Court Opinion

ID: 2670811
Source: CourtListenerOpinion
Date Created: 2014-04-22 15:34:43.991708+00
Date Added: 2024-06-11T13:07:56.029035
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
                ______________________

        BRAINTREE LABORATORIES, INC.,
               Plaintiff-Appellee,

                           v.

           NOVEL LABORATORIES, INC.,
               Defendant-Appellant.
              ______________________

                      2013-1438
                ______________________

    Appeal from the United States District Court for the
District of New Jersey in No. 11-CV-1341, Judge Peter G.
Sheridan.
                 ______________________

                Decided: April 22, 2014
                ______________________

   JOHN J. REGAN, Wilmer Cutler Pickering Hale and
Dorr LLP, of Boston, Massachusetts, argued for plaintiff-
appellee. With him on the brief were MARK C. FLEMING,
NISHAT A. SHAIKH, JENNIFER C. BROWN, and MICHAEL A.
GREENE; and CHRISTOPHER R. NOYES, of New York, New
York.

    RONALD M. DAIGNAULT, Robins, Kaplan, Miller &
Ciresi L.L.P., of New York, New York, argued for defend-
ant-appellant.     With him on the brief were DAVID
LEICHTMAN, MATTHEW B. MCFARLANE and OREN D.
LANGER.
2 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

                  ______________________
     Before DYK, PROST, and MOORE, Circuit Judges.
    Opinion for the court filed by Circuit Judge PROST.
 Opinion concurring in part, dissenting in part, and con-
    curring in the result filed by Circuit Judge DYK.
    Dissenting opinion filed by Circuit Judge MOORE.
PROST, Circuit Judge.
    This is a patent infringement case under the Hatch-
Waxman Act. See 35 U.S.C. § 271(e)(2)(A). Defendant-
Appellant Novel Laboratories, Inc. (“Novel”) appeals the
grant of summary judgment by the United States District
Court for the District of New Jersey that U.S. Patent No.
6,946,149 (“’149 patent”) held by Braintree Laboratories,
Inc. (“Braintree”) is infringed by the composition covered
by Novel’s abbreviated new drug application (“ANDA”).
See Braintree Labs., Inc. v. Novel Labs., Inc., No. 11-CV-
1341, 2013 WL 211252 (D.N.J. Jan. 18, 2013) (“Infringe-
ment Opinion”). The district court entered summary
judgment of infringement based on its construction of four
disputed claim terms. See Braintree Labs., Inc. v. Novel
Labs., Inc., No. 11-CV-1341, 2012 WL 4120907 (D.N.J.
Sept. 19, 2012) (“Claim Construction Order”). Novel
challenges the district court’s claim construction for two of
those terms. Following a six-day bench trial on Novel’s
invalidity defenses, the district found that Novel failed to
prove that the asserted claims were invalid.             See
Braintree Labs., Inc. v. Novel Labs., No. 11-CV-1341, 2013
WL 2970739 (D.N.J. June 4, 2013) (“Validity Opinion”).
Novel also appeals those findings.
    Because we agree with Novel that the district court
erred in its construction of the claim term “clinically
significant electrolyte shifts,” we reverse the district
court’s claim construction of that term, vacate the district
court’s grant of summary judgment of infringement, and
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 3

remand for further factual findings to determine whether
the composition covered by Novel’s ANDA product in-
fringes under the new claim construction articulated
herein. Further, we affirm the district court’s findings
that the asserted claims of the ’149 patent are not invalid.
                     I. BACKGROUND
    Braintree is a pharmaceutical company that manufac-
tures the SUPREP® Bowel Prep Kit (“SUPREP”), which
helps to prepare patients for colonoscopies. The colon
needs to be visually clear in order to successfully perform
a colonoscopy, so prior to the examination patients typi-
cally drink several liters of a solution to induce diarrhea.
    By the late 1990s, two colon cleansing options existed,
both of which had some disadvantages. The first option
was considered the safest but required patients to drink
large volumes of unappetizing isotonic prep formulas,
resulting in low patient compliance. The second option
was to administer a low-volume, hypertonic prep. How-
ever, this option caused severe electrolyte shifts, leading
to heart failure, kidney failure, neurological impairment,
and even death.
    Braintree’s ’149 patent discloses a combination of
magnesium sulfate, potassium sulfate, and sodium sul-
fate, which can be digested in small volumes to safely and
effectively induce colonic purging without causing clinical-
ly significant electrolyte shifts. See, e.g., ’149 patent
abstract.
    Claim 15, which the parties agree is representative,
recites:
   A composition for inducing purgation of the colon
   of a patient, the composition comprising from
   about 100 mL to about 500 mL of an aqueous hy-
   pertonic solution comprising an effective amount
   of Na2SO4, an effective amount of MgSO4, and an
   effective amount of K2SO4, wherein the composi-
4 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

   tion does not produce any clinically significant
   electrolyte shifts and does not include phosphate.
Ex Parte Reexamination Certificate, ’149 patent col. 2
ll. 23-30 (emphases added).
    Braintree alleges that SUPREP is a commercial em-
bodiment of the ’149 patent. Novel is a generic drug
manufacturer.
                 II. PROCEDURAL HISTORY
    On November 8, 2010, Novel filed an ANDA for a pro-
posed generic copy of SUPREP. A few months later,
Novel sent Braintree a Paragraph IV certification of
invalidity/noninfringement letter asserting that “each of
the claims of the ’149 patent is either invalid or is not
infringed” by Novel’s product.      On March 9, 2011,
Braintree filed this action seeking a declaration that
Novel’s ANDA product infringes the ’149 patent. Novel
asserted counterclaims of noninfringement and invalidity.
    After construing claim terms, the district court grant-
ed summary judgment of infringement in Braintree’s
favor and denied Novel’s motion for reconsideration,
ruling that SUPREP meets all limitations of the asserted
claims. See Infringement Opinion at *10. Following a
bench trial regarding validity, the district court found
that Novel “did not show proof that met the clear and
convincing standard” that the asserted claims were antic-
ipated, nor were they obvious or indefinite. Validity
Opinion at *25-26.
                     III. DISCUSSION
    This appeal concerns challenges to the district court’s
claim constructions, its grant of summary judgment
regarding infringement, and its findings following a bench
trial regarding validity. Regarding claim construction,
Novel argues that the district court misconstrued the
claim terms “purgation” and “clinically significant electro-
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 5

