Astrazeneca Ab v. Mylan Pharmaceuticals Inc. ( 2021 )

Case: 21-1729 Document: 47 Page: 1 Filed: 12/08/2021
United States Court of Appeals
for the Federal Circuit
______________________
ASTRAZENECA AB, ASTRAZENECA
PHARMACEUTICALS LP,
Plaintiffs-Appellees
v.
MYLAN PHARMACEUTICALS INC., KINDEVA
DRUG DELIVERY L.P.,
Defendants-Appellants
______________________
2021-1729
______________________
Appeal from the United States District Court for the
Northern District of West Virginia in No. 1:18-cv-00193-
IMK-RWT, 1:19-cv-00203-IMK, Judge Irene M. Keeley.
______________________
Decided: December 8, 2021
______________________
DAVID I. BERL, Williams & Connolly LLP, Washington,
DC, argued for plaintiffs-appellees. Also represented by
ARTHUR JOHN ARGALL, III, KEVIN HOAGLAND-HANSON,
JESSICA BODGER RYDSTROM, JESSICA PALMER RYEN;
DOUGLAS ALEXANDER BEHRENS, GARY RUBMAN,
CHRISTOPHER NEIL SIPES, Covington & Burling LLP,
Washington, DC.
ANDREW DUFRESNE, Perkins Coie LLP, Madison, WI,
argued for defendants-appellants. Also represented by
Case: 21-1729 Document: 47 Page: 2 Filed: 12/08/2021
2 ASTRAZENECA AB v. MYLAN PHARMS. INC.
DAVID LEE ANSTAETT, EMILY JANE GREB; DAN L. BAGATELL,
Hanover, NH; SHANNON BLOODWORTH, NATHAN K. KELLEY,
Washington, DC; VINNY LEE, Viatris Inc., Canonsburg, PA.
______________________
Before TARANTO, HUGHES, and STOLL, Circuit Judges.
Opinion for the court filed by Circuit Judge STOLL.
Opinion dissenting in part filed by Circuit Judge
TARANTO.
STOLL, Circuit Judge.
AstraZeneca AB and AstraZeneca Pharmaceuticals LP
(collectively, “AstraZeneca”) sued Mylan Pharmaceuticals
Inc. and Kindeva Drug Delivery L.P. (collectively, “Mylan”)
for infringement of all claims of U.S. Patent Nos. 7,759,328;
8,143,239; and 8,575,137 (collectively, the “asserted pa-
tents”). After claim construction, Mylan stipulated to in-
fringement and the district court entered judgment
accordingly. The district court thereafter held a bench trial
on invalidity and determined that Mylan failed to prove by
clear and convincing evidence that the asserted claims are
invalid as obvious. Mylan appeals from the stipulated
judgment of infringement and the final judgment of no in-
validity. First, Mylan challenges the district court’s claim
construction of “0.001%,” the claimed amount of the excip-
ient PVP, on which the stipulated judgment of infringe-
ment was based. For the reasons below, we disagree with
the district court’s construction and therefore vacate the
judgment of infringement and remand. Second, Mylan
challenges several factual findings underlying the district
court’s determination of nonobviousness. Because we dis-
cern no clear error in the district court’s finding that the
prior art taught away from the claimed invention, we af-
firm the determination of nonobviousness.
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ASTRAZENECA AB v. MYLAN PHARMS. INC. 3
BACKGROUND
I
All of the asserted patents are listed in the U.S Food
and Drug Administration’s publication “Approved Drug
Products with Therapeutic Equivalence Evaluations,” com-
monly known as the Orange Book, as covering Astra-
Zeneca’s Symbicort® pressurized metered-dose inhaler
(pMDI). The Symbicort® pMDI is approved for the treat-
ment of asthma and chronic obstructive pulmonary disease
(COPD). AstraZeneca has marketed a dry powder inhaler
version of Symbicort® (Symbicort® Turbuhaler) since the
early 1990s. Both the Symbicort® pMDI and the Sym-
bicort® Turbuhaler administer two active ingredients to
the lungs—formoterol, a bronchodilator that opens the air-
way, and budesonide, a steroid that reduces inflammation
in the lungs.
A dry powder inhaler, as its name suggests, is a powder
formulation that requires a patient to take a deep, fast
breath to properly inhale the medication. This type of
treatment has drawbacks for young children and elderly
patients who may have trouble taking a deep enough
breath to deliver the medication to the lower part of the
lungs, which is often done in emergency situations when a
patient is having trouble breathing, making it difficult for
the patient to take a deep breath in the first place. A for-
mulation administered using a pMDI, by contrast, uses a
propellant gas that is in liquid form when under pressure
in the pMDI device. When the patient activates the pMDI
device by pressing down on a button, the propellant causes
the medication to come out as a spray, much like an aerosol
can. This type of delivery side steps the need for a patient
to take a deep breath to get the medication fully into the
lungs—“all the work is done for [the patient] by the gas
that’s been liquefied.” J.A. 9558 (Trial Tr. 107:6–11). This
makes it easier for children and elderly patients to take the
medication.
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4 ASTRAZENECA AB v. MYLAN PHARMS. INC.
The asserted patents reflect the work of the inventors
to develop a stable formoterol/budesonide composition for
administration via a pMDI. The claims are directed to
pharmaceutical compositions comprising formoterol
fumarate dihydrate and budesonide, as well as a number
of inactive ingredients at specified concentrations. The in-
active ingredients include HFA 227 (a propellant),
PVP K25 (a formulation stabilizer), and PEG-1000 (a lub-
ricant). Claim 13 of the ’328 patent is representative of the
claims on appeal and recites:
13. A pharmaceutical composition[ 1] comprising
formoterol fumarate dihydrate, budesonide,
HFA227, PVP K25, and PEG-1000, wherein the
formoterol fumarate dihydrate is present at a con-
centration of 0.09 mg/ml, the budesonide is present
at a concentration of 2 mg/ml, the PVP K25 is pre-
sent at a concentration of 0.001% w/w, and the
PEG-1000 is present at a concentration of
0.3% w/w.
’328 patent col. 8 ll. 58–64 (emphasis added to disputed
limitation).
II
3M Company submitted Abbreviated New Drug Appli-
cation (ANDA) No. 211699 to the FDA, seeking approval to
manufacture and sell a generic version of the Symbicort®
pMDI. Certain interests in ANDA No. 211699 were later
transferred to Mylan. After those interests were trans-
ferred, Mylan notified AstraZeneca via a Paragraph IV let-
ter that it had submitted ANDA No. 211699 for a generic
1 The parties agree that the term “pharmaceutical
composition” means “suspension for therapeutic admin-
istration.” In a suspension, the active ingredient remains
as a solid in the liquid, whereas in a solution, the active
ingredient would dissolve in the liquid.
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ASTRAZENECA AB v. MYLAN PHARMS. INC. 5
version of the Symbicort® pMDI (Mylan’s ANDA Product).
Mylan’s Paragraph IV letter argued that the asserted pa-
tents are invalid, unenforceable, and/or not infringed. See
21 U.S.C. § 355(j)(2)(A)(vii)(IV). On October 12, 2018,
AstraZeneca sued Mylan for infringement under 35 U.S.C.
§ 271(e)(2) based on Mylan’s submission of ANDA
No. 211699 seeking approval for its ANDA Product.
Not long before trial, the district court held a claim con-
struction hearing to settle a late-arising dispute between
the parties concerning the construction of “0.001%,” the
claimed concentration of PVP. Although the parties had
originally agreed that no construction of this term was nec-
essary, the dispute became apparent during briefing on
Mylan’s motion for partial summary judgment of nonin-
fringement under the doctrine of equivalents. The district
court construed “0.001%” according to its “plain and ordi-
nary meaning, that is, expressed with one significant
digit.” AstraZeneca AB v. Mylan Pharms. Inc., Civil Action
No. 1:18CV193 c/w 1:19CV203, 2020 WL 4670401, at *7
(N.D. W. Va. Aug. 12, 2020). Mylan thereafter stipulated
to infringement of certain claims of the asserted patents
and the district court entered final judgment of infringe-
ment.
The district court then held a bench trial on validity of
the asserted claims. The district court determined that
Mylan failed to prove by clear and convincing evidence that
the asserted claims would have been obvious in view of the
prior art and entered a final judgment of no invalidity.
