Nalpropion Pharmaceuticals v. Actavis Laboratories Fl, Inc.

United States Court of Appeals
for the Federal Circuit
______________________
NALPROPION PHARMACEUTICALS, INC.,
Plaintiff-Appellee
v.
ACTAVIS LABORATORIES FL, INC.,
Defendant-Appellant
______________________
2018-1221
______________________
Appeal from the United States District Court for the
District of Delaware in No. 1:15-cv-00451-RGA, Judge
Richard G. Andrews.
______________________
Decided: August 15, 2019
______________________
DOMINICK A. CONDE, Venable LLP, New York, NY, ar-
gued for plaintiff-appellee. Also represented by
CHRISTOPHER P. BORELLO, JOSHUA DANIEL CALABRO,
ZACHARY GARRETT, BRENDAN M. O'MALLEY.
JONATHAN D. BALL, Greenberg Traurig LLP, New York,
NY, argued for defendant-appellant. Also represented by
SCOTT JOSEPH BORNSTEIN, JUSTIN ALBANO MACLEAN,
RICHARD CHARLES PETTUS.
______________________
2 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
Before PROST, Chief Judge, LOURIE and WALLACH, Circuit
Judges.
Opinion for the court filed by Circuit Judge LOURIE.
Opinion dissenting in part filed by Chief Judge PROST.
LOURIE, Circuit Judge.
Actavis Laboratories FL, Inc. (“Actavis”) appeals from
the judgment of the U.S. District Court for the District of
Delaware that (1) its proposed naltrexone hydrochloride
and bupropion hydrochloride extended-release tablets,
which are the subject of Abbreviated New Drug Application
No. 208043 (the “ANDA product”), would infringe claim 1
of U.S. Patent 7,375,111 (“the ’111 patent”), claims 26 and
31 of U.S. Patent 7,462,626 (“the ’626 patent”), and claim
11 of U.S. Patent 8,916,195 (“the ’195 patent”); (2) the as-
serted claims are not invalid; (3) the effective date of any
FDA approval of ANDA No. 208043 shall be no earlier than
the latest expiration of the ’111, ’626, and ’195 patents; and
(4) Actavis is permanently enjoined from manufacturing,
using, or selling its ANDA product before the expiration of
the patents in suit. Orexigen Therapeutics, Inc. v. Actavis
Labs. FL, Inc., 282 F. Supp. 3d 793 (D. Del. 2017) (“Deci-
sion”); Final Judgment, Orexigen Therapeutics, Inc. v. Ac-
tavis Labs. FL, Inc., No. 1:15-cv-451 (D. Del. Oct. 26, 2017),
ECF No. 186. Because we conclude that the district court
did not err in finding claim 11 of the ’195 patent not invalid
for lack of written description, but did err in finding that
claim 1 of the ’111 patent and claims 26 and 31 of the ’626
patent would not have been obvious in view of the prior art,
we affirm-in-part and reverse-in-part.
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 3
FL, INC.
BACKGROUND
Appellee Nalpropion Pharmaceuticals, Inc. (“Nal-
propion”) 1 holds New Drug Application No. 200063 for and
markets Contrave® for weight management in overweight
or obese adults. Relevant here are the three Orange Book-
listed patents for Contrave® that Nalpropion asserted
against Actavis: the ’626, ’195, and ’111 patents.
The ’626 patent is drawn to a method for treating over-
weight or obesity comprising (1) diagnosing an individual
as suffering from overweight or obesity by body mass index,
(2) administering bupropion in an amount effective to in-
duce weight loss, and (3) administering naltrexone in an
1 Takeda Pharmaceutical Company Limited
(“Takeda Ltd.”), Takeda Pharmaceuticals International
GmbH, Takeda Pharmaceuticals USA, Inc. (“Takeda
USA”), and Takeda Pharmaceuticals, America, Inc. (collec-
tively, “Takeda”) and Orexigen Therapeutics, Inc. (“Orex-
igen”) filed this suit in the District of Delaware. At the time
of filing, Orexigen owned all three patents in suit, Takeda
Ltd. was the exclusive licensee of the patents, and Takeda
USA held approved New Drug Application No. 200063 for
extended-release tablets containing 8 mg of naltrexone hy-
drochloride and 90 mg of bupropion hydrochloride. During
the litigation, Orexigen acquired all of Takeda’s rights to
Contrave®, including ownership of the NDA. Stipulation
and Order at 1, Orexigen Therapeutics, Inc. v. Actavis Labs.
FL, Inc., No. 1:15-cv-451 (D. Del. Oct. 5, 2017), ECF No. 92.
After this appeal was taken, however, Orexigen com-
menced bankruptcy proceedings under Chapter 11 of Title
11 of the United States Code in the U.S. Bankruptcy Court
for the District of Delaware and transferred ownership of
the patents-in-suit to Nalpropion. Unopposed Motion for
Substitution of Nalpropion Pharms. Inc. for Orexigen Ther-
apeutics, Inc. at 1, Nalpropion Pharm. Inc. v. Actavis Labs.
FL, Inc., No. 18-1221 (Fed. Cir. Aug. 28, 2018), ECF No. 30.
4 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
amount effective to enhance the weight loss activity of bu-
propion. ’626 patent col. 38 l. 60–col. 39 l. 4. Nalpropion
asserted claims 26 and 31. Claim 26 depends from claim
25, which recites:
A method of treating overweight or obesity, com-
prising administering a weight loss effective
amount of a first and second compound to an indi-
vidual who has been diagnosed as suffering from
overweight or obesity in order to treat said over-
weight or obesity, wherein said first compound is
bupropion, or a pharmaceutically acceptable salt
thereof, and said second compound is naltrexone,
or a pharmaceutically acceptable salt thereof, and
wherein the weight loss activity of said first and
second compounds is enhanced compared to the ad-
ministration of the same amount of either com-
pound alone.
Id. col. 40 ll. 16–26. Claim 26 adds the additional limita-
tion that naltrexone and bupropion “are administered to-
gether.” Id. col. 40. ll. 27–30. Claim 30 depends from claim
25 and requires that at least one of the drugs be in a “sus-
tained-release formulation,” id. col. 40 ll. 41–44, while
claim 31, which depends from claim 30, requires that the
drugs be “administered in a single oral dosage form,” id.col. 40 ll. 45–49.
