Court Opinion

ID: 206857
Source: CourtListenerOpinion
Date Created: 2011-03-13 06:48:33+00
Date Added: 2024-06-11T09:06:17.857967
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
              __________________________

  ADAMS RESPIRATORY THERAPEUTICS, INC.,
   ADAMS RESPIRATORY OPERATIONS, INC.,
  AND ADAMS RESPIRATORY PRODUCTS, INC.,
             Plaintiffs-Appellants,

                          v.
PERRIGO COMPANY, L. PERRIGO COMPANY, AND
  PERRIGO RESEARCH AND DEVELOPMENT
               COMPANY,
           Defendants-Appellees.
              __________________________

                      2010-1246
              __________________________

   Appeal from the United States District Court for the
Western District of Michigan in case No. 07-CV-0993,
Judge Gordon J. Quist.
             ___________________________

               Decided: August 5, 2010
             ___________________________

    DOMINICK A. CONDE, Fitzpatrick, Cella, Harper &
Scinto, of New York, New York, argued for plaintiffs-
appellants. With him on the brief were JOHN D. CARLIN,
NINA SHREVE, COLLEEN TRACY and TARA BYRNE.
ADAMS RESPIRATORY   v. PERRIGO CO                        2

   WILLIAM A. RAKOCZY, Rakoczy Molino Mazzochi Si-
wik, LLP, of Chicago, Illinois, argued for defendants-
appellees. With him on the brief were CHRISTINE J. SIWIK,
ALICE L. RIECHERS, GREGORY A. DUFF and ROBERT M.
TEIGEN.
              __________________________

  Before LINN, MOORE, and FRIEDMAN, Circuit Judges.
MOORE, Circuit Judge.

    Adams Respiratory Therapeutics, Inc. (Adams) ap-
peals the judgment of the district court that the guaifene-
sin product described in Perrigo Co.’s (Perrigo’s)
Abbreviated New Drug Application (ANDA) would not
infringe the asserted claims of U.S. Patent No. 6,372,252
(the ’252 patent). Because the court based its judgment of
noninfringement on an erroneous claim construction, we
vacate and remand.

                       BACKGROUND

     Guaifenesin is an expectorant used to thin, loosen,
and help expel mucus that causes congestion. It was first
approved by the Food and Drug Administration (FDA) in
1952. For many years, drug companies sold products
containing guaifenesin in both immediate release (IR) and
extended release forms without FDA approval. In 1989,
the FDA published standards for IR guaifenesin products
in Cold, Cough, Allergy, Bronchodilator, and Antiasth-
matic Drug Products for Over-the-Counter Human Use;
Expectorant Drug Products for Over-the-Counter Human
Use; Final Monograph; Final Rule (Monograph). The
FDA determined that IR guaifenesin products that com-
plied with the Monograph would be deemed safe and
effective. The Monograph did not address the safety and
efficacy of extended release guaifenesin products.
3                         ADAMS RESPIRATORY   v. PERRIGO CO

    In 2000, Adams filed a New Drug Application (NDA)
for an extended release guaifenesin product, Mucinex®.
Its extended release tablets contain an IR portion of
guaifenesin (designed to be quickly released into the
stomach) and a sustained release portion. Mucinex®
tablets were designed to be taken every twelve hours,
while IR guaifenesin tablets must be taken every four
hours to maintain their therapeutic effect. Adams estab-
lished the safety and efficacy of Mucinex® by showing that
it was bioequivalent to a standard IR product (Or-
ganidin®) that complied with the Monograph. Adams
submitted pharmacokinetic data showing that one
Mucinex® tablet (1200 mg) produces the same maximum
concentration of guaifenesin in the blood (Cmax) as one
Organidin® tablet (400 mg) taken every four hours for
twelve hours (three tablets total). The FDA approved
Adams’ NDA for Mucinex® and ordered all unapproved
extended release formulations off the market.

