114 Given that this is in Dr Broesamle's handwriting this document confirms that he was considering the dosage range for DRSP for contraceptive and hormonal replacement therapy purposes. Given the similarity between this and the document above I infer that they are notes of the same meeting. I thus infer that Dr Broesamle was considering 2 to 4mg or 3mg as the dosage range for DRSP for contraceptive purposes for optimum effect and side effect (which must mean minimised) level.
115 The next document is a letter from P&V to Dr Ulrich and Dr Broesamle dated 14 January 1999 which thanks them for a "pleasant and interesting meeting in Berlin on 14 January 1998 [sic]". The letter continues:
We look forward to cooperating with your [sic] regarding the drawing up of a new patent application and expect to receive further material from you by the end of January.
116 I thus infer that the handwritten notes relate to a meeting between Dr Broesamle, Dr Ulrich and P&V and that at that meeting Dr Broesamle informed P&V of his consideration of the possible dosage for DRSP for contraceptive purposes for optimum effect and side effect level to be 2 to 4mg or 3mg. I infer this because, as the patent attorneys agreed, it is essentially a matter for the client to instruct the patent attorney about such matters as dosage range, and Dr Broesamle was the representative of the client. From this, it must also be inferred that Dr Broesamle was aware of some or perhaps all of Schering AG's research about DRSP. He could not have considered any range in a vacuum and Schering AG had already carried out substantial research about, and obtained other patents involving, DRSP. Dr Broesamle's handwritten notes contain other details which are inconsistent with any inference other than that as at 14 January 1999 Dr Broesamle was well aware of DRSP, its, solubility, operation, and potential dosage levels for optimum contraceptive effect and side effect levels. As noted, given his responsibility for fertility and hormone patents, the inference I would draw is that, as any competent patent attorney would, he familiarised himself with the information available within Schering AG about DRSP (and EE) as part of the briefing of P&V.
117 There is a facsimile from Schering AG (copied to Dr Ulrich, Dr Broesamle, Dr Heil, Dr Lipp and Mr Hilmann amongst others) to P&V dated 18 January 1999 enclosing the list summarising "open questions" dated 13 November 1998 and the material needed to answer those questions in order to prepare a first draft (I infer, of the priority documents) and a statement that Schering AG will try to provide this information to P&V by the end of the month.
118 On 17 March 1999, P&V sent a letter to Dr Ulrich and Dr Broesamle about the "Patent application for DRSP" enclosing a first draft of the specification including claims and ending with the statement:
We are looking forward to further discussions with you on this matter. In particular, your comments on the claims as well as our questions will be greatly appreciated.
119 Given the detail already within the first draft of the specification and the questions posed by P&V, I infer that Schering AG must have sent to P&V a considerable amount of material relevant to the proposed patent application, consistent with the terms of the 14 January 1999 letter.
120 The draft specification includes the following:
The claimed pharmaceutical composition is novel because it cites a narrower dosage range than that indicated in the prior art. The lower limit has been set to 2 mg per dosage unit/day because it is indicated to be the lowest dosage required to obtain ovulation inhibition. The upper limit has arbitrarily been set at 5 mg per dosage unit. Is that realistic, or could the limit be higher without causing adverse effects? What are the adverse effect[s] at higher doses?
This dosage level has been found to be particularly advantageous for the purposes of contraception as well as for other therapeutic uses. Is this correct, or are the indicated dosage levels inappropriate for the therapeutic uses of the compound?
121 The draft claims include as claim 1:
A pharmaceutical composition comprising, as an active agent, 6β, 7β; 15β, 16β-dimethylene-3-oxo-17α-pregn-4-ene-21, 17-carbolactone (drospirenone) together with one or more pharmaceutically acceptable carriers or excipients, the amount of drospirenone corresponding to a daily dosage, on administration of the composition, of from about 2 mg to about 5 mg (what is a suitable upper limit of the dosage - that is, one at which the severity of adverse effects is not prohibitive?).
122 From this I infer that P&V had considered the material about DRSP which had been provided to them and was querying whether the dosage range of DRSP could be more than 4mg (as Schering AG had indicated in the 14 January 1999 meeting) and up to 5mg without causing adverse side effects. No question was raised about the lower, 2mg, dosage range. From this I infer that, having reviewed the available material, P&V accepted what had been discussed with Schering AG on 14 January 1999, that 2mg was the lowest dose for optimum therapeutic effect for contraceptive purposes, but queried whether the maximum dosage range which could be claimed was 4mg as had been discussed or could be 5mg or more without adverse side effects.
123 On 26 August 1999 P&V sent a letter to Dr Ulrich which thanked Dr Ulrich for a fax with "details regarding DRSP". This is the fax which has not been found. The letter asked for comments on the draft claims. Draft claim 1 refers to a dosage for DRSP from about 2mg to about 4mg.
