Endo Pharmaceuticals Inc. v. Actavis LLC , 922 F.3d 1365 ( 2019 )

United States Court of Appeals
for the Federal Circuit
______________________
ENDO PHARMACEUTICALS INC.,
MALLINCKRODT LLC,
Plaintiffs-Appellees
v.
ACTAVIS LLC, FKA ACTAVIS INC., ACTAVIS
SOUTH ATLANTIC LLC, TEVA
PHARMACEUTICALS USA, INC.,
Defendants-Appellants
______________________
2018-1054
______________________
Appeal from the United States District Court for the
District of Delaware in No. 1:14-cv-01381-RGA, Judge
Richard G. Andrews.
______________________
Decided: May 3, 2019
______________________
MARTIN JAY BLACK, Dechert LLP, Philadelphia, PA, ar-
gued for plaintiffs-appellees. Also represented by SHARON
K. GAGLIARDI; BLAKE GREENE, Austin, TX; JONATHAN
LOEB, Mountain View, CA; ROBERT RHOAD, Princeton, NJ.
JEFFREY J. TONEY, Kasowitz, Benson, Torres & Fried-
man LLP, Atlanta, GA, for plaintiff-appellee Mallinckrodt
LLC. Also represented by RODNEY R. MILLER, PAUL
GUNTER WILLIAMS.
2 ENDO PHARM. INC. v. ACTAVIS LLC
JOHN C. O'QUINN, Kirkland & Ellis LLP, Washington,
DC, argued for defendants-appellants. Also represented by
WILLIAM H. BURGESS; CHARLES A. WEISS, ERIC H. YECIES,
Holland & Knight, LLP, New York, NY.
______________________
Before WALLACH, CLEVENGER, and STOLL, Circuit Judges.
Opinion for the court filed by Circuit Judge WALLACH.
Dissenting opinion filed by Circuit Judge STOLL.
WALLACH, Circuit Judge.
Appellees Endo Pharmaceuticals Inc. (“Endo Pharma-
ceuticals”) and Mallinckrodt LLC (“Mallinckrodt”) (collec-
tively, “Endo”) sued Appellants Actavis LLC, Actavis South
Atlantic LLC, and Teva Pharmaceuticals USA, Inc. (collec-
tively, “Actavis”) in the U.S. District Court for the District
of Delaware (“District Court”), alleging that two Abbrevi-
ated New Drug Applications filed by Actavis infringed
claims 1–6 (“the Asserted Claims”) of Mallinckrodt’s U.S.
Patent No. 8,871,779 (“the ’779 patent”), which Endo Phar-
maceuticals licenses. The District Court held that Actavis
failed to “prove[] by clear and convincing evidence that any
of the [A]sserted [C]laims . . . were invalid” as obvious or
anticipated, Endo Pharm. Inc. v. Actavis Inc., No. 14-1381-
RGA, 2017 WL 3731001, at *1 (D. Del. Aug. 30, 2017), and
entered final judgment of infringement, based on a stipu-
lation by Actavis, J.A. 1.
Actavis appeals, challenging the invalidity determina-
tion. We have jurisdiction pursuant to 28 U.S.C.
§ 1295(a)(1) (2012). We affirm.
BACKGROUND
I. The ’779 Patent
Entitled “Process for Preparing Morphinan-6-One
Products with Low Levels of α,β-Unsaturated Ketone
ENDO PHARM. INC. v. ACTAVIS LLC 3
Compounds,” the ’779 patent generally relates to com-
pounds known as “morphinan alkaloids,” such as “oxy-
morphone,” which have “great medical importance” and
“are used extensively for pain relief.” ’779 patent col. 1 ll.
24–30. “Morphinan compounds and analogs thereof typi-
cally have a ring structure . . . corresponding to Formula
(1)”:
Id. col. 1 ll. 38–53. “[P]harmaceutically desirable
morphinan compounds” often “have a ketone group[1] on
the C-ring of Formula (1) and a saturated bond[, i.e., single
bond,] between the two carbon atoms positioned α and β to
the ketone on the C-ring.” Id. col. 2 ll. 21–24. “[T]hese
compounds may be referred to as morphinan-6-one com-
pounds.” Id. col. 2 ll. 28–29. “[T]he ketone is present on
the C(6) carbon atom, with the α and β carbon atoms being
the C(7) and C(8) positions . . . .” Id. col. 2 ll. 25–26.
In describing the prior art, the ’779 patent explains
that “[v]arious processes for producing morphinan-6-one
1 A ketone comprises “a carbonyl group”— an oxygen
atom double-bonded to a carbon atom—where the carbon
atom of the carbonyl group is single-bonded to two carbon
atoms. J.A. 2952 (testimony of Actavis’s expert).
4 ENDO PHARM. INC. v. ACTAVIS LLC
compounds are known,” and “many . . . involve some form
of catalytic hydrogenation[2] of α,β-unsaturated ketone in-
termediate compounds [(‘ABUKs’)],” i.e., applying catalytic
hydrogenation to compounds containing ketone groups
with double bonds between the α and β carbon atoms to
convert the double bonds to single bonds. Id. col. 2 ll. 29–
32. However, “[ABUKs] may persist as impurities in the
final products.” Id. col. 2 ll. 43–45. These hydrogenation
processes also “may tend to undesirably reduce the ketone[,
a key functional part of morphinan-6-one compounds,] as
well as reducing or removing the α,β-unsaturation.” Id. col.
2 ll. 47–48.
The ’779 patent discloses “processes for preparing
highly pure morphinan-6-one products” having a relatively
low concentration of ABUKs present as impurities, which
“involve treating a reaction mixture including a
morphinan-6-one compound and an [ABUK] with a sulfur-
containing compound.” Id. col. 5 ll. 6–10. These processes
can “effectively reduce[] the concentration of undesirable
[ABUKs] to acceptable levels,” id. col. 5 ll. 11–13, with the
process employing a sulfur-containing compound that can
reduce ABUK concentration “from levels of about 0.5% (by
weight) or more to levels of not more than about 0.1% . . . ,
or lower (e.g., about 0.01% . . . , about 0.001% . . . , or
2 Generally, catalytic hydrogenation is a process by
which hydrogen, along with a catalyst, is added to a com-
pound containing double bonds, i.e., an unsaturated com-
pound, to convert it to a compound containing single bonds,
i.e., a saturated compound. See J.A. 2993–94 (testimony of
Actavis’s expert). A “catalyst activates the hydrogen,” and
“[t]he hydrogen adds a double bond and takes a molecule
that has a double bond and one hydrogen on each carbon to
a single bond with two hydrogens on each carbon.”
J.A. 2993.
ENDO PHARM. INC. v. ACTAVIS LLC 5
lower), with minimal side reactions, ketone reduction,
and/or any other undesirable effects,” id. col. 5 ll. 17–22.