lyte shifts.” Based on these erroneous claim construc-
tions, Novel argues that the district court improperly
granted Braintree’s motion for summary judgment on
infringement. Regarding validity, Novel argues that the
district court erred when it failed to find that (1) U.S.
Patent No. 4,975,286 (“Hechter”) anticipates the asserted
claims of the ’149 patent; (2) the prior art, as understood
by a person of skill in the art, renders the asserted claims
obvious; and (3) the asserted claims are invalid because
the term “purgation” is indefinite under 35 U.S.C.
§ 112, ¶ 2. We address each of Novel’s challenges in turn.
                  A. Claim Construction
    Claim construction is a question of law, Markman v.
Westview Instruments, Inc., 52 F.3d 967, 976-79 (Fed. Cir.
1995) (en banc), aff’d, 517 U.S. 370 (1996), that we review
de novo without deference. Cybor Corp. v. FAS Techs.,
Inc., 138 F.3d 1448, 1454-55 (Fed. Cir. 1998) (en banc).
                       1. Purgation
    The district court construed “purgation” to mean “an
evacuation of a copious amount of stool from the bowels
after oral administration of the solution.” Claim Con-
struction Order at *6. In adopting this construction, the
district court rejected Novel’s argument that “purgation
means cleansing,” concluding that “[a]lthough cleansing is
a term in the specification of the ’149 [p]atent, [the as-
serted claims] clearly adopt purgation as the methodology
to improve visualization of the colon.” Id. at *3.
    On appeal, the parties dispute the construction of the
claim term “purgation” because the asserted claims cover
compositions “comprising from about 100 mL to about
500 mL of an aqueous hypertonic solution.” Ex Parte
Reexamination Certificate, ’149 patent col. 2 ll. 24-26.
Braintree sells SUPREP in a kit containing two six-ounce
bottles of concentrated solution, along with a dilution cup.
A patient must dilute each of the two six-ounce bottles
6 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

with ten ounces of water to form two sixteen-ounce solu-
tions. Each of those half-dose sixteen ounce solutions has
a total volume of 473 mL, which is within the range found
in the asserted claims of the ’149 patent, but Braintree
concedes that neither dose accomplishes a full cleansing.
Thus, Braintree’s “one bottle” infringement theory asserts
that one (half-dose) bottle of SUPREP, diluted with water
to become a sixteen ounce solution, falls within the as-
serted claims. This infringement theory can prevail if
purgation means the “evacuation of a copious amount of
stool from the bowels after oral administration of the
solution,” which is something less than a full cleansing.
     Novel argues that SUPREP does not infringe the as-
serted claims if “purgation” means cleansing, because a
full cleansing only occurs after ingesting 946 mL of solu-
tion (i.e., two doses). Pointing to the specification, Novel
alleges that the physiological event that the inventor
contemplated was cleansing the colon for a colonoscopy.
See, e.g., ’149 patent title, abstract. Novel also relies on a
passage in the specification which indicates that a dosage
amount is “effective” only if it produces a clean colon in
preparation for a colonoscopy or other surgical proce-
dures. Id. at col. 5 ll. 19-24 (“Optimally, the effective dose
may be divided and administered, to the patient in two, or
more administrations over an appropriate time period.
Generally, 2 doses administered of equal portions of the
effective dose, separated by 6 to 24 hours produce satis-
factory purgation.”). Thus, Novel argues that an effective
amount of solution must cleanse the colon.
    Novel also points to Braintree’s 2010 patent term ex-
tension request, where Braintree represented to the U.S.
Patent and Trademark Office (“PTO”) that “[t]he
SUPREP product is an osmotic laxative for cleansing (i.e.,
purging) of the colon . . . .” J.A. 22172 (emphasis added).
Therefore, Novel argues that Braintree’s representation
that purgation is equivalent to cleansing reflects the
proper construction of “purgation.”
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 7

     While we have considered all of Novel’s arguments
supporting its proposed construction of “purgation,” we
find them unpersuasive. “In construing claims, the ana-
lytical focus must begin and remain centered on the
language of the claims themselves, for it is that language
that the patentee chose to use to ‘particularly point[] out
and distinctly claim[] the subject matter which the pa-
tentee regards as his invention.’” Interactive Gift Express,
Inc. v. Compuserve Inc., 256 F.3d 1323, 1331 (Fed. Cir.
2001) (quoting 35 U.S.C. § 112, ¶ 2 (1975), amended by 35
U.S.C. § 112(b)). The asserted claims here only require
that the compositions “induce” (i.e., bring about or start)
diarrhea. The claims do not contain language that re-
quires achieving a fully cleansed colon for a colonoscopy.
Thus, while cleansing is the goal specifically articulated
in the specification, it is not a claim requirement. See
Comaper Corp. v. Antec, Inc., 596 F.3d 1343, 1348 (Fed.
Cir. 2010) (citation omitted) (“There is an inference . . .
that two different terms used in a patent have different
meanings.”).
     Novel’s reliance on the claim term “effective amount”
is also misplaced. The district court construed “effective
amount” as an amount of solution “necessary to produce a
colonic purgation, while not producing clinically signifi-
cant electrolyte shifts,” and Novel has not challenged this
construction. Claim Construction Order at *5. Since an
“effective amount” only requires purgation and not a full
cleansing, it is consistent to construe purgation as an
evacuation of a copious amount of stool. Although the
specification contemplates a scenario in which an effective
amount could produce a full cleansing, it does so only in
terms of a preferred embodiment. See Enzo Biochem, Inc.
v. Applera Corp., 599 F.3d 1325, 1342 (Fed. Cir. 2010)
(citation omitted) (“‘[I]t is improper to read limitations
from a preferred embodiment described in the specifica-
tion—even if it is the only embodiment—into the claims
8 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

absent a clear indication in the intrinsic record that the
patentee intended the claims to be so limited.’”).
    Finally, we conclude that Braintree’s statement that
SUPREP is a product for “cleansing (i.e., purging)” in its
patent term extension request does redefine “purgation”
as “cleansing.” Whether a statement to the PTO that
includes “i.e.” constitutes a clear and unmistakable disa-
vowal of claim scope depends on the context. See, e.g.,
Toshiba Corp. v. Imation Corp., 681 F.3d 1358, 1370-71
(Fed. Cir. 2012). In this case, the post-issuance statement
of the patentee does not modify the plain meaning of the
word “purgation.” Thus, we hold that Braintree’s state-
ment was not a clear and unmistakable disavowal. See
SkinMedica, Inc. v. Histogen Inc., 727 F.3d 1187, 1199-
1201 (Fed. Cir. 2013); Elbex Video, Ltd. v. Sensormatic
Elecs. Corp., 508 F.3d 1366, 1371 (Fed. Cir. 2007).
    For the aforementioned reasons, we affirm the district
court’s construction of the claim term “purgation.”
        2. Clinically Significant Electrolyte Shifts
     The district court originally construed “clinically sig-
nificant electrolyte shifts” to require “alterations in blood
chemistry that are outside the normal upper or lower
limits of their normal range or other untoward effects.”
Claim Construction Order at *6. Later, in considering the
parties’ summary-judgment motions, the district court
amended its construction and re-defined “clinically signif-
icant electrolyte shifts” to be “alterations in blood chemis-
try that are both outside the normal upper or lower limits
of their range and accompanied by or manifested as other
untoward effects.” Infringement Opinion at *7 (emphases
added). The district court explained that it modified its
original construction to make it conjunctive because the
specification refers to “electrolyte shifts leading to serious
health problems for the patient.” Id. It further explained
that the phrase “untoward effects” may refer to “those
fatal side effects of the [prior art] solution because such
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 9

