       NOTE: This disposition is nonprecedential.

  United States Court of Appeals
      for the Federal Circuit
              __________________________

  MITSUBISHI CHEMICAL CORPORATION AND
 MITSUBISHI TANABE PHARMA CORPORATION,
              Plaintiffs-Appellees,

                         and
      ENCYSIVE PHARMACEUTICALS INC.,
               Plaintiff-Appellee,

                         and
    GLAXO GROUP LIMITED, SMITHKLINE
                 BEECHAM PLC,
  AND SMITHKLINE BEECHAM CORPORATION
      (DOING BUSINESS AS GLAXOSMITHKLINE),
                Plaintiffs-Appellees,

                           v.
     BARR LABORATORIES, INC. AND PLIVA-
             HRVATSKA D.O.O.,
             Defendants-Appellants.
              __________________________

                      2010-1432
              __________________________

   Appeal from the United States District Court for the
Southern District of New York in Case No. 07-CV-11614,
Judge John G. Koeltl.
MITSUBISHI CHEMICAL   v. BARR LABS                       2


              ___________________________

                Decided: August 2, 2011
              ___________________________

    DAVID G. CONLIN, Edwards Angell Palmer & Dodge
LLP, of Boston, Massachusetts, argued for all plaintiffs-
appellees. With him on the brief for plaintiffs-appellees
Mitsubishi Chemical Corporation, et al. were KATHLEEN
B. CARR, DAVID COTTA, ADAM P. SAMANSKY and THOMAS H.
WINTNER; and ANTHONY J. VIOLA, of New York, New York.
Of counsel were ANDRE K. CIZMARIK and BARBARA L.
MOORE.     On the brief for plaintiff-appellee Encysive
Pharmaceuticals Inc were MARTIN L. KATZ and JEFFREY
M. DRAKE, Wood Philips Katz Clark & Mortimer, of
Chicago, Illinois. Also on the brief for defendants-
appellees Glazxo Group Limited, et al were WILLIAM F.
LEE, LISA J. PIROZZOLO and CHRISTOPHER R. NOYES,
Wilmer Cutler Pickering Hale and Dorr LLP, of Boston,
Massachusetts.

   STEVEN H. REISBERG, Willkie Farr & Gallagher LLP of
New York, New York, argued for the defendants-
appellants. With him on the brief were THOMAS J.
MELORO, JR. and HEATHER M. SCHNEIDER.
              __________________________

    Before BRYSON, DYK, and PROST, Circuit Judges.
BRYSON, Circuit Judge.

     Barr Laboratories, Inc., and Pliva-Hrvatska d.o.o.
(collectively, “Barr”) appeal from a judgment that Barr
infringed each of the four claims of U.S. Patent No.
5,214,052 (“the ’052 patent”), assigned to plaintiff Mitsu-
3                         MITSUBISHI CHEMICAL   v. BARR LABS


bishi Chemical Corporation (together with other plain-
tiffs, “Mitsubishi”). We affirm.

                             I

    Argatroban, also known as argipidine, is a drug that
acts as an anticoagulant by inhibiting the enzyme throm-
bin. Argatroban is clinically useful in the treatment of
heparin-induced thrombocytopenia, a condition caused by
the more widely used anticoagulant heparin. Argatro-
ban’s structure and utility as an anticoagulant have been
known since at least the early 1980s. Argatroban is a
zwitterion, i.e., a molecule with both positive and negative
regions of electrical charge. Zwitterions generally have
low aqueous solubility at neutral pH levels, with higher
solubility in very acidic or very basic solutions. Argatro-
ban’s low aqueous solubility at neutral pH levels presents
problems for its use in pharmaceutical applications that
require administration of high concentrations of the drug.

    The ’052 patent issued to Mitsubishi in 1993 as a con-
tinuation of an application filed in 1988. The specification
of the ’052 patent explains that the solubility of argatro-
ban increases dramatically when a saccharide and etha-
nol are added to an aqueous solution. The ’052 patent has
four claims:

    1. A method for dissolving an arginineamide,
    comprising:

       dissolving [argatroban] and/or its salt in a sol-
         vent containing ethanol, water and a sac-
         charide.

    2. The method according to claim 1, wherein the
    saccharide is at least one member selected from
MITSUBISHI CHEMICAL   v. BARR LABS                        4


   the group consisting of sorbitol, glucose, glycerin
   and sucrose.

   3. A pharmaceutical composition for injection,
   comprising:

       [argatroban] and/or its salt together with
         ethanol, water and a saccharide.

