The Patent Appeal Board (PAB) recently released two decisions relating to patent applications claiming compositions comprising the insomnia drug doxepin and uses thereof.[1] The PAB held that both applications should be refused by the Commissioner of Patents.
Of particular note, in reaching such decisions, the PAB did not rely on the prior art cited by each respective Examiner during prosecution. Rather, the PAB conducted its own prior art search, and found the claims to be anticipated and/or obvious in view of the original applicant's SOMAXON Pharmaceuticals LLC's (Somaxon's) own press releases, published shortly before the earliest priority date of each application. The Somaxon press releases related to the results of Phase 2 and Phase 3 clinical trials published on the now defunct Somaxon webpage, which the PAB accessed through the Wayback Machine Internet Archive. These decisions should serve as a reminder to applicants to properly manage and monitor the disclosure of any results prior to the filing of patent applications.
A detailed description of each decision is provided below.
The claims of Canadian Patent Application No. 2,687,118 (the '118 Application) relate to use of doxepin or a pharmaceutically acceptable salt thereof in a dosage of 3 mg or 6 mg for treating sleep maintenance insomnia characterized by early awakenings during the eighth hour of sleep in a patient who is identified to have a sleep disorder in which, for a given eight hour period of desired sleep, the patient experiences a sleep period that terminates during the final 60 minutes of said period. Claims of the '118 Application are also directed to the use of doxepin at a dosage of 3 mg or 6 mg for an elderly patient to treat insomnia characterized by a different symptom.
The application was rejected in a Final Office Action on March 25, 2020, as being anticipated and obvious contrary to subsection 28.2(1) and section 28.3, respectively, of the Patent Act.
In conducting the novelty and obviousness analysis, the Board followed relevant case law by first construing the claims and identifying the essential elements of the claims.
In finding that the claims were anticipated, the PAB reviewed the relevant Somaxon press releases to determine whether the claimed subject matter was both disclosed and enabled by these references. Although the claims are directed to very specific symptoms to identify a patient population, the PAB held that these specific symptoms are encompassed by the diagnostic criteria of primary insomnia and do not identify a distinct patient group. In other words, the group of patients suffering from the symptoms as claimed are inherent to the disorder and are not part of a distinct group, on the basis that the specific symptoms are within the diagnostic criteria of the disorder. Therefore, if the prior art discloses the use of the claimed dose of doxepin for the treatment of primary insomnia, then the prior art discloses and enables the use of the claimed dose of doxepin for the specific symptoms as claimed.
In finding that the claims were also obvious, the PAB followed the four-step approach set out in Apotex v Sanofi-Synthelabo (2008 SCC 61) (Sanofi). First, the person skilled in the art and the relevant common general knowledge were identified.
Secondly, the PAB agreed with the Examiner that the common inventive concept of the claims "is the use of 3 or 6 mg of doxepin to treat sleep maintenance insomnia causing disruptions to sleep efficiency in the eighth hour of a sleep period". The PAB noted that the inventive concept should include all of the essential elements of the claims.
At the third step, the PAB identified what, if any, differences exist between the matter cited as forming part of the "state of the art" and the inventive concept of the claim or the claim as construed. The PAB found that the main difference lies in the specific sleep disorders as claimed. The cited prior art discloses that low dose doxepin produced an increase in sleep efficiency during the final hour of an eight hour sleep period, even though it was not known whether this improvement was due to prevention of early awakening, prevention of fragmented sleep or both. Another difference was the use of low dose doxepin to treat transient insomnia in adults and the use of an oral tablet formulation to treat insomnia in elderly patients.
Lastly, at the fourth step, the PAB determined whether these differences constitute steps which would have been obvious to the person skilled in the art or they require any degree of invention. The PAB held the successful use of low dose doxepin to treat sleep maintenance insomnia in the eighth hour of sleep disclosed in the Somaxon press releases suggests that doxepin would improve symptoms of early awakenings and fragmented sleep during the eighth hour of sleep. The PAB relied on Bristol-Myers Squibb Canada Co v Teva Canada Limited (2017 FCA 76) for basing their analysis on the premise that the obviousness analysis is concerned with whether bridging the difference between the prior art and a second point constitutes steps that require any degree of invention, or is based on the common general knowledge available to the person of ordinary skill in the art.