side effects are referred to in the specification” and “is
meant to show that electrolyte abnormalities are not
clinically significant unless they lead to serious adverse
health effects, like those caused by [the prior art].” Id.
    On appeal, Novel argues that in requiring both altera-
tions in blood chemistry and other untoward effects, the
district court ignored the inventor’s clear definition of the
term “clinically significant electrolyte shifts” in the speci-
fication. See ’149 patent col. 2 ll. 47-51 (“The terms ‘clini-
cally significant’ as used herein are meant to convey
alterations in blood chemistry that are outside the normal
upper or lower limits of their normal range or other
untoward effects.”).
    In defending the district court’s final construction,
Braintree argues that the preferred embodiment—
referred to as Solution D in the ’149 patent—caused
alterations in some patients’ blood chemistry, but those
alterations were found to be “clinically insignificant.” ’149
patent col. 10 ll. 32-33. Thus, according to Braintree, the
definition found in the specification would exclude Solu-
tion D, which is the preferred embodiment in the ’149
patent. And “[a] claim construction that excludes the
preferred embodiment ‘is rarely, if ever, correct and would
require highly persuasive evidentiary support.’” Adams
Respiratory Therapeutics, Inc. v. Perrigo Co., 616 F.3d
1283, 1290 (Fed. Cir. 2010) (citation omitted).
    Under our precedent, the patentee’s lexicography
must govern the claim construction analysis. See Phillips
v. AWH Corp., 415 F.3d 1303, 1316 (Fed. Cir. 2005) (en
banc). Therefore, we disagree with the district court’s
modification of the clear language found in the specifica-
tion. We reverse the district court’s claim construction
and construe “clinically significant electrolyte shifts” to be
“alterations in blood chemistry that are outside the nor-
mal upper or lower limits of their normal range or other
untoward effects.”
10 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

                      B. Infringement
    We review the grant of summary judgment under the
law of the regional circuit. Lexion Med., LLC v. Northgate
Techs., Inc., 641 F.3d 1352, 1358 (Fed. Cir. 2011). The
Third Circuit reviews the grant of summary judgment de
novo. Nicini v. Morra, 212 F.3d 798, 805 (3d Cir. 2000)
(en banc). Summary judgment is appropriate if the
movant “shows that there is no genuine dispute as to any
material fact and the movant is entitled to judgment as a
matter of law.” Fed. R. Civ. P. 56(a).
    Based on its construction of “purgation,” which does
not require a full cleanse, the district court found that one
bottle of SUPREP meets the “purgation” claim limitation,
as it will induce an evacuation of a copious amount of
stool from the bowels and is a composition comprising
473 mL of an aqueous hypertonic solution. Infringement
Opinion at *9-10. We affirm the district court’s construc-
tion of this term, and we likewise affirm the district
court’s finding that one (half-dose) bottle of SUPREP
practices this claim limitation.
    The district court also found that SUPREP practices
the “wherein the composition does not produce any clini-
cally significant electrolyte shifts” limitation. Id. at *6-8.
It based its conclusion not only on its erroneous construc-
tion of the term “clinically significant electrolyte shifts”
but also on its importation of the claim terms “a patient”
into this limitation. Id. at *8. The words “a patient” are
found in the preamble. See Ex Parte Reexamination
Certificate, ’149 patent col. 2 ll. 23-24. The district court
explained that, based on its review of the record, “it
appears that the administration of the composition and
evaluation of the electrolyte levels in [the asserted claims]
were meant to be done on a per patient basis.” Infringe-
ment Opinion at *8. It defined “a patient” to mean “one or
more patients.” Id. It then found that “at least one
patient to whom SUPREP is administered will experi-
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 11

ence, or has experienced, no clinically significant electro-
lyte shifts.” Id.
    “[I]f the claim preamble is ‘necessary to give life,
meaning, and vitality’ to the claim, then the claim pream-
ble should be construed as if in the balance of the claim.”
Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298,
1305 (Fed. Cir. 1999) (citations omitted). Conversely, a
preamble is not limiting “where a patentee defines a
structurally complete invention in the claim body and
uses the preamble only to state a purpose or intended use
for the invention.” Rowe v. Dror, 112 F.3d 473, 478 (Fed.
Cir. 1997).
    Neither party has argued on appeal that the district
court erred in importing “a patient” into this limitation.
However, the parties are at odds over whether the district
court’s definition of “a patient” is correct. Novel argues
that the district court’s definition limits the utility of the
claimed compositions to administration in a single pa-
tient. Indeed, such an interpretation would allow a
composition to meet the claims even if 99 patients out of
100 experienced clinically significant electrolyte shifts, as
long as one patient did not.
    In support of the district court’s definition of “a pa-
tient,” Braintree argues that “a patient” must mean one
or more patients, as it cannot be the case that no in-
fringement can occur if SUPREP causes a clinically
significant electrolyte shift in a single patient.
    We agree with Novel and conclude that, in this case,
the district court’s definition of “a patient” is incorrect. In
view of the proper claim construction of “clinically signifi-
cant electrolyte shifts,” the district court’s application of
the claim terms “a patient” leads to the absurd result of
infringement even if a composition causes clinically
significant electrolyte shifts in a large percentage of
patients. Therefore, we instead interpret “a patient” to
mean the general class of persons to whom the patented
12 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

compositions are directed, i.e., a patient population. This
definition of a patient is consistent with the “invention
the patentee intended to define and protect.” Rowe, 112
F.3d at 478. Indeed, in the specification, the inventor
states that his “objective was to find a well tolerated
orally administered colonic purgative that . . . avoided the
risks of upset or electrolyte balance in patients.” ’149
patent col. 4 ll. 45-48 (emphasis added). In addition, the
inventor states that a preferred embodiment has been
“well tolerated by normal people.” Id. at col. 11 ll. 43-44
(emphasis added). And in the ’149 patent’s abstract, the
inventor described his invention as “[a] compromise
between convenient, distasteful, solid or low volume,
hyperosmotic solutions which cause considerable fluid and
electrolyte imbalances in patients and large volume,
difficult to consume, iso-osmotic solutions . . . .” Id. at
abstract (emphasis added).
    We note that there is evidence in the record that at
least some patients experienced alterations in blood
chemistry that are outside the normal upper or lower
limits of their normal range. See, e.g., J.A. 924, 5059-71,
6683, 6694, 6759, 6831, 6833, 6849, 6857. Therefore, we
conclude that there remains a genuine dispute as to
whether SUPREP avoids producing any clinically signifi-
cant electrolyte shifts in a patient population. We vacate
the district court’s grant of summary judgment of in-
fringement, and we remand this matter to the district
court for further factual findings concerning whether such
alterations qualify as “clinically significant electrolyte
shifts” in accordance with the proper claim construction
articulated here within.
                       C. Invalidity
    Invalidity must be proven by clear and convincing ev-
idence. WMS Gaming Inc. v. Int’l Game Tech., 184 F.3d
1339, 1355 (Fed. Cir. 1999). On appeal from a bench trial,
we review the district court’s conclusions of law de novo
BRAINTREE LABORATORIES, INC.    v. NOVEL LABORATORIES, INC. 13

