Warner Chilcott Company, LLC v. Teva Pharmaceuticals USA, Inc. ( 2016 )

NOTE: This disposition is nonprecedential.
United States Court of Appeals
for the Federal Circuit
______________________
WARNER CHILCOTT COMPANY, LLC, WARNER
CHILCOTT (US), LLC,
Plaintiffs-Appellants
v.
TEVA PHARMACEUTICALS USA, INC.,
Defendant-Appellee
RANBAXY, INC., RANBAXY LABORATORIES
LIMITED, WATSON LABORATORIES, INC. -
FLORIDA,
Defendants
______________________
2015-1588
______________________
Appeal from the United States District Court for the
District of New Jersey in No. 2:11-cv-06936-SRC-CLW,
Judge Stanley R. Chesler.
______________________
Decided: March 18, 2016
______________________
JEFFREY B. ELIKAN, Covington & Burling LLP, Wash-
ington, DC, argued for plaintiffs-appellants. Also repre-
sented by GEORGE FRANK PAPPAS, KEVIN B. COLLINS,
BRADLEY KEITH ERVIN.
2 WARNER CHILCOTT CO. v. TEVA PHARMACEUTICALS USA, INC.
ELIZABETH HOLLAND, Goodwin Procter LLP, New
York, NY, argued for defendant-appellee. Also represent-
ed by ROBERT V. CERWINSKI, LINNEA P. CIPRIANO;
CHRISTOPHER T. HOLDING, Boston, MA; WILLIAM M. JAY,
Washington, DC; DAVID ZIMMER, San Francisco, CA.
______________________
Before LOURIE, DYK, and HUGHES, Circuit Judges.
LOURIE, Circuit Judge.
Warner Chilcott Company, LLC and Warner Chilcott
(US), LLC (collectively, “Warner Chilcott”) appeal from
the decision of the United States District Court for the
District of New Jersey holding claim 16 of U.S. Patent
7,645,459 (“the ’459 patent”) and claim 20 of U.S. Patent
7,645,460 (“the ’460 patent”) invalid as obvious. Warner
Chilcott Co., LLC v. Teva Pharm. USA, Inc., 89 F. Supp.
3d 641 (D.N.J. 2015) (“Opinion”). Because the district
court did not err in concluding that the asserted claims
are invalid, we affirm.
BACKGROUND
Warner Chilcott owns the ’459 and ’460 patents,
which are directed to oral dosage forms comprising
risedronate (a bisphosphonate) and disodium ethylene-
diaminetetraacetic acid (herein referred to as “EDTA”),
and methods of treating diseases characterized by abnor-
mal calcium and phosphate metabolism, e.g., osteoporosis.
Because risedronate complexes with calcium ions in food,
its absorption is significantly diminished when adminis-
tered in a fed state, viz., taken with or soon after a meal.
A chelating agent, such as EDTA, can preferentially bind
calcium ions, thus blocking calcium–risedronate complex
formation in a fed state and thereby freeing up
risedronate for absorption. However, the chelating agent
may also bind the calcium ions from the intestinal wall in
a fasted state, and thereby increase absorption in a more
WARNER CHILCOTT CO. v. TEVA PHARMACEUTICALS USA, INC. 3
undesirable fashion by widening the tight junctions
between cells. During prosecution of the patents, the
examiner originally rejected the claims as obvious over
prior art disclosing the use of EDTA for increasing
bisphosphonate absorption. The patentee overcame that
rejection by adding the limitation “pharmaceutically
effective absorption,” which is defined by the specifica-
tion 1 as:
an amount of a chelating compound high
enough to significantly bind the metal ions
and minerals in food but low enough not to
significantly alter absorption of the
bisphosphonate as compared to absorption
in the fasted state. That is, absorption is
similar with or without food. Given the
high variability of bisphosphonate absorp-
tion, fed exposure within about 50% of
fasting exposure is expected to be “phar-
maceutically effective absorption.”
’459 patent, col. 4 ll. 59–66.
Warner Chilcott’s commercial embodiment of the ’459
and ’460 patents is Atelvia®, an oral formulation for
treating osteoporosis, comprising 35 mg risedronate and
100 mg EDTA. Teva Pharmaceuticals USA, Inc. (“Teva”)
filed an Abbreviated New Drug Application (“ANDA”)
with the U.S. Food and Drug Administration, seeking
approval for a generic version of Atelvia®. Warner Chil-
cott filed suit, asserting infringement of the ’459 and ’460
patents by the filing of Teva’s ANDA. The only claims at
issue during trial were claim 16 of the ’459 patent and
claim 20 of the ’460 patent, both of which Teva had stipu-
lated to infringing.
1 The ’459 and ’460 patent specifications are sub-
stantially similar, and therefore are referred to jointly.
4 WARNER CHILCOTT CO. v. TEVA PHARMACEUTICALS USA, INC.
The asserted dependent claims, with the text of the
parent claims incorporated, read as follows:
16. An oral dosage form having pharmaceutically
effective absorption comprising:
(a) [about 35 mg] of risedronate sodium;
(b) [about 100 mg] of disodium EDTA; and
(c) an enteric coating [that is a methacryl-
ic acid copolymer] which provides for re-
lease of the risedronate sodium and the
disodium EDTA in the lower gastrointes-
tinal tract of a mammal.
’459 patent, col. 38 l. 49 – col. 39 l. 13.
20. An oral dosage form having pharmaceutically
effective absorption comprising:
(a) [about 35 mg of ] risedronate sodium;
(b) [about 100 mg] of disodium EDTA; and
(c) an enteric coating [that is a methacryl-
ic acid copolymer] which provides for im-
mediate release of the risedronate sodium
and the disodium EDTA in the small in-
testine of a mammal.
’460 patent, col. 24 l. 47 – col. 25 l. 20.
The district court held a bench trial and concluded
that the asserted claims were invalid as obvious. The
court noted that the parties agreed that Brazilian Patent
Application BR2001-06601 (“BR ’601”) contains all of the
limitations of the claims except “pharmaceutically effec-
tive absorption.” Opinion, 89 F. Supp. 3d at 646.
First, the district court found that the claimed 35 mg
risedronate dose was disclosed as the most commonly
prescribed regimen (a 35 mg dose), and by BR ’601’s
teaching of an “effective quantity” of bisphosphonate. Id.
WARNER CHILCOTT CO. v. TEVA PHARMACEUTICALS USA, INC. 5
at 653–54. The court next found that BR ’601 discloses
20–175 mg EDTA, which includes the claimed 100 mg
amount. Id. at 654–56. Because the compounds “work
independently of each other and are not interdependent,”
as confirmed by the specification’s broad disclosure of
greatly varying ratios of bisphosphonate to EDTA that all
supposedly exhibit pharmaceutically effective absorption,
the court found that the claimed 100 mg amount of EDTA
was not critical within the range disclosed in the prior art.
Id. at 655–56. The court therefore found that BR ’601
discloses the claimed ingredients and amounts “in the
same combination, for substantially the same function.”
Id. at 657.
The district court then analyzed whether BR ’601 dis-
closes the “pharmaceutically effective absorption” limita-
tion. The court found that BR ’601 teaches using an
amount of EDTA sufficient to bind ions in food, albeit an
amount inherently low enough not to significantly alter
absorption. Id. at 657–58. The court credited expert
testimony that substantially more than 175 mg of EDTA
would be required to increase intestinal permeability even
in the fasted state. Id. at 658. The court, however, found
insufficient evidence to show that any embodiment of BR
’601 would necessarily produce similar fed/fasted absorp-
tion, and thus found that the reference did not inherently
disclose pharmaceutically effective absorption. Id. at
658–59. Accordingly, the court found that BR ’601 did not
anticipate the asserted claims. Id. at 659.
Instead, the district court concluded that BR ’601 ren-
ders the claims obvious. The court found that one of skill
would have recognized the food-effect problem with
bisphosphonates and the solution of using chelators to
block calcium ions. Id. at 661. The court characterized
that solution as having been “well explored in the litera-
ture,” and reviewed the references teaching that EDTA
increases absorption by reducing calcium–bisphosphonate
complex formation, as well as references explicitly noting
6 WARNER CHILCOTT CO. v. TEVA PHARMACEUTICALS USA, INC.
that EDTA may also do so by damaging the tight junc-
tions and thereby enhancing permeability. Id. at 661–68.
The court also found that other references teach using a
chelator to solve the food effect and suggest using EDTA
for less variable absorption. Id. at 661–62. The court
noted that another reference disclosed eliminating the
food effect for a different drug that also has reduced
absorption due to calcium-complexes, by using an amount
of EDTA equimolar to the calcium ions expected in the
stomach. Id. at 662. The court further found that the
reference teaches that 250 of mg EDTA does not change
absorption in a fasted state and thus provides similar
bioavailability irrespective of diet. Id.
The district court additionally rejected Warner Chil-
cott’s arguments of teaching away by the prior art, in-
stead finding that the art was either irrelevant or the
earlier concerns were addressed by later references like
BR ’601. Id. at 662–68. Instead, the court determined
that one of skill in the art would have been motivated to
modify or combine BR ’601 with other prior art references
to achieve the claimed invention, based on the teachings
found within the references, with a reasonable expecta-
tion of success in achieving similar absorption in
fed/fasted states. Id. at 675–80.
The district court also considered Warner Chilcott’s
evidence of objective considerations, but concluded that
that evidence did not show nonobviousness. The court
found some long-felt need for improving patient compli-
ance, although there existed alternatives such as weekly
dosing, but relatedly, no proof of improved compliance as
an unexpected result of the claimed invention, id. at 668;
simultaneous invention by a third party, Takeda, id. at
670–71; insufficient evidence of skepticism by skilled
artisans, id. at 671–72; and no nexus between the claimed
invention and Teva’s alleged failures or copying, id. at
672. The court therefore concluded that the asserted
claims would have been obvious in view of the prior art.
WARNER CHILCOTT CO. v. TEVA PHARMACEUTICALS USA, INC. 7
Warner Chilcott timely appealed to this court. We
have jurisdiction pursuant to 28 U.S.C. § 1295(a)(1).
DISCUSSION
Patents are presumed to be valid, and overcoming
that presumption requires clear and convincing evidence.
35 U.S.C. § 282; Microsoft Corp. v. i4i Ltd. P’ship, 564
U.S. 91, 131 S. Ct. 2238, 2242 (2011). A patent claim is
invalid as obvious if an alleged infringer proves that the
differences between the claims 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.” 35 U.S.C. § 103(a)
(2006). 2
Obviousness is ultimately a conclusion of law prem-
ised on underlying findings of fact, including the scope
and content of the prior art, the differences between the
claimed invention and the prior art, and the evidence of
secondary factors, such as long-felt need, industry skepti-
cism, and copying. KSR Int’l Co. v. Teleflex Inc., 550 U.S.
398, 427 (2007); Graham v. John Deere Co., 383 U.S. 1,
17–18 (1966). “The presence or absence of a motivation to
combine references in an obviousness determination is
[also] a pure question of fact.” Alza Corp. v. Mylan Labs.,
464 F.3d 1286, 1289 (Fed. Cir. 2006). In addition to
common knowledge or teachings in the prior art itself, a
“design need or market pressure or other motivation” may
provide a suggestion or motivation to combine prior art
elements in the manner claimed. Rolls Royce, PLC v.
United Techs. Corp., 603 F.3d 1325, 1339 (Fed. Cir. 2010);
2 Because the ’459 and ’460 patents were filed
before the effective date of the America Invents Act, the
earlier, pre-Act version of § 103(a) applies to this appeal.
See Leahy–Smith America Invents Act, Pub. L. No. 112-
29, 125 Stat. 284, 293 (2011).
8 WARNER CHILCOTT CO. v. TEVA PHARMACEUTICALS USA, INC.
accord KSR, 550 U.S. at 420. Moreover, when there are
“a finite number of identified, predictable solutions,” one
of skill in the art “has good reason to pursue the known
options within his or her technical grasp.” KSR, 550 U.S.
at 421.
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. Golden Blount, Inc. v. Robert H. Peterson
Co., 365 F.3d 1054, 1058 (Fed. Cir. 2004). A factual
finding is only clearly erroneous if, despite some support-
ing evidence, we are left with the definite and firm convic-
tion that a mistake has been made. United States v. U.S.
Gypsum Co., 333 U.S. 364, 395 (1948).