The ’195 patent is also directed to methods of treating
overweight or obesity, but the claims are drawn to specific
dosages of sustained-release naltrexone and bupropion
that achieve a specific dissolution profile. At issue here is
claim 11:
A method of treating overweight or obesity having
reduced adverse effects comprising orally adminis-
tering daily about 32 mg of naltrexone and about
360 mg of bupropion, or pharmaceutically accepta-
ble salts thereof, to a person in need thereof,
wherein the bupropion or pharmaceutically
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 5
FL, INC.
acceptable salt thereof is administered as a sus-
tained release formulation, wherein the naltrexone
or pharmaceutically acceptable salt thereof is ad-
ministered as a sustained release formulation, and
wherein said sustained release formulation of nal-
trexone has an in vitro naltrexone dissolution pro-
file in a dissolution test of USP Apparatus 2 Paddle
Method at 100 rpm in a dissolution medium of wa-
ter at 37° C. of:
a) between 39% and 70% of naltrexone re-
leased in one hour;
b) between 62% and 90% of naltrexone re-
leased in two hours; and
c) at least 99% in 8 hours;
wherein about 16 mg of said sustained re-
lease formulation of naltrexone or a phar-
maceutically acceptable salt thereof is
administered twice daily, and about 180
mg of said sustained release formulation of
bupropion or a pharmaceutically accepta-
ble salt thereof is administered twice daily.
’195 patent col. 31 l. 5–col. 32 l. 3.
Finally, the ’111 patent is directed to a composition of
sustained-release bupropion and naltrexone for affecting
weight loss. Asserted here is claim 1:
A composition for affecting weight loss comprising:
(a) a sustained release formulation of bu-
propion or a pharmaceutically acceptable
salt thereof in an amount effective to in-
duce weight loss in an individual; and
(b) a sustained release formulation of nal-
trexone or a pharmaceutically acceptable
salt thereof in an amount effective to
6 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
enhance the weight loss effect of the bu-
propion or salt thereof;
wherein said composition is in a single oral
dosage form fixed combination.
’111 patent col. 41 ll. 26–35.
Actavis filed an ANDA seeking to enter the market
with a generic version of Contrave® prior to the expiration
of the patents in suit, and Nalpropion responded by bring-
ing an action for patent infringement, alleging that Ac-
tavis’s ANDA product would infringe the ’111, ’626, and
’195 patents. Actavis in turn brought invalidity counter-
claims, challenging claim 11 of the ’195 patent as invalid
for lack of adequate written description and challenging
claim 1 of the ’111 patent and claims 26 and 31 of the ’626
patents as invalid as obvious. The district court held a
bench trial on all of these issues and held each claim not
invalid and infringed. Decision, 282 F. Supp. 3d at 797.
First, the district court considered Actavis’s written de-
scription argument. Actavis argued that claim 11 of the
’195 patent lacked adequate written description support
because its claimed dissolution profile was achieved using
the USP Apparatus 2 Paddle Method (“USP 2”), but the
specification discloses data obtained using the different
USP Apparatus 1 Basket Method (“USP 1”). The court was
not persuaded that the use of a different method from what
is prescribed in the claim presented a written description
problem, holding that “whether the dissolution data re-
ported in the specification was obtained using the basket
method or the paddle method is not relevant to whether the
inventors had possession of the invention.” Id. at 802. In-
stead, the court credited Nalpropion’s expert who opined
that a person of ordinary skill would recognize that the in-
ventors possessed an embodiment of the invention as de-
scribed in Table 10, regardless whether USP 2 or a
“‘substantially equivalent’ method” was used. Id. at 801
(citation omitted).
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 7
FL, INC.
Next, the district court addressed the question of obvi-
ousness of claim 1 of the ’111 patent and claims 26 and 31
of the ’626 patent. Actavis argued that it would have been
obvious for a person of skill to combine bupropion and nal-
trexone for treating overweight and obesity because both
drugs were known to cause weight loss, but the court disa-
greed, finding Actavis’s argument to be “a classic case of
hindsight bias.” Id. at 809.
Actavis appealed from the district court judgment, and
we have jurisdiction under 28 U.S.C. § 1295(a)(1).
DISCUSSION
On appeal from a bench trial, we review a district
court’s conclusions of law de novo and its findings of fact
for clear error. Braintree Labs., Inc. v. Novel Labs., Inc.,
749 F.3d 1349, 1358 (Fed. Cir. 2014). “A factual finding is
clearly erroneous when, despite some supporting evidence,
we are left with a definite and firm conviction that the dis-
trict court was in error.” Alcon Research Ltd. v. Barr Labs.,
Inc., 745 F.3d 1180, 1186 (Fed. Cir. 2014) (citing Alza Corp.
v. Mylan Labs., Inc., 464 F.3d 1286, 1289 (Fed. Cir. 2006)).
“The burden of overcoming the district court’s factual find-
ings is, as it should be, a heavy one.” Polaroid Corp. v.
Eastman Kodak Co., 789 F.2d 1556, 1559 (Fed. Cir. 1986).
“Where there are two permissible views of the evidence, the
factfinder’s choice between them cannot be clearly errone-
ous.” Anderson v. City of Bessemer City, 470 U.S. 564, 574
(1985) (citing United States v. Yellow Cab Co., 338 U.S.
338, 342 (1949)).
Whether a claim satisfies the written description re-
quirement is a question of fact, Ariad Pharm., Inc. v. Eli
Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc),
that we review for clear error, Alcon, 745 F.3d at 1190.
“Whether an invention would have been obvious at the
time it was made is a question of law, which we review de
novo, based on underlying facts, which we review for clear
error.” Tokai Corp. v. Easton Enters., Inc., 632 F.3d 1358,
8 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
1366 (Fed. Cir. 2011) (citing Media Techs. Licensing, LLC
v. Upper Deck Co., 596 F.3d 1334, 1337 (Fed. Cir. 2010)).