and findings of fact for clear error. Brown & Williamson
Tobacco Corp. v. Philip Morris Inc., 229 F.3d 1120, 1123
(Fed. Cir. 2000).
                 1. Anticipation by Hechter
    Anticipation is a question of fact, and a district court’s
findings on this issue are reviewed for clear error. See
Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1082
(Fed. Cir. 2008). Below, the district court found that
Novel “did not show proof that met the clear and convinc-
ing standard” that the asserted claims were anticipated
by Hechter. Validity Opinion at *25. The district court
credited Braintree’s expert witness’s opinion that Hechter
does not disclose several limitations of the asserted
claims. Id. at *24. On appeal Novel argues again that
Hechter anticipates the asserted claims of the ’149 patent.
     Hechter teaches first mixing 60 grams of a dry powder
composition with one-liter of water and then later adding
three additional liters of water prior to administration.
Hechter col. 3 ll. 52-62. Novel argues that Hechter ex-
pressly discloses the preparation of a one-liter hypertonic
solution because during the first step, the composition in
Hechter is mixed with one-liter of water. See id. at col. 3
ll. 55-59. It alleges that Hechter further discloses that 1.6
liters, or 40% of its four-liter solution, is capable of cleans-
ing the colon (Id. at col. 4 ll. 13-16); 40% of one-liter is 400
mL. Novel also claims that the initial solution in Hechter
is inherently hypertonic.
    We note that during prosecution, the examiner initial-
ly rejected the claims over Hechter. See J.A. 21889.
Braintree then added the word “hypertonic” to its claims,
explaining that Hechter taught administering 3 to 4 liters
of an isotonic solution, while the claims were directed to
hypertonic solutions. J.A. 21906, 21913-14. In response,
the examiner withdrew the rejections. J.A. 21922.
14 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

     After reviewing Hechter and the ’149 patent’s prose-
cution history, we conclude that Novel’s argument is
flawed for at least three reasons. First, Hechter does not
disclose administering this initial one-liter solution to a
patient. And we find no clear error in the district court’s
finding that skilled artisans would not have administered
Hechter’s initial mixing solution because, as the ’149
patent explains, “concentrating the large volume, [isotonic
preparations] into smaller volumes does not achieve the
same effectiveness, and is not as safe.” ’149 patent col. 3
ll. 26-28. Second, although theoretically the initial one-
liter solution described in Hechter could be hypertonic in
a patient, both parties’ experts agreed that the only way
to know whether Hechter’s initial mixing solution was
hypertonic would be to test it. See J.A. 21251-52, 21422,
21622. But Novel has no evidence to suggest that the
initial mixture in Hechter has been tested in a patient
population, let alone that it was found to be hypertonic.
Id. Thus, Novel lacks clear and convincing evidence that
Hechter teaches this limitation. Third, Hechter actually
teaches away from administering a hypertonic solution,
stating that its solution needs to be isotonic in order to
avoid clinically significant electrolyte shifts. See Hechter
col. 2 ll. 9-39, col. 2 ll. 60-67, col. 3 ll. 15-16, col. 3 ll. 38-40.
For at least these three reasons, we affirm the district
court’s finding that Hechter does not anticipate the as-
serted claims of the ’149 patent.
                         2. Obviousness
    Obviousness is a question of law, reviewed de novo,
based on underlying factual findings, reviewed for clear
error. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
The district court found that Novel, which relied on
sixteen prior art references, failed to prove obviousness by
clear and convincing evidence. Validity Opinion at *24.
“[D]iscount[ing] [Novel’s expert’s] testimony on credibility
grounds because some of his conclusions did not appear to
be as reasonable,” the district court found that the prior
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 15

art “did not direct a [skilled artisan] to combine sodium
sulfate, magnesium sulfate, and potassium sulfate in a
small volume hypertonic solution that causes purgation,
does not produce clinically significant electrolyte shifts,
and does not contain phosphate.” Id. at *22. The district
court also found that the inventor’s “detailed experimen-
tation” was far from the “tweaking” and “modifying” that
Novel’s expert claimed. Id. at *23.
     Novel relies on many references as an attempt to
demonstrate that, at the time of the invention, one of skill
in the art knew that: (1) sulfate salts caused purgation of
the colon; (2) hypertonic, low-volume colon-cleansing
solutions were preferable; (3) clinically significant electro-
lyte shifts should be avoided; (4) bowel preps should be
administered in a split-dose regimen; and (5) bowel preps
should typically avoid phosphates. It adds that the prior
art consisted only of a limited number of known agents
that may be combined to cleanse the colon without ingest-
ing phosphate and without producing clinically significant
electrolyte shifts. Further, Novel argues that all compo-
nents in the asserted claims were known purgatives at
the time of invention. Thus, Novel alleges that the as-
serted claims “‘simply arrange[] old elements with each
performing the same function it had been known to per-
form’ and yields no more than one would expect from such
an arrangement, [so] the combination is obvious.” KSR
Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007) (citation
omitted). Finally, Novel argues that before the ’149
patent’s priority date, there was a need to: (1) avoid the
use of phosphates in particular patient populations; and
(2) develop a low-volume solution to improve patient
compliance and efficacy. Novel claims the district court
failed to consider the limited number of choices to meet
those market preferences and pressures.
   We disagree. As the district court correctly noted,
Novel did not prove that one of skill in the art would have
been motivated to combine so many references. In other
16 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

words, it failed to prove a “plausible rational[e] as to why
the prior art references would have worked together.”
Power-One, Inc. v. Artesyn Techs., Inc., 599 F.3d 1343,
1352 (Fed. Cir. 2010). Further, in building its obvious-
ness case, Novel relies on expert testimony which the
district court found to be less credible. Validity Opinion
at *25. And the prior art, including Hechter, taught that
safe bowel preps should be isotonic, not hypertonic like
the claimed compositions. See, e.g., Hechter col. 2 ll. 60-
64. Therefore, we conclude that the district court did not
err in finding that Novel failed to demonstrate that the
asserted claims of the ’149 patent would have been obvi-
ous at the time of the invention.
                     3. Indefiniteness
     We review de novo the district court’s decision regard-
ing indefiniteness, as it is a question of law. Ergo Licens-
ing, LLC v. CareFusion 303, Inc., 673 F.3d 1361, 1363
(Fed. Cir. 2012). The district court found that Novel
failed to prove the claims indefinite by clear and convinc-
ing evidence. Validity Opinion at *25-26. It rejected
Novel’s argument that a skilled artisan would not under-
stand the word “copious”—a term not used in any claim
and only found in the district court’s construction of
“purgation.” Id. at *25. On appeal, Novel argues that the
district court noted but then ignored the clear import of
the testimony from the inventor, who admitted explicitly
that the term purgation “does not have a defined volume.”
J.A. 21048-49. It points to further testimony on the
record from a Braintree employee, in which the employee
admitted: “I don’t think there’s any clear definition about
what copious diarrhea means.” J.A. 21304.
    We are not persuaded by Novel’s indefiniteness argu-
ment. It has failed to show why the word “copious,” a
word that is not found in the claims but rather is used in
the district court’s construction of “purgation,” is indefi-
nite in this context. Descriptive words like “copious” are
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 17

commonly used in patent claims, to “avoid[] a strict nu-
merical boundary to the specified parameter.” See Pall
Corp. v. Micron Separations, Inc., 66 F.3d 1211, 1217
(Fed. Cir. 1995). Further, when asked what copious
would mean to one of skill in the art, Braintree’s expert
witness stated “[w]ell, copious is a lot. . . . I think anyone
who has taken a bowel prep prior to [a] colonoscopy,
knows that it’s quite a bit of diarrhea that comes out.”
J.A. 20161. We agree, and therefore we conclude that one
of skill in the art would understand what a “copious”
amount of diarrhea is in this context.
                      IV. CONCLUSION
    For the foregoing reasons, we affirm the district
court’s claim construction of “purgation.” However, we
conclude that the district court erred in construing the
claim term “clinically significant electrolyte shifts.” We
reverse its claim construction and vacate its grant of
summary judgment of infringement. Regarding validity,
we affirm the district court’s findings that the asserted
claims of the ’149 patent are not anticipated, not obvious,
and not indefinite. We remand this case to the district
court for further proceedings consistent with this opinion.
    AFFIRMED-IN-PART, REVERSED-IN-PART,
      VACATED-IN-PART, AND REMANDED
  United States Court of Appeals
      for the Federal Circuit
                 ______________________

        BRAINTREE LABORATORIES, INC.,
               Plaintiff-Appellee,

                            v.

