Thursday, February 19, 2015

Golden Bonus Rule Applied

Janssen Inc v Teva Canada Ltd / bortezomib (NOC) 2015 FC 184 Barnes J
            2,435,146 – bortezomib formulation – VELCADE

In this NOC proceeding Barnes J held the claimed invention to be obvious using an obvious-to-try analysis. While the case turned largely on the facts, it does make one important legal point of general interest, which is that the discovery of a non-obvious characteristic of an otherwise obvious invention cannot support a patent. This is known in UK law as the “golden bonus” rule. And while not as legally noteworthy, Barnes J’s decision is a very good example of the application of the obvious to try analysis to hold a patent invalid. Finally, the argument turned in part on the identity of the skilled person, and the case illustrates the established law that the patent must be read as a whole when identifying the expertise of the person skilled in the art.

The compound bortezomib was known to be an active proteasome inhibitor. Clinical trials had established that it is useful in the treatment of certain types of cancer. However, bortezomib itself is not stable enough for commercial exploitation. The evident problem facing the inventors of the ‘146 patent was to provide a stable formulation of bortezomib. This problem was solved by the invention of Claim 30 in particular, which is for “the lyophilized (freeze-dried) mannitol ester of bortezomib which forms as a reaction product when the bulking agent, mannitol, is combined with bortezomib” [4].

The question is whether this solution to the formulation problem was obvious. Janssen’s non-obviousness argument turned essentially on two points. First, there are many choices to be made in developing a stable drug formulation, and “it is not self-evident that it would be possible to obtain a workable formulation” [95]. Second, mannitol is a common bulking agent which is used precisely because it is normally inert. The fact that the mannitol ester of bortezomib was formed during lyophilization and that this resulted in greater stability of bortezomib, was unexpected and therefore not self-evident [74].

The first question turned on the facts. Bortezomib was known to be unstable in solution, and Barnes J found that “the person of skill would immediately consider solid state formulations for which there were two well-known options: lyophilization and powder filling. . . . The formulation also needed a bulking agent. Here there were a number of well-known choices. Mannitol was a commonly used bulking agent for freeze-dried formulations. Mannitol was also known to be a stabilizer. There were no apparent reasons to avoid mannitol or to think that it would not work in this application” [111]. Thus, even though it could not have been predicted in advance that lyophilization using mannitol as a bulking agent would solve the formulation problem, this solution was one of a small number of obvious choices, and no unexpected hurdles were encountered once this particular choice was made [115]. This is a classic example of an invention which is obvious to try.

The other point was that the creation of a stabilizing mannitol ester was unexpected. The evidence established that a medical chemist would expect the formation of such an ester [98], so the question was whether a skilled team would be include a medical chemist, or only a formulator; or, if the team included only a formulator, whether the formulator would acquaint herself with the basic medical chemistry of boronic compounds. There was a related question as to the scope of the enquiry that would be expected by a skilled person. It was accepted that the so-called “Wu reference” was the primary prior art [80], and that work cited papers describing the relevant chemistry. Janssen’s expert opined that the skilled formulator would read the Wu reference, but would ignore all the cited papers based on their titles, without reading any of them.

Barnes J’s rejection of this narrow view of the skills and interests of the skilled person turned on the evidence generally, but a couple of general points are worth noting. First, some of the claims were conceded to require the skills of a medicinal chemist [91]. Janssen’s expert took the view that the skilled person was defined only with respect to the particular claim in issue, namely Claim 30. Barnes J rejected this:

[92] I do not agree that individual patent claims can be construed independently from the rest of the claims or from the specification as a whole. The idea that individual claims may require interpretation by persons of skill with different sets of qualifications is unworkable. Patent law teaches that the person of skill may be a character of composite skills. It also teaches that a patent is to be read as a whole.

Another problem for Janssen is that the argument that the creation of the mannitol ester was the inventive concept in Claim 30 implies that the skilled person had to be a medical chemist in order to understand the invention of Claim 30. That is, Janssen was trying to define the inventive concept in a way that required the skills of a medical chemist, and then ensure that it was non-obvious by defining the skilled person so as to exclude the skills of a medical chemist. “For the purposes of identifying the person of skill, Janssen cannot have it both ways” [86].

But in any event, even if the creation of the mannitol ester and its stabilizing properties was unexpected, that is irrelevant:

[99] Before considering the inventiveness of those choices, I will, however, briefly comment on the argument that the discovery of the formation of an ester was part of the inventive concept of Claim 30.

[100] Dr. Stella claims not to have been aware that he had created a mannitol ester when he arrived at the compound/formulation described in Claim 30. Nevertheless, he had in his hands what he was asked as a formulator to develop – a stable and useful formulation for bortezomib. That was so whether or not it was known that an ester had formed. The later characterization of the compound by others (who presumably did know what to expect) did not add anything inventive to Dr. Stella’s work. If a patentee obtains a workable formulation, the later discovery of one of its inherent characteristics does not add anything inventive to what had already been discovered: see Alcon Canada Inc. v Apotex Inc., 2012 FC 410 at para 45, [2012] FCJ No 1707 (QL). The question that remains is only whether Dr. Stella’s development of the formulation for bortezomib described in Claim 30 was obvious.

This, in my view, is a correct application of what is known in the UK law as the “golden bonus” rule, which is usually traced back to Hallen v Brabantia [1991] RPC 195, 216 (CA). This rule says that if an invention is obvious for one reason, it does not become non-obvious merely because it has some non-obvious benefits (the "golden bonus"). While Barnes J cites his own prior Patanol decision, 2012 FC 410, this decision goes somewhat beyond Patanol. In Patanol the patentees had discovered the previously unknown mechanism of action of a known use for a known product, and Barnes J held that this could not support a new use patent. While this case does follow the same principle, it goes somewhat beyond Patanol in that the invention in this case was clearly novel.

This Bortezomib Formulation decision is a particularly good example of the golden bonus rule because on the facts, it was only after the inventors had the developed the formulation successfully (with ““a lot of whooping and hollering in the lab” [115]), that they realized that an ester had formed [116]. The formation of the ester was incidental to the invention. This is why the golden bonus rule makes sense. The point of the non-obviousness requirement is to ensure that patents are not granted for inventions that would have been developed even without the lure of a patent, and the consequent high prices. If the invention is desirable and easy to make without the golden bonus, then it does not get less desirable or more difficult when the golden bonus is unexpectedly realized. See also the evidence of Teva’s expert at [56.98-99] giving a good explanation of the logic of the golden bonus rule (without referring to it as such).

Note that in 2007 FC 455 [309-10], after adverting to a submission regarding the “golden bonus” holding from Hallen, Gauthier J remarked that she “is not convinced that all these principles apply in Canada.” However, the particular point she doubted was the argument that “if the person skilled in the art had many equally obvious choices, all courses of action that present themselves without the exercise of inventiveness are obvious.” That is quite a different proposition. See also 2007 FCA 217 [26].

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