc. v. Prince
Mfg., Inc., 73 F.3d 1573, 1581 (Fed. Cir. 1996). Thus,
even if the two proposed constructions before us presented
an “equal choice”—and they do not—the narrower con-
struction would be more appropriate.
    We therefore reverse the district court’s claim con-
struction and conclude that the proper construction of the
disputed claim term is “fine granules having an average
particle diameter of precisely 400 µm or less.”
                     II. Infringement
    As explained above, the dispute as to literal infringe-
ment turned on whether the patent required virtual
dissection of hard agglomerates prior to particle size
measurement. Even using virtual dissection, however,
Takeda measured Zydus’s ANDA product as having an
average particle diameter of 412.28 µm—well outside the
claimed range as we have now construed it. Appellants’
Br. 31; J.A. 8338. Thus, there can be no dispute that
10       TAKEDA PHARMACEUTICAL CO.   v. ZYDUS PHARMACEUTICALS
                                                          USA

Zydus’s ANDA product does not literally infringe claim 1
of the ’994 patent. 1
    We therefore reverse the district court’s finding of lit-
eral infringement.
                        III. Invalidity
    Zydus raises several challenges to the validity of
the ’994 patent based on a failure to satisfy the require-
ments of 35 U.S.C. § 112. A number of those arguments
related to the claim construction adopted by the district
court, which we have now reversed, and are therefore
moot. We will address the remaining arguments in turn.
                       A. Indefiniteness
    We review a district court’s ruling on indefiniteness
de novo, as it is a question of law. ePlus, Inc. v. Lawson
Software, Inc., 700 F.3d 509, 516 (Fed. Cir. 2012).
“Whether a claim is invalid for indefiniteness requires a
determination whether those skilled in the art would
understand what is claimed when the claim is read in
light of the specification.” Morton Int’l, Inc. v. Cardinal
Chem. Co., 5 F.3d 1464, 1470 (Fed. Cir. 1993). As always,
the party challenging the patent bears the burden of
proving invalidity by clear and convincing evidence.
Microsoft Corp. v. i4i Ltd. P’ship, 131 S. Ct. 2238, 2242
(2011).
   Zydus argues that the ’994 patent is indefinite be-
cause it does not specify the method of measurement that

     1  Although it was not necessary for us to consider
whether the ’994 patent requires deagglomeration in our
infringement analysis, we do consider that question below
in the context of Zydus’s invalidity arguments. See infra
Section III.C.
TAKEDA PHARMACEUTICAL CO.    v. ZYDUS PHARMACEUTICALS     11
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should be used to determine average particle diameter. 2
Zydus insists that there are several methods that could
potentially be used to take that measurement, and the
same sample could be either infringing or non-infringing
depending on the measurement technique used. Thus,
the skilled artisan has no way to determine whether his
or her product infringes the ’994 patent based on the
information provided in the specification.
     We disagree. It is true that there was evidence from
both parties’ experts that there are several possible ways
to measure average particle diameter. Indeed, the patent
specification itself identifies laser diffraction as just one
“example” of such a measurement technique, ’994 patent
col. 5 ll. 46-50, and the experts agreed that optical micros-
copy is another equally viable method. Additionally, the
experts agreed that different measurement techniques
could indeed produce different results. The variation
arises from the difficulty in measuring the average diam-
eter of particles that are not perfect spheres. By necessi-
ty, both techniques involve indirect measurements; laser
diffraction involves analyzing the diffraction patterns of a
laser beam passed through a field of particles, while
optical microscopy involves equating a pixelated image
with an equivalent spherical diameter. See J.A. 3733-34,
3736-37. Because the two methods use different means of
approximating average particle diameter, they can pro-
duce different results even for the same sample.
   However, we do not believe that the mere possibility
of different results from different measurement tech-

    2    Zydus actually argued that this fact rendered the
claim invalid for lack of enablement. However, in support
of its argument Zydus cited the legal standard for indefi-
niteness and relied on cases applying that same standard.
We have therefore construed Zydus’s argument to be one
of indefiniteness, rather than enablement.
12       TAKEDA PHARMACEUTICAL CO.   v. ZYDUS PHARMACEUTICALS
                                                         USA

niques renders claim 1 indefinite. Rather, the evidence
established that both methods of measurement accurately
report average particle diameter; the experts agreed that
“the correct but differing particle size results obtained
using various instruments are all equally correct, but
each simply may be expressing its correct results in
different terms.” J.A. 3983 (testimony of Zydus’s expert
Dr. Harry Brittain); see also J.A. 4148-49 (testimony of
Takeda’s expert Dr. Stephen Byrn).
     Moreover, there is no evidence that the differences be-
tween these techniques are in fact significant; there was
evidence before the trial court that although the results
may be different, there is a “high degree of correlation for
the results” between the two techniques, which should
“give equivalent numbers with respect to any variants
associated with either technique.” See J.A. 3738, 3792.
And indeed, there was no evidence in this case that differ-
ent measurement techniques in fact produced significant-
ly different results for the same sample. To the contrary,
the measurements of Zydus’s ANDA product using laser
diffraction and optical microscopy, though not exactly the
same, were substantially similar. Compare J.A. 8338
with J.A. 2115. Any theoretical minor differences be-
tween the two techniques are therefore insufficient to
render the patent invalid. See PPG Indus., Inc. v. Guard-
ian Indus. Corp., 75 F.3d 1558, 1563 (Fed. Cir. 1996)
(finding no indefiniteness despite failure to specify which
method should be used to measure ultraviolet transmit-
tance because all conventional methods produced “essen-
tially identical results”). 3

