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Walking Speed Claims Held Obvious In First Pharmaceutical Patent “Common Issues” Validity Trial

On May 15, 2020, the Federal Court issued its first decision in a “common issues trial” under the new Patented Medicines (Notice of Compliance) Regulations involving Taro, Pharmascience, the multiple sclerosis drug fampridine and Canadian Patent No. 2,562,277. While the Taro and Pharmascience matters formally remained separate actions, the Defendants cooperated and the trial relating to the validity of the 277 Patent in the two actions was heard at the same time.

Background

Patients with MS often have ambulatory issues, including reduced walking speed. It was known that these symptoms were highly unpredictable and can vary, even within the same patient on the same day. The 277 Patent generally relates to the twice-daily use of a 10 mg dose of fampridine sustained release tablets for improving walking and walking speed in patients with MS. Claim 17, for example, provides:

17. Use of a sustained release 4-aminopyridine composition for improving walking in a subject with multiple sclerosis in need thereof for a time period of at least two weeks at a unit dose of 10 milligrams of the 4-aminopyridine twice daily.

Construction

The main issues between the parties were:

  1. whether the asserted claims require a clinically meaningful improvement in walking; and
  2. whether a method of identifying patients who respond to fampridine, the so-called “post hoc responder analysis”, was part of the invention of the 277 Patent.

With respect to the first issue, Justice Manson, relying on the clear terms in the asserted claims, held that “clinical meaningfulness” was not part of the asserted claims as it would require the Court to include a qualitative, subjective indicia that engage the skill and judgment of a physician and which would make it nearly impossible to establish infringement.

With respect to the post hoc responder analysis, Justice Manson noted that Biogen, in closing arguments, did not advance the “tortured” construction advanced by its expert witnesses that sought to read the responder analysis into the asserted claims. In concluding that the responder analysis was not part of the asserted claims, Justice Manson held:

[105] As detailed in the Agreed Statement of Facts, the 277 Application included claims to the use of a fampridine SR composition, and claims to a method for selecting individuals based on responsiveness to treatment. In an August 26, 2011 Office Action, the patent examiner objected to the claims as filed for being directed to a plurality of inventions. In its February 27, 2012 response to the Office Action, Acorda elected to proceed with the use claims in the 277 Application, and file a divisional application for the method claims for selecting so-called responders. The divisional application remains in good standing with the Canadian Intellectual Property Office.

[106] Throughout the trial, Biogen characterized the divisional application as “forced.” This is an overstatement, as the August 26, 2011 Office Action was an objection, rather than a rejection by way of a “final action.” At this point in the prosecution process, Acorda’s election to proceed with the use claims and file a divisional for the method claims was voluntary. If Acorda felt that the unity of invention objection was not merited, it could have advocated that the responder method was indeed part of the claimed use invention.

[107] The responder analysis method claims that were divided out into the pending divisional application may have merit, but those claims are clearly not before the Court.

Anticipation – Disclosure

The Defendants main piece of prior art was a financial document, referred to as an S-1, filed by the patentee, Acorda Therapeutics, with the US Securities and Exchange Commission more than one year prior to the Canadian filing date of the 277 Patent. The S-1 document disclosed that  Acorda’s fampridine SR tablets were provided by Elan and  the result of MS-F201, a small increasing-dose clinical trial designed to determine the optimal dose level of fampridine SR, and which disclosed that in this trial “[m]ost of the improvement in strength and walking speed was apparent within the first three weeks of the Fampridine-SR treatment, at doses from 10 to 25 mg twice a day.”

The S-1 also disclosed that Acorda was conducting a second clinical trial also using the Elan tablets, MS-F202, which included administering 10 mg fampridine SR twice a day over 12 weeks to assess improvement in walking speed in patients with MS. While protocol details of this ongoing second trial were set out, no results were disclosed from which Biogen argued that there could not be any disclosure that 10 mg fampridine, twice a day, resulted in a statistically significant improvement in walking.

Justice Manson, following the Supreme court of Canada in Sanofi and the Court of Appeal in Hospira, held that anticipation does not require the disclosure of the result of the MS-F202 trial:

[138] Despite the lack of results from the MS-F202 study, the disclosure requirement is satisfied if performing what is described in the prior art reference would necessarily result in infringement (Sanofi at para 25; Hospira at para 73). Performing the MS-F202 study protocol would necessarily result in infringement of the 277 Patent, and hence the disclosure requirement is satisfied for claims 17, 18, 31, and 32.

Anticipation – Enablement

Justice Manson agreed that without the responder analysis, a skilled person seeking to recreate the MS-F202 trial would fail, as the inventors did, to achieve statistically significant improvements in walking. However, the skilled person, aware of post hoc analyses and “n-of-1” trials would undertake routine trial and error experiments and would be able to perform the claimed invention without the exercise of inventive skill. Justice Manson concluded that the asserted claims 17, 18 31 and 32 of 277 lacked novelty.

Obviousness

Justice Manson, applying Hospira, held that prior art cannot be excluded from the obviousness analysis solely because it would not have been located by a skilled person after a reasonable and diligent search. The S-1 reference, in combination with an Acorda-sponsored poster presented at a scientific conference in Baltimore in 2002 and a journal article  teaching the pharmacokinetic parameters of Elan’s sustained release fampridine tablets, rendered all asserted claims obvious, including those claiming inherent pharmacokinetic parameters of Elan’s tablets:

[192] Once the POSITA arrived at the claimed dosing regimen of 10 mg bid fampridine SR, there is nothing inventive about identifying the approximate plasma concentrations that result from this dosing regimen. Indeed, the CavSS for 10 mg bid of Elan’s fampridine SR composition was reported in Hayes 2003 to be approximately 21 ng/mL. The resulting fampridine plasma concentrations when dosing the Elan composition at 10 mg bid are merely inherent properties of the formulation itself. The allegedly inventive step is the knowledge that this low dose results in a statistically significant improvement in walking or increase in walking speed for some MS subjects with walking disability. Because this step is not inventive in light of the state of the art and the POSITA’s common general knowledge, neither are the corresponding pharmacokinetic properties of the fampridine SR composition.

Justice Manson also concluded that the obviousness of the asserted claims were not saved by the post hoc responder analysis that Biogen’s expert  sought to infuse into the asserted claims:

[196] While Biogen somewhat distanced itself from Dr. Leist’s infusion of the post hoc responder analysis into the inventive concept, I accept the Defendants’ submission that the responder analysis, which is not claimed, cannot be used to make uninventive claims inventive. Importation of an unclaimed, allegedly inventive step from the disclosure into the plain language of the claims runs contrary to purposive construction of claims that are unequivocal and complete on their face (BVD Company v Canadian Celanese Ltd, [1937] SCR 221 at 237).

Costs

The parties, consistent with recent jurisprudence of the Court involving complex pharmaceutical patent litigation, agreed to a lump sum award representing 30% of the parties actual legal spend plus 100% of all reasonable disbursements, with one exception. The Defendants sought 100% of the cost associated with preparing the evidence of Dr. Kealey, whose expert evidence was directed to establishing when the S-1 document was available to the public. Justice Manson held that “there is no question that this document was available to the public before the relevant date of April 2004” and pursuant to Rule 400 awarded the Defendants all legal costs, and the entirety of the disbursements, associated with preparing Dr. Kealey’s expert report and testimony.

A copy of the Judgment and Reasons may be found here.

Taro was successfully represented by Scott Beeser and Jonathan Stainsby of Aitken Klee.

Pharmascience was successfully represented by Aleem Abdulla, also of Aitken Klee.