   4. The composition according to claim 3, wherein
   the saccharide is at least one member selected
   from the group consisting of sorbitol, glucose,
   glycerin and sucrose.

    Mitsubishi has marketed Argatroban Injection, a
product meeting the limitations of claims 3 and 4, since
the U.S. Food and Drug Administration (“FDA”) approved
Mitsubishi’s New Drug Application No. 20-883 in 2000.
Argatroban Injection consists of a high concentration of
argatroban dissolved in a solution of ethanol, water, and
sorbitol at a pH between 3.2 and 7.5.

     Barr filed an Abbreviated New Drug Application
(“ANDA”) to market a generic version of Argatroban
Injection and notified Mitsubishi of the ANDA in late
2007. Mitsubishi promptly filed suit against Barr, alleg-
ing direct and indirect infringement of the ’052 patent. In
the district court, the parties stipulated that the commer-
cial manufacture, use, importation, sale, or offer for sale
of the product described in Barr’s ANDA would infringe
all four claims of the ’052 patent; Barr defended by con-
tending that the four asserted claims were invalid.

    Barr made two arguments as part of its invalidity de-
fense. It first contended that each of the claims is antici-
pated by a Japanese article published in 1986 by a
Mitsubishi employee, Toshihiro Yamamoto. In the alter-
5                          MITSUBISHI CHEMICAL   v. BARR LABS


native, Barr argued that all of the ’052 claims would have
been obvious over a combination of several references
other than the Yamamoto article.

    In the course of the litigation, the parties disputed the
appropriate English translation of a single sentence in
Yamamoto describing the preparation of an argatroban
solution that was administered to laboratory rats for
experimental purposes. The district court considered four
translations of the original Japanese text. After examin-
ing each translation, the court concluded that the only
reliable translation was that of Mitsubishi’s expert,
Martin Cross. Mr. Cross translated the relevant sentence
as follows: “In 7.5% D-sorbitol-4% ethanol, an argipidine
solution dissolved under hydrochloric acid acidity (pH 1.5
to 1.7) was intraperitoneally administered at a dosage of 1
ml/kg, 15 minutes before common carotid artery occlu-
sion.”

    Using Mr. Cross’s translation, the district court de-
termined that Yamamoto does not anticipate any claim of
the ’052 patent. The court found that claims 1 and 2 are
not anticipated because a person of ordinary skill in the
art would have understood Yamamoto to teach dissolution
of argatroban in hydrochloric acid alone, i.e., without
ethanol or a saccharide. The court credited testimony to
that effect by Mitsubishi’s expert witness, Dr. Stephen
Byrn. The court noted that Dr. Byrn’s testimony was
corroborated by one of the inventors of the ’052 patent,
Tatsuo Nomura, a native Japanese speaker, who testified
that the disputed sentence from Yamamoto should be
understood to mean “in hydrochloric acid the [argatroban]
was dissolved and after that it’s been put into D-sorbitol
and ethanol.”
MITSUBISHI CHEMICAL   v. BARR LABS                        6


    Based on that evidence, the district court found that
the language “In 7.5% D-sorbitol-4% ethanol” in the
Yamamoto article refers to “how the [argatroban] solution
was administered, not how it was dissolved.” The court
concluded that a person of ordinary skill in the art at the
time would have understood the Yamamoto reference to
mean that the argatroban was dissolved in acid, “with
ethanol and sorbitol added after the argatroban was
already dissolved.” The court discredited contrary testi-
mony by Barr’s expert witness, Dr. Thomas Needham.
The court found that Dr. Needham’s original interpreta-
tion of Yamamoto was “scientifically implausible,” and
that his revised interpretation involved a lengthy series of
steps that would have been explicitly disclosed in the
Yamamoto article if the article had intended to describe a
composition of the sort recited in claims 1 and 2.

    The district court also concluded that Yamamoto does
not anticipate claims 3 and 4 of the ’052 patent because
the solution disclosed in Yamamoto is not a “pharmaceu-
tical composition for injection.” The court construed the
term “pharmaceutical composition for injection” as “a
composition that is suitable for treating medical condi-
tions by injection.” The court credited Dr. Byrn’s testi-
mony that in order to be suitable for injection into human
patients, a pharmaceutical composition must have a pH
above 3. The court determined that the solution in Ya-
mamoto, which has a pH between 1.5 and 1.7, is not a
pharmaceutical composition for injection because it is too
acidic to be suitable for administration to human patients.

