NOTE: This disposition is nonprecedential.

United States Court of Appeals 

for the Federal Circuit ______________________

SANOFI-AVENTIS DEUTSCHLAND GMBH,

Appellant

v.

MYLAN PHARMACEUTICALS INC.,

Appellee

______________________

2019-1368, 2019-1369

______________________

Appeals from the United States Patent and Trademark 

Office, Patent Trial and Appeal Board in Nos. IPR2017-

01526, IPR2017-01528.

______________________

Decided: November 19, 2019 

______________________

ADAM BANKS, Weil, Gotshal & Manges LLP, New York, 

NY, argued for appellant. Also represented by ELIZABETH 

WEISWASSER, ANISH R. DESAI, ANDREW GESIOR, AARON L. J.

PEREIRA; ROBERT T. VLASIS, III, Washington, DC. 

 DOUGLAS H. CARSTEN, Wilson, Sonsini, Goodrich & 

Rosati, PC, San Diego, CA, argued for appellee. Also represented by JEFFREY WILLIAM GUISE, ALINA LEONIDOVNA 

LITOSHYK, ELHAM FIROUZI STEINER, LORELEI WESTIN; 

NICOLE W. STAFFORD, Austin, TX; WENDY L. DEVINE, San 
SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS 

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Francisco, CA; ADAM WILLIAM BURROWBRIDGE, LORA 

MARIE GREEN, RICHARD TORCZON, Washington, DC. 

 ______________________

Before NEWMAN, TARANTO, and CHEN, Circuit Judges.

Opinion for the court filed by Circuit Judge TARANTO.

Dissenting opinion filed by Circuit Judge NEWMAN.

TARANTO, Circuit Judge.

Sanofi-Aventis Deutschland GMBH’s owns U.S. Patent 

Nos. 7,476,652 and 7,713,930, which describe and claim 

certain formulations of a particular kind of insulin. Mylan 

Pharmaceuticals Inc. sought and obtained from the Patent 

and Trademark Office (PTO) inter partes reviews of all 

claims of those patents under 35 U.S.C. §§ 311–319. In 

those reviews, the PTO’s Patent Trial and Appeal Board 

agreed with Mylan that the subject matter of the claims is 

unpatentable for obviousness. Sanofi appeals, challenging

the Board’s findings that a relevant artisan would have 

had a motivation to combine prior-art references to arrive 

at the claimed inventions with a reasonable expectation of 

success, and also challenging the Board’s evaluation of 

Sanofi’s evidence of commercial success. We reject Sanofi’s 

challenges and affirm the Board’s decisions.

I

The ’930 patent issued from a continuation of the application that issued as the ’652 patent, and the two share 

a specification. The patents involve a genetically engineered form of insulin—insulin glargine (sometimes called 

simply “glargine”)—identified in the patent as “Gly(A21)-

Arg(B31)-Arg(B32)-human insulin.” ’652 patent, col. 2, 

lines 56–57. The patents describe and claim formulations 

of glargine that include a nonionic surfactant—polysorbates or poloxamers in the ’652 patent, esters and ethers of 
SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS 

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polyhydric alcohols in the ’930 patent. Claim 7 of the ’652 

patent is illustrative for present purposes:

7. A pharmaceutical formulation comprising 

Gly(A21), Arg(B31), Arg(B32)-human insulin,

at least one chemical entity chosen from polysorbate and poloxamers;

at least one preservative; and

water,

wherein the pharmaceutical formulation has a 

pH in the acidic range from 1 to 6.8.

’652 patent, col. 11, lines 21–28.

The parties accept that certain background facts were

publicly known at the 2002 priority date for these patents. 

Glargine is a modified version of human insulin that, when 

injected as part of an acidic solution, acts for longer in a 

subject than does natural human insulin. Glargine stays

in solution at relatively acidic pH levels, and in the priorart glargine product (which lacked the surfactants claimed 

in the patents now at issue), it was injected into a patient 

as part of an acidic solution. Once the glargine-containing 

solution is in tissue under the skin, the higher, substantially neutral pH of the tissue causes glargine to precipitate 

out of solution and to aggregate into hexamers, which then 

act as a reservoir of glargine that is slowly released into the 

patient’s blood over twenty-four hours. Natural human insulin is more soluble than glargine at the neutral pH level 

of human tissue below an injection site. Natural human 

insulin is generally injected in a solution of comparably

neutral pH; and when injected, it rapidly dissociates into 

monomers—the physiologically active form of insulin. 

Such rapid disassociation allows for faster processing by 

the body but also necessitates more frequent injections.

Sanofi first commercially sold glargine in the U.S. in 

May 2001, under the trade name Lantus®, whose product 
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label identifies, among other things, a pH of 4 and the inclusion of some zinc. Physician’s Desk Reference at 709 

(55th ed. 2001) (Lantus® Label); J.A. 6690. Some patients 

soon began reporting problems with turbidity in the vials, 

i.e., before injection. Sanofi determined that the turbidity 

was caused by undesirable “non-native” aggregation of the 

glargine protein while still in solution. Non-native aggregation denatures the insulin protein and is substantially 

irreversible. By contrast, “native” aggregation preserves 

the structure of the insulin protein and is reversible. 

Glargine’s mechanism of action requires some amount of 

desirable native aggregation after injection under the skin 

for its slow-release property to take effect. Sanofi resolved

the vial-turbidity problem by adding a nonionic surfactant 

to the glargine formulation to prevent non-native aggregation.

