Dr James Rowe has had over 30 years’ experience in the pharmaceutical industry. He obtained a Bachelor of Pharmacy degree in 1966, a Masters of Science in 1976, and a PhD in Pharmaceutics in 1980. He is also somewhat familiar with the inside of a courtroom. In 1998 and 1999 he gave evidence on behalf of generic manufacturer Alphapharm Pty Ltd, in a dispute with originating pharmaceutical manufacturer Aktiebolaget Hässle (a member of the Astra group, now AstraZeneca) over a patent covering the compound omeprazole, better known as heartburn drug Prilosec (or, in some markets, Losec).
The omeprazole case went on to become a leading authority on the law of inventive step in Australia, after it was successfully appealed by Astra to the High Court of Australia (Aktiebolaget Hässle v Alphapharm Pty Ltd  HCA 59).
This year Dr Rowe has again appeared in court on behalf of generic manufacturers – Generic Health Pty Ltd and Lupin Australia Pty Ltd – where it seems his past has come back to haunt him. In the decision in Bayer Pharma Aktiengesellschaft v Generic Health Pty Ltd (No 2), issued earlier this month, Justice Jagot concluded that Dr Rowe’s evidence was inconsistent with the evidence he had given in his 1998 affidavits in the omeprazole case, and that this tended ‘to undermine the weight which would otherwise be given to [his] evidence’.
There is a lesson in this for all litigants when selecting expert witnesses. It is natural that the opinions of a skilled professional might change over time, not least because new knowledge and experience may bring to light information that was not previously available. However, in this case the priority date of the Bayer patent was 31 August 1999, i.e. the critical date for assessing the claimed invention was contemporary with the time at which Dr Rowe gave evidence in the omeprazole case. And even though the omeprazole patent had a priority date in 1986, it seems to me that it should have been reasonably foreseeable that Dr Rowe’s earlier evidence would be used against him.
The Issue: Enteric CoatingsThe dispute between Bayer and the generic manufacturers Generic Health and Lupin relates to a patent covering an oral contraceptive comprising a pharmaceutical combination of ethinylestradiol and drospirenone (or DRSP). Bayer sells its products under the brand names Yasmin and Yaz in Australia. The generic respondents have been selling an oral contraceptive product under the name Isabelle since February 2012, which was said by Bayer to infringe the patent.
The reason that Dr Rowe’s evidence in the omeprazole case was highly pertinent to the present case is that in both instances the issue of whether or not the patents were valid depended, at least in part, on whether or not the use, or non-use, of an ‘enteric coating’ involved an inventive step. Dr Rowe gave evidence on this question in both cases.
At the risk of oversimplifying (you can read both cases if you need more detail) an enteric coating is an acid-resistant tablet coating which is designed to protect the active ingredient within the tablet as it passes through the stomach. Some compounds are degraded or destroyed in acidic environments, and of course the stomach is such an environment. The term for this sensitivity to acids is ‘acid labile’. Both omeprazole and DRSP are acid labile compounds.
In the omeprazole case, the claimed formulation included an enteric coat, such that the tablet would pass through the stomach, and the active ingredient would not be released until it reached the intestine. This involves delay, and can result in variability in the time of release and effectiveness of absorption. These are undesirable characteristics in an oral contraceptive, where the effectiveness of release must be highly consistent. I am sure I do not need to spell out the potential consequences if this is not the case!
The Yasmin and Isabelle products have no enteric coat. In this respect, the court summarised evidence given by Bayer’s expert, Professor Martyn Davies, as follows (at ):
As the development team would develop a formulation that they expect to work rather than one that they expect not to work, the obvious solution for DRSP would be to create an enteric coated formulation. Professor Davies said that the fact that the immediate release form of DRSP (as set out in the patent) works is very surprising and contradicts what we know about acid labile poorly soluble drugs. The expectation for DRSP, given that it is poorly soluble and acid labile, is that it could not be effectively delivered in an immediate release form.
The Problem with Dr Rowe’s EvidenceIn 1998 and 1999, Dr Rowe gave evidence to the effect that, in 1986, it would have been obvious for a formulation chemist to apply an enteric coating to a tablet containing an acid labile compound (omeprazole) as the active ingredient.
In 2012 and 2013, Dr Rowe gave evidence to the effect that, in 1999, it would have been obvious to first attempt a formulation without an enteric coating, despite having knowledge that the active ingredient (DRSP) is a poorly-soluble acid labile compound.
Of course there are differences in the circumstances of each case, including the passage of time, and the other properties of the compounds involved. It may well be that these two positions are not, in the particular circumstances of this case, as incompatible as they first appear. But if that is so, the onus was upon Dr Rowe, particularly when questioned on the inconsistencies in cross-examination, to provide a convincing explanation for his apparent change of position.
At paragraphs  to  of the Bayer decision, Justice Jagot sets out three reasons why she found Dr Rowe’s explanations to be unconvincing:
- in his 1998 evidence, Dr Rowe described erythromycin (also an acid labile compound) as being ‘usually formulated’ with an enteric coat, whereas his recent evidence gave the distinct impression that it is usually not enteric coated;
- in 1998 he described the use of an enteric coated dosage form for omeprazole as ‘ideal’. without mention of problems such as the risk of dose-dumping and large variability, whereas in the case of DRSP his evidence was to the effect that an enteric coating would cause the type of problems which he earlier said an enteric coating would resolve; and
- in 1998, Dr Rowe had described the use of an enteric coating as ‘simple’, ‘conventional’, ‘obvious’ and ‘routine’, whereas his recent evidence described enteric coating as a more complex process which would lead him to ‘explore all other formulation possibilities thoroughly rather than resorting to enteric coating.’
ConclusionArguably, the Australian courts have been no less inconsistent than Dr Rowe, rejecting his seemingly contradictory evidence on both occasions. This is, perhaps, an issue which we may see raised in the inevitable appeal.
But even so, presenting expert evidence that is vulnerable to this kind of challenge seems like an unnecessary risk. No doubt the generic defendants believed that they had this adequately covered, but it is an argument that could have been avoided altogether if Dr Rowe had not been called upon as an expert witness.
Of course, every case is different, and the benefits of having the best-qualified experts providing evidence must always be weighed up against any potential disadvantages of calling a particular witness. It is almost inevitable that ‘professional’ experts will be called upon repeatedly in highly specialised areas of technology, in which the choice of appropriately experienced and skilled people is limited.
It is not, therefore, a question of there being any firm rules, or any ‘right’ answer. What can be taken from this judgment, however, is the observation that the past history of an expert as a witness in other matters is always a relevant consideration when preparing evidence.
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