    In 2002, Adams obtained the ’252 patent concerning
extended release formulations of guaifenesin. The pre-
ferred embodiment of the ’252 patent is Mucinex®. In
2005, a third-party requested that the PTO conduct a
reexamination of the ’252 patent. During reexamination
the PTO rejected claim 24, which claimed an extended
release product having a Cmax “equivalent” to the Cmax of
an IR product when dosed as described in the claim. The
PTO indicated that claim 24 would likely be rejected
under 35 U.S.C. § 112, paragraph 1 because the claim
term “equivalent” was not defined. See Amendment in
Response to Final Office Action in Ex Parte Reexamina-
tion and Patent Owner’s Statement of the Interviews, at
21 (Aug. 21, 2006). Adams asserted that “one of ordinary
skill in the art would recognize ‘equivalent’ as being the
FDA bioequivalence guidelines of 80 – 125%.” Adams
attached an excerpt of the guidelines, U.S. Department of
ADAMS RESPIRATORY   v. PERRIGO CO                         4

Health and Human Services, Approved Drug Products
with Therapeutic Equivalence Evaluations, p. ix-x (19th
ed. 1999) (FDA guidelines), which state:

   Two formulations whose rate and extent of ab-
   sorption differ by -20%/+25% or less are generally
   considered bioequivalent.        The use of the -
   20%/+25% rule is based on a medical decision
   that, for most drugs, a -20%/+25% difference in
   the concentration of the active ingredient in blood
   will not be clinically significant.

                              **    *

   For approval of ANDAs, in most cases, the generic
   manufacturer must show that a 90% confidence
   interval for the ratio of the mean response (usu-
   ally AUC and Cmax) of its product to that of the
   innovator is within the limits of 0.8 to 1.25, using
   the log transformed data.

Adams also submitted the declaration of Dr. Crooks,
which indicated that one of ordinary skill in the art would
understand the term equivalent to mean within the FDA
bioequivalent range of 80 to 125%. J.A. 635. 1 The Exam-

   1     Dr. Crooks opined:
     [O]ne of ordinary skill in the art would understand
that the phrase “a Cmax in a human subject equivalent to
the Cmax obtained when the first of three doses of a stan-
dard immediate release formulation having one third the
amount of guaifenesin is dosed every four hours” refers to
the Cmax (including the normal FDA bioequivalent range
of -80%/+125%) of a standard IR guaifenesin formulation,
as exemplified by OrganidinTM NR, and that the relevant
dosage strength is 1/3 of the modified release (“MR”)
product being tested, e.g., 400 mg IR for a 1200 mg MR
product or 200 mg IR for a 600 mg MR product.
5                           ADAMS RESPIRATORY   v. PERRIGO CO

iner ultimately rejected various claims, including claim
24, under 35 U.S.C. § 103. The Board reversed, conclud-
ing that none of the rejected claims were invalid.

    In 2007, Perrigo filed an ANDA seeking to market 600
mg guaifenesin extended-release tablets before the expi-
ration of the ’252 patent. Perrigo included in its ANDA a
paragraph IV certification (a certification under 21 U.S.C.
§ 355(j)(2)(A)(vii)(IV)) asserting that the claims of the ’252
patent were invalid or would not be infringed by its
product.

    Adams sued Perrigo for infringement of the ’252 pat-
ent under 35 U.S.C. § 271(e)(2)(A), asserting that Per-
rigo’s ANDA product would infringe claims 26, 33, 34, and
39. After construing the claims (as discussed below), the
district court granted summary judgment of noninfringe-
ment with respect to all claims. Adams appeals. We have
jurisdiction under 28 U.S.C. § 1295(a)(1).

                        DISCUSSION

    This court reviews a grant of summary judgment de
novo. Immunocept, L.L.C. v. Fulbright & Jaworski,
L.L.P., 504 F.3d 1281, 1286 (Fed. Cir. 2007). “Summary
judgment is appropriate when there is no genuine issue
as to any material fact and the moving party is entitled to
judgment as a matter of law.” Id.

