Court Opinion

ID: 1035421
Source: CourtListenerOpinion
Date Created: 2013-07-27 00:01:57.291438+00
Date Added: 2024-06-11T12:45:28.131342
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
                ______________________

     TEVA PHARMACEUTICALS USA, INC.,
 TEVA PHARMACEUTICAL INDUSTRIES, LTD.,
       TEVA NEUROSCIENCE, INC., AND
YEDA RESEARCH AND DEVELOPMENT CO., LTD.,
             Plaintiffs-Appellants,

                           v.

           SANDOZ, INC., AND MOMENTA
            PHARMACEUTICALS INC.,
              Defendants-Appellants,

                         AND

 MYLAN PHARMACEUTICALS INC., MYLAN INC.,
         AND NATCO PHARMA LTD.,
            Defendants-Appellants,

                          AND

      SANDOZ INTERNATIONAL GMBH, AND
               NOVARTIS AG,
                  Defendants.
            ______________________

             2012-1567, -1568, -1569, -1570
                ______________________

   Appeals from the United States District Court for the
Southern District of New York in consolidated Nos. 08-
CV-7611 and 09-CV-8824, Judge Barbara S. Jones.
                ______________________
2                TEVA PHARMACEUTICALS USA   v. SANDOZ INC.

                Decided: July 26, 2013
                ______________________

    ELIZABETH J. HOLLAND, Kenyon & Kenyon, LLP, of
New York, New York, argued for plaintiffs-appellees. Of
counsel on the brief were WILLIAM G. JAMES, II, of Wash-
ington, DC; DAVID M. HASHMALL, Goodwin Procter, LLP,
of New York, New York; JOHN C. ENGLANDER, HENRY C.
DINGER, DARYL L. WIESEN, JOHN T. BENNETT, and
NICHOLAS K. MITROKOSTAS, of Boston, Massachusetts.

    DEANNE E. MAYNARD, Morrison & Foerster, LLP, of
Washington, DC, argued for defendants-appellants,
Sandoz Inc., et al. With her on the brief were BRIAN R.
MATSUI, and MARC A. HEARRON; DAVID C. DOYLE, ANDERS
T. AANNESTAD and BRIAN M. KRAMER, of San Diego,
California.

    EVAN R. CHESLER, Cravath Swaine & Moore LLP, of
New York, New York, argued for defendants-apellants,
Mylan Pharmaceuticals, Inc., et al. On the brief were
SHANNON M. BLOODWORTH and BRANDON M. WHITE,
Perkins Coie, LLP, of Washington, DC; and DAVID L.
ANSTAETT and DAVID E. JONES, of Madison, Wisconsin. Of
counsel was JOHN SINGLETON SKILTON, Perkins Coie, LLP,
of Madison, Wisconsin.
                ______________________
 TEVA PHARMACEUTICALS USA    v. SANDOZ INC.                3
 Before RADER, Chief Judge, MOORE, Circuit Judge, and
               BENSON, District Judge. *
MOORE, Circuit Judge.
    The defendants in these consolidated patent in-
fringement actions (collectively, Appellants) appeal from
the district court’s judgment that various claims of the
nine patents-in-suit asserted by the plaintiffs (collectively,
Teva) are infringed, and from the court’s holdings regard-
ing indefiniteness, nonenablement, and obviousness. 1 We
hold that Group I claims are invalid for indefiniteness,
but that Group II claims have not been proven indefinite. 2
We also hold that the district court did not err in its
conclusions that the claims are infringed, and that the
Appellants failed to prove that the claims would have
been obvious and are not enabled. Accordingly, we affirm
the district court’s judgments of infringement and no
invalidity with respect to Group II claims, reverse its
judgment of no invalidity with respect to Group I claims,
and remand.