The Asserted Claims recite:
1. A hydrochloride salt of oxymorphone comprising
less than 0.001% of 14-hydroxymorphinone.[3]
2. The hydrochloride salt of claim 1 comprising less
than 0.0005% of 14-hydroxymorphinone.
3. A pharmaceutical acceptable form comprising
the oxymorphone hydrochloride according to
claim 1.
4. A hydrochloride salt of a morphinan-6-one com-
pound corresponding to Formula (2):
3 Relevant to this appeal, 14-hydroxymorphinone,
also referred to as “oxymorphone ABUK,” is an ABUK im-
purity in oxymorphone and “is considered a precursor to
oxymorphone because it can be made into oxymorphone by
adding a hydrogen, resulting in a single bond.” Endo, 2017
WL 3731001, at *1; see id. at *2. In turn, 14-hydroxyco-
deinone is an ABUK impurity in oxycodone and referred to
as “oxycodone ABUK.” Id. at *8.
6 ENDO PHARM. INC. v. ACTAVIS LLC
comprising less than 0.001% measured by
[high performance liquid chromatography]
of an [ABUK] corresponding to Formula
(3):
wherein the morphinan-6-one compound is
oxymorphone and wherein X is —N(R17)—;
R1 and R2 are hydrogen;
R3 is hydroxy;
R10 is hydrogen;
R14 is hydroxy; and
ENDO PHARM. INC. v. ACTAVIS LLC 7
R17 is methyl.
5. The hydrochloride salt of claim 4 comprising less
than 0.0005% of 14-hydroxymorphinone.
6. A pharmaceutical formulation comprising the
oxymorphone hydrochloride according to claim 4.
Id. col. 37 l. 58–col. 38 l. 61 (emphases added).
II. Prior Art References
The District Court determined three references consti-
tute the prior art in this case. See Endo, 2017 WL 3731001,
at *6–8. We present each in turn.
A. Weiss
A scientific article from 1957, see Ulrich Weiss, Deriv-
atives of Morphine. II. Demethylation of 14-Hydroxyco-
deinone. 14-hydroxymorphinone and 8,14-
Dihydroxydihydromorphinone, 22 J. Organic Chemistry
1505, 1505–08 (1957) (“Weiss”) (J.A. 2295–98), discloses,
inter alia, the use of catalytic hydrogenation to convert ox-
ymorphone ABUK to oxymorphone. See J.A. 2297 (employ-
ing palladium charcoal “as catalyst” and teaching arriving
at the result of 14-hydroxydihydromorphinone, i.e., oxy-
morphone). Weiss also recounts 8,14-dihydroxy-7,8-dihy-
dromorphinone (“oxymorphone diol”) as “the product of
hydration of the double bond of [oxymorphone ABUK],”
J.A. 2295, the “ready conversion of [oxymorphone ABUK]
into [oxymorphone diol],” J.A. 2296, and the reversion of
oxymorphone diol to oxymorphone ABUK through the ap-
plication of hydrochloride, see J.A. 2295, 2297.
B. Chapman
Entitled “Process for Preparing Oxycodone Hydrochlo-
ride Having Less Than 25 [Parts Per Million (‘ppm’)] 14-
hydroxycodeinone,” U.S. Patent Application No.
2005/0222188 (“Chapman”) (J.A. 2464–90) discloses, inter
alia, processes that employ catalytic hydrogenation to
8 ENDO PHARM. INC. v. ACTAVIS LLC
purify oxycodone ABUK into the salt form of oxycodone.
See J.A. 2473 (“In certain embodiments of the present in-
vention, the 14-hydroxycodeinone [i.e., oxycodone ABUK]
is converted to oxycodone by hydrogenation . . . in conjunc-
tion with a . . . catalyst . . . .”). Chapman recites processes
that convert oxycodone ABUK to 8,14-dihydroxy-7,8-dihy-
drocodeinone (“oxycodone diol”), a precursor to oxycodone
ABUK, which can revert to oxycodone ABUK through the
compound’s conversion to salt form and thereby frustrate
purification. See J.A. 2473–74. But Chapman provides a
reaction that can remove oxycodone diol from a sample
prior to the completion of purification, and prevent oxyco-
done diol’s reversion to oxycodone ABUK. See J.A. 2483–
84 (Example 3).
C. Rapoport
A scientific article from 1967, see Henry Rapoport et
al., The Synthesis of Thebaine and Northebaine from Co-
deinone Dimethyl Ketal, 89 J. Am. Chemical Soc’y 1942,
1942–47 (1967) (“Rapoport”) (J.A. 2908–13), discloses, in-
ter alia, a process involving the use of bisulfite addition to
convert oxycodone ABUK to oxycodone, see J.A. 2908–09.
This process takes advantage of differences in solubility of
the products of reactions between bisulfites and oxycodone
ABUK to separate oxycodone from oxycodone ABUK. See
J.A. 2908–09.
DISCUSSION
Actavis contends that the District Court erred by, inter
alia, (1) misconstruing the claim term 14-hydroxy-
morphinone, see Appellants’ Br. 67–74; and (2) determin-
ing that the Asserted Claims were not obvious in light of
the prior art, see id. at 36–66. We address each argument
in turn.
ENDO PHARM. INC. v. ACTAVIS LLC 9
I. Claim Construction
A. Standard of Review and Legal Standard
“The proper construction of a patent’s claims is an issue
of Federal Circuit law . . . .” Powell v. Home Depot U.S.A.,
Inc., 663 F.3d 1221, 1228 (Fed. Cir. 2011) (citation omit-
ted). “[C]laim construction must begin with the words of
the claims themselves.” Amgen Inc. v. Hoechst Marion
Roussel, Inc., 457 F.3d 1293, 1301 (Fed. Cir. 2006) (citation
omitted). “[W]ords of a claim are generally given their or-
dinary and customary meaning” that they “would have to
a person of ordinary skill in the art [(‘PHOSITA’)] in ques-
tion at the time of the invention.” Phillips v. AWH Corp.,
415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc) (internal
quotation marks and citations omitted). The PHOSITA “is
deemed to read the claim term not only in the context of
the particular claim in which the disputed term appears,
but in the context of the entire patent, including the speci-
fication.” Id. at 1313. 4 Prosecution history may also be
used to supply additional evidence of claim terms’ intended
meaning. See Home Diagnostics, Inc. v. LifeScan, Inc., 381
F.3d 1352, 1356 (Fed. Cir. 2004). 5 “We review the district
court’s evaluation of the patent’s intrinsic record during
claim construction de novo.” Info-Hold, Inc. v. Applied Me-
dia Techs. Corp., 783 F.3d 1262, 1265 (Fed. Cir. 2015).
While courts may consider extrinsic evidence in claim
construction, “such evidence is generally of less
4 “A specification includes both the written descrip-
tion and the claims of the patent.” Monsanto Tech. LLC v.