The district court rejected Actavis’s invalidity argu-
ments that (1) claim 11 of the ’195 patent is invalid for lack
of adequate written description and (2) claim 1 of the ’111
patent and claims 26 and 31 of the ’626 patent are invalid
as obvious. We address the court’s holdings in turn.
I. Written Description
Claim 11 of the ’195 patent recites a method of treating
overweight or obesity comprising orally administering
about 16 mg of naltrexone and about 180 mg of bupropion,
both in sustained-release formulations administered twice
daily. This method claim also requires that the claimed
naltrexone formulation have an in vitro dissolution profile
in a dissolution test of USP Apparatus 2 Paddle
Method at 100 rpm in a dissolution medium of wa-
ter at 37ºC. of:
a) between 39% and 70% of naltrexone released in
one hour;
b) between 62% and 90% of naltrexone released in
two hours; and
c) at least 99% in 8 hours . . . .
’195 patent col. 31 l. 14–col. 32 l. 3.
Example 1 of the specification discloses formulations of
sustained-release naltrexone with varying amounts of ei-
ther hydroxypropylmethyl cellulose (HPMC) or polyeth-
ylene oxide as excipients. The HPMC formulations range
from 5% HPMC to 66% HPMC, and dissolution of these for-
mulations was tested in Example 2 using 10-mesh baskets
at 100 rpm. The 15% HPMC tablet released 39% of its nal-
trexone at one hour and 62% at two hours. Id. col. 17–18
(Table 5).
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 9
FL, INC.
The first example in the specification to discuss a nal-
trexone-bupropion combination is Example 3, which de-
scribes tri-layer tablets with sustained-release naltrexone
and bupropion layers on opposite sides of an inert layer.
That formulation includes 10% HPMC. Dissolution of nal-
trexone was measured and reported in Table 10, but the
specification is silent as to whether the data were obtained
using USP 1 or USP 2. Id. at col. 20 ll. 1–11.
In finding adequate written description support for the
claimed dissolution profile, the district court found that the
values in Table 10—67% release in one hour and 85% re-
lease in two—fell squarely within the claimed range in
claim 11. Decision, 282 F. Supp. 3d at 802. The court found
the lower bounds were supported by the dissolution data
for the 15% HPMC formulation in Table 5. Id.
Actavis had argued that neither table provided ade-
quate written description support because the data listed
were obtained using USP 1, but the court held that the dis-
solution technique used was not relevant because a person
of skill would understand in the context of the patent that
the inventors possessed the claimed invention. The court
relied on Nalpropion’s expert’s testimony that a person of
skill would understand that the inventors possessed the in-
vention—whether USP 2 or a substantially equivalent
method was used to measure it.
On appeal, Actavis repeats its argument that Tables 5
and 10 fail to provide adequate written description support
for the claimed dissolution profile because the data in those
tables were obtained using USP 1. According to Actavis,
both inventor and expert testimony demonstrated that the
two dissolution methods would produce different results.
Actavis further argues that the data in Table 5 cannot sup-
port the claimed range because a person of ordinary skill
in the art would not appreciate that the 15% HPMC data
were relevant to the claims.
10 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
Nalpropion responds that there was no evidence that
the data in either table were obtained using USP 1. Even
if USP 1 had been used, however, Nalpropion submits that
a person of skill would understand the inventors to have
had possession of their invention “irrespective of whether
they used USP 1 or USP 2 because those methods are ‘sub-
stantially equivalent.’” Appellee’s Br. 22 (citing J.A. Deci-
sion, 282 F. Supp. 3d at 801–02). We conclude that the
district court did not clearly err in finding that the inven-
tors had possession of the invention consisting of treating
overweight and obesity with the stated amounts of bu-
propion.
It is important to take note of the peculiarity of claim
11, which begins clearly enough by reciting a method of
treating overweight or obesity by carrying out the specific,
positive steps of administering a formulation of specific
amounts of sustained-release naltrexone and bupropion in
twice a day. The claim then records the dissolution data
resulting from that formulation.
But that dissolution profile for naltrexone as measured
by USP 2 relates only to the measurement of resultant in
vitro parameters, not to the operative steps to treat over-
weight or obesity. And the district court concluded, on the
facts, that USP 1 and USP 2 would be “substantially equiv-
alent,” Decision, 282 F. Supp. 3d at 801 (citation omitted).
Thus, it found that, irrespective of the method of measure-
ment used, the specification shows that the inventors pos-
sessed the invention of treating overweight or obesity with
naltrexone and bupropion in particular amounts and ade-
quately described it. We conclude that this finding does not
present clear error.
As we explained in Ariad, the written description of an
invention “must ‘clearly allow persons of ordinary skill in
the art to recognize that [the inventor] invented what is
claimed.’” 598 F.3d at 1351 (alteration in original) (quoting
Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir.
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 11
FL, INC.
1991) (Rich, J.) (citing In re Gosteli, 872 F.2d 1008, 1012
(Fed. Cir. 1989))). “In other words, the test for sufficiency
is whether the disclosure of the application relied upon rea-
sonably conveys to those skilled in the art that the inventor
had possession of the claimed subject matter as of the filing
date.” Id. (emphasis added). It is not necessary that the
exact terms of a claim be used in haec verba in the specifi-
cation, and equivalent language may be sufficient.
To support their respective positions, both parties point
to evidence regarding whether a person of skill would un-
derstand USP 1 and USP 2 to be “substantially equiva-
lent.” But the court credited Nalpropion’s expert, Dr.
Treacy, as more credible over what it interpreted as un-
trustworthy, self-serving statements by Actavis’s expert,
Dr. Mayersohn. See Decision, 282 F. Supp. 3d at 801–02
(“It seems to me that Dr. Mayersohn’s theoretical opinion
that the methods would yield different results is at odds
with his reliance on a prior art reference using the basket
method to argue that claim 11, which specifies the paddle
method, was obvious.”). The district court performed pre-
cisely its fact-finding function, weighing credibility of tes-
timony. See Fed. R. Civ. P. 52(a)(6) (“Findings of fact,
whether based on oral or other evidence, must not be set
aside unless clearly erroneous, and the reviewing court
must give due regard to the trial court’s opportunity to
judge the witnesses’ credibility.”). We do not disturb this
finding.