           NOVEL LABORATORIES, INC.,
               Defendant-Appellant.
              ______________________

                       2013-1438
                 ______________________

    Appeal from the United States District Court for the
District of New Jersey in No. 11-CV-1341, Judge Peter G.
Sheridan.
                 ______________________
DYK, Circuit Judge, concurring in part, dissenting in part,
and concurring in the result.
    I agree with Judge Prost that the district court erred
in its construction of “clinically significant electrolyte
shifts” and that the correct construction of that term is
“alterations in blood chemistry that are outside the nor-
mal upper or lower limits of their normal range or other
untoward effects.” Op. of Prost, J., at 9. Although it
seems to me that Novel established non-infringement as a
matter of law under the correct “clinically significant
electrolyte shifts” construction, I join the remand to the
2 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

district court for further proceedings on that issue. 1 I also
agree that the asserted claims of the ’149 patent are not
invalid. Thus I join parts I–II, III(A)(2), III(B) (except the
second paragraph) and III(C).
    However, I respectfully dissent from the majority’s
conclusion that Novel’s ANDA meets the volume limita-
tion of the asserted claims. Under the proper interpreta-
tion of the volume limitation, Novel established non-
infringement as a matter of law. In my view, the majori-
ty’s contrary conclusion is inconsistent with established
authority under the Hatch-Waxman Act.

    1   The sole evidence in the summary judgment rec-
ord concerning the percentage of individuals experiencing
such electrolyte shifts is data from two clinical studies of
SUPREP, and those data are sufficient to show that the
claim limitation was not met. The first, BLI800-202, a
Phase II study of eighteen patients, showed that a majori-
ty of patients experienced clinically significant electrolyte
shifts. J.A. 5059–69; 6642, 6683; 6756, 6759; 6831; 6912;
7000, 7002; 7094, 7100; 7386; Def.’s Br. in Supp. of Mot.
for Summ. J. 8, Braintree Labs., Inc. v. Novel Labs., Inc.,
No. 3:11-cv-1341 (D.N.J. Oct. 9, 2012), ECF No. 159-1.
The second, BLI800-303, a Phase III study of sixty-three
patients, showed that a significant minority or about one-
third of patients experienced clinically significant electro-
lyte shifts. J.A. 9679 (expert report of Dr. Goldfarb (Nov-
el’s expert witness) summarizing BLI800-303 data).
Braintree’s expert witness Dr. Peura also testified that
“abnormal electrolyte values have been observed in some
patients taking SUPREP.” J.A. 10322 (emphasis re-
moved).
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 3

                               I
    I agree with the majority that the district court’s
construction of “purgation” was correct. But even under
that construction, Novel’s ANDA does not meet the
claimed volume limitation. The asserted claims include a
volume limitation that requires that the solution be
between 100-500 mL, as seen in representative claim 15:
   A composition for inducing purgation of the colon
   of a patient, the composition comprising from
   about 100 ml to about 500 ml of an aqueous hy-
   pertonic solution . . . wherein the composition does
   not produce any clinically significant electrolyte
   shifts . . . .
Ex Parte Reexamination Certificate No. 6,946,149C1 col.
2 ll. 23–30 (emphasis added). The asserted claims also
include claims 18–20, and 23. Claims 19–20 and 23 are
method of use claims.
     In ANDA litigation, because a generic company seek-
ing FDA approval does not yet “make[], use[], offer[] to
sell, or sell[]” the product and therefore cannot infringe
under 35 U.S.C. § 271(a), pharmaceutical companies must
rely on 35 U.S.C. § 271(e)(2)(A), which creates an “artifi-
cial” act of infringement when the generic company sub-
mits an ANDA seeking approval “‘for a drug claimed in a
patent or the use of which is claimed in a patent.’” Eli
Lilly & Co. v. Medtronic, Inc., 496 U.S. 661, 675, 676
(1990) (quoting § 271(e)(2)(A)). The infringement occurs
only if the generic company seeks approval for a patented
composition or use that has been approved by the FDA.
Bayer Schering Pharma AG v. Lupin, Ltd., 676 F.3d 1316,
1319 (Fed. Cir. 2012) (citing Warner-Lambert Co. v.
Apotex Corp., 316 F.3d 1348, 1356 (Fed. Cir. 2003) (“‘[T]he
use’ in § 271(e)(2)(A) refers to the use for which the FDA
has granted an NDA.”)); Glaxo, Inc. v. Novopharm, Ltd.,
4 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

110 F.3d 1562, 1567–68 (Fed. Cir. 1997) (composition is
determined by the composition in the ANDA). 2
      Under the Hatch-Waxman Act, the infringement in-
quiry “must focus on what the ANDA applicant will likely
market if its application is approved.” Id. at 1569. Nov-
el’s ANDA does not cover administration of the drug for
purgation sufficient for “evacuation of a copious amount of
stool from the bowels.” Claim Construction Order at *6.
Rather, Novel’s ANDA states specifically that the drug “is
indicated for cleansing of the colon as a preparation for
colonoscopy in adults.” J.A. 5280. The ANDA limits its
dose regimen (the SUPREP regimen) as follows: “The dose
for colon cleansing requires administration of two bottles
of [oral solution]. Each bottle is administered as 16 oz
[i.e., 473 mL] of [oral solution] . . . .” J.A. 5280 (emphases
added). Therefore, the volume of the dose in Novel’s
ANDA is 946 mL. 3 Braintree’s infringement argument,

    2   Section 271(e)(2)(A) reads as follows:
        (2) It shall be an act of infringement to submit—

        (A) an application under [21 U.S.C. § 355(j)] or de-
        scribed in [21 U.S.C. § 355(b)(2)] for a drug
        claimed in a patent or the use of which is claimed
        in a patent.

