NOTE: This disposition is nonprecedential.

 

United States Court of Appeals 

for the Federal Circuit ______________________ 

NOVARTIS PHARMA AG, NOVARTIS 

TECHNOLOGY LLC, NOVARTIS 

PHARMACEUTICALS CORPORATION,

Appellants

v.

REGENERON PHARMACEUTICALS, INC.,

Appellee

______________________ 

2023-1334

______________________ 

Appeal from the United States Patent and Trademark 

Office, Patent Trial and Appeal Board in No. IPR2021-

00816.

______________________ 

Decided: September 23, 2024

______________________ 

WILLIAM M. JAY, Goodwin Procter LLP, Washington, 

DC, argued for appellants. Also represented by GERARD J.

CEDRONE, JOSHUA WEINGER, Boston, MA. ELIZABETH 

HOLLAND, Allen Overy Shearman Sterling US LLP, New 

York, NY; WILLIAM G. JAMES, II, Washington, DC. 

 ANISH R. DESAI, Weil, Gotshal & Manges LLP, New 

York, NY, argued for appellee. Also represented by ADAM 

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2 NOVARTIS PHARMA AG v. REGENERON PHARMACEUTICALS, INC. 

BANKS, ELIZABETH WEISWASSER; PRIYATA PATEL,

CHRISTOPHER PEPE, Washington, DC. 

 ______________________ 

Before PROST, REYNA, and CHEN, Circuit Judges.

CHEN, Circuit Judge. 

Novartis Pharma AG, Novartis Technology LLC, and 

Novartis Pharmaceuticals Corporation (collectively, Novartis) appeal from a Patent Trial and Appeal Board 

(Board) final written decision finding all claims of U.S. Patent No. 9,220,631 (’631 patent) unpatentable under 

35 U.S.C. § 103. See Regeneron Pharms., Inc. v. Novartis 

Pharma AG, No. IPR2021-00816, 2022 WL 18460885, at 

*48 (P.T.A.B. Oct. 25, 2022) (Decision). Novartis raises a 

laundry list of fact-intensive arguments. For the following 

reasons, we affirm. 

I.

Novartis is the assignee of the ’631 patent, which relates “to a small volume syringe such as a syringe suitable 

for ophthalmic injections.” ’631 patent col. 1 ll. 5–7. The 

’631 patent describes a syringe that can be used to treat 

ocular diseases by injecting a vascular endothelial growth 

factor (VEGF) antagonist into a patient’s eye. Id. at claim 

1; id. col. 8 l. 64 – col. 9 l. 4. 

As set out in the ’631 patent, syringe design has many 

dueling considerations. For example, a syringe and its contents must be sterile to avoid infection. Id. col. 1 ll. 15–18. 

One of the claimed ways to sterilize a syringe is to use a 

hydrogen peroxide sterilization process. Id. col. 9 ll. 49–52. 

But some therapeutics are sensitive to that sterilization 

process, so the syringe may be sealed to prevent hydrogen 

peroxide from interacting with the drug compound. Id.

col. 1 ll. 31–40. A tight seal, however, can increase the 

amount of force required to administer the drug. That force 

is called the break-loose force, and a high break-loose force 

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NOVARTIS PHARMA AG v. REGENERON PHARMACEUTICALS, INC. 3

is undesirable. Id. col. 1 ll. 36–40, col. 5 ll. 27–31. One 

way to reduce the break-loose force is to lubricate the syringe with silicone oil. Id. col. 4 ll. 48–50. But silicone oil 

creates its own issues for eye injections because it can 

cause complications if it gets into a patient’s eye. Id. col. 3 

ll. 39–42, col. 4 ll. 50–55. 

Given that backdrop, the present invention claims a 

sterile pre-filled syringe that is used for eye injections and

meets certain silicone oil and break-loose force limitations. 

Claims 1 and 21 are illustrative for purposes of this appeal:

1. A pre-filled, terminally sterilized syringe for intravitreal injection, the syringe comprising a glass 

body forming a barrel, a stopper and a plunger and 

containing an ophthalmic solution which comprises 

a VEGF-antagonist, wherein:

(a) the syringe has a nominal maximum fill 

volume of between about 0.5 ml and about 

1 ml,

(b) the syringe barrel comprises from about 

1 μg to 100 μg silicone oil,

(c) the VEGF antagonist solution comprises no more than 2 particles >50 μm in 

diameter per ml and wherein the syringe 

has a stopper break loose force of less than 

about 11N.

