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

Case: 20-1799 Document: 39 Page: 3 Filed: 09/01/2021

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.

Case: 20-1799 Document: 39 Page: 4 Filed: 09/01/2021

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

Case: 20-1799 Document: 39 Page: 5 Filed: 09/01/2021

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).

Case: 20-1799 Document: 39 Page: 6 Filed: 09/01/2021

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-

Case: 20-1799 Document: 39 Page: 7 Filed: 09/01/2021

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.

Case: 20-1799 Document: 39 Page: 8 Filed: 09/01/2021

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.

Case: 20-1799 Document: 39 Page: 9 Filed: 09/01/2021

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

Case: 20-1799 Document: 39 Page: 11 Filed: 09/01/2021

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.

Case: 20-1799 Document: 39 Page: 12 Filed: 09/01/2021

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).

Case: 20-1799 Document: 39 Page: 13 Filed: 09/01/2021

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.

Case: 20-1799 Document: 39 Page: 14 Filed: 09/01/2021

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

Case: 20-1799 Document: 39 Page: 15 Filed: 09/01/2021

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.

Case: 20-1799 Document: 39 Page: 17 Filed: 09/01/2021

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.