35 U.S.C. § 271(e)(2)(A).
    3   See also J.A. 22172 (Braintree’s Patent Term Ex-
tension Request) (“The SUPREP product . . . contains only
2 x 16 ounces of solution (i.e., approximately 2 x 0.47 L =
.94L of solution), as indicated in the approved label . . . .”);
J.A. 4262 (Jack A. Di Palma et al., A Randomized Clinical
Study Evaluating the Safety and Efficacy of a New, Re-
duced-Volume, Oral Sulfate Colon-Cleansing Preparation
for Colonoscopy, 104 Am. J. Gastroenterology 2275, 2276
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 5

adopted by the district court and by the majority here, is
the “one bottle” infringement theory, which asserts that
because one (half-dose) bottle of Novel’s proposed generic
falls within the 100-500 mL volume range and would
cause a “purgation,” the ANDA infringes.
    Here, “one bottle” consisting of 473 mL is not the dose
approved by the FDA. The approved NDA for SUPREP
does not permit a dose regimen of only one 16 oz bottle
(473 mL), but requires both administrations of the “split-
dose” regimen of two bottles (946 mL). Nor does the NDA
recommend a one bottle dose to induce purgation as a
possible alternative. Since no clinical studies have been
conducted to support a one bottle regimen for purgation,
the FDA has not approved such a use. See 21 U.S.C.
§ 355(d)(1). Because there is no underlying NDA approval
for a one bottle regimen for purgation, Novel is precluded
from seeking an ANDA for such a regimen. 4 Instead,
Novel’s ANDA properly seeks approval for a 946 mL, two
bottle regimen to induce colon cleansing, based on
Braintree’s approved NDA. Therefore, Novel’s ANDA
does not infringe the ’149 patent, which claims a composi-
tion with a volume of 100-500 mL for inducing purgation
and a method of using the same.

(2009)) (“The total preparation volume [of SUPREP] is
960 ml.”).
    4    A generic may not file an ANDA that differs from
the approved NDA in “route of administration, dosage
form, or strength” unless it has obtained special permis-
sion from the FDA to do so, 21 U.S.C. § 355(j)(2)(C), and
Novel neither sought nor received such permission here.
A generic may not seek approval for a use that differs
from the approved NDA under any circumstances. See
Warner-Lambert,      316     F.3d    at   1356     (citing
§ 355(j)(2)(A)(i)).
6 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

    The majority’s contrary interpretation is inconsistent
with this court’s longstanding precedent. An ANDA
cannot infringe an asserted patent when the FDA-
approved dose is not the dose claimed in the patent. As
we held in Allergan, Inc. v. Alcon Labs., Inc., 324 F.3d
1322, 1332 (Fed. Cir. 2003), “a method of use patent
holder may not sue an ANDA applicant for induced in-
fringement of its patent, if the ANDA applicant is not
seeking FDA approval for the use claimed in the patent
and if the use claimed in the patent is not FDA-approved.”
(emphasis added) (citing Warner-Lambert, 316 F.3d at
1354–55). While the patent here includes both composi-
tion and method of use claims, all claims are limited to
the use of a specified volume of the composition.
    In particular, the majority’s decision is contrary to our
decision in Bayer Schering, where we held that because
“the FDA has not approved [the use claimed in the pa-
tent] . . . the defendants cannot be held liable for in-
fringement of the patent.” 676 F.3d at 1326. There, the
patent claimed the use of a particular drug to achieve
three effects simultaneously, “a contraceptive effect, an
antiandrogenic effect, and an antialdosterone effect.” Id.
at 1319 (quoting U.S. Patent No. 5,569,652). But the
FDA-approved NDA and label indicated the use of the
branded drug only “for oral contraception.” Id. (internal
quotation marks omitted). We held that the accused
ANDAs did not infringe because they did not seek ap-
proval for two of the claimed uses. Id. at 1326. There was
no infringement under § 271(e)(2)(A) because “the defend-
ants’ ANDAs [sought] approval to market the generic
[drug] for contraceptive use, and there is no valid patent
on the use of the drug for that purpose alone.” Id.
    Crucially, we found it irrelevant that the drug did, in
fact, cause the three claimed effects simultaneously—
simply because a patient could practice the claims by
using the drug to achieve all three effects did not mean
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 7

that the corresponding ANDA infringed. Id. at 1325–26.
“[Nothing] on the [approved] label provide[d] any safety or
efficacy information associated with the possible use of
[the drug] in treating patients who are in need of those
[claimed] effects.” Id. at 1322. As we noted there:
   [T]he point is not simply that the method of use
   [claimed in the patent] was not described in the
   Indications and Usage section that shows lack of
   FDA approval; the point is that the label, taken in
   its entirety, fails to recommend or suggest to a
   physician that [the drug] is safe and effective for
   inducing the claimed combination of effects in pa-
   tients in need thereof.
Id. at 1324. So too here—just because a patient could
ingest only one bottle of Novel’s generic to achieve a
purgation does not make Novel’s ANDA infringing. It is
undisputed that Novel’s proposed label fails to recom-
mend or suggest to a physician that the solution should be
taken to achieve purgation, rather than cleansing, or that
it suggests taking a dosage below the 946 mL level for any
purpose.
     Similarly, in Warner-Lambert, 316 F.3d at 1356, we
held that “because an ANDA may not seek approval for an
unapproved or off-label use of a drug . . . it necessarily
follows that 35 U.S.C. 271(e)(2)(A) does not apply to a use
patent claiming only such [an unapproved or off-label]
use.” See also AstraZeneca LP v. Apotex, Inc., 633 F.3d
1042, 1059–60 (Fed. Cir. 2010) (assuming that an ANDA
seeking approval for a twice-daily dose regimen could not
infringe a patent claiming a once-daily dose regimen). In
short, Braintree’s patent claims a composition and a
method, both of which require using a 100-500 mL solu-
tion. Novel’s ANDA seeking FDA approval for a 946 mL
solution cannot infringe the ’149 patent.
8 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

                              II
    Even if there were no Hatch-Waxman issue,
Braintree’s theory would be unsupportable. Braintree’s
“one bottle” theory rests on a demonstrably incorrect
claim construction. Here, “volume” refers to the total
volume of the recommended dosage and not some portion
of that total volume—whether or not the recommended
dosage is given in one bottle or two bottles.
    The ’149 patent specification describes the two catego-
ries of bowel cleansing options in the prior art to the ’149
patent, each with its own disadvantages. The first were
“large volume” isotonic solutions that did not cause elec-
trolyte shifts in patients. ’149 patent col. 1 ll. 31, 48–53.
The second were “small volume” hypertonic preparations
that caused severe electrolyte shifts in many patients,
often with life-threatening results. Id. col. 2 ll. 41–44, col.
4 ll. 23–26. The inventors of the ’149 patent further
recognized that although “[c]linical trials have shown use
of the 4 liter [i.e., large volume] [isotonic] solution to be
safe and efficacious [i.e., did not cause electrolyte shifts],”
that patient “compliance [with ingesting such solutions] is
poor because of the large volume of solution.” Id. col. 4 ll.
1–5. The ’149 patent attempted to address both issues by
creating a small volume solution for patient ingestion that
did not cause clinically significant electrolyte shifts. The
volume limitation was critical to distinguish the ’149
patent from the prior art. The specification explains that
the prior art solutions were customarily ingested in
multiple administrations, such that a solution with a total
volume of 4 liters would be divided into administrations of
500 mL or less. 5 The specification suggested the same