21. A blister pack comprising a pre-filled syringe 

according to claim 17, wherein the syringe has been 

sterili[z]ed using EtO or H2O2 with a Sterility Assurance Level of at least 10–6. 

Id. at claims 1, 21.

Regeneron Pharmaceuticals, Inc., (Regeneron) petitioned for, and the Board instituted, inter partes review of 

all claims of the ’631 patent. Regeneron asserted several 

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4 NOVARTIS PHARMA AG v. REGENERON PHARMACEUTICALS, INC. 

different grounds of unpatentability under 35 U.S.C. § 103. 

Decision, 2022 WL 18460885, at *2. 

Before the Board, Novartis did not meaningfully dispute that all limitations are disclosed in the prior art. At a 

high level, Sigg1 discloses a pre-filled terminally sterilized 

syringe containing a VEGF-antagonist, and Boulange2

teaches a stopper with the claimed silicone oil and breakloose force limitations. Id. at *20. But Novartis argued 

that a skilled artisan would not have been motivated to 

combine the prior art with a reasonable expectation of success in achieving the claimed invention. Novartis also contended that its evidence of objective indicia of 

nonobviousness counseled against finding the claimed invention obvious.

In a 128-page opinion, the Board found all claims unpatentable under 35 U.S.C. § 103 over combinations of

prior art references that all include Sigg and Boulange. 

Specifically, the Board concluded that a skilled artisan 

would have been motivated to combine Sigg’s terminally 

sterilized pre-filled syringe with one of Boulange’s stopper 

configurations, Stopper C, which has the claimed stopper 

with a break-loose force of less than 11N. The Board found 

that Boulange’s baked-on siliconization method, used with 

its Stopper C, would help reduce the amount of silicone oil, 

which a skilled artisan would have wanted to minimize to 

avoid negative interactions with the drug product. Id. at 

*20–21. The Board also found that a skilled artisan would 

have had a reasonable expectation of success with this combination because Boulange’s Stopper C was sealed tightly

enough to be terminally sterilized using Sigg’s vaporized 

hydrogen peroxide sterilization process. Id. at *23–25. After considering Novartis’s objective-indicia evidence, the 

Board concluded that “[t]he stronger evidence of 

1 PCT Patent Publication No. WO 2011/006877. 2 PCT Patent Publication No. WO 2009/030976. 

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NOVARTIS PHARMA AG v. REGENERON PHARMACEUTICALS, INC. 5

obviousness cannot be overcome with the weaker evidence 

of long-felt need and failure of others.” Id. at *37. Based 

on these findings, the Board did not address Regeneron’s 

alternative grounds of unpatentability. 

Novartis appeals the Board’s decision, raising thirteen 

arguments, some of which also include additional sub-arguments. None of these arguments is persuasive, but we 

address only Novartis’s principal arguments. We have jurisdiction under 28 U.S.C. § 1295(a)(4)(A).

II.

Novartis first argues that the Board erred in finding a 

motivation to combine Sigg and Boulange because, in Novartis’s view, the prior art teaches away from combining 

those references. “What the prior art teaches, whether it 

teaches away from the claimed invention, and whether it 

motivates a combination of teachings from different references are questions of fact.” In re Fulton, 391 F.3d 1195, 

1199–200 (Fed. Cir. 2004). We review the Board’s factual 

findings for substantial evidence. PersonalWeb Techs.,

LLC v. Apple, Inc., 917 F.3d 1376, 1381 (Fed. Cir. 2019). 

Substantial evidence review asks “whether a reasonable 

fact finder could have arrived at the agency’s decision, 

which requires examination of the record as a whole, taking into account evidence that both justifies and detracts 

from an agency’s decision.” Id. (citation omitted).

The Board found a motivation to combine Sigg’s sterilization process with Boulange’s Stopper C because Boulange’s baked-on siliconization process “would help reduce 

the amount of ‘residual’ or ‘free’ silicone oil that can enter 

the protein formulation and cause negative effects.” Decision, 2022 WL 18460885, at *21. Novartis contends three

pieces of evidence allegedly teach away from using Boulange’s Stopper C. We address each in turn.