Having found USP 1 and USP 2 substantially equiva-
lent, the district court found Table 5 and Table 10 ade-
quately supported the dissolution data ranges in claim 11.
Particularly, the court was not convinced that relying on
data from two tables presented a written description issue,
noting that it found “nothing odd or invalidating about the
inventors looking to different tables of dissolution data and
other places in the specification to determine the ranges for
the claimed dissolution profile,” and finding that “multiple
tests are necessarily required to establish a range.”
12 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
Decision, 282 F. Supp. 3d at 803. The court relied on the
15% HPMC data in Table 5, crediting both expert’s testi-
mony that 15% HPMC formulations were the first listed in
the table in which a person of skill in the art would observe
“a sustained release profile.” Id. at 802 (quoting J.A.
11369:6–19, 11409:10–17). The court also credited Dr.
Treacy’s testimony that the 99% dissolution at eight-hour
data point was supported by Table 10’s disclosure, dis-
counting Dr. Mayersohn’s view that the dissolution profile
would plateau and never reach the claimed 99% at eight
hours. Id. While Actavis may disagree with the court’s
findings, these findings are supported by the record, and
we do not disturb them. See Anderson, 470 U.S. at 573–74
(“If the district court’s account of the evidence is plausible
in light of the record viewed in its entirety, the court of ap-
peals may not reverse it even though convinced that had it
been sitting as the trier of fact, it would have weighed the
evidence differently.”).
The district court was convinced by its fact findings
that Actavis had not proven by clear and convincing evi-
dence that claim 11 of the ’195 patent is invalid for lack of
adequate written description. While as a general matter
written description may not be satisfied by so-called equiv-
alent disclosure, in this case, buttressed by the district
court’s fact-finding, and where the so-called equivalence re-
lates only to resultant dissolution parameters rather than
operative claim steps, we affirm the district court’s conclu-
sion. Rigidity should yield to flexible, sensible interpreta-
tion.
II. Obviousness
Actavis also challenges claim 1 of the ’111 patent and
claims 26 and 31 of the ’626 patent as obvious in view of
O’Malley and Jain. We begin by reviewing the relevant ref-
erences.
O’Malley is U.S. Patent 6,541,478, entitled “Smoking
Cessation Treatments Using Naltrexone and Related
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 13
FL, INC.
Compounds.” J.A. 7912. O’Malley teaches that weight
gain is “[t]he significant problem” with smoking cessation
and discloses use of opioid antagonists, including naltrex-
one, alone or with other withdrawal attenuating agents to
minimize weight gain during treatment. O’Malley col. 1 l.
59– 62. Claim 1 of O’Malley is drawn to a method of treat-
ing a person for nicotine dependency and minimizing
weight gain during smoking cessation therapy comprising
“administering . . . an effective amount of naltrexone and
another compound selected from the group consisting of . . .
bupropion. . . .” Id. col. 12 ll. 30–37.
Jain2 is a research paper entitled “Bupropion SR vs.
Placebo for Weight Loss in Obese Patients with Depressive
Symptoms.” J.A. 7171. Jain notes that “[p]reliminary
studies suggest that bupropion SR is also an effective ad-
junct to diet for weight loss during acute and long-term
therapy in nondepressed patients” and “is associated with
weight loss in overweight or obese depressed patients.”
J.A. 7171. The authors then describe their double-blind
study where sustained-release bupropion was adminis-
tered in conjunction with a 500-kcal deficit diet. Sus-
tained-release bupropion was found to be more effective
than placebo at reducing weight in obese patients with de-
pressive symptoms.
Additional references provide context for the obvious-
ness arguments in this case: (1) Anderson for bupropion,
(2) Atkinson and Bernstein for naltrexone, and (3) Dante
for both naltrexone and its combination with bupropion.
2 desh K. Jain et al., Bupropion SR vs. Placebo for
Weight Loss in Obese Patients with Depressive Symptoms,
10 OBESITY RES. 1049–56 (2002), J.A. 7171–78 (“Jain”).
14 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
Anderson 3 discloses a 48-week double-blind, placebo-
controlled trial where sustained-release bupropion was ad-
ministered to obese adults. J.A. 7160. Adjusted for pla-
cebo, subjects lost 2.2% and 5.5% of net bodyweight with
300 mg/d and 400 mg/d of sustained-release bupropion, re-
spectively. Id.Atkinson 4 examined the effects of long-term naltrexone
administration on body weight and obesity, administering
naltrexone to 60 obese subjects over 8 weeks. J.A. 8948.
Atkinson found a small but significant weight loss in
women but no significant effect in men. Similarly, Bern-
stein 5 teaches a method for curbing carbohydrate cravings
and overeating through long-term administration of low-
dose naltrexone. Bernstein comments that the administra-
tion of naltrexone as described “would benefit . . . obese per-
sons.” J.A. 7181 ¶ 13.
Dante, U.S. Patent 5,817,665, teaches use of an opioid
antagonist like naltrexone with serotonin or norepineph-
rine reuptake inhibitors to treat mental and emotional dis-
orders. Of note are Examples 2 and 3. Example 2 describes
a woman in her thirties who was started on naltrexone
without making any other changes. Dante col. 6 ll. 16–17.
She rapidly lost her craving for sweets and lost thirty
pounds in three weeks. Id. col. 6. l. 18–19. Example 3 de-
scribes similar results in an obese man. Id. col. 6. ll. 32–
3 James Anderson et al., Bupropion SR Enhances
Weight Loss: A 48-Week Double-Blind, Placebo-Controlled
Trial, 10 OBESITY RES. 633–41 (2002), J.A. 7160–68 (“An-
derson”).
4 Richard Atkinson et al., Effects of Long-Term Ther-
apy with Naltrexone on Body Weight in Obesity, 38 CLIN.
PHARMACOL. THER. 419–22 (1985), J.A. 8948–51 (“Atkin-
son”).
5 U.S. Patent Application 2002/0198227, J.A. 7179–
85 (“Bernstein”).
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 15
FL, INC.