    The district court then addressed Barr’s obviousness
argument. At trial, Barr had asked the court not to
consider Yamamoto for purposes of obviousness. Instead,
Barr relied on several combinations of nine other prior art
references. Four of those references discuss argatroban,
7                         MITSUBISHI CHEMICAL   v. BARR LABS


but the court concluded that those references “are not
focused on argatroban’s solubility or any particular meth-
ods of formulating argatroban.” In particular, the court
did not find anything in those references that suggested
the use of ethanol or a saccharide as a component of a
solvent for argatroban.

    The other five references relied on by Barr address
solvent systems more generally. Those references discuss
solvent systems that include ethanol, water, and a sac-
charide. The court concluded, however, that the refer-
ences did not provide any direction to a person of ordinary
skill in the art to use that co-solvent combination to
dissolve argatroban. Three of the references disclose
numerous solvent systems, and the court found that none
of them would have directed a person of ordinary skill in
the art to use the particular co-solvent system claimed in
the ’052 patent. The other two references concern disso-
lution of compounds whose solubility profiles are different
from those of zwitterions.

    The district court determined that Barr had not met
its burden to show by clear and convincing evidence that
the prior art references would have motivated one of
ordinary skill in the art to dissolve argatroban in a sol-
vent containing ethanol, water, and a saccharide. In
addition, the court concluded that secondary considera-
tions such as commercial success and long-felt need
supported its conclusion that the ’052 claims would not
have been obvious. Barr appeals from the court’s rulings
on validity.
MITSUBISHI CHEMICAL   v. BARR LABS                       8


                             II

                             A

    Barr argues that Yamamoto anticipates each claim of
the ’052 patent. As part of its argument, Barr challenges
the district court’s adoption of Mr. Cross’s translation of
the sentence in Yamamoto that describes the preparation
of the argatroban solution. The court found Mr. Cross’s
translation reliable because it was corroborated by a
native Japanese speaker and independently corroborated
by Dr. Byrn’s explanation of how the composition dis-
closed in Yamamoto was prepared. The court was also
persuaded by Mr. Cross’s explanation of how his transla-
tion comported with standard Japanese sentence struc-
ture.

    The district court did not find any of the remaining
translations reliable. The court discredited the transla-
tion of Barr’s expert Charles Aschmann because neither
he nor Barr’s other translation expert, Gregor Hartmann,
could identify source text in the original Japanese corre-
sponding to a portion of Mr. Aschmann’s translation. Mr.
Hartmann himself produced two translations of Yama-
moto, but the court discredited his final translation
because Mr. Hartmann acknowledged significant errors in
his original version and because he had not consulted
with a native Japanese speaker while preparing his
translation. Finally, the court discredited a translation
that Mitsubishi submitted to the FDA (“the FDA transla-
tion”) as part of its New Drug Application for Argatroban
Injection. The court was persuaded by Mr. Cross’s testi-
mony that the FDA translation contained several errors.

   Barr points out that the FDA translation and Mr.
Aschmann’s translation, unlike the Cross translation,
9                          MITSUBISHI CHEMICAL   v. BARR LABS


were not prepared for purposes of this litigation. Barr
also relies on the testimony of Mr. Aschmann and Mr.
Hartmann that the relevant sentence in Yamamoto was
straightforward to translate, which contrasted with the
testimony of Mr. Cross, who said that he found the trans-
lation difficult. Finally, Barr argues that the district
court did not properly interpret the meaning of two Japa-
nese words in the relevant sentence.

    The fact-finder’s selection of a particular translation
as the best translation of a foreign language reference
raises pure questions of fact. See Hodosh v. Block Drug
Co., Inc., 786 F.2d 1136, 1142-43 (Fed. Cir. 1986); see also
Gray v. Noholoa, 214 U.S. 108, 112 (1909). The district
court’s selection of the appropriate translation in this case
was based in large part on a credibility determination,
and such determinations are “virtually never” overturned
for clear error. Honeywell Int’l, Inc. v. Hamilton Sund-
strand Corp., 523 F.3d 1304, 1314 (Fed. Cir. 2008), quot-
ing Anderson v. City of Bessemer City, 470 U.S. 564, 575
(1985). Although Barr contends that Mr. Cross’s transla-
tion should be disregarded because it was prepared for
purposes of litigation, that is not a sufficient reason to
conclude that the district court’s choice of the Cross
translation was clearly erroneous. Barr’s remaining
arguments relate to inferences drawn from the competing
testimony of expert witnesses. The district court is in the
best position to draw those inferences, and we find sub-
stantial evidentiary support for the court’s acceptance of
Mr. Cross’s translation and its rejection of the other
translations.

