Five Takeaways from Combination Drug Treatment and Dissolution Range Patent Rulings in Orexigen v. Actavis

October 17, 2017

By Chad J. Peterman, Bruce M. Wexler & Simon F. Kung

On October 13, 2017, Judge Richard G. Andrews of the District of Delaware issued a decision holding in favor of Orexigen Therapeutics, Inc. (“Orexigen”) in a Hatch-Waxman case against Actavis Laboratories FL, Inc. (“Actavis”) involving Orexigen’s weight-loss drug Contrave®.[1] Below, we discuss the background of the case and five of the key holdings from the decision that could impact litigation and prosecution strategy for pharmaceutical patents.

Case Background

Contrave®, a drug developed by Orexigen and approved by the FDA in September 2014, is indicated for use as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in certain adults. Contrave® contains as its active ingredients a combination of naltrexone and bupropion.

Actavis submitted an Abbreviated New Drug Application (“ANDA”) to make and sell a generic version of Contrave®. Orexigen asserted claims from U.S. Patent Nos. 7,462,626 (the “’626 patent”), 7,375,111 (the “’111 patent”), and 8,916,195 (the “’195 patent”) against Actavis. Following a three-day bench trial before Judge Andrews, the Court held that each of the asserted claims of these three patents-in-suit were valid and infringed by Actavis.[2]

Five Takeaways from the Court’s Decision

1. Written Description of Dissolution Profiles

The Court held that a claim in the ’195 patent to a dissolution profile was not invalid for lack of written description, where the claim drew support from several different areas of the specification for the endpoints of the claimed dissolution ranges. The Court found “nothing odd or invalidating about the inventors looking to different tables of dissolution data and other places in the specification to determine the ranges for the claimed dissolution profile,” recognizing that “[a] single test on a single tablet could provide only a single data point at each time; rather, multiple tests are necessarily required to establish a range.”[3]

Actavis further argued that the patent claim lacked written description support, alleging that data in the patent specification was generated using a USP Apparatus I basket method rather than the claimed USP Apparatus II paddle method test. Actavis, however, had previously argued that this claim was invalid as obvious, and, in doing so, Actavis and its expert relied on prior art data generated using the USP Apparatus I basket method.[4] Actavis dropped its obviousness defense going into trial, but Orexigen brought out on cross-examination of Actavis’s expert his earlier reliance on the USP Apparatus I basket method data. In rejecting Actavis’s written description argument, the Court noted, among other things, that “even [Actavis’s] own expert was willing to favorably compare the two methods when it was to [Actavis’s] benefit to do so.”[5]

2. Uncorroborated Third Party Activities as Alleged Prior Art

Actavis identified for the first time in its pre-trial order submission its intent to call a third-party fact witness to trial who claimed to have administered naltrexone and bupropion to two patients prior to the filing of the ’626 and ’111 patents.[6] In resolving a dispute about the timeliness of this disclosure, the Court allowed a 2.5 hour deposition to occur about a week before trial at the witness’s location in Baton Rouge, LA.[7] At trial, Orexigen’s cross-examination of this witness showed that he was deviating from his prior testimony, and that he in fact had no “independent recollection of any of the facts of the treatments he administered.” The Court found that this witness “testified directly” from a fax document created after the inventions of the ’626 and ’111 patents.[8] The Court further found that “[t]he contents of the [fax] . . . were not corroborated at trial,” and held that the purported underlying activities described in the later fax (i.e. the alleged treatments), “are not themselves prior art.”[9]

3. Requisite Motivation to Select Individual Components of a Combination Drug Product

The Court held that Actavis had not shown obviousness of the asserted claims of the ’626 and ’111 patents, finding, inter alia, that that a person skilled in the art would not have been motivated based on the prior art to “pursue the combination of bupropion and naltrexone for weight loss.”[10] The Court found, for example, that the two drugs had only limited efficacy for weight loss when administered individually. The Court observed that “[b]ased on the lack of knowledge of the mechanism of action, combined with the modest effectiveness, I do not think a person of ordinary skill would have found bupropion to be an obvious starting point for further study.”[11] Moreover, the Court found that “the prior art disclosed that naltrexone was not effective for weight loss.”[12] The Court observed that Actavis’s argument—that it would have been obvious to combine naltrexone and bupropion for weight loss—was “a classic case of hindsight bias,” where “[Actavis] begins with the combination [Orexigen] ultimately patented and then seeks to justify that combination by combining prior art references that simply would not guide a person of ordinary skill to choose this combination.”[13]

4. Knowledge of “Particular Administration” That Is Infringing

The Court rejected Actavis’s non-infringement arguments based on the asserted possibility of there being some tablets outside the claimed dissolution range of the ’195 patent. The Court noted that while “some of the tablets fall slightly outside of the claimed range for the two hour dissolution data,” Actavis “does not appear to dispute that some of the tablets it tested fall squarely within the claimed dissolution profile.”[14] The Court rejected Actavis’s “suggest[ion] that in order to prevail on its infringement claim, [Orexigen] must prove that [Actavis] knows of some particular administration of the ANDA product that will meet the claimed dissolution profile.”[15] The Court found that Orexigen had shown “by a preponderance of the evidence that at least some of [Actavis’s] tablets will meet the claimed dissolution profile.”[16]

5. Induced Infringement of Dissolution Claims

The Court also rejected Actavis’s non-infringement argument that, because the label from the ANDA “‘does not even mention the dissolution profile’ of its product,” Orexigen cannot prove that Actavis intends to induce infringement of the ’195 patent.[17] The Court held that “[w]hether the patient who performs the method by administering the tablets knows that the tablets meet the dissolution profile is irrelevant for the purposes of infringement.”[18] The Court found that “[Actavis] knows that the tablets meet all of the claim limitations and, through its proposed label, encourages patients to administer the tablets in a manner that infringes the claimed method.”[19]