First, Boulange discloses that Stopper C’s break-loose 

force increased from 4.7N to 8.4N over the equivalent of 

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6 NOVARTIS PHARMA AG v. REGENERON PHARMACEUTICALS, INC. 

three months. This data is presented in Table 5. J.A. 3943. 

Novartis contends this data teaches away from using Stopper C because a skilled artisan would want a consistent 

break-loose force over a syringe’s shelf life.

Substantial evidence supports the Board’s finding that 

this evidence does not teach away from using Stopper C. 

At the outset, we note that claim 1 does not require a consistent force over time. Rather, as the Board recognized, 

the claim language merely requires a break-loose force of 

less than about 11N, and a break-loose force of 8.4N meets 

that claim limitation. The ’631 patent’s written description 

also provides that forces less than 20N were known in the 

prior art to be acceptable for intravitreal injections. ’631 

patent col. 5 ll. 35–38. That disclosure supports the 

Board’s finding that a break-loose force of 8.4N would not 

teach away from using Stopper C. The Board also credited 

the testimony of Regeneron’s expert witness, Mr. Koller, 

that most pre-filled syringes are expected to experience 

some amount of force increase over their shelf life. Novartis did not submit any evidence showing that a skilled artisan would have been dissuaded from using a syringe that 

has a roughly 4N increase in break-loose force over time. 

Oral Arg. at 4:56–5:17 (available at https://oralarguments.cafc.uscourts.gov/default.aspx?fl=23-1334_0806202

4.mp3). On this record, substantial evidence supports the 

Board’s finding. 

Second, following the results disclosed in Table 5, Boulange states that Stopper C was “markedly inferior” to 

Stopper B1. J.A. 3943. Novartis contends this statement 

teaches away from using Stopper C because a skilled artisan would have been motivated to use Stopper B1 instead 

of Stopper C.

Substantial evidence supports the Board’s finding that 

this evidence does not teach away from using Stopper C. 

“In assessing whether prior art teaches away, that ‘better 

alternatives exist in the prior art does not mean that an 

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NOVARTIS PHARMA AG v. REGENERON PHARMACEUTICALS, INC. 7

inferior combination is inapt for obviousness purposes.’” 

Bayer Pharma AG v. Watson Lab’ys, Inc., 874 F.3d 1316, 

1327 (Fed. Cir. 2017) (quoting In re Mouttet, 686 F.3d 1322, 

1334 (Fed. Cir. 2012)). The Board credited Mr. Koller’s expert testimony to find that a skilled artisan would have 

been motivated to use Stopper C because it was comprised 

of rubber and coated with silicone oil—a common stopper 

design in the prior art. Decision, 2022 WL 18460885, at 

*22. Plus, Stopper C’s break-loose force was within the 

claimed “about 11N” and lower than the ’631 patent’s disclosure of 20N being a known, acceptable break-loose force 

for intravitreal injections. Id. In view of the foregoing, the 

Board reasonably found that a skilled artisan “would understand Stopper C is an acceptable alternative to Stopper 

B1 . . . even though it is categorized as ‘markedly inferior’ 

to Stopper B1.” Id.

Finally, Boulange states that Stopper C’s “friction 

forces . . . were relatively high, something which does not 

appear to be acceptable for a medical device.” J.A. 3945. 

This statement came after the results presented in Table 

7, and in the experiment that generated those results, 

Stopper C was not siliconized (i.e., lubricated with silicone 

oil). Decision, 2022 WL 18460885, at *22. In contrast, 

Stopper C was siliconized for the experiment that generated the results in Table 5, which—as already discussed—

the Board found did not teach away from using Stopper C. 

Because a skilled artisan would be considering using siliconized Stopper C, the Board reasonably found that this 

statement about Table 7’s results did not teach away from 

the results disclosed in Table 5. 

III.

Novartis challenges the Board’s finding of a reasonable 

expectation of success in combining Sigg and Boulange to 

achieve the claimed invention. We review the Board’s finding of a reasonable expectation of success for substantial 

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8 NOVARTIS PHARMA AG v. REGENERON PHARMACEUTICALS, INC. 

evidence. Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1366 (Fed. Cir. 2016). 