    Barr next argues that even accepting Mr. Cross’s
translation of the Yamamoto reference, Yamamoto antici-
pates the two method claims of the ’052 patent, claims 1
and 2. Barr challenges the district court’s construction of
MITSUBISHI CHEMICAL   v. BARR LABS                       10


the term “dissolving” in claim 1. The court found that
claim 1 is limited to compositions in which argatroban is
completely dissolved in a solvent that contains ethanol,
water, and a saccharide, i.e., no further dissolution of
argatroban takes place once those three co-solvents are
present in the composition. Barr contends that claim 1
covers any system in which some argatroban is dissolved
in a solvent containing ethanol, water, and a saccharide,
even if most of the argatroban in the solution has been
dissolved previously in another solvent system.

     We need not resolve this dispute, because Yamamoto
fails to anticipate claim 1 or claim 2 under either con-
struction of the term “dissolving.” The district court
credited the testimony of Dr. Byrn and Mr. Nomura that
Yamamoto contemplated that hydrochloric acid would be
used to completely dissolve a particular quantity of arga-
troban, and only then would ethanol and sorbitol be added
to the solution. Under Dr. Byrn’s interpretation of the
Yamamoto article, Yamamoto would not anticipate claims
1 and 2 under either the district court’s claim construc-
tion or the construction proposed by Barr.

    Barr contends that Dr. Byrn’s reading of Yamamoto
would require hydrochloric acid to be added to the solu-
tion both at the outset and again after ethanol and sorbi-
tol were added, in order to adjust the pH of the solution to
a final level between 1.5 and 1.7. Barr argues that the
record contains no plausible explanation for why a person
of skill in the art would choose to add hydrochloric acid to
the solution in two separate steps. However, the district
court discredited the competing method of preparation
proffered by Dr. Needham because his first proposed
method was scientifically impossible, his second method
involved a nine-step sequence that would be expected to
have been disclosed by the reference, and he admitted in a
11                        MITSUBISHI CHEMICAL   v. BARR LABS


deposition that he did not know how a person of skill in
the art would have interpreted Mr. Cross’s translation of
Yamamoto. Even if the method of preparation disclosed
in Yamamoto, as translated by Mr. Cross, is subject to
multiple interpretations, Barr has not shown that Dr.
Byrn’s interpretation is implausible.       Moreover, the
district court took note of the fact that Yamamoto’s de-
scription of the argatroban solution was quite cryptic
because, as both experts agreed, Yamamoto was focused
on the pharmacological activity of the argatroban mole-
cule, rather than on “argatroban’s solubility or on treating
the rats.” In order to anticipate, the teaching of a refer-
ence must be clear and unambiguous. In re Turlay, 304
F.2d 893, 899 (CCPA 1962). Because Yamamoto does not
clearly teach the methods set forth in claims 1 and 2 of
the ’052 patent, Barr has not shown that claims 1 and 2
are anticipated by Yamamoto.

                             B

     Barr also contends that Yamamoto anticipates the
two product claims of the ’052 patent, claims 3 and 4.
Barr’s argument focuses on the phrase “pharmaceutical
composition for injection” in the preamble of claim 3. The
district court construed “pharmaceutical composition for
injection” to mean “a composition that is suitable for
treating medical conditions by injection.” Barr proffers
the following construction: “a medicinal drug composition
that can be administered by injection.” Barr explains that
the word “medicinal” in its construction modifies only the
word “drug,” and that claim 3 therefore covers any compo-
sition that includes a “medicinal drug,” i.e., argatroban,
along with ethanol, water, and a saccharide, regardless of
whether it can be injected into a patient with therapeutic
effect.
MITSUBISHI CHEMICAL   v. BARR LABS                       12


     In support of its construction, Barr cites to our deci-
sion in Novartis Pharmaceuticals Corp. v. Eon Labs
Manufacturing, Inc., 363 F.3d 1306 (Fed. Cir. 2004). In
that case, this court determined that a composition claim
to a “hydrosol . . .” was limited to “a medicinal prepara-
tion . . . prepared outside the body.” Id. at 1311. The
court found support for that narrow construction in the
patent specification, which referred to the claimed hydro-
sol as a “pharmaceutical composition” prepared as an
“injectable solution.” Id. at 1310. The court cited a
dictionary definition of the noun “pharmaceutical” as
meaning “medicinal drug.” Id., quoting Webster’s Third
New International Dictionary 1694 (2002). However, as
its ensuing claim construction demonstrated, the court in
Novartis Pharmaceuticals applied the term “pharmaceuti-
cal” to the entire “preparation” claimed. Cf. Forest Labs.,
Inc. v. Abbott Labs., 239 F.3d 1305, 1311 (Fed. Cir. 2001)
(a drug “may be part of a pharmaceutical composition, but
it is a distinct component of that composition”).