CD #1633 – Patent Application No. 2,687,124
Canadian Patent Application No. 2,687,124 (the '124 Application) relates to orally disintegratable pharmaceutical composition comprising low dose doxepin to promote sleep onset by avoiding first-pass metabolism of the drug in the liver.
The '124 Application was rejected in a final Office Action on October 21, 2019 as being obvious contrary to section 28.3 of the Patent Act.
While agreeing with the relevant art cited by the Examiner in the final Office Action, the PAB also conduced their own prior art search, as described above. The Somaxon press release was published about a month before the earliest priority date of the application and disclosed an oral formulation of doxepin, in dosages encompassed by the claims, that successfully reduces the time to sleep onset at the initial treatment period. Therefore, the PAB considered the Somaxon press release to be relevant to the assessment of obviousness.
In finding that the claims were obvious, the PAB again followed the four-step approach set out in Sanofi. The PAB asserted that the main difference between the inventive concept of the claims and the Somaxon press release lies in specifying that the oral tablet formulation is disintegratable. The PAB further noted that additional differences over the cited prior art include the specific nature of the excipient(s).
The PAB further established that the three-pronged "obvious to try" analysis as set out in the context of the fourth step in Sanofi, was appropriate for this case: 1) is it more or less evident that what is being tried ought to work? 2) what is the nature and amount of effort required? 3) is there motive in the prior art to achieve the invention?
With regard to the self-evidence factor, citing Justice Roy in Les Laboratoires Servier v Apotex Inc (2019 FC 616) at para 269, the PAB noted that an amount of uncertainty is allowed in the "obvious to try" analysis and concluded that it would have been more or less self-evident to the person skilled in the art, based on the disclosure in the Somaxon press release and the relevant common general knowledge, that an oral disintegrating formulation of doxepin ought to be effective in reducing the time to sleep onset.
The PAB further noted that while the application discloses several formulations comprising doxepin with various commercially available quick dissolving excipients, there is no evidence that these formulations are not routine or that an arduous investigation of excipients used was required. The PAB further asserted that there is no evidence that any of these formulations were tested for their ability to reduce time to sleep onset, but instead are proposed for that purpose on the expectation that they would be effective. Therefore, the PAB was of the view that the specific formulations as recited in the claims required nothing more than routine experimentation to achieve.
Regarding the third factor which asks whether there is motive in the prior art to achieve the invention, this includes considerations provided in the prior art to find the solution the patent addresses. Indeed, the PAB noted that although the specific formulation is not disclosed, it was the PAB's view that the person skilled in the art would know that these results could be achieved using an oral transmucosal absorbing formulation, and that the next logical step would have been the development of a dosage formulated using orally disintegrating excipients to ensure that first-pass metabolism of doxepin is avoided and usefulness to treat insomnia patients having difficulty falling asleep.
With respect of the specific nature of the excipient(s) defined in some of the claims, the PAB was of the opinion that determining specific therapeutic formulations would be based on their common general knowledge of sleep onset insomnia, efficacy of doxepin in treating sleep onset insomnia, absorption, distribution and elimination of doxepin and excipients for therapeutic use.
As a result, the PAB concluded that the claims on file define subject-matter that would have been obvious to the person skilled in the art, as of the relevant date, having regard to the Somaxon press release in view of their common general knowledge, contrary to section 28.3 of the Patent Act.
[1] Doxepin is a tricyclic antidepressant medication that was first approved in the 1960s by the FDA as a treatment for depression. In 2010, doxepin was also approved as a treatment for insomnia. Doxepin is available as a generic medication and is sold under brand names such as Silenor®, Sinequan®, Quitaxon® and Aponal®.