     3 Indeed, the evidence showed that four samples of
Zydus’s ANDA product, each measured using optical
microscopy, produced average particle diameters of 457.1
µm, 446.5 µm, 443.4 µm, and 444.0 µm. Appellants’ Br.
31; J.A. 8338. Plainly, then, there is the potential for
TAKEDA PHARMACEUTICAL CO.    v. ZYDUS PHARMACEUTICALS     13
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    Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d
1313 (Fed. Cir. 2003), on which Zydus relies, does not
compel a contrary result. Amgen involved patents relat-
ing to the production of erythropoietin, a naturally occur-
ring hormone that controls the formation of red blood cells
in bone marrow. One of the disputed claims related to an
erythropoietin glycoprotein product “having glycosylation
which differs from that of human urinary erythropoietin,”
or uEPO. Id. at 1340. However, the district court had
found that “two uEPO preparations produced from the
same batch of starting materials could nevertheless have
different glycosylation patterns.” Id. at 1341. Thus, the
claim itself was a moving target; as we explained, “one
must know what the glycosylation of uEPO is with cer-
tainty before one can determine whether the claimed
glycoprotein has a glycosylation different from that of
uEPO.” Id. (emphasis added). We therefore affirmed the
district court’s finding that the claims requiring “glycosyl-
ation which differs” were invalid for indefiniteness. Id. at
1342. That is a far cry from this case. Here, the claim
term itself could not be more straightforward; as we ruled
above, the claim plainly requires an average particle
diameter of 400 µm or less. That there is more than one
way of determining the average particle diameter of a
particular sample does not render that clear claim lan-
guage indefinite. 4

inconsistent results even within the same method of
measurement, but that surely does not render a claim
indefinite.
    4   Honeywell International, Inc. v. International
Trade Commission, 341 F.3d 1332 (Fed. Cir. 2003), is no
more persuasive. There, the patent-in-suit related to the
production of a polyester yarn product. Because the
specification did not discuss which sample preparation
method should be used, and the particular method chosen
14   TAKEDA PHARMACEUTICAL CO.   v. ZYDUS PHARMACEUTICALS
                                                        USA

    Therefore, we conclude that Zydus has not met its
burden of establishing by clear and convincing evidence
that claim 1 of the ’994 patent is invalid for indefinite-
ness.
                 B. Written Description
    The test for written description is “whether the disclo-
sure of the application . . . reasonably conveys to those
skilled in the art that the inventor had possession of the
claimed subject matter as of the filing date.” Ariad
Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010) (en banc). The question of whether a patent
specification contains sufficient written description is a
question of fact that we review for clear error. Pozen Inc.
v. Par Pharm., Inc., 696 F.3d 1151, 1166 (Fed. Cir. 2012).
    Zydus argues that claim 1 addresses average particle
size in the finished tablet, while the specification only
teaches how to measure particle size pre-tableting with no
discussion of how to ensure particle size is not altered by
that process. Thus, Zydus argues that the specification
does not demonstrate that the inventors were in posses-
sion of the claimed invention—tablets with particles of
400 µm or less post-tableting.
    However, Zydus’s argument depends on there actually
being an impact on particle size from the tableting pro-
cess, and the evidence showed the opposite. Indeed,
actual testing conducted by Takeda’s expert showed no

was “critical to discerning whether [an infringing yarn]
has been produced by the claimed process,” we affirmed
the Commission’s conclusion that the claims were indefi-
nite. Id. at 1340. Here, by contrast, no extensive manipu-
lation of the samples is required prior to measurement,
and, as discussed above, Zydus did not present clear and
convincing evidence that the method of measurement is in
fact outcome-determinative in the infringement analysis.
TAKEDA PHARMACEUTICAL CO.    v. ZYDUS PHARMACEUTICALS      15
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effect from compression forces on the granules in Zydus’s
ANDA product. J.A. 3756-57, 3872-73. This case is
therefore distinguishable from Eli Lilly & Co. v. Teva
Pharmaceuticals USA, Inc., 619 F.3d 1329 (Fed. Cir.
2010), on which Zydus relies. There, we upheld a finding
of invalidity where the invention related to particle size of
a formulated drug but the specification only disclosed how
to measure particle size pre-formulation. Id. at 1345.
However, the evidence in that case demonstrated that the
particle size of Teva’s product fell outside the claimed
range before formulation and within it after formulation.
Id. at 1344. Thus, without disclosing how to measure
particle size post-formulation, the inventors had not
demonstrated that they had in fact invented a formulated
drug with sufficiently small particles. By contrast, here,
the evidence established only a hypothetical possibility
that tableting could affect particle size in a relevant way. 5
We simply cannot say that the district court committed
clear error by finding that such evidence was not clear
and convincing proof of invalidity. 6