Mylan petitioned the PTO for inter partes reviews of 

all claims of the ’652 and ’930 patents, arguing unpatentability for obviousness based on combining either the Lantus® Label or an article by Owens1 with one or more of 

three secondary references.2 The parties do not dispute 

that, for each claim, the asserted combinations of 

 

1 David R. Owens, et al., Pharmacokinetics of 125ILabeled Insulin Glargine (HOE 901) in Healthy Men: Comparison with NPH Insulin and the Influence of Different 

Subcutaneous Injection Sites, 23 DIABETES CARE 813 (2000) 

(Owens).

2 The three secondary references are: W.D. 

Lougheed, et al., Physical Stability of Insulin Formulations, 32 DIABETES 424 (1983) (Lougheed); Farmaceutiska 

Specialiteter I Sverige, Summary of Product Characteristics Entry for Insuman Infusat (2000) (FASS); and Ulrich 

Grau & Christopher D. Saudek, Stable Insulin Preparation 

for Implanted Insulin Pumps: Laboratory & Animal Trials, 

36 DIABETES 1453 (1987) (Grau).
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references teach every claim limitation. The main dispute 

is whether a relevant artisan would have been motivated 

to combine these references in the way claimed in the two 

patents at issue, with a reasonable expectation of success.

On December 13, 2017, the Board, acting as delegee of 

the PTO’s Director, 37 C.F.R. §§ 42.4, 42.108, instituted the 

two requested reviews. Mylan Pharm. Inc. v. SanofiAventis Deutschland GmbH, IPR2017-01526, 2017 WL 

6403855 (P.T.A.B. Dec. 13, 2017) (covering the ’652 patent); 

Mylan Pharm. Inc. v. Sanofi-Aventis Deutschland GmbH, 

No. IPR2017-01528, 2017 WL 6403082 (P.T.A.B. Dec. 13, 

2017) (covering the ’930 patent). On December 12, 2018, 

the Board issued final written decisions in both proceedings, determining that all claims in both patents are unpatentable for obviousness based on combinations of 

Lantus® Label or Owens with Lougheed, FASS, and/or 

Grau. Mylan Pharm. Inc. v. Sanofi-Aventis Deutschland 

GmbH, IPR2017-01526, 2018 WL 6584915 (P.T.A.B. Dec. 

12, 2018) (Decision); Mylan Pharm. Inc. v. Sanofi-Aventis 

Deutschland GmbH, IPR2017-01528, 2018 WL 6584640

(P.T.A.B. Dec. 12, 2018).3 The Board found that a relevant 

artisan would have been motivated to make the required 

combination based on a recognition that insulins had an 

aggregation problem in vials with air space and that surfactants (like the standard ones claimed here) offered a solution. Decision at *12–18. The Board also determined 

that, given the prior-art analysis, Sanofi’s evidence of commercial success was too weak to support a conclusion of 

nonobviousness. Id. at *18–20. 

 

3 The Board’s final written decisions are substantively identical for present purposes. In its appeal to this 

court, Sanofi has not made separate arguments regarding 

the two decisions. Accordingly, we hereafter discuss and 

cite only the decision in IPR2017-01526 (Decision), but our 

analysis applies equally to IPR2017-01528.
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Sanofi timely appealed under 35 U.S.C. §§ 141(c), 319. 

We have jurisdiction under 28 U.S.C. § 1295(a)(4)(A).

II

We review the Board’s compliance with legal standards 

de novo, Pride Mobility Products Corp. v. Permobil, Inc., 

818 F.3d 1307, 1314 (Fed. Cir. 2016), and its underlying 

factual determinations for substantial evidence, Personal 

Web Technologies, LLC v. Apple, Inc., 848 F.3d 987, 991 

(Fed. Cir. 2017). Among the factual determinations in an 

obviousness analysis are “findings as to . . . the presence or 

absence of a motivation to combine or modify with a reasonable expectation of success[] and objective indicia of 

non-obviousness.” Ariosa Diagnostics v. Verinata Health, 

Inc., 805 F.3d 1359, 1364 (Fed. Cir. 2015).

A

Sanofi challenges the Board’s finding of a motivation to 

combine the prior-art references to arrive at the claimed 

glargine formulation with certain surfactants. Sanofi argues that (1) KSR International Co. v. Teleflex Inc., 550 

U.S. 398 (2007), required the Board to find that the prior 

art disclosed an aggregation problem for glargine specifically (not just insulins in general); (2) the Board improperly 

relied on each patent’s own (shared) specification in finding 

a motivation to combine; and (3) substantial evidence does 

not support the Board’s finding because key evidence cited 

by the Board concerned insulins in general rather than 

glargine specifically. The first two contentions assert legal 

errors, the third evidentiary insufficiency. We address the

contentions in turn. We find each one unpersuasive. 

1

Sanofi argues that the Board was required, under KSR, 

to find in the prior art a recognition of an aggregation problem for glargine specifically, not just for insulins generally. 

In Sanofi’s view, KSR demands more than a factually supported finding that recognition of an aggregation risk for 
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insulins generally would have motivated a relevant artisan 

to address aggregation for this particular insulin. We reject Sanofi’s view of KSR.

The Supreme Court in KSR explained that, “because 

inventions in most, if not all, instances rely upon building 

blocks long since uncovered, and claimed discoveries almost of necessity will be combinations of what, in some 

sense, is already known,” “it can be important to identify a 

reason that would have prompted a person of ordinary skill 

in the relevant field to combine the elements in the way the 

claimed new invention does.” Id. at 418–19. But KSR

stressed flexibility and realism over rigidity and formalism 

in assessing what such reasons might be:

In KSR, the Supreme Court criticized a rigid 

approach to determining obviousness based on the 

disclosures of individual prior-art references, with 

little recourse to the knowledge, creativity, and 

common sense that an ordinarily skilled artisan 

would have brought to bear when considering combinations or modifications. KSR, 550 U.S. at 415–

22. Rejecting a blinkered focus on individual documents, the Court required an analysis that reads 

the prior art in context, taking account of “demands 

known to the design community,” “the background 

knowledge possessed by a person having ordinary 

skill in the art,” and “the inferences and creative 

steps that a person of ordinary skill in the art 

would employ.” Id. at 418. This “expansive and 

flexible approach,” id. at 415, is consistent with our 

own pre-KSR decisions acknowledging that the inquiry “not only permits, but requires, consideration 

of common knowledge and common sense.” DyStar 

Textilfarben GmbH & Co. Deutschland KG v. C.H. 