56. While these examples address only administration of
naltrexone, the claims in Dante focus on its combination
with bupropion. Claim 1 of Dante is drawn to “[a] method
of treating depression comprising administering to a pa-
tient a pharmacologically effective dose of an opioid antag-
onist” and a “nontricyclic antidepressant[].” Id. col. 8 ll.
19–30. Claim 7 requires that the “nontricyclic antidepres-
sant” be “selected from a group” including bupropion. Id.col. 8. ll. 47–51.
Despite these references, the district court rejected Ac-
tavis’s obviousness argument. According to the district
court, the weight loss effects of bupropion were known to
be relatively modest at best, and prior art references re-
ported potential risks, including a potential for seizures.
Because a person of skill would not understand bupropion’s
mechanism of action and because of its modest effective-
ness, the court concluded that a person of skill would not
have found bupropion to be an obvious starting point for
further study. Decision, 282 F. Supp. 3d at 807.
The district court was also convinced that a person of
skill would not have understood naltrexone to be effective
for weight loss. The court did not find Bernstein to disclose
weight loss and read Atkinson’s disclosure of weight loss in
women to be counterbalanced by increased body weight in
men. Id. at 808.
As for the combination of the two drugs, the district
court concluded that Dante and O’Malley did not teach a
person of ordinary skill that the combination was effective
for weight loss. Id. at 809. According to the court, neither
reference teaches anything about weight loss or that nal-
trexone enhances bupropion’s weight loss effects. The
court likewise discounted the disclosure in Jain because
men experienced weight gain. Id.
Finally, persuaded that the synergistic effect of the
combination was an unexpected result and that others had
failed to develop safe and effective weight loss drugs, the
16 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
district court held that secondary considerations supported
a finding of nonobviousness. Id. at 810.
On appeal, the parties primarily dispute whether a
person of skill would have been motivated to combine bu-
propion, as disclosed by Jain, and naltrexone, as disclosed
in O’Malley, to arrive at the claimed composition of the ’111
patent and the method of the ’626 patent with a reasonable
expectation of success. Actavis argues that the district
court incorrectly interpreted the prior art and discounted
the fact that both compounds were known to affect weight
loss and had been administered together for that purpose.
Appellant’s Br. 56. In response, Nalpropion submits that
naltrexone was not known to affect weight loss, bupropion
had safety concerns and yielded only modest weight loss,
and the combination had been used only to treat depression
or to minimize weight gain in smoking cessation therapy.
Nalpropion also argues that naltrexone was not known to
enhance bupropion’s effectiveness for weight loss.
Obviousness is a question of law, supported by under-
lying fact questions. In re Baxter Int’l, Inc. 678 F.3d 1357,
1361 (Fed. Cir. 2012). In evaluating obviousness, we con-
sider the scope and content of the prior art, differences be-
tween the prior art and the claims at issue, the level of
ordinary skill in the pertinent art, and any secondary con-
siderations. Graham v. John Deere Co. of Kan. City, 383
U.S. 1, 17–18 (1966); see also Apple Inc. v. Samsung Elecs.
Co., 839 F.3d 1034, 1048 (Fed. Cir. 2016) (en banc) (“Objec-
tive indicia of nonobviousness must be considered in every
case where present.”).
We agree with Actavis and conclude that the claims at
issue would have been obvious to a person of skill in the art
in view of O’Malley and Jain. The prior art here discloses
the claimed components of the composition claims and the
steps of the method claims including the use claimed by the
method.
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 17
FL, INC.
The references teach that bupropion causes weight
loss. For example, Jain specifically teaches that sustained-
release bupropion was “an effective adjunct to diet for
weight loss” in both non-depressed and depressed patients,
J.A. 7171, and was well-tolerated, J.A. 7177. This state-
ment is confirmed by Anderson, which discloses the results
from a 48-week, double-blind, placebo-controlled trial. J.A.
7160. Notably, Anderson’s data indicate that administra-
tion of sustained-release bupropion yielded weight loss in
non-depressed patients. J.A. 7161, 7165. Anderson’s re-
ported weight loss was dependent on bupropion SR dosage.
J.A. 7165. Even Dr. Weber, a named inventor of the ’626
and ’111 patents, confirmed that bupropion had been con-
sidered safe and had weight loss effects. J.A. 11028–29.
Likewise, the record indicates that naltrexone can
cause weight loss. Atkinson reports statistically signifi-
cant weight loss in female obese patients and states that
“naltrexone or similar drugs may have a role in the clinical
treatment of obesity.” J.A. 8950. While Atkinson reports
weight loss only in women, the claims are not limited to
men, and Dante discloses weight loss in two examples—for
both a man and a woman. In Example 2, an obese woman
was started on 25 mg of naltrexone and rapidly “lost her
craving for sweets and a weight loss effort which was
stalled took off. She lost thirty pounds in three weeks.”
Dante col. 6 ll. 16–19. Similarly, 25–50 mg of naltrexone
was administered to an obese man in Example 3, and he
reported losing about 10 pounds a week and no longer
craved sweets. Id. col. 6 ll. 32–51. Bernstein also discloses
that naltrexone reduces carbohydrate cravings and admin-
istration of it would benefit “obese persons.” J.A. 7181 ¶
13.
Given that both drugs had shown weight loss effects,
we conclude that a person of ordinary skill would have been
motivated to combine them. In fact, such persons did so.
O’Malley teaches a combination of effective amounts of sus-
tained-release bupropion and naltrexone for minimizing
18 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
weight gain. Likewise, Dante teaches use of an opioid an-
tagonist, preferably naltrexone, and an antidepressant, in-
cluding bupropion, for decreasing sugar cravings, noting
that naltrexone administration alone led reduced sugar
cravings and weight loss in two examples. A person of skill
would have understood that a combination for reducing
weight gain and decreasing carbohydrate cravings may af-
fect weight loss as well. See, e.g., J.A. 7156 (speculating
that success of a weight-loss treatment could be linked to
beneficial effects on “food cravings”); 7172 (explaining that
patient hunger is relevant to efficacy and outcomes of a
weight-loss treatment); 7181 (explaining “obese persons”
would benefit from a method for reducing carbohydrate
cravings).
