Court Opinion

ID: 809904
Source: CourtListenerOpinion
Date Created: 2012-10-11 15:12:12+00
Date Added: 2024-06-11T12:39:48.217505
License: Public Domain

NOTE: This disposition is nonprecedential.

United States Court of Appeals
    for the Federal Circuit
          __________________________

HOFFMANN-LA ROCHE INC. AND GENENTECH,
                  INC.,
          Plaintiffs-Appellants,
                        v.
     APOTEX INC. AND APOTEX CORP.,
          Defendants-Appellees,
                      AND

  WATSON LABORATORIES, INC., WATSON
        PHARMACEUTICALS, INC.,
     WATSON PHARMA, INC., COBALT
        PHARMACEUTICALS INC.,
    AND COBALT LABORATORIES, INC.,
           Defendants-Appellees,
                      AND

MYLAN INC., MYLAN PHARMACEUTICALS INC.,
GENPHARM INC. (NOW KNOWN AS GENPHARM
        ULC), AND GENPHARM, L.P.,
             Defendants-Appellees.
          __________________________

            2012-1270, -1271, -1272
          __________________________
HOFFMANN-LA ROCHE   v. APOTEX                             2

    Appeals from the United States District Court for the
District of New Jersey in Nos. 07-CV-4417, 07-CV-4539,
and 07-CV-4661, Judge Stanley R. Chesler.
              ____________________________

               Decided: October 11, 2012
             ____________________________

     MARK E. WADDELL, Loeb & Loeb LLP., of New York,
New York, argued for plaintiffs-appellants. With him on
the brief were WARREN K. MACRAE and JOHN M. GRIEM,
JR. Of counsel on the brief were JONATHAN S. FRANKLIN,
Fulbright & Jaworski L.L.P., of Washington, DC; and
MICHAEL R. GRIFFINGER, DAVID E. DE LORENZI and
SHEILA F. MCSHANE, Gibbons P.C., of Newark, New Jer-
sey.

    DEANNE M. MAZZOCHI, Rakoczy Molino Mazzochi Si-
wik LLP, of Chicago, Illinois, argued for all defendants-
appellees. With her on the brief were WILLIAM A.
RAKOCZY, TARA M. RAGHAVAN and ERIC R. HUNT for Wat-
son Laboratories, Inc, et al. Of counsel on the brief were
STEVEN E. FELDMAN, JAMES P. WHITE, DANIEL R. CHERRY,
PHILIP D. SEGREST, LOUISE T. WALSH and SHERRY L.
ROLLO, Husch Blackwell LLP, of Chicago Illinois, for
Apotex Inc., et al; and EDGAR H. HAUG and RICHARD R.
PARKE, Frommer Lawrence & Haugh LLP, of New York
New York, for Maylan Inc. et al.
               __________________________

      Before NEWMAN, LOURIE, and O’MALLEY, Circuit
                       Judges.
   Opinion for the court filed by Circuit Judge LOURIE.
   Dissenting opinion filed by Circuit Judge NEWMAN.
3                            HOFFMANN-LA ROCHE   v. APOTEX

LOURIE, Circuit Judge.
     Hoffmann-La Roche, Inc. (“Roche”) appeals from the
decision of the United States District Court for the Dis-
trict of New Jersey, denying Roche’s motion for a prelimi-
nary injunction. See Hoffmann-La Roche Inc. v. Apotex
Inc., No. 2:07-CV-04417, 2012 WL 869572 (D.N.J. Mar.
14, 2012) (“Preliminary Injunction Order”). Because the
district court did not abuse its discretion in denying
Roche’s request for a preliminary injunction, we affirm.
                      BACKGROUND
                            I.
    This patent appeal relates to methods of treating os-
teoporosis in post-menopausal women. Roche owns U.S.
Patents 7,410,957 (“the ’957 patent”) and 7,718,634 (“the
’634 patent”), which cover the administration of Roche’s
osteoporosis drug, Boniva®. The ’957 patent is the parent
patent of the ’634 patent. Both patents disclose and claim
methods of treating osteoporosis by orally administering
once a month a tablet that contains about 150 mg of a salt
of ibandronic acid, which is the active ingredient in
Boniva®. Claim 1 of the ’634 patent is representative of
the claims on appeal:
       1. A method for treating or inhibiting
            postmenopausal osteoporosis in a
            postmenopausal woman in need of
            treatment or inhibition of post-
            menopausal osteoporosis by admini-
            stration of a pharmaceutically
            acceptable salt of ibandronic acid,
            comprising:

