Bayer Pharma Ag v. Watson Laboratories, Inc.

United States Court of Appeals
for the Federal Circuit
______________________
BAYER PHARMA AG, BAYER INTELLECTUAL
PROPERTY GMBH, BAYER HEALTHCARE
PHARMACEUTICALS, INC.,
Plaintiffs-Appellees
v.
WATSON LABORATORIES, INC., ACTAVIS
PHARMA, INC.,
Defendants-Appellants
______________________
2016-2169
______________________
Appeal from the United States District Court for the
District of Delaware in No. 1:12-cv-00517-GMS, Judge
Gregory M. Sleet.
______________________
Decided: November 1, 2017
______________________
DAVID I. BERL, Williams & Connolly LLP, Washing-
ton, DC, argued for plaintiffs-appellees. Also represented
by BRUCE GENDERSON, DOV PHILIP GROSSMAN, AARON P.
MAURER, ADAM LAWRENCE PERLMAN, THOMAS S.
FLETCHER, GALINA I. FOMENKOVA.
WILLIAM M. JAY, Goodwin Procter LLP, Washington,
DC, argued for defendants-appellants. Also represented
2 BAYER PHARMA AG v. WATSON LABS., INC.
by ELIZABETH HOLLAND, ROBERT V. CERWINSKI, BRIAN
ROBINSON, New York, NY; DAVID ZIMMER, Boston, MA.
______________________
Before LOURIE, MOORE, and O’MALLEY, Circuit Judges.
MOORE, Circuit Judge.
Watson Laboratories, Inc. appeals the District of
Delaware’s final judgment holding Watson failed to prove
by clear and convincing evidence that claims 9 and 11 of
U.S. Patent No. 8,613,950 (“the ’950 patent”) would have
been obvious. We hold the district court clearly erred in
finding a skilled artisan would not have been motivated to
use the claim elements. Considering the district court’s
clear error together with the remainder of its fact find-
ings, we conclude that claims 9 and 11 of the ’950 patent
would have been obvious. We therefore reverse.
BACKGROUND
In 2003, the Food & Drug Administration (“FDA”)
granted Bayer 1 approval to market vardenafil hydrochlo-
ride trihydrate to treat erectile dysfunction (“ED”) under
the name Levitra. Vardenafil belongs to a class of ED
drugs called phosphodiesterase inhibitors. When the FDA
approved Levitra, two other phosphodiesterase inhibitors
were already on the market: Pfizer launched sildenafil
under the name Viagra in 1998, and Eli Lilly launched
tadalafil under the name Cialis in 2003. Levitra, Viagra,
and Cialis are each formulated as immediate-release
tablets that are swallowed whole.
1 For purposes of this opinion, Bayer Pharma AG,
Bayer Intellectual Property GmbH, and Bayer Healthcare
Pharmaceuticals, Inc. are referred to as “Bayer” both
collectively and individually.
BAYER PHARMA AG v. WATSON LABS., INC. 3
The ’950 patent issued on December 24, 2013. It
claims priority to March 1, 2005 and lists Bayer as its
assignee. It is directed to a formulation of vardenafil “in
the form of an uncoated tablet which disintegrates rapidly
in the mouth,” commonly referred to as an oral disinte-
grating tablet (“ODT”). See ’950 patent at claim 8. Bayer
markets a commercial embodiment of the ’950 patent,
vardenafil ODT, under the name Staxyn.
Watson filed an Abbreviated New Drug Application
(“ANDA”) with the FDA seeking approval to market a
generic version of Staxyn. Bayer filed the instant case
asserting infringement of the ’950 patent. Claims 9 and
11, both of which depend from claim 8, are the only claims
at issue:
8. A drug formulation in the form of an uncoated
tablet which disintegrates rapidly in the mouth
and releases the drug in the mouth without swal-
lowing the tablet comprising vardenafil hydro-
chloride trihydrate, and at least two sugar
alcohols.
9. The drug formulation according to claim 8,
wherein said sugar alcohols are a mixture of sor-
bitol and mannitol.
11. The drug formulation of claim 8, wherein at
least one sugar alcohol is sorbitol.
The parties agree that claim 8’s requirement that the
formulation “releases the drug in the mouth” means it is
an immediate-release formulation.
The district court held a six-day bench trial to consid-
er the validity of the ’950 patent. Watson argued the
claimed formulation of vardenafil would have been obvi-
ous to a person of ordinary skill in the art based on multi-
ple exemplary references showing a motivation to:
4 BAYER PHARMA AG v. WATSON LABS., INC.
(1) create an ODT formulation of vardenafil 2; (2) select
mannitol and sorbitol as sugar alcohols3; and (3) make the
2 The prior art relied on by Watson at trial and dis-
cussed herein are, for the vardenafil ODT limitation:
(1) Chang et al., “Fast Dissolving Tablets,” Pharmaceuti-
cal Technology, Vol. 24 No. 6 (“Chang”); (2) U.S. Patent
Application Pub. No. 2002/0091129 (“Boolell”); (3) U.S.