    5   See, e.g., ’149 patent col. 1 ll. 53–56 (“Because the
[large] solutions are isotonic, patients are required to
ingest a significant amount of volume of these solutions,
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 9

method of dividing the total volume for ingesting the
claimed solution:
    Optimally, the effective dose may be divided and
    administered, to the patient in two, or more ad-
    ministrations over an appropriate time period.
    Generally, 2 doses administered of equal portions
    of the effective dose, separated by 6 to 24 hours
    produce satisfactory purgation.
Id. col. 5 ll. 19–24 (emphasis added). The specification
thus makes clear that the total volume is the combination
of the divided doses. Under the correct construction as
envisioned by drafters of the ’149 patent, “volume” re-
ferred to the total claimed 100-500 mL volume of solution
ingested by the patient as the recommended dose to
induce purgation, even if this total volume has been
divided into smaller administrations of unspecified size.
This ensured that the claimed volume limitation did not
run afoul of the prior art solutions such as Hechter, which
suggested dividing a “large volume” solution of 4 liters
into individual administrations of about eight ounces or
237 mililiters. Hechter col. 4 ll. 2–12, col. 6 ll. 14–35.
     Indeed, Braintree’s own arguments that Hechter does
not anticipate the ’149 patent focus on the total volume of
the disclosed Hechter solution and are inconsistent with
its “one bottle” infringement theory. Hechter disclosed a
4 liter isotonic solution that would be created from a 1
liter hypertonic stock solution. Hechter col. 3 ll. 55–62.

up to one eight ounce glass [i.e., 237 mL] every ten
minutes for a total of one gallon of fluid [i.e., about 4 L] to
achieve effective purging.” (emphasis added)); id. col. 2 ll.
32–34 (“Patients are typically required to take two (2)
three ounce doses of [Fleets Phospho-Soda] separated by a
three to 12 hour interval for a total of six ounces (180
ml).”).
10 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

Novel argued that because Hechter taught that only 40%
of the 4 liter isotonic solution must be ingested to achieve
colon-cleansing, it inherently disclosed a 400 mL hyper-
tonic stock solution capable of colon-cleansing. Appel-
lant’s Br. 47–49. But Braintree’s expert witness in this
case disagreed, objecting that there could be no anticipa-
tion from consuming only a portion of the recommended
dose. See J.A. 21624 (Peura direct testimony) at 962:7–13
(explaining that he disagreed with Novel’s inherent
disclosure theory, because “[w]ell, a liter is a liter. You
know, there may be two 500 milliliters components to a
liter or four 250, or ten 100; there’s no teaching in Hecht-
er that would suggest that . . . this liter would ever be
administered to anybody, and there’s surely no teaching
that you can divide this liter into component parts.”).
Braintree’s own argument that Hechter does not antici-
pate the claimed invention depends, in part, on an as-
sumption that the relevant volume is the total amount of
a disclosed solution, not the volume of individual admin-
istrations or separate components of that solution.
    In short, the specification of the ’149 patent and
Braintree’s own expert made clear that the invention was
directed at “small volume” solutions of 100-500 mL total—
not large volume solutions that could be divided into 100-
500 mL administrations. Braintree’s “one bottle” theory
of infringement therefore leads to the surprising result
that although large volume solutions of 4 liters are dero-
gated in the specification, if administered in 500 mL
increments, such solutions would infringe the ’149 patent.
Therefore, the entire premise of the ’149 patent—that a
recommended dosage of a small volume would improve
patient compliance—is ignored by Braintree’s one bottle
theory.
      Because Novel’s ANDA does not meet the volume
limitation of the asserted claims, under this court’s ANDA
infringement precedent and under the language of the
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 11

specification, it cannot infringe the ’149 patent. I respect-
fully dissent from the contrary conclusion reached by the
majority.
  United States Court of Appeals
      for the Federal Circuit
                 ______________________

        BRAINTREE LABORATORIES, INC.,
               Plaintiff-Appellee,

                            v.

           NOVEL LABORATORIES, INC.,
               Defendant-Appellant.
              ______________________

                       2013-1438
                 ______________________

    Appeal from the United States District Court for the
District of New Jersey in No. 11-CV-1341, Judge Peter G.
Sheridan.
                 ______________________
MOORE, Circuit Judge, dissenting.
    I join the majority opinion except for Part III-B be-
cause I disagree with the majority’s construction of “a
patient.” I agree with the district court that “a patient”
means “one or more patients” in accordance with the plain
language of the asserted claims and with our precedent. I
would affirm the district court’s summary judgment of
infringement because undisputed evidence shows that at
least one patient who was treated with the accused com-
position has experienced “clinically significant electrolyte
shifts” within the meaning of the claims. Therefore, I
respectfully dissent.
    Reexamined claim 15 of U.S. Patent No. 6,946,149
(’149 patent), which is representative of the asserted
2 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

claims, recites “[a] composition for inducing purgation of
the colon of a patient, . . . wherein the composition does
not produce any clinically significant electrolyte shifts
. . . .” Everyone agrees that the preamble term “a patient”
limits the scope of the claim. The disagreement centers
on the meaning of “a patient.” The district court held that
it meant one or more patients. The majority concludes
that it means “a general class of persons,” or “a patient
population.” Maj. Op. at 11–12.
    The plain and ordinary meaning of “a patient” is one
or more patients. We have, on many occasions, construed
the article “a.” Not surprisingly, this word appears in
many patent claims. We have repeatedly held that “a,”
when used in a “comprising” claim, means one or more.
“As a general rule, the words ‘a’ or ‘an’ in a patent claim
carry the meaning ‘one or more.’ The exceptions to this
rule are extremely limited: a patentee must evince a clear
intent to limit ‘a’ or ‘an’ to ‘one.’” 01 Communique Lab.,
Inc. v. LogMeIn, Inc., 687 F.3d 1292, 1297 (Fed. Cir.
2012); see also SanDisk Corp. v. Kingston Tech. Co., Inc.,
695 F.3d 1348, 1360–61 (concluding that “a” means “one
or more”); Baldwin Graphic Sys., Inc. v. Siebert, Inc., 512
F.3d 1338, 1342 (Fed. Cir. 2008) (“[T]his court has repeat-
edly emphasized that the indefinite article ‘a’ or ‘an’ in
patent parlance carries the meaning of ‘one or more’ in
open-ended claims containing the transitional phrase
‘comprising.’”). In the few instances where we have ever
deviated from this general rule, we concluded that the
intrinsic evidence made it clear that the patentee intend-
ed “a” to mean one and only one. See Tivo, Inc. v. EchoS-
tar Commc’ns Corp., 516 F.3d 1290, 1303–04 (Fed. Cir.
2008); Insituform Techs., Inc. v. Cat Contracting, Inc., 99
F.3d 1098, 1105–06 (Fed. Cir. 1996).
    Strangely, the majority does not conclude that “a pa-
tient” means “one or more,” consistent with our general
rule, or that it means “only one,” consistent with the only
exception that we have allowed. “A patient,” according to
BRAINTREE LABORATORIES, INC.     v. NOVEL LABORATORIES, INC. 3