Patrick Co., 464 F.3d 1356, 1367 (Fed. Cir. 2006).

Randall Mfg. v. Rea, 733 F.3d 1355, 1362 (Fed. Cir. 2013); 

see also Arctic Cat Inc. v. Bombardier Recreational Prod. 
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Inc., 876 F.3d 1350, 1359 (Fed. Cir. 2017) (“The court 

should consider a range of real-world facts to determine 

whether there was an apparent reason to combine the 

known elements in the fashion claimed by the patent at issue.”) (citation and internal quotation marks omitted).

The Board did not depart from KSR when it made, and 

relied on, findings that a relevant artisan would have recognized a potential aggregation-in-the-vial problem with 

glargine as part of the general recognition of aggregation 

problems with insulins. Nothing in KSR demands the kind 

of prior-art identifications of a problem at the level of specificity that Sanofi urges. The Board thus properly examined the evidence in this particular case to determine

whether a relevant artisan would have recognized an insulin aggregation problem in the prior art and expected 

glargine to share that problem. Decision at *14–16. 

Whether the Board was correct is a case-specific matter of 

evidentiary sufficiency—a matter we discuss more fully infra.

2

We also reject Sanofi’s contention that the Board committed legal error when it cited the shared patent specification. The “background of the invention” portion of the 

specification includes the following passage:

The specific preparation of insulin glargine, 

which leads to the prolonged duration of action, is 

characterized, in contrast to previously described 

preparations, by a clear solution having an acidic 

pH. Especially at acidic pH, insulins, however, 

show a decreased stability and an increased proneness to aggregation on thermal and physicomechanical stress, which can make itself felt in the 

form of turbidity and precipitation (particle formation (Brange et al., J. Ph. Sci 86:517-525 (1997)).
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The proneness to aggregation can additionally 

be promoted by hydrophobic surfaces which are in 

contact with the solution (Sluzky et al., Proc. Natl. 

Acad. Sci. 88:9377-9381 (1991). Surfaces which can 

be considered as hydrophobic are the glass vessels 

of the preparations, the stopper material of the 

sealing caps or the boundary surface of the solution 

with the air supernatant. In addition, very fine silicone oil droplets can function as additional hydrophobic aggregation nuclei in the taking of the daily 

insulin dose by means of customary, siliconized insulin syringes and accelerate the process.

’652 patent, col. 2, line 66 through col. 3, line 17. The Board 

cited this material in finding that insulin was known to aggregate on hydrophobic surfaces, at the air/water interface 

of a container, and in acidic solutions. Decision at *14–15.

Sanofi challenges the Board’s reliance on this material 

as legally improper, invoking our longstanding recognition 

that a tribunal should not “look[] to knowledge taught by 

the inventor . . . and then use[] that knowledge against its 

teacher.” Panduit Corp. v. Dennison Mfg. Co., 774 F.2d 

1082, 1092 (Fed. Cir. 1985), vacated on other grounds, 475 

U.S. 809 (1986); see also InTouch Techs., Inc. v. VGO 

Commc’ns, Inc., 751 F.3d 1327, 1351 (Fed. Cir. 2014). But 

the Board did not violate that principle, because it did not 

use the specification for its teachings about the inventor’s 

discovery. Rather, it used the specification for its teachings 

about prior-art knowledge, and that use of a specification 

is not just common, given patent drafters’ standard practice of reciting prior art in setting out the background of 

the invention, but permissible. E.g., Smith & Nephew, Inc. 

v. Rea, 721 F.3d 1371, 1378–79 (Fed. Cir. 2013); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342,

1362 (Fed. Cir. 2007); cf. WesternGeco LLC v. ION Geophysical Corp., 889 F.3d 1308, 1329–30 (Fed. Cir. 2018) (specification confirmed Board’s understanding of prior art in 

anticipation context).
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The Board understood the patent specification, on this

issue, to be addressing what was already known—a reading that is reasonable given the language used and citations to prior art. Moreover, the Board used the cited 

material not as the sole support for any finding but in conjunction with support from other sources. The Board found 

evidence of insulin aggregation on hydrophobic surfaces 

and at air/water interfaces in a handful of other prior-art 

references. Decision at *14–15. The Board cited four additional references to support the finding that insulin was 

known to aggregate in acidic solutions. Id. at *15. The 

Board’s use of the patent specification, we conclude, did not 

rest on legal error.

3

We further conclude that the Board’s finding of a motivation to combine is supported by substantial evidence.

While the Board must provide “a reasoned basis” for its actions, “‘we will uphold a decision of less than ideal clarity if 

the agency’s path may reasonably be discerned.’” In re 

NuVasive, Inc., 842 F.3d 1376, 1383 (Fed. Cir. 2016) (quoting Bowman Transp., Inc. v. Ark.–Best Freight System, 

Inc., 419 U.S. 281, 285, 286 (1974)). The Board “must articulate a reason why a [relevant artisan] would combine 

the prior art references.” Id. at 1382. And the finding of 

such a reason must be supported by substantial evidence, 

which is “such relevant evidence as a reasonable mind 

might accept as adequate to support a conclusion.” Id. at 

1380 (citation and internal quotation marks omitted); see

also Intelligent Bio-Systems, Inc. v. Illumina Cambridge 

Ltd., 821 F.3d 1359, 1366 (Fed. Cir. 2016) (explaining that 

review for substantial evidence “requires examination of 

the record as a whole, taking into account evidence that 

both justifies and detracts from an agency’s decision”) (citation and internal quotation marks omitted).

