by Dennis Crouch
Nalpropion Pharmaceuticals, Inc. v. Actavis Laboratories FL, Inc. (Fed. Cir. 2019)
It is always surprising to see the Federal Circuit reverse a non-obviousness holding; However, the most important aspect of this decision is likely the written description discussion.
This Hatch-Waxman litigation was triggered by the Abbreviated New Drug Application (ANDA) filed by Actavis — seeking permission from the FDA to begin marketing weight loss drugs naltrexone hydrochloride and bupropion hydrochloride extended-release tablets. Nalpropion is the branded distributor of the Contrave and owner of the Orange Book listed patents U.S. Patents 7,375,111, 7,462,626, and 8,916,195. The lawsuit was started by Orexigen who held rights at the time. Nalproprion bought rights from Orexigen out of Bankruptcy in a $75 million asset purchase. (The problem is that the pills are not overly effective — ~10% weight loss, but only when combined with diet changes and exercise.)
The patentee won the district court litigation and obtained an injunction against generic entry by Actavis until expiration of the patents in suit. On appeal, the Federal Circuit has partially reversed — finding some of the asserted claims obvious.
The active ingredients were already known in the art, and so the claims at issue are directed toward (1) a method of treating obesity with naltrexone and bupropion and (2) a sustained release formulation of the two drugs in a single pill.
The key prior art taught use of the two drugs (in sustained release form) to avoid weight gain associated with smoking cessation (rather than losing weight for obese/overweight patients). A second reference taught using bupropion for weight loss. Another reference taught the use of the two drugs as a treatment of depression and included case studies showing weight loss. The district court considered these references but found the weight loss effect were not clear enough and that there were too many potential side-effects to encourage experimentation.
On appeal, the Federal Circuit reversed — finding the claims obvious as a matter of law.
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. . . .
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 [in the prior art]. O’Malley [the first reference] teaches a combination of effective amounts of sustained-release bupropion and naltrexone for minimizing weight gain. Likewise, Dante teaches use of an opioid antagonist, preferably naltrexone, and an antidepressant, including bupropion, for decreasing sugar cravings, noting that naltrexone administration alone led reduced sugar cravings and weight loss in two examples. A person of skill would have understood that a combination for reducing weight gain and decreasing carbohydrate cravings may affect weight loss as well. . . .
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’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.
As a result here, the court held these claims obvious.
Power of a Portfolio: Important note here is that the the obviousness decision invalidated claims from only two of the three patents. The claims in the third patent include more specific dosing and and extended release elements that were not found in the prior art. (E.g., 32 mg of naltrexone; 360 mg bupropion; release of 39-70% within one hour; …). U.S. Patent No. 8,916,195. End result appears likely the same — injunction to prevent generic entry.
Dissent on Written Description: Chief Judge Prost wrote in dissent — arguing that the claims of the third ‘195 patent should also be found invalid as lacking written description. The particular issue is that the patent claimed use of a particular standard (“USP 2”) for measuring the extended-release profile of the pills; but the specification apparently discloses a different standard (“USP 1”). In the case the patentee’s expert testified that the two methods are “substantially equivalent,” and that was enough to satisfy both the district court and the majority here (Judges Lourie and Wallach). Chief Judge Prost disagreed — arguing that disclosure of a “substantial equivalent” of the claimed invention is not sufficient.
A substantially equivalent disclosure, even if it would render the claim limitation obvious, cannot satisfy the written description requirement. See Ariad (“[A] description that merely renders the invention obvious does not satisfy the requirement.”); Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (“The question is not whether a claimed invention is an obvious variant of that which is disclosed in the specification.”).
Chief Judge Prost went on to argue (1) that the claim element is certainly “limiting”; and (2) no evidence of record shows that the two methods produce the same results. For its part, the majority explains that “[i]t is not necessary that the exact terms of a claim be used in haec verba in the specification, and equivalent language may be sufficient.
I pulled up the prosecution history on this case using PAIR. Originally the claims did not mention any dissolution test at all for measuring the sustained release. Later, the patentee added that the test was a “standard” test. The examiner rejected that amendment as failing the written description requirement and the patentee then changed the test to USP 2 (“a dissolution test of USP Apparatus 2 Paddle Method at 100 rpm in a dissolution medium of water at 37 deg C”). The office action response states that “there is sufficient disclosure in the specification to demonstrate possession of the claimed release profile” as amended. The examiner then allowed the case — mentioning the USP 2 profile in the reasons for allowance. All of this tends to favor Judge Prost’s analysis. On the other hand – when I read the patent document it actually discloses the use of USP 2 in the specification or “other test conditions substantially equivalent thereto.” However, the example given of actual dissolution measurements uses USP 1.
= = = =
Dominick Conde of Venable (NY) argued the case for Nalpropion; Jonathan Ball of Greenberg Traurig (NY) argued for Actavis assisted by Justin MacLean, et al.