    *  Honorable Dee V. Benson, District Judge, United
States District Court for the District of Utah, sitting by
designation.
    1   The asserted patents are: U.S. Patent Nos.
5,800,808 (’808 patent), 5,981,589 (’589 patent), 6,048,898
(’898 patent), 6,054,430 (’430 patent), 6,342,476 (’476
patent), 6,362,161 (’161 patent), 6,620,847 (’847 patent),
6,939,539 (’539 patent), and 7,199,098 (’098 patent).
    2   The six Group II claims are: claims 1 and 2 of the
’430 patent, claim 1 of the ’476 patent, claim 1 of the ’161
patent, and claims 1 and 8 of the ’098 patent. The re-
maining claims are collectively referred to as Group I
claims.
4                 TEVA PHARMACEUTICALS USA    v. SANDOZ INC.
                       BACKGROUND
    Appellants submitted Abbreviated New Drug Applica-
tions (ANDAs) to the Food and Drug Administration
(FDA) seeking approval to market generic versions of
Copaxone®, a drug used in treating multiple sclerosis.
Two proposed generic products, the Mylan accused prod-
uct and the Sandoz accused product, are at issue in this
appeal. Teva, which markets Copaxone®, sued Appel-
lants for patent infringement under 35 U.S.C.
§ 271(e)(2)(A). The patents-in-suit, which share a com-
mon specification, are listed in the Approved Drug Prod-
ucts with Therapeutic Equivalence Evaluations (Orange
Book) entry for Copaxone®. The patents-in-suit include
claims reciting a product called copolymer-1 and claims
reciting methods of making copolymer-1.
     Copolymer-1 consists of four different amino acids (al-
anine, glutamic acid, lysine, and tyrosine) combined in a
certain ratio to make a polypeptide product. A sample of
polymeric material like copolymer-1 typically consists of a
mixture of individual polymer molecules that have vary-
ing molecular weights. There are different ways to de-
scribe the resulting distribution of molecular weight
values. One approach uses statistical measures, includ-
ing the peak average molecular weight (Mp), number
average molecular weight (Mn), and weight average
molecular weight (Mw). Mp is the molecular weight of the
most abundant molecule in the sample. Mn is the arith-
metic mean, or the total mass of all the molecules in the
sample divided by the total number of molecules. Mw is
still another average molecular weight measure that is
calculated differently from Mp and Mn. In a typical poly-
mer sample, Mp, Mn, and Mw have different values.
    A second approach describes how many molecules in a
polymer sample have molecular weights that fall within
an arbitrarily set range. For example, if 99% of the
constituent molecules in a sample have molecular weights
 TEVA PHARMACEUTICALS USA   v. SANDOZ INC.               5
between 1 kilodalton (kDa) and 100 kDa, the sample may
be described as having 99% of its mole fraction within the
molecular weight range of 1 kDa to 100 kDa.
    The claims of the patents-in-suit use both approaches.
Claim 1 of the ’589 patent is representative of Group I
claims, which use the first approach:
   Copolymer-1 having a molecular weight of about 5
   to 9 kilodaltons, made by a process comprising the
   steps of:
   reacting protected copolymer-1 . . . ; and
   purifying said copolymer-1, to result in copolymer-
   1 having a molecular weight of about 5 to 9 kilo-
   daltons.
’589 patent claim 1 (emphases added). Claim 1 of the ’430
patent is representative of Group II claims, which use the
second approach: “Copolymer-1 having over 75% of its
mole fraction within the molecular weight range from
about 2 kDa to about 20 kDa . . . .” ’430 patent claim 1
(emphasis added).
    In its claim construction order, the district court did
not distinguish in detail between the different contexts in
which the term “molecular weight” is used in Group I and
Group II claims. The court rejected the Appellants’
argument that the term “molecular weight” was insolubly
ambiguous because it could refer to Mp, Mn, Mw, or yet
another average molecular weight measure.             Teva
Pharms. USA, Inc. v. Sandoz, Inc., 810 F. Supp. 2d 578,
586–93, 596 (S.D.N.Y. 2011) (Markman Order). It con-
strued “molecular weight” as Mp and held that the claims
are not indefinite. Id. After a bench trial, the court held
that the asserted claims are not invalid for obviousness or
lack of enablement, and that the Mylan and Sandoz
accused products infringe all of the asserted claims. Teva
Pharms. USA, Inc. v. Sandoz, Inc., 876 F. Supp. 2d 295
(S.D.N.Y. 2012) (Opinion).
6                 TEVA PHARMACEUTICALS USA    v. SANDOZ INC.
   This appeal followed. We have jurisdiction under 28
U.S.C. § 1295(a)(1).
                       DISCUSSION
                      I. Definiteness
    A patent’s specification “must conclude with one or
more claims particularly pointing out and distinctly
claiming the subject matter which the inventor . . . re-
gards as the invention.” 35 U.S.C. § 112(b) (2012). “A
claim is indefinite only when it is not amenable to con-
struction or insolubly ambiguous.” Biosig Instruments,
Inc. v. Nautilus, Inc., 715 F.3d 891, 898 (Fed. Cir. 2013).
To prove indefiniteness, “an accused infringer must
demonstrate by clear and convincing evidence that one
skilled in the relevant art could not discern the bounda-
ries of the claim based on the claim language, the specifi-
cation, the prosecution history, and the knowledge in the
relevant art.” Wellman, Inc. v. Eastman Chem. Co., 642
F.3d 1355, 1366 (Fed. Cir. 2011). Indefiniteness is a
question of law that we review de novo. Id. at 1365–66.
    Appellants argue that the term “molecular weight”