124 From this it is clear that Dr Ulrich had sent to P&V further information about DRSP. It is also apparent that either in discussions or in the fax from Dr Ulrich, Schering AG had instructed P&V that the dosage range for DRSP which was to be claimed was about 2 to about 4mg. As the patent attorneys said, P&V would not have taken it upon itself to make this decision. I also do not infer that Dr Ulrich was responsible for making this decision. In accordance with the discussion above, it was Dr Broesamle, in consultation with the Head of Patents and Licensing, who was responsible for deciding what P&V should be instructed. Even if the instruction was contained in the missing fax, Dr Ulrich would have been conveying instructions upon which Dr Broesamle, in consultation with the Head of Patents and Licensing, had decided. I also have no difficulty inferring that the instruction was given with the objective of achieving an optimal therapeutic effect and to minimise side effects, consistent with the objectives which had been discussed between Schering AG and P&V since 14 January 1999. Given the contemporaneous references to optimal therapeutic effect and optimal (minimal) side effects, and the question raised by P&V about a possible 5mg dosage for the upper end of the range in the context of side effects, I consider that there is no reason to infer other than that Schering AG gave this instruction to P&V honestly believing that the instructed range would achieve these objectives. To infer otherwise, would suggest that Schering AG and P&V were in the business of making inaccurate and misleading contemporary notes of their discussions, in effect, identifying objectives of the dosage range which neither of them believed they were seeking to achieve in the patent specification and claims. This is nonsensical.
125 On 30 August 1999 Dr Ulrich sent to P&V the draft specification for the priority documents which said it enclosed "our comments" (not, I note, "my comments"). This is consistent with my conclusions above that Dr Ulrich was not the relevant decision-maker. While involved in the process, she was communicating the comments of Schering AG which, as I infer, Dr Broesamle authorised, given his role. The comments written on the draft specification include details about prior Schering AG patents (which, as I would expect, means that those involved in preparing the priority documents for the PCT application knew the details of those earlier patents and, necessarily given the detail of the comments, the research which underlay those patents), the dissolution test (discussed below) and other matters. There is no comment, however, about the range of DRSP in claim 1 (or otherwise) of 2 to 4mg. From this I infer that Schering AG was satisfied that the 2 to 4mg range for DRSP was appropriate and fulfilled the initially identified objectives of optimum therapeutic effect and optimum (meaning minimal) side effects.
126 In February 2002 P&V instructed FB Rice & Co, patent attorneys, to prepare the Australian patent application based on the priority documents (which had been filed on 31 August 1999) and the PCT application. Dr Warner of FB Rice & Co amended the claims in accordance with her usual practice to ensure satisfaction of the requirements of Australian patents law. FB Rice & Co filed the Australian patent application on 14 March 2002. Davies Collison Cave took over the Australian patent application from FB Rice & Co thereafter as Bayer had decided to consolidate its pharmaceutical patent portfolio in Australia. The patent, as noted, was granted on 30 June 2005.
127 At least insofar as the 2 to 4mg dosage range is concerned (and perhaps otherwise as well) there is no suggestion that the preparation, filing or prosecution of the Australian patent (in contrast to the PCT application and the priority documents on which it was based) was itself carried out other than in good faith and on the basis of reasonable skill and knowledge. No such suggestion could be made given the evidence. As Bayer submitted:
Dr Jacqueline Warner also gave written and oral evidence. Dr Warner is an Associate at FB Rice and a Registered Patent Attorney. Dr Warner obtained a PhD in 1993 from the University of Sydney after graduating from the University of Sydney in 1988 with a First Class Honours Degree in Science, double majoring in organic chemistry.
Dr Warner's PhD involved research on biosynthetic models for the formation of naturally occurring anti-malarial and prostaglandin-like compounds. Dr Warner did post doctoral research in the organic chemistry department at Cambridge University, England on the topic of mannosidase inhibitors for use in enzyme purification.
In 1996, Dr Warner completed a Graduate Diploma in Legal Studies at the University of Technology in Sydney and in 2000 qualified as an Australian patent attorney. Dr Warner works in all areas of chemistry, including pharmaceutical chemistry.
Dr Warner was responsible for the prosecution of the Australian application from about February 2002 to March 2003.
Dr Warner considers that she handled the prosecution of the Application in good faith with all due skill and knowledge in accordance with accepted Australian patent attorney practice. Dr Warner was also, at all relevant times, well qualified to handle the prosecution of the Application in Australia.
128 Insofar as Davies Collison Cave are concerned:
Mr Mark Roberts gave written and oral evidence. Mr Roberts has been a principal of Davies Collison Cave Patent and Trade Mark attorneys since 2002. Mr Roberts has a first class Honours Bachelor of Science degree. His honours studies were in the field of molecular radiation biology at the Peter MacCallum Cancer Institute.