    The problem with Barr’s construction is that the word
“pharmaceutical” in claim 3 modifies the entire “composi-
tion” referred to in the claim, not simply the argatroban
component of the composition. Claims to “pharmaceutical
compositions” are typically distinct from claims to medici-
nal compounds themselves. See Forest Labs., 239 F.3d at
1311. Each of the constituent parts of the composition
must be pharmaceutically acceptable, although only the
composition as a whole needs to be medicinal in nature.
See Schering Corp. v. Geneva Pharm., 339 F.3d 1373,
1382 (Fed. Cir. 2003) (a “pharmaceutical composition”
includes a drug along with a “pharmaceutically acceptable
carrier”); In re Gardner, 427 F.2d 786, 787 (CCPA 1970)
(a “pharmaceutical composition” is an active compound
“in a suitable pharmaceutical carrier”). The specification
of the ’052 patent makes clear that “[t]he solution contain-
13                        MITSUBISHI CHEMICAL   v. BARR LABS


ing any of the [argatroban] in the solvent of alcohol and
water and optionally saccharide thus obtained can consti-
tute the pharmaceutical composition of the invention.”
’052 patent, col. 4, ll. 27-31 (emphases added). The dis-
trict court correctly determined that the term “pharma-
ceutical” is relevant to the entire composition disclosed in
claim 3, not just to the argatroban component.

    Significantly, the district court refused to limit claim
3 to those compositions that are “safe, effective, and
reliable for use in humans.” In re Krimmel, 292 F.2d 948,
954 (CCPA 1961). The specification does not require this
restrictive construction, nor is this property necessary for
patentability. See In re ’318 Patent Infringement Litig.,
583 F.3d 1317, 1324 (Fed. Cir. 2009) (“human trials are
not required for a therapeutic invention to be pat-
entable”). Instead, the court imposed a “minimal re-
quirement that a composition meeting claim 3 must have
some medicinal aspect or must pertain to treatment of a
clinical indication.” We agree with Mitsubishi that the
claim extends only to those compositions with “some
medicinal aspect.” 1

    Barr correctly points out that claim 3 is structured as
a “comprising” claim that reads on compositions that
include components beyond those explicitly claimed.
While claim 3 is open-ended, the addition of new com-
pounds to the composition that would defeat the “phar-

     1  Barr briefly argues that the term “pharmaceutical
composition” should not be read to limit claim 3 at all
because it appears in the preamble to the claims. See Am.
Med. Sys., Inc. v. Biolitec, Inc., 618 F.3d 1354, 1358-59
(Fed. Cir. 2010). Barr did not make that argument before
the district court, however, and therefore cannot raise it
for the first time on appeal. See Conoco, Inc. v. Energy &
Envtl. Int’l, L.C., 460 F.3d 1349, 1358-59 (Fed. Cir. 2006).
MITSUBISHI CHEMICAL   v. BARR LABS                        14


maceutical” character of the overall composition would
move the composition outside the scope of the claimed
invention. As the district court noted, Barr’s claim con-
struction would allow a “plainly toxic composition, such as
a cleaning fluid or a pesticide,” to meet the limitations of
claim 3, even though such a composition would not be
medicinal under any definition of that word. See, e.g.,
Webster’s Third New International Dictionary 1402 (defin-
ing “medicinal” as “tending to cure disease or relieve
pain,” “sanative,” “having wholesome effect,” or “salu-
tary”). We therefore reject Barr’s attempt to broaden the
phrase “pharmaceutical composition for injection” to cover
any composition that includes a medicinal product, re-
gardless of its suitability for injection into humans. To
the contrary, a “pharmaceutical composition,” as claimed
in the ’052 patent, is a composition consisting of a medici-
nal drug in a pharmaceutically acceptable carrier.