renders all of the asserted claims indefinite because it can
refer to different measures, including Mp, Mw, and Mn.
They contend that the scope of the claims varies signifi-
cantly depending on the measure and that a skilled
artisan cannot ascertain the boundaries of the claims.
Appellants argue that Teva inconsistently defined “mo-
lecular weight” as Mw and Mp during prosecution of two of
the familial patents, reinforcing the ambiguity. Further,
Appellants contend that the specification does not resolve
which molecular weight measure is intended.
    Appellants also contend that their indefiniteness ar-
guments apply equally to Group I and Group II claims.
They argue that even Group II claims, which refer to a
molecular weight range, “necessarily refer to a copolymer-
1 percentage above or below a certain average molecular
 TEVA PHARMACEUTICALS USA   v. SANDOZ INC.               7
weight.” Sandoz Reply Br. 17. Appellants contend that,
because all of the claims recite “molecular weight,” they
must be indefinite.
     Teva counters that the prosecution history clarifies
that “molecular weight” should be construed as Mp. It
contends that its response to an indefiniteness rejection of
the ’539 patent claims unequivocally stated that a person
of skill in the art reading the specification would under-
stand that the term “molecular weight” refers to Mp. Teva
argues that the district court correctly determined that its
response during prosecution of the ’847 patent, where it
stated that “[o]ne of ordinary skill in the art could under-
stand that kilodalton units implies [sic] a weight average
molecular weight,” was not contradictory. J.A. 3229. It
contends that a skilled artisan would discount this state-
ment because it does not explicitly define “molecular
weight” as Mw and because it contains an evident scien-
tific error—any molecular weight measurement, not just
Mw, may be expressed in kilodalton units.
    Teva also contends that the specification resolves any
ambiguity in the meaning of “molecular weight.” Teva
contends that the specification’s reference to the Size
Exclusion Chromatography (SEC) method indicates that
“molecular weight” means Mp because determining Mn
and Mw requires further calculations from SEC data that
the specification does not describe. It further argues that
Figure 1 confirms this conclusion because only Mp can be
obtained directly from the molecular weight plot in that
figure.
    Finally, Teva contends that Group II claims refer to
exact molecular weight values and are therefore not
ambiguous. It argues that Group II claims recite percent-
ages of molecules in a copolymer-1 sample that fall within
a specified molecular weight range, not average values.
    We agree with Appellants that Group I claims are in-
definite and agree with Teva that Group II claims are not.
8                  TEVA PHARMACEUTICALS USA     v. SANDOZ INC.
It is undisputed that Group I claims contain an ambiguity
because their plain language does not indicate which
average molecular weight measure is intended. Teva’s
attempt to resolve this ambiguity hinges in part on the
prosecution history. But two of its prosecution statements
directly contradict each other and render the ambiguity
insoluble.
    During prosecution of the ’539 patent, the Examiner
rejected pending claims as indefinite, stating that “the
term ‘average molecular weight’ . . . is indefinite since its
method of measurement is not specified, i.e. [Mn], [Mw] . . .
etc.” J.A. 3245. Teva stated in its response that “[o]ne of
ordinary skill in the art, upon reviewing the specification,
would understand that ‘average molecular weight’ refers
to the molecular weight at the peak of the molecular
weight distribution curve shown in Figure 1,” i.e., Mp.
J.A. 3258. The claims were allowed. During prosecution
of the ’847 patent, the Examiner made an analogous
rejection over the same claim term, stating that “the term
‘average’ molecular weight . . . is meaningless as a limita-
tion without specifying its basis, e.g., [Mw], [Mn], etc.” J.A.
3220. Teva overcame the rejection by responding that
“[o]ne of ordinary skill in the art could understand that
kilodalton units implies [sic] a weight average molecular
weight,” i.e., Mw. J.A. 3229. The only basis upon which
the Examiner could have agreed that the ’539 patent
claims were not indefinite was that “molecular weight”
means Mp. In contrast, the only basis for the Examiner’s
withdrawal of the indefiniteness rejection of the ’847
patent claims was that the same term means Mw. Teva’s
two definitions cannot be reconciled.
    The specification does not resolve the ambiguity.
Teva’s expert, Dr. Gregory Grant, testified that after
examining the curve depicted in Figure 1 and the accom-
panying legend, a skilled artisan would know that the
claim terms “molecular weight” and “average molecular
weight” denote Mp. Dr. Grant also testified that Example
 TEVA PHARMACEUTICALS USA   v. SANDOZ INC.               9
1’s discussion of gel filtration, which refers to the SEC
method for measuring molecular weight, tells a skilled
artisan that “molecular weight” refers to Mp. See ’808
patent, col. 3 ll. 6–8. He explained that only Mp, which is
simply the highest point of a molecular weight curve, can
be read directly from a plot of SEC data.
    On de novo review of the district court’s indefiniteness
holding, we conclude that Dr. Grant’s testimony does not
save Group I claims from indefiniteness. As Dr. Grant
himself opined, SEC does not exclusively provide Mp—
both Mn and Mw can also be obtained from the data gen-