Patent No. 6,683,080 (“Fryburg”); (4) “Pfizer/Scherer deal
on fast-acting Viagra,” SCRIP World Pharmaceutical
News, No. 2332/22 (May 6th/8th 1998) (“SCRIP”);
(5) Habib et al., “Fast Dissolving Drug Delivery Systems,”
17 Critical Reviews in Therapeutic Drug Carrier Systems
61 (2000) (“Habib”); (6) Ghosh et al., “Intraoral Delivery
Systems: An Overview, Current Status, and Future
Trends” in Drug Deliver to the Oral Cavity: Molecules to
Market (Ghosh et al., eds., 2005) (“Ghosh”); (7) U.S.
Patent Application Pub. No. 2002/0002172 (“Bell-Huff”);
(8) European Patent Application Pub. No. EP1120120
(“Furitsu”); and (9) PCT Application Pub. No. WO
02/05820 (“Chen”).
3 The prior art relied on by Watson at trial and dis-
cussed herein are, for the sorbitol and mannitol limita-
tion: (1) Fu et al., “Orally Fast Disintegrating Tablets:
Developments, Technologies, Taste-Masking and Clinical
Studies,” 21 Critical Reviews in Therapeutic Drug Carrier
Systems 443 (2004) (“Fu”); (2) Bauer et al., “Particle
design by surface modifications: spray-dying and co-
granulation of mannitol/sorbitol mixtures,” 11 S.T.P.
Pharma Sciences 203 (2001) (“Bauer”); (3) Joshi et al,
“Added Functionality Excipients: An Answer to Challeng-
ing Formulations,” Pharmaceutical Technology, June
2004 (“Joshi”); (4) U.S. Patent No. 6,544,552 (“Sparks”);
(5) U.S. Patent Application Pub. No. 2003/0119642
(“Norman”); (6) SPI Pharma, “Quick-Dissolving Tablets
Made Easy with Pharmaburst™,” Special Delivery
(Spring 2002) (“Pharmaburst”); (7) Ghosh.
BAYER PHARMA AG v. WATSON LABS., INC. 5
ODT formulation immediate-release. The district court
rejected each of Watson’s arguments. It found a person of
ordinary skill in the art would not have been motivated to
create an ODT formulation of vardenafil and would not
have used mannitol and sorbitol as excipients. It found
the prior art taught away from formulating vardenafil
ODT as immediate-release. The district court also ad-
dressed Bayer’s objective evidence of nonobviousness and
found it supported its conclusion that Watson failed to
prove by clear and convincing evidence that claims 9 and
11 would have been obvious. Watson appeals. We have
jurisdiction pursuant to 28 U.S.C. § 1295(a)(1).
DISCUSSION
A patent may not issue “if the differences between the
subject 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 person
having ordinary skill in the art to which said subject
matter pertains.” 35 U.S.C. § 103. Obviousness depends
on the following factual determinations: “(1) the scope and
content of the prior art; (2) the differences between the
prior art and the claims at issue; (3) the level of ordinary
skill in the art at the time the invention was made; and
(4) objective evidence of nonobviousness, if any.” In re
Kubin, 561 F.3d 1351, 1356 (Fed. Cir. 2009) (citing Gra-
ham v. John Deere Co., 383 U.S. 1, 17–18 (1966)). On
appeal from a bench trial, we review the district court’s
findings of fact for clear error. Pfizer, Inc. v. Apotex, Inc.,
480 F.3d 1348, 1359 (Fed. Cir. 2007). “A finding is ‘clearly
erroneous’ when[,] although there is evidence to support
it, the reviewing court on the entire evidence is left with
the definite and firm conviction that a mistake has been
committed.” United States v. U.S. Gypsum Co., 333 U.S.
364, 395 (1948). Based on the underlying factual find-
ings, whether a claimed invention would have been obvi-
ous is a question of law reviewed de novo. Pfizer, 480
F.3d at 1359.
6 BAYER PHARMA AG v. WATSON LABS., INC.
A. Vardenafil ODT Limitation
The district court determined that Watson failed to
meet its burden of proving by clear and convincing evi-
dence that there would have been a motivation to formu-
late vardenafil as an ODT formulation. This
determination rested largely on the court’s finding the
testimony of Bayer’s expert, Dr. Wicks, more persuasive
than the testimony of Watson’s expert, Dr. Jacobs. The
district court found it important that, according to Dr.
Wicks, no ED ODT drug was on the market as of the
’950 patent’s priority date. J.A. 9–10 (citing J.A. 676
at 855:15–19). It credited Dr. Wicks’ testimony that a
person of ordinary skill in the art would not have focused
on an ODT formulation of vardenafil “because of the
rarity of ODT formulations.” J.A. 9 (citing J.A. 671
at 833:21–834:2). It cited Dr. Wicks’ testimony in finding
that a person of ordinary skill in the art “would not have
considered vardenafil to be a good candidate for formula-
tion as an ODT because vardenafil was known as an [ED]
medication and ODTs were not considered particularly
applicable to this area.” J.A. 9 (citing J.A. 675–76
at 852:13–853:4, 853:25–854:4).
The district court cited the absence of any other ODT
formulations of ED drugs on the market as of the
’950 patent’s priority date. It cited the Fu reference,
which, like the SCRIP reference, showed Pfizer an-
nounced plans to launch an ODT version of Viagra
(sildenafil) in May 1998, but noted Pfizer still had not
brought the product to market by March 2005. J.A. 9
(citing J.A. 19103–04). Despite the fact that the 2005
Ghosh reference stated that Pfizer was continuing to
develop an ODT formulation of sildenafil, the court found
this not persuasive because it concluded that the refer-
ence’s claim was based on a publication from 1998. J.A. 9
(citing J.A. 19196–97, 19210). It cited the Habib refer-
ence, which did not list ED drugs in its table titled “Vari-
ous Therapeutic Areas in Which the Fast-Dissolve Dosage
BAYER PHARMA AG v. WATSON LABS., INC. 7
Forms are Most Applicable,” to support finding that ODTs
were not particularly applicable to ED drugs. J.A. 9
(citing J.A. 19265).
The clear error in the district court fact finding that
there was no motivation to formulate ED drugs in ODTs,
is that it concluded that the record did not contain an
indication that ED drugs would be good candidates for
ODT formulations. See, e.g., J.A. 9 (finding “vardenafil
was known as an [ED] medication and ODTs were not
considered particularly applicable to this area”). This is
simply not accurate. Watson relied on nine prior art
references to support its assertion that there would have
been a motivation to create an ODT formulation of var-
denafil. Dr. Jacobs testified that the Chang reference
states “drugs for [ED] would be good candidates for ODT
formulation.” J.A. 448 at 310:20–311:11. He testified the
Boolell and Fryburg references each disclose formulating
vardenafil as an ODT. J.A. 448–49 at 3:11:17–312:6. He
testified that numerous companies had already begun
formulating ODT versions of ED drugs: Pfizer filed the
Bell-Huff patent application directed to sildenafil ODT;
Eisai filed the Furitsu patent application claiming an
ODT formulation of phosphodiesterase inhibitors; and
Lavipharm filed the Chen international patent applica-
tion, identifying ODT versions of sildenafil. J.A. 449–50
at 314:3–319:1. Watson’s post-trial briefing identifies the
same set of references, all of which were produced as trial
exhibits and filed with the court.
These six references—Chang, Boolell, Fryburg, Bell-
Huff, Furitsu, and Chen—are absent from the district
court’s decision. While it is certainly not necessary for a
district court to evaluate all references presented to it,
nowhere here does it mention these key references in
analyzing whether the prior art taught vardenafil ODT or
whether a skilled artisan would have been motivated to
formulate vardenafil ODT. These references are highly
relevant to whether a person of ordinary skill in the art
8 BAYER PHARMA AG v. WATSON LABS., INC.
would have been motivated to formulate ODT vardenafil.
And their express disclosures cause the district court fact
finding regarding motivation to combine to be clear error.
See Pfizer, 480 F.3d at 1363 (holding the district court
clearly erred when it failed to consider relevant prior art).
The district court’s finding that “the [person of ordi-
nary skill in the art] would not have considered vardenafil
to be a good candidate for formulation as an ODT because
vardenafil was known as an erectile dysfunction medica-
tion and ODTs were not considered particularly applica-
ble to this area” is contradicted by the references cited by
Dr. Jacobs that the court failed to consider. J.A. 9; see
also id. (“[T]here was no reason for the [person of ordinary
skill in the art] to focus on an ODT vardenafil because of
the rarity of ODT formulations.”). All six of the prior art
references disregarded by the district court identify ED
drugs as ODT formulations. Chang identifies ED drugs
as one of five drug classes considered candidates for fast-
dissolving tablets. J.A. 19024. Boolell states ED drugs
such as sildenafil and vardenafil can be “administered
orally, buccally or sublingually in the form of tablets” and
“may also be administered as fast-dispersing or fast-
dissolving dosage forms.” J.A. 19689–90 ¶¶ 49–54, 63.
Fryburg provides the same disclosure, limited to varden-
afil. J.A. 19677 at 6:31–39. Bell-Huff, Furitsu, and Chen
show that between 1999 and 2001, more than one compa-
ny sought patent protection on ODT formulations of ED
drugs. Bell-Huff is directed to “rapidly disintegrating oral
dosage forms which contain sildenafil.” J.A. 19683 ¶ 2.
Furitsu is titled “Tablets Immediately Disintegrating in
the Oral Cavity” and is directed to phosphodiesterase
inhibitors, the class in which vardenafil, sildenafil, and
tadalafil belong. J.A. 19077. And Chen is directed to
sildenafil formulations, one example of which includes a
“fast dissolving tablet.” J.A. 19797. All of these refer-
ences indicate a person of ordinary skill in the art would
have considered ODT formulations applicable to ED
BAYER PHARMA AG v. WATSON LABS., INC. 9
drugs. And several of these references indicate a person
of ordinary skill in the art would have considered ODT
formulations to be applicable to vardenafil in particular.
Bayer argues that Watson’s arguments concerning
many of its references, such as Chang, Boolell, and Fry-
burg, were insignificant and the district court did not
clearly err by failing to address them. It argues that
while Watson asserts on appeal that the district court
ignored its key prior art, Watson flooded the district court
with references without adequately addressing them. We
do not agree.
Watson produced a significant number of references to
support its argument that a person of ordinary skill in the
art would have been motivated to formulate an ODT
formulation of vardenafil. While it may at times be
unwise for a party to rely on numerous prior art refer-
ences when challenging a patent on obviousness grounds,
Watson’s approach was not untenable here. Watson
produced these nine references to support a narrow point:
they each “disclosed formulating vardenafil and other
approved ED drugs into ODTs.” J.A. 935. Its expert,
Dr. Jacobs, addressed each of these nine references after
he was asked, “were there any references that discussed
formulating erectile dysfunction drugs in particular into
ODTs?” J.A. 448–50 at 310:20–319:1. Chang, Boolell,
and Fryburg were the first three references he discussed.
J.A. 448–49 at 310:20–313:13. Watson addressed the
same nine references in its post-trial briefing under the
heading, “The Prior Art Suggested Formulating Varden-
afil and Other Approved ED Drugs as ODTs.” J.A. 935.
While Watson’s discussion of the various references was
at times succinct, Dr. Jacobs’ testimony and Watson’s
arguments were tailored to the simple point that ODT
formulations of ED drugs were known. It is unnecessary,
for example, to delve deeply into the meaning of a patent
application directed to an “intraoral quickly disintegrat-
ing tablet containing a phosphodiesterase inhibitor” to
10 BAYER PHARMA AG v. WATSON LABS., INC.
explain that application discloses an ODT formulation of
an ED drug. J.A. 19077 (Furitsu); see J.A. 450 at 316:23–
318:10 (Dr. Jacobs’ testimony); J.A. 936–37 (Watson’s
post-trial briefing). Chang’s listing of “drugs for [ED]”
among five types of drugs that can be considered for ODTs
speaks for itself. J.A. 19024; see J.A. 448 at 310:24–
311:16 (Dr. Jacobs’ testimony); J.A. 937 (Watson’s post-
trial briefing). Watson clearly presented and preserved
its arguments relating to the prior art for the vardenafil
ODT limitation. In light of these references, the district
court clearly erred in determining that one of skill would
not have been motivated to make ODT formulations of ED
drugs.
Dr. Wicks’ testimony does not cast doubt on the
weight of Watson’s evidence regarding the vardenafil
ODT limitation. Many of the references Watson relies on
for this limitation were unchallenged by Dr. Wicks. For
example, Dr. Wicks did not present testimony on Chang’s
disclosure that ED drugs can be considered candidates for
ODTs. He did not question or critique any of the three
patent applications directed to ODT formulations of ED
drugs—Bell-Huff, Furitsu, and Chen. His only discussion
of Bell-Huff concerned the immediate-release limitation,
and he did not mention Furitsu or Chen at all. Rather,
Dr. Wicks’ testimony that a person of ordinary skill in the
art would not have considered ODTs applicable to ED
drugs, on which the district court relied, was expressly
limited to the Habib and Fu references. See J.A. 9;
J.A. 676 at 853:25–854:4 (Q: “Okay. So in light of the
information that we saw in Habib and Fu, if the person of
ordinary skill were to think about alternate formulations
of vardenafil, would they focus on ODTs?” A: “No.
There’s no indication that they’re applicable.”). In fact,
Dr. Wicks expressly conceded that the prior art described
ED drugs as candidates for ODT formulations. J.A. 690
at 911:23–912:2. This case does not present a situation in
which the district court’s credibility determination can be
BAYER PHARMA AG v. WATSON LABS., INC. 11
understood to discount the prior art references it failed to
address based on one expert’s characterization of the prior
art. See, e.g., Senju Pharm. Co. v. Lupin Ltd, 780 F.3d
1337, 1351 (Fed. Cir. 2015) (deferring to district court’s
credibility determination to credit competing testimony
regarding the prior art’s teaching).
It is well within the district court’s discretion to credit
one expert’s competing testimony over another. We “must
give due regard to the trial court’s opportunity to judge
the witnesses’ credibility.” Fed. R. Civ. P. 52(a)(6); see
FilmTec Corp. v. Hydranautics, 982 F.2d 1546, 1553 (Fed.
Cir. 1992) (“We will not invade the province of the district
court to judge matters of credibility.”). But a district
court cannot, through a credibility determination, ignore
the wealth of evidence, especially as in this case where
the expert did not even address it. The district court’s
finding that ODTs were not considered applicable to ED
drugs is clearly erroneous in light of Watson’s evidence.
See J.A. 9.
The remainder of the district court’s findings underly-
ing the motivation to formulate vardenafil ODT focused
too heavily on the commercial availability of ODT formu-
lations of ED drugs as of the ’950 patent’s priority date.
See, e.g., J.A. 9 (finding “it important that prior art refer-
ences from 2004 listing ODTs on the market and likely to
come to market in the next few years did not list any
drugs for the treatment of erectile dysfunction”); J.A. 10
(“[N]o ODT of an erectile dysfunction drug was on the
market by March 2005.”). It is unclear why the district
court found it important that no ODT ED drug had gained
FDA approval as of ’950 patent’s priority date. The
motivation to combine inquiry is not limited to what
products are forthcoming or currently available on the
market. Particularly given the lengthy FDA approval
process, the pharmaceutical industry is no exception. Any
motivation, “whether articulated in the references them-
selves or supported by evidence of the knowledge of a
12 BAYER PHARMA AG v. WATSON LABS., INC.
skilled artisan, is sufficient.” Outdry Techs. Corp. v. Geox
S.p.A., 859 F.3d 1364, 1370–71 (Fed Cir. 2017). Here, the
motivation to formulate an ODT version of vardenafil is
plainly evident from the face of multiple prior art refer-
ences disclosing ODT formulations of ED drugs. No
further rationale for developing vardenafil ODT was
necessary. On review of the entire record evidence before
the district court, we are left with the definite and firm
conviction that the district court clearly erred when it
found there would not have been a motivation to formu-
late vardenafil ODT.
B. Sorbitol and Mannitol Limitation
Claim 9 requires the vardenafil ODT formulation con-
tain a mixture of sorbitol and mannitol, and claim 11
more generally requires that the ODT formulation contain
at least two sugar alcohols, one of which must be sorbitol.
Neither party disputes that it was known—if not neces-
sary—to include a sugar alcohol in ODT formulations.
The parties’ dispute rests on whether a person of ordinary
skill in the art would have been motivated to select the
claimed combination of sugar alcohols, sorbitol and man-
nitol.
The district court found a person of ordinary skill in
the art would not have been motivated to use mannitol
and sorbitol in an ODT formulation, finding Dr. Wicks’
testimony on this limitation more credible than
Dr. Jacobs’. It found Dr. Jacobs’ reliance on the Bauer
reference unpersuasive because Bauer’s disclosure that
the combination of mannitol and sorbitol could optimize
tableting properties was based on a 1978 article. J.A. 12
(citing J.A. 467 at 385:19–386:12; J.A. 18593–94 (Bauer)).
It noted Dr. Jacobs relied on the Pharmaburst reference,
which advertised an off-the-shelf excipient containing a
combination of mannitol and sorbitol, but found it con-
tained no working examples or experimental data.
J.A. 12–13 (citing J.A. 454–55 at 335:23–336:1). It found
BAYER PHARMA AG v. WATSON LABS., INC. 13
Dr. Jacobs’ testimony that a skilled artisan would have
been motivated to use a mixture of sorbitol and mannitol
to avoid the need for specialized packaging unpersuasive
in light of his contrary testimony that “there is no need
for specialized packaging” when a particular manufactur-
ing process is employed. J.A. 13 (citing J.A. 453 at 328:3–
15 (discussing the Joshi reference); J.A. 446 at 301:16–
302:1). It found persuasive Dr. Wicks’ testimony that
“every ODT on the market in the relevant prior art time
frame contained only a single sugar alcohol: mannitol,”
and that “there were no known problems with the use of
mannitol in the existing ODTs.” J.A. 12 (citing J.A. 683
at 884:1–19; J.A. 685 at 891:11–17). It found “there was
nothing in the prior art that would have given the [person
of ordinary skill in the art] a reason to use sorbitol in
addition to mannitol in an ODT.” J.A. 12 (citing J.A. 686
at 894:12–15).
We do not question the district court’s credibility de-
terminations. However, the district court’s analysis for
the sorbitol and mannitol limitation again focused on the
commercial availability of products while failing to ad-
dress relevant prior art. Upon consideration of the entire
record and under a proper analysis, we conclude that the
district court clearly erred in finding a person of ordinary
skill in the art would not have been motivated to formu-
late an ODT with sorbitol and mannitol.
The parties do not dispute that as of the ’950 patent’s
priority date, a company named SPI Pharma marketed an
off-the-shelf ODT excipient product called Pharmaburst.
The parties agree Pharmaburst existed in three different
forms: two using only mannitol and a third, Pharmaburst
B2, containing mannitol and sorbitol. The ’950 patent
specification uses Pharmaburst B2 in an example. See
’950 patent at 6:31–34. Thus there can be no question
that it was known as of the ’950 patent’s priority date to
use sorbitol and mannitol in ODT formulations.
14 BAYER PHARMA AG v. WATSON LABS., INC.
Dr. Jacobs testified that the Norman reference, not
addressed by the district court, discloses examples of ODT
formulations using sorbitol and mannitol created by SPI
Pharma. See J.A. 19727–28 at Exs. 1, 3, and 4; J.A. 453–
54 at 331:21–332:23 (Dr. Jacobs’ testimony). The district
court mentioned Dr. Jacobs relied on the Sparks refer-
ence, J.A. 12, but did not explain why Sparks’ examples
using sorbitol and mannitol in ODT formulations were not
relevant to whether a skilled artisan would have used
sorbitol and mannitol in vardenafil ODT, or give any
reason why that reference would not inform the obvious-
ness analysis. See J.A. 19671 at Exs. 1, 2 (explaining
tablet disintegration times of 3 and 7 seconds); J.A. 453
at 330:18–331:23 (Dr. Jacobs’ testimony). Dr. Wicks
likewise provided no rebuttal testimony regarding these
references. Other than critiquing its lack of examples or
experimental data, J.A. 12–13, the district court’s decision
does not otherwise mention the Pharmaburst advertise-
ment, or its disclosure that it is “an ‘off the shelf’ excipient
which allows you to develop your own quick dissolve
formulations in-house quickly and much more cost effec-
tively.” J.A. 18554; see also J.A. 454–55 at 335:18–337:9
(Dr. Jacobs’ testimony). Its decision does not mention
Ghosh’s similar disclosure that Pharmaburst “is a highly
flexible, rapidly disintegrating excipient that imparts a
smooth creamy mouth feel, and is manufactured under
cGMPs.” J.A. 19173; J.A. 455 at 337:13–23 (Dr. Jacobs’
testimony).
The district court clearly erred when it found “there
was nothing in the prior art that would have given the
[person of ordinary skill in the art] a reason to use sorbi-
tol in addition to mannitol in an ODT.” J.A. 12. The
Joshi reference states using sorbitol with mannitol in
ODTs is advantageous because it “enable[s] strong bind-
ing and result[s] in a more robust tablet at low compres-
sion forces.” J.A. 19820–21; J.A. 938 (Watson’s post-trial
briefing). It explains that, “[i]n addition to contributing to
BAYER PHARMA AG v. WATSON LABS., INC. 15
the robustness of tablets, the sorbitol also imparts a sweet
taste and a unique texture to the mannitol, thereby
improving the ODT formulation’s mouthfeel” without
affecting pharmacopeial conformity standards. 4
J.A. 19821. Particularly in light of the district court’s
finding that a person of ordinary skill in the art “would
have expected a vardenafil ODT to have a bitter taste,”
J.A. 10, these disclosures are relevant to whether a skilled
artisan would have been motivated to use sorbitol and
mannitol in vardenafil ODT. The district court’s finding
that nothing in the prior art provided a reason to use
sorbitol in addition to mannitol in an ODT is clearly
erroneous in light of Watson’s evidence. See J.A. 12.
The district court’s remaining findings on the motiva-
tion to use sorbitol and mannitol in an ODT formulation 5
focused solely on the ODT market as of the ’950 patent’s
priority date. See J.A. 12 (“[E]very ODT on the market in
the relevant prior art time framed contained only a single
sugar alcohol: mannitol.”); id. (“[T]here were no known
problems with the use of mannitol in the existing ODTs.”).
Dr. Wicks likewise critiqued Pharmaburst because it was
not “in any approved product in the United States as of
March 2005.” J.A. 683 at 884:20–23; see also J.A. 684
at 885:2–15 (testifying that a person of ordinary skill in
4 While the district court found part of Dr. Jacobs’
testimony regarding Joshi—that it would have been
desirable to add sorbitol to mannitol to avoid the need for
specialized packaging—unpersuasive, it never addressed
Joshi’s express disclosures regarding the benefits of using
sorbitol with mannitol. See J.A. 13 (citing J.A. 453
at 328:3–15).
5 Because it is not necessary to our analysis, we do
not address the district court’s finding that the Bauer
reference was not relevant because it was based on a 1978
article. See J.A. 12.
16 BAYER PHARMA AG v. WATSON LABS., INC.
the art would look to currently-available ODT products to
know whether the FDA considered the excipients safe and
effective). Accepting fully Dr. Wicks’ testimony on this
point, the motivation to combine inquiry for drug formula-
tions is not limited to what already has or could gain FDA
approval. We have previously explained:
There 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. 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 ap-
plications.
Allergan, Inc. v. Sandoz Inc., 726 F.3d 1286, 1292 (Fed.
Cir. 2013). While FDA approval may be relevant to the
obviousness inquiry, see id. at 1291–92, a lack of FDA
approval cannot negate an otherwise apparent motivation
to formulate a product. The district court clearly erred in
finding no motivation to use sorbitol and mannitol in
ODTs; Watson’s evidence expressly demonstrated that
sorbitol and mannitol in ODTs was known in the art and
that there were advantageous reasons to use them.
C. Immediate-Release Limitation
The district court found that even if a skilled artisan
would have been motivated to make an ODT formulation
of vardenafil, the prior art taught away from formulating
vardenafil ODT as immediate release. J.A. 10–11. The
parties agree that only two types of ODT formulations
were known in the art: immediate-release ODTs, which
are released in the mouth, and delayed-release ODTs,
which are released in the stomach. The district court
found, based again on expert testimony, that a person of
ordinary skill in the art would have expected vardenafil
ODT to have a bitter taste, which would have discouraged
him from creating a formulation that releases vardenafil
BAYER PHARMA AG v. WATSON LABS., INC. 17
in the mouth. J.A. 10. It also found a person of ordinary
skill in the art would have been concerned with using an
immediate-release formulation because it would be ex-
pected to increase bioavailability, and Levitra’s label
suggested an increase in vardenafil blood levels would be
a problem for older men. J.A. 11. The district court found
these two concerns would have taught away from an
immediate-release formulation. Id.
We do not disturb the district court’s findings relating
to vardenafil’s expected bitter taste and increased bioa-
vailability, but the district court erred when it elevated
those findings to teaching away. “A reference teaches
away when it suggests that the line of development
flowing from the reference’s disclosure is unlikely to be
productive of the result sought by the applicant.” Santa-
rus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed.
Cir. 2012) (quoting Medichem, S.A. v. Rolabo, S.L., 437
F.3d 1157, 1165 (Fed. Cir. 2006) (alterations omitted)).
The district court did not find that a person of ordinary
skill in the art would have believed vardenafil’s expected
bitter taste and increased bioavailability would have
likely rendered an immediate-release formulation unpro-
ductive. Instead, the district court’s analysis focused on
whether a person of ordinary skill in the art would “nec-
essarily have made an immediate-release ODT rather
than a delayed-release ODT.” J.A. 10; see J.A. 11 (finding
teaching away based on these “two fundamental concerns
when considering an immediate-release formulation over
a delayed release ODT formulation”). But the teaching
away inquiry does not focus on whether a person of ordi-
nary skill in the art would have merely favored one dis-
closed option over another disclosed option. In assessing
whether prior art teaches away, that “better alternatives
exist in the prior art does not mean that an inferior
combination is inapt for obviousness purposes.” In re
Mouttet, 686 F.3d 1322, 1334 (Fed. Cir. 2012). When
there are only two possible formulations and both are
18 BAYER PHARMA AG v. WATSON LABS., INC.
known in the art at the time, the fact that there may be
reasons a skilled artisan would prefer one over the other
does not amount to a teaching away from the lesser
preferred but still workable option. The district court’s
finding that a person of ordinary skill in the art would
have first pursued a delayed-release formulation over an
immediate-release formulation is insufficient to support a
finding of teaching away.
The evidence before the district court supports its
finding that a person of ordinary skill in the art may have
preferred a delayed-release formulation over immediate
release—not that an immediate-release formulation was
unlikely to be productive in vardenafil ODT. Rather than
testify that a skilled artisan would have believed the taste
of vardenafil is too bitter to formulate as an immediate-
release ODT, Dr. Wicks merely testified that “the consid-
eration would lead them to a delayed-release ODT.”
J.A. 678 at 863:22–864:7 (answering “would the person of
ordinary skill have a reason to make a formulation of
vardenafil, an ODT formulation, that releases the drug in
the mouth, the immediate-release type?”). Nor did
Dr. Wicks point to prior art suggesting vardenafil would
have tasted too bitter. Dr. Wicks conceded “[t]he taste of
vardenafil was not reported in the literature” and dis-
claimed that a person of ordinary skill in the art “would
have assumed that vardenafil was as bitter as sildenafil.”
J.A. 694 at 925:16–926:4. When asked about bioavailabil-
ity concerns due to Levitra’s label, Dr. Wicks again fo-
cused on why those concerns would have caused a skilled
artisan to prefer a delayed-release formulation. See
J.A. 681 at 874:17–23 (testifying “the making of a de-
layed-release ODT would be far simpler”). Dr. Wicks
opined that the bioavailability concerns “would clearly
teach away from making an immediate-release formula-
tion,” but when asked why, he answered “[b]ecause you
would get much greater control with a delayed-release
formulation.” J.A. 681 at 873:8–25. This testimony
BAYER PHARMA AG v. WATSON LABS., INC. 19
supports the district court’s finding that the taste and
bioavailability of vardenafil raised concerns, and that a
skilled artisan may have preferred a delayed-release
formulation, but it does not support a finding of teaching
away. See KSR Int’l Co. v. Teleflex Inc., 550 U.S.
398, 425–26 (2007) (holding expert’s declaration did not
support finding teaching away because it did not indicate
the prior art system “was somehow so flawed that there
was no reason to upgrade it”).