    We also review claim construction de novo. Cybor
Corp. v. FAS Techs., Inc., 138 F.3d 1448, 1455-56 (Fed.
Cir. 1998) (en banc). The words of a claim are generally
given their ordinary and customary meaning as under-
stood by a person of ordinary skill in the art when read in
the context of the specification and prosecution history.
ADAMS RESPIRATORY   v. PERRIGO CO                        6

See Phillips v. AWH Corp., 415 F.3d 1303, 1313 (Fed. Cir.
2005) (en banc).
                     I.   Equivalent
    The parties dispute the meaning of the term “equiva-
lent” in claim 24, from which asserted claims 26, 33, 34,
and 39 depend. Claim 24 recites:

   24. A modified release product having two por-
   tions, wherein a first portion comprises a first
   quantity of guaifenesin in an immediate release
   form which becomes fully bioavailable in the sub-
   ject’s stomach and a second portion comprises a
   second quantity of guaifenesin in a sustained re-
   lease form wherein the ratio of said first quantity
   to said second quantity provides a Cmax in a hu-
   man subject equivalent to the Cmax obtained when
   the first of three doses of a standard immediate
   release formulation having one third the amount
   of guaifenesin is dosed every four hours over a 12
   hour period and wherein said product also pro-
   vides therapeutically effective bioavailability for
   at least twelve hours after a single dose in a hu-
   man subject according to serum analysis.

’252 patent, claim 24 (emphasis added).

    The district court construed “equivalent” as “within
80% to 125% of the value with which it is being compared,
at a 90% confidence interval.” Adams, Civ. No. 1:07-CV-
993, D.I. 176 at 36 (W.D. Mich. July 24, 2009) (Claim
Construction Order). The court based its construction on
Adams’ statements during reexamination, concluding that
“Adams explicitly stated during reexamination that
‘equivalent’ meant ‘the FDA bioequivalence guidelines.’”
Id.
7                         ADAMS RESPIRATORY   v. PERRIGO CO

    On appeal, Adams challenges the requirement of a
90% confidence interval. It notes that the specification
does not require or even mention any confidence interval.
Adams argues that during reexamination, it expressly,
consistently, and repeatedly defined equivalent to mean
within the 80 to 125% range, but it never included in that
definition a 90% confidence interval. It asserts that the
90% requirement makes sense in the context of drug
approval, where the FDA is concerned with safety and
consistency. But in the context of proving infringement,
Adams argues that it must simply show that it is more
likely than not that Perrigo’s ANDA, if approved, would
permit Perrigo to market a product that infringes the ’252
patent. Adams asserts that by requiring the 90% confi-
dence interval, the court required Adams to prove that
Perrigo’s product would infringe 90% of the time.

    Perrigo argues that the inventors “expressly defined
‘equivalent’ as FDA’s bioequivalence guidelines, i.e.,
‘within 80% to 125% of the value with which it is being
compared, at a 90% confidence interval.” Perrigo Br. 20.
Perrigo asserts that the 80 to 125% range “means abso-
lutely nothing in terms of establishing bioequivalence
under FDA’s guidelines without the 90% confidence
interval, as, among other things, it is the confidence
interval itself that must fall within the 80-125% range.”
Id. at 23.

    We construe “equivalent” to require a Cmax that is 80%
to 125% of the value to which it is being compared.
Contrary to Perrigo’s assertion, Adams did not define
equivalent as meeting all of the requirements of the
FDA’s bioequivalence guidelines. When Adams referred
to the FDA guidelines in the context of defining the term
equivalent, it referred specifically to the 80 to 125%
range. J.A. 545 (“the FDA bioequivalence guidelines of 80
ADAMS RESPIRATORY   v. PERRIGO CO                        8

to 125%”); id. 626 (“FDA bioequivalent range of -80%
/+125%”); id. 635 (“FDA bioequivalent range of -80%
/+125%”). Adams never adopted or even mentioned the
90% confidence interval. The range and the confidence
interval are independent concepts. The range reflects “a
medical decision that, for most drugs, a -20%/+25% differ-
ence in the concentration of the active ingredient in blood
will not be clinically significant.” FDA Guidelines at ix.
On the other hand, the 90% confidence interval reflects
the FDA’s concern that a generic drug consistently match
the performance of the branded drug. See id. at x. Patent
infringement does not require bioequivalence, and Adams
did not import the 90% confidence interval into its claim.
Requiring a 90% confidence interval would inappropri-
ately raise the bar for establishing infringement. Adams
must show that it is more likely than not that Perrigo’s
ANDA product will have a Cmax within the 80 to 125%
range. Adams is not required to show that Perrigo’s
product will meet this requirement 9 times out of 10.
              II.   Evidence of Equivalence
    The court determined that Adams had failed to pre-
sent admissible evidence of equivalence to create a genu-
ine issue of material fact on its infringement claim.
Adams, 2010 WL 565195, at *7. To establish that Per-
rigo’s ANDA product would have a Cmax equivalent to a
standard IR product, Adams presented evidence that
Perrigo’s ANDA product was bioequivalent to Mucinex®
and that Mucinex® was bioequivalent to a standard IR
product. “Stated differently, Adams argue[d] that if A is
equivalent to B, and B is equivalent to C, then A must be
equivalent to C.” Id. The district court stated that it was
legally impermissible to show infringement by comparing
the accused product to a commercial embodiment. Id.
The court referred to “Zenith’s admonition against com-
paring the accused device to the commercial embodi-
9                         ADAMS RESPIRATORY   v. PERRIGO CO