Although Mr Roberts joined DCC as a technical assistant in the chemical/ biotechnology group in 1994, he also has experience in the pharmaceutical industry. In 1998 Mr Roberts undertook a month's work experience in the Corporate Patent department of BASF Algin Germany. From 1998 to 1999 Mr Roberts was employed as a patent advisor within the Global IP department at Glaxo Wellcome PLC in the UK. In that role Mr Roberts was involved in the preparation and prosecution of European patent applications.
As a principal at DCC, Mr Roberts specialises in the drafting, preparation and prosecution of patent applications, including for patents for pharmaceutical inventions. As a result of his time at BASF and Glaxo Wellcome, Mr Roberts has a knowledge and understanding of European patent law and practice.
Mr Roberts briefly handled the prosecution of the Australian patent in the late Dr Peter Stearne's absence in late 2004, including by preparing and sending a detailed response to the examination report that was issued by the APO in relation to the Patent Application, which ultimately led to acceptance of the Application.
It is Mr Roberts' opinion that the Australian application was framed in good faith and with reasonable skill and knowledge and prosecuted by appropriately qualified attorneys with all reasonable care and skill and in accordance with accepted and usual Australian patent attorney practice.
129 Otherwise, as Bayer submitted about Dr McCann's evidence relating to the actions of the Australian patent attorneys:
(a) the Australian Application was at all times prosecuted by registered Australian patent attorneys with a scientific background appropriate for the subject matter of the Patent, namely Dr Jacqueline Warner, the late Dr Peter Stearne and Mr Mark Roberts, and that the Australian attorneys all possessed more than sufficient skill and knowledge to prosecute the Australian Application;
(b) those involved in the prosecution of the Australian Application did not take a course of action that would have been inconsistent with Australian practice in 2002 to 2004 in an effort to obtain claims of a wider breadth than what they would otherwise fairly be entitled to;
(c) the professionals involved in the drafting and prosecution of the Australian Application acted fairly, reasonably and sought to obtain, in good faith, the scope of protection for which Bayer was entitled….
130 Having regard to these matters it will be apparent that I do not accept the overall approach of Generic Health to the documents. Generic Health's approach seems to be to assume that Schering AG did not intend to identify a range which would meet the objectives of optimum therapeutic effect and minimal side effects. Generic Health's approach is disclosed by its submissions about the note containing the statements:
(a) Amount of drospirenone (and estradiol) for therap. effect (contraceptive without increased blood pressure).
(b) quick release in gastiric environ of sparingly sol.subst…
…
upper limit? (side effects?)
amount of drospirenone: 2-4mg, eg 2.5-3.5mg,
131 Generic Health made this submission:
Generic Health submits that this involves a reference to the possibility of adverse side effects at a dosage of 4 mg and that the inference that should be drawn is that the author, likely someone involved in the "framing" process, harboured concerns about the side effects arising from a dosage of 4 mg.
132 A more natural reading of the notes is that 4mg was being considered as the upper limit at which side effects might be largely avoided. This reading is consistent with the subsequent P&V draft (see below) which raised the upper limit, arbitrarily, to 5mg and asked Schering AG if that would involve side effects. The fact that the next version of the specification went back to 4mg strongly suggests that Schering AG instructed P&V that the upper limit to achieve its object of minimal side effects was 4mg, not 5mg.
133 Generic Health dismissed the other notes as nothing more than "records of a discussion about different compositions". The documents are more than this. They show active consideration of a dosage range to achieve the stated objectives of optimum therapeutic effect and minimal side effects.
134 The fact, which I accept, that Schering AG had not reached a concluded view about at least the upper dosage range by the time of the 14 January 1999 meeting (in the sense that it considered P&V's arbitrary upper range of 5mg thereafter) is beside the point. It is plain Schering AG did reach that view before any patent application was lodged because it must be inferred that Schering AG made P&V change the maximum dosage back to 4mg. And why might Schering AG have done so? For the obvious reason that it believed that the dosage range of 2 to 4mg satisfied its stated objectives of optimum therapeutic effect and minimal side effects. Accordingly, I find unpersuasive Generic Health's submission that:
…it can be inferred that the upper limit of 4 mg was selected some time between 17 March 1999 and 26 August 1999, albeit by persons unknown and for reasons unknown.
135 The persons who decided are not unknown. They must have been Dr Broesamle in consultation with the Head of Patents and Licensing because there was no challenge to Dr Broesamle's evidence that this was how all final decisions about the patent family were made. The reasons for the decision are not unknown. The reasons must have been to achieve the identified objectives of optimum therapeutic effect and minimal side effects because these were the only objectives for the range identified.