Warner Chilcott argues that the district court misin-
terpreted “pharmaceutically effective absorption” and
erroneously equated the invention with overcoming the
food effect. Instead, Warner Chilcott insists, the limita-
tion requires similar fed and fasted absorption of the
drug, not merely absorption of an effective amount in
either fed or fasted state. Warner Chilcott further con-
tends that the specific amounts of risedronate and EDTA
are critical, as only the claimed formulation has been
shown to achieve such absorption. Based on the prior
art’s warnings against the clinical use of EDTA, Warner
Chilcott contends, one of skill in the art would have been
dissuaded from using as high as 100 mg of EDTA to
increase drug absorption, particularly if that increase was
understood to be effectuated at least in part by altering
the permeability of the intestinal wall. As a result,
Warner Chilcott disputes the district court’s finding of a
motivation to modify the prior art to achieve the claimed
invention. Warner Chilcott lastly faults the district court
for discounting the objective evidence of nonobviousness,
including evidence of Teva’s copying of the claimed formu-
lation, particularly because Teva’s expert failed to account
for such evidence in his analysis.
WARNER CHILCOTT CO. v. TEVA PHARMACEUTICALS USA, INC. 9
Teva responds that the prior art teaches the use of
EDTA not only to overcome the food effect but also to
achieve similar fed/fasted absorption. Teva points out
that the specification teaches that broad ranges of EDTA
produce the claimed pharmaceutically effective absorp-
tion, and contends that 100 mg is not a critical amount
because the compounds work independently and therefore
changes to the proportions would not affect drug absorp-
tion. Moreover, Teva emphasizes, the claims do not
require identical fasted/fed absorption, only similar
results with up to ±50% variation. Teva further counters
that the prior art teaches increasing bisphosphonate
absorption by blocking calcium-complex formation, with
an equimolar amount of EDTA to calcium ions at the site
of drug release, to achieve a constant rate of absorption.
Teva argues that the prior art only inconsistently teaches
away from using EDTA, and only from much larger
quantities, and that BR ’601 addresses the clinical viabil-
ity concerns with a delayed release formulation. Teva
also asserts that the objective evidence presented only
further supports the obviousness of providing relatively
constant absorption regardless of fasted/fed state.
We agree with Teva that the district court did not err
in concluding that the asserted claims would have been
obvious to one of skill in the art at the time of the inven-
tion. The inventors were not faced with a dearth of prior
art: as the district court found, the broad disclosure of BR
’601 nearly anticipates, and the only claim limitation it
lacks is “pharmaceutically effective absorption.” Warner
Chilcott gives the pharmaceutically effective absorption
limitation the prominence that it must. Although com-
mon sense tells us that any pharmaceutical composition
entitled to a patent would have to be pharmaceutically
effective, as would any such formulation approved by the
FDA, the fact is that, without that limitation specifically
referring to the fed/fasted absorption defined in the speci-
fication, the asserted claims would not have issued from
10 WARNER CHILCOTT CO. v. TEVA PHARMACEUTICALS USA, INC.
the original prosecution. Although Warner Chilcott
defined the limitation such that it is not equivalent to
merely overcoming the food effect, the district court found
that pharmaceutically effective absorption would have
been a logical and obtainable goal for a drug with bioa-
vailability that is significantly affected by co-
administration with food.
We further agree with the district court that Teva
proved by clear and convincing evidence that it would
have been obvious in view of the prior art to use a chelat-
ing agent to bind calcium ions to mitigate the food effect
for risedronate and thereby achieve similar fed/fasted
absorption. The district court articulated its understand-
ing of the prior art references and the teachings that
would have led one of ordinary skill in the art to use
EDTA to sufficiently reduce or negate the food effect to
obtain the claimed invention. Moreover, in view of the
broad disclosures in the specification providing embodi-
ments with varying amounts of EDTA, and nothing in the
asserted claims teaching one of skill in the art that or how
only the specific 100 mg amount produces pharmaceuti-
cally effective absorption, Warner Chilcott failed to show
the criticality of the claimed amount. We discern no clear
error in the district court’s factual findings on the teach-
ings of the prior art or the motivation to modify or com-
bine the art. We therefore find no error in the district
court’s conclusion that the asserted claims would have
been obvious in view of the prior art.
CONCLUSION
We have considered the remaining arguments and
conclude that they are unpersuasive. For the foregoing
reasons, we conclude that the district court did not err in
holding that claim 16 of the ’459 patent and claim 20 of
the ’460 patent are invalid as obvious under 35 U.S.C.
§ 103, and we therefore affirm the district court’s decision.
AFFIRMED