Gilead Sciences Inc. v Canada (Health) [2013 FC 1270]
Bristol-Myers Squibb v Canada(Health) [2013 FC 1271]
Gilead Sciences Inc. v Canada(Health) [2013 FC 1272]
Background
In three judgments all dealing with the same Canadian patent Justice Barnes refused to allow a Notice of Compliance to issue to Teva for disoproxil tenofovir and its salt form tenofovir disoproxil fumarate. The two patents at issue were Canadaian Patent 2,261,619 and 2,298,059.
Claim 32 of the ‘619 Patent reads:
A compound having the structure [a diagram of the molecule was then produced here]
Tenofovir is used for the treatment of HIV/AIDS. Gilead sells one drug (Atripla) while Gilead sells Truvada and Viread. While the applications were commenced separately and remain separate they raise identical issues and so are dealt with by issuing a single set of reasons.[5]
These drugs are all ‘prodrugs’ which means that they are inactive until they have entered the body and been transformed by enxymatic action or chemical reaction.
Teva’s evidence concerning both patents has overcome the presumption of validity in s. 43(2) of the Patent Act.
Teva has also accepted that their preparation of the prodrug would infringe Claim 32 of the ‘619 patent if it is valid.
Is claim 32 of the ‘619 Patent anticipated by the ‘214 Application?
Anticipation requires that you be able to look at a prior single publication and find all of the information needed to produce the claimed invention without the exercise of inventive skill.[23] The ‘214 application does not expressly disclose the present drug at issue. The ‘214 Application would not be read to include tenofovir disoproxil and teaches nothing about a carbonate prodrug solution to improve upon bioavailability. For these reasons the anticipation assertion fails.
Is the ‘619 Patent Obvious?
A patent is not obvious merely because the prior art establishes that something might work – it requires something more. As well it cannot be a selective analysis of the prior art.[33]
The ability to predict success is the lynchpin of an obvious to try analysis.[35] Tenofovir disoproxil was the first carbonate based prodrug with no comparators. Inferences would need to be drawn by a person of skill from other prodrugs where there had been success.[36] Carbonates or carbomates would not have been looked into by a person of skill. As well a person of skill would not have predicted any of the potential promoiety options would work.[38] There were numerous scientific experiments pointing away from using carbonates in prodrugs.
The prodrug of tenofovir (tenofovir disoproxil) was necessarily inventive since the expert evidence established that the prodrug form has a significant number of options to choose from. It is a complex problem with no predictable solution but rather many different potentially fruitless paths.
The length of the process to develop the prodrug form is relevant to how self-evident the solution is.[68] The long process and difficulty in development are indicative of an inventive, non-obvious solution. Therefore a prohibition order should issue for the ‘619 patent.
‘059 Patent Validity
Teva argued that the ‘059 Patent was invalid due to obviousness. Both compounds were known and disclosed in the prior art. Gilead argued that although the fumarate was known it was rarely used in FDA approved pharmaceuticals and that any references in prior art are irrelevant to the ‘059 patent. Gilead argued that it was impossible to predict whether suitable properties would result from fumaric acid let alone whether a salt would form at all.
Gilead raised an argument referred to as the ‘Rule of 2 or 3’ to support their argument that fumaric acid was not obvious to try. The rule is based on the concept that where a pKa of the salt former is less than that of the free base by 2 or 3 units (or more) than a person of ordinary skill would likely overlook it as a salt former.
Teva in turn pointed to several references regarding exceptions to the rule of 2 or 3. This coupled with the information that these salt formers had already been approved by the FDA means that fumaric salt would be one of several obvious salt formers to try. This does not end the inventiveness inquiry. It is necessary to assess whether it would be more or less self-evident that a person of skill would arrive at a pharmaceutically acceptable salt of tenofovir disoproxil.
Salt screening is a well known or routine pre-formulation procedure. Gilead argued that there are multiple choices for a person of skill to develop a suitable salt and as such there was no clear path to fumaric acid. Although a person of skill would not have had a high degree of certainty in predicting fumaric acid for production of an acceptable salt formulation, routine salt screening would have enabled it to emerge. The actual process used by Gilead supports this – they only screend fumaric acid and citric acid which was known to likely be unstable.
The absence of evidence on the part of Gilead about the complexity of the process to identify fumaric acid for the production of a suitable salt form led the court to the conclusion that:
the development of TDF was routine and not the end product of an onerous or inventive process of discovery. [84]
The Application is therefore allowed in part with respect to the ‘059 Patent. A prohibition order with respect to the ‘619 Patent was issued by the Court.