The Board’s findings with respect to the motivation to 

combine are detailed and well supported. The Board found 
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that insulins “had a known tendency to aggregate in the 

presence of hydrophobic surfaces” and at air-water interfaces and that a relevant artisan would have expected 

glargine to behave similarly to other insulins when in contact with hydrophobic surfaces and at air-water interfaces.

Decision at *14. The Board also found that nonionic surfactants, including the claimed ones, were well known and 

had been used successfully to stabilize insulin formulations, and so would have been looked to by a relevant artisan concerned about aggregation in glargine. Id. at *11–

12, *17. The record contains substantial evidence to support those findings. 

Two references by Brange disclose that insulins with a 

variety of amino acid structures each display some degree 

of aggregation. J.A. 6762; J.A. 6797. Likewise, as already 

discussed, the shared specification of the ’652 and ’930 patents itself indicates, in a discussion introduced by discussing glargine, that insulins tend to aggregate on 

hydrophobic surfaces (like the glass of vials), especially in 

acidic solutions like those used for glargine. See ’652 patent, col. 2, line 66 through col. 3, line 17. Mylan’s expert 

explained, with citations to prior art, that “insulin aggregation is a well-established problem in the field and described in detail by numerous references.” J.A. 6475.

Sanofi argued that the prior art discloses aggregation 

only in insulin pumps, but the Board disagreed, finding instead that “it is the air-water interfaces and interactions 

with hydrophobic surfaces that promote insulin aggregation, and not the type of device used to deliver the insulin 

formulation.” Decision at *15. Prior art supports the 

Board’s determination. See, e.g., J.A. 6796 (noting that insulin has a tendency to aggregate on hydrophobic surfaces); 

J.A. 14535 (“It has been suggested that insulin is destabilized by adsorption at hydrophobic interfaces (air-water or 

water-pump materials). . . .”); J.A. 6906; J.A. 6951. The 

Board also reasonably understood Mylan’s expert to testify 

that aggregation “was known in the art not to be unique to 
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[insulin] pumps,” J.A. 12246 (quoted in Decision at *15), 

and found that Sanofi’s expert, in suggesting otherwise, relied on evidence that went no further than indicating that 

insulin pumps showed a greater tendency for aggregation 

than other container types, Decision at *15.

Other evidence reasonably supports the Board’s finding that a relevant artisan would have understood glargine 

to come within the general recognition of an aggregation 

problem for insulins. The Lantus® Label discloses glargine 

formulated as a solution with an acidic pH, J.A. 6690, and 

both the Lantus® Label and Owens teach glargine formulations in vials known to contain hydrophobic surfaces and 

an air-water interface, J.A. 6693; J.A. 6699–700. There 

was evidence, too, that, while insulin exists in equilibrium 

as monomers, dimers, and hexamers, an acidic environment shifts the equilibrium toward monomers, which are 

more susceptible to aggregation. J.A. 6769–70; J.A. 6798–

99; J.A. 6830; J.A. 14535. And relatedly, although Lantus® 

contains zinc, which can affect rates of aggregation, the evidence supports the Board’s findings, Decision at *15, that 

zinc does not bind to insulin in an acidic solution, like the 

Lantus® solution, J.A. 13741, and, more generally, that 

zinc in the Lantus® solution would not have led a relevant 

artisan to see glargine as immune from the general problem of insulin aggregation in vials.

The evidence also supports the Board’s finding that the 

prior art taught use of nonionic surfactants like those 

claimed in the present patents to address the aggregation 

problem. For example, Lougheed teaches the addition of 

polysorbate 20 or polysorbate 80 to insulin formulations to 

reduce aggregation. J.A. 6706 (“[A]ggregate formation [in 

insulin formulations] was inhibited by the nonionics . . . 

Tween 20, [and] Tween 80.”). Both FASS and Grau teach 

the use of a poloxamer to stabilize an insulin formulation. 

J.A. 6725 (“Addition of a stabilizer poly(oxyethylene, oxypropylene), glycol, prevents precipitation and flocculation 

of the insulin.”); J.A. 6732 (“Genapol, a surface-active 
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polyethylene-polypropylene glycol, effectively prevents adsorption of insulin to hydrophobic surfaces.”). Mylan’s expert declaration provides further support when it points, 

with citations to prior art, to “the routine use of polysorbates and poloxamers in insulin formulations for inhibiting 

protein aggregation.” J.A. 6475–76.

Sanofi points to our non-precedential decision in Novartis Pharmaceuticals Corp. v. Watson Laboratories, Inc.,

611 F. App’x 988 (Fed. Cir. 2015), but that decision does 

not undermine the Board’s finding here. In Novartis, we 

affirmed a district court’s determination of non-obviousness where the prior art teaching was reasonably found to 

differ significantly from the claimed invention. Id. at 995–

96 (concluding that it would not be obvious to modify rivastigmine in the way claimed to solve the well-known 

problem of oxidative degradation with physostigmine, because the prior art taught that rivastigmine had “greater 

chemical stability” than physostigmine). That ruling does 

not help Sanofi in challenging the Board’s determination of 

obviousness based on findings that the glargine compound 

is similar to other insulins in the respects relevant to the 

obviousness analysis.

B

Sanofi also challenges the Board’s finding that a relevant artisan would have had a reasonable expectation of 

success in adding the claimed surfactants to the existing 

glargine preparation in the way claimed in the patents at 

issue here. Its focus on this issue, as on the related motivation-to-combine issue, is the contention that the Board 

looked at insulins generally and did not make adequately 

supported findings about glargine specifically. We reject 

Sanofi’s challenge.

1

As a preliminary matter, we address Sanofi’s argument

that the Board improperly relied, in its reasonable-
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expectation-of-success analysis, on evidence submitted by 

Mylan in reply to Sanofi’s patent owner’s response. We review the Board’s decisions regarding the scope of proper reply material for an abuse of discretion. Ericsson Inc. v. 

Intellectual Ventures I LLC, 901 F.3d 1374, 1379 (Fed. Cir. 

2018). We see no abuse of discretion in the present IPRs.

Under the governing IPR rules, there is no impropriety 

when the Board considers reply evidence to the extent that 

the evidence is offered to show why a patent owner’s response is wrong in its criticisms of the sufficiency of the 

petition’s case for unpatentability, including where the patent owner’s response introduces what amounts to a new 

defense to an otherwise-sufficient case of unpatentability 

in the petition. See, e.g., Idemitsu Kosan Co. v. SFC Co., 

870 F.3d 1376, 1381 (Fed. Cir. 2017) (reply evidence may 

respond to teaching-away contention in patent owner’s response). Here, Mylan’s petitions made its case for finding

a reasonable expectation of success, see, e.g., J.A. 384; J.A.

457, and after Sanofi made arguments against such a finding in its patent owner’s response, Mylan’s reply included 

rebuttal argument and evidence addressing Sanofi’s 

points, J.A. 1819–37; J.A. 12231–91 (excerpts of reply expert declaration); see J.A. 2414–18 (excerpts of Sanofi’s 

specification of objected-to passages). The Board allowed 

Sanofi to file at least one sur-reply on the issue of reasonable expectation of success, as well as several motions to exclude, but the Board found all of Sanofi’s objections either 

unpersuasive, because Mylan’s reply evidence was proper

rebuttal evidence, or moot, because the Board had not relied on particular objected-to evidence. See Decision at *5–

6; J.A. 15304–06. We see no abuse of discretion in the 

Board’s rulings in this regard.

2

On the merits, Sanofi argued to the Board that, although surfactants were known to stabilize insulins generally, a relevant artisan would not have expected the same 
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result for glargine specifically because its mechanism of action depends on some favorable native aggregation. To the 

extent that Sanofi contends that the Board did not consider 

this argument, Sanofi is incorrect. The Board thoroughly 

considered Sanofi’s argument but found it unpersuasive. 

To the extent that Sanofi contends that there is no substantial evidence to support a finding of reasonable expectation 

of success for glargine specifically, we conclude that Sanofi 

is incorrect in that contention as well.

The Board began its reasonable expectation of success 

analysis by finding that a number of nonionic surfactants—

including the claimed nonionic surfactants—were shown in 

the prior art to have been successfully used to prevent aggregation of various types of insulins and other peptides. 

Decision at *17. The prior art supports this determination. 

See, e.g., J.A. 6706–07 (“[A]ggregate formation [in insulin 

formulations] was inhibited by the nonionic[] [surfactants],” including polysorbate 20 and polysorbate 80.); J.A. 

6725 (“Addition of a stabilizer poly(oxyethylene, oxypropylene), glycol,” a poloxamer, “prevents precipitation and flocculation of the insulin.”). Mylan’s expert declared that a 

relevant artisan, when considering which nonionic surfactants to use in a glargine formulation, would look to 

nonionic surfactants (such as polysorbates) approved by 

the Food and Drug Administration (FDA) for use in other 

protein formulations, and the Board, after its prior-art recitation, credited that statement. Decision at *17.

The Board found “unpersuasive [Sanofi’s] arguments 

that an ordinarily skilled artisan would not have reasonably expected success when adding a nonionic surfactant to 

insulin glargine in view [of] their success stabilizing other 

insulins and proteins.” Id. For example, Sanofi contended 

that adding a nonionic surfactant to a strong acid had the 

potential to cause undesirable hydrolysis or saponification. 

But the Board explained that Sanofi did not put forth any 

evidence that the prior-art glargine compounds existed in 

a strong acid, and it pointed to evidence that polysorbates 
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had in fact been used in pharmaceutical formulations at 

acidic pH (3.0 to 4.0). Id. at *18 (citing J.A. 7450–51; J.A.

12907). 

The Board also credited Mylan’s evidence that the 

presence of phenols in a glargine formulation would not 

have dissuaded a relevant artisan from expecting success 

in using nonionic surfactants. Id. The Board reasonably 

did so. The Board noted that other pharmaceutical formulations include both nonionic surfactants and phenols. Decision at *18 (citing, e.g., J.A. 12911). There also was 

evidence, including from Sanofi’s expert, that phenols in 

insulin formulations stabilize hexamers, whereas surfactants prevent irreversible denaturation of monomers but 

do not prevent hexamer formation. J.A. 14249–53; J.A.

14387; see J.A. 6732; J.A. 6910. Moreover, the testimony 

of Sanofi’s expert about a problem was carefully limited,

stating only that nonionic surfactants in a glargine formulation “could” disrupt the native aggregation that phenols 

promote. J.A. 14307–09. Mylan’s expert, in contrast, 

stated unequivocally that a nonionic surfactant’s potential

interference with phenols would not dissuade a relevant 

artisan from using both in a formulation. J.A. 12298.

