Patently Confusing: Apotex

On Thursday, July 5, 2007, the Supreme Court of Canada (“SCC”) granted the application for leave to appeal in the case of Apotex Inc. v Sanofi-Synthelabo Canada Inc., 2006 FCA 421, an appeal from the Federal Court of Appeal. This intellectual property law case deals with the requirements for patent protection.

On April 28, 2003, Sanofi-Synthelabo Canada Inc. and Sanofi-Synthelabo commenced an application in the Federal Court. The application sought an order to prohibit the Minister of Health from issuing a Notice of Compliance (“NOC”) to Apotex Inc., in accordance with subsection 6(1) of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, with respect to its 75 mg clopidogrel bisulfate tablets until 2012, the expiration of Sanofi’s ‘777 Patent. This patent pertains to the invention of clopidogrel and its pharmaceutical compositions and preparation, as well as the invention of the bisulfate salt of the dextro-rotatory isomer, part of the compound of clopidogrel. Clopidogrel is part of a larger chemical compound, referred to as a racemate, which is a substance that contains equal amounts of two optical isomers, the levo-rotatory isomer and the dextro-rotatory isomer. The dextrorotatory isomer part of the compound, commonly referred to as clopidogrel, is more beneficial than the racemate and levo-rotatory isomer because it is better tolerated, less toxic, and contains all the platelet aggregation inhibiting activity.

Prior to Sanofi’s application in the Federal Court, Apotex attempted to obtain a Notice of Allegation (NOA) for a generic version of the Sanofi clopidogrel tablet, commercially referred to as Plavix. Apotex claimed in this NOA that sections 1, 3, 10, and 11 of the ‘777 Patent are invalid because of their anticipation by the ‘875 Patent, which was published on October 8, 1985. In the alternative, Apotex also claims that the above sections of the ‘777 Patent are invalid on the grounds of obviousness or double patenting. The Applications Judge found that the ‘777 Patent was valid, rejecting Apotex’s claims. He determined that the ‘777 Patent was not anticipated by prior art because the only replication that an ordinary skilled person skilled in the art who applied the teachings of the ‘875 Patent would be able to produce is the racemate, rather than the dextro-rotatory isomer. The ‘875 Patent did not explain how to separate a dextro-rotatory isomer of the racemate and found that the sections of the ‘777 Patent are not obvious, as chemists must first separate and test the optical isomer before determining which isomer contained the beneficial properties. The judge also held that the selection of the bisulfate salt was not obtained by following a prior patent, as there was sufficient inventive ingenuity, and hence, was not anticipated or obvious.

At the Federal Court of Appeal, Apotex’s appeal was dismissed and the Application Judge’s decision was found to be correct. While the appellant argued that there was anticipation by the ‘875 Patent, rendering the ‘777 Patent invalid because there was no “inventive step or skill,” the Federal Court of Appeal found that the ‘875 Patent did not specifically lead to the claimed invention as there are no references to methods for separating the isomers, leaving it impossible to know which procedure for separating the isomers will be effective. Apotex argued that a person skilled in the art would have knowledge of various methods for separating the isomers and through trial and error, would be able to eventually acquire the isomer. The Federal Court of Appeal agreed with the Application Judge’s finding that determination of clopidogrel consisted of months of thorough inquiry. The benefits of clopidogrel would be unknown prior to its production and testing, leaving it unable to be anticipated from following the ‘875 Patent. Further, Apotex claimed that the ordinary person skilled in the art would be led to the claimed invention through the ‘875 Patent’s teachings without error and in this case, the inventor of the compound was not a skilled person in the art, which would account for his difficulty in separating the isomer without error. The Federal Court of Appeal, however, dismissed Apotex’s argument, finding that the inventor was a person skilled in the art and stating that the prior patent was “lacking in clarity and direction for the separation of the isomers in question…despite Mr. Badorc’s (inventor) intuitive abilities, he was unable to replicate the experiment without difficulty and without error,” demonstrating that the allegation that ‘777 Patent is invalid based on anticipation is unfounded. Apotex also claimed that the invention, clopidogrel, and its benefits would be obvious to the person skilled in the art because isomer separation techniques were well known. The Federal Court of Appeal, however, repudiated this allegation and found that a person skilled in the art would not have been directed to the dextro-rotatory isomer of the racemate and its bisulfate salt or the pharmaceutical compositions without difficulty and error. Further, Apotex submitted that the ‘777 Patent was invalid for double patenting; however, the Federal Court of Appeal, for the same reasons as stated above, dismissed this claim as well, finding that the ‘875 Patent and the ‘777 Patent affirm “different and distinct compounds.”

While the scientific details are complex, this case deals with the ever-pressing issue of patent protection involving “selection patents.” Selection patents claim “an advantage for a compound within a previously disclosed class of compounds which has not been disclosed in the prior patent,” as described by Justice Noel. Unlike originating patents, which occur where there is “an originating invention involving the discover of a new reaction or a new compound,” selection patents build on previously known classes of products and discover a new special use or benefit from the product. In this particular circumstance, Apotex claimed that the ‘777 Patent was an invalid selection patent because it is within the ambit of the ‘875 Patent. As the pharmaceutical industry booms and drug companies increasingly attempt to develop and market products to a wide-range of consumers, selection patents, such as clopidogrel, can become a source of conflict among players in the pharmaceutical industry as selection patents may become confused with the originating patent and hence, labelled invalid. While selection patents exist to promote further research and inventive skills to discover new benefits for compounds within a known class, a new inventive step must be present, where a special advantage of one or more members of an existing category of products is uncovered which could not be predicted prior to the finding. Considering the murky grounds and potential for confusion, the SCC’s decision will be a source of clarification in this area.