E.I. DuPont de Nemours & Co., 878 F.3d 1336, 1341 (Fed.
Cir. 2018) (internal quotation marks and citation omitted).
5 “The prosecution history . . . consists of the com-
plete record of the proceedings before the [U.S. Patent and
Trademark Office] . . . .” Phillips, 415 F.3d at 1317 (cita-
tion omitted).
10 ENDO PHARM. INC. v. ACTAVIS LLC
significance than the intrinsic record.” Wi-LAN, Inc. v. Ap-
ple Inc., 811 F.3d 455, 462 (Fed. Cir. 2016) (citation omit-
ted). When, as here, “the district court . . . look[s] beyond
the patent’s intrinsic evidence and . . . consult[s] extrinsic
evidence,” such “factfinding must be reviewed for clear er-
ror.” Teva Pharm. USA, Inc. v. Sandoz, Inc., 135 S. Ct. 831,
841 (2015). “A factual finding is clearly erroneous if, de-
spite some supporting evidence, we are left with the defi-
nite and firm conviction that a mistake has been made.”
Profectus Tech. LLC v. Huawei Techs. Co., 823 F.3d 1375,
1379 (Fed. Cir. 2016) (internal quotation marks and cita-
tion omitted).
B. The District Court Properly Construed 14-Hydroxy-
morphinone as 14-Hydroxymorphinone Hydrochloride
The District Court, relying on intrinsic and extrinsic
evidence, determined that a PHOSITA would understand
the 14-hydroxymorphinone limitations stated in claims 1–
2 and 5 to mean “14-hydroxymorphinone hydrochloride,”
i.e., the “salt form” of 14-hydroxymorphinone. Endo, 2017
WL 3731001, at *14 (internal quotation marks omitted).
Actavis argues that this limitation requires no construction
because of “[t]he plain language of the claims, and the un-
disputed chemical difference between 14-hydroxy-
morphinone [i.e., oxymorphone ABUK] and its
hydrochloride salt.” Appellants’ Br. 67. We disagree with
Actavis.
The District Court correctly construed 14-hydroxy-
morphinone as 14-hydroxymorphinone hydrochloride. We
begin with the claims. See Phillips, 415 F.3d at 1314. The
Asserted Claims expressly employ the term 14-hydroxy-
morphinone three times, once each in claims 1–2 and 5. In-
dependent claim 1 teaches “[a] hydrochloride salt of
oxymorphone comprising” a certain amount of “14-hy-
droxymorphinone,” ’779 patent col. 37 ll. 58–59 (emphasis
added), while claim 2, which is dependent on claim 1,
claims “[t]he hydrochloride salt of claim 1 comprising” a
ENDO PHARM. INC. v. ACTAVIS LLC 11
lesser amount of “14-hydroxymorphinone,” id. col. 37 ll. 60–
61 (emphasis added). Claim 3, which is also dependent on
claim 1, does not expressly use the term 14-hydroxy-
morphinone, but refers to the entire compound taught in
claim 1 as “oxymorphone hydrochloride.” Id. col. 37 ll. 62–
63. In turn, claim 5 claims “[t]he hydrochloride salt of
claim 4 comprising” a certain amount of “14-hydroxy-
morphinone.” Id. col. 38 ll. 58–59 (emphasis added).
Therefore, the Asserted Claims only claim 14-hydroxy-
morphinone as part of the salt-, or hydrochloride-, form of
the claimed compounds, and not as a separate non-salt,
non-hydrochloride component. This indicates that, as used
in the Asserted Claims, 14-hydroxymorphinone means 14-
hydroxymorphinone hydrochloride.
Next, we turn to the broader specification. See Trs. of
Columbia Univ. v. Symantec Corp., 811 F.3d 1359, 1363
(Fed. Cir. 2016) (“The specification is always highly rele-
vant to the claim construction analysis and is, in fact, the
single best guide to the meaning of a disputed term.” (in-
ternal quotation marks, brackets, and citation omitted)).
Relevant here, 14-hydroxymorphinone is mentioned in Ex-
ample 3. See ’779 patent col. 37 l. 36. Example 3 recites
that “an oxymorphone [hydrochloride] sample was treated
with a sulfur-containing compound,” id. at col. 37 ll. 18–19,
the sample having contained a certain amount of “14-hy-
droxymorphinone . . . impurity,” id. col. 37 ll. 24–25. Fol-
lowing treatment, “oxymorphone base” was filtered out, id.
col. 37 l. 31 (emphasis added), a sample of which contained,
inter alia, “no detectable amount of 14-hydroxy-
morphinone,” id. col. 37 ll. 35–36. No distinction is made
between the 14-hydroxymorphinone in the oxymorphone
hydrochloride and oxymorphone base samples, but it is pre-
sented as part of these compounds, not as discrete com-
pounds or as possessing a separate hydrochloride or base
form. Nevertheless, 14-hydroxymorphinone’s use in the
12 ENDO PHARM. INC. v. ACTAVIS LLC
broader specification is relatively unsupportive of either
proffered construction. 6
Finally, we look to extrinsic evidence. See Phillips, 415
F.3d at 1319 (allowing courts to look to extrinsic evidence
to, inter alia, better understand the field of the invention
and the meaning of a term to a PHOSITA). The District
Court considered the testimony of Actavis’s expert, in
which he “agree[d]” that a PHOSITA reading Example 3 of
the ’779 patent “would have to assume that the ABUK im-
purity there was the ABUK oxymorphone [hydrochloride],”
i.e., the salt form,” J.A. 3117; see Endo, 2017 WL 3731001,
at *14, as is permitted, see Key Pharm. v. Hercon Labs.
Corp., 161 F.3d 709, 716 (Fed. Cir. 1998) (“[T]rial courts
generally can hear expert testimony for background and
education on the technology implicated by the presented
claim construction issues, and . . . have broad discretion in
this regard.”). Indeed, Actavis’s expert acknowledged that,
“when you form[] the salt from a combination of the oxy-
morphone and the ABUK[, i.e., the 14-hydroxy-
morphinone], the [14-hydroxymorphinone] gets formed
into a salt at the same time,” and that a “[PHOSITA] would
be aware of that.” J.A. 3116; see J.A. 3413 (stating, by
Endo’s expert, that a PHOSITA “would know that if you
have oxymorphone ABUK in the form of
a[] . . . salt, . . . then the ABUK will exist in the form of
the . . . salt also”). Accordingly, the intrinsic and extrinsic
evidence support the District Court’s construction of 14-
6 Although we may also consider the prosecution his-
tory, see Home Diagnostics, 381 F.3d at 1356, neither the
parties nor we have identified anything in the prosecution
history that further elucidates the proper construction of
this limitation, see generally Appellants’ Br.; Appellees’ Br.