erated by the SEC method after some calculations. J.A.
1005. His testimony is consistent with that of one of
Appellants’ experts, who opined that SEC “can give at
least peak average, number average, and weight average
‘molecular weights.’” J.A. 1229. Furthermore, as illus-
trated in the figure below, the peaks of the curves in
Figure 1 do not correspond to the values denoted as
“average molecular weight” in the figure’s legend (Appel-
lants’ additions in color). In fact, the 7.7 kDa value is
closer to the Mw than to the Mp of the corresponding
batch, which makes it difficult to conclude that Mp is the
intended measure. J.A. 5285. Thus, we hold that Group I
claims are indefinite.
10                TEVA PHARMACEUTICALS USA     v. SANDOZ INC.
    Group II claims, by contrast, do not recite average mo-
lecular weight values. Instead of describing copolymer-1
in terms of a statistical measure, such as Mw, Group II
claims recite the percentage of copolymer-1 molecules in a
sample falling within an arbitrarily set molecular weight
range. The numbers that set the boundaries of that
range, such as “2 kDa” and “20 kDa” in the ’430 patent
claim 1, refer to precise points on the “Molecular Weight”
axis, rather than to statistical properties of the polymer
molecular weight curves. Like the numbers 10,000 (i.e.,
10 kDa) and 20,000 (i.e., 20 kDa) in the figure above, “2
kDa” and “20 kDa” refer to exact values rather than
statistical measures. The scope of Group II claims is thus
readily ascertainable. We hold that Group II claims are
not invalid for indefiniteness.
                      II. Enablement
    A patent’s specification must describe the invention
and “the manner and process 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 . . . to make
and use the same.” 35 U.S.C. § 112(a). “To be enabling,
the specification of a patent must teach those skilled in
the art how to make and use the full scope of the claimed
invention without undue experimentation.” MagSil Corp.
v. Hitachi Global Storage Techs., Inc., 687 F.3d 1377,
1380 (Fed. Cir. 2012) (internal quotation marks omitted).
Enablement is a question of law that we review without
deference, based on underlying factual inquiries that we
review for clear error after a bench trial. Cephalon, Inc. v.
Watson Pharm., Inc., 707 F.3d 1330, 1336 (Fed. Cir.
2013).
    The district court held that Appellants failed to prove
that the asserted claims are not enabled for making
copolymer-1 at the claimed molecular weight because a
person of skill in the art would be able to measure it using
either of two known calibration methods, “self-standards”
 TEVA PHARMACEUTICALS USA   v. SANDOZ INC.              11
or “universal calibration.” See Opinion, 876 F. Supp. 2d
at 382–99. The court determined that polymer literature
at the time of filing described both methods in detail, and
that those methods could be adapted to copolymer-1. The
court also found that Teva’s own extensive post-filing
experimentation with measurement methods did not
conclusively establish lack of enablement. The court thus
rejected Appellants’ experts’ testimony that undue exper-
imentation would be required, holding instead that the
specification and background knowledge in the art pro-
vided sufficient guidance on measuring the molecular
weight.
     Appellants argue that the district court erred in its
enablement analysis. They contend that the specification
states only that the SEC column should be “calibrated”
and does not disclose which calibration standards should
be used to measure the molecular weight. ’808 patent,
col. 3 ll. 6–8. Appellants argue that general SEC calibra-
tion methods do not readily apply because copolymer-1 is
complex and exhibits unpredictable behavior.          They
further point to expert testimony that the commercially
available standards that a skilled artisan would have
been most likely to pick are in fact unreliable for measur-
ing the molecular weight of copolymer-1.
     Appellants also argue that the evidence of Teva’s own
difficulties with identifying appropriate calibration meth-
ods, which they contend the district court disregarded,
confirms that the claims are not enabled. Appellants
contend that Teva’s various internal documents show the
allegedly challenging development of calibration stand-
ards for measuring the molecular weight of copolymer-1,
and point out that Teva deleted references to the stand-
ards from the patent application before filing. They argue
that Teva’s problems with molecular weight measure-
ments continued after filing, noting that Teva switched
calibration standards during the FDA approval process.
Appellants thus contend that the asserted claims are not
12                TEVA PHARMACEUTICALS USA     v. SANDOZ INC.
enabled because the specification does not teach which
standards a skilled artisan must use to calibrate copoly-
mer-1 molecular weight measurements.
    We perceive no clear error in the fact findings on
which the district court based its enablement conclusion.
Dr. Grant testified at length that it would have been
routine for a skilled artisan to measure the molecular
weight of copolymer-1. See, e.g., J.A. 19671, 20474,
20752–54. He explained that, by calibrating the SEC
column mentioned in the specification using methods that
were well known at the time of filing, a skilled artisan
could confirm the synthesis of copolymer-1 within the
claimed molecular weight range. Id. The district court
weighed this testimony against that of Appellants’ experts
and found it to be more convincing. See, e.g., Opinion, 876
