Nalproprion Pharmaceuticals, Inc. v. Actavis Laboratories FL, Inc. (Fed. Cir. 2019)

By Kevin E. Noonan --

Last week, the Federal Circuit reversed findings of non-obviousness and affirmed (over Chief Judge Prost's dissent) a finding that claims asserted in ANDA litigation were not invalid for failure to satisfy the written description requirement in Nalproprion Pharmaceuticals, Inc. v. Actavis Laboratories FL, Inc.

ANDA litigation arose over Nalproprion Pharma's Contrave^® extended-release tablets of the combination of naltrexone hydrochloride and buproprion hydrochloride, for treatment of obesity, and Orange Book-listed U.S. Patent Nos. 7,375,111; 7,462,626; and 8,916,195.  The following claims were at issue in this litigation:

Claim 11 of the '195 patent:

A method of treating overweight or obesity having reduced adverse effects comprising orally administering daily about 32 mg of naltrexone and about 360 mg of bupropion, or pharmaceutically acceptable salts thereof, to a person in need thereof, wherein the bupropion or pharmaceutically acceptable salt thereof is administered as a sustained release formulation, wherein the naltrexone or pharmaceutically acceptable salt thereof is ad- ministered as a sustained release formulation, and wherein said sustained release formulation of naltrexone has an in vitro naltrexone dissolution pro- file in a dissolution test of USP Apparatus 2 Paddle Method at 100 rpm in a dissolution medium of water at 37° C. of:
    a) between 39% and 70% of naltrexone re- leased in one hour;
    b) between 62% and 90% of naltrexone re- leased in two hours; and
    c) at least 99% in 8 hours;
    wherein about 16 mg of said sustained re- lease formulation of naltrexone or a pharmaceutically acceptable salt thereof is administered twice daily, and about 180 mg of said sustained release formulation of bupropion or a pharmaceutically acceptable salt thereof is administered twice daily.

Claim 1 of the '195 patent:

A composition for affecting weight loss comprising:
    (a) a sustained release formulation of bupropion or a pharmaceutically acceptable salt thereof in an amount effective to in- duce weight loss in an individual; and
    (b) a sustained release formulation of naltrexone or a pharmaceutically acceptable salt thereof in an amount effective to enhance the weight loss effect of the bupropion or salt thereof;
wherein said composition is in a single oral dosage form fixed combination.

Claims 26 and 31 of the '626 patent:

A method of treating overweight or obesity, comprising administering a weight loss effective amount of a first and second compound to an individual who has been diagnosed as suffering from overweight or obesity in order to treat said overweight or obesity, wherein said first compound is bupropion, or a pharmaceutically acceptable salt thereof, and said second compound is naltrexone, or a pharmaceutically acceptable salt thereof, and wherein the weight loss activity of said first and second compounds is enhanced compared to the administration of the same amount of either compound alone, wherein naltrexone and buproprion are administered together.

A method of treating overweight or obesity, comprising administering a weight loss effective amount of a first and second compound to an individual who has been diagnosed as suffering from overweight or obesity in order to treat said overweight or obesity, wherein said first compound is bupropion, or a pharmaceutically acceptable salt thereof, and said second compound is naltrexone, or a pharmaceutically acceptable salt thereof, and wherein the weight loss activity of said first and second compounds is enhanced compared to the administration of the same amount of either compound alone, wherein at least one of sad drugs are in a sustained release formulation and are administered in a single oral dosage form.

(where the italicized portions of these claims were recited in independent and/or dependent claims related to asserted claims 26 and 31).

The District Court found that defendant Actavis had not established that claim 11 of the '195 patent was invalid for failure to satisfy the written description requirement of 35 U.S.C. § 112(a) with regard to the claim limitation reciting USP dissolution methods ("USP1" versus "USP2").  The claims expressly recited the USP 2 Paddle Method, but Actavis argued that the specification disclosed only the UPS 1 Basket Method.  The District Court based its decision on the skilled worker not having a doubt that the inventors had possession of the invention based on the nature of the dissolution method disclosed in the specification.  The Court held that disclosure of a "substantially equivalent method" was sufficient to satisfy the requirement.

The District Court also rejected Actavis' arguments that claims 26 and 31 of the '626 patent and claim 1 of the '195 patent were obvious, on the grounds that "it would have been obvious for a person of skill to combine bupropion and naltrexone for treating overweight and obesity because both drugs were known to cause weight loss," holding that this argument amounted to "a classic case of hindsight bias."

The Federal Circuit reversed the District Court regarding its obviousness decision in an opinion by Judge Lourie, joined by Chief Judge Prost and Judge Wallach, and affirmed the District Court on its written description determination over Chief Judge Prost's dissent.  The majority's written description decision was based in part on the "peculiarity" of the structure of claim 11, which is directed to a method for treating obesity using specific amounts of the two drugs and reciting the method for determining the dissolution profile of what the majority termed "resultant in vitro parameters," which were not the "operative steps to treat overweight or obesity."  The majority found no clear error in the District Court's holding 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."  The majority noted that this determination by the District Court was supported by more credible testimony from Nalproprion Pharma's expert and "untrustworthy, self-serving statements by Actavis's expert."  The majority stated that it refused to disturb the District Court's weighing of witness credibility in the performance of its "fact-finding function."  The majority further recognized (in the face of the Chief Judge's dissent) that "[w]hile as a general matter written description may not be satisfied by so-called equivalent disclosure," under these facts the District Court had not clearly erred.

Turning to the District Court's non-obvious determination for claims 26 and 31 of the '626 patent and claim 11 of the '195, patent, the panel unanimously held these determinations to be error as a matter of law.  The opinion sets forth the teachings of the asserted references, characterizing them as disclosing the use of an opioid antagonist like naltrexone and "withdrawal attenuating agents," including buproprion for minimizing weight gain, inter alia, during smoking cessation, and bupropion or naltrexone alone in weight loss regimes.  The Federal Circuit disagreed with the District Court's conclusion of non-obviousness, stating that:

The prior art here discloses the claimed components of the composition claims and the steps of the method claims including the use claimed by the method.  . . .  The references teach that bupropion causes weight loss.  . . .  Likewise, the record indicates that naltrexone can cause weight loss.  . . .  Given that both drugs had shown weight loss effects, we conclude that a person of ordinary skill would have been motivated to combine them.  In fact, such persons did so.

The panel rejected as unpersuasive Nalproprion Pharma's argument that the FDA would not and had not approved buproprion for weight loss, saying that this was not dispositive for the question of whether the skilled worker would have had a motivation to combine the asserted references.  Further, the opinion states:

The inescapable, real-world fact here is that people of skill in the art did combine bupropion and naltrexone for reductions in weight gain and reduced cravings—goals closely relevant to weight loss.  Contrary to Nalpropion Pharma's view, persons of skill did combine the two drugs even without understanding bupropion's mechanism of action but with an understanding that bupropion was well-tolerated and safe as an antidepressant.  . . .  ("The precise mechanism for bupropion SR that is responsible for effects on weight loss is unknown.")  . . .  Thus, we conclude that skilled artisans would have been motivated to combine the two drugs for weight loss with a reasonable expectation of success [citations to the record omitted].

The Court found "every limitation of the claims at issue" was found in the asserted art, and rejected Nalproprion Pharma's purported evidence for secondary considerations (failure of others, unexpected results) to rebut their finding that these claims were obvious.  According to the Court, "the inventors only combined two drugs known to affect weight loss.  Both drugs were known to affect weight loss, and combining them for this known purpose as claimed in the patents yields no unpredictable result."  The Federal Circuit thus found claim 11 of the '195 patent and claims 26 and 31 of the '626 patent to be invalid for obviousness.

The Chief Judge's dissent on the written description question was based on the majority's reliance on "substantially equivalent disclosure" to support claim language not having clear and explicit support in the specification.  The Chief Judge characterizes the majority's decision as "add[ing] what appears to me to be a new rule to this court's long-standing written description jurisprudence."  She sets forth three reasons for her disagreement with the majority:

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.

Important to the Chief Judge's reasoning, inter alia, were arguments from the prosecution history where the patentee appeared to rely on the dissolution profile (and the manner of determining it) to distinguish the claims from the prior art.  The Chief also disagreed with the District Court's (and the majority's) disregard for defendant's expert testimony and found his assertion that the USP1 an USP2 methods would not have produced the same dissolution profile results to have been relevant to the written description issue before each court.

Nalproprion Pharmaceuticals, Inc. v. Actavis Laboratories FL, Inc. (Fed. Cir. 2019)
Panel: Chief Judge Prost and Circuit Judges Lourie and Wallach
Opinion by Circuit Judge Lourie; dissenting in part opinion by Chief Judge Prost

Comments

[Jim Demers]

Have to agree with Judge Probst on this one - the patentee had a reason for switching up the USP tests between the spec (and prosecution arguments!) and the claims. And that reason was the scope of the claims.