ENDO PHARM. INC. v. ACTAVIS LLC 13
hydroxymorphinone as 14-hydroxymorphinone hydrochlo-
ride. 7
II. Obviousness
A. Standard of Review and Legal Standard
“Obviousness is a question of law, reviewed de novo,
based upon underlying factual questions which are re-
viewed for clear error following a bench trial.” Pozen Inc.
v. Par Pharm., Inc., 696 F.3d 1151, 1160 (Fed. Cir. 2012)
(internal quotation marks, italics, and citation omitted). A
patent claim is invalid “if the differences between the sub-
ject matter sought to be patented and the prior art are such
that the subject matter as a whole would have been obvious
at the time the invention was made to a [PHOSITA].”
35 U.S.C. § 103(a) (2006). 8 Relevant underlying findings of
7 Actavis’s argument that the Asserted Claims are
anticipated by the prior art is dependent on our adopting
their proffered construction of 14-hydroxymorphinone. See
Appellants’ Br. 66–67, 74–75. Since we do not adopt Ac-
tavis’s construction, we need not address their anticipation
argument. See Knowles Elecs. LLC v. Iancu, 886 F.3d 1369,
1373 n.3 (Fed. Cir. 2018) (explaining that “we need not ad-
dress the appellant’s conditional [invalidity] arguments”
where the lower tribunal “did not err in its construction of
[a] disputed limitation” (internal quotation marks, brack-
ets, and citation omitted)).
8 Congress amended § 103 when it enacted the
Leahy-Smith America Invents Act (“AIA”). Pub. L. No.
112-29, § 3(c), 125 Stat. 284, 287 (2011). Likewise, Con-
gress amended 35 U.S.C. § 102 through the AIA. See id.
§ 3(b), 125 Stat. at 285–87. However, because the applica-
tion that led to the ’779 patent has never contained (1) a
claim having an effective filing date on or after March 16,
2013, or (2) a reference under 35 U.S.C. §§ 120, 121, or
365(c) to any patent or application that ever contained such
14 ENDO PHARM. INC. v. ACTAVIS LLC
fact include: (1) “the scope and content of the prior art,”
(2) “differences between the prior art and the claims at is-
sue,” (3) “the level of ordinary skill in the pertinent art,”
and (4) the presence of objective indicia of nonobviousness
such “as commercial success, long felt but unsolved needs,
failure of others,” and unexpected results. Graham v. John
Deere Co. of Kan. City, 383 U.S. 1, 17 (1966); see United
States v. Adams, 383 U.S. 39, 50–52 (1966). “An obvious-
ness determination requires finding that a [PHOSITA]
would have been motivated to combine or modify the teach-
ings in the prior art and would have had a reasonable ex-
pectation of success in doing so.” Regents of Univ. of Cal.
v. Broad Inst., Inc., 903 F.3d 1286, 1291 (Fed. Cir. 2018)
(citation omitted).
B. The District Court Did Not Clearly Err in Finding a
PHOSITA Would Not Have a Reasonable Expectation of
Success in Combining the Prior Art
The District Court held that a PHOSITA “would have
understood that it would not be feasible” to employ Chap-
man’s solution to the reappearing ABUK problem to
Weiss’s catalytic hydrogenation process for oxymorphone.
Endo, 2017 WL 3731001, at *9. The District Court also ex-
plained that a PHOSITA would not have a reasonable ex-
pectation of success in employing “sulfur addition and
separation as a method of producing low-ABUK oxy-
morphone,” id., because Rapoport does not “teach[] that
low-ABUK oxymorphone can be achieved through bisulfite
addition combined with extraction,” id. at *10. The District
Court also considered certain confidential communications
between the U.S. Food and Drug Administration (“FDA”)
and producers of oxymorphone, including Mallinckrodt
a claim, the pre-AIA §§ 102 and 103 apply. See id. § 3(n)(1),
125 Stat. at 293.
ENDO PHARM. INC. v. ACTAVIS LLC 15
(“FDA communications”). Id. at *12; see J.A. 2890–903. 9
The District Court held that the FDA communications did
9 The FDA communications mandated that opioid
manufacturers reduce ABUK impurities in oxycodone and
oxymorphone to below 0.001%. J.A. 2895; see J.A. 2904.
Although the District Court concluded that the FDA com-
munications are not prior art, see Endo, 2017 WL 3731001,
at *6–7, we disagree. The District Court determined that
(1) “the documents [were not] generally available as re-
quired for them to be § 102(b) prior art,” id. at *6 (internal
quotation marks and citation omitted); see 35 U.S.C.
§ 102(b) (stating a patent may be invalid if “the invention
was patented or described in a printed publication in this
or a foreign country or in public use or on sale in this coun-
try, more than one year prior to the date of the application
for patent in the United States”); and (2) “declar[ing] a de-
sire to have a product that has a particular characteristic,
but . . . [not] provid[ing] any teachings on how to achieve
that goal,” is not enough to make a reference prior art un-
der, inter alia, § 102(f), Endo, 2017 WL 3731001, at *6 n.4;
see 35 U.S.C. § 102(f) (prohibiting the grant of a patent to
one who “did not himself invent the subject matter sought
to be patented”). However, we have stated that § 102(f)
“does not pertain only to public knowledge, but also applies
to private communications between the inventor and an-
other which may never become public.” OddzOn Prods.,
Inc. v. Just Toys, Inc., 122 F.3d 1396, 1401–02 (Fed. Cir.
1997). Moreover, we have also provided that, “[u]nder an
obviousness analysis, a reference need not work to qualify
as prior art; it qualifies as prior art, regardless, for what-
ever is disclosed therein.” Geo. M. Martin Co. v. All. Mach.
Sys. Int’l LLC, 618 F.3d 1294, 1302 (Fed. Cir. 2010) (inter-
nal quotation marks and citation omitted). Thus, confiden-
tiality and the absence of any teachings of how to
accomplish a stated goal do not bar the FDA communica-
tions from being considered prior art here. See id.;
16 ENDO PHARM. INC. v. ACTAVIS LLC
not provide a reasonable expectation of success because
they “were not teachings and provided no substantive in-
formation about how the companies were to go about pro-
ducing low-ABUK oxymorphone” and instead “recognized
the challenge the mandate posed for the companies.” Endo,
2017 WL 3731001, at *12. Actavis challenges the District
Court’s finding of a lack of reasonable expectation of suc-
cess and argues the District Court’s conclusions “must be
reversed.” Appellants’ Br. 66; see id. at 56–66. We disagree
with Actavis.
The District Court did not clearly err in concluding that
a PHOSITA would lack a reasonable expectation of success
in combining Weiss, Chapman, and Rapoport. First, a
PHOSITA would not have a reasonable expectation of suc-
cess in employing Weiss’s catalytic hydrogenation process
for oxymorphone with Chapman’s process to remove diol
during hydrogenation. Although Weiss discloses a method
of purifying oxymorphone ABUK through catalytic hydro-
genation, it does not provide key reaction conditions, see
J.A. 2295–98; see also J.A. 3456 (stating, by Endo’s expert,
that Weiss “omits[, inter alia,] . . . the time that the hydro-
genation reaction is run[,] . . . the amount and composition
of the . . . catalyst[,] . . . precisely what catalyst [is]
us[ed,] . . . [and] the pressure of the hydrogen gas,” each of
which can “affect the effectiveness of the hydrogenation
procedure”), 10 or any level of achieved purification of
OddzOn, 122 F.3d at 1401–02. As discussed below, the Dis-
trict Court considered the FDA communications in its rea-
sonable expectation of success analysis and properly
determined that they were insufficient.
10 With regard to each prior art reference, the District
Court, citing cognizable evidence, see, e.g., J.A. 3456 (testi-
mony of Endo’s expert regarding Weiss), 3483 (same re-
garding Chapman), 3516 (same regarding Rapoport), found
Endo’s expert “credible and more convincing” than
ENDO PHARM. INC. v. ACTAVIS LLC 17
oxymorphone, let alone purification to the degree claimed
by the Asserted Claims, see J.A. 2295–98; see also J.A. 3005
(stating, by Actavis’s expert, that Weiss does not “measure
[or] quantify the amount of ABUK[, i.e., 14-hydroxy-
morphinone]”), 3458–59 (same, by Endo’s expert); ’779 pa-
tent col. 37 l. 58–col. 38 l. 61 (claiming oxymorphone
containing 10 ppm or less of 14-hydroxymorphinone).
Weiss also explains that the catalytic hydrogenation pro-
cess produces oxymorphone diol, see J.A. 2295–96, which is
undesirable because it can revert to 14-hydroxy-
morphinone upon the process’ completion and thereby frus-
trate purification, see J.A. 3476–82 (describing, by Endo’s
expert, how the process disclosed by Weiss produces oxy-
morphone diol, and how a significant amount of this diol is
likely to revert to 14-hydroxymorphinone as a result of
steps undertaken later in the process). With respect to the
comparative effect of catalytic hydrogenation on oxy-
morphone ABUK and oxycodone ABUK, Weiss discloses
that the former produces oxymorphone diol much more
readily than the latter produces oxycodone diol, see
J.A. 2296 (explaining that the “ready conversion of [oxy-
morphone ABUK] into [oxymorphone diol] suggested the
possibility” of a similar result in an oxycodone process, but
finding “[t]he total yield of [oxycodone diol] obtained in this
fashion was very small”), indicating that the process is
much less effective on oxymorphone ABUK because oxy-
morphone diol can revert to oxymorphone ABUK and
thereby hinder purification, see J.A. 3014 (explaining, by
Actavis’s expert, that oxymorphone diol can “go[] to the un-
desired oxymorphone ABUK”), 3455 (stating, by Endo’s
Actavis’s, see Endo, 2017 WL 3731001, at *9; see also id. at
*8–11. We do not disturb these credibility findings on ap-
peal. See Celsis in Vitro, Inc. v. CellzDirect, Inc., 664 F.3d
922, 929 (Fed. Cir. 2012) (“The district court has wide dis-
cretion to weigh expert credibility. This court defers to
such credibility determinations.” (citations omitted)).
18 ENDO PHARM. INC. v. ACTAVIS LLC
expert, that oxymorphone diol is a precursor to oxy-
morphone ABUK, and its presence can cause “ABUK lev-
els . . . to increase after hydrogenation ends”).
In turn, Chapman discloses processes involving the
catalytic hydrogenation of oxycodone ABUK, see J.A. 2473,
and that these processes create oxycodone diol, see
J.A. 2470, which can hinder purification by “revert[ing] to
some ABUK and build[ing] up ABUK after an attempted
purification,” J.A. 3021. Chapman also describes a process
that can reduce oxycodone diol in an oxycodone sample, see
J.A. 2473–74, but Endo’s expert explained that this would
likely be ineffective in achieving the same purity as the ox-
ymorphone claimed by the Asserted Claims, see J.A. 3483–
91. This is because the only example of this process pro-
vided by Chapman, see J.A. 2383–84, discloses a “long re-
action time” of “nearly 22 hours” only reducing the
oxyocodone diol content of an oxycodone sample from 2,900
ppm to 400 ppm, and “with 400 ppm [of diol], that’s a lot of
ABUK you can make,” J.A. 3483. Moreover, the longer the
reaction runs, the less diol is progressively removed and
the more “other side reactions are going to come in and
compete,” such that one would “start to hydrogenate other
parts of the molecule and introduce other material” and,
therefore, would not “have any [of the desired] prod-
uct . . . left at all.” J.A. 3486–87; see ’779 patent col. 2
ll. 46–51 (“[K]nown hydrogenation methods may tend to
undesirably reduce the ketone as well as reducing or re-
moving the [ABUK],” and “are not normally capable of effi-
ciently and economically reducing the levels of [diol] to
below 10 to 100 [ppm], or less.”).
A PHOSITA would not have had a reasonable expecta-
tion of success in combining Weiss and Chapman because
Weiss disclosed a material difficulty with using catalytic
hydrogenation to purify oxymorphone to the FDA-
mandated level, i.e., the production of relatively large
amounts of oxymorphone diol, see J.A. 2295–96; see also
J.A. 3479 (explaining, by Endo’s expert, that a PHOSITA
ENDO PHARM. INC. v. ACTAVIS LLC 19
would have understood Weiss to teach “that they’re going
to have a higher concentration of the diol in the oxy-
morphone ABUK reactions than they will in the oxycodone
and therefore there’s a higher chance that they’ll regener-
ate the oxymorphone ABUK after the end of the reaction
than they would have in the oxycodone case”), and Chap-
man did not describe a viable solution to this difficulty, see
J.A. 3483 (explaining, by Endo’s expert, that a PHOSITA
reading Chapman would not know how to achieve a suffi-
ciently low amount of diol), 3486–87 (discussing, by Endo’s
expert, the problem of hydrogenating too much of the mol-
ecule); see also J.A. 2473–74. Moreover, Endo’s expert tes-
tified that, because oxymorphone ABUK and oxycodone
ABUK “are different molecules, . . . they are going to have
different reactivities,” J.A. 3466; see J.A. 3220 (stating, by
an inventor of another patent, that molecules like oxy-
morphone and oxymorphone ABUK can slow hydrogena-
tion and are much less stable than oxycodone and
oxycodone ABUK), and, therefore, a PHOSITA would have
been unlikely to apply Chapman to oxymorphone ABUK,
see J.A. 3445–46; see also J.A. 3455 (stating, by Endo’s ex-
pert, that the position that a PHOSITA would have utilized
oxycodone ABUK purification methods on oxymorphone
ABUK “ignores differences between the reactivities of ox-
ycodone and oxymorphone[,] . . . [and] trivializes the re-
moval of the oxymorphone diol” and how “ABUK levels are
expected to increase after hydrogenation ends”).