ment.” Id. at *7 (citing Zenith Labs. v. Bristol-Meyers
Squibb Co.,19 F.3d 1418, 1423 (Fed. Cir. 1994) (“As we
have repeatedly said, it is error for a court to compare in
its infringement analysis the accused product or process
with the patentee’s commercial embodiment or other
version of the product or process; the only proper com-
parison is with the claims of the patent.”)). The court
determined that to establish infringement, equivalence
must be shown by a two-way crossover study comparing
Perrigo’s ANDA product and a standard IR product, as
required by the FDA to establish bioequivalence. 2 Id. at
*8. Adams did not do this type of study, and thus the
court concluded that it could not establish infringement
literally or under the doctrine of equivalents. Id.

    Adams asserts that it raised a genuine issue of mate-
rial fact on infringement, sufficient to preclude summary
judgment. Adams argues that there is no absolute bar
against comparing an accused product to a commercial
embodiment of the claimed invention. It asserts that
where the commercial product meets the claim limita-
tions, a comparison to that product may be used to estab-
lish infringement, citing Glaxo Wellcome, Inc. v. Andrx
Pharmaceuticals, Inc., 344 F.3d 1226, 1234 (Fed. Cir.
2003), and Glaxo Group Ltd. v. Torpharm, 153 F.3d 1366,
1373 (Fed. Cir. 1998). Adams also asserts that it does not
need to perform a two-way crossover study to establish
that the accused product has a Cmax equivalent to the Cmax
of a standard IR product. Adams seeks to rely on phar-
macokinetic (PK) data to establish infringement. It
explains that (1) Perrigo’s product has a Cmax that is
bioequivalent (within 80 to 125% at a 90% confidence

    2   In a two-way crossover study, each individual
takes each product on two separate occasions, and the
resulting Cmax values are compared.
ADAMS RESPIRATORY   v. PERRIGO CO                        10

interval) to the Cmax of Mucinex®, and (2) Mucinex® has a
Cmax that is bioequivalent (within 80 to 125% at a 90%
confidence interval) to that of Organidin®, and Adams
asserts that these two facts are probative of whether
Perrigo’s Cmax is equivalent (within 80 to 125%) to that of
Organidin®, a standard IR product. Adams further as-
serts that Mucinex® (one 1200 mg tablet) has a mean Cmax
of 103% of that of Organidin® (one 400 mg tablet taken
every four hours for twelve hours). Id. (citing ’252 patent
col.18 ll.5-9). Adams also produced evidence of the mean
Cmax value of Perrigo’s 600 mg tablets and compared it to
Mucinex® 600 mg. 3 Adams Principal Br. 39 (citing J.A.
15931). Adams argues that the actual Cmax values provide
sufficient evidence of infringement to create a genuine
issue of material fact, i.e., evidence that Perrigo’s ANDA
product will have a Cmax within 80 to 125% of the Cmax of
Organidin® and therefore infringe.

    We agree. Our case law does not contain a blanket
prohibition against comparing the accused product to a
commercial embodiment. In Zenith, the patent claimed a
crystalline product with a certain X-ray diffraction pat-
tern having 37 lines. The accused product was compared
to a commercial product that exhibited only 30 of the 37
lines. Thus, the comparison was insufficient to establish
infringement. As we later explained, “[i]n Zenith, the
patentee’s expert failed to verify that the reference sam-
ple exhibited all 37 lines of the x-ray diffraction pattern.
Thus, even assuming the comparison was correct, the
patentee failed to prove that all of the express limitations
of the claim were satisfied.” Glaxo Group, 153 F.3d at
1373. By contrast, in Glaxo Group, we accepted the
comparison of an accused product to a commercial em-