Nalpropion suggests that, even in view of these refer-
ences, a person of skill would not have been motivated to
develop bupropion for weight loss (1) because bupropion
yielded only a “paltry 2.8% placebo-adjusted weight loss,”
which was too insignificant to obtain FDA approval as a
weight loss drug, Appellee’s Br. 41, (2) because bupropion
carried a seizure risk, and (3) because its mechanism of ac-
tion was unknown.
We are not persuaded. Nalpropion argues that bu-
propion does not possess sufficient weight loss efficacy to
obtain FDA approval by itself. But, while bupropion alone
may not have been entitled to FDA approval as a weight-
loss treatment, “[t]here is no requirement in patent law
that the person of ordinary skill be motivated to develop
the claimed invention based on a rationale that forms the
basis for FDA approval.” Allergan, Inc. v. Sandoz Inc., 726
F.3d 1286, 1292 (Fed. Cir. 2013). “Motivation to combine
may be found in many different places and forms; it cannot
be limited to those reasons the FDA sees fit to consider in
approving drug applications.” Id. Instead, “[t]he 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
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 19
FL, INC.
issue.’” Arctic Cat Inc. v. Bombardier Recreational Prods.
Inc., 876 F.3d 1350, 1359 (Fed. Cir. 2017) (quoting Inter-
continental Great Brands LLC v. Kellogg N. Am. Co., 869
F.3d 1336, 1344 (Fed. Cir. 2017), cert. denied, 139 S. Ct.
143 (2018)). The inescapable, real-world fact here is that
people of skill in the art did combine bupropion and nal-
trexone for reductions in weight gain and reduced crav-
ings—goals closely relevant to weight loss. Contrary to
Nalpropion’s view, persons of skill did combine the two
drugs even without understanding bupropion’s mechanism
of action but with an understanding that bupropion was
well-tolerated and safe as an antidepressant. See J.A. 7165
(“The precise mechanism for bupropion SR that is respon-
sible for effects on weight loss is unknown.”); see also J.A.
7157 (same). Thus, we conclude that skilled artisans would
have been motivated to combine the two drugs for weight
loss with a reasonable expectation of success.
We next consider the specific language of the claims in
relation to the prior art. Claim 1 of the ’111 patent requires
(1) a sustained-release formulation of bupropion or a phar-
maceutically acceptable salt thereof in an amount effective
to induce weight loss in an individual; and (2) a sustained-
release formulation of naltrexone or a pharmaceutically ac-
ceptable salt thereof in an amount effective to enhance the
weight loss effect of the bupropion or salt thereof; (3) in a
single oral dosage form fixed combination. 6 Jain discloses
300 and 400 mg per day dosages of sustained-release
6 Actavis argues that the preamble, which recites “a
composition for affecting weight loss,” is not limiting, while
Nalpropion argues that it is limiting because it recites the
fundamental purpose of the invention. Appellee’s Br. 49.
Because neither party asked the district court to construe
the preamble, these arguments are waived. Interactive Gift
Exp., Inc. v. Compuserve Inc., 256 F.3d 1323, 1346 (Fed.
Cir. 2001).
20 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
bupropion as facilitating weight loss, meeting the first lim-
itation. O’Malley discloses a sustained-release formulation
of naltrexone administered with bupropion as a “with-
drawal attenuating agent,” O’Malley col. 2 ll. 59–66, that
“enhance[s] the efficacy of the nicotine dependency treat-
ment,” id. col. 4 ll. 25–33, a treatment designed to minimize
weight gain, id. col. 8 ll. 45–48. The naltrexone dosages in
O’Malley—from 12.5 mg to 150 mg—are amounts effective
to enhance the weight loss effects of bupropion. Id. col. 5
ll. 46–50. 7 O’Malley also discloses a single oral dosage form
of bupropion and naltrexone.
Next, we turn to claims 26 and 31 of the ’626 patent.
Claim 25, from which both claims 26 and 31 depend, re-
quires administering a weight-loss effective amount of a
first and a second compound to treat an individual suffer-
ing from overweight or obesity for that condition. The first
and second compounds are bupropion and naltrexone, and
the weight loss effects of the compounds are “enhanced”
compared to the administration of either compound alone.
Claim 26 adds the requirement that the two drugs be ad-
ministered together, and claim 31 requires that at least one
of the drugs is in a sustained-release formulation and that
they are administrated in a single oral dosage form. As
with the ’111 patent, the combination of O’Malley and Jain
meets these requirements, with Jain disclosing effective
amounts of sustained-release bupropion for weight loss and
O’Malley disclosing its combination with naltrexone in a
single dosage form.
7 Claim 2 of the ’111 patent depends from claim 1,
and thus requires an amount of naltrexone effective to en-
hance the weight loss effect of bupropion. That claim is
drawn to about 5 mg to about 50 mg of naltrexone. Thus,
about 5 mg to 50 mg of naltrexone constitutes an amount
effective to enhance the effect of bupropion. See 35 U.S.C.
§ 112 ¶ 4 (2010).
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 21
FL, INC.
Having concluded that every limitation in the claims at
issue was met by O’Malley and Jain, we consider objective
indicia of nonobviousness. Nalpropion argues that many
others tried and failed to find a combination effective for
weight loss and that the claimed combination exhibited un-
expected results. But the inventors only combined two
drugs known to affect weight loss. Both drugs were known
to affect weight loss, and combining them for this known
purpose as claimed in the patents yields no unpredictable
result. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416
(2007) (“The combination of familiar elements according to
known methods is likely to be obvious when it does no more
than yield predictable results.”). The result—a combina-
tion drug that affected weight loss—could not have been
unexpected. To the extent Nalpropion maintains that the
failure of others supports a finding of nonobviousness, that
factor alone cannot overcome the clear record in this case
that the combination of the two drugs was known and that
both drugs would have been understood to be useful for this
purpose.
Because we conclude that claim 1 of the ’111 patent and
claims 26 and 31 of the ’626 patent would have been obvi-
ous to a person of skill in the art in view of O’Malley and
Jain, we reverse the district court’s holding that these
claims are not invalid.