F. Supp. 2d at 398 (Appellants’ expert “failed to address
the extensive literature that existed [at the time of filing]
regarding SEC, self-standards, and universal calibra-
tion.”); see also id. at 392. We thus agree with Teva that
the district court did not err in concluding that utilizing
the calibration methods discussed by Dr. Grant would not
require undue experimentation.
    Appellants’ arguments relating to Teva’s own alleged
calibration struggles also fail to demonstrate that the
district court committed a reversible error. Appellants’
assertion that the district court ignored Teva’s internal
experimentation is simply inaccurate. See id. at 391.
Moreover, Appellants point to no evidence that under-
mines the district court’s understanding that “it is entire-
ly plausible that Teva experimented with different
methods to deal with regulatory and other scale-up issues,
rather than to correct faulty measurements.” Id.; see also
Edwards Lifesciences AG v. CoreValve, Inc., 699 F.3d
1305, 1309–10 (Fed. Cir. 2012) (explaining that failure to
enable a commercial embodiment does not demonstrate
nonenablement under 35 U.S.C. § 112(a)). Nor do Appel-
lants adequately explain why the claimed invention
 TEVA PHARMACEUTICALS USA   v. SANDOZ INC.               13
cannot be practiced without the calibration method that
Teva deleted from its draft patent application. We there-
fore affirm the district court’s conclusion of no invalidity
for lack of enablement.
                     III. Obviousness
     A patent claim is invalid under 35 U.S.C. § 103 “if the
differences between the claimed invention and the prior
art are such that the claimed invention as a whole would
have been obvious before the effective filing date of the
claimed invention to a person having ordinary skill in the
art to which the claimed invention pertains.” “Obvious-
ness . . . is a legal conclusion based on underlying facts.”
Allergan, Inc. v. Sandoz Inc., _ F.3d _, 2013 WL 1810852,
at *4 (Fed. Cir. May 1, 2013). “The underlying factual
considerations in an obviousness analysis include the
scope and content of the prior art, the differences between
the prior art and the claimed invention, the level of ordi-
nary skill in the art, and any relevant secondary consid-
erations,” which include “commercial success, long-left but
unsolved needs, failure of others, and unexpected results.”
Id. (citations omitted).
    The district court held that the asserted claims would
not have been obvious in view of copolymer-1 compounds
with a molecular weight higher than 10 kDa disclosed in
U.S. Patent No. 3,849,550 (Teitelbaum) and other prior
art references. Opinion, 876 F. Supp. 2d at 401–19. It
found that Teitelbaum disclosed a preference for copoly-
mer-1 compositions having molecular weights of 18–20
kDa and greater, and that other references explicitly
taught away from the claimed lower molecular weight
copolymer-1. The court also determined that various
secondary considerations supported the conclusion of
nonobviousness.
    Appellants argue that the asserted claims would have
been obvious because the claimed copolymer-1 differs
from known copolymer-1 by only one kilodalton unit and
14                TEVA PHARMACEUTICALS USA    v. SANDOZ INC.
behaves similarly to the prior art material. Specifically,
they contend that there is no evidence that copolymer-1
with a molecular weight less than 10 kDa exhibits an
improved toxicity profile over the prior art copolymer-1.
Appellants also dispute the district court’s conclusion that
the prior art taught away from the claimed invention.
They acknowledge that one paragraph in a 1974 prior art
reference stated that copolymer-1 with a molecular weight
lower than 17 kDa was ineffective for treating multiple
sclerosis. See J.A. 49058–59. But they counter that more
recent art taught that copolymer-1 of lower molecular
weight yielded promising results in human trials. See
J.A. 36696–702. With regard to secondary considerations,
Appellants urge that Teva failed to prove a nexus between
lower molecular weight and Copaxone®’s commercial
success. They further contend that there was no long-felt
need for the claimed material because higher molecular
weight copolymer-1 was known to be effective.
     We see no error in the district court’s obviousness
analysis. The court did not clearly err when it found that
the prior art expressed a preference for higher molecular
weight copolymer-1, and therefore taught away from the
claimed invention. See, e.g., Teitelbaum, col. 1 ll. 61–62,
col. 2 ll. 19–32; see also J.A. 20391–93, 49058–59. The
court also did not clearly err in the fact findings relevant
to secondary considerations, which further support the
conclusion of nonobviousness. For example, the court
found that “Copaxone® is coextensive with the asserted
claims,” Opinion, 876 F. Supp. 2d at 406, triggering a
presumption of a nexus between the drug’s commercial
success and the claimed invention, see Brown & William-
son Tobacco Corp. v. Philip Morris, Inc., 229 F.3d 1120,
1130 (Fed. Cir. 2000). Because Copaxone®’s commercial
success is undisputed and Appellants have not rebutted
the presumption of a nexus, this consideration favors
Teva. We affirm the district court’s determination that
 TEVA PHARMACEUTICALS USA   v. SANDOZ INC.              15
Appellants failed to establish that the claimed invention
would have been obvious.
                    IV. Infringement
    Claim construction is an issue of law that we review
de novo. Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448,