   3    This Cmax value was designated confidential by
the parties.
11                        ADAMS RESPIRATORY   v. PERRIGO CO

bodiment where the commercial embodiment met all of
the claim limitations. Id. The asserted claims character-
ized the product as having an infra-red (IR) spectrum
with 29 main peaks. Id. Glaxo’s expert compared the
spectrum of the accused product to the spectrum of a
sample that contained all 29 main peaks, and Torpharm
argued that this comparison was improper in light of
Zenith. Id. We concluded that this comparison was
sufficient to preclude summary judgment on infringement
because the comparison sample met all of the claim
limitations. Id. Perrigo is correct that here, the accused
product must meet all limitations of the claim. However,
when a commercial product meets all of the claim limita-
tions, then a comparison to that product may support a
finding of infringement.

    Perrigo argues that as a factual matter, one could not
establish infringement based on the available data.
However, Perrigo’s argument appears to assume that the
claim requires a 90% confidence interval. For example,
Perrigo’s expert testified that “one cannot properly calcu-
late the confidence interval necessary to determine
equivalence with a comparison of this kind.” Adams,
2010 WL 565195, at *8. Perrigo has not explained why,
as a factual matter, Adams’ evidence necessarily fails to
establish infringement under the correct construction of
equivalent.

    If Adams had relied on the mere fact of bioequivalence
of the two sets of products (and no PK data or Cmax val-
ues), that would not be enough to survive summary
judgment. If product A is bioequivalent to B, and B is
bioequivalent to C, then it is entirely possible that A is
not equivalent to C because bioequivalence indicates a
range of values (80 to 125%). Bioequivalence values on
the low or high end of the range would not indicate
ADAMS RESPIRATORY   v. PERRIGO CO                        12

equivalence (e.g., if A is consistently 80% of B, and B is
consistently 80% of C, then A is likely to be 64% of C).
However, here, in addition to its evidence of bioequiva-
lence, Adams presented actual PK data and Cmax values.
In light of this evidence, a fact-finder could reasonably
conclude that it is more likely than not that Perrigo’s
ANDA product will have a Cmax equivalent to that of a
standard IR product. Therefore, Adams has raised a
genuine issue of material fact on infringement under the
proper construction of the term equivalent, sufficient to
preclude summary judgment.
                    III.   Bioavailable
     Perrigo asserts that we have an alternative basis to
affirm the judgment of noninfringement. Perrigo argues
that claim 24 requires an IR portion of guaifenesin that
becomes “fully bioavailable in the subject’s stomach.”
Perrigo asserts that Adams can not establish that Per-
rigo’s ANDA product would meet this limitation either
literally or under the doctrine of equivalents.

    In its initial Claim Construction Order, the court con-
strued “fully bioavailable in the subject’s stomach” as “the
active pharmaceutical ingredient is thoroughly absorbed
in the subject’s stomach.” Claim Construction Order at
31. When granting summary judgment of noninfringe-
ment, the court concluded that a finding of infringement
based on absorption at a site other than the stomach
would entirely vitiate the claim term. Adams, 2010 WL
565195, at *11. However, the court later sua sponte
reconsidered its construction of the term “fully bioavail-
able in the subject’s stomach.” Adams, 1:07-cv-993, D.I.
314 (W.D. Mich. Mar. 3, 2010) (Reconsideration Order).
The court concluded that it erred by equating bioavailabil-
ity to absorption. Id. at 2. The court explained that the
specification “generally referred to the bioavailability in
13                        ADAMS RESPIRATORY   v. PERRIGO CO

connection with the rate of release of the drug.” Id. at 3.
The court determined that “the inventors, acting as their
own lexicographers, used the term ‘bioavailable’ to en-
compass both release and availability in the stomach for
absorption, wherever that absorption might occur.” Id.
The court thus construed “immediate release form which
becomes fully bioavailable in the subject’s stomach” as “a
form intended to rapidly release in the stomach substan-
tially all of the active pharmaceutical ingredient for
absorption.” Id. at 4. Thus, the court vacated the portion
of its earlier opinion granting summary judgment on the
basis of bioavailability. Id. at 4-5.

    On appeal, Perrigo asserts that “bioavailable” is com-
monly understood by those of skill in the art to mean
absorption. Perrigo asserts that construing bioavailabil-
ity in terms of release would require us to rewrite every
single claim of the ’252 patent by crossing out “bioavail-
able” and inserting “release.” It cites Chef America, Inc.
v. Lamb-Weston, Inc., 358 F.3d 1371, 1374-75 (Fed. Cir.
2004), in which we concluded that the court may not
rewrite unambiguous patent claim language.

    Adams asserts that bioavailable in the context of the
patent means release into the stomach, rather than
absorption into the body. Adams points out that the
specification repeatedly states that the IR portion of
guaifenesin is released in the stomach, but it never states
that it is absorbed in the stomach. Adams further notes
that the district court’s construction covers the preferred
embodiment, while Perrigo’s proposed construction would
exclude all formulations because guaifenesin is primarily
absorbed in the small intestine.

   The district court correctly construed the term “im-
mediate release form which becomes fully bioavailable in
ADAMS RESPIRATORY   v. PERRIGO CO                        14

the subject’s stomach” to mean “a form intended to rap-
idly release in the stomach substantially all of the active
pharmaceutical ingredient for absorption.” Perrigo and
Adams each proposed a reasonable construction of the
term bioavailable in the abstract. Adams' construction is
consistent with the use of this term in the specification;
Perrigo’s is not. Claim terms are not construed in a
vacuum divorced from the specification. Although the
specification never expressly defines bioavailable, it uses
the term when describing the availability of the drug for
absorption, not the actual absorption. For example, the
specification explains that “every medicament has differ-
ent solubility properties and pH dependencies which
affect its dissolution rate, and hence its bioavailability.”
’252 patent col.2 ll.51-53. It further explains that “[t]he
immediate release portion of the bi-layer tablet is formu-
lated to dissolve in aqueous media of low pH, such as that
found in the stomach, to quickly release the guaifenesin
contained within the portion. This results in rapid
bioavailability of a high concentration of guaifenesin.” Id.
col.10 ll.48-52. The specification says nothing about
absorption of guaifenesin in the stomach; in fact, it ex-
plains that “[g]uaifenesin is readily absorbed from the
intestinal tract.” Id. col.2 ll.3-4. Thus, as used in the
specification, bioavailability refers to the availability of
guaifenesin for absorption, not the subsequent actual
absorption itself.

    Adams’ construction—requiring release and availabil-
ity for absorption—covers the preferred embodiment.
Perrigo’s construction—requiring both release and actual
absorption—excludes the preferred embodiment and
essentially all guaifenesin formulations, as the specifica-
tion explains that absorption occurs in the intestinal
tract. A claim construction that excludes the preferred
embodiment “is rarely, if ever, correct and would require
15                         ADAMS RESPIRATORY   v. PERRIGO CO

highly persuasive evidentiary support.” Vitronics Corp. v.
Conceptronic Inc., 90 F.3d 1576, 1583-84 (Fed. Cir. 1996).
We therefore agree with the district court that one of skill
in the art would understand bioavailable in this invention
to require release and availability for absorption.

    Perrigo argues that even if we construe the term
bioavailable to refer to release, we should construe the
term “fully” to have its ordinary meaning: “thoroughly,”
“completely,” “entirely.” We agree that nothing in the
specification imparts any special meaning to the term
“fully.” This term should be given its plain and ordinary
meaning. In light of these constructions, the district court
properly denied summary judgment of noninfringement
on the limitation “immediate release form which becomes
fully bioavailable in the subject’s stomach.”
              IV.   Doctrine of Equivalents
    Adams argues that it should be allowed to establish
infringement of claim 34 under the doctrine of equiva-
lents. Claim 34 depends from claim 26, which depends
from claim 24. Claim 34 adds the limitation that the total
amount of guaifenesin released into the patient, AUCinf , 4
must be at least at least 3500 hr*ng/mL:

     34. The modified release product of claim 26
     [which claims the modified release product of
     claim 24 wherein the total quantity of guaifenesin
     is 600 mg] wherein the Cmax of said product is at
     least 1000 ng/mL and said product has an AUCinf
     of at least 3500 hr*ng/mL.

     4  AUC refers to the area under a plasma concentra-
tion versus time curve, i.e., the total amount of guaifene-
sin absorbed by the subject.
ADAMS RESPIRATORY   v. PERRIGO CO                        16

Perrigo’s product has four mean AUC values, all of which
are less than 3500 hr*ng/mL. The highest value calcu-
lated was 3493.38 hr*ng/mL, which is within 0.189% of
3500 hr*ng/mL.

    The district court stated that the term “at least” indi-
cates an absolute lower limit of the range, citing Quantum
Corp. v. Rodime, PLC, 65 F.3d 1577 (Fed. Cir. 1995).
Adams, 2010 WL 565195, at *11. It stated that allowing
Adams to show infringement under the doctrine of
equivalents would vitiate the 3500 hr*ng/mL claim limi-
tation. Id.

    On appeal, Adams argues that it should be allowed to
establish infringement under the doctrine of equivalents.
Adams asserts that we previously concluded that in-
fringement under the doctrine of equivalents could apply
to claims requiring a specific numeric range. Adams Br.
48 (citing Abbott Labs. v. Dey, L.P., 287 F.3d 1097, 1100,
1105-08 (Fed. Cir. 2002)). It asserts that the question is
whether Perrigo’s AUC value is insubstantially different
from the claimed AUC value, citing U.S. Philips Corp. v.
Iwasaki Co., 505 F.3d 1371 (Fed. Cir. 2007). Adams
contends that because 3494.38 hr*ng/mL is only 0.189%
different from 3500 hr*ng/mL, a genuine issue of material
fact exists with respect to whether the two values are
insubstantially different.

    Perrigo argues that because claim 34 does not use
words of approximation, Adams cannot expand this
element to ensnare Perrigo’s ANDA product. Perrigo
asserts that “[t]his Court has expressly held that the
claim term “‘at least’ means ‘as the minimum’ and there-
fore when coupled with a specific number sets forth an
absolute lower limit of a range.” Perrigo Br. 59 (citing
Quantum Corp. v. Rodime, PLC, 65 F.3d 1577 (Fed. Cir.
17                         ADAMS RESPIRATORY   v. PERRIGO CO

1995)). Perrigo also cites Lantech, Inc. v. Keip Machine
Co., 32 F.3d 542 (Fed. Cir. 1994), in which we stated that
“at least” “sets forth the minimum number of a particular
element required.”

     We previously determined that the doctrine of equiva-
lents may apply to claims containing specific numeric
ranges. See Philips, 505 F.3d at 1378 (concluding that
“resort to the doctrine of equivalents is not foreclosed with
respect to the claimed concentration range”); Abbott, 287
F.3d at 1107-08 (“The fact that a claim recites numeric
ranges does not, by itself, preclude Abbott from relying on
the doctrine of equivalents.”); Jeneric/Pentron, Inc. v.
Dillon Co., 205 F.3d 1377, 1383 (Fed. Cir. 2000) (noting
that “the district court will have the opportunity to adju-
dicate fully the merits of infringement under the doctrine
of equivalents” of a claim to composition comprising
specific weight percentages of various oxides). In Philips,
we addressed a claim requiring the presence of a halogen
“in a quantity between 10-6 and 10-4 μmol/mm3,” which we
construed as “between 1 x 10-6 and 1 x 10-4 μmol/mm3.”
505 F.3d at 1376. We rejected the argument that apply-
ing the doctrine of equivalents would vitiate this claim
limitation because “[a] reasonable juror could make a
finding that a quantity of halogen outside that [claimed]
range is insubstantially different from a quantity within
that range without ‘ignor[ing] a material limitation’ of the
patent claim.” Id. at 1379. We thus concluded that the
doctrine of equivalents was not foreclosed with respect to
the claimed range. Id. at 1380. Similarly, in Abbott, we
concluded that the doctrine of equivalents could apply to a
claim requiring a 68.8% to 94.5% by weight of a phosphol-
ipid. 287 F.3d at 1107-08. Abbott’s expert testified that
95% phospholipid “would be exactly the same as the
claimed phospholipid.” Id. at 1107. We concluded that
“[a]lthough this testimony expands the upper limit be-
ADAMS RESPIRATORY   v. PERRIGO CO                         18

yond the range literally recited by the claim, it does not
eliminate the upper limit altogether.” Id. We therefore
concluded that infringement under the doctrine of equiva-
lents would not eliminate the upper limit of the phosphol-
ipid claim. Id. “The fact that a claim recites numeric
ranges does not, by itself, preclude Abbott from relying on
the doctrine of equivalents.” Id. at 1107-08. Finally, in
Jeneric, the district court denied Jeneric’s request for a
preliminary injunction, concluding that Jeneric failed to
establish a likelihood of success on infringement under
the doctrine of equivalents. 205 F.3d at 1383. Although
we affirmed the court’s denial of Jeneric’s request for a
preliminary injunction, we indicated that the record on
infringement under the doctrine of equivalents was
premature. Id. at 1384. We noted that the accused
composition contained 0.041% of lithium oxide, which fell
outside the claimed range of 0.5% to 3%. Id. We con-
cluded that “[a] full record will show whether that differ-
ence is insubstantial.” Id. We are bound by these cases
which hold that the doctrine of equivalents can apply to a
range—a numerical limitation in a claim. The mere
existence of a numerical value or range in a claim, absent
more limiting language in the intrinsic record, does not
preclude application of the doctrine of equivalents.

    Here, the claimed value of at least 3500 hr*ng/mL is
comparable to the specific numeric ranges in Philips,
Abbott, and Generic. The recitation of a specific numeri-
cal value does not by itself foreclose the application of the
doctrine of equivalents. See Philips, 505 F.3d at 1378;
Abbott, 287 F.3d at 1107-08; Jeneric/Pentron, 205 F.3d at
1383. The addition of “at least” in this case does not
change this analysis. At least 3500 is the simplest way to
express greater than or equal to 3500, an open-ended
range.
19                         ADAMS RESPIRATORY   v. PERRIGO CO

    Perrigo contends that we have expressly held that “at
least” sets forth an absolute minimum value, citing Quan-
tum, 65 F.3d 1577, and Lantech, 32 F.3d 542. Neither of
these cases, however, require this result. In Quantum, we
determined that amending the term “at least 600 dpi” to
“at least approximately 600 dpi” improperly broadened a
claim during reexamination. 65 F.3d at 1581. We re-
jected the attempt to broaden the literal scope of the claim
through reexamination. Id. We did not address in-
fringement or discuss whether the doctrine of equivalents
could apply to the value “at least 600 tpi.” Id. Lantech,
cited by Perrego, actually supports the application of the
doctrine of equivalents. In Lantech, the district court
found that a device with one conveyor literally infringed a
claim with the term “comprising at least two conveyor
means.” 32 F.3d at 543, 546-47. We reversed, reasoning
that the claims unambiguously described two distinct
conveyors, precluding a finding a literal infringement. Id.
at 547. However, we remanded for further proceedings
regarding infringement under the doctrine of equivalents.
Id. at 548. Thus, although Quantum and Lantech both
contain broad statements about the term “at least,”
neither case supports Perrigo’s position that the term “at
least” forecloses the application of the doctrine of equiva-
lents.

    The fact that the claim does not contain words of ap-
proximation (i.e., “about at least 3500 hr*ng/mL”) does
not affect the analysis—“terms like ‘approximately’ serve
only to expand the scope of literal infringement, not to
enable application of the doctrine of equivalents.” Philips,
505 F.3d at 1379. The proper inquiry is whether the
accused value is insubstantially different from the
claimed value. Here, Adams introduced sufficient evi-
dence from which a reasonable factfinder could conclude
that an AUC value of 3493.38 hr*ng/mL is insubstantially
ADAMS RESPIRATORY   v. PERRIGO CO                       20

different from a value of 3500 hr*ng/mL. 5 Therefore, we
vacate the district court’s grant of summary judgment of
noninfringement of claim 34 on the doctrine of equiva-
lents.

                       CONCLUSION

    For the foregoing reasons, we vacate the order of the
district court and remand for further proceedings consis-
tent with this opinion.

             VACATED AND REMANDED

   5     We caution that the term 3500 hr*ng/mL should
not be read “with greater precision than the claim lan-
guage warrants.” Phillips, 505 F.3d at 1377. “In some
scientific contexts, ‘1’ represents a less precise quantity
than ‘1.0,’ and ‘1’ may encompass values such as 1.1 that
‘1.0’ may not.” Id.