Finally, Nalpropion filed a motion to strike Actavis’s
reply brief. Plaintiff-Appellee Nalpropion Pharms. Inc.’s
Motion to Strike, Nalpropion Pharm. Inc. v. Actavis Labs.
FL, Inc., No. 18-1221 (Fed. Cir. Dec. 27, 2018), ECF No. 54.
We deny this motion as moot.
CONCLUSION
We have considered both parties’ remaining arguments
and find them unpersuasive. For the reasons detailed
above, we hold that the district court did not clearly err in
finding claim 11 of the ’195 patent not invalid for lack of
adequate written description and affirm its judgment in
22 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
this respect. We reverse, however, the court’s judgment
that claims 26 and 31 of the ’626 patent and claim 1 of the
’111 patent are not invalid.
AFFIRMED-IN-PART AND REVERSED-IN-PART
COSTS
No costs.
United States Court of Appeals
for the Federal Circuit
______________________
NALPROPION PHARMACEUTICALS, INC.,
Plaintiff-Appellee
v.
ACTAVIS LABORATORIES FL, INC.,
Defendant-Appellant
______________________
2018-1221
______________________
Appeal from the United States District Court for the
District of Delaware in No. 1:15-cv-00451-RGA, Judge
Richard G. Andrews.
______________________
PROST, Chief Judge, dissenting in part.
Today, the majority adds what appears to me to be a
new rule to this court’s long-standing written description
jurisprudence. It holds that a “substantially equivalent”
disclosure may satisfy the written description requirement
when the relevant claim limitation recites only “resultant
dissolution parameters rather than operative claim steps.”
Majority Op. 12. Respectfully, that is not the law. Prem-
ised on my understanding of this court’s precedent, I would
find claim 11 of the ’195 patent invalid for lack of adequate
written description. Consequently, I must dissent from
Section I of the majority’s opinion.
2 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
The disputed limitation is the wherein clause directed
to the dissolution profile for sustained-release naltrexone,
as measured by the USP Apparatus 2 Paddle Method
(“USP 2”):
wherein said sustained-release formulation of nal-
trexone has an in vitro naltrexone dissolution pro-
file in a dissolution test of USP Apparatus 2 Paddle
Method at 100 rpm in a dissolution medium of wa-
ter at 37º C. of
a) between 39% and 70% of naltrexone re-leased
in one hour;
b) between 62% and 90% of naltrexone re-leased
in two hours; and
c) at least 99% in 8 hours . . . .
’195 patent col. 31 ll. 11–21 (hereinafter “the USP 2
clause”).
The majority and I agree that the essence of the
claimed invention is “a method of treating overweight or
obesity.” Majority Op. 10. We also agree that claim 11 in-
cludes one operative step, which relates to orally adminis-
tering, among other things, a specific amount of sustained-
release naltrexone formulation. Id.I part ways with the majority, however, for at least
three reasons. First, the USP 2 clause is limiting. Second,
the majority’s “substantially equivalent” rule is incon-
sistent with this court’s precedent. Third, the district court
clearly erred in finding that the ’195 patent’s written de-
scription includes a disclosure “substantially equivalent” to
USP 2.
As to the limiting effect of the USP 2 clause, the major-
ity determines that the clause is nonlimiting because it re-
lates only to the measurement of dissolution data resulting
from the oral administration step. See Majority Op. 10.
This conclusion is wrong. A clause is limiting if, as here,
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 3
FL, INC.
the clause “relate[s] back to and clarif[ies] what is required
by the count.” Griffin v. Bertina, 285 F.3d 1029, 1033 (Fed.
Cir. 2002). Indeed, the USP 2 clause does not “merely state
the inherent result of performing the manipulative steps.”
Id.; compare Bristol-Myers Squibb Co. v. Ben Venue Labs.,
Inc., 246 F.3d 1368, 1375 (Fed. Cir. 2001) (concluding a
statement directed to the intended result of administering
express dosage amounts to be nonlimiting where the result
“does not change those amounts or otherwise limit the
claim”). Rather, the USP 2 clause “is part of the process
itself.” Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329–30
(Fed. Cir. 2005).
Specifically, the USP 2 clause clarifies what the
claimed invention requires by reciting a property of the
claimed naltrexone formulation necessary to “treat[] over-
weight or obesity.” ’195 patent col. 31 ll. 5−6. Claim 11
requires the sustained-release naltrexone to be formulated
such that it obtains the recited dissolution profile as par-
ticularly measured by USP 2—not as generally measured
by any method. The ’195 patent disclosure confirms this
view.
According to the ’195 patent, oral dosage forms of sus-
tained-release naltrexone “comprise naltrexone and a sus-
tained-release carrier.” Id. col. 13 ll. 1–2. Sustained-
release carriers, such as hydroxypropylmethyl cellulose
(“HPMC”) or polyethylene oxide (“PolyOx”), are mixed with
naltrexone to effect sustained, as opposed to immediate, re-
lease. Id. col. 13 ll. 1–12, col. 16 ll. 8–26. The amount of
sustained-release carrier determines the in vitro release
rate (dissolution) profile of the naltrexone formulation. Id.col. 13 ll. 35–45. Thus, the dissolution profile, as measured
using USP 2, reflects the amount of sustained-release car-
rier included in the orally administered naltrexone formu-
lation.
The prosecution history also evidences the material
role of the USP 2 clause. In response to an obviousness
4 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
rejection during prosecution, Applicant argued that, hav-
ing used a different method, there was no basis to conclude
that the prior art inherently disclosed a formulation that
falls within the claimed dissolution profile. J.A. 7039
(Prosecution History, Applicant’s Remarks). Applicant
specifically emphasized the significance of the claimed dis-
solution profile as performed “under the specific dissolution
test conditions recited in the . . . claims.” Id.; see also
Hoffer, 405 F.3d at 1329–30 (stating that a clause cannot
be ignored if it is material to patentability).
Applicant did not stop there. Applicant further stated
that “there are sustained-release [naltrexone] formulations
which fall outside the scope of the . . . claimed dissolution
profiles.” J.A. 7039. There is no evidence to the contrary
in the record. Even during litigation, neither party identi-
fied any evidence that a 32 mg dose of any sustained-re-
lease naltrexone formulation necessarily contains an
amount of sustained-release carrier that inherently gener-
ates the claimed USP 2 dissolution profile measurement.