       (a) commencing the administration of the
             pharmaceutically acceptable salt of
HOFFMANN-LA ROCHE   v. APOTEX                             4

              ibandronic acid by orally adminis-
              tering to the postmenopausal
              woman, on a single day, a first dose
              in the form of a tablet, wherein the
              tablet comprises an amount of the
              pharmaceutically acceptable salt of
              ibandronic acid that is equivalent to
              about 150 mg of ibandronic acid;
              and
       (b) continuing the administration by orally
              administering, once monthly on a
              single day, a tablet comprising an
              amount of the pharmaceutically ac-
              ceptable salt of ibandronic acid that
              is equivalent to about 150 mg of
              ibandronic acid.
’634 patent, col.7 ll.23–39. According to the specification,
treating osteoporosis with orally-administered ibandro-
nate was known in the art. Id. col.1 ll.59–66, col.2 ll.10–
29. However, when administered orally on a continuous
basis, ibandronate was known to cause skin irritations
and result in digestive tract side effects. Id. To remedy
those problems, the inventors discovered that a once-
monthly dose of 150 mg, among other infrequent dosing
regimens, was effective at treating osteoporosis in post-
menopausal women. Id. at col.2 ll.43–59, col.3 ll.13–24.
In 2005, the United States Food and Drug Administration
(“FDA”) approved once-monthly Boniva® to treat osteopo-
rosis in post-menopausal women.
                            II.
   In 2007, the Defendants submitted Abbreviated New
Drug Applications (“ANDAs”) to the FDA for approval to
engage in the commercial manufacture, use, or sale of
generic versions of once-monthly ibandronate products to
5                             HOFFMANN-LA ROCHE   v. APOTEX

treat osteoporosis. Thereafter, Roche sued the Defen-
dants in the United States District Court for the District
of New Jersey, asserting, inter alia, that the Defendants
infringed various claims of the ’957 and ’634 patents
under 35 U.S.C. § 271(e)(2) by submitting their ANDA
filings.
    During the pretrial proceedings, Roche filed a motion
for a preliminary injunction. The court denied the mo-
tion, finding that Roche failed to establish a reasonable
likelihood that it would prevail against the Defendants’
obviousness challenge. In so finding, the district court
relied on six prior art references: (1) the “Update: Biphos-
phonates” article in the Spring 1999 issue of “Lunar
News” (“the Lunar News article”); (2) a 1996 research
report by Ravn et al. in the journal “Bone” (“the Ravn
study”); (3) U.S. Patent 6,432,932 (“Daifotis”); (4) U.S.
Patent 6,143,326 (“Möckel”); (5) a 2001 research report by
Reiis et al. published in the “Journal of Bone and Mineral
Research” (“the Reiis study”); and (6) U.S. Patent Applica-
tion Publication No. 2003/0118634 (“Schofield”).
    The court issued a series of findings concerning the
likelihood that Roche would defeat the Defendants’ obvi-
ousness challenge. Regarding the Lunar News article, the
court found that the article, in discussing that ibandro-
nate can be given as an oral agent “once/month” and still
be “quite potent” to effectively treat osteoporosis, taught
two of the three key limitations in the asserted claims: (1)
the oral administration of ibandronate, and (2) once-
monthly, for the treatment of osteoporosis. Preliminary
Injunction Order, 2012 WL 869572, at *3–4. The only
limitation that the Lunar News article failed to disclose
was the 150 mg dose. Id. at *4.
   The court found that the remaining references, in
combination with the Lunar News article, showed that
HOFFMANN-LA ROCHE   v. APOTEX                             6

Roche was not likely to prevail on the merits of its in-
fringement claim. First, the court found that the Ravn
study concluded that daily dosing of ibandronate to post-
menopausal women at 2.5 mg and 5 mg levels was an
effective treatment, and noted that those two dose levels
yield total monthly doses of 75 mg and 150 mg respec-
tively. Id. at *4. Second, the court found that Daifotis
taught that “a once weekly dose of ibandronate in the
amount of 35 mg, 40 mg, or 50 mg” would have been
“useful for inhibiting bone resorption,” and that those
skilled in the art would have likely observed that 35 mg
per week corresponds to 5 mg a day, similar to Ravn’s
finding that 5 mg per day was an effective dose. Id. at
*4–5. Third, the court found that Möckel disclosed “the
use of oral ibandronate to treat osteoporosis, and teaches
that a single dose of ibandronate should be in the range of
.1 mg to 250 mg.” Id. at *5. Fourth, the district court
found that the Reiis study disclosed that intermittent
dosing of ibandronate with a total dose was as effective as
continuous administration for treating osteoporosis in
postmenopausal women. Id.
      The district court found that Schofield’s disclosure
was “very, very close” to the patented treatment methods.
Id. at *6. Specifically, the court found that Schofield
expressed the “total dose concept” for treating osteoporo-
sis, namely, that one may treat osteoporosis by adminis-
tering a particular amount of ibandronate “as a daily
dose, or one may administer the proportionally equivalent
amount intermittently,” including a monthly dose that
has an equivalent daily dose of between 5 mg and 10 mg,
i.e., a 150 mg to 300 mg monthly dose. Id. at *5–6.
    In addition to those references, the district court con-
sidered extensive expert testimony, including concessions
by Roche’s technical expert. According to the district
court, Roche’s expert made five key concessions: (1) that
7                             HOFFMANN-LA ROCHE    v. APOTEX

the Lunar News article provided a motivation to investi-
gate monthly dosing with bisphosphonates such as iban-
dronate; (2) that in the 2000–02 timeframe the art was
trending away from daily dosing and toward longer inter-
val dosing; (3) that, by the critical date, a skilled artisan
would have reason to investigate treatment with monthly
ibandronate; (4) that once one chooses a particular treat-
ment agent and a particular dosing time interval, deter-
mining a dose within the broad therapeutic range is a
relatively routine matter; and (5) that, by May 2002, one
skilled in the art would have expected that a once-
monthly dose of 150 mg of ibandronate would have had
some effectiveness. Id. at *6–7.
     Finally, the district court rejected Roche’s evidence of
teaching away and secondary considerations. The court
found that while the prior art showed there were uncer-
tainties in the field, “the field as a whole appeared to be
moving toward osteoporosis treatment regimens involving
intermittent dosing,” and one-month periods between
dosing were “well-known.” Id. at *7. Regarding Roche’s
evidence of secondary considerations, the court found that
Roche “had not detailed its position on secondary consid-
erations in briefing” its motion for a preliminary injunc-
tion and had not “substantively pointed out such
evidence.” Id. The court also specifically considered and
rejected Roche’s evidence of commercial success. Id. at *7
n.6.
    In considering all the evidence presented, the district
court found that Roche failed to prove a likelihood that it
would successfully defend against the Defendants’ obvi-
ousness challenge. Roche timely appealed from the
decision, and while its appeal was pending, the district
court concluded on summary judgment that claims 1–8 of
the ’634 patent would have been obvious to those of skill
in the art, relying on the prior art submitted during the
HOFFMANN-LA ROCHE    v. APOTEX                              8

motion for preliminary injunction as well as three addi-
tional references. See Hoffmann-La Roche Inc. v. Apotex
Inc., No. 2:07-CV-04417, 2012 WL 1637736 (D.N.J. May 7,
2012). No judgment has yet been entered on that deci-
sion, and any such judgment will be subject to appeal. We
thus express no opinion on the summary judgment pro-
ceedings in the context of this appeal. We have jurisdic-
tion over Roche’s appeal of the denial of its motion for a
preliminary       injunction     pursuant       to      28
U.S.C. §§ 1292(a)(1) and (c)(1).
                        DISCUSSION
                              I.
    The grant or denial of a preliminary injunction under
35 U.S.C. § 283 lies within the sound discretion of the
district court. Novo Nordisk of N. Am., Inc. v. Genentech,
Inc., 77 F.3d 1364, 1367 (Fed. Cir. 1996). Accordingly,
when a preliminary injunction is denied, to obtain rever-
sal the patentee must show “not only that one or more of
the findings relied on by the district court was clearly
erroneous, but also that denial of the injunction amounts
to an abuse of the court’s discretion upon reversal of
erroneous findings.” Reebok Int’l Ltd. v. J. Baker, Inc., 32
F.3d 1552, 1555 (Fed. Cir. 1994).
    As the moving party, Roche had to establish a right to
a preliminary injunction in light of four factors: (1) a
reasonable likelihood of success on the merits; (2) irrepa-
rable harm if a preliminary injunction is not granted; (3)
the balance of hardships tipping in its favor; and (4) the
impact of the injunction on the public interest. Novo
Nordisk, 77 F.3d at 1367. Regarding the likelihood of
success on the merits, it was Roche’s burden to show, in
light of the burdens and presumptions that will inure at
trial, that it will likely prove infringement and that it will
likely withstand any invalidity challenge to the patent.
9                             HOFFMANN-LA ROCHE    v. APOTEX

Titan Tire Corp. v. Case New Holland, Inc., 566 F.3d
1372, 1376 (Fed. Cir. 2009).
    One ground of invalidity is obviousness. Under the
Patent Act, “[a] patent may not be obtained . . . 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(a). Although the ultimate determination of
obviousness under § 103 is a question of law, it is based
on several underlying factual findings, including (1) the
scope and content of the prior art; (2) the level of ordinary
skill in the pertinent art; (3) the differences between the
claimed invention and the prior art; and (4) evidence of
secondary factors, such as commercial success, long-felt
need, and the failure of others. Graham v. John Deere
Co., 383 U.S. 1, 17–18 (1966).
                             II.
    Roche does not take issue with the preliminary in-
junction framework that the district court employed.
Indeed, Roche concedes that the district court adhered
carefully to the framework that we set forth in Titan Tire.
566 F.3d at 1376. Instead, Roche raises two primary
arguments directed at the district court’s obviousness
analysis. First, Roche argues that the court erred by
applying an “obvious to try” standard because the prior
art taught multiple possible dosing regimens with unpre-
dictable results. To support that argument, Roche points
to evidence that its success was not predictable. Second,
Roche argues that the district court erred by failing to
consider Roche’s evidence of unexpected results.
    We disagree. Rather than apply an unsupported “ob-
vious to try” analysis, the district court carefully evalu-
HOFFMANN-LA ROCHE    v. APOTEX                             10

ated each reference and the testimony of Roche’s expert.
It was not clear error for the district court to find that the
cited references disclose every claim limitation and that,
while uncertainties remained, the field was trending
towards intermittent dosing based on the total dosing
concept, including a once-monthly dose of 150 mg. In-
deed, Roche’s expert essentially conceded as much, and
the references disclose that it was advantageous to inter-
mittently dose ibandronate to treat osteoporosis in post-
menopausal women, including a once-monthly dose; that
an effective amount of the intermittent dose can be calcu-
lated by multiplying the daily dose by the dosing period;
and that 150 mg would be an effective once-monthly dose.
Thus, the district court concluded that only “a finite
number of identified, predictable solutions” existed. KSR
Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007). On the
record before it, the district court’s conclusion was not
clear error.
    Second, Roche’s argument that the district court erred
by failing to consider evidence of unexpected results lacks
merit. It is true in the context of obviousness that “a
district court must always consider any objective evidence
of nonobviousness presented in a case.” Transocean
Offshore Deepwater Drilling, Inc. v. Maersk Contractors
USA, Inc., 617 F.3d 1296, 1305 (Fed. Cir. 2010); see also
In re Cyclobenzaprine Hydrochloride Extended-Release
Capsule Patent Litig., 676 F.3d 1063, 1075–80 (Fed. Cir.
2012). However, in denying Roche’s motion for a prelimi-
nary injunction, the district court expressly found that
Roche failed to detail its secondary considerations posi-
tion in its briefing or “substantively point[] out such
evidence.”     Preliminary Injunction Order, 2012 WL
869572, at *7. That finding was not clearly erroneous.
    It appears that the secondary considerations evidence
that Roche points to on appeal was not submitted or
11                            HOFFMANN-LA ROCHE    v. APOTEX

mentioned as part of its motion for a preliminary injunc-
tion. Instead, Roche attempted, in a single line near the
end of its reply brief, to “incorporate by reference” its
entire forty-page brief relating to a separate motion, J.A.
21958, a brief that, among numerous arguments, con-
tained a few conclusory sentences with citations to por-
tions of Roche’s evidence of unexpected results. J.A.
24834–36. “District judges are not archaeologists,” and it
was not the court’s burden to “excavate masses of papers
in search of revealing tidbits” to help Roche satisfy its
burden to obtain a preliminary injunction. Nw. Nat’l Ins.
Co. v. Baltes, 15 F.3d 660, 662–63 (7th Cir. 1994). In any
event, a cursory review of Roche’s unexpected results
evidence fails to show that the district court clearly erred
in light of the references and Roche’s expert’s testimony.
    The dissent asserts that “the panel majority mounts a
one-sided argument against patent validity” and that the
“arguments presented by [her] colleagues were previously
considered and rejected during patent reexamination.”
Respectfully, the dissent appears to be sitting as a trial
court and assumes the majority is also. But we are an
appellate court, reviewing, not what the Patent Office
decided, but what the district court decided.
    We are assuredly aware of the effort and cost of devel-
oping a new drug. But we owe the district court deference
on review of the grant or denial of a preliminary injunc-
tion unless it abuses its discretion or makes clearly erro-
neous findings that affected the exercise of its discretion.
While the dissent makes its own argument for the nonob-
viousness of the claimed invention, we do not find that the
district court made clearly erroneous findings in its de-
termination that Roche did not show a likelihood of suc-
cess on the question of obviousness, referring to the record
presented to the district court at that stage of the proceed-
HOFFMANN-LA ROCHE   v. APOTEX                            12

ings. Ultimately, we decline to find that the district court
abused its discretion.
                       CONCLUSION
    We have considered Roche’s remaining arguments
and conclude that they are without merit. For the forego-
ing reasons, the decision of the district court is
                       AFFIRMED
     NOTE: This disposition is nonprecedential.

 United States Court of Appeals
     for the Federal Circuit
            __________________________

 HOFFMANN-LA ROCHE INC. AND GENENTECH,
                   INC.,
           Plaintiffs-Appellants,

                         v.
      APOTEX INC. AND APOTEX CORP.,
           Defendants-Appellees,

                       AND

   WATSON LABORATORIES, INC., WATSON
         PHARMACEUTICALS, INC.,
      WATSON PHARMA, INC., COBALT
         PHARMACEUTICALS INC.,
     AND COBALT LABORATORIES, INC.,
            Defendants-Appellees,

                       AND

MYLAN INC., MYLAND PHARMACEUTICALS INC.,
GENPHARM INC. (NOW KNOWN AS GENPHARM
        ULC), AND GENPHARM, L.P.,
             Defendants-Appellees.
            __________________________

               2012-1270,-1271,-1272
            __________________________
HOFFMANN-LA ROCHE    v. APOTEX                               2

    Appeal from the United States District Court for the
District of New Jersey in Nos. 07-CV-4417, 07-CV-4539, and
07-CV-4661, Judge Stanley R. Chesler.
                __________________________

NEWMAN, Circuit Judge, dissenting.

    The only issue on this appeal is whether to preserve the
status quo during this litigation, or whether to change it
irretrievably. The Supreme Court has reminded us that the
grant or denial of a preliminary injunction requires consid-
eration of the equities as between the parties, as well as the
probable outcome of the case upon trial. Winter v. Natural
Res. Def. Council, Inc., 555 U.S. 7, 20 (2008); eBay Inc. v.
MercExchange, LLC, 547 U.S. 388, 391 (2006). In a case in
which the outcome is uncertain at the preliminary stage, the
equities may nonetheless loom large. With respect to this
case, although the panel majority mounts a one-sided argu-
ment against patent validity, the patent carries the pre-
sumption of validity, and the arguments presented by my
colleagues were previously considered and rejected during
patent examination.

    In contrast, the equities in this case weigh on the side of
preserving the status quo during the litigation. The pat-
entee Roche had established, for the first time, that the
medicament ibandronate can be effectively and safely ad-
ministered once a month in the dosage of 150 mg, and
conducted the panoply of biological and clinical evaluations
needed to bring such a product to public benefit. It was
necessary to establish not only that once-a-month admini-
stration is effective, but also to find the effective monthly
dosage, and to establish that this dose can safely be ingested
all at once, without undesirable side effects. To establish
this efficacy and safety and dosage, the proceedings for
regulatory approval consumed millions of dollars, in three
3                              HOFFMANN-LA ROCHE     v. APOTEX

“phases” of clinical trials involving thousands of post-
menopausal women, and requiring 12 years of costly effort.
Pls.’ Mem. Supp. Mot. Prelim. Inj. 4. Roche’s successful
product Boniva® was the result of heavy risk-laden invest-
ment—investment for which the defendants now seek the
benefits, having borne neither the cost, nor the risk of
failure.

     As equitable factors, the patentee’s initiative and com-
mitment and investment, as compared with the defendants
who seek only the successful products of others, warrant
appropriate weight in deciding whether the status quo
should be preserved until the challenge to patent validity is
decided. Economic factors are not irrelevant to the equities.
 Cf. Weinberger v. Romero–Barcelo, 456 U.S. 305, 312 (1982)
(“The essence of equity jurisdiction has been the power of
the Chancellor to do equity and to mould each decree to the
necessities of the particular case. Flexibility rather than
rigidity has distinguished it.” (quoting Hecht Co. v. Bowles,
321 U.S. 321, 329 (1944))). In determining whether Roche
must share the benefits of its efforts before expiration of the
patent on which Roche relied in making these efforts, the
economic equities should not be ignored.

    The district court, in considering the likelihood of out-
come, apparently refused to consider Roche’s evidence of
unpredictable results. The district court simply found that
a single 150 mg once-a-month dosage of ibandronate would
have been obvious because 150 mg is 30 times 5 mg, which
was a daily dose disclosed in the prior art. One must won-
der at the need for twelve years of experimental determina-
tion of efficacy and safety, were the result as clear and
inexorable as the judges now find.

    Roche’s expert, Dr. Anastasia Daifotis, explained that
the oral absorption of ibandronate is non-linear for doses
HOFFMANN-LA ROCHE   v. APOTEX                             4

larger than 50 mg, testifying that “orally administered
Boniva® resulted in similar bioavailability in amounts up to
50 mg” but “the serum levels of ibandronate increase dis-
proportionately if doses greater than 50 mg are adminis-
tered.” J.A. 38127–28 ¶108. Dr. Daifotis cited data which
show the disproportionate uptake of ibandronate into the
blood stream for a monthly 150 mg dose over monthly 50 mg
and 100 mg doses, and over a mixed regimen consisting of a
50 mg first dose, followed by two monthly oral doses of 100
mg (50/100 mg):

J.A. 38132 ¶112 (Reginster et al., Monthly Oral Ibandronate
Is Well Tolerated and Efficacious in Postmenopausal
Women: Results From the Monthly Oral Pilot Study, J. Clin.
5                              HOFFMANN-LA ROCHE    v. APOTEX

Endocrin. Metab., Vol. 90, pp. 5018–24 (2005)). Dr. Daifotis
explained that “[t]his was a surprising finding concerning
the disproportionate amount of ibandronate that becomes
available from oral administration of amounts above about
50 mg, and it was unknown as of May 2002,” J.A. 38127–28
¶108. Dr. Daifotis explained that “[t]he benefit of this
surprising result was that a patient could receive higher
than thought possible amounts of active drug to be available
to inhibit osteoclasts, while at the same time not adversely
affecting the safety profile of a 150 mg dose of ibandronate,”
J.A. 38133 ¶115.

     Dr. Daifotis stated that later clinical testing showed
that the 150 mg dose monthly is superior to the 2.5 mg daily
dosage of ibandronate that had been approved for the
treatment and prevention of postmenopausal osteoporosis.
J.A. 38133–35 ¶¶116–19. She cited clinical trial data show-
ing that a 150 mg monthly dose of ibandronate is “superior”
at increasing bone density in the lumbar spine of postmeno-
pausal women, as compared to 100 mg and 50/50 mg
monthly doses and a 2.5 mg daily dose:
HOFFMANN-LA ROCHE   v. APOTEX                             6

J.A. 38135 ¶118 (Miller et al., Monthly Oral Ibandronate
Therapy in Postmenopausal Osteoporosis: 1-Year from the
Mobile Study, J. Bone Miner. Res., Vol. 20, pp. 1315–22
(2005)). This experimental evidence refutes the defendants’
contention, apparently accepted by my colleagues, that the
150 mg once-a-month dose was a matter of simple arithme-
tic. The evidence was that the dosage amount and effec-
tiveness were unexpected and unpredicted, and required
extensive clinical testing, due to ibandronate’s unique
pharmacokinetic and bioavailability profile in the human
body.

    My colleagues state that the district court properly de-
clined to consider this evidence, arguing that Roche only
“incorporate[d] by reference” arguments from its concurrent
summary judgment briefs. Maj. op. at 11. However, both
parties referred the district court to their summary judg-
7                             HOFFMANN-LA ROCHE    v. APOTEX

ment briefs. 1 See Pls.’ Reply Mem. Supp. Mot. Prelim. Inj. 8
(“To avoid repetition, Plaintiffs incorporate by reference
their opposition to Defendants’ motion for summary judg-
ment of obviousness.”); Defs.’ Mem. Opp’n Pls.’ Mot. Prelim.
Inj. 21 (“Defendants have already addressed the matters in
Defendants’ Obviousness Brief and will be addressing them
further in their reply brief.”). The record states that the
district court approved this practice. See D.Ct. op. at 6
(“The parties reference the briefs filed in regard to a pend-
ing motion for summary judgment that the ’634 patent is
invalid based on obviousness.”).

     In the section of the Plaintiffs’ summary judgment brief
entitled “Unexpected Results,” Roche discusses evidence
that “it was unexpected that the 150 mg monthly oral dose
of ibandronate was found superior to 2.5 mg daily ibandro-
nate.” J.A. 24835. Of record were the reports of Roche’s
experts Dr. Bilezikian, Dr. Daifotis, and Dr. Harris, and
Roche explained that “each opines that, at the time of the
inventions, a POSA would not have had any reasonable
expectation of succeeding with a safe, effective, and well-
tolerated once-monthly oral dosage of ibandronate in an
amount as large as 150 mg.” J.A. 24836. At the prelimi-
nary injunction hearing Dr. Bilezikian, Plaintiffs’ expert
witness, corrected the Defendants’ mistaken premise that
oral bioavailability of amino bisphosphonates is fixed,
explaining that “there’s a huge range” based in part on
“absorption kinetics.” J.A. 205.

    1   Apotex’s Mot. for Summ. J. (Feb. 10, 2012); Roche’s
Mot. for Prelim. Inj. (Feb. 11, 2012); Apotex’s Resp. to Mot.
for Prelim. Inj. (Feb. 21, 2012); Roche’s Resp. to Mot. for
Summ. J. (Feb. 21, 2012); Apotex’s Resp. to Mot. for Summ.
J. (Feb. 29, 2012); Roche’s Reply to Mot. for Prelim. Inj.
(Feb. 29, 2012); Apotex’s Reply to Mot. for Summ. J. (March
2, 2012).
HOFFMANN-LA ROCHE    v. APOTEX                               8

    By not considering this evidence, “the district court con-
travened this court's precedent requiring that a fact finder
consider all evidence relating to obviousness before finding a
patent invalid on those grounds.” In re Cyclobenzaprine
Hydrochloride Extended-Release Capsule Patent Litig., 676
F.3d 1063, 1075 (Fed. Cir. 2012).

     In view of the presumption of validity, 35 U.S.C. § 282,
“an alleged infringer who raises invalidity as an affirmative
defense has the ultimate burden of persuasion to prove
invalidity by clear and convincing evidence, as well as the
initial burden of going forward with evidence to support its
invalidity allegation.” Titan Tire Corp. v. Case New Hol-
land, Inc., 566 F.3d 1372, 1376 (Fed. Cir. 2009) (citing Tech.
Licensing Corp. v. Videotek, Inc., 545 F.3d 1316, 1327 (Fed.
Cir.2008)). “If the trial court determines that the chal-
lenger's evidence is sufficient to raise ‘a substantial ques-
tion’ of invalidity, the trial court must then afford the
patentee the opportunity to show that the invalidity defense
‘lacks substantial merit.’” Titan Tire, 545 F.3d at 1378.
Such evidence must be considered, whether the issue is of
likelihood or of finality. See Cyclobenzaprine, 676 F.3d at
1078 (all evidence relevant to obviousness or nonobvious-
ness must be considered).

    Moreover, it is harder for the party asserting invalidity
to meet its burden “when . . . the infringer attempts to rely
on prior art that was before the patent examiner during
prosecution.” Glaxo Group Ltd. v. Apotex, Inc., 376 F.3d
1339, 1348 (Fed. Cir. 2004) (quotations omitted). In this
case, all of the references considered by the district court
were previously considered by the PTO and rejected. See
D.Ct. op. at 16 (“Weighing in favor of Plaintiffs is the undis-
puted fact that all of the prior art brought forward by De-
fendants on this motion was before the examiner during
prosecution of the patents.”). Thus the finding that the
9                              HOFFMANN-LA ROCHE     v. APOTEX

examiner considered and rejected the asserted prior art
weighs strongly against a preliminary finding that the
patented subject matter is likely to be ruled obvious as a
matter of law.

    Although the issue at this stage is solely that of likeli-
hood, the panel majority opinion recites only the evidence
that weighs on the side of invalidity, ignoring the contrary
evidence, and discarding the effect of the burden of proof.
No mention is made of the equities that apply at the pre-
liminary injunction stage. When the equities are consid-
ered, and on an objective view of the facts of patent validity,
the fair and just action is to preserve the status quo during
the litigation. See Apple, Inc. v. Samsung Electronics Co.,
Ltd., 678 F.3d 1314 (Fed. Cir. 2012) (in determining
whether to issue a preliminary injunction, the court must
consider the equitable factors of hardship and public inter-
est along with the likelihood that the patent is invalid).
From my colleagues’ unbalanced analysis of the issue of
obviousness, and their failure to consider the equitable
factors that weigh heavily for preserving the status quo
during the litigation, I respectfully dissent.