[Ip-health] Conservative ruling to uphold patent on Bayer's Yasmin (DSP+EE) in South Africa

Eduard Grebe ed at eduardgrebe.net
Fri Oct 3 07:23:47 PDT 2014


Dear All

Marcus Low alerted me to the attached judgment of South Africa's Supreme
Court of Appeal in the matter of Pharma Dynamics Pty Ltd. v Bayer Pharma
AG. The case arose from the appeal of a  successful patent infringement
suit filed against Pharma Dynamics (a South African generic distributor) by
Bayer over their product Ruby, which like Bayer's Yasmin contains the
combination of drospirenone (DSP) and ethinylstradiol (EE) as an oral
contaceptive.

Bayer's product has been the subject of a number of patent disputes in
other countries, including the UK and Australia, where the patent was
upheld, and the EU, where it was invalidated. In this case, the dispute
turned both on whether Pharma Dynamics's product in fact infringes the
patent in question and (as a counterclaim advanced by Pharma Dynamics)
whether the patent is in fact valid.

I am not an IP lawyer, but the judgment strikes me as extraordinarily
conservative (i.e. pro-patent-holder). While a number of issues arose, the
most striking aspect of the judgment is that the Court essentially
recognised the formulation of DSP without an enteric coating (i.e. in
rapidly soluble form) as a sufficiently inventive step to attract
patentability in terms of the South African Patents Act. The judgment
mentions that it has been known since the late 1960s that DSP+EE can be
used as an effective contraceptive. The inventive step in this case is
simply the 'counter-intuitive' 'discovery' that rapidly soluble DSP is
highly bioavailable and can be used in an oral tablet. On this matter the
litigants' expert witnesses are quoted as follows:

[22] In this light Prof Davies [Bayer's expert] contended that the
> invention covered by the patent is the following (p 2 137):
>
„The very fact that against all expectations for a drug which is poorly
> soluble such as drospirenone and which is acid labile, against all
> expectations that if you used a rapid dissolution, a formulation that
> achieves a rapid dissolution, as per claim 1 of the 2004 specification . .
> . what you get is good bioavailability, in other words, good absorption in
> vivo. That is against all expectation due to the acid lability of the drug.
> So that is the inventive step.‟

And at 2 504:
>
„There was a research proposal which they [the formulating team at Bayer]
> undertook, there was no expectation of success and they found to their
> surprise that they had a formulation which was rapidly dissolving on a
> poorly soluble acid labile compound good bioavailability in vivo against
> all experience, against all of the scientific knowledge that they had and
> we still cannot understand how it works. . . .‟

[23] Dr Rue [Pharma Dynamics's expert] disagreed. In his view the fact that
> a rapidly dissolving micronised form of DSP, known to be acid labile, would
> not in fact degrade in vivo would have been experimentally determined by
> the skilled formulator through in vivo tests performed as a matter of
> routine at an early stage of the development. The three arm test eventually
> conducted by Bayer, so he testified, should have been done as a matter of
> routine at an earlier stage. Had this been done, the „problem‟ contemplated
> by Bayer in the light of the in vitro results, would routinely have been
> established to be no real problem at all. His answer to Prof Davies‟ view
> that the invention, protected by the patent in suit served to resolve a
> particular problem was therefore in short that the skilled formulator would
> have known at an early stage that the perceived problem was not a real
> problem at all.


The Court accepted the first argument:

[38] As to the third inquiry contemplated in Ensign-Bickford, it appears to
> be common cause that the development of DSP as an oral contraceptive
> without an enteric coating went beyond and was a step different from the
> state of the art at the priority date. Dr Rue‟s thesis is that it fails the
> obvious test on the fourth step of the Ensign-Bickford inquiry, in that the
> taking of this step would be obvious to the skilled formulator after in
> vivo testing, which would have been done as a matter of routine. However,
> in evaluating Dr Rue‟s views, I believe they fall foul of at least two
> well- established principles in assessing obviousness. The first is that
> one must guard against the dangers of hindsight or ex post facto
> explanation of the invention (see eg Gentiruco AG v Firestone SA (Pty) Ltd
> 1972 (1) SA 589 (A) at 660G; Roman Roller CC & another v Speedmark Holdings
> (Pty) Ltd 1996 (1) SA 405 (A) at 418I-J). It is all too easy after the
> event and with the brilliance of hindsight, to say that a skilled
> formulator would have arrived at the invention earlier by doing an in vivo
> test.
>


[39] The second principle relates to Dr Rue‟s view that it would have been
> „obvious to try‟ uncoated DSP, as a matter of routine, in an in vivo test.
> The principle is, however, that before an invention will be found to be
> obvious on the „obvious to try‟ basis, it must be established by expert
> evidence that those skilled in the art would have carried out a test that
> led to the invention, not only because it was the obvious thing to do, but
> also because they would consider that a reasonable possibility existed that
> the test might lead to a useful result (see eg B-M Group (Pty) Ltd v
> Beecham Group Ltd 1978 BP 373 (T) at 405A-C). In this case it seems that,
> in the light of the in vitro results, the in vivo experiment that
> eventually led to the unsuspected invention did not seem to have the
> slightest hope of success before it was actually done.
>


[40] But what I find most unappealing about Dr Rue‟s theory is that it
> lacks any form of logical underpinning. It makes no sense for a formulator
> to take the time to do in vitro acid stability tests, and then to ignore
> the results by proceeding to carry out what are very expensive and
> time-consuming clinical trials on humans. What his proposition amounts to
> is that the skilled formulator would have conducted in vivo bioavailability
> tests regardless of the fact that he or she had no expectation that the
> formulation would not degrade in the stomach and therefore to take a step
> which was strongly contra-indicated. Stated somewhat differently: that the
> skilled formulator would disregard the considerable costs, delays and risks
> associated with carrying out in vivo tests in circumstances where the
> formulator had no expectation whatsoever that the test might lead to any
> useful result.


I leave it to others more versed in patent law to interrogate the judgment
further.

Best,
Eduard

-- 
Eduard Grebe, PhD
Centre for Social Science Research
University of Cape Town



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