AstraZeneca AB v. Mylan Pharms. Inc., 522 F. Supp. 3d
200 (N.D. W. Va. Mar. 2, 2021) (Judgment Op.). The dis-
trict court’s ultimate determination was based on several
underlying factual findings, including a finding that one of
the prior art references Mylan relied on in its obviousness
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6 ASTRAZENECA AB v. MYLAN PHARMS. INC.
combination, Rogueda, 2 taught away from the claimed in-
vention. Id. at 219–20.
Mylan appeals. We have jurisdiction under 28 U.S.C.
§ 1295(a)(1).
DISCUSSION
On appeal, Mylan challenges the district court’s con-
struction of “0.001%,” the claimed concentration of PVP.
Mylan also challenges several of the factual findings un-
derlying the district court’s nonobviousness determination,
including its finding that the prior art taught away from
the claimed invention. We address each issue in turn.
I
We begin with Mylan’s challenge to the district court’s
construction of “0.001%,” the claimed concentration of PVP.
Our review of the district court’s claim construction is de
novo where, as here, it is decided only on the intrinsic evi-
dence. Teva Pharms. USA, Inc. v. Sandoz, Inc., 574 U.S.
318, 331 (2015).
The question here is whether the concentration of PVP
being “0.001%” means 0.001% within one significant fig-
ure—encompassing a concentration of PVP in the range of
0.0005% to 0.0014%, as AstraZeneca contends and as the
district court construed this term—or it has a narrower
meaning in view of the specification and the prosecution
history—precisely 0.001% w/w PVP with only “minor vari-
ations,” as Mylan contends. This is a close call. Ultimately,
for the reasons below, we conclude that Mylan’s proposed
construction, albeit articulated differently, is correct be-
cause it “most naturally aligns with the patent’s descrip-
tion of the invention,” as further informed by the
prosecution history. Takeda Pharm. Co. Ltd. v. Zydus
Pharms. USA, Inc., 743 F.3d 1359, 1363 (Fed. Cir. 2014)
2 PCT Pub. No. WO 2002/03958.
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ASTRAZENECA AB v. MYLAN PHARMS. INC. 7
(quoting Renishaw PLC v. Marposs Societa’ per Azioni,
158 F.3d 1243, 1250 (Fed. Cir. 1998)). We therefore con-
strue “0.001%” as that precise number, with only minor
variations, i.e., 0.00095% to 0.00104%.
We begin, as we must, with the claim language itself.
The parties agree that the term “0.001%,” being expressed
using only a single significant figure, would ordinarily, as
an abstract number on a page, encompass a range from
0.0005% to 0.0014%. Oral Arg. at 14:18–15:15,
21:48–22:22, http://oralarguments.cafc.uscourts.gov/de-
fault.aspx?fl=21-1729_08312021.mp3. This is a standard
scientific convention, and numbers falling within that
range would typically be rounded up or down to 0.001%.
AstraZeneca argues that this “ordinary meaning” controls
absent lexicography or disclaimer. Appellees’ Br. 39 (first
citing Toshiba Corp. v. Imation Corp., 681 F.3d 1358, 1369
(Fed. Cir. 2012); and then citing Thorner v. Sony Comput.
Ent. Am., 669 F.3d 1362, 1365–67 (Fed. Cir. 2012)). We
disagree, as this narrow view of our precedent would ne-
cessitate adopting an acontextual construction of this dis-
puted claim term, improperly isolating the numerical term
from the more complete term “PVP K25 is present at a con-
centration of 0.001% w/w,” as well as the specification and
prosecution history descriptions of PVP concentrations.
Indeed, as we have explained, the “ordinary meaning
of a claim term is not ‘the meaning of the term in the ab-
stract.’ . . . Instead, ‘the “ordinary meaning”’ of a claim
term is its meaning to the ordinary artisan after reading
the entire patent.’” Eon Corp. IP Holdings v. Silver Spring
Networks, 815 F.3d 1314, 1320 (Fed. Cir. 2016) (quoting
Phillips v. AWH Corp., 415 F.3d 1303, 1321 (Fed. Cir.
2005) (en banc)); see also Trs. of Columbia Univ. v. Syman-
tec Corp., 811 F.3d 1359, 1363 (Fed. Cir. 2016) (“The only
meaning that matters in claim construction is the meaning
in the context of the patent.”). Consistent with Phillips,
therefore, we must read the claims in view of both the writ-
ten description and prosecution history. 415 F.3d at 1315,
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8 ASTRAZENECA AB v. MYLAN PHARMS. INC.
1317; Eon, 815 F.3d at 1320 (“A party is . . . ‘not entitled to
a claim construction divorced from the context of the writ-
ten description and prosecution history.’” (quoting Nystrom
v. TREX Co., 424 F.3d 1136, 1144–45 (Fed. Cir. 2005))); Ul-
timate Pointer, L.L.C. v. Nintendo Co., 816 F.3d 816,
823–24 (Fed. Cir. 2016) (rejecting patentee’s proposed “or-
dinary meaning” construction because it was divorced from
“the repeated direct-pointing description and indirect-
pointing criticism in the specification”). As we explain in
detail below, both the written description and prosecution
history place considerable emphasis on the stability of the
claimed formulations, i.e., formulations with 0.001% w/w
PVP, compared to formulations with slightly higher or
slightly lower concentrations of PVP, including for exam-
ple, 0.0005% w/w. Thus, taken as a whole, the intrinsic
record supports a narrower construction of 0.001% to re-
flect that term’s application to the PVP concentration in
particular, and the testing evidence in the written descrip-
tion and prosecution history showing that very minor dif-
ferences in the concentration of PVP—down to the ten-
thousandth of a percentage (fourth decimal place)—impact
stability.
We turn first to the written description—which “is al-
ways highly relevant to the claim construction analysis”
and indeed is often “the single best guide to the meaning of
a disputed term.” Phillips, 415 F.3d at 1315 (quoting
Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582
(Fed. Cir. 1996)). According to the written description,
“[s]tability is one of the most important factors which de-
termines whether a compound or a mixture of compounds
can be developed into a therapeutically useful pharmaceu-
tical product.” ’328 patent col. 1 ll. 21–24. The inventors
discovered that “certain HFA formulations comprising for-
moterol and budesonide together with” PVP and PEG “ex-
hibit excellent physical suspension stability.” Id. at col. 1
ll. 32–35. Specifically, the written description explains
that “[t]he concentration of PVP (0.001% w/w) used in this
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ASTRAZENECA AB v. MYLAN PHARMS. INC. 9
formulation has been found to give consistently stable for-
mulations over the required dose range.” Id. at col. 2
ll. 17–21. And the written description repeatedly touts the
superior stability of formulations with 0.001% w/w PVP.
See, e.g., id. at col. 6 ll. 30–31 (“formulations with 0.001%
w/w PVP gave the best suspension stability overall”),
ll. 40–42 (“the formulation containing 0.001% PVP is the
most stable”), ll. 49–51 (“the most stable formulation is . . .
with 0.001% w/w PVP”), ll. 52–54 (“the suspension with
0.001% w/w PVP is the most stable”).
The inventors’ conclusion that formulations with
0.001% w/w PVP are the “most stable” is evidenced by the
data they provided in the specification. As part of their ex-
periments, the inventors tested formulations including
PVP at concentrations of 0.0001%, 0.0005%, 0.001%,
0.01%, 0.03%, and 0.05% w/w and characterized each for-
mulation for stability. Figures 3 and 5 provide stability re-
sults for 80 µg budesonide formulations, which corresponds
to the claimed 2 mg/mL budesonide concentration. Figure
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10 ASTRAZENECA AB v. MYLAN PHARMS. INC.
3 provides stability results for these formulations based on
OSCAR 3 data:
Id. Fig. 3. In Figure 3, “the bottom line, . . . with low trans-
mission readings, clearly shows that the formulation con-
taining 0.001% PVP is the most stable.” Id. at col. 6
ll. 40–42. As shown above, the formulation with 0.001%
w/w PVP has a lower transmission measurement than the
formulation with 0.0005% w/w PVP, meaning the formula-
tion with 0.001% w/w PVP is more stable than the 0.0005%
w/w PVP formulation. The Turbiscan4 data provided in
Figure 5 is even more significant, showing that the
3 OSCAR refers to “Optical Suspension Characteri-
zation” equipment, which “utili[z]es changes in light trans-
mission with time, to characteri[z]e a pre-agitated
suspension formulation.” Id. col. 3 ll. 10–16.
