On Aug 15, 2019, Federal Circuit affirmed-in-part & reversed-in-part
district court’s decision regarding Contrav® patents related to extended
release composition & method of use patents.
This appeal is related to Nalpropion’s patents, US 7,375,111;
US 7,462,626 and US 8,916,195. The ’626 patent is drawn to a method for
treating over-weight or obesity comprising administering this combination. 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. The ’111 patent is
directed to a composition of sustained-release bupropion and naltrexone for
affecting weight loss.
Appellee Nalpropion Pharmaceuticals, Inc. holds NDA for
& market Contrave® for weight management in overweight or obese adults.
Actavis filed ANDA with USFDA to market generic version of Contrave®. In
response to the infringement suit in district court, Actavis 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. Actavis appealed.
a. Appeal regarding
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. 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”). According to Actavis,
both inventor and expert testimony demonstrated that the two dissolution
methods would produce different results.
Federal Circuit said that 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. Dissolution profile 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. Federal Circuit sided with
district court & said that, irrespective of the method of measurement used,
the specification shows that the inventors possessed the invention of treating
overweight or obesity with naltrexone and bupropion in particular amounts and
adequately described it. District court correctly concluded, on the facts, that
USP 1 and USP 2 would be “substantially equivalent.” 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.
Federal Circuit, however, said that…”While as a general matter written description may not be satisfied by
so-called equivalent disclosure, in this case, buttressed by the district
court’s fact-finding, and where the so-called equivalence relates only to
resultant dissolution parameters rather than operative claim steps, we affirm
the district court’s conclusion. Rigidity should yield to flexible, sensible
interpretation”.
b. Appeal
regarding obviousness –
Actavis challenged claim 1 of the ’111 patent and claims 26
and 31 of the ’626 patent as obvious in view of O’Malley and Jain.
O’Malley (US 6,541,478) in general relates to Smoking Cessation Treatments
Using Naltrexone and Related compounds. Claim 1 of O’Malley is drawn to a
method of treating 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. . . .” Jain is a research paper entitled “Bupropion SR vs.
Placebo for Weight Loss in Obese Patients with Depressive Symptoms.” Jain discloses
that “preliminary studies suggest that bupropion SR is also an effective adjunct
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.
District court rejected Actavis’s obviousness argument &
said that the weight loss effects of bupropion were known to be relatively
modest at best, and prior art references reported 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 effectiveness, a
person of skill would not have found bupropion to be an obvious starting point
for further study. The district court was also convinced that a person of skill
would not have understood naltrexone to be effective for weight loss. As for
the combination of the two drugs, the district court concluded that prior arts
did not teach a person of ordinary skill that the combination was effective for
weight loss. According to the court, neither reference teaches anything about
weight loss or that naltrexone enhances bupropion’s weight loss effects.
On appeal, the parties primarily dispute whether a person of
skill would have been motivated to combine bupropion and naltrexone with reasonable
expectation of success. Federal Circuit held that, given that both drugs had
shown weight loss effects, a person of ordinary skill would have been motivated
to combine them. A person of skill would have understood that a combination for
reducing weight gain and decreasing carbohydrate cravings may affect weight
loss as well. Nalpropion argued that bupropion does not possess sufficient
weight loss efficacy to obtain FDA approval by itself. Therefore, a person of
skill would not have been motivated to develop bupropion for weight loss.
Federal Circuit, however disagreed & said that “[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.” Also, every limitation in the claims at issue was met by
O’Malley and Jain. Federal Circuit finally rejected objective indicia of
nonobviousness & reversed the district court’s holding that these claims
are not invalid.
Thus, Federal Circuit affirmed written description decision
& reversed non-obviousness decision of district court.
Dissent:
Chief Judge, Prost in dissent criticized the “substantially
equivalent” test for written description requirement. She said that based on her
understanding of this court’s precedent, she would find claim 11 of the ’195
patent invalid for lack of adequate written description. She essentially
differed in 3 aspects: First, the USP 2 clause is limiting. Second, the
majority’s “substantially equivalent” rule is inconsistent with this court’s
precedent. Third, the district court clearly erred in finding that the ’195
patent’s written description includes a disclosure “substantially equivalent”
to USP 2.
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