Belcher Pharmaceuticals, LLC v. Hospira, Inc.

Case: 20-1799 Document: 39 Page: 1 Filed: 09/01/2021
United States Court of Appeals
for the Federal Circuit
______________________
BELCHER PHARMACEUTICALS, LLC,
Plaintiff-Appellant
v.
HOSPIRA, INC.,
Defendant-Appellee
______________________
2020-1799
______________________
Appeal from the United States District Court for the
District of Delaware in No. 1:17-cv-00775-LPS, Judge
Leonard P. Stark.
______________________
Decided: September 1, 2021
______________________
PETER MCCREERY LANCASTER, Dorsey & Whitney LLP,
Minneapolis, MN, argued for plaintiff-appellant. Also rep-
resented by KENNETH LEVITT.
MATTHEW S. FREIMUTH, Willkie Farr & Gallagher LLP,
New York, NY, argued for defendant-appellee. Also repre-
sented by DEVON WESLEY EDWARDS, THOMAS J. MELORO.
______________________
Before REYNA, TARANTO, and STOLL, Circuit Judges.
REYNA, Circuit Judge.
Case: 20-1799 Document: 39 Page: 2 Filed: 09/01/2021
2 BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC.
This is an appeal from a decision of the U.S. District
Court for the District of Delaware that U.S. Patent
No. 9,283,197, which Appellant Belcher Pharmaceuticals,
LLC asserted against Appellee Hospira, Inc. in a patent in-
fringement suit under the Hatch-Waxman Act, is unen-
forceable for inequitable conduct. The district court
concluded that Belcher’s Chief Science Officer engaged in
inequitable conduct by withholding material information
from the U.S. Patent and Trademark Office during prose-
cution of the ’197 patent with the requisite deceptive in-
tent. For the reasons below, we affirm.
BACKGROUND
Epinephrine
Epinephrine (also called adrenaline) is a hormone as
well as a grandfathered drug product that has been on the
market since approximately 1938 and used for a variety of
medical purposes. It has long been understood that epi-
nephrine degrades in two ways pertinent to this appeal:
racemization and oxidation. Racemization involves a
change in the arrangement of a molecule around a “chiral
center,” such that levorotatory epinephrine (“l-epineph-
rine”), the more potent isomer, converts to dextrorotatory
epinephrine (“d-epinephrine”), the less potent isomer. Ox-
idation involves a change in a compound’s chemical compo-
sition due to reaction with oxygen or other oxidizing
agents. Oxidation of l-epinephrine yields adrenalone,
which is deemed an impurity in l-epinephrine drug prod-
ucts.
A handbook for pharmacists published in 1986 ex-
plained that, in l-epinephrine solutions, there is an inverse
relationship between racemization and pH and a propor-
tional relationship between oxidation and pH. See
KENNETH A. CONNORS ET AL., CHEMICAL STABILITY OF
PHARMACEUTICALS: A HANDBOOK FOR PHARMACISTS 438–47
(John Wiley & Sons 2d. ed. 1986) [hereinafter Connors]
(J.A. 1335–46). In other words, when an epinephrine
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BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC. 3
solution becomes more acidic (i.e., pH decreases), racemi-
zation increases and oxidation decreases, and when the so-
lution becomes more basic (i.e., pH increases), oxidation
increases and racemization decreases. Id. Accordingly,
Connors taught that “there is an optimum pH at which rac-
emization and oxidation can be balanced to minimize loss
of intact drug by these two routes; this is approximately pH
3.0-3.8.” Id. at 441.
Belcher’s NDA
On November 30, 2012, Belcher Pharmaceuticals, LLC
(“Belcher”) submitted New Drug Application (“NDA”)
No. 205029 for a 1 mg/mL injectable l-epinephrine formu-
lation. J.A. 1559, 1562. The NDA was literature-based,
meaning that Belcher did not perform any clinical or non-
clinical studies on its epinephrine formulation to support
its application. J.A. 1560. The NDA described the devel-
opment of Belcher’s formulation. It first discussed Swiss
company Sintetica SA’s (“Sintetica”) “original formulation”
of 1 mg/mL injectable l-epinephrine, which Sintetica devel-
oped in the 1930s and registered in Switzerland in 1947.
J.A. 1564–65. The formulation included sodium metabisul-
phite as an antioxidant preservative and about a 10 per-
cent overage 1 of epinephrine to ward off activity loss, and
it had a pH range of 2.2 to 4.0. J.A. 1565–66. The manu-
facturing process involved a continuous flow of nitrogen
gas to remove oxygen and thereby enhance stability.
J.A. 1566.
According to the NDA, in the early 2000s, market de-
mand shifted to epinephrine formulations that did not in-
clude “preservatives and sulfites,” which had been found to
cause side effects. J.A. 1566. The NDA explained that
1 An overage refers to an added amount of the active
ingredient or excipient compared to what is described in
the product’s label.
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4 BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC.
“[t]he switch was very simple” and involved increasing the
sodium chloride concentration and increasing the epineph-
rine overage from 10 percent to 15 percent. J.A. 1566–67.
The NDA described the new composition as having a pH
range of 2.8 to 3.3. J.A. 1567. Given the removal of the
sulfite antioxidant, “careful attention was paid to the nitro-
gen purge during the whole process” to maximize stability
in the absence of the antioxidant. Id.Belcher’s NDA named as reference product Sintetica’s
preservative- and sulfite-free 1 mg/mL epinephrine formu-
lation manufactured for the U.S. market by American Re-
gent Laboratories, Inc. J.A. 1575. Belcher submitted data
from four batches of the reference product, made from No-
vember 2002 to April 2003, for validation of the product’s
stability. J.A. 1578–82. This data showed that the batches
included overages of 10 to 15 percent and maintained, over
a 24-month period, a pH range of 3.1 to 3.3, and undetect-
able levels of the impurity adrenalone. J.A. 1578–82. Ac-
cording to Belcher, this data met U.S. Pharmacopeia
(“USP”) specifications, including the requirement for a pH
between 2.2 and 5.0. J.A. 1578; see also J.A. 1595.
Belcher’s NDA also described the sterilization process
and the “in[-]process pH” value. J.A. 1584–95. Belcher ex-
plained that lowering the in-process pH from a range of 2.8
to 3.3 (called “old”) to a range of 2.4 to 2.6 (called “new”),
when coupled with effective removal of oxygen using a ni-
trogen purge, “reinforces the manufacturing process ro-
bustness and reproducibility” and “reduces the impact of
possible residues of oxygen in the solution.” J.A. 1595.
On February 7, 2013, the U.S. Food and Drug Admin-
istration (“FDA”) sent a letter to Belcher asking for certain
additional information, including (i) “data that support
evaluation of [the] drug product for potential racemization
from manufacturing process conditions and over the shelf
life,” and (ii) clarification on whether the Sintetica batches
on which Belcher relied for stability validation were
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BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC. 5
manufactured in the same way as that proposed for mar-
keting. J.A. 1483. Belcher forwarded the letter to Sin-
tetica asking for assistance in responding to the FDA’s
requests. J.A. 1481.
Belcher responded to the FDA on March 8, 2013. Ad-
dressing the FDA’s question on racemization, Belcher ex-
plained that “[r]acemization of the enantiomerically pure
L-Epinephrine isomer in injectable formulations of epi-
nephrine is a well-known process,” citing literature au-
thored by Fylligen2 and Stepensky. 3 J.A. 1430.
Responding to the FDA’s inquiry on manufacturing process
for the stability validation batches, Belcher stated that the
only difference between the relied-upon Sintetica batches
and Belcher’s proposed formulation “is related to the
in[-]process pH” and that it “consider[ed] the in[-]process
pH change to be a very minor change not requiring addi-
tional stability studies.” J.A. 1432. Belcher also explained
that the release specification of 2.2 to 5.0 “complies with
[the] USP specification and stays unchanged between all
the batches.” Id.The FDA responded on October 4, 2013, asking Belcher
to evaluate the effect of an in-process pH range of 2.4 to 2.6
on racemization. Belcher Pharms., LLC v. Hospira, Inc.,
450 F. Supp. 3d 512, 524 (D. Del. 2020). On October 17,
2013, Belcher’s regulatory consultants, INC Research, rec-
ommended that Belcher revert to the 2.8 to 3.3 pH range
shown in the Sintetica batch data because deviating from
that range would delay the FDA’s approval. Id.; see also
2 G. Fyllingen et al., Racemization and oxidation in
adrenaline injections, 2(5) ACTA PHARM. NORD. 355–62
(1990).
3 D. Stepensky et al., Long-term stability study of L-
adrenaline injections: kinetics of sulfonation and racemiza-
tion pathways of drug degradation, 93(4) J. PHARM. SCI.
969–80 (April 2004).
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6 BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC.
J.A. 668–69 (Trial Tr. 138:5–139:11). Belcher followed that
advice. In its response to the FDA, Belcher stated that it
had “refocused [its] studies on determining the effect of the
in-process pH of 2.8 - 3.3 on the formation of d-epinephrine
during each step of the manufacturing process, which was
used to manufacture the 3 primary stability batches . . .
provided in the NDA.” J.A. 1464. Belcher accordingly re-
quested approval of the drug proposed in the NDA “with
the exception[] of changing the [in-process] pH from 2.4 -
2.6 back to the initial pH of 2.8 - 3.3.” J.A. 1471. The FDA
approved the NDA on July 29, 2015.
The ’197 Patent
On August 15, 2014, Jugal Taneja, Belcher’s CEO, filed
U.S. Patent Application No. 14/460,845 (“’845 applica-
tion”), which issued as U.S. Patent No. 9,283,197 (“the ’197
patent”). J.A. 1003–27. The application was directed to
certain epinephrine formulations and was entitled “More
Potent and Less Toxic Formulations of Epinephrine and
Methods of Medical Use.” J.A. 1016, 1025–27. Mr. Taneja
later assigned the application to Belcher.
The patent describes the problem of l-epinephrine’s
degradation and the resulting need for product overages
and sulfite antioxidants, and it claims to provide an answer
to this need. ’197 patent col. 2 ll. 50–59. According to the
patent, an answer “seemed impossible” and “had never
been accomplished before.” Id. at col. 4 ll. 31–35. The pa-
tent similarly states that the idea of raising the in-process
pH above the range of 2.2 to 2.6 “was contradictory to one
skilled in the art” before the claimed invention. Id. at col. 4
ll. 41–47. But “[i]nadvertently,” the patent states, “in-
creasing the in-process pH to 2.8-3.3[] unexpectedly re-
duced the racemization of l-epinephrine to d-epinephrine
at release by approximately two-thirds, from 14% to 5%,
respectively.” Id. at col. 4 ll. 48–51. The inventor’s alleged
discovery of raising the pH “led to new methods of manu-
facturing sulfite-free, l-epinephrine solution with an in-
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BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC. 7
process pH of 2.8 to 3.3, approximately 3.0, which was a
nonobvious solution to the problem of racemization. Most
importantly, with these new methods, overages could
greatly be reduced.” Id. at col. 4 ll. 55–59.