4 Turbiscan analyzers are “concentrated dispersion
and emulsion stability and instability analy[z]ers” that
characterize sample “homogeneity, concentration[,] and
mean particle diameter.” Id. at col. 3 ll. 48–50, ll. 62–65.
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ASTRAZENECA AB v. MYLAN PHARMS. INC. 11
formulation comprising 0.0005% w/w PVP (second from the
top) was one of the least stable formulations tested:
Id. Fig. 5. Consistent with the OSCAR data, “the suspen-
sion with 0.001% w/w PVP is the most stable (bottom bold
line)” of the formulations tested. Id. at col. 6 ll. 52–54.
Based on the written description, it is clear that the in-
ventors understood that a formulation comprising
0.001% w/w PVP is more stable than (and indeed, different
from) a formulation with even a slight difference in the con-
centration of PVP, e.g., a formulation with 0.0005% w/w
PVP. This data leaves little room for doubt that slight
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12 ASTRAZENECA AB v. MYLAN PHARMS. INC.
differences in the concentration of PVP—down to the ten-
thousandth of a percentage (fourth decimal place)—mat-
ters for stability in the context of this invention. Thus,
while an acontextual read of the term 0.001% might encom-
pass amounts of an excipient or active ingredient between
0.0005% and 0.0014%, the written description suggests
that the claimed formulations with 0.001% w/w PVP were
intended to be more exact. The construction we adopt to-
day, which allows for only minor variations in the PVP con-
centration at the fourth decimal place (0.00095% to
0.00104%), reflects the level of exactness the inventors
used in the written description in concluding that
0.001% w/w PVP is the most stable formulation compared
to formulations with slightly more or less PVP.
This construction is also supported by the prosecution
history, which “often inform[s] the meaning of the claim
language by demonstrating how the inventor understood
the invention.” Phillips, 415 F.3d at 1317. The original
version of claim 2 that was filed in the application that led
to the ’328 patent recited a PVP concentration “from about
0.0005 to about 0.05 %w/w.” J.A. 15919. The Examiner
rejected the claims as obvious over two prior art references
of record, explaining that “one would have been expected to
determine the optimum amount of PVP.” J.A. 16205. The
inventors then amended the claims, deleting the PVP
range limitation from claim 2 in its entirety and amending
claim 1 to recite that the “PVP is present in an amount of
0.001% w/w.” J.A. 16213. This amendment narrowed the
scope of claim 1, which previously did not recite any PVP
concentration, by limiting the amount of PVP to
0.001% w/w without using the “about” qualifier that had
been previously included in claim 2. The inventors argued,
in support of their proposed claim amendment, that they
had “surprisingly demonstrated that 0.001% w/w PVP gave
the best suspension stability when compared to a range of
PVP concentrations from 0.0001% to 0.05% w/w.”
J.A. 16222.
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ASTRAZENECA AB v. MYLAN PHARMS. INC. 13
The Examiner once again rejected the claims, stating
that it was “imperative” for the inventors to show “critical-
ity of the invention comprising 0.001% w/w PVP by testing
the invention comprising slightly more and less than
0.001% w/w PVP.” J.A. 16307 (emphasis added); id. (“Ap-
plicant fails to provide examples, which show the criticality
of 0.001% w/w PVP versus the invention where the PVP
concentration is slightly greater or less than 0.001% w/w
PVP.”). In response, the inventors asserted that the “criti-
cality of 0.001% w/w PVP in a formulation containing
2 mg/ml budesonide” was illustrated by the data provided
in the written description—specifically, Figures 3 and 5—
which compared the stability of a 0.001% w/w PVP formu-
lation to formulations with 0.0001%, 0.0005%, 0.01%,
0.03%, and 0.05% w/w PVP. J.A. 16326; see also ’328 pa-
tent Figs. 3, 5. The inventors further claimed that
formulations with higher or lower concentrations of
PVP were less able to maintain a good suspension
of a 2 mg/ml budesonide formulation over time.
Nothing in the prior art would have led one to ex-
pect that 0.001% w/w PVP would provide this ben-
efit in a formulation containing 2 mg/ml
budesonide (or any other concentration of
budesonide, for that matter).
J.A. 16326–27 (emphasis added).
At this time, the inventors once again sought to obtain
claims reciting a variety of different PVP concentrations,
including “0.001% w/w to 0.01% w/w” PVP (claim 1),
“0.0001% to 0.001% w/w” PVP (claim 18), and “0.0001%,
0.0005%, or 0.001% w/w” PVP (claim 23). J.A. 16319–21.
For claims specifically directed to 2 mg/mL budesonide for-
mulations (the claimed concentration of budesonide in the
asserted claims), however, the inventors only sought
claims specifying “0.001% w/w” PVP, J.A. 16320 (claim 16),
consistent with their assertion that 0.001% w/w PVP was
critical for stability of a 2 mg/mL budesonide formulation.
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14 ASTRAZENECA AB v. MYLAN PHARMS. INC.
After the Examiner rejected the claims because they were
“not commensurate in scope with the unexpected results”
that the inventors presented, J.A. 16447, AstraZeneca can-
celed these claims, narrowed a previously presented claim
to recite a PVP concentration of 0.001% w/w, J.A. 16455
(claim 25), and introduced several new claims that, like-
wise, recited a PVP concentration of exactly 0.001% w/w,
J.A. 16456–57 (claims 45–48) including formulations with
2 mg/mL budesonide, id. (claim 46). The Examiner ulti-
mately allowed the claims, stating in the reasons for allow-
ance that the “results provided in the specification . . . for
the stability of the instant composition overcomes any ob-
viousness type rejection that could have been deduced
from” the prior art of record. J.A. 16479.
Over the course of the prosecution history, the inven-
tors narrowed the claimed concentration of PVP to
0.001% w/w from a broader range without using the quali-
fier “about.” The inventors did this not just once but mul-
tiple times, each time emphasizing to the Examiner that
0.001% w/w PVP—not concentrations slightly more or less
than 0.001% w/w—was critical to stability of the claimed
2 mg/mL budesonide formulation. And, importantly, the
prosecution history shows that the inventors knew how to
claim ranges or describe numbers with approximation, e.g.,
by using the term “about” to qualify the amount of PVP
claimed. Yet, in the asserted claims, the inventors chose to
claim exactly 0.001% w/w PVP. Under our precedent, this
provides further support for construing 0.001% narrowly.
See, e.g., Takeda, 743 F.3d at 1365 (rejecting district court’s
construction of “400 µm” that permitted a 10% margin of
error in the particle size measurement where the intrinsic
record demonstrated the inventors knew to use the term
“about” in claim language to allow for margin of error in
numerical measurements but chose not to use “about” in
the disputed claim term). Indeed, the public should rea-
sonably be able to rely on these amendments and
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ASTRAZENECA AB v. MYLAN PHARMS. INC. 15
arguments in the prosecution history to inform the scope of
the claimed invention.
We recognize that, as the parties agreed, there needs
to be some room for experimental error in the PVP concen-
tration. The construction we adopt today reflects a margin
of error that is best supported by the intrinsic record. This
construction, which allows for only minor variations in the
PVP concentration at the fourth decimal place, represent-
ing a 5% variation in the PVP concentration—as opposed
to AstraZeneca’s, which would allow up to a 50% variation
in the PVP concentration—more accurately reflects the
level of exactness the inventors used in the written descrip-
tion in concluding that 0.001% w/w PVP is the most stable
formulation, as well as the arguments and amendments in
the prosecution history asserting that 0.001% w/w PVP is
“critical” compared to formulations with slightly more or
less PVP.
We are not persuaded by AstraZeneca’s arguments to
the contrary. AstraZeneca first argues that the written de-
scription and prosecution history only ever express the
PVP concentration with one significant figure, whereas the
concentration of some of the other ingredients, e.g.,
budesonide, are expressed using additional significant fig-
ures. Appellees’ Br. 34–35; see also ’328 patent col. 7
ll. 62–65. Thus, according to AstraZeneca, adopting
Mylan’s proposed construction would effectively make the
concentration of PVP more precise than the inventors in-
tended, because the inventors could have used additional
significant figures to reflect the need for greater precision
with the concentration of PVP. In light of the specification
and prosecution history, we disagree. Though true that the
inventors expressed the concentration of PVP using a sin-
gle significant figure throughout the written description,
this fact does not dictate the result that AstraZeneca seeks.
As explained above, the written description repeatedly dif-
ferentiates between formulations comprising 0.001% w/w
PVP and, e.g., those comprising 0.0005% w/w PVP,
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16 ASTRAZENECA AB v. MYLAN PHARMS. INC.
emphasizing that the level of precision required in the con-
text of this invention with respect to the concentration of
PVP is down to the ten-thousandth of a percentage. Aztra-
Zeneca’s proposed construction ignores that context.
AstraZeneca also argues that Mylan’s proposed con-
struction is an impermissible attempt to limit the scope of
the claims to the preferred embodiment. Appellees’
Br. 40–41. We are not persuaded. We are, of course, mind-
ful not to limit claims to their preferred embodiments. But
AstraZeneca’s proposed construction would read on two
distinct formulations described in the written descrip-
tion—namely, a formulation comprising 0.0005% w/w PVP
and one comprising 0.001% w/w PVP. Yet, the inventors
chose to claim only one of these formulations, which sup-
ports construing the claims as limited to that formulation.
Second, we have explained that “during prosecution, an ap-
plicant may have cancelled pending claims but not
amended the specification to delete disclosure relevant
only to the cancelled claims. In such cases, unasserted or
cancelled claims may provide ‘probative evidence’ that an
embodiment is not within the scope of an asserted claim.”
PSN Ill., LLC v. Ivoclar Vivadent, Inc., 525 F.3d 1159, 1166
(Fed. Cir. 2008). Such is the case here. The inventors pre-
viously included claims covering alternative embodiments
described in the written description—including claims to
formulations with 0.0005% w/w PVP. That the inventors
later canceled these claims provides further evidence that
formulations with 0.0005% w/w PVP are not within the
scope of the claims at issue here.
Nor do we agree with AstraZeneca that the prosecution
history is irrelevant because there is no clear and unmis-
takable disavowal of claim scope. Appellees’ Br. 39, 45–46.
We have stated that “[a]ny explanation, elaboration, or
qualification presented by the inventor during patent ex-
amination is relevant, for the role of claim construction is
to ‘capture the scope of the actual invention’ that is dis-
closed, described, and patented.” Fenner Invs., Ltd.
Case: 21-1729 Document: 47 Page: 17 Filed: 12/08/2021
ASTRAZENECA AB v. MYLAN PHARMS. INC. 17
v. Cellco P’ship, 778 F.3d 1320, 1323 (Fed. Cir. 2015) (quot-
ing Retractable Techs., Inc. v. Becton, Dickinson & Co.,
653 F.3d 1296, 1305 (Fed. Cir. 2011)). “Accordingly, even
in the absence of a clear and unmistakable disavowal, . . .
the prosecution history can be evaluated to determine how
a person of ordinary skill would understand a given claim
term.” Aptalis Pharmatech, Inc. v. Apotex Inc.,
718 F. App’x 965, 971 (Fed. Cir. 2018).
* * *
Although the term “0.001%” without any broader con-
text might indicate a range from 0.0005% to 0.0014%, here,
in the context of the concentration of PVP, in light of the
testing data in the specification and the amendments and
arguments in the prosecution history, we conclude that the
construction of this term most consistent with the intrinsic
evidence is not so broad. Accordingly, we construe
“0.001%” as that precise number, with only minor varia-
tions, i.e., 0.00095% to 0.00104%. We therefore vacate the
stipulated judgment of infringement and remand for the
district court to find in the first instance whether Mylan’s
ANDA Product infringes the asserted claims under the
proper claim construction.
II
We turn next to Mylan’s challenge to the district court’s
nonobviousness determination. Following a bench trial, we
review the district court’s legal determinations de novo and
its factual findings for clear error. See Merck Sharp &
Dohme Corp. v. Hospira Inc., 874 F.3d 724, 728 (Fed. Cir.
2017). “A factual finding is only clearly erroneous if . . . we
are left with the definite and firm conviction that a mistake
has been made.” Id. “Obviousness is a question of law
based on underlying findings of fact.” OSI Pharms., LLC
v. Apotex Inc., 939 F.3d 1375, 1382 (Fed. Cir. 2019) (quot-
ing In re Kubin, 561 F.3d 1351, 1355 (Fed. Cir. 2009)).
“What the prior art teaches, whether a person of ordinary
skill in the art would have been motivated to combine
Case: 21-1729 Document: 47 Page: 18 Filed: 12/08/2021
18 ASTRAZENECA AB v. MYLAN PHARMS. INC.
references, and whether a reference teaches away from the
claimed invention are questions of fact.” Meiresonne
v. Google, Inc., 849 F.3d 1379, 1382 (Fed. Cir. 2017) (citing
Apple Inc. v. Samsung Elecs. Co., 839 F.3d 1034, 1047–48
(Fed. Cir. 2016) (en banc)).
Mylan argues on appeal that several factual findings
underlying the district court’s nonobviousness determina-
tion are clearly erroneous, including its finding that the
prior art reference Rogueda taught away from the claimed
invention. Because we discern no clear error in the district
court’s teaching away finding, which on its own is sufficient
to sustain the nonobviousness determination, we affirm.
Rogueda is a PCT publication that is directed to “stable
pharmaceutical aerosol formulation[s] intended for inhala-
tion.” Rogueda, Abstract. Rogueda’s novel formulations
are suspensions “contain[ing] an active substance, an aer-
osol propellant, a polar fluorinated molecule and an excip-
ient,” with the “preferred propellant” being “HFA 134a or
HFA 227 or a mixture thereof.” Id. In the course of devel-
oping these novel formulations, Rogueda prepared certain
control formulations to compare its novel formulations to.
Mylan relied on two of these control formulations—specifi-
cally, control formulations 3 and 9—as rendering obvious
the claimed formulations. The table below summarizes the
components of the control formulations as well as repre-
sentative claim 13 of the ’328 patent.
Case: 21-1729 Document: 47 Page: 19 Filed: 12/08/2021
ASTRAZENECA AB v. MYLAN PHARMS. INC. 19
Component Claim 13 Control 3 Control 9
Formoterol 0.0167%
Fumarate 0.09 mg/mL w/w (0.16 No
Dihydrate mg/mL)
0.259% w/w
Budesonide 2 mg/mL No (2.59
mg/mL)
PVP K25 0.001% w/w 0.001% w/w 0.001% w/w
PEG-1000 0.3% w/w 0.1% w/w 0.3% w/w
HFA227 Yes Yes Yes
See id. at p. 24 l. 16–p. 25 l. 5, p. 25 ll. 29–33; ’328 patent
col. 8 ll. 58–64.
Rogueda conducted a number of studies to characterize
its novel formulations as compared with the control formu-
lations. These tests included monitoring the extent of drug
adhesion to the dispensing device, the extent to which the
formulations creamed (which refers to whether the active
ingredient floated out of the suspension, much like curdled
milk), and an evaluation of the particle size. With respect
to adhesion to the dispensing device, Rogueda concluded
that both the budesonide and formoterol novel formula-
tions exhibited a “drastic[]” reduction in the amount of
drug adhesion compared to their controls (controls 9 and 3,
respectively). Rogueda p. 27 ll. 25–38. AstraZeneca’s ex-
pert Dr. Paul M. Young testified that a skilled artisan look-
ing at the adhesion test results in Rogueda would conclude
that the control formulations “were not suitable” and
“clearly don’t work.” J.A. 10152–53 (Trial Tr. 684:3–6,
685:8–14); see also J.A. 10148–54 (Trial Tr. 680:1–686:21).
Dr. Young also testified that a skilled artisan, therefore,
would not have used the control formulations as a starting
Case: 21-1729 Document: 47 Page: 20 Filed: 12/08/2021
20 ASTRAZENECA AB v. MYLAN PHARMS. INC.
point for optimization or experimentation given the poor
adhesion results reported in Rogueda. J.A. 10154 (Trial.