1454–55 (Fed. Cir. 1998) (en banc). In construing a claim
term, we look at the term’s plain meaning. Phillips v.
AWH Corp., 415 F.3d 1303, 1313 (Fed. Cir. 2005) (en
banc). “There are only two exceptions to this general rule:
1) when a patentee sets out a definition and acts as his
own lexicographer, or 2) when the patentee disavows the
full scope of a claim term either in the specification or
during prosecution.” Thorner v. Sony Computer Entm’t
Am., LLC, 669 F.3d 1362, 1365 (Fed. Cir. 2012). In order
for the doctrine of prosecution disclaimer to apply, a
statement in prosecution must constitute a clear and
unmistakable disclaimer of claim scope. Omega Eng’g,
Inc. v. Raytek Corp., 334 F.3d 1314, 1326 (Fed. Cir. 2003).
Infringement is a question of fact reviewed for clear error
after a bench trial. Alza Corp. v. Mylan Labs., Inc., 464
F.3d 1286, 1289 (Fed. Cir. 2006).
    The district court construed “copolymer-1” to mean “a
mixture of polypeptides composed of alanine, glutamic
acid, lysine, and tyrosine in a molar ratio of approximate-
ly 6:2:5:1.” Markman Order, 810 F. Supp. 2d at 585; see
’808 patent, col. 1 ll. 32–43. This construction is not in
dispute. The court explained after trial that, in order to
facilitate a comparison with the accused products, it
converted the 6:2:5:1 ratio into percentages (42.9% ala-
nine, 14.3% glutamic acid, 35.7% lysine, and 7.1% tyro-
sine). Opinion, 876 F. Supp. 2d at 336, 339–40. Based on
various examples of copolymer-1 disclosed in the refer-
ences cited in the specification, the court determined that
an accused product meets the “approximately 6:2:5:1”
limitation as long as its amino acid composition does not
vary from the “ideal” percentages by an aggregate of more
16                TEVA PHARMACEUTICALS USA   v. SANDOZ INC.
than 12%. Id. at 340. The court found that the Mylan
accused product and the Sandoz accused product differ
from the “ideal” percentages by an aggregate of 4.4% and
4.5% respectively, and thus infringe literally. Id. at 335–
44, 356–63. The court also found that Mylan and Sandoz
infringe under the doctrine of equivalents because the
overall differences between the amino acid amounts in the
claims and the accused products are insubstantial. Id. at
345–49, 358.
                  A. Standard of Review
    The parties dispute whether the district court’s con-
sideration of the percentages in conjunction with its
consideration of the “approximately 6:2:5:1” limitation
constitutes a “derivative” claim construction or a part of
its infringement analysis. The former is a question of
law; the latter is a question of fact. We hold that whether
the amino acid percentages in the accused products meet
the “approximately 6:2:5:1” limitation is a part of the
district court’s infringement analysis. Thus, we review
the district court’s conclusions for clear error.
                B. “Approximately 6:2:5:1”
    Appellants argue that the district court erred in its
analysis of “approximately 6:2:5:1.” They contend that
the 6:2:5:1 ratio captures relative proportions of the four
amino acids in copolymer-1 to one another. Appellants
argue that the court “eviscerated” these relationships by
analyzing “approximately 6:2:5:1” in terms of an aggre-
gate amount of percent variation in the amino acid con-
tent. Mylan Br. 30. Appellants urge that examples of
copolymer-1 in the references cited in the specification
define the scope of “approximately 6:2:5:1,” and argue
that these examples allow for at most 16% variation of
any particular amino acid from the “ideal” 6:2:5:1 ratio.
    Appellants point out that their products contain the
four amino acids in the ratios 4.6: 1.6: 3.7: 1.0 (Mylan
 TEVA PHARMACEUTICALS USA    v. SANDOZ INC.               17
product) and 4.6: 1.5: 3.7: 1.0 (Sandoz product). They
argue that the accused products do not literally infringe
the asserted claims because, for example, the ratio of
lysine to tyrosine, 3.7: 1, deviates by more than 16% from
the “ideal” ratio of 5:1. Appellants further contend that
the district court erred in its finding of infringement
under the doctrine of equivalents because its analysis
vitiated the “6:2:5:1” requirement.
    Teva counters that the district court rightly decided,
based on the intrinsic record and expert testimony, that
“approximately 6:2:5:1” covers compositions that differ
from the “ideal” percentages by an aggregate of at most
12%. Teva argues that Appellants improperly seek to
limit the scope of the claims to prior art examples of
copolymer-1. It also contends that Appellants fail to
adequately explain why the district court’s analysis
should have focused on the relative ratios of the four
amino acids to one another rather than their proportions
relative to the whole.
    Teva further contends that Appellants perform a
“mathematical sleight of hand” by normalizing the ratio
relative to tyrosine, the least abundant amino acid in
copolymer-1. Teva Br. 32. Teva points out that, while the
6:2:5:1 ratio sets the scale at 14 (= 6 + 2 + 5 +1), Appellant
Mylan’s expression of the ratio in its product bases the
scale on the incommensurate value of 10.9 (= 4.6 +1.5 +
3.7 + 1.0). 3 Teva argues that, in order to properly com-
pare the Mylan accused product to the claims, the correct
way to express the accused amino acid ratio is 6.0: 2.0:
4.7: 1.3 (i.e., a total of 14) or to perform the comparison in
terms of percentages. Teva contends that either of these
approaches demonstrates that the accused products meet
the “copolymer-1” limitation as construed by the district

