Goodmans IP Represents Apotex in Successful Patent Challenge re: Eli Lilly’s EFFIENT® (prasugrel)

On July 13, 2018, the Federal Court dismissed Eli Lilly’s application under the Patented Medicines (Notice of Compliance) Regulations for an order prohibiting Apotex from marketing its Apo-prasugrel product until after the expiry of Canadian Patent No. 2,432,644 (the “644 Patent”). The Public Judgment and Reasons are reported as Eli Lilly Canada v. Apotex, 2018 FC 736. Apotex was represented by the Goodmans IP Team, including Andrew Brodkin and Jenene Roberts.

Apotex alleged that the 644 Patent was invalid on the following grounds:

(a) the claims cover non-patentable subject matter;

(b) claims 22 and 29 are obvious;

(c) the 644 Patent does not make correct and full disclosure; and

(d) claim 29 is overbroad.

Manson, J. dismissed Eli Lilly’s application on the grounds that Apotex’s allegation that claims 22 and 29 were obvious was justified.

The 644 Patent

The 644 Patent relates to pharmaceutical compositions comprising two known compounds, prasugrel and aspirin. The 644 Patent states that prasugrel and aspirin were known to possess inhibitory activity against platelet aggregation and thrombogenesis and are useful for preventing or treating diseases caused by thrombus or embolus.

However, according to the 644 Patent, pharmaceutical compositions containing both compounds were not known.

The 644 Patent provides that the use of prasugrel and aspirin in combination results in more potent effectiveness than the use of each component alone and that the two agents can be administered separately and sequentially.

The parties agreed that the only claims at issue were claims 22 and 29 (the “Asserted Claims”).

Claims Construction

The parties were in general agreement on the construction of the Asserted Claims. However, the parties disagreed as to the following:

• Whether the skilled person would understand the appropriate time interval between the administration of the two agents when they are administered sequentially, as covered by Claim 29; and
• Whether claims 22 and 29 incorporate the notion that prasugrel combined with aspirin produces a synergistic effect with respect to the prevention and treatment of thrombosis.

The Court addressed these two issues when discussing Apotex’s invalidity allegations below.

Patentable Subject Matter

Apotex alleged that the claims of the 644 Patent are invalid as they do not relate to an invention, but rather they claim a “mere aggregate and not a patentable combination” given that the “purported invention” relates to an additive combination of prasugrel plus aspirin without any new or different result as compared to their separate uses.

Apotex also alleged that the Asserted Claims are not restricted to combinations of prasugrel and aspirin that exhibit a synergistic effect, as the disclosure does not assert that the combination of prasugrel and aspirin exhibit a synergistic effect.

The Court acknowledged that there was ambiguity in the Asserted Claims as to whether either claim covers the synergistic effect produced by prasugrel combined with aspirin. However, the Court held that the 644 Patent as a whole, when read purposively with a mind willing to understand, disclosed patentable subject matter:

[85] … The combination of prasugrel and aspirin was a new and useful treatment for diseases caused by thrombus or embolus, in that it possessed new, useful and synergistic inhibitory activity against platelet aggregation, without acceptable bleeding risks or other side effects.

[90] …[T]he use of prasugrel combined with aspirin results in an effect on platelet aggregation that is new, useful and more than the mere sum of the effects of the two agents taken alone.

Obviousness

The court considered the four-part test for obviousness set out in the Supreme Court of Canada’s decision in Apotex Inc v Sanofi-Synthelabo Canada Inc (2008 SCC 61).

The Court stated that the test for obviousness and the use of the inventive concept was not qualified in light of the recent decisions of Ciba Specialty Chemicals Water Treatments Ltd v SNF Inc (2017 FCA 225) and Bristol-Myers Squibb Canada Co v Teva Canada Limited (2017 FCA 76). Rather, the test focuses on whether an invention as claimed is obvious based on the claim(s), and if there is ambiguity in the claim(s) under consideration, reference can be made to the disclosure to understand whether an invention as claimed is obvious or not over the prior art.

The Court also stated that any criticism that the prior art relied upon by Apotex and put to their experts was curated with hindsight is without merit or irrelevant.

Inventive Concept of Claims 22 and 29

The inventive concept of the Asserted Claims was that the antithrombotic effect of prasugrel plus aspirin is greater than the sum of the effects of each agent alone.

Differences between the prior art and the inventive concept

The Court stated that, while the first and second thienopyridines (ticlopidine and clopidogrel) had been combined with aspirin to treat and prevent diseases caused by thrombus or embolus, there had not been a disclosure of the use of the third generation thienopyridine (prasugrel) with aspirin.

Whether those differences constitute steps that would have been obvious

The Court stated that there were no material differences that would not have been obvious having regard to what was known in the prior art and what is claimed in the Asserted Claims. It was self-evident to try, and the skilled person would reasonably have expected, that combining the third generation thienopyridine (prasugrel) with aspirin, simultaneously or sequentially, would produce a beneficial, complementary mechanism of action.

There was a clear motive from the prior art to find the solution of the 644 Patent.

The skilled person would know that conducting tests to confirm the benefits of prasugrel and aspirin was an obvious step forward. While the tests did require expertise, the skilled person would have known how to conduct these tests and analyze the results.

Further, while the effects of the combined use of prasugrel and aspirin could not be predicted with exact certainty, the skilled person could reasonably expect to achieve the same synergistic, therapeutic effect that was shown in the prior art with respect to the second thienopyridine clopidogrel (and potentially the first thienopyridine ticlopidine) combined with aspirin.

It was more or less self-evident and obvious to try the combination of prasugrel with aspirin.

Therefore, the court held that claims 22 and 29 were obvious and invalid.

Insufficiency & Overbreadth

Apotex alleged that the 644 Patent failed to disclose how to administer prasugrel and aspirin sequentially, as it did not specify the appropriate time interval between administering the two agents. Apotex alleged that the skilled person would need to determine that time interval experimentally.

Apotex also alleged that claim 29 is overbroad for similar reasons, namely that the inventors did not invent or describe the maximum time interval for sequential administration of prasugrel and aspirin.

The Court held that the disclosure in the 644 Patent was sufficient to enable the skilled person to put the invention as claimed in claims 22 and 29 into practice. The skilled person would know that as long as aspirin and prasugrel were both administered within the known life-span of the platelet, they would exert an effect.

The Court also held that claim 29 was not overly broad for similar reasons.

Author: Jaclyn Tilak