The Board did not expressly address Sanofi’s arguments about the potential for discoloration or peroxide formation. But the Board rejected them implicitly as bases 

for finding no reasonable expectation of success: those arguments were within the pages of the patent owner’s response that recited various potential negative 

consequences that the Board addressed collectively, finding Sanofi’s arguments in those pages unpersuasive 

whether considered with respect to motivation to combine 

or reasonable expectation of success. Decision at *18. The 

Board is not required to “expressly discuss each and every 

negative and positive piece of evidence lurking in the record.” Novartis AG v. Torrent Pharm. Ltd., 853 F.3d 1316, 

1328 (Fed. Cir. 2017). Sanofi has not shown that its evidence on these two particular potential consequences 
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undermines the Board’s finding that, considering all relevant factors, an ordinary artisan would have had a reasonable expectation of success in adding a nonionic surfactant 

to a glargine formulation. Decision at *18. We conclude 

that the Board’s finding is supported by substantial evidence.

C

Lastly, Sanofi challenges the Board’s analysis of commercial success. The Board accepted that Sanofi’s product 

was a commercial success. Decision at *19. The Board 

found that Sanofi’s commercial success evidence was ultimately “weak” so as not to warrant an ultimate conclusion 

on obviousness different from the one strongly indicated by 

the motivation-to-combine and reasonable-expectation-ofsuccess analysis. Decision at *19 n.14, *20. We reject 

Sanofi’s challenge to the Board’s reasoning—whether it is 

viewed as a factual finding of only a weak nexus of commercial success to the claimed invention or as part of the 

ultimate legal weighing to determine obviousness. See Intercontinental Great Brands LLC v. Kellogg N. America 

Co., 869 F.3d 1336, 1347 (Fed. Cir. 2017).

Certain facts are not in dispute. Sanofi enjoyed commercial success with Lantus®, but that success began with 

the original glargine formulation, which lacked the surfactant claimed in the ’652 and ’930 patents. Decision at *19. 

Recognizing that, standing alone, that fact would suggest 

that the success is not traceable to the new glargine-surfactant combination, Sanofi asserted to the Board that, had 

it not reformulated the Lantus® product to include a 

nonionic surfactant, it “‘could have’” suffered potential regulatory action and a loss of sales. Id. (quoting Sanofi’s patent owner’s response). That assertion on its face is only 

about what “‘could have occurred.’” Id. And the evidence 

offered by Sanofi in support, which the Board cited but did 

not expressly discuss, plainly goes no further. Sanofi’s evidence consists only of its experts’ hypothetical conjectures 
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about what “could have” happened to future Lantus® sales 

in the absence of reformulation with a nonionic surfactant. 

J.A. 15045–47; J.A. 14319–22. Moreover, Sanofi in fact 

continued to sell its original Lantus® product, without a 

nonionic surfactant, even after FDA approval of its reformulated product. J.A. 7495. 

It is against this background that the Board relied on 

another fact in deeming Sanofi’s evidence of commercial 

success “weak” as a factor in the obviousness analysis. It 

explained that Sanofi owned two so-called “blocking patents” giving Sanofi exclusive rights to the glargine compound itself—the last of which expired in 2014, many years 

after the 2002 priority date—which gave Sanofi control 

over another’s commercial domestic entry into the market 

with the improvement claimed in the ’652 and ’930 patents. 

Decision at *19. Relying on our decisions in Galderma Laboratories, L.P. v. Tolmar, Inc., 737 F.3d 731, 740 (Fed. Cir. 

2013), and Acorda Therapeutics, Inc. v. Roxane Laboratories, Inc., 903 F.3d 1310, 1337 (Fed. Cir. 2018), the Board 

determined that Sanofi’s blocking patents made Sanofi’s 

commercial success with the modified Lantus® product—

following its commercial success with the original Lantus® 

product—“weak” as evidence of obviousness. Id. at *19–20.

We see no reversible error in that ruling. We have explained that the existence of a blocking patent in circumstances like those present here “may deter non-owners and 

non-licensees [of that patent] from investing the resources 

needed to make, develop, and market such a later, ‘blocked’

invention, because of the risk of infringement liability and 

associated monetary or injunctive remedies,” Acorda, 903 

F.3d at 1337, and thus, depending on the record made in a 

particular case, justify discounting evidence of commercial 

success because the blocking patent can help explain why, 

for reasons other than non-obviousness, no one else arrived 

at the later patent’s improvement despite a potential economic benefit from meeting a market demand (as evidenced by commercial success), id. at 1339. In this case, 
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the existing glargine compound patents were listed in the 

FDA’s Approved Drugs with Therapeutic Equivalence Evaluations (27th ed. 2007) for the original Lantus® product. 

J.A. 9787. Although Sanofi’s expert knew of those patents, 

he did not consider them in his commercial-success analysis. See Decision at *19. On the other hand, Mylan’s expert 

testified that the existing patents “‘would have blocked 

competitors from commercializing a product that embodied’” the claimed glargine formulations and “‘provided 

strong disincentives for others to develop and commercialize’” the claimed glargine formulations. Id. (quoting J.A. 

13787). Sanofi did not present arguments and evidence 

that would allow us to find reversible error in the Board’s 

analysis.

Sanofi argues that the Board’s blocking-patent analysis was flawed because the glargine compound patents did 

not block all long-acting insulins from entering the market. 

That objection is misplaced. The specific question at issue, 

the Board properly recognized, is obviousness of the 

claimed invention, not of other products that might address 

a similar need. Sanofi itself has insisted throughout the 

present proceedings that the issue is the obviousness of the 

claimed glargine-surfactant combination, not the obviousness of the insulin-surfactant combinations, much less of 

other insulin products. We see no error in the Board’s consideration of the relevance of blocking patents to the potential discouragement of others from coming up with the 

specific invention at issue. 