    3  These arguments apply equally to Sandoz’s ac-
cused product.
18                TEVA PHARMACEUTICALS USA    v. SANDOZ INC.
court. Teva further argues that, when rounding error is
taken into account, it becomes clear that the accused
products contain the four amino acids in the 6:2:5:1 ratio.
Finally, it contends that the district court correctly de-
termined that Appellants infringe under the doctrine of
equivalents because the differences between the claims
and the accused products are insubstantial.
    We agree with Teva that the district court did not
clearly err in concluding that the accused products literal-
ly infringe the asserted claims. We see no basis for over-
turning the district court’s finding that the 6:2:5:1 ratio
must be converted to percentages to ensure a comparison
on the same scale with the amino acid percentages in the
accused products. That comparison reveals that, in the
aggregate, the four percentages in Mylan’s product
(42.7%, 14.4%, 33.6%, and 9.2%) differ from the “ideal”
percentages (42.9%, 14.3%, 35.7%, and 7.1%) by only
4.5%. 4 Furthermore, no single amino acid differs from its
corresponding “ideal” percentage by more than about 2%.
Id. at 338.
     The district court did not clearly err in determining
that these small differences from the “ideal” percentages
mean that the accused products literally infringe. The
court’s conclusion is supported by its findings regarding
prior art examples of copolymer-1. See id. at 339–40.
These examples show that, even when one of the amino
acids (lysine) differs from its “ideal” percentage by more
than 5%, the material is still considered “copolymer-1.”
Id. (discussing “Batch 2”); J.A. 49042. The district court’s
conclusion is reinforced by the undisputed testimony of
Teva’s expert, Dr. George Gokel, that the amino acid
content in copolymer-1 is uncertain due to experimental