The Board found that a skilled artisan would have had 

a reasonable expectation of success because Boulange’s 

Stopper C was sealed tightly enough to be terminally sterilized using Sigg’s vaporized hydrogen peroxide sterilization process. Decision, 2022 WL 18460885, at *23–25. 

Novartis contends the Board erred because Boulange’s syringes were not sufficiently gas-tight to be able to use Sigg’s 

sterilization process. 

Novartis’s argument appears to be premised on an incorrect view of the claim term “terminally sterilized.” Relying on Sigg, Novartis notes that very few products have 

the “required tightness . . . to avoid ingress of sterilizing 

gasses into the” pre-filled syringe. Appellant’s Br. 43–44. 

But the Board construed “terminally sterilized” to require 

only minimizing the contact between the drug product and 

the sterilizing agent, and Novartis does not challenge this 

construction on appeal. Decision, 2022 WL 18460885, at 

*6. Thus, the Board did not need to find a reasonable expectation of success in “avoiding ingress of sterilizing 

gases”; it needed to find only a reasonable expectation of 

success in “minimizing” the ingress of sterilizing gases. 

Substantial evidence supports the Board’s finding of a 

reasonable expectation of success. The Board credited 

Mr. Koller’s testimony that it was standard to design prefilled syringes to be gas-tight to protect the drug from degrading over its shelf life and to prevent sterilizing gas 

from entering the syringe. Id. at *24. Boulange also supports the Board’s finding by describing that lower breakloose forces are achievable in the invention “without having 

to add lubricant and while preserving the tightness of the 

contact region between said two parts.” Id. (quoting 

J.A. 3930). The Board’s finding is further buttressed by the 

fact that the record evidence “does not demonstrate that 

any special tightness or specific stopper material, coating, 

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NOVARTIS PHARMA AG v. REGENERON PHARMACEUTICALS, INC. 9

or dimensions[] would have been required to achieve terminal sterilization.” Id. at *25. 

IV.

Novartis next challenges the Board’s finding that Sigg 

discloses claim 21’s limitation of achieving a sterility assurance level of at least 10–6 using vaporized hydrogen peroxide. We review the Board’s findings about the scope and 

content of the prior art for substantial evidence. Ethicon 

Endo-Surgery, Inc. v. Covidien LP, 812 F.3d 1023, 1028,

1034 (Fed. Cir. 2016). 

The Board found that Sigg discloses this limitation because Sigg defines sterility for a health care product as

achieving a sterility assurance level of 10–6 and describes 

vaporized hydrogen peroxide as a “sterilization” treatment. 

Decision, 2022 WL 18460885, at *42. Relying on expert 

witness testimony, the Board also determined that a 

skilled artisan would have known a sterility assurance 

level of 10–6 was based on regulatory requirements for 

health care products, and therefore pre-filled syringes are 

required to meet that sterility assurance level. Id. Substantial evidence supports these findings.

Novartis’s main argument is that it disagrees with 

Mr. Koller’s testimony that a skilled artisan knows sterilization refers to a sterility assurance level of 10–6 whereas 

sanitization refers to a sterility assurance level of 10–3. Novartis points out that Sigg at one-point states that the two 

terms are “interchangeable,” so Novartis posits that they 

cannot refer to different sterility assurance levels. 

This argument ignores the applicable standard of review. Substantial evidence supports the Board’s finding, 

and on the facts of this case, one inconsistent piece of evidence does not undermine that finding. 

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10 NOVARTIS PHARMA AG v. REGENERON PHARMACEUTICALS, INC. 

V.

We have considered Novartis’s remaining arguments 

and find them unpersuasive.3 For the foregoing reasons, 

we affirm the Board’s decision.

AFFIRMED

3 Two of those arguments are worth mentioning. 

First, Novartis argues that the Board erred in relying on 

non-prior art. Substantial evidence supports the Board’s 

findings even ignoring the alleged non-prior art evidence. 

Second, on objective indicia of nonobviousness, the parties 

extensively redacted this portion of the public version of 

the Board’s decision, but we note that substantial evidence 

supports the Board’s findings on this matter as well.

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