Naltrexone & Bupropion – USA

On Oct. 13, 2017, District court of Delaware issued an opinion & found Contrave® patents valid & infringed by Actavis.

Plaintiff (Orixegen) brought this patent infringement action on June 3, 2015, alleging that Defendant (Actavis) had infringed seven of Plaintiffs patents by filing Abbreviated New Drug Application ("ANDA") No. 208043 seeking to enter the market with a generic version of Plaintiffs Contrave® (Naltrexone HCl and Bupropion HCl ER Tablet) product. The Court held a three day bench trial on June 5-7,2017 for three patents-in-suit: U.S. Patent Nos. 7,462,626 ("the '626 patent"), 7,375,111 ("the ' 111 patent"), and 8,916,195 ("the ' 1 9 5 patent"). The '626 patent is directed to methods of treating overweight or obesity using a combination of naltrexone and bupropion. The '111 patent is directed to compositions for use in weight loss treatments comprising a combination of sustained release formulations of bupropion and naltrexone. The '195 patent is directed to methods of treating overweight or obesity using a combination of naltrexone and bupropion. Defendant contends that it does not infringe any of the asserted claims. Defendant also argues that claim 11 of the '195 patent is invalid for lack of written description and all asserted claims of the '111 and '626 patents are invalid as obvious in view of the prior art.

WRITTEN DESCRIPTION:

Defendant argued that claim 11 of the '195 patent is invalid for lack of written description because the ranges given for the claimed dissolution profile "were improperly cobbled together" and were measured using a different method than that required by the claim. Plaintiff responded that simply because the claims draw support from different parts of the specification does not mean that a person of ordinary skill would not believe that the inventor was in possession of the invention. Plaintiff also argued that there is no legal requirement that all claim limitations be set out in a single place in the specification. Plaintiff pointed to the prosecution history, which shows the applicant cited to specific portions of the specification as support for claim 11, resulting in a notice of allowance for this claim.

Court agreed with Plaintiff that the specification would indicate to a person of ordinary skill that all of the dissolution data reported in the patent was obtained "using Apparatus 2 ... at a spindle rotation speed of 100 rpm and a dissolution medium of water, at 37° C., or other test conditions substantially equivalent thereto." Therefore Defendant has not proven by clear and convincing evidence that claim 11 of the '195 patent is invalid for lack of written description.

OBVIOUSNESS:

Defendant argued that claims 26 and 31 of the '626 patent and claim 1 of the '111 patent are invalid as obvious over the prior art.2 (D.I. 162 at 22, 27-28). Specifically, Defendant argued that a person of ordinary skill in the art would have been motivated to combine the teachings of the Jain and O'Malley references to administer the combination of naltrexone and bupropion for treating overweight and obesity with a reasonable expectation of success. Jain discloses a placebo-controlled study of sustained release bupropion for reducing weight and depressive symptoms in obese patients. Jain does not discuss naltrexone, nor does it suggest combining bupropion with naltrexone or any other drug. O'Malley discloses the use of an opioid antagonist, such as naltrexone, during smoking cessation to minimize weight gain. O'Malley also discloses that the opioid antagonist may be administered "in combination with at least one withdrawal attenuating agent ... such as clonidine, acamprosate, antihypertensives, antidepressants, antianxiety agents, agents which alter serotonergic function or other agents. One of the antidepressants disclosed in O'Malley is bupropion.

Court agreed with Plaintiff that Defendant's suggestion that bupropion would be an obvious choice for further study in the treatment of overweight and obesity suffers from impermissible hindsight bias. It seems clear that the weight loss effects of bupropion were known to be relatively modest at best. There is also no dispute that the prior art references reported potential risks associated with bupropion, including the risk of seizure. Based on the lack of knowledge of the mechanism of action, combined with the modest effectiveness, Court do not think a person of ordinary skill would have found bupropion to be an obvious starting point for further study. Court also agreed with Plaintiff that the prior art cited by Defendant does not teach a person of ordinary skill that naltrexone was effective for weight loss.

INFRINGEMENT:

Plaintiff asserted that Defendant directly infringes claim 1 of the '111 patent and indirectly infringes claim 11 of the '195 patent and claims 2, 15, 26, and 31 of the '626 patent. Prior to trial, the only non-infringement argument raised by Defendant as to the '111 patent was that it could not be infringed because it was invalid. Therefore Defendant infringes claim 1 of the '111 patent. Defendant's non-infringement arguments as to claim 11 of the '195 patent all center on whether its proposed ANDA product meets the claimed dissolution profile. Plaintiff has adduced sufficient evidence to prove by a preponderance of the evidence that at least some of Defendant's tablets will meet the claimed dissolution profile. Plaintiff presented evidence that Defendant's proposed label induces infringement by meeting all limitations of claims 26 and 31 of the '626 patent.

CONCLUSION:

Defendants failed to prove by clear and convincing evidence that claims 26 and 31 of the '626 patent, claim 1 of the '111 patent, and claim 11 of the '195 patent are invalid. Plaintiff proved by a preponderance of the evidence that Defendant directly infringes claim 1 of the '111 patent and indirectly infringes claims 26 and 31 of the '626 patent and claim 11 of the '195 patent.