Tr. 686:18–21).
With respect to the particle size, Rogueda concluded
that the novel formulations had a narrower size distribu-
tion and smaller average particle size than the control for-
mulations, noting that the particles in the novel
formulations existed as “individual particles and not as
clusters.” Rogueda p. 30 ll. 9–12; see also id. at pp. 29–31.
Dr. Young testified that, for the novel formulations, the
particle size reported by Rogueda “is a suitable size for in-
halation.” J.A. 10162 (Trial Tr. 694:17–18). By contrast,
for the control formulations, Dr. Young explained that the
particle size reported by Rogueda was significantly larger,
indicating that there were “huge agglomerates . . . floating
around” in the formulations, rendering them “completely
unsuitable.” J.A. 10162–63 (Trial Tr. 694:24–695:8). Con-
sidering Rogueda’s data in its entirety, Dr. Young testified
that a skilled artisan would consider the control formula-
tions “just unsuitable,” and therefore would not have any
reason to use these control formulations as a basis for ex-
perimentation. J.A. 10164 (Trial Tr. 696:7–18).
Under this court’s precedent, a prior art reference is
said to teach away from the claimed invention if a skilled
artisan “‘upon reading the reference, would be discouraged
from following the path set out in the reference, or would
be led in a direction divergent from the path that was
taken’ in the claim.” Meiresonne, 849 F.3d at 1382 (quoting
Galderma Lab’ys, L.P. v. Tolmar, Inc., 737 F.3d 731, 738
(Fed. Cir. 2013)). And a “reference that properly teaches
away can preclude a determination that the reference ren-
ders a claim obvious.” In re Mouttet, 686 F.3d 1322, 1333
(Fed. Cir. 2012). The district court, applying this standard,
credited Dr. Young’s testimony discussed above in finding
that a skilled artisan “would have been discouraged from
incorporating the formulations in Controls 3 and 9” be-
cause “the data cut against the very goal a [skilled artisan]
Case: 21-1729 Document: 47 Page: 21 Filed: 12/08/2021
ASTRAZENECA AB v. MYLAN PHARMS. INC. 21
would have been trying to achieve—a stable product with
a consistent dose.” Judgment Op., 522 F. Supp. 3d
at 219–20. The district court concluded, therefore, that
“Rogueda teaches away and does not render the claims ob-
vious.” Id. at 220. We discern no clear error in this finding
and therefore affirm the district court’s determination of
nonobviousness.
We are unpersuaded by Mylan’s arguments that
Rogueda does not teach away. Mylan first argues that the
district court’s finding is contrary to this court’s precedent,
which holds that a reference that “‘merely expresses a gen-
eral preference for an alternative invention but does not
criticize, discredit, or otherwise discourage investigation
into’ the claimed invention does not teach away.”
Meiresonne, 849 F.3d at 1382 (quoting Galderma, 737 F.3d
at 738). Specifically, Mylan points to a one-off sentence in
the district court’s opinion—stating that “Rogueda did not
necessarily disparage the formulations in Controls 3
and 9,” Judgment Op., 522 F. Supp. 3d at 219–20—as sup-
porting the notion that Rogueda merely expresses a prefer-
ence for the novel formulations over the control
formulations. Appellants’ Br. 57. We disagree. Although
true Rogueda itself does not contain explicit disparagement
of the control formulations, the district court properly re-
lied on expert testimony regarding how a skilled artisan
would interpret the data in Rogueda to find implicit dispar-
agement. Indeed, whether a reference teaches away must
be determined from the viewpoint of a skilled artisan. And,
as discussed above, the district court credited Dr. Young’s
testimony that a person of ordinary skill in the art would
have known that the control formulations were unsuitable
for further experimentation, thus “discouraging investiga-
tion into” these formulations.
Mylan’s remaining arguments amount to no more than
asking us to reweigh the evidence on appeal. For instance,
Mylan argues that the control formulations “were stable
during the critical seconds after shaking.” Appellants’
Case: 21-1729 Document: 47 Page: 22 Filed: 12/08/2021
22 ASTRAZENECA AB v. MYLAN PHARMS. INC.
Br. 59. It also argues that there were known solutions to
can adhesion and particle aggregation and, therefore, the
problems Dr. Young discussed with respect to the control
formulations were not real problems. Id. at 60–61. The
district court, sitting as fact finder, considered this testi-
mony and nevertheless found that a skilled artisan would
have been discouraged from using Rogueda’s control for-
mulations as a basis for further experimentation. Absent
clear error, we will not disturb the district court’s weighing
of the evidence on appeal.
CONCLUSION
We have considered the parties’ remaining arguments
and find them unpersuasive. Because we conclude that the
district court erred in its claim construction, we vacate the
stipulated judgment of infringement and remand for fur-
ther proceedings on infringement consistent with our claim
construction. We also conclude that the district court did
not clearly err in finding the prior art taught away from the
claimed invention and therefore affirm the judgment of no
invalidity.
AFFIRMED-IN-PART, VACATED-IN-PART, AND
REMANDED
COSTS
No costs.
Case: 21-1729 Document: 47 Page: 23 Filed: 12/08/2021
United States Court of Appeals
for the Federal Circuit
______________________
ASTRAZENECA AB, ASTRAZENECA
PHARMACEUTICALS LP,
Plaintiffs-Appellees
v.
MYLAN PHARMACEUTICALS INC., KINDEVA
DRUG DELIVERY L.P.,
Defendants-Appellants
______________________
2021-1729
______________________
Appeal from the United States District Court for the
Northern District of West Virginia in No. 1:18-cv-00193-
IMK-RWT, 1:19-cv-00203-IMK, Judge Irene M. Keeley.
______________________
TARANTO, Circuit Judge, dissenting in part.
I join the Background section of the court’s opinion and
part II of the Discussion section, which affirms the district
court’s rejection of Mylan’s obviousness challenge. But I do
not join part I of the Discussion section, which addresses a
dispute over claim construction pertinent to the judgment
of infringement. In that section, the court holds that, in
claims reciting a concentration of “0.001% w/w” (weight per
weight) of a particular suspension agent in the claimed
composition, the term “0.001%” should not be construed (as
the district court construed it) to have its conventional sig-
nificant-figure meaning, but, instead, to mean “that precise
Case: 21-1729 Document: 47 Page: 24 Filed: 12/08/2021
2 ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC.
number, with only minor variations”—which the court then
equates to what the term would mean if it were rewritten
as “0.0010%” (adding an extra significant figure). I respect-
fully dissent from that holding.
In my view, “0.001%” should be construed to have its
significant-figure meaning, i.e., the interval 0.0005% to
0.0014%, as the district court held, with only one possible
interval-shrinking change that cannot matter in this case.
The possible change is to exclude those concentration levels
which are in the overlap area between the significant-fig-
ure interval of “0.001%” and the significant-figure interval
of “0.0005%” (i.e., 0.00045% to 0.00054%), another concen-
tration level addressed separately in the patent’s testing
description. If that exclusion were adopted, the language
as construed would cover the interval 0.00055% to
0.0014%. But we need not resolve whether the exclusion of
the overlap of the two significant-figure intervals is actu-
ally a proper part of the construction, because a finding of
infringement is compelled regardless.
I
A
AstraZeneca owns U.S. Patent Nos. 7,759,328,
8,143,239, and 8,575,137, which share a specification, and
AstraZeneca was the assignee during prosecution. The pa-
tents describe and claim a suspension composition in a
pressurized metered dose inhaler (pMDI) for the treatment
of asthma and other respiratory diseases. ’328 patent, col.
1, lines 14–35; id., col. 8, line 16, through col. 10, line 5.
The composition, characterized by five specified compo-
nents, contains two active ingredients (budesonide and for-
moterol), a propellant (an HFA, i.e., heptafluoropropane),
and two excipients (PVP, i.e., polyvinylpyrrolidone; and
PEG, i.e., polyethylene glycol). Id., col. 8, lines 17–26. The
’328 patent claims particular grades of the two excipients
(PVP K25 and PEG-1000) by concentration in units of
weight percent (% w/w). The PVP K25 functions as a
Case: 21-1729 Document: 47 Page: 25 Filed: 12/08/2021
ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC. 3
suspension agent. Claim 13 of the ’328 patent, which all
parties have treated as representative for claim-construc-
tion purposes, reads:
A pharmaceutical composition comprising for-
moterol fumarate dihydrate, budesonide, HFA 227,
PVP K25, and PEG-1000,
wherein the formoterol fumarate dihydrate is
present at a concentration of 0.09 mg/ml,
the budesonide is present at a concentration of
2 mg/ml,
the PVP K25 is present at a concentration of
0.001% w/w,
and the PEG-1000 is present at a concentration
of 0.3% w/w.