Second, the District Court did not clearly err in finding
that a PHOSITA lacked a reasonable expectation of success
in employing Rapoport’s sulfur addition and separation
process to remove oxymorphone impurities. Rapoport dis-
closes a process for purifying oxycodone ABUK through the
use of bisulfite additions, but it does not state that any re-
sulting compounds have the purity levels of those in the
Asserted Claims. See J.A. 2908–13. According to Endo’s
expert, Rapoport explains that 25% of ABUK impurities re-
main following completion of the process, which is “not a
20 ENDO PHARM. INC. v. ACTAVIS LLC
very good partition ratio.” J.A. 3516. In addition, he re-
counted that the process described by Rapoport not only
fails to remove a significant amount of ABUK, but “re-
sult[s] in a large loss of the desired compound” as well.
J.A. 3517. Therefore, he explained that a PHOSITA would
not believe that Rapoport “would ever be able to get
to . . . 10 [ppm],” as claimed in the ’779 patent. J.A. 3517;
see J.A. 2911.
Third, based on the teachings of Weiss, Chapman, and
Rapoport, the District Court did not clearly err in finding
the FDA communications would not provide a PHOSITA
with a reasonable expectation of success of achieving the
claimed purity levels for oxymorphone. Relevant here, the
FDA communications recount the FDA’s “processes for ad-
dressing the problem of impurities” in oxymorphone that
had been determined to be mutagenic. J.A. 2893. The FDA
limited ABUK content in oxymorphone to 0.001%, i.e., 10
ppm, to satisfy FDA approval guidelines. See J.A. 2895; see
also J.A. 2904 (providing that, in January 2004, “[the FDA]
inform[ed] Mallinckrodt that a 0.001% limit [for ABUK]
will be required for . . . oxymorphone”). The FDA commu-
nications introduced a market force incentivizing purifica-
tion of oxymorphone to the level of the oxymorphone
claimed by the Asserted Claims. See J.A. 2895; Plantron-
ics, Inc. v. Aliph, Inc., 724 F.3d 1343, 1354 (Fed. Cir. 2013)
(“[M]otivation to combine may be found explicitly or implic-
itly in[, inter alia,] market forces; design incen-
tives; . . . any need or problem known in the field of
endeavor at the time of invention . . . ; and the background
knowledge, creativity, and common sense of [a PHOSITA].”
(internal quotation marks and citation omitted)); see also
Allergan, Inc. v. Sandoz Inc., 726 F.3d 1286, 1291–92 (Fed.
Cir. 2013) (“The potential for FDA approval . . . may
properly be considered, . . . in determining whether [a
PHOSITA] would be motivated to develop a drug prod-
uct . . . .”). However, the FDA communications recite a goal
without teaching how the goal is attained. See J.A. 2890–
ENDO PHARM. INC. v. ACTAVIS LLC 21
903; see also Innogenetics, N.V. v. Abbott Labs., 512 F.3d
1363, 1373 (Fed. Cir. 2008) (“[K]nowledge of a problem and
motivation to solve it are entirely different from motivation
to combine particular references.”). 11 Instead, the District
Court found that the FDA communications “reveal that the
FDA recognized the challenge the mandate posed for the
companies.” Endo, 2017 WL 3731001, at *12. The FDA
communications convey nothing that would have a led a
PHOSITA to view Rapoport’s teachings in a different light,
see J.A. 3517, or to believe that the sulfur process it de-
scribes might be more effective on oxymorphone ABUK, see
J.A. 2890–903. Therefore, these communications would
not have been enough to overcome the disclosures of Weiss,
Chapman, and Rapoport, which indicate that a PHOSITA
would not reasonably believe their disclosed methods were
fruitful avenues to achieve the FDA-mandated oxy-
morphone purity level. See Abbott Labs. v. Sandoz, Inc.,
544 F.3d 1341, 1352 (Fed. Cir. 2008) (stating, in the context
of certain FDA regulations on extended-release
11 Indeed, the District Court considered the FDA com-
munications’ import in its motivation to combine or modify
analysis. See Endo, 2017 WL 3731001, at *11–12. Actavis
argues the District Court clearly erred in finding the FDA
communications did not provide a motivation to combine
the prior art. Appellants’ Br. 44. Even if the FDA commu-
nications provided a general motivation to the opioid indus-
try to achieve a particular purity level, see Plantronics, 724
F.3d at 1354, we need not resolve whether it provided the
legally-required motivation to combine because we con-
clude that a PHOSITA would not have a reasonable expec-
tation of success based on the prior art, see Intelligent Bio-
Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367
(Fed. Cir. 2016) (explaining that reasonable expectation of
success and motivation to combine are “two different legal
concepts”).
22 ENDO PHARM. INC. v. ACTAVIS LLC
formulations, that “knowledge of the goal does not render
its achievement obvious”). 12
This conclusion is further supported by the fact that
the inventors of the ’779 patent engaged in extensive ex-
perimentation, involving much failure, to ultimately pro-
duce the oxymorphone of the Asserted Claims. See, e.g.,
J.A. 3142 (stating, by an inventor of the ’779 patent, that
the inventors “tried many different” ways to achieve the
oxymorphone of the purity claimed, “but none of [the prior
art] tell[s] you which ones will get you below the FDA-
mandated level”), 3249–64 (describing, by a different in-
ventor of the ’779 patent, a subset of the experiments en-
gaged in to reach the purity of the claimed oxymorphone),
3464 (acknowledging, by Endo’s expert, the “extensive ex-
perimentation” engaged in by the inventors of the ’779 pa-
tent to achieve the compounds claimed by the Asserted
Claims). The inventors also testified to their concerns
when they became aware of the FDA’s purity requirement
because it represented a dramatic, and potentially prob-
lematic, change in light of then-current knowledge and ca-
pabilities. See, e.g., J.A. 3248 (expressing, by an inventor
of the ’779 patent, that he “was fairly shocked and con-
cerned” because “[10 ppm was] a fairly low number,” and
12 The dissent raises the concern that, after the FDA
imposed a purity requirement for oxymorphone, Endo im-
properly “claimed the FDA mandate[d]” purity levels, ra-
ther than “a specific process.” Dissent Op. 6; see id. (“This
is not the type of innovation that the patent system and the
obviousness standard were designed to protect.”). This pol-
icy issue does not bear on the legal issue of obviousness
presented in this appeal. Instead, patent law allows a
party like Endo to gain from its efforts by securing a patent
on a composition. See 35 U.S.C. § 101 (allowing “[w]hoever
invents or discovers any new and useful . . . composition of
matter” to “obtain a patent therefor”).
