On November 27, 2014, Justice Barnes dismissed the first of two of Janssen’s prohibition applications in respect of Teva’s generic version of the multiple myeloma drug VELCADE, this application dealing with Canadian Patent No. 2,435,146.
The 146 Patent generally relates to a genus of boronic acid and ester compounds, including bortezomib, that are inhibitors of certain proteolytic enzymes and are useful in the treatment of multiple myeloma. Having found that bortezomib was unstable in solution, the inventors lyophilized (freeze-dried) bortezomib using mannitol as a bulking agent and found the resulting composition to be stable and reconstitutable in water. Analysis of the lyophilized product revealed that the bortezomib had reacted with the mannitol to form an ester.
Claim 30 covered the compound bortezomib in the form of the lyophilized mannitol ester.
Person skilled in the art
Janssen argued that the person skilled in the art was a formulation scientist who would not appreciate that bortezomib and mannitol would react to form an ester and would ignore prior art references describing the chemistry of bortezomib and. Justice Barnes rejected Janssen’s argument that the person skilled in the art can be defined by considering claim 30 in isolation, holding that the person of skill may be a character of composite skills, and must be capable of understanding the entirety of the patent. Because the patent speaks to matters of chemical synthesis in addition to formulation, the person skilled in the art has the composite expertise of a formulator and a medicinal chemist. Such a skilled person would not embark on the task of formulating bortezomib without regard to the available knowledge of its chemical properties.
Faced with a compound that was unstable in solution, the person of skill would immediately consider a solid state formulation for which lyophilization was one of two well-known options. Mannitol was a commonly used bulking agent for freeze-dried formulations and was a likely choice. The choice of a routinely used stabilizing method and the selection of a routinely used bulking agent cannot be said to be inventive. The fact that the formulator had a few choices to make and would need to test the formulation to ensure its efficacy does not render the exercise non-obvious.
Janssen argued that the invention could not be obvious because one of the named inventors was unaware that he had created an ester when he lyophilized bortezomib with mannitol. Justice Barnes rejected this argument, holding that the inventor had obtained a workable formulation, and the later characterization of the compound by others did not add anything inventive to what had already been discovered.
Teva was represented by Aitken Klee LLP.
A copy of Justice Barnes’ Reasons for Judgment can be found here.