Moreover, and most tellingly, the parties do not even
dispute that the USP 2 clause is limiting. Indeed, Appellee
expressly agrees that the USP 2 clause is limiting for pur-
poses of infringement. Appellee’s sole written description
argument is that the ’195 patent’s disclosure of USP Appa-
ratus 1 Basket Method (“USP 1”) provides adequate writ-
ten description for the USP 2 clause. See Oral Arg. at
15:09–33, No. 2018-1221,
http://www.cafc.uscourts.gov/oral-argument-recordings
(“[F]or purposes of infringement you need to use [USP 2].
But if you look in terms of the 112 issues, . . . the patent is
clear that USP 1 and USP 2 are equivalent to one other.”).
By concluding that the USP 2 clause is nonlimiting, the
majority has sua sponte addressed a claim construction ar-
gument never presented to the district court.
To the extent that the majority determined that con-
struing the USP 2 clause was necessary to resolve the
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 5
FL, INC.
written description dispute, it should have adopted the dis-
trict court’s undisputed, implied construction, which
treated the clause as limiting. 1 Applied Med. Res. Corp. v.
U.S. Surgical Corp., 448 F.3d 1324, 1333 (Fed. Cir. 2006)
(explaining that this court has “decline[d] to construe [a
claim term] in the first instance and appl[ied] the undis-
puted claim construction adopted by the district court”).
As the USP 2 clause is limiting and the original patent
disclosure fails to literally or inherently disclose it, the
written description inquiry should end there. PowerOasis,
Inc. v. T-Mobile USA, Inc., 522 F.3d 1299, 1306 (Fed. Cir.
2008) (explaining that to satisfy the written description re-
quirement, “the written description [must] actually or in-
herently disclose the claim element”). But it does not.
After determining that the USP 2 clause is nonlimiting, the
majority adopts Appellee’s view that disclosure of USP 1
can provide adequate written description support for the
USP 2 clause because the two testing methods are “sub-
stantially equivalent.” Majority Op. 12; see also id. at 10–
11.
Such a conclusion problematically articulates a new
rule for written description. According to the majority,
written description for nonlimiting clauses may be satisfied
by disclosure that is “substantially equivalent” even
though the same disclosure would not be sufficient for
1 Although the district court did not explicitly artic-
ulate a construction of the USP 2 clause, a reading of its
opinion compels the conclusion that it construed the USP 2
clause to have limiting effect. E.g., Orexigen Therapeutics,
Inc. v. Actavis Labs. FL, Inc., 282 F. Supp. 3d 793, 801 (D.
Del. 2017) (“Claim 11 includes the limitation that the nal-
trexone have a specific dissolution profile measured ‘in a
dissolution test of [USP 2] . . . .’”).
6 NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES
FL, INC.
limiting clauses. This rule, however narrow, is at odds
with this court’s precedent.
Written description requires sufficient disclosure to
“clearly allow persons of ordinary skill in the art to recog-
nize that the inventor invented what is claimed.” Ariad
Pharm., Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010) (en banc) (brackets omitted). A substantially
equivalent disclosure, even if it would render the claim lim-
itation obvious, cannot satisfy the written description re-
quirement. See id. at 1352 (“[A] description that merely
renders the invention obvious does not satisfy the require-
ment.”); Lockwood v. Am. Airlines, Inc., 107 F.3d 1565,
1572 (Fed. Cir. 1997) (“The question is not whether a
claimed invention is an obvious variant of that which is dis-
closed in the specification.”).
In any event, even if the majority’s “substantially
equivalent” rule was appropriate, I would still disagree
with its affirmance on the written description issue. In
finding that USP 1 and USP 2 are substantially equiva-
lent, the majority overlooks the district court’s clear error.
Not a shred of record evidence supports this fact-finding.
And other record evidence refutes it.
The record contains no evidence showing that the two
methods produce the same results. Oral Arg. at 24:04–12
(Q: Do you have positive tests, confirmative testing saying
[USP 1 and USP 2] are the same thing? A: No. Neither
side submitted any testing data on that point.). Indeed,
Appellee’s expert, Dr. Treacy, testified that he had formed
no opinion about any differences between USP 1 and USP
2. See J.A. 11410:24–11411:2.
Instead, the record includes evidence that the two
methods do not produce the same results. First, Dr.
Soltero, one of the inventors named on the ’195 patent, tes-
tified that USP 1 and USP 2 results are not comparable.
He confirmed that “just because you got a certain profile
[using] a USP 1 method, you would not necessarily expect
NALPROPION PHARMACEUTICALS v. ACTAVIS LABORATORIES 7
FL, INC.
that you would get the same release profile [using] USP 2.”
See J.A. 11319:17–11321:12. The trial court’s opinion does
not even mention this testimony.
Second, Appellant’s expert, Dr. Mayersohn, opined that
a skilled artisan would not have understood the two meth-
ods to yield the same results. J.A. 11356:22–11357:3. The
district court discounted Dr. Mayersohn’s testimony, find-
ing that his “theoretical opinion that the methods would
yield different results is at odds with his reliance on a prior
art reference using [USP 1] to argue that claim 11, which
specifies [USP 2], was obvious.” See Majority Op. 11 (citing
Orexigen, 282 F. Supp. 3d at 801–02).
The standard for obviousness is not, however, the same
as the standard for written description. Based on our prec-
edent, teachings related to USP 1 may render methods us-
ing USP 2 obvious, but Dr. Mayersohn’s testimony that the
two would not produce the same results is nonetheless rel-
evant for written description. See Ariad, 598 F.3d at 1352;
Lockwood, 107 F.3d at 1572.
In a record devoid of evidence showing that USP 1 and
USP 2 are “substantially equivalent,” the district court
clearly erred in disregarding Dr. Soltero’s testimony and in
discounting Dr. Mayersohn’s, which indicate that they are
not substantially equivalent.
For the foregoing reasons, I respectfully dissent from
Section I.