For at least those reasons, and in light of the strength 

of the motivation-to-combine and reasonable-expectationof-success part of the obviousness analysis, we reject 

Sanofi’s argument that its commercial-success evidence 

undermines the Board’s determination of obviousness.
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III

For the foregoing reasons, we affirm the Board’s decisions that all claims of the ’652 and ’930 patents are unpatentable for obviousness.4

AFFIRMED

 

4 On November 5, 2019, Sanofi filed a letter with the 

court asking the court to vacate the Board’s decision and 

remand for reconsideration by a different Board panel under this court’s decision regarding the Appointments 

Clause in Arthrex, Inc. v. Smith & Nephew, Inc., No. 2018-

2140, ––– F.3d –––, 2019 WL 5616010 (Fed. Cir. Oct. 31, 

2019). We reject the request. Sanofi did not raise an Appointments Clause issue in its opening brief in this court 

(or its reply brief). Our precedent holds that failure to raise 

the Arthrex Appointments Clause issue in the opening brief 

forfeits the challenge. Customedia Technologies, LLC v. 

Dish Network Corp., Nos. 2018-2239, -2240, -2310, 2019-

1000, -1002, -1003, -1027, -1029, ––– F.3d –––, 2019 WL 

5677703 (Fed. Cir. Nov. 1, 2019); Customedia Technologies, 

LLC v. Dish Network Corp., No. 2019-1001, ––– F.3d –––, 

2019 WL 5677704 (Fed. Cir. Nov. 1, 2019).
NOTE: This disposition is nonprecedential.

United States Court of Appeals 

for the Federal Circuit ______________________

SANOFI-AVENTIS DEUTSCHLAND GMBH,

Appellant

v.

MYLAN PHARMACEUTICALS INC.,

Appellee

______________________

2019-1368, 2019-1369

______________________

Appeals from the United States Patent and Trademark 

Office, Patent Trial and Appeal Board in Nos. IPR2017-

01526, IPR2017-01528.

______________________

NEWMAN, Circuit Judge, dissenting.

The court today rules that it was obvious to create this 

new formulation to remedy the unforeseen deterioration of 

glargine insulin when stored in glass ampoules with an air 

space. The court reasons that the “background knowledge”

of insulin science renders these new compositions obvious—although neither the problem nor its remedy is shown 

in the prior art.

The court today enlarges the criteria of invalidity, to 

include hindsight analysis of foreseeability of the problem

and its solution, citing information in the inventor’s patent 
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specification as prior art against the invention. The court

thus adds to the unpredictability of judicial assessment of 

“obviousness.” I respectfully dissent.

Sanofi’s inventors discovered the cause of the 

instability on storage, and devised a solution, 

none of which is in the prior art

It was of critical importance to preserve glargine’s

property of insulin activity and extended release after injection into the body, while finding a remedy for the instability that was observed during prolonged storage. The law

of obviousness for medicinal products requires pragmatic,

as well as wise application, for physiological properties and 

bodily responses to new products cannot be reliably known 

without experimental evaluation.

The panel majority discards Sanofi’s testimony concerning the complex molecule that is glargine insulin and 

its extended release properties after injection under the 

skin. The majority ignores the known uncertainties of insulin formulation instability. Instead, the PTAB and now 

the panel majority look for and find the various components of Sanofi’s new composition in the scientific literature, and rule that this stabilized new glargine formulation 

could obviously be made and would obviously be successful

in preserving extended-release properties and full insulin 

activity without adverse physiologic response, while avoiding the observed deterioration in ampoules.

The PTAB found that a person of skill would have recognized a potential aggregation problem in the vial, a finding contrary to the fact that the potential aggregation was 

not recognized. A cited reference to Chawla states that 

“[u]nder normal use by the patient, aggregation of insulin 

does not appear to be a significant problem in the commercially available syringes and infusion test sets.” J.A.6953. 

Nonetheless, the PTAB, and now my colleagues, plug that 

gap with retrospective judicial prescience.
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Sanofi’s inventors discovered that the turbidity appearing in some vials was not a simple “aggregation in the vial.”

Unlike insulin, which was known to undergo reversible aggregation, the glargine turbidity was found to be an irreversible chemical reaction. This reaction of glargine was 

not reported in the prior art. Nor does the prior art suggest 

how such a product would behave upon entering the human body.

Although there was no evidence or suggestion for the 

inactivation of glargine when stored in glass ampoules, my 

colleagues hold that a person of ordinary skill would have 

foreseen this problem and known its solution. That 

Sanofi’s inventors knew of the tendency of insulin to aggregate, as so stated in their specification, is evidence not of 

obviousness, but of nonobviousness, for glargine had undergone clinical development without this problem being 

apparent. Sanofi explained the uncertainties in insulin reactivity, citing the known potential for discoloration and 

peroxide formation, and that such reactions cannot be predicted. The PTAB brushed off these uncertainties as “unpersuasive” without any analysis, as do my colleagues. 

Maj. Op. at 16–17, 20. However, the behavior of a new composition inside the body requires experimentation and evidence, not speculation and hindsight.

As reiterated in In re Cyclobenzaprine Hydrochloride 

Extended-Release Capsule Patent Litig., 676 F.3d 1063, 

1079 (Fed. Cir. 2012), “[t]he objective considerations, when 

considered with the balance of the obviousness evidence in 

the record, guard as a check against hindsight bias”). In 

Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1538 (Fed. 

Cir. 1983), this court observed that objective indicia may 

be the most important evidence of nonobviousness—yet the 

court here discards this evidence entirely. Id. (“It is jurisprudentially inappropriate to disregard any relevant evidence on any issue in any case, patent cases included. Thus 

evidence rising out of the so-called ‘secondary considerations’ must always when present be considered en route to 
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4

a determination of obviousness. Indeed, evidence of secondary considerations may often be the most probative and 

cogent evidence in the record.” (internal citations omitted)).