Claims 6 and 7 of the ’197 patent, which are at issue in
this appeal, cover pharmaceutical epinephrine formula-
tions having a pH between 2.8 and 3.3 and certain concen-
trations of l-epinephrine, d-epinephrine, and adrenalone at
the time of release and 12 months later. These claims read
as follows:
6. An injectable liquid pharmaceutical formulation
of l-epinephrine sterile solution; said liquid phar-
maceutical formulation having a pH between 2.8
and 3.3; said injectable liquid pharmaceutical for-
mulation compounded in an aqueous solution as
1.0 to 1.06 mg/mL l-epinephrine, and further in-
cluding a tonicity agent; said liquid pharmaceutical
formulation including no more than about 6% d-ep-
inephrine and no more than about 0.5% adrenalone
at release, and no more than about 12% d-epineph-
rine and no more than about 0.5% adrenalone over
a shelf-life of at least 12 months.
7. The said injectable liquid pharmaceutical formu-
lation of claim 6 further having a concentration of
1 mg per mL l-epinephrine.
’197 patent col. 7 ll. 1–13.
The prosecution of the ’197 patent involved a single of-
fice action. On August 15, 2014, the examiner rejected the
claims as obvious based on Canadian Patent Application
No. 2002643 A (“Helenek”) in view of additional references.
See J.A. 1042. Helenek, the examiner explained, taught a
1 mg/mL epinephrine injection that was free of preserva-
tives and antioxidants, was made in an oxygen free (i.e.,
nitrogen) environment, and had a pH range of 2.2 to 5.0.
J.A. 1042–43.
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8 BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC.
On November 5, 2015, Mr. Tajena’s counsel responded
arguing that Helenek’s 2.2 to 5.0 pH range failed to render
obvious the claimed range of 2.8 to 3.3 because the claimed
range “was unexpectedly found to be critical by the Appli-
cant to reduce the racemization of l-epinephrine.”
J.A. 1073; see also J.A. 1074 (arguing that “[t]he Applicant
has ‘[shown] that that [sic] the particular range is critical,
generally by showing that the claimed range achieves un-
expected results relative to the prior art range’” (second al-
teration in original) (quoting In re Woodruff, 919 F.2d 1575,
1578 (Fed. Cir. 1990))).
On December 16, 2015, after holding an interview, the
examiner withdrew the pending rejections, made an exam-
iner’s amendment approved by the applicant, and allowed
the patent. J.A. 1086–88, 1091. In discussing the reasons
for allowance, the examiner explained that the cited art
failed to render the claims unpatentable “in view of Appli-
cant’s demonstration of criticality of a pH range between
2.8 and 3.3.” J.A. 1088. According to the examiner,
Applicant has demonstrated that pH range of be-
tween 2.8 and 3.3 is critical to prevent racemiza-
tion of l-epinephrine . . . . [T]here is nothing in the
prior art that would teach or suggest the instantly
claimed pH range of between 2.8 and 3.3 would re-
sult in the limited racemization and impurities as
instantly claimed.
Id.The ’197 patent issued on March 15, 2016, and the FDA
thereafter listed the ’197 patent for Belcher’s NDA
No. 205029 in its publication called “Approved Drug Prod-
ucts with Therapeutic Equivalent Evaluations” (often re-
ferred to as the “Orange Book”). Belcher, 450 F. Supp. 3d
at 518–19.
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BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC. 9
Procedural History
Hospira, Inc. (“Hospira”) submitted NDA No. 209359 to
the FDA seeking approval of a 0.1 mg/mL injectable l-epi-
nephrine formulation (“Hospira’s NDA product”). Id. at
518. Hospira’s NDA included a certification under
21 U.S.C. § 355(b)(2)(A)(iv) (commonly known as “Para-
graph IV”) that the ’197 patent’s claims are invalid, unen-
forceable, and/or not infringed by Hospira’s NDA product.
Id. at 519.
On June 16, 2017, Belcher sued Hospira for infringing
the ’197 patent based on Hospira’s submission of its NDA
seeking approval for its NDA product. Id. Belcher asserted
claims 6 and 7. Id. The parties stipulated that Hospira’s
NDA product did not literally infringe those claims. Id.The district court accordingly held a two-day bench trial in
June 2019 on Belcher’s theory of infringement under the
doctrine of equivalents, as well as Hospira’s affirmative de-
fenses and counterclaims of non-infringement, invalidity,
and unenforceability. Id. at 518–19.