    The district court concluded that the argatroban
preparation described in Yamamoto is not a “pharmaceu-
tical composition” because it is too acidic to be injected
into a human patient. The court found that a pH of 1.5 to
1.7 “is an extremely low pH . . . which is not acceptable for
use in a medicine.” The court based its conclusion on
testimony by expert witnesses of both parties. Dr. Byrn
testified that a solution injected at a pH below 3 could
cause extreme pain and tissue damage. He also testified
that he would not consider the preparation used in Ya-
mamoto to be a medicine. Similarly, Dr. Needham testi-
fied that “there are pH ranges that should not be included
in an injectable.” The district court also found it proba-
tive that Barr did not identify any intravenous drug
compositions having a pH range similar to that of the
composition identified in Yamamoto. Barr does not
challenge those findings of the district court; rather, it
relies solely on its claim construction argument. Barr has
15                         MITSUBISHI CHEMICAL   v. BARR LABS


not demonstrated by clear and convincing evidence that
Yamamoto disclosed an argatroban composition with a
pharmaceutically acceptable carrier.

     Finally, Barr argues that claims 3 and 4, as construed
by the district court, would be invalid for lack of enable-
ment. We disagree. Under the proper construction of
“pharmaceutical composition,” as set forth above, the
claims are clearly enabled. The specification of the ’052
patent discloses methods of preparing three sample
solutions containing argatroban, ethanol, water, and a
saccharide to be administered by injection. ’052 patent,
col. 5, line 47, to col. 6, line 15. The examples mention
only those four components of the composition, in addition
to a diluting solution that is “weak[ly] acidic.” Id., col. 5,
ll. 56-57; col. 6, ll. 14-15. The specification notes that the
compositions “may contain stabilizer, buffer, preservative
and the like which are acceptable for the injection . . . .”
Id., col. 4, ll. 43-44. Because the specification provides
straightforward guidance for preparation of the claimed
pharmaceutical compositions, it enables claims 3 and 4.

                             III

    Barr briefly argues in the alternative that the claims
of the ’052 patent are obvious over a combination of prior
art references. Barr first cites U.S. Patent No. 4,258,192
(“the ’192 patent”), issued in 1981, which discloses the
dissolution of argatroban in a solution of water and glu-
cose. Barr argues that it would have been obvious to a
person of ordinary skill in the art to add ethanol to the
solution disclosed in the ’192 patent. The district court
found to the contrary, however, based on testimony by
experts for both sides. Dr. Byrn testified that “a person in
1987 would expect that ethanol would depress solubility
of argatroban in water” because argatroban is a zwit-
MITSUBISHI CHEMICAL   v. BARR LABS                       16


terion, and Dr. Needham admitted that the prior art
suggested that the solubility of zwitterions is reduced by
the addition of ethanol. The court did not clearly err in
concluding that the prior art taught away from the use of
ethanol to dissolve argatroban. 2

    Barr next points to a 1984 article by Matsui that dis-
closes argatroban dissolved in high concentrations in an
“acidic ethanol solution.” Barr does not argue that it
would have been obvious to add a saccharide to the solu-
tion disclosed in Matsui. Instead, Barr contends that
Matsui teaches the addition of ethanol to the aqueous
solution of argatroban and glucose disclosed in the ’192
patent. The district court found that Barr had not dem-
onstrated that a person of ordinary skill in the art would
have viewed ethanol (as opposed to acid) as being respon-
sible for dissolving the argatroban in the solution dis-
closed in Matsui, and Barr makes no argument on appeal
to challenge that finding.

    Finally, Barr points out that several prior art refer-
ences disclose solvent systems that include ethanol,
water, and a saccharide. However, Barr does not chal-
lenge the district court’s finding that those references are
not specific to argatroban or, more generally, to zwitteri-
ons. The district court did not credit Dr. Needham’s
testimony that a person of ordinary skill in the art would
have been directed to the specific co-solvent system dis-
closed in the ’052 patent, because there were a very large
number of such systems disclosed in the prior art. Barr

   2    In its reply brief, Barr challenges Dr. Byrn’s tes-
timony that ethanol was known to reduce the solubility of
zwitterions such as argatroban. Barr did not raise that
argument in its opening brief, and we therefore decline to
consider it. See SmithKline Beecham Corp. v. Apotex
Corp., 439 F.3d 1312, 1319 (Fed. Cir. 2006).
17                        MITSUBISHI CHEMICAL   v. BARR LABS


has pointed to no evidence in the record that undermines
the court’s factual finding that references disclosing
numerous solvent systems would not have taught the use
of ethanol, water, and a saccharide as a solvent system for
dissolving argatroban.

    Because Barr has failed to show that the district court
clearly erred in finding that the claims of the ’052 patent
are not anticipated and has failed to show that those
claims would have been obvious, we uphold the judgment
of the district court.

                      AFFIRMED