     4 In Sandoz’s product, the corresponding percent-
ages are 43.6%, 14.7%, 33.4%, 8.3%, amounting to an
aggregate difference of 4.5% from the “ideal” percentages.
 TEVA PHARMACEUTICALS USA   v. SANDOZ INC.              19
variations and measurement errors. Id. at 339; J.A.
19825–28. We need not decide whether a material that
differs by 12% from the 6:2:5:1 ratio (expressed in per-
centages) infringes the asserted claims because the Mylan
and Sandoz accused products deviate from the ratio by
less than 5%. We see no clear error in the district court’s
determination that these products, which differ from the
“ideal” percentages by less than 5% in the aggregate, meet
the “approximately 6:2:5:1” limitation. Given this conclu-
sion, we do not need to reach the parties’ arguments
regarding infringement under the doctrine of equivalents.
                 3. Prosecution Disclaimer
    The district court also rejected Appellants’ argument
that Teva disclaimed copolymer-1 compositions having
Mw greater than 10 kDa during prosecution. Markman
Order, 810 F. Supp. 2d at 596–98. Appellants challenge
this conclusion on appeal. They contend that their pro-
posed products have Mw less than 10 kDa and thus do not
infringe.
    During prosecution of several of the asserted patents,
Teva overcame rejections based on the Teitelbaum patent
by arguing that, in contrast to Teitelbaum’s copolymer-1
with a “minimum molecular weight of 10 kilodaltons,” the
pending claims cover “copolymer-1 having a molecular
weight of about 5 to 9 kilodaltons.” E.g., J.A. 34747.
Teitelbaum does not explain whether its references to
“molecular weight” mean Mp or Mw, but cites an article
that describes the measurement process in more detail.
Teitelbaum, col. 4 ll. 31–32 (citing J.A. 49043).
    Appellants argue that Teva’s statements constitute a
disclaimer of copolymer-1 compositions with Mw greater
than 10 kDa. They contend that the article cited in
Teitelbaum describes a technique that can measure only
Mw. Appellants argue that an ordinary artisan would
thus understand the prosecution history statements to
20                TEVA PHARMACEUTICALS USA     v. SANDOZ INC.
refer to Mw and to surrender coverage of any copolymer-1
with Mw greater than 10 kDa.
    We agree with Teva that its prosecution history
statements do not constitute a clear and unmistakable
disclaimer. The phrase “molecular weight of 10 kilodal-
tons” does not expressly refer to any specific molecular
weight measurement—indeed, Group I claims are indefi-
nite due in part to the ambiguity in the meaning of “mo-
lecular weight.” The connection between this statement
and the article cited in Teitelbaum is too attenuated to
limit the scope of the claims to copolymer-1 with Mw less
than 10 kDa. Moreover, the technique discussed in that
article can yield Mw or a different type of molecular
weight measure, which fails to resolve the ambiguity.
                       CONCLUSION
    We have considered the parties’ remaining arguments
and do not find them to be persuasive. We hold that the
district court did not err in its conclusions that the claims
are infringed, that Appellants failed to prove that the
claims would have been obvious and are not enabled, and
that Appellants failed to prove that Group II claims are
indefinite. We also hold that the district court erred in
concluding that Group I claims have not been proven
indefinite. Accordingly, we affirm the district court’s
judgments of infringement and no invalidity with respect
to Group II claims, reverse its judgment of no invalidity
with respect to Group I claims, and remand. 5
                           COSTS
     No costs.

     5 We note that, according to the Orange Book, all of
Teva’s Copaxone® patents expire on the same date: May
24, 2014. We remand for the district court to determine
whether there exists any need to modify its injunction.
TEVA PHARMACEUTICALS USA   v. SANDOZ INC.   21
AFFIRMED-IN-PART, REVERSED-IN-PART AND
              REMANDED