the majority, requires multiple patients, a patient popula-
tion, or patient class. But there is no plain meaning of “a”
that excludes the singular. We give claim terms their
plain and ordinary meaning unless the patentee acted as
its own lexicographer or there was a disavowal of claim
scope. Thorner v. Sony Computer Entm’t Am. LLC, 669
F.3d 1362, 1365 (Fed. Cir. 2012). Neither of these cir-
cumstances is present here. Although the majority is
correct that the specification sometimes uses the plural
“patients,” at other places it uses the singular “patient.”
See ’149 patent col. 2 ll. 43–44, col. 2 l. 65, col 3 l. 3, col. 5
l. 21. The patentee obviously knew how to refer to “pa-
tients” generally or as a class, but chose to draft the
claims to recite only “a patient.” Nothing in the specifica-
tion of the ’149 patent or its prosecution history defines
the singular “a patient” as a plural “patient population”
contrary to the words of the claims. In fact, the patent
lists only one object of the invention—and it is described
in terms of impact on a single patient: “One purpose of
the present research was to develop a safe, effective, and
well tolerated small volume solution made up of a high
concentration of poorly absorbable salts that induce colon
cleansing catharsis after oral ingestion without clinically
significant alternation [sic] of sodium, chloride, bicar-
bonate, potassium, calcium, and phosphate level and
balance or other untoward effects on the recipient.” Id.
col. 3 ll. 32–38.
     I agree with the majority that the patent defines “clin-
ically significant electrolyte shifts” as “alterations in blood
chemistry that are outside the normal upper or lower
limits of their normal range or other untoward effects.”
Id. col. 2 ll. 47–51. According to the patent, clinical
significance is measured in an individual patient. Name-
ly, are the electrolyte shifts in an individual patient
clinically significant, i.e., are they outside the normal
range? “Clinical significance” can sometimes refer to a
measure of statistical significance and other times to a
4 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

measure of deviation from normal in an individual pa-
tient. This patent, as discussed above, expressly defines
it as a measure in an individual patient. See also id. col.
2 ll. 43–44 (the invention avoids electrolyte shifts that are
“clinically significant to the patient”); id. col. 3 ll. 66–67
(“clinically significant electrolyte shifts on bodily chemis-
try”); id. col. 3 ll. 35–38 (“clinically significant alternation
[sic] . . . or other untoward effects on the recipient”).
Extrinsic evidence of record likewise demonstrates that
clinical significance is a measure applied to a single
patient. For example, the record includes a laboratory
report on an individual patient that directs the analyst to
indicate whether the test results were “Clinically Signifi-
cant” or “Not Clinically Significant” for that patient, J.A.
6756, and expert reports confirm this single-patient
meaning of the term, see J.A. 5059; J.A. 5153–54. Indeed,
the use of the term “clinical significance” to refer to indi-
vidual patients is well-established in the medical arts.
See, e.g., Alan E. Kazdin, The Meanings and Measurement
of Clinical Significance, 67 J. Consulting & Clinical
Psychol. 332, 332–33 (1999) (asking whether “the criteri-
on of clinical significance may not be met” when “the client
improves, but at the end of treatment the client’s behavior
has not changed enough for it to fall within the normative
range”). I see no basis in the specification or the prosecu-
tion history to rewrite the patent claims.
    This claim covers “[a] composition for inducing purga-
tion of the colon of a patient . . . wherein the composition
does not produce any clinically significant electrolyte
shifts . . . .” To infringe, the composition must induce
purgation in the colon of a patient without producing
clinically significant electrolyte shifts (i.e., shifts outside
the normal range) in that patient. Infringement is proven
if the composition causes these reactions in a single
patient. The majority believes this to be an “absurd
result” because it would allow “a composition to meet the
claims even if 99 patients out of 100 experienced clinically
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 5

significant electrolyte shifts, as long as one patient did
not.” 1 Maj. Op. 11. I understand the majority’s concern.
But this is a question of damages, not infringement.
     Infringement, whether on a large or small scale, is
still infringement. 2 See, e.g., Lucent Techs., Inc. v. Gate-
way, Inc., 580 F.3d 1301, 1318 (Fed. Cir. 2009). Lucent
makes clear that there is no “rare infringement” exception
to liability, and that even one instance of infringement is
adequate to support a judgment of infringement. Id.
(affirming a finding of direct infringement where a jury
“could have reasonably concluded that . . . more likely
than not one person somewhere in the United States had
performed the claimed method”); see also Broadcom Corp.
v. Emulex Corp., 732 F.3d 1325, 1333 (Fed. Cir. 2013) (“It
is well settled that an accused device that sometimes, but
not always, embodies a claim nonetheless infringes.”).
The law responds to rare infringement not by eliminating
liability, but by providing for a correspondingly low award
of damages. See Lucent, 580 F.3d at 1334 (“The damages
award ought to be correlated, in some respect, to the
extent the infringing method is used by consumers.”).
Likewise, the decision whether to award injunctive relief
in a patent infringement suit, which is at the discretion of
the district court, includes consideration of the extent of
infringement or harm to the patentee. See Robert Bosch
LLC v. Pylon Mfg. Corp., 659 F.3d 1142, 1148–50 (Fed.
Cir. 2011).

    1   To be sure, there is evidence in the record in this
case that the claimed composition infringes in numerous
instances, not just one. See Maj. Op. at 12.
    2   It may be that the FDA would not approve a drug
that has efficacy in a small percentage of the patients who
take it, but that is not the standard we use in assessing
infringement of patent claims.
6 BRAINTREE LABORATORIES, INC. v. NOVEL LABORATORIES, INC.

    And here lies the heart of the majority’s problem.
This is an ANDA case. In ANDA cases in which the
accused product has not yet been marketed, a damages
remedy is of course not available. Instead, the district
court “shall order the effective date of any approval of the
drug . . . involved in the infringement to be a date which
is not earlier than the date of the expiration of the patent
which has been infringed,” and the court “may” grant
“injunctive relief.” 35 U.S.C. § 271(e)(4)(A), (B). Thus,
while the injunction remedy rests within the discretion of
the district court, the order to delay the approval of the
ANDA until patent expiration is not discretionary. Id. I
don’t like this result either, but this is exactly what the
statutory language commands. The statute requires the
court to delay approval until expiration of the patent,
even if there is only a single infringement. And since the
generic can’t launch without FDA approval, the statute
creates a de facto injunction.
    In an effort to avoid this outcome, the majority re-
writes the claim language to allow infringement only if
the drug works in a patient population rather than a
patient. 3 But this we cannot do. Chef Am., Inc. v. Lamb-
Weston, Inc., 358 F.3d 1371, 1374 (Fed. Cir. 2004) (“[W]e
construe the claim as written . . . .”); Process Control Corp.
v. HydReclaim Corp., 190 F.3d 1350, 1357 (Fed. Cir. 1999)

    3   Changing “a patient” to “a patient population” is
pernicious for practical reasons as well. Infringement will
now be measured by whether a patient population experi-
ences purgation without abnormal shifts in electrolytes.
What percentage of people constitutes a patient popula-
tion? Is the patient population everyone who takes the
drug? A statistically significant number of people who
take the drug—which would be 99.5%? A majority? And
have we now written an indefinite or unsupported claim
for the patentee?
BRAINTREE LABORATORIES, INC.   v. NOVEL LABORATORIES, INC. 7

(“[A] nonsensical result does not require the court to
redraft the claims . . . .”). If the result commanded by the
statute is unsatisfactory, the proper response is for Con-
gress to amend the statute, making the delayed approval
discretionary rather than mandatory, not for us to redraft
the patent to avoid such a result. For these reasons, I
respectfully dissent. I would affirm the district court’s
summary judgment of infringement.