The High Court of Malaya dismissed both the plaintiffs’ claim and defendants’ counterclaim with costs in an action filed by Sanofi-Aventis against Fresenius Kabi for alleged infringement of a patent for an anti-cancer drug.

In Sanofi-Aventis (Malaysia) Sdn Bhd & Anor v. Fresenius Kabi (Malaysia) Sdn Bhd & Anor, the High Court of Malaya has dismissed both Sanofi-Aventis’ claim and Fresenius Kabi’s counterclaim over the alleged infringment of Sanofi-Aventis’ Malaysian patent MY-118481-A for an anti-cancer drug called Taxotere.

The Aventis patent is directed to a process for the manufacture of docetaxel trihydrate, which is an active ingredient in Taxotere. Docetaxel trihydrate is also an active ingredient in a drug called Daxotel which is manufactured by the second defendant in India by a process (the Dabur process) which was patented (the Dabur patent). The second defendant exported the drug to Malaysia for marketing, distribution and sale through the first defendant, which was the marketing authorization holder of the drug. The plaintiffs asserted that the process claimed in the Dabur patent infringed the process in the Aventis patent and sought declarations for alleged infringement, delivery of all of the defendants’ products and for damages. In response to the said action, the defendants disputed the claim and filed a counterclaim arguing that the Aventis patent was invalid for lack of novelty and/or inventive step pursuant to Section 56(2)(a) of the Patent Act of 1983.

The Aventis patent claims the process for the preparation of docetaxel trihydrate, which comprises crystallizing docetaxel from a mixture of water and an aliphatic alcohol containing one to three carbon atoms, and then drying the product obtained under defined conditions of temperature, pressure and humidity.

The defendants admitted that the active ingredient of their product is also docetaxel trihydrate. However, the plaintiffs claimed that the Dabur process infringed the scope of the claims of the Aventis patent.

In order to support the arguments that were put forward, expert evidence was presented by the plaintiffs and the defendants. The plaintiffs called three expert witnesses while the defendants called six expert witnesses. The issues in the action were as follows:

1. whether the defendants’ use of the process claimed in the Dabur patent infringed the process claimed in the Aventis patent;

2. whether the defendants had infringed or would infringe the Aventis patent, respectively, through its previous or its potential future importation, marketing, distribution, use, sale and/or offer for sale of Daxotel in Malaysia; and

3. whether the Aventis patent was valid.

Infringement Action

In the case, the plaintiffs alleged that Daxotel was produced by a process that infringed the Aventis patent. As provided for in Section 36(3)(a)(ii) read with Section 58 of the 1983 Patent Act of Malaysia, patent infringement is committed if a product is obtained by means of a patented process.

In order to decide on infringement, the court construed the claims of the Aventis Patent and then analyzed the defendants’ Dabur process.

The Aventis Patent

The Aventis patent discloses a process for producing docetaxel trihydrate. Docetaxel has anti-cancer properties.

In order to produce the trihydrate form of docetaxel, purified docetaxel is dissolved in a solvent, e.g. ethanol (C2 alcohol) or alcohol containing 1-3 carbon atoms. Water is then added to the dissolved docetaxel, and docetaxel is recrystallized from this mixture of solvent and water. Finally, the product crystallized out is then dried under defined conditions of temperature, pressure and humidity to produce the trihydrate form.

The Dabur Process

The defendants claimed that the process for the manufacture of Daxotel is described in the Dabur patent, which comprises three steps. Step 1 involves purifying crude taxane (which includes docetaxel) by adding the crude compound to a mixture of chlorinated alkane, stirring the mixture, filtering the same under a vacuum, and repeating again. Step 2 involves purifying further the taxane obtained from Step 1 by dissolving it in alkyl ketone, cooling, filtering, further adding an alkane and slowly stirring the mixture, filtering further and drying the material under a vacuum. Lastly, Step 3 states that “the taxane obtained in Step 2 is dissolved in an aliphatic nitrile, most preferably acetonitrile… at 50-70°[Celsius]. To this solution, purified water… is added slowly and then the mixture is stirred further at 10-25° C for 2-4 hours. The precipitated material is filtered and then dried at 35-45°C under 650-700 mm mercury vacuum for 36-40 hours with powdering at regular intervals under relative humidity [pf] 80-90%.”

Court Decision on the Infringement Action

After construing the claims of the Aventis patent by reference to the test in the Catnic case and applying the Improver Questions, the court decided the following:

1. The Dabur process, which uses acetonitrile as the organic solvent (not C1 to C3 alcohols), does not infringe the Aventis patent.

2. The Dabur process does not infringe the Aventis patent because the former does not control humidity and has a widely different pressure.

3. The Dabur process uses precipitation and not crystallization.

The court concluded that the Dabur process of the defendants was innovative and discovered a new process for the production of docetaxel trihydrate using acetonitrile as a solvent.

Validity of the Aventis Patent

In response to the infringement action filed by the plaintiffs, the defendants filed a counterclaim. The defendants alleged that the claims of the Aventis patent were not novel in that the claims were anticipated by Holton, US Patent No. 5229526 entitled “Metal Alkoxides,” and the corresponding Malaysian patents, i.e. Malaysian Patent Numbers MY-128181-A and MY-109876-A of Florida State University (the Holton patents). Hence, the claims of the Aventis patent allegedly did not comply with Section 14 of the Patents Act.

The defendants also alleged that the Aventis claims were not inventive in view of the Holton patents. Hence, the claims of the Aventis patent allegedly did not comply with Section 15 of the Patents Act.

Court Decision on the Validity of the Aventis Patent

The court rejected the arguments of the defendants that the Aventis patent lacked novelty. The court concluded that the person skilled in the art who read the Holton patents would not be led to perform a process that produces docetaxel trihydrate as there are no conditions specified for either the crystallization or the drying stage. Hence, the claims of the Aventis patent were novel.

Moreover, the court rejected the arguments of the defendants that there was a lack of inventive step for the Aventis patent. The Holton patents disclose that Docetaxel could be crystallized from methanol and water and that there were four possibilities of what would form. However, there was no condition for drying disclosed in the Holton patents. Hence, the claims of the Aventis patent involved an inventive step.

Conclusion

The court decided that the Aventis patent did not embrace the same process as the Dabur patent. Hence, the Dabur process did not infringe the Aventis patent. The court also decided that the Aventis patent was not invalid for lack of novelty and inventiveness. Hence, the defendants’ counterclaim was dismissed with costs. The case was interesting because the patents concerned were both process patents, and the Malaysian Patents Act, which suggested that infringement includes obtaining a product by means of a patented process, did not help the plaintiffs; the defendants’ process claim was still patentable.