The trial witnesses included Mr. Darren Rubin,
Belcher’s Chief Science Officer. Mr. Rubin testified that he
was a consultant for Belcher from 2010 to 2014 and became
its Chief Science Officer in 2015. J.A. 675–76 (Trial
Tr. 145:20–146:1). He holds degrees in biology, medical sci-
ences, and business but is neither a registered patent agent
nor an attorney. J.A. 675–76 (Trial Tr. 145:12–146:21).
Within Belcher, Mr. Rubin was referred to as the head of
intellectual property. See, e.g., J.A. 2071. His job respon-
sibilities included overseeing regulatory approval, product
development, and working on intellectual property matters
including patent application drafting, prosecution, and lit-
igation. J.A. 675–76 (Trial Tr. 145:22–146:21). Mr. Rubin
explained that he was involved in the development of
Belcher’s NDA product and participated in drafting the
NDA. Id.Case: 20-1799 Document: 39 Page: 10 Filed: 09/01/2021
10 BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC.
Mr. Rubin also testified that he was involved in the
prosecution of the ’197 patent. He helped draft the appli-
cation, including its claims and specification, and helped
respond to the examiner’s office action. J.A. 679 (Trial
Tr. 149:13–19), 695 (Trial Tr. 165:14–22). In fact, he
served as liaison between named inventor Mr. Taneja,
Belcher’s patent prosecution attorney, and the U.S. Patent
and Trademark Office (“PTO”). J.A. 679–80 (Trial
Tr. 149:13–150:18). He “project-managed everything” in
that role, and “it all led to [him].” J.A. 680 (Trial
Tr. 150:15–18). He prepared a response to the examiner’s
office action during the ’197 patent’s prosecution and “dug
into the case law.” J.A. 681–82 (Trial Tr. 151:21–152:4). In
an email, he asserted that he “made sure” to get claim 6
allowed without a preservative-free or sulfite-free limita-
tion. J.A. 2069–70.
Mr. Rubin testified that he possessed knowledge of cer-
tain facts pertinent to this appeal before and during the
’197 patent’s prosecution. For example, he knew of Sin-
tetica’s epinephrine formulations that had a pH range of
2.8 to 3.3 and that Belcher’s NDA described that range as
“old.” J.A. 682 (Trial Tr. 152:5–19), 723–24 (Trial
Tr. 193:5–194:15). Mr. Rubin also admitted that he knew
of Stepensky before the ’197 patent was filed. J.A. 705
(Trial Tr. 175:15–25). Indeed, Belcher cited Stepensky in
two separate communications to the FDA during the ap-
proval process. J.A. 1430, 1472 n.5. Mr. Rubin had also
sent Belcher’s regulatory consultant an email attaching
Stepensky and quoting a portion of it. See J.A. 1509–22.
Mr. Rubin also admitted that, by October 29, 2013, he
possessed a label for a 1 mg/mL epinephrine product that
a company named JHP had already introduced to the mar-
ket. J.A. 711–12 (Trial Tr. 181:21–182:21). JHP’s label de-
scribed its epinephrine product as having a pH in the range
of 2.2 to 5.0. J.A. 1503. Belcher also acquired three batches
of the JHP product and sent them to Sintetica for testing,
which showed that the JHP product had a pH within the
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BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC. 11
range of 2.8 to 3.3 (specifically 2.9, 2.9, and 3.1) at 15
months, i.e., three months before the expiration of its 18-
month shelf life. J.A. 1523.
On March 31, 2020, the district court decided, among
other things, that the ’197 patent is unenforceable for ineq-
uitable conduct. Regarding materiality, the district court
credited the testimony of Hospira’s expert witness, Dr. Pi-
nal, that each of the three pieces of information that Mr.