136 Similarly, the fact that side effects are not expressly referred to in the inventor's typed notes of 13 November 1998 does not mean that the dosage range of 0.5 to 7mg was recorded without any regard at all to possible side effects. Schering AG had been researching DRSP and EE for many years and had carried out multiple studies of its effects. While Schering AG did not select this range of 0.5 to 7.0mg for the Yasmin patents family, I infer that this was because it did not achieve the goals of optimum therapeutic effect and minimal side effects in the context of contraception. It cannot be inferred, as Generic Health would have it, that this range was merely arbitrary. Given all the work that had been done, no such inference would be drawn about any range proposed by Schering AG in this period.
137 Other documents which pre-date the PCT application: As noted above, it is apparent that Schering AG provided P&V with information about DRSP on at least two occasions, before 17 March 1999 and 26 August 1999 respectively. I would infer that, at the least, the material provided to P&V included the five reports which Schering had included in the table it prepared in August 1998. It is obvious from the documents referred to above that Schering AG considered those reports in the context of the preparation of the priority documents and the PCT application. The P&V patent attorneys involved were themselves highly qualified chemists with specialist expertise in the preparation of pharmaceutical patents. They must have had access to substantial information about DRSP to prepare even the first draft of the specification. It is rational to infer that this information included these reports which Schering AG had identified as relevant to DRSP only a few months before P&V were instructed. The information also necessarily included the earlier patents referred to in the specification itself, considered separately below.
138 There is one other report which must be considered. It is report No. 9274 entitled "PK/PD study of the combination DRSP/EE after repeated oral administration" dated 1 July 1993, which relates to 2mg and 4mg formulations of DRSP (the 9274 report). This document is an internal Schering AG document consisting of multiple "fly sheets". Generic Health submitted that the 9274 report cannot shed any light on the s 115(1)(a) issue because there is no proof that it was relied upon (or even known to) those involved in the framing of the patent, and in particular those involved in the selection of the 4mg upper limit. I disagree. While I accept that Dr Broesamle does not explain where or how he located the report, this has to be weighed along with a number of other factors. The report records a trial conducted by Schering AG. The report, on its face, discloses the existence of a sophisticated system for information control and retention. For example, the report is signed by multiple persons in respect of compliance with specific study standards and quality assurance requirements. The report records that the clinical study, which it summarises, took place over many years and was subject to quality assurance audits on no less than six occasions between 12 December 1989 and 2 June 1993. The report records how many pages it contains in total (185) and the extracts available are consecutively page numbered. The clinical study with which the report is concerned was a randomised double-blind study comparing two doses of DRSP and EE with Microgynon, a commercially available contraceptive. As such, the clinical study must have involved more than a trivial cost to Schering AG. Schering AG was in the business of developing innovator pharmaceutical products. Patent protection is an integral part of that business. Against these factors (which would weigh against the report having been overlooked for the Yasmin patent), is to be weighed the lack of direct evidence about the relevance of the 9274 report to the preparation of the patent and its absence from the table and handwritten notes discussed above (which refer to the other reports).
139 Importantly, the 9274 report deals expressly with the aldosterone antagonist effect of DRSP. The patent also refers to DRSP being an "aldosterone antagonist" which has diuretic properties and "is therefore suitable for counteracting the water-retentive properties of ethinylestradiol".
140 While, unfortunately, there is no short statement of the relevance of aldosterone to contraceptive activity, there is evidence that aldosterone is a hormone which retains sodium in the body and is thus involved in control of blood pressure. Hormones associated with fertility, estrogens and progesterone, affect sodium and water retention in the kidneys but these two hormones, in a layperson's terms, counteract each other. If levels of these hormones are not regulated throughout the contraceptive cycle, levels of aldosterone can increase causing sodium retention and increased blood pressure.
141 Weighing up all of the circumstances, I am unable to accept that in instructing P&V, Schering AG had forgotten the information in the 9274 report and overlooked the existence of that report. Information control must be vital to an innovator pharmaceutical company. Schering AG was working on DRSP for years, carrying out various studies, and filing various patents along the way. Yet Generic Health would have it that a clinical trial directed at the specific quality of the aldosterone antagonist effect of DRSP compared to another contraceptive which concluded that the combination of DRSP and EE tested had a clearly demonstrable aldosterone antagonist effect, was not considered by Schering AG when it instructed P&V to prepare a patent application for the same compounds (DRSP and EE) claiming the very same aldosterone antagonist effect. The notion that Schering AG would overlook one of its own clinical trials, let alone one that was concerned with comparing DRSP with a commercially available contraceptive to test the aldosterone antagonist effect of DRSP when it was arranging for a patent to be prepared for DRSP as a contraceptive with an aldosterone antagonist effect, is one I am unable to accept.
142 In case this inference is incorrect, I reach conclusions below on the two bases - the first being that Schering AG did consider the 9274 report when instructing P&V and the alternative being that Schering AG did not consider the 9274 report when instructing P&V.
143 Assