throbber
NOTE: This disposition is nonprecedential.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 rep-
`resented by JEFFREY WILLIAM GUISE, ALINA LEONIDOVNA
`LITOSHYK, ELHAM FIROUZI STEINER, LORELEI WESTIN;
`NICOLE W. STAFFORD, Austin, TX; WENDY L. DEVINE, San
`
`

`

`2
`
`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`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 ap-
`plication that issued as the ’652 patent, and the two share
`a specification. The patents involve a genetically engi-
`neered 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—polysorb-
`ates or poloxamers in the ’652 patent, esters and ethers of
`
`

`

`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`3
`
`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 poly-
`sorbate 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 prior-
`art 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, substan-
`tially 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 in-
`sulin 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
`
`

`

`4
`
`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`label identifies, among other things, a pH of 4 and the in-
`clusion 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 aggre-
`gation 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 aggrega-
`tion.
`Mylan petitioned the PTO for inter partes reviews of
`all claims of the ’652 and ’930 patents, arguing unpatenta-
`bility for obviousness based on combining either the Lan-
`tus® 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 125I-
`Labeled Insulin Glargine (HOE 901) in Healthy Men: Com-
`parison with NPH Insulin and the Influence of Different
`Subcutaneous Injection Sites, 23 DIABETES CARE 813 (2000)
`(Owens).
`three secondary references are: W.D.
`2 The
`Lougheed, et al., Physical Stability of Insulin Formula-
`tions, 32 DIABETES 424 (1983) (Lougheed); Farmaceutiska
`Specialiteter I Sverige, Summary of Product Characteris-
`tics 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).
`
`

`

`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`5
`
`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. Sanofi-
`Aventis 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 proceed-
`ings, determining that all claims in both patents are un-
`patentable 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 sur-
`factants (like the standard ones claimed here) offered a so-
`lution. Decision at *12–18. The Board also determined
`that, given the prior-art analysis, Sanofi’s evidence of com-
`mercial success was too weak to support a conclusion of
`nonobviousness. Id. at *18–20.
`
`
`3 The Board’s final written decisions are substan-
`tively 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.
`
`

`

`6
`
`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`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 rea-
`sonable 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 ar-
`gues 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 specifi-
`cally (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 prob-
`lem for glargine specifically, not just for insulins generally.
`In Sanofi’s view, KSR demands more than a factually sup-
`ported finding that recognition of an aggregation risk for
`
`

`

`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`7
`
`insulins generally would have motivated a relevant artisan
`to address aggregation for this particular insulin. We re-
`ject 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 al-
`most 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 com-
`binations or modifications. KSR, 550 U.S. at 415–
`22. Rejecting a blinkered focus on individual docu-
`ments, 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 in-
`quiry “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.
`
`

`

`8
`
`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`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 is-
`sue.”) (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 rec-
`ognized 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 spec-
`ificity that Sanofi urges. The Board thus properly exam-
`ined the evidence in this particular case to determine
`whether a relevant artisan would have recognized an insu-
`lin 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 in-
`fra.
`
`2
`We also reject Sanofi’s contention that the Board com-
`mitted legal error when it cited the shared patent specifi-
`cation. 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 prone-
`ness to aggregation on thermal and physicome-
`chanical stress, which can make itself felt in the
`form of turbidity and precipitation (particle for-
`mation (Brange et al., J. Ph. Sci 86:517-525 (1997)).
`
`

`

`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`9
`
`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 sil-
`icone oil droplets can function as additional hydro-
`phobic aggregation nuclei in the taking of the daily
`insulin dose by means of customary, siliconized in-
`sulin 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 ag-
`gregate 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 prac-
`tice 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); Phar-
`maStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342,
`1362 (Fed. Cir. 2007); cf. WesternGeco LLC v. ION Geophys-
`ical Corp., 889 F.3d 1308, 1329–30 (Fed. Cir. 2018) (speci-
`fication confirmed Board’s understanding of prior art in
`anticipation context).
`
`

`

`10
`
`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`The Board understood the patent specification, on this
`issue, to be addressing what was already known—a read-
`ing that is reasonable given the language used and cita-
`tions to prior art. Moreover, the Board used the cited
`material not as the sole support for any finding but in con-
`junction 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 addi-
`tional 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 moti-
`vation to combine is supported by substantial evidence.
`While the Board must provide “a reasoned basis” for its ac-
`tions, “‘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) (quot-
`ing Bowman Transp., Inc. v. Ark.–Best Freight System,
`Inc., 419 U.S. 281, 285, 286 (1974)). The Board “must ar-
`ticulate 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”) (ci-
`tation and internal quotation marks omitted).
`The Board’s findings with respect to the motivation to
`combine are detailed and well supported. The Board found
`
`