Rubin withheld (JHP’s product, Sintetica’s product, and
Stepensky) were but-for material to patentability because
they disclosed two aspects of the asserted claims: the pH
range and the impurity levels. Belcher, 450 F. Supp. 3d at
535, 547–48; J.A. 760–61 (Trial Tr. 230:19–231:10).
The district court also concluded that clear and con-
vincing evidence demonstrated that Mr. Rubin acted with
requisite intent to deceive the PTO. Belcher, 450 F. Supp.
3d at 550. The district court explained that Mr. Rubin
knew of JHP’s product, Sintetica’s product, and Stepensky
before and during the ’197 patent’s prosecution. Id. at 549–
50. It also noted that Mr. Rubin was a key player in the
FDA approval process as well as the ’197 patent’s prosecu-
tion. Id. at 548–50. From his dealings with the FDA, Mr.
Rubin knew that Belcher described the claimed pH range
of 2.8 to 3.3 as “old”; that Belcher disclosed Stepensky,
which teaches an overlapping pH range of 3.25 to 3.70; that
Belcher had submitted data on Sintetica’s and JHP’s prod-
ucts showing a pH within the claimed range; and that
Belcher switched from a lower pH range to the claimed 2.8
to 3.3 pH range at least in part to expedite FDA approval
because that range matched the pH range of Sintetica’s
products. Id.
But when dealing with the PTO, the district court ex-
plained, Mr. Rubin did not merely withhold this infor-
mation but also used emphatic language to argue that the
claimed pH range of 2.8 to 3.3 was a “critical” innovation
that “unexpectedly” reduced racemization. Id. at 549–50.
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12 BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC.
The district court found implausible Mr. Rubin’s testimony
at trial that he withheld JHP’s product, Sintetica’s product
and Stepensky because he believed that they were irrele-
vant given their high overages. Id. at 548–50. The court
further found that Mr. Rubin’s “repeated efforts to evade
questioning and inject attacks of the prior art into his an-
swers raised serious questions as to his credibility.” Id.
at 549. The district court therefore concluded that the
facts, taken together, persuaded it that Mr. Rubin’s decep-
tive intent was “the only reasonable inference that can be
drawn.” Id. at 550. Belcher appealed. We have jurisdic-
tion under 28 U.S.C. § 1295(a)(1).
STANDARD OF REVIEW
We review a district court’s determination of inequita-
ble conduct under a two-tiered standard. Specifically, we
review factual determinations of materiality and intent for
clear error. Star Sci., Inc. v. R.J. Reynolds Tobacco Co.,
537 F.3d 1357, 1365 (Fed. Cir. 2008). We further review
the ultimate decision on inequitable conduct for an abuse
of discretion. Id. An abuse of discretion occurs when the
trial court’s decision is clearly unreasonable, arbitrary, or
fanciful; when the court’s decision is based on an erroneous
construction of the law; when the court’s factual findings
are clearly erroneous; or when the record contains no evi-
dence upon which the court rationally could have based its
decision. Larson Mfg. Co. of S.D. v. Aluminart Prods.,
559 F.3d 1317, 1327 (Fed. Cir. 2009) (citation omitted).
DISCUSSION
Inequitable conduct is a defense to patent infringement
that, if proven, renders the asserted patent unenforceable.
Therasense, Inc. v. Becton, Dickinson & Co., 649 F.3d 1276,
1285 (Fed. Cir. 2011). “To prevail on an inequitable con-
duct defense, a defendant must establish both the materi-
ality of the withheld reference and the applicant’s intent to
deceive the PTO.” Aventis Pharma S.A. v. Hospira, Inc.,
675 F.3d 1324, 1334 (Fed. Cir. 2012).
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BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC. 13
Materiality
A prior art reference may constitute material infor-
mation, even where the reference is not sufficient to inval-
idate the claim in district court, if the disclosure of the
reference would have blocked the issuance of a patent un-
der the PTO’s evidentiary standards. Aventis, 675 F.3d at
1334 (quoting Therasense, 649 F.3d at 1292). Thus, prior
art is but-for material information if the PTO would not
have allowed a claim had it been aware of the undisclosed
prior art. Therasense, 649 F.3d at 1291. “[T]he standard
for establishing but-for materiality in the inequitable con-
duct context only requires a preponderance of the evidence,
‘giv[ing] claims their broadest reasonable construction.’”
Aventis, 675 F.3d at 1334 (quoting Therasense, 649 F.3d at
1291–92).
Belcher does not challenge the district court’s decision
that the asserted claims are invalid as obvious based on,
inter alia, JHP’s epinephrine product, testing of which
showed the product had a pH within the claimed range. 4
See Belcher, 450 F. Supp. 3d at 545; Appellant’s Br. 30
(“Belcher does not appeal the obviousness finding.”). Be-
cause that is the case, the product is “necessarily material
to patentability.” Aventis, 675 F.3d at 1334; see also The-
rasense, 649 F.3d at 1276 (“[I]f a claim is properly invali-
dated in district court based on the deliberately withheld
reference, then that reference is necessarily material be-
cause a finding of invalidity in a district court requires
4 The district court also found inequitable conduct
based on the withholding of Stepensky and Sintetica’s prior
epinephrine product. Belcher, 450 F. Supp. 3d at 550–51.
We do not recount the entire factual analysis performed by
the district court, TransWeb, LLC v. 3M Innovative Prop-
erties Co., 812 F.3d 1295, 1304 (Fed. Cir. 2016), but focus
our analysis only on those aspects that are key to our deci-
sion.
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14 BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC.
clear and convincing evidence, a higher evidentiary burden
than that used in prosecution at the PTO.”).
We further reject Belcher’s argument that the withheld
art, including the JHP product, is immaterial because it is
“cumulative” of Helenek’s disclosure of “epinephrine for-
mulations with pH between 2.2 and 5.0, including epineph-
rine solutions with a pH range of 3.0 to 4.0.” Appellant’s
Br. 54–55. Belcher’s argument is directly at odds with its
argument during prosecution that the claimed range was
“critical,” J.A. 1074, which is one way to circumvent obvi-
ousness when a claimed range overlaps with a range dis-
closed in the prior art, see, e.g., E.I. DuPont de Nemours &
Co. v. Synvina C.V., 904 F.3d 996, 1008 (Fed. Cir. 2018)
(“[W]here there is a range disclosed in the prior art, and
the claimed invention falls within that range, the burden
of production falls upon the patentee to come forward with
evidence of teaching away, unexpected results or critical-
ity, or other pertinent objective indicia indicating that the
overlapping range would not have been obvious in light of
that prior art.” (internal citations and quotation marks
omitted)). The examiner allowed the claims only after ac-
cepting Belcher’s criticality argument. J.A. 1088. The trial
record later established that the JHP product had a pH
within the alleged critical range of 2.8 to 3.3. Belcher’s al-
leged critical improvement over the prior art was therefore
already within the public domain, just not before the exam-
iner. As such, we see no clear error in the district court’s
determination that this information would have been but-
for material to patentability.
Intent
“To satisfy the intent requirement, ‘the accused in-
fringer must prove by clear and convincing evidence that
the applicant knew of the reference, knew that it was ma-
terial, and made a deliberate decision to withhold it.’”
Aventis, 675 F.3d at 1334–35 (quoting Therasense, 649 F.3d
at 1290). “[I]nequitable conduct requires clear and
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BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC. 15
convincing evidence of a specific intent to deceive the PTO
and that ‘the specific intent to deceive must be the single
most reasonable inference able to be drawn from the evi-
dence.’” Aventis, 675 F.3d at 1335 (quoting Therasense,
649 F.3d at 1290) (citation and quotation marks omitted).
The district court explained that, although there was
no direct evidence of deceptive intent, the evidence of rec-
ord persuaded it “clearly and convincingly[] that this is the
only reasonable inference that can be drawn.” Belcher,
450 F. Supp. 3d at 550. The court specifically noted that
Mr. Rubin was an active participant in the FDA approval
process and understood that Belcher had stated to the FDA
that the 2.8 to 3.3 pH range was an “old” range. Id. Mr.
Rubin also understood that Belcher had reverted from its
original pH range (2.4 to 2.6) to the 2.8 to 3.3 range because
the latter range corresponded to the reference product
made by Sintetica, and therefore using that range would
expedite FDA approval. Id. When later drafting the patent
application and through his communications with the PTO
during prosecution, however, Mr. Rubin performed an
about-face and emphatically and repeatedly advanced the
position that the 2.8 to 3.3 pH range was a “critical” inno-
vation contrary to the knowledge of a person of ordinary
skill in the art that yielded “unexpected results,” namely
reducing racemization of l-epinephrine. However, the dis-
trict court found that this argument was “false” and a “fic-
tion” because Mr. Rubin knew about the prior art’s
teachings of that pH range. Id. at 549–50.
It is in this context that we consider Mr. Rubin’s with-
holding of the prior art, including the JHP product, that
disclosed the pH range of 2.8 to 3.3. Mr. Rubin claimed at
trial that he withheld the references because he believed
that they were irrelevant—even though they directly un-
dercut the most important patentability argument—be-
cause they were different from the asserted claims in
certain respects, including their high overages. Id. at 550.
Case: 20-1799 Document: 39 Page: 16 Filed: 09/01/2021
16 BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC.
Belcher adopts this argument on appeal and contends
that Mr. Rubin withheld the references not because he had
deceptive intent, but because he genuinely believed that
the withheld products, including the JHP product, were ir-
relevant given their high overages. Appellant’s Br. 61, 63.
Belcher appears to argue that while Mr. Rubin was acting
in a “self-serving manner in order to . . . maintain an exist-
ing patent,” id. at 63–64 (quoting Chen v. Bouchard,
347 F.3d 1299, 1309 (Fed. Cir. 2003)), that behavior by it-
self is not enough to establish that he had a deceptive in-
tent. According to Belcher, the record provides
corroboration that his mental state was a genuine belief
about the irrelevance of the references, rather than a desire
to deceive the PTO. Appellant’s Br. 63–64.
In Aventis, we rejected similar post hoc rationales for
withholding material prior art. See 675 F.3d at 1335–37.
There we found no clear error in the district court’s finding
of intent where it “did not rely solely on its finding that [the
inventor] was not credible but instead viewed [his] testi-
mony in light of the other evidence to reach its intent con-
clusion.” Id. at 1336. The same is true here. The district
court found Mr. Rubin’s reasons for withholding the JHP
product to be implausible and not credible. Belcher, 450 F.
Supp. 3d at 549. But the district court also relied on other
record evidence to support its intent finding, including Mr.
Rubin’s prior knowledge of the JHP product, his central
role in both FDA approval and patent prosecution, and his
arguments to the examiner about the “criticality” of the 2.8
to 3.3 pH range despite knowing that Sintetica’s batches
used the same range. See id. at 548–51. As in Aventis, we
conclude that the district court did not clearly err in finding
that the single most reasonable inference is that Mr. Rubin
possessed the specific intent to deceive the PTO when with-
holding the JHP product.
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BELCHER PHARMACEUTICALS, LLC v. HOSPIRA, INC. 17
CONCLUSION
We conclude that the district court did not clearly err
in making its factual findings regarding materiality and
intent, nor did it abuse its discretion in ultimately deciding
that the ’197 patent is unenforceable for inequitable con-
duct. We have considered Belcher’s remaining arguments
and find them unpersuasive. We therefore affirm.
AFFIRMED
COSTS
No costs.