Id., col. 8, lines 58–64.
The limitation in dispute in the representative claim
states the concentration of the PVP excipient: “the PVP
K25 is present at a concentration of 0.001% w/w.” Id., col
8, lines 62–63. The ’137 and ’239 patents claim concentra-
tion ranges of excipients, and only some claims claim a par-
ticular grade of each excipient. Both require a range
defined in part by “0.001%”: “the PVP is present at a con-
centration in the range of 0.001% to 0.01% w/w.” See ’137
patent, col. 8, lines 22–23; ’239 patent, col. 9, lines 1–2.
The specification discusses testing of the suspension
stability of various five-component formulations. See ’328
patent, col. 5, line 28, through col. 6, line 28. The specifi-
cation describes formulations with varying PVP concentra-
tions and those formulations’ assessed stability. Id., col. 5,
line 60, through col. 6, line 31. The six concentrations of
PVP tested are reported as “0.0001%,” “0.0005%,”
“0.001%,” “0.01%,” “0.03%,” and “0.05%” w/w. Id. The spec-
ification states that several of those formulations were
“considered excellent,” id., col. 6, line 29, and formulations
Case: 21-1729 Document: 47 Page: 26 Filed: 12/08/2021
4 ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC.
with “0.001%” w/w PVP “gave the best suspension ability
overall,” id., col. 6, lines 30–31.
In AstraZeneca’s initial application for what became
the ’328 patent, original claim 1 recited the five-component
composition with no concentration limitations, while sev-
eral dependent claims contained such limitations, includ-
ing one claiming PVP “present from about 0.0005 to about
0.05 %w/w” and a PEG concentration range. J.A. 15919.
The examiner rejected the claims for obviousness over two
references (U.S. Patent Appl. Publ. No. 2003/0018019 to
Meade and U.S. Patent No. 6,309,623 to Weers). J.A.
16204–05. The examiner listed several bases for the rejec-
tion, including that “one would have been expected to de-
termine the optimum amount of PVP and PEG (which may
have fallen within the [claimed] range).” J.A. 16205.
AstraZeneca then amended its claim 1 to include a con-
centration of the claimed PVP (but none of the four other
components), stating: “PVP is present in an amount of
0.001% w/w.” J.A. 16213. In support of allowance, Astra-
Zeneca argued that neither prior-art reference disclosed a
PVP concentration. AstraZeneca identified a reference
(U.S. Patent No. 6,123,924 to Mistry) that, it observed, dis-
closed concentrations of PVP notably higher than its newly
claimed “0.001%,” i.e., the reference disclosed concentra-
tions from “0.0025%” to “0.5% w/w.” J.A. 16222. Astra-
Zeneca argued that it had made the “surprising discovery”
that “0.001%” PVP gave “consistently stable formulations
. . . at a much lower concentration than indicated in the
prior art.” J.A. 16222 (internal quotation marks and cita-
tion omitted). After AstraZeneca’s amendment, the exam-
iner again rejected the claims, stating, as one ground, that
neither Meade nor Weers “disclose[s] any particular range
of PVP” and AstraZeneca “fails to provide examples, which
show the criticality of 0.001 % w/w PVP versus the inven-
tion where the PVP concentration is slightly greater or less
than 0.001 % w/w PVP.” J.A. 16307; see also J.A. 16306.
Case: 21-1729 Document: 47 Page: 27 Filed: 12/08/2021
ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC. 5
On continued examination, AstraZeneca then can-
celled some claims and submitted new and amended claims
reciting, for different amounts of budesonide, several dif-
ferent concentrations and ranges of concentrations of PVP
(in one claim for PVP K25 specifically) whose testing is de-
scribed in the specification, from “0.0001%” to “0.01%” w/w.
J.A. 16319–28. The examiner, however, issued another re-
jection for obviousness over the two references originally
cited, noting that “[w]ith respect to the experimental re-
sults provided by the Applicants, the claims are much
broader than what are being interpreted as unexpected re-
sults” and that the “specification states . . . that only
0.001% PVP is used in all formulations.” J.A. 16447.
AstraZeneca responded by cancelling some claims and sub-
mitting new and amended claims that added concentration
levels or ranges for each component, including, now, a PVP
concentration (in one claim for PVP K25 specifically) lim-
ited to “0.001%” w/w. J.A. 16455–57. AstraZeneca dis-
claimed any concession as to the scope of unexpected
results, J.A. 16460, and also disagreed with the examiner’s
assertion that the specification states that “only 0.001%
PVP is used in all formulations” but deemed that issue
“moot in light of the current amendments,” id. After the
examiner suggested a narrowing of all PVP terms to PVP
K25, and AstraZeneca agreed, the examiner allowed the
claims, which issued with PVP K25 language as slightly
modified after allowance.
AstraZeneca’s subsequent continuation applications is-
sued as the ’239 and ’137 patents, with claims reciting PVP
(with some but not all claims limited to PVP K25) at con-
centration levels not limited to “0.001%” but including a
range of “0.001% to 0.01% w/w.” ’239 patent, col. 8, line 61,
through col. 10, line 48; ’137 patent, col. 8, line 16, through
col. 10, line 49.
Case: 21-1729 Document: 47 Page: 28 Filed: 12/08/2021
6 ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC.
B
After Mylan sought FDA approval of an Abbreviated
New Drug Application and sent AstraZeneca a Paragraph
IV Certification Notice Letter, J.A. 7034–82, AstraZeneca
brought this Hatch-Waxman suit in the District of Dela-
ware, asserting infringement of the ’328, ’239, and ’137 pa-
tents. The parties exchanged proposed claim constructions
for “0.001% w/w,” a term that appeared in all asserted
claims. Mylan proposed a construction of “0.0010% w/w,”
J.A. 7027, which added a zero at the end to create two sig-
nificant figures. This was the same position Mylan took in
its Notice Letter, which stated that the claim term had one
meaning if left at one significant figure (as written) and
another meaning if changed to two significant figures (as
urged by Mylan), the interval defined by the latter being
much smaller than the interval defined by the former. J.A.
7080–82. 1 AstraZeneca proposed that no construction was
1 In its Notice Letter, Mylan explained “significant
figures” generally:
The significant figures of a number are digits that
carry meaning contributing to its measurement
resolution. This includes all digits beginning with
the first non-zero digit. That is, leading zeros are
not significant figures regardless of whether or not
a decimal point is present. Trailing zeros are al-
ways significant when a decimal point is present.”
J.A. 7080 n.6 (citing http://ccnmtl.columbia.edu/pro-
jects/mmt/frontiers/web/chapter_5/6665.html). As to the
claim phrase, “0.001% w/w PVP K25,” Mylan wrote:
The claim phrase “0.001% w/w PVP K25” is amena-
ble to two potential constructions, based on the
number of significant figures a person of ordinary
skill in the art would accord the value 0.001% w/w.
Were the person of ordinary skill to accord the
Case: 21-1729 Document: 47 Page: 29 Filed: 12/08/2021
ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC. 7
necessary. In the alternative, it proposed “0.001% w/w, ex-
pressed using one significant digit.” J.A. 7013. “In an ef-
fort to streamline claim construction,” Mylan then agreed
that no construction was necessary for the PVP concentra-
tion terms. J.A. 5612; 12927 n.3.