Nonetheless, my colleagues find that this problem and 

its solution were obvious, drawing on “the knowledge 

taught by the inventor . . . and then use[ing] that 

knowledge against its teacher.” Panduit Corp. v. Dennison 

Mfg. Co., 774 F.2d 1082, 1092 (1986). See Innogenetics, 

N.V. v. Abbott Labs., 512 F.3d 1363, 1373–74 

(Fed.Cir.2008) (cautioning against “the pitfalls of hindsight 

that belie a determination of obviousness.”). The objective 

considerations of nonobviousness cannot be ignored.

The court states that the commercial success of Sanofi’s 

product is “too weak to support a conclusion of nonobviousness.” Maj. Op. at 5. Mylan argues that the commercial 

success of this product cannot be considered, on the theory 

that Sanofi’s “blocking patents” prevented others from entering this field. The record states that the last of the 

glargine basic patents expired in 2014. Mylan offered no 

evidence of development of competitive formulations, although the Hatch-Waxman Act insulates such development 

from infringement. My colleagues err in viewing this theory as negating nonobviousness, for by statute medicinal 

product development cannot be blocked.

Here, the glargine was reformulated to preserve its stability, and achieved marked commercial success. On the 

correct law, obviousness was not established.

The patent specification is not prior art

The court holds that “The Board’s use of the patent 

specification, we conclude, did not rest on legal error.” Maj. 

Op. at 10. This is incorrect. The court’s ratification of reliance on the inventor’s specification to invalidate the invention disclosed therein, is plain error. A patent 

specification may be edifying and must be descriptive and 

enabling, but it is not prior art. See Graham v. John Deere 
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Co., 383 U.S. 1, 36 (1966) (avoid the “temptation to read 

into the prior art the teachings of the invention at issue.”). 

The law of innovation and obviousness

Innovation requires stable laws and consistent application of those stable laws. My colleagues state that an “expansive and flexible approach” must be applied to the 

question of obviousness, and that “creative steps” may be 

obvious, citing KSR International Co. v. Teleflex Inc., 550

U.S. 398, 415 (2007). Maj. Op. at 7. However, KSR’s guidance is in the context of the statute. The statutory standards of novelty and nonobviousness require objectivity, 

consistency, and predictability.

An effective patent system requires providing patentees with reasonable reliance on their patents as granted by 

the government, lest the incentive for innovation be diminished.1 Stability of legal rules is the foundation of commercial activity. The courts and the PTAB must apply the 

same law as did the examiner on granting the patent. 

Here, the PTAB and now this court place a fresh spin on 

the law, to the detriment of consistency and reliability. 

 

1 In recent legislative hearings, witnesses explained 

the disincentive flowing from inconsistent and unpredictable judicial rulings—to the detriment of inventors, industry, the public, and the nation’s economic and competitive 

vigor. See The State of Patent Eligibility in America: Hearings Before the S. Comm. on Intellectual Property, 116th 

Cong. (2019), https://www.judiciary.senate.gov/meetings/the-state-of-patent-eligibility-in-america-part-i; 

https://www.judiciary.senate.gov/meetings/the-state-of-patent-eligibility-in-america-part-ii; https://www.judiciary.senate.gov/meetings/the-state-of-patent-eligibility-inamerica-part-iii. 
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On application of correct law, the patentability of these 

new and improved formulations of glargine should be sustained.

The recent ruling on the Appointments Clause 

of the Constitution

Promptly after this court’s holding in Arthrex, Inc. v. 

Smith & Nephew, Inc., No. 2015-2140, ___ F.3d ____, 2019 

WL 5616010 (Fed. Cir. Oct. 31, 2019) that the method of 

appointment of administrative patent judges violates the 

Appointments Clause, Sanofi moved to brief the application of this ruling to the PTAB decisions here on appeal. 

See Sanofi Letter under Rule28(j) (“Sanofi requests that 

the Court allow briefing to address whether factors, including the ‘exceptional importance’ of the issue and the ‘significant change in law’ Arthrex reflects, warrant an exception 

to any waiver here.” (citing Arthrex, 2019 WL 5616010 at 

*6)). Sanofi pointed out that “these issues were not addressed in Customedia,” and that “[w]aiver is ‘exercised on 

the facts of individual cases.’” Id.

My colleagues deny the motion, ruling that our recent 

Customedia rulings establish that the Arthrex ruling cannot be applied to pending appeals, unless the appellant had 

raised an Appointments Clause challenge in its principal 

brief on appeal. Maj. Op. at 20 n.4. However, at the time 

these appeals were filed, there was no holding of illegality 

of appointments of the PTAB’s Administrative Patent 

Judges. It is well established that when the law changes 

while a case is on appeal, the changed law applies. Thorpe 

v. Hous. Auth. of Durham, 393 U.S. 268, 282 (1969). “[I]n 

great national concerns . . . the court must decide according to existing laws, and if it be necessary to set aside a 

judgment, rightful when rendered, but which cannot be affirmed but in violation of law, the judgment must be set 

aside.” United States v. Schooner Peggy, 1 Cranch 103, 110

(1801).
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While the law of the case doctrine stands for the idea 

that when a court decides a matter of law or fact, its decision controls those same issues in subsequent stages of the 

same case, Christianson v. Colt Indus. Operating Corp., 

486 U.S. 800, 815–16 (1988), here an administrative ruling 

is on appeal to the court. As this court observed in Dow 

Chem. Co. v. Nova Chems. Corp. (Can.), 803 F.3d 620, 629 

(Fed. Cir. 2015), a change in governing law applies to the 

pending appeal when the change occurs while the case is 

on appeal.

Thus, Sanofi is entitled to the same benefit of the Arthrex decision as are the Arthrex parties. The foundation 

of a nation ruled by law is that the same rules, as well as 

the same law, will be applied in the same way to parties in 

pending litigation.

The majority errs in denying Sanofi’s motion.