    5    Additionally, in Eli Lilly we were affirming the
district court’s finding of invalidity, whereas here a ruling
in Zydus’s favor would require us to conclude that the
district court had committed clear error, a much higher
standard.
    6    Takeda also points out that the district court
found that a skilled artisan would have known how to
extract granules from a finished tablet to measure their
size. However, that fact is only relevant to the enable-
ment inquiry, which Zydus has not challenged on this
basis.
16   TAKEDA PHARMACEUTICAL CO.   v. ZYDUS PHARMACEUTICALS
                                                        USA

                     C. Enablement
    Under the enablement requirement of 35 U.S.C.
§ 112, “the specification must enable one of ordinary skill
in the art to practice the claimed invention without undue
experimentation.” Transocean Offshore Deepwater Drill-
ing, Inc. v. Maersk Drilling USA, Inc., 699 F.3d 1340,
1355 (Fed. Cir. 2012) (quoting Nat’l Recovery Techs., Inc.
v. Magnetic Separation Sys., Inc., 166 F.3d 1190, 1196
(Fed. Cir. 1999)). Enablement is a question of law that we
review de novo based on underlying factual findings.
CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1337
(Fed. Cir. 2003).
    Zydus argues that the patent is invalid for lack of en-
ablement because a skilled artisan would not be able to
determine the average particle diameter using the coulter
counter method of measurement without undue experi-
mentation. The district court concluded that Zydus had
not met its burden of establishing lack of enablement by
clear and convincing evidence because it had submitted
only “conclusory statements” regarding the amount of
experimentation necessary, and because there was no
dispute that a skilled artisan would know how to measure
particle size using laser diffraction and/or optical micros-
copy. See Opinion at 29-30.
    We agree with the district court. It is well established
that the “enablement requirement is met if the descrip-
tion enables any mode of making and using the inven-
tion.” Johns Hopkins Univ. v. CellPro, Inc., 152 F.3d
1342, 1361 (Fed. Cir. 1998) (emphasis added) (internal
quotation marks omitted). Thus, because the patent
identifies laser diffraction as a viable measurement
technique, and there is no dispute that a skilled artisan
would know how to use laser diffraction to measure
particle diameter, Zydus has not established that the
patent is invalid for lack of enablement on this basis.
TAKEDA PHARMACEUTICAL CO.    v. ZYDUS PHARMACEUTICALS     17
USA

    However, we note for the record that if the district
court had been correct that the patent requires deagglom-
eration prior to particle size measurement, we would be
forced to reach a different conclusion regarding enable-
ment. Specifically, nothing in the written description
directs a skilled artisan to evaluate whether a sample
contains “more than nominal” hard agglomerates prior to
measurement, such that optical microscopy should be
used, nor does it explain how one would make that deter-
mination. Similarly, it does not explain how to conduct
virtual dissection of deagglomerates using optical micros-
copy. Thus, if the patent required deagglomeration prior
to measurement in certain circumstances, as the district
court found that it did, it could not be said that the writ-
ten description informed a skilled artisan how to make
and use the claimed invention. However, for the reasons
that follow, we believe that the district court clearly erred
in making that finding and will not invalidate the patent
on that basis.
     Takeda argues that the skilled artisan would simply
have known to use optical microscopy (and deagglomera-
tion) when a sample contains more than “nominal” hard
agglomerates. But the virtual dissection of agglomerates
runs counter to the lone methodology disclosed in the
specification. The only method of measurement discussed
in the specification is laser diffraction, which cannot
account for hard agglomerates. Indeed, there is no indica-
tion in the specification that the inventors themselves
undertook deagglomeration of their own samples prior to
measurement, or even evaluated whether deagglomera-
tion was necessary. We cannot conclude that the patent
affirmatively requires a step that was entirely absent
from (and even precluded by) the procedure described in
the specification.
    And indeed, this conclusion is entirely consistent with
the underlying objective of the patent; it is the actual size
of the granule itself—regardless of how many cores it is
18   TAKEDA PHARMACEUTICAL CO.   v. ZYDUS PHARMACEUTICALS
                                                        USA

comprised of—that determines whether or not the gran-
ules have a rough feeling in the mouth. If large hard
agglomerates are “virtually” dissected (a telling phrase)
for measurement purposes, a sample could be measured
as having an average particle diameter of 400 µm or less
despite the fact that the actual size of the granules would
create significant roughness in the mouth.
    In light of our conclusion that the ’994 patent does not
require deagglomeration prior to particle size measure-
ment, we conclude that it is not invalid for lack of ena-
blement based on a failure to explain when and how to do
so.
                       CONCLUSION
     For the foregoing reasons, we reverse the district
court’s claim construction ruling and resulting finding of
literal infringement, affirm the court’s judgment of no
invalidity, and remand for further proceedings consistent
with this opinion.
 REVERSED-IN-PART, AFFIRMED-IN-PART, AND
               REMANDED