ENDO PHARM. INC. v. ACTAVIS LLC 23
“[i]t represent[ed] a fundamentally significant paradigm
shift from the way the current [active pharmaceutical in-
gredient] manufacturing companies monitor and control
their impurities”); see also J.A. 3386 (stating, by the project
manager for Mallinckrodt’s project to lower ABUK content
in opioids, that “[g]iven that the target level that we were
asked to reach for the ABUK[] impurities was orders of
magnitude lower than where we currently stood, there
were a number of challenges on both the process chemistry
side as well as the analytical chemistry side”). Thus, the
District Court did not clearly err in finding no reasonable
expectation of success.
Actavis argues, and the dissent accepts, that the Dis-
trict Court erred as a matter of law by imposing a height-
ened standard in its application of the reasonable
expectation of success test. See Appellants’ Br. 56–57; Dis-
sent Op. 2–4. We disagree. Although Actavis points to the
District Court’s usage of the phrase “definitive solution,”
Appellants’ Br. 56–57 (quoting Endo, 2017 WL 3731001, at
*9), 13 “[w]e will not find legal error based upon an isolated
statement stripped from its context,” Waymo LLC v. Uber
Techs., Inc., 870 F.3d 1350, 1361 (Fed. Cir. 2017) (internal
quotation marks and citation omitted). Instead, the Dis-
trict Court articulated the proper legal standard, see Endo,
2017 WL 3731001, at *6 (“That ‘expectation of success need
only be reasonable, not absolute.’” (quoting Pfizer, Inc. v.
Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007))), and ap-
plied the correct standard, see, e.g., id. at *10 (explaining
13 The dissent selectively chooses other statements
made by the District Court. See Dissent Op. 3–4. Regard-
less, for the reasons explained, we are confident the Dis-
trict Court applied the correct standard. Indeed, we agree
that, if the District Court had applied a ‘definitive solution’
or ‘actual success’ standard to measure reasonable expec-
tation of success, it would be legal error.
24 ENDO PHARM. INC. v. ACTAVIS LLC
that, for Rapoport’s sulfur addition and separation process,
a PHOSITA would not understand “that this was a prom-
ising method” and stating a “single experiment on a differ-
ent compound” was insufficient to render the process
“obvious to a [PHOSITA]” (emphasis added)), *12 (finding
“the FDA mandate [did not] provide[] a [PHOSITA] with a
reasonable expectation of success” (emphasis added)). For
instance, where the District Court stated that a PHOSITA
“would not find a definitive solution in Chapman” to the
diol problem, id. at *9, it did not solely base its finding on
this statement. The District Court carefully surveyed each
expert’s testimony on this issue, see id. at *8–9, found Ac-
tavis’s expert’s testimony “not credible in light of [Endo’s
expert’s] explanation of what would happen,” and con-
cluded that a PHOSITA “would have understood that it
would not be feasible to simply run the reaction as [Ac-
tavis’s expert] suggested,” id. at *9. We do not find error
in this reasoning. For the reasons stated above, the Dis-
trict Court did not commit clear error in finding that a
PHOSITA lacked a reasonable expectation of success, such
that the Asserted Claims would not have been obvious. 14
14 Actavis also argues that the District Court erred in
its finding of non-obviousness because a secondary consid-
eration, i.e., simultaneous invention, supports obviousness.
See Appellants’ Br. 56. Actavis argues three patent appli-
cations and one patent close in time to the ’779 patent’s in-
vention date, all of which disclose compounds of a purity
comparable to those claimed by the Asserted Claims, sup-
port obviousness. See id. at 51–52. However, the three ap-
plications refer to formulations of oxycodone, not
oxymorphone, see J.A. 2459–63 (U.S. Patent Application
No. 2006/0111383, entitled “Preparation of Oxycodone”),
2464–90 (Chapman), 2613–75 (U.S. Provisional Patent Ap-
plication No. 60/557,492, entitled “Process for Preparing
Oxycodone Substantially Free of 14-Hydroxycodeinone and
ENDO PHARM. INC. v. ACTAVIS LLC 25
CONCLUSION
We have considered Actavis’s remaining arguments
and find them unpersuasive. Accordingly, the Final Judg-
ment of the U.S. District Court for the District of Delaware
is
AFFIRMED
Compositions Thereof”), and we agree with the District
Court’s reasoning that the one successful purification of ox-
ymorphone to the level of that claimed by the Asserted
Claims, disclosed in the patent cited by Actavis, is unper-
suasive with regard to obviousness, see Endo, 2017 WL
3731001, at *12.
United States Court of Appeals
for the Federal Circuit
______________________
ENDO PHARMACEUTICALS INC.,
MALLINCKRODT LLC,
Plaintiffs-Appellees
v.
ACTAVIS LLC, FKA ACTAVIS INC., ACTAVIS
SOUTH ATLANTIC LLC, TEVA
PHARMACEUTICALS USA, INC.,
Defendants-Appellants
______________________
2018-1054
______________________
Appeal from the United States District Court for the
District of Delaware in No. 1:14-cv-01381-RGA, Judge
Richard G. Andrews.
______________________
STOLL, Circuit Judge, dissenting.
I respectfully dissent. The FDA set a regulatory re-
quirement that ABUK content in oxymorphone products be
less than 0.001% (10 ppm). Mallinckrodt then claimed this
requirement in the ’779 patent. Not only does the FDA’s
mandate disclose every limitation of claim 1, but it is the
only prior art reference that discloses the 0.001% oxy-
morphone ABUK limitation. Compare J.A. 2736, 2895,
with ’779 patent col. 37 ll. 58–59. Yet, the district court de-
termined that this mandate did not disclose “anything sub-
stantive relevant to obviousness.” Endo Pharm. Inc. v.
Actavis Inc., No. CV-14-1381, 2017 WL 3731001, at *7
2 ENDO PHARM. INC. v. ACTAVIS LLC
(D. Del. Aug. 30, 2017) (“Decision”). It further erred by im-
posing a requirement that a reference must teach how to
solve a problem to provide a motivation to combine, conflat-
ing enablement and reasonable expectation of success re-
quirements with motivation. See id. at *12. Finally, the
district court applied an erroneously heightened standard
for reasonable expectation of success by requiring a “defin-
itive solution” and proof of actual success. Id. at *9. The
majority would disregard a number of these errors as
harmless, affirming on the lack of a reasonable expectation
of success. Given the significance of the court’s errors, how-
ever, I cannot agree. While we owe deference to a district
court’s factual findings, such deference is not due where
the trial court applies the incorrect standard to arrive at
those findings. I would vacate the district court’s decision
and remand for a proper analysis under the correct legal
standards.
The district court found that the FDA Communications
do not disclose how to achieve low-ABUK oxymorphone,
“nor do they disclose that this result had ever been
achieved in the past . . . . There is simply no disclosure of
anything substantive relevant to obviousness in these com-
munications.” Id. at *7. The district court further found
that “[s]ince the FDA mandate was nothing more than a
directive and provided no substantive teachings on how to
produce low-ABUK oxymorphone, it cannot serve as a ‘mo-
tivation to combine’ in an obviousness analysis.” Id. at *12.
I fail to see how the FDA Communications do not disclose
“anything substantive relevant to obviousness,” when they
disclose every limitation of claim 1 and are the only refer-
ences that expressly disclose the limitation of oxymorphone
ABUK content less than 0.001%. Id. at *7. It can hardly
be disputed that the FDA communications motivated the
actual development of the ’779 invention. Indeed, as one of
the inventors of the ’779 patent testified, “no special atten-
tion was focused on” ABUK impurities prior to the FDA’s
structural alert. J.A. 3138 at 222:19–21.
ENDO PHARM. INC. v. ACTAVIS LLC 3
The district court also erred by elevating the reasona-
ble expectation of success standard to require that the prior
art provide a definitive solution to the problem and proof of
actual success. For example, in addressing Rapoport,
which discloses a sulfur addition reaction followed by ex-
traction, the court required proof that Rapoport’s technique
was actually used and worked. Specifically, the district
court found that a person of ordinary skill would not have
thought Rapoport promising because of its poor extraction
partition ratio combined with “the lack of any examples of
this method being used successfully.” Decision, 2017 WL
3731001, at *10 (emphasis added). This is the wrong
standard. Had Rapoport disclosed successful use of sulfur
addition and extraction to achieve ABUK levels of less than
10 ppm, it would anticipate the claims. As we have repeat-
edly held, obviousness requires only a reasonable expecta-
tion of success, not proof of actual success. See PAR
Pharm., Inc. v. TWI Pharm., Inc., 773 F.3d 1186, 1198
(Fed. Cir. 2014). The district court further erred by requir-
ing proof of actual success regarding Dr. Gokel’s proffered
combination of Rapoport with conventional precipitation or
chromatography. It discounted Dr. Gokel’s suggestion as
“purely hypothetical,” stating that there “is no evidence an-
yone ever combined these methods prior to the invention
date and Dr. Gokel himself never did any experiments to
show that they would work.” Decision, 2017 WL 3731001,
at *10 (emphasis added). As mentioned above, obviousness
does not require proof of successful use of a combination,
and the court erred by requiring as much.
The district court may have recited the correct legal
standard, but contrary to what the majority states, the dis-
trict court certainly did not apply that standard in its anal-
ysis. See Majority Op. 23–24. For example, the district
court’s finding that a person of ordinary skill would not
have found Rapoport “promising” was partially based on
“the lack of any examples of [Rapoport] being used success-
fully.” Decision, 2017 WL 3731001, at *10. Further, the
4 ENDO PHARM. INC. v. ACTAVIS LLC
district court noted that the Macfarlan Smith experi-
ment—the “single experiment on a different compound”—
did not show ABUK reduction to below 0.001%. Id. In
other words, there was no evidence that a sulfur addition
technique actually worked. As mentioned above, a reason-
able expectation of success does not require proof of actual
success. These statements are thus not examples of the
district court applying the correct standard, as the majority
believes, and instead show the opposite. See Majority
Op. 23–24.
The district court similarly erred when considering
Chapman. After reviewing testimony from both experts,
the district court credited Mallinckrodt’s expert, Dr. Da-
vies, and stated that “even if a person of ordinary skill
would view the oxycodone art as informative in researching
possible solutions to reducing ABUK levels in oxy-
morphone, he would not find a definitive solution in Chap-
man.” Decision, 2017 WL 3731001, at *9 (emphasis added).
This heightened requirement also goes beyond the reason-
able expectation of success standard and constitutes legal
error. Further, the district court’s finding that a person of
ordinary skill “would have understood that it would not be
feasible to simply run [Chapman’s] reaction to completion
as Dr. Gokel suggested,” focuses on the wrong question. Id.
It is not required for catalytic hydrogenation to be run to
completion in order to achieve 10 ppm ABUK. In fact,
Dr. Gokel testified that Chapman itself—which achieved
5 ppm ABUK—was not run to completion: “Q: Now, did he
run that part of the process to completion to convert the
diol into the ABUK so he could then hydrogenate it and
make the oxycodone drug? . . . A: He did not, but he could
have.” J.A. 3019–20 at 103:22–104:6.
Finally, the district court erred by conflating the re-
quirements of reasonable expectation of success and moti-
vation to combine. The district court required that the
FDA Communications teach how to achieve the claimed in-
vention in order to provide a motivation to combine. See
ENDO PHARM. INC. v. ACTAVIS LLC 5
Decision, 2017 WL 3731001, *12. Whether a reference
teaches how to achieve the claimed invention speaks to en-
ablement or reasonable expectation of success—entirely
separate inquiries from motivation to combine. “[O]ne
must have a motivation to combine accompanied by a rea-
sonable expectation of achieving what is claimed in the pa-
tent-at-issue.” Intelligent Bio-Sys., Inc. v. Illumina
Cambridge Ltd., 821 F.3d 1359, 1367 (Fed. Cir. 2016) (em-
phasis added). Motivation to combine refers to “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.” KSR Int’l Co. v. Teleflex Inc.,
550 U.S. 398, 418 (2007). A reasonable expectation of suc-
cess, on the other hand, addresses whether a person of or-
dinary skill in the art would have understood that the
proposed combination or modification would have been rea-
sonably likely to be successful. See, e.g., UCB, Inc. v. Ac-
cord Healthcare, Inc., 890 F.3d 1313, 1325–26 (Fed. Cir.
2018).
Our case law does not require that a reference teach
how to achieve the claimed invention in order to provide a
motivation to combine. The FDA Communications disclose
all the limitations of claim 1. They also disclose a reason
to modify Weiss, Chapman, or Rapoport to achieve ABUK
levels of less than 10 ppm: the FDA required such levels
because it had determined that ABUK levels higher than
10 ppm were genotoxic. If these communications also
taught “how the goal is attained,” they would anticipate the
asserted claims—we would have no need to address obvi-
ousness.
For all these reasons, I would vacate the district court’s
decision and remand to allow the district court to apply the
correct obviousness test and properly consider the role of
the FDA mandate—the sole reason for the ’779 patent’s ex-
istence—in the obviousness analysis. This is not a typical
Hatch-Waxman case where the patentee provided the pub-
lic with a new drug, formulation, or manufacturing process.
6 ENDO PHARM. INC. v. ACTAVIS LLC
While Mallinckrodt’s patent specification is directed to a
specific process for achieving the FDA’s objective,
Mallinckrodt did not claim that process. Mallinckrodt in-
stead claimed the FDA mandate. The FDA sought to make
oxymorphone safer for the public and Mallinckrodt took ad-
vantage by claiming the directive itself, securing exclusive
rights to a drug first approved in 1959. This is not the type
of innovation that the patent system and the obviousness
standard were designed to protect.