The case was then transferred to the Northern District
of West Virginia, where Mylan again asserted that the
term “0.001%” required construction and requested addi-
tional briefing, a request that the court granted. Astra-
Zeneca presented the same construction as it did in the
Delaware court. But Mylan in its opening brief in West
Virginia now argued for a new construction—the term
“0.001%” meant “that precise number, with only minor var-
iations.” J.A. 6804. In its reply brief, however, Mylan
equated that construction with its construction originally
proposed in Delaware, J.A. 7708 (“Defendants’ construc-
tion of ‘0.0010%’ PVP permits minor concentration varia-
tions.”), as it did in oral argument to the West Virginia
court, J.A. 7913, 7915 (arguing that the term “requires two
significant figures”).
value two significant figures, then the proper con-
struction would be 0.0010% w/w PVP K25 and, it
would follow, that rounding would literally encom-
pass between 0.00095% and 0.00105% w/w PVP
K25. Alternatively, were the person of ordinary
skill to accord the value one significant figure, then
the proper construction would be 0.001% w/w PVP
K25, and it would follow that rounding would liter-
ally encompass between 0.0005% to 0.0014% w/w
PVP K25. For the reasons set forth below, the
phrase “0.001% w/w PVP K25” should be construed
as having at least two significant figures, i.e.,
“0.0010% w/w PVP K25.”
J.A. 7080–81 (citation to J.A. 7080 n.6 omitted).
Case: 21-1729 Document: 47 Page: 30 Filed: 12/08/2021
8 ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC.
The West Virginia district court “construe[d] the term
‘0.001%’ consistent with its plain and ordinary meaning,
that is, expressed with one significant digit.” AstraZeneca
AB v. Mylan Pharms. Inc., No. 1:18-CV-193 c/w 1:19-CV-
203, 2020 WL 4670401, at *7 (N.D. W. Va. Aug. 12, 2020).
Based on the rules of rounding, the court determined that
the plain meaning of the term “0.001%” encompassed the
range of 0.0005% to 0.0014%. Id. at *5 (citing Noven
Pharms., Inc. v. Actavis Laboratories UT, Inc., C.A. No. 15-
249-LPS, 2016 WL 3625541, at *3, 5 (D. Del. July 5, 2016)).
The court found that neither the specification nor the pros-
ecution history supported Mylan’s construction. Id. at *5–
6. Mylan stipulated to infringement under AstraZeneca’s
construction. The district court entered a final judgment
of infringement.
II
A
“[T]he words of a claim are generally given their ordi-
nary and customary meaning,” as understood by a skilled
artisan at the time of the invention. Phillips v. AWH Corp.,
415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc) (citations
and internal quotations omitted). It is undisputed that the
term “0.001%” here, which states a concentration of a com-
ponent, has an ordinary meaning. The ordinary meaning
of that term is the significant-figure meaning. See, e.g.,
Viskase Corp. v. American Nat’l Can Co., 261 F.3d 1316,
1320 (Fed. Cir. 2001) (recognizing the “standard scientific
convention” of significant figures); Valeant Pharms. Int’l
Inc. v. Mylan Pharms. Inc., 955 F.3d 25, 34 (Fed. Cir. 2020)
(similar); U.S. Philips Corp. v. Iwasaki Elec. Co., 505 F.3d
1371, 1377–78 (Fed. Cir. 2007) (noting that a claimed range
“should not be read . . . with greater precision than the
claim language warrants” based on the number of signifi-
cant figures). The parties do not dispute that there is pre-
cisely one significant figure in the term “0.001%”—the “1”
at the third decimal place preceded by only zeroes.
Case: 21-1729 Document: 47 Page: 31 Filed: 12/08/2021
ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC. 9
The significant-figure meaning of “0.001%” reflects its
place in the entire claim phrase at issue. The phrase, in
representative claim 13 of the ’328 patent, is: “PVP K25 is
present at a concentration of 0.001% w/w.” ’328 patent, col.
8, lines 62–63. The claim requires a weight ratio to be “at”
a stated number, and the weight ratio is based on so many
particles that it is effectively a continuous (not discrete)
function. Sensibly, in this situation, Mylan does not read
claim 13 as limited to a single exact point on the real-num-
ber line, but instead recognizes that the language refers to
some interval that answers the question: How close does a
result have to be to the real number 0.001% to be “at” that
number? The significant-figure convention for real-world-
measurement situations supplies an answer by giving a
well-defined interval as the ordinary meaning, in the art,
of a statement of a single number like the statement at is-
sue here. Under this ordinary-meaning approach, the sig-
nificant-figure interval meant by “0.001%” is 0.0005% to
0.0014%, based on rules of rounding and the single signifi-
cant figure at the third decimal place. The district court so
concluded, and Mylan has not disputed that conclusion.
AstraZeneca, 2020 WL 4670401, at *5.
B
Mylan, accepting the need for some interval to define
the “0.001%” claim term, proposes a different definition—
“that precise number, with only minor variations.” Mylan’s
Opening Br. at 20–21. In its opening brief, Mylan makes
no meaningful affirmative argument for the correctness of
“minor variations” as an interpretation. Id. at 34–45. Ra-
ther, almost its entire argument is a negative one—against
the significant-figure interpretation of “0.001%”—and that
argument, at every turn, relies ultimately on a single two-
part point: first, the specification identifies a concentration
level of “0.0005%” that the inventors tested separately from
a level of “0.001%,” and that AstraZeneca originally in-
cluded in its claims before narrowing them during prosecu-
tion; and second, the significant-figure interval of “0.001%”
Case: 21-1729 Document: 47 Page: 32 Filed: 12/08/2021
10 ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC.
overlaps with portions of the significant-figure interval of
“0.0005%” (including 0.0005% itself). Id. But neither on
that basis nor otherwise has Mylan provided sound support
for its proposed construction.
One problem with Mylan’s proposed “minor variations”
construction is that, without additional precision, it actu-
ally adds to the uncertainty of claim scope compared to the
ordinary meaning. Such a construction works against the
core purpose of claim construction, which is to clarify claim
scope. See, e.g., U.S. Surgical Corp. v. Ethicon, Inc., 103
F.3d 1554, 1568 (Fed. Cir. 1997) (“Claim construction is a
matter of resolution of disputed meanings and technical
scope, to clarify and when necessary to explain what the
patentee covered by the claims, for use in the determina-
tion of infringement.” (emphasis added)); Arlington Indus.
Inc. v. Bridgeport Fittings, Inc., 759 F.3d 1333, 1338 (Fed.
Cir. 2014) (quoting U.S Surgical statement); O2 Micro Int’l
Ltd. v. Beyond Innovation Tech. Co., Ltd., 521 F.3d 1351,
1362 (Fed. Cir. 2008) (same); see also Avid Tech., Inc. v.
Harmonic, Inc., 812 F.3d 1040, 1050 (Fed. Cir. 2016) (stat-
ing that “the aim of claim construction [is] to give the finder
of fact an understandable interpretation of claim scope to
apply to the accused systems”).
Relatedly, the phrase “minor variations,” without fur-
ther construction to identify how much variation is too
large to be “minor,” effectively reinstates the “about” lan-
guage that AstraZeneca used in its original claim 1 but re-
moved in favor of the more precise “0.001%.” AstraZeneca’s
withdrawal of its “about” language does not imply that
“0.001%” was meant to have a non-interval meaning. In-
stead, AstraZeneca chose to express the PVP concentration
with a number having a well-defined interval (the ordinary
significant-figure meaning), not one having the uncertain
scope of “about” or “minor variation.”
For some patents, the intrinsic evidence may support
displacement of the ordinary meaning (although it might
Case: 21-1729 Document: 47 Page: 33 Filed: 12/08/2021
ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC. 11
present a risk that the adopted construction is itself indef-
inite). But that is not so here. We “look at the ordinary
meaning in the context of the written description and the
prosecution history.” Medrad, Inc. v. MRI Devices Corp.,
401 F.3d 1313, 1319 (Fed. Cir. 2005) (citations omitted). In
this case, those sources simply do not show a use of “minor
variations” or a comparable phrase that would accomplish
the one thing Mylan insists its phrase does, namely, dis-
place the ordinary, significant-figure meaning so as to ex-
clude concentrations down to 0.0005% (thereby avoiding
the overlap on which Mylan’s argument is premised).
No such phrase is used at all in the specification, much
less to imply departure from the ordinary meaning. In the
prosecution history, the one phrase to which Mylan points
is the examiner’s mention (quoted above) of a need for
AstraZeneca to show criticality by showing unexpected re-
sults of a “0.001%” concentration level compared to concen-
trations levels “slightly greater or less” than 0.001% PVP.
Mylan’s Opening Br. at 13 (quoting J.A. 16307). But noth-
ing about that phrase implies a displacement of the ordi-
nary significant-figure meaning. It is simply unclear if the
examiner meant to include “0.0005%” and other tested con-
centration levels tested within the meaning of “slightly
greater or less.” 2 Thus, even if “slightly greater or less” is
assumed to have the same meaning as “minor variations,”
the examiner’s use of this phrase in discussing criticality
does not establish the exclusion of “0.0005%,” much less
that “minor variations” properly replaces the ordinary sig-
nificant-figure meaning of the claim phrase at issue.
2 The court’s opinion itself seems to use “slightly”
and “minor” to refer to, rather than exclude, the difference
between “0.001%” and the other concentration levels whose
testing is discussed in the specification. E.g., Op. 8, 13, 14.
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12 ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC.
C
Mylan tries to supply more precision to the term “minor
variations” by asserting that a “minor variation” here
equals exactly the significant-figure interval that would ex-
ist if “0.001%” were changed to “0.0010%”—the latter hav-
ing two significant figures, not one. Mylan’s Opening Br.
at 42 (stating that its construction is “alternatively stated
as ‘0.0010 [%] w/w PVP’”); see id. at 21, 27, 33 n.7. But
Mylan does not explain why “minor variations” itself has
this two-significant-figure meaning. Mylan’s “0.0010%” as-
sertion amounts to an alternative construction.
On its merits, this construction should be rejected, for
the simplest of claim-construction reasons. Adopting this
construction requires rewriting the claim term. And that
rewriting is counter to the specification and prosecution
history. It is undisputed that AstraZeneca uniformly used
just one significant figure when referring to PVP concen-
trations in its compositions, both in the specification and
the prosecution history, never using more significant fig-
ures. AstraZeneca, 2020 WL 4670401, at *5–6. In this re-
spect, this case is critically different from Viskase, in which
the patentees did use an extra significant figure in the
prosecution history to distinguish their invention from the
prior art and this court relied on that fact in adopting its
claim construction. See 261 F.3d at 1321–22.
Twice in its opening brief Mylan makes a passing sug-
gestion, without development into an argument, that “the
specification showed that the inventors varied PVP concen-
trations . . . with precision out to four decimal places.”
Mylan’s Opening Br. at 43; see also id. at 27. To the extent
that Mylan suggests that the use of four decimal places to
state some concentration values indicates that all concen-
tration values should be read to express a degree of preci-
sion to four decimal places, that suggestion is meritless.
Most fundamentally, the specification never uses four dec-
imal places to refer to the degree of precision of the
Case: 21-1729 Document: 47 Page: 35 Filed: 12/08/2021
ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC. 13
specified numbers, i.e., the interval around the stated fig-
ure meant to be captured by that figure. The specification
uses four decimal places only to refer to the absolute con-
centration level—which, if small enough, makes use of four
decimal places unavoidable just to identify the level (i.e.,
concentrations of “0.0001%” and “0.0005%” PVP). Absolute
levels and degrees of precision are distinct.
Moreover, nothing in the patent suggests that the de-
gree of precision for “0.001%” is to the fourth decimal place
just because stating the absolute level for some tested con-
centrations—“0.0005%” and “0.0001%”—requires use of
four decimal places. Indeed, Mylan has identified no basis
in the patent for inferring that the degree of precision is
uniform, in absolute (interval size) terms, across different
absolute levels of concentration—e.g., that the degree of
precision at the 0.0005% concentration level must be the
same as the degree of precision at the 0.001% concentration
level. Of course, the ordinary significant-figure meaning is
disuniform in precisely that way: A single-significant-fig-
ure number written using the fourth decimal place has a
significant-figure interval that is smaller in absolute terms
than a single-significant-figure number written using only
the third decimal place. Nothing in the patent displaces
that ordinary result. And Mylan’s suggestion is not aided
by considering the underlying interest in suspension sta-
bility. Mylan has not argued, or pointed to any intrinsic or
extrinsic evidence indicating, either that the sensitivity of
suspension stability to variation is (as a scientific matter)
uniform across different absolute levels of concentration or
that, even if it is, any such conclusion would be clear
enough to displace the ordinary meaning.
D
What remains of Mylan’s argument is simply the fact
that the significant-figure interval for “0.001%” overlaps
with the significant-figure interval for “0.0005%”—which is
the single fact to which Mylan repeatedly returns in each
Case: 21-1729 Document: 47 Page: 36 Filed: 12/08/2021
14 ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC.
section of its brief’s argument about claim construction.
Notably, of the various concentration levels tested and de-
scribed in the specification—“0.0001%,” “0.0005%,”
“0.001%,” “0.01%,” “0.03%,” and “0.05%” w/w PVP—the
only pair with overlapping significant-figure intervals is
“0.0005%” and “0.001%.” 3 The same is true of the prosecu-
tion history, in which, not surprisingly, AstraZeneca dis-
cussed as its invention only concentration levels reflected
in the specification. So Mylan has only the single overlap
to work with. But that overlap, as already explained, does
not support a “minor variations” or extra-significant-digit
or four-decimal-places construction. And in any event, it
cannot help Mylan.
First, Mylan’s argument on this score is a negative one:
that the significant-figure construction is decisively wrong
because (a) the specification reports that the inventors sep-
arately tested concentrations identified as “0.0005%” and
“0.001%” (among other PVP amounts) and reached differ-
ent conclusions about the stability of the formulations with
those two levels, and (b) there is overlap between the sig-
nificant-figure intervals of the two figures—respectively,
0.00045% to 0.00054%, and 0.0005% to 0.0014%. The two
premises are correct, but Mylan’s conclusion that overlap
negates the distinction reflected in the specification is
wrong.
Overlap does not imply the absence of a distinction:
Two ranges—here the significant-figure intervals of two
numbers—are different even if they overlap. Consider a
patent in which one claim requires an amount of 3 to 7 (by
3 For example, the concentration “0.01%” encom-
passes an interval of 0.005% to 0.014%, which does not
overlap with either the concentration below it, “0.001%”
(significant-figure interval of 0.0005% to 0.0014%), or the
concentration above it, “0.03%” (significant-figure interval
of 0.025% to 0.034%).
Case: 21-1729 Document: 47 Page: 37 Filed: 12/08/2021
ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC. 15
some measure) of some component and another claim re-
quires an amount of 1 to 4 of the same component. The two
claims, despite their overlap, would still be distinct in their
coverage, and—given that each covers amounts not in the
other—one might be valid and the other invalid (so that, if
an original application contained both claims, the appli-
cant might withdraw one but keep the other without limit-
ing the scope of the retained claim). Similarly, here, the
significant-figure intervals of the identified figures are dif-
ferent, each including absolute concentration levels that
are not present in the other, and so test results could differ,
as the specification indicates they did. Contrary to Mylan’s
suggestion, the ordinary significant-figure interpretation
of the two terms, “0.0005%” and “0.001%,” does not erase
the distinction between them just because they overlap.
Second, even if the overlap supported some limitation
on the construction that defines claim scope, Mylan cannot
succeed. Whether by implied disclaimer or an inference of
the proper degree of precision at the “0.001%” level, the
most this overlap could possibly support would be an exclu-
sion of the small range with the one significant-figure in-
terval for which there is overlap. Under this approach, the
intrinsic evidence would limit the meaning of “0.001%” to
its significant-figure interval minus the overlap with the
significant-figure interval of “0.0005%,” leaving a claim
scope of 0.00055% to 0.0014% w/w PVP. But it is undis-
puted that Mylan’s ANDA product falls within even this
narrower range. Therefore, we need not decide whether
this overlap-area exclusion is ultimately justified as a
claim construction. Claims must be construed “only to the
extent necessary to resolve the controversy.” Vivid Techs.,
Inc. v. American Science & Eng’g, Inc., 200 F.3d 795, 803
(Fed. Cir. 1999); see Nidec Motor Corp. v. Zhongshan Broad
Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017).
Case: 21-1729 Document: 47 Page: 38 Filed: 12/08/2021
16 ASTRAZENECA AB v. MYLAN PHARMACEUTICALS INC.
III
For those reasons, I respectfully dissent from the ma-
jority’s holding that the term “0.001%” should be construed
as “that precise number, with only minor variations” or as
“0.0010%.” I would affirm the judgment of infringement as
well as the judgment of no invalidity.