`

`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`11
`
`that insulins “had a known tendency to aggregate in the
`presence of hydrophobic surfaces” and at air-water inter-
`faces and that a relevant artisan would have expected
`glargine to behave similarly to other insulins when in con-
`tact with hydrophobic surfaces and at air-water interfaces.
`Decision at *14. The Board also found that nonionic sur-
`factants, including the claimed ones, were well known and
`had been used successfully to stabilize insulin formula-
`tions, and so would have been looked to by a relevant arti-
`san concerned about aggregation in glargine. Id. at *11–
`12, *17. The record contains substantial evidence to sup-
`port 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 pa-
`tents itself indicates, in a discussion introduced by discuss-
`ing 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 pa-
`tent, col. 2, line 66 through col. 3, line 17. Mylan’s expert
`explained, with citations to prior art, that “insulin aggre-
`gation is a well-established problem in the field and de-
`scribed 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 in-
`stead that “it is the air-water interfaces and interactions
`with hydrophobic surfaces that promote insulin aggrega-
`tion, 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 in-
`sulin has a tendency to aggregate on hydrophobic surfaces);
`J.A. 14535 (“It has been suggested that insulin is destabi-
`lized 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
`
`

`

`12
`
`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`[insulin] pumps,” J.A. 12246 (quoted in Decision at *15),
`and found that Sanofi’s expert, in suggesting otherwise, re-
`lied 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 find-
`ing 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 formu-
`lations 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 environ-
`ment 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 ev-
`idence 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 prob-
`lem 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, oxy-
`propylene), glycol, prevents precipitation and flocculation
`of the insulin.”); J.A. 6732 (“Genapol, a surface-active
`
`

`

`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`13
`
`polyethylene-polypropylene glycol, effectively prevents ad-
`sorption of insulin to hydrophobic surfaces.”). Mylan’s ex-
`pert declaration provides further support when it points,
`with citations to prior art, to “the routine use of polysorb-
`ates and poloxamers in insulin formulations for inhibiting
`protein aggregation.” J.A. 6475–76.
`Sanofi points to our non-precedential decision in No-
`vartis 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-obvious-
`ness 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 ri-
`vastigmine in the way claimed to solve the well-known
`problem of oxidative degradation with physostigmine, be-
`cause 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 rele-
`
`vant 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 moti-
`vation-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-
`
`

`

`14
`
`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`expectation-of-success analysis, on evidence submitted by
`Mylan in reply to Sanofi’s patent owner’s response. We re-
`view the Board’s decisions regarding the scope of proper re-
`ply 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 re-
`sponse is wrong in its criticisms of the sufficiency of the
`petition’s case for unpatentability, including where the pa-
`tent 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 re-
`sponse). 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 find-
`ing 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 ex-
`pert 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 reasona-
`ble expectation of success, as well as several motions to ex-
`clude, 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 re-
`lied 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, alt-
`hough surfactants were known to stabilize insulins gener-
`ally, a relevant artisan would not have expected the same
`
`

`

`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`15
`
`result for glargine specifically because its mechanism of ac-
`tion 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 substan-
`tial 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 ag-
`gregation 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[] [surfac-
`tants],” including polysorbate 20 and polysorbate 80.); J.A.
`6725 (“Addition of a stabilizer poly(oxyethylene, oxypropyl-
`ene), glycol,” a poloxamer, “prevents precipitation and floc-
`culation of the insulin.”). Mylan’s expert declared that a
`relevant artisan, when considering which nonionic surfac-
`tants 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 rec-
`itation, credited that statement. Decision at *17.
`The Board found “unpersuasive [Sanofi’s] arguments
`that an ordinarily skilled artisan would not have reasona-
`bly 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
`
`

`

`16
`
`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`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 formu-
`lations include both nonionic surfactants and phenols. De-
`cision 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 surfac-
`tants 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 formu-
`lation “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 argu-
`ments about the potential for discoloration or peroxide for-
`mation. But the Board rejected them implicitly as bases
`for finding no reasonable expectation of success: those ar-
`guments were within the pages of the patent owner’s re-
`sponse
`that
`recited
`various
`potential negative
`consequences that the Board addressed collectively, find-
`ing 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 rec-
`ord.” Novartis AG v. Torrent Pharm. Ltd., 853 F.3d 1316,
`1328 (Fed. Cir. 2017). Sanofi has not shown that its evi-
`dence on these two particular potential consequences
`
`

`

`SANOFI-AVENTIS DEUTSCHLAND v. MYLAN PHARMACEUTICALS
`INC.
`
`17
`
`undermines the Board’s finding that, considering all rele-
`vant factors, an ordinary artisan would have had a reason-
`able 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 evi-
`dence.
`
`C
`Lastly, Sanofi challenges the Board’s analysis of com-
`mercial 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 ulti-
`mately “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-of-
`success 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 com-
`mercial success to the claimed invention or as part of the
`ultimate legal weighing to determine obviousness. See In-
`tercontinental Gre

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket