Wednesday, March 27, 2013

Astrazeneca Canada Inc. v. Ranbaxy Pharmaceuticals Canada Inc.: Not So "Obvious to Try"

Wednesday, March 27, 2013
Earlier this week, the Federal Court granted Astrazeneca’s order prohibiting the Minister of Health from issuing a notice of compliance to Ranbaxy in relation to tableted dosage forms of the proton pump inhibitor, omeprazole until the expiry of Canadian Patent No. 2,170,647.

A copy of the decision can be found at the following link:

Omeprazole is used to treat gastroesophageal reflux disease (GERD) and other gastric ailments.

The only issue at question was whether Ranbaxy’s invalidity allegations were justified (see paragraph [2] of the FC decision) and in particular, was the subject matter of the claims of the ‘647 patent obvious in view of the prior art.

The question of obviousness was assessed using the four question analysis set out by the Supreme Court of Canada in Apotex Inc. v Sanofi-Synthelabo Canada Inc., 2008 SCC 61 at paragraph 67, [2008] 3 SCR 265:
(1) (a) Identify the notional “person skilled in the art”;  
(b) Identify the relevant common general knowledge of that person; 
(2) Identify the inventive concept of the claim in question or if that cannot readily be done, construe it;  
(3) Identify what, if any, differences exist between the matter cited as forming part of the “state of the art” and the inventive concept of the claim or the claim as construed;  
(4) Viewed without any knowledge of the alleged invention as claimed, do those differences constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention? (paragraph [11] of FC decision) 
The Parties were generally in agreement with respect to the answer to the first three questions with the inventive concept being the “formulation of a tablet of enteric coated pellets of omeprazole, whose pellets can retain their acid resistance after tablet compression”. (see paragraph [61] of the FC decision).

The main point of contention between the Parties was with respect to the fourth question. Astrazeneca argued “that the prior art would have directed the skilled person away from concluding that an acid sensitive drug, such as omeprazole, could have been formulated into a multiple unit tableted enteric dosage form.” (paragraph [16] of the FC decision). In contrast, Ranbaxy argued that the “person skilled in the art would view the making of a tablet formulation of enteric coated omeprazole pellets to be something that could be accomplished directly and without difficulty using routine formulation and optimization techniques known at the time”. (paragraph [33] of the FC decision).

The “obvious to try” test was considered appropriate in this case for assessing the fourth question. The Federal Court addressed the “obvious to try” test using the following questions as originally put forward in Sanofi-Synthelabo:
1. Is it more or less self-evident that what is being tried ought to work? Are there a finite number of identified predictable solutions known to persons skilled in the art?  
2. What is the extent, nature and amount of effort required to achieve the invention? Are routine trials carried out or is the experimentation prolonged and arduous, such that the trials would not be considered routine?  
3. Is there a motive provided in the prior art to find the solution the patent addresses? (paragraph [65] of FC decision) 
Several key facts were considered relevant to answering these questions, namely: ·

  • The experts “agree[d] that there are numerous variables which must be accounted for including: the amount of plasticizer, the composition of plasticizer, what coating agent should be used, what quantity of coating agent should be used, the size of the sub-unit, what external additives, the rate and magnitude of pressure applied during tabletting, the quantity and composition of cushioning material, and whether all of this complies with pharmacopeial standards.” (paragraph [68] of FC decision) · 
  • There was a 2011 paper that indicated “that as a result of the numerous considerations “…production of such a dosage form [is] technologically an extremely complex process.”” (see paragraph [72] of the FC decision) · 
  • Only five drugs that had gone to market in enteric coated pellet format. (see paragraphs [21] and [72] of FC decision) 

In view of the above, the Federal Court concluded that “the need for a solution is evident from the prior art; namely, an enteric coating suitable for dispersed omeprazole delivery, however, that solution is not provided for in the prior art. The prior art teaches away from the existence of such a solution or alternately indicates that such a solution is extremely complex and technically difficult to produce. Therefore, the enteric coating is not self-evident and so it is necessary to move on to the second stage of the “obvious to try” test.” (paragraph [70] of FC decision). The Federal Court further concluded that “facts point to a significant amount of effort required to obtain the desired result.” (paragraph [73] of the FC decision). The Federal Court appears to have found the 2011 article particularly persuasive noting in the decision that “[p]resumably manufacturing and drug delivery technology have advanced between 1994 [the priority date of the patent] and 2011. It is therefore reasonable to presume that in 1994, development of such dosage forms remained at least an extremely complex process.” From the decision, the expert for Ranbaxy appears to have dismissed this paper “due to its origin in Slovenia” (paragraph [20]).

As a Patent Agent I found the reliance on the 2011 paper particular interesting as it supports the use of post filing art to counter obviousness objections, however, such a strategy must be used cautiously to avoid calling into question enablement of the claimed invention. With respect to whether there was motivation in the prior art, the Federal Court noted that “[i]n the context of the “obvious to try” test, motivation disclosed in the prior patent would be indicative of a marketplace that would actively seek the (subsequently) patented solution. If other parties were motivated to find the solution and yet were unable or unwilling to do so prior to the patent being obtained, this factor would point to a solution that was not “obvious to try”.” (paragraph [82] of the FC decision)

By Claire Palmer