Non-Limiting Clauses and Written Description Based on Substantially Equivalent Disclosure

August 16, 2019 – Article

Nalpropion Pharmaceuticals, Inc. v Actavis Laboratories FL, Inc (Fed. Cir. Aug. 15, 2019) is a precedential opinion written by Judge Lourie with Judge Wallach and a dissent from Judge Prost in a case centered on an ANDA litigation in which Actavis sought approval for their generic version to Nalpropion’s patents for the Contrave® product. Footnote 1 in the opinion outlines the rather complex history of the ownership/license interests as they changed over time.

The opinion address questions of written description and obviousness of certain claims of the patents-in-suit. For the purpose here, I found the dispute centered on Claim 11 of U.S. patent no. 8,916,195 (‘the ‘195 patent) to be the most interesting. That claim is:

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 administered as a sustained release formulation, and wherein said sustained release formulation of naltrexone has an in vitro naltrexone dissolution profile 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 released in one hour;

b) between 62% and 90% of naltrexone released in two hours; and

c) at least 99% in 8 hours;

wherein about 16 mg of said sustained release 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.

The center of the written description dispute is the 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”). The court was not persuaded that the use of a different method from what is prescribed in the claim presented a written description problem, holding that “whether the dissolution data reported in the specification was obtained using the basket method or the paddle method is not relevant to whether the inventors had possession of the invention.”

The majority and the dissent essentially disagreed as to what import to provide the dissolution profile

Judge Lourie opined:

But that dissolution profile for naltrexone as measured by USP 2 relates only to the measurement of resultant in vitro parameters, not to the operative steps to treat overweight or obesity. And the district court concluded, on the facts, that USP 1 and USP 2 would be “substantially equivalent,” Decision, 282 F. Supp. 3d at 801 (citation omitted). Thus, it found 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. We conclude that this finding does not present clear error.

Judge Prost had a different take:

I part ways with the majority, however, for at least three reasons. 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.

The issue of written description is one of fact and such questions of fact are reviewed for clear error. How the majority reviewed that question and to what they give most importance is interesting. The majority opinion giving more credence to the expert testimony, as did the district court while Judge Prost’s view was that there was no evidence to support the notion that the two manners of determining the dissolution profiled were substantially equivalent and rather there was evidence that there were not.

The majority opinion relied on the district court’s analysis of the facts, while giving more credibility to Nalpropion’s expert over Actavis’s expert: “[t]he district court performed precisely its fact-finding function, weighing credibility of testimony.” Judge Prost was not so moved:

In finding that USP 1 and USP 2 are substantially equivalent, the majority overlooks the district court’s clear error. Not a shred of record evidence supports this fact-finding. And other record evidence refutes it. The record contains no evidence showing that the two methods produce the same results.

Instead, the record includes evidence that the two methods do not produce the same results. First, Dr. Soltero, one of the inventors named on the ’195 patent, testified that USP 1 and USP 2 results are not comparable. He confirmed that “just because you got a certain profile [using] a USP 1 method, you would not necessarily expect that you would get the same release profile [using] USP 2.” See J.A. 11319:17–11321:12. The trial court’s opinion does not even mention this testimony.

Second, Appellant’s expert, Dr. Mayersohn, opined that a skilled artisan would not have understood the two methods to yield the same results. J.A. 11356:22–11357:3. The district court discounted Dr. Mayersohn’s testimony, finding that his “theoretical opinion that the methods would yield different results is at odds with his reliance on a prior art reference using [USP 1] to argue that claim 11, which specifies [USP 2], was obvious.” See Majority Op. 11 (citing

Orexigen, 282 F. Supp. 3d at 801–02).

The standard for obviousness is not, however, the same as the standard for written description.