While the district court did not clearly err in its fact
finding that a skilled artisan would have had concerns
over an immediate-release formulation due to vardenafil’s
expected bitter taste and bioavailability, obviousness
“does not require that the motivation be the best option,
only that it be a suitable option from which the prior art
did not teach away.” 6 Par Pharm., Inc. v. TWI Pharm.,
Inc., 773 F.3d 1186, 1197–98 (Fed. Cir. 2014). We deter-
mine whether a skilled artisan would have found the
claimed combination obvious weighing the four Graham
factors, which includes the district court’s fact findings
regarding the bitter taste and bioavailability of immediate
release formulations. See Apple Inc. v. Samsung Elecs.
Co., 839 F.3d 1034, 1048 (Fed. Cir. 2016) (en banc).
6 We also note the district court did not address
record evidence that may have alleviated concerns with
an immediate-release formulation, including that
Pharmaburst “is a highly flexible, rapidly disintegrating
excipient that imparts a smooth creamy mouth feel, and is
manufactured under cGMPs.” J.A. 19173. It did not
address evidence that using sorbitol with mannitol in
ODTs benefited tableting properties, taste, and mouth-
feel. J.A. 19820–21 (adding sorbitol to ODTs “imparts a
sweet taste and a unique texture to the mannitol, thereby
improving the ODT formulation’s mouthfeel”).
20 BAYER PHARMA AG v. WATSON LABS., INC.
D. Objective Evidence
The district court found Watson’s copying of the
claimed invention and Staxyn’s unexpected increased
duration of action compared to Levitra supported its
conclusion of nonobviousness. J.A. 16–19. We do not
disturb these findings. Copying is one of the objective
indicia we have held is probative of nonobviousness.
Apple, 839 F.3d at 1052. Both Bayer’s evidence of copying
and unexpected results weigh in favor of the nonobvious-
ness of the claimed combination.
E. Legal Conclusion of Obviousness
We consider whether the claimed invention would
have been obvious de novo based on underlying findings of
fact. Pfizer, 480 F.3d at 1359. Watson demonstrated by
clear and convincing evidence that there would have been
a motivation to formulate an ODT version of vardenafil.
In fact, the prior art was explicit in the suggestion to
make such a combination and the district court clearly
erred in its fact finding to the contrary. The prior art of
record expresses a clear motivation to formulate ODT
versions of ED drugs and that multiple companies were
formulating ODT versions of ED drugs. See J.A. 19024,
19077, 19683 ¶ 2, 19797. Watson also demonstrated by
clear and convincing evidence that there was an express
motivation in the prior art to use sorbitol and mannitol as
the excipients in the ODT formulation of the ED drug and
the district court clearly erred in its fact finding to the
contrary. Pharmaburst B2 was a known, off-the-shelf
ODT excipient product that permitted formulation of ODT
products “in-house quickly and much more cost effective-
ly.” J.A. 18554. The district court did not clearly err in
its fact finding that a person of ordinary skill in the art
would have had concerns using an immediate-release
formulation due to vardenafil’s expected bitter taste and
bioavailability; however, it clearly erred when it conclud-
ed that those findings taught away from the immediate
BAYER PHARMA AG v. WATSON LABS., INC. 21
release. Bayer presented evidence of copying and unex-
pected results that weigh in favor of a conclusion of non-
obviousness.
Weighing all four Graham factors, we conclude
claims 9 and 11 of the ’950 patent would have been obvi-
ous. The repeated suggestion in the prior art to make an
ODT formulation of an ED drug and the suggestion to use
the combination of sorbitol and mannitol as excipients are
strong evidence of a motivation to make the claimed
combination. The parties agree that ODTs were known to
exist as either immediate-release or delayed-release
formulations. A skilled artisan motivated to formulate
vardenafil ODT would have been faced with a design need
for its release profile, and an immediate-release formula-
tion would have been one of two options. See KSR, 550
U.S. at 402 (“When there is a design need or market
pressure to solve a problem and there are a finite number
of identified, predictable solutions, a person of ordinary
skill in the art has good reason to pursue the known
options within his or her technical grasp.”). While a
skilled artisan may have preferred a delayed-release
formulation over the claimed immediate-release formula-
tion, “that the prior art as a whole suggests the desirabil-
ity of a particular combination need not be supported by a
finding that the prior art suggests that the combination
claimed . . . is the preferred, or most desirable, combina-
tion.” In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004).
Weighing this evidence together with the objective evi-
dence of unexpected results and copying, we conclude that
a skilled artisan would have found the claimed combina-
tion obvious. The district court’s final judgment is re-
versed.
CONCLUSION
For the reasons discussed above, we reverse the dis-
trict court’s holding that Watson failed to prove by clear
and convincing evidence that claims 9 and 11 of the
22 BAYER PHARMA AG v. WATSON LABS., INC.
’950 patent would have been obvious.
REVERSED
COSTS
Costs to Watson.