INNsight articles by Duncan Curley

Yasmin® is an oral contraceptive pill containing two steroidal hormones, ethinylestradiol and drospirenone.  It is marketed by Bayer Schering Pharma AG (“Bayer”) for the prevention of pregnancy in women.  Yasmin® is one of a number of birth-control products of Bayer, which together recorded worldwide sales of approximately $1.56 billion in 2010.

Two European patents claim the combination of ethinylestradiol and drospirenone for use as a contraceptive and protect pharmaceutical compositions containing this combination. They are European patent nos. 1,380,301 B1 and 1,598,069 B1.  Both patents are presently under opposition at the European Patent Office (“the EPO”); the opponents include Teva, Sandoz and Gideon Richter (“Richter”).  Despite the existence of the opposition proceedings at the EPO, Richter decided to initiate a separate challenge to the validity of both patents in nullity proceedings brought before the English Patents Court.  Richter’s case was issued at the end of October 2009.  Richter put forward two lines of attack on the validity of each patent: added subject matter and obviousness.  The case came on for a six day trial before Mr Justice Floyd in February 2011 and judgment was given on validity of both patents on 17 March 2011, so that the time from issue of the claim to judgment at first instance was approximately 15½ months, which is about average for patent cases of medium complexity brought before the English Patents Court.

The Judge addressed first the attack based on added subject matter (“added matter”).  Section 72(1)(d) of the UK Patents Act 1977 provides that the court can revoke a patent for an invention on the ground that the subject matter disclosed in the patent specification extends beyond that disclosed in the application for the patent, as filed.  Assessing whether subject matter has been added between the filing of the patent application and the patent as granted is a highly technical objection to validity.  It requires a forensic examination of the technical content of the patent application as filed compared to that contained in the granted patent.

Added matter is not always available as a ground of attack on validity in the national courts, because it tends to be dealt with comprehensively during prosecution of the relevant patent, usually in the context of amendments that are proposed by the applicant in order to address objections raised by the EPO’s Examining Division.  However, a famous victory for generic companies on the subject of added matter was the UK clarithromycin case (Abbott Laboratories v Ranbaxy UK and others).  Following the expiry of a supplementary protection certificate to clarithromycin based on the original product patent (that had also expired), Abbott attempted to assert another patent claiming a solvent free crystalline form of clarithromycin against a series of potential generic entrants to the UK market. The patent application for the crystalline form contained no claim to the solvent free compound. The Judge in that case (Pumfrey, J.) readily accepted that the claim in the granted patent to solvent free crystalline clarithromycin constituted additional subject matter and the patent was revoked. 
 
The clarithromycin case was clearcut, but there may be grey areas, because a patent application is taken to disclose anything that is implicit, in the sense that it is an inevitable consequence of carrying out the explicit disclosure contained in the patent application.  Sometimes therefore, the demarcation between what constitutes added matter and what constitutes implicit disclosure is not always clear.  Evidence from a suitably-qualified expert may be required, both on the technical meaning of added or altered wording (and what those words imply) and the effect of a deletion of words on the technical content of the patent.  It is worth noting that, as a general proposition, when assessing whether to run a case based on added matter, unless the case is clearcut (as in the clarithromycin case), it may be difficult to persuade a Judge to revoke a patent on the basis of highly technical objections that require a “spin” on words that is potentially unfair to the patentee.
 
Richter made a number of objections based on added matter, but all except one failed in the English nullity case (and the one that succeeded was overcome by Bayer by offering an amendment).  It is useful to look more carefully at the main objection, because it demonstrates the approach of the English courts in interpreting the disclosure of the patent application and the granted patent in a way that is fair to the patentee, when assessing whether matter has been added. 

Richter asserted that the disclosure of the patent application (PCT application WO 01/15701) was that good bioavailability of drospirenone may be obtained only by micronising/spraying.  Richter contended that the granted ‘301 patent taught that good bioavailability could be obtained by any method which produces rapid dissolution.  The relevant disclosure in the patent application was as follows:

“Drospirenone, which may be prepared substantially as described in, e.g., US 4,129,564 or WO 98/06738, is a sparingly soluble substance in water and aqueous buffers at various pH values.  Furthermore, drospirenone is rearranged to an inactive isomer under acid conditions and hydrolysed under alkaline conditions.  To ensure good availability of the compound, it is therefore advantageously provided in a form that promotes rapid dissolution thereof. 

[…]

Without wishing to be limited to any particular theory, it appears that the in vitro dissolution rate of drospirenone is connected to the dissolution rate in vivo resulting in rapid adsorption of drospirenone in vivo on oral administration of the compound.  This is an advantage because isomerization of the compound in the gastric environment and/or hydrolysis in the intestine is substantially reduced, leading to a high bioavailability of the compound”.

These paragraphs were carried through into the patent as granted.

The Judge held that the first paragraph (above) made it clear that the patentee considered that it would be advantageous to formulate the product in a form that promoted rapid dissolution.  This suggestion in the patent application was a general one; it was not linked to a specific way of achieving rapid dissolution.  Furthermore, the second paragraph (above) was stated in general terms.  It did not limit the disclosure in the patent application to a specific technique for promoting dissolution (such as micronising/spraying).  The Judge concluded that it would be implicit to the skilled person - reading the application sensibly - that any method of arriving at a formulation which achieved rapid dissolution would serve.  Since the application taught that good bioavailability could be obtained by any formulation that gives rapid dissolution, matter had not been added in the granted patent specification.

In addition to its other added matter attacks, Richter also ran a nullity case based on obviousness over four items of prior art.  In 2008, Barr Laboratories Inc. had scored a victory over Bayer by running obviousness in an invalidity case in the USA in relation to the patent protection around the Yasmin® product.  The Judge in the English case was shown the judgment of the U.S. Court of Appeals of the Federal Circuit, but he was unimpressed.  Richter could not replicate Teva’s success before the English Patents Court in relation to obviousness and all of its attacks were dismissed.  The U.S. decision was held to be of no assistance, because it was reached on the basis of different evidence. 

The next phase of the battle over the patents protecting Yasmin® in Europe will now be the hearing before the EPO’s Opposition Division in relation to the ‘301 patent.  This hearing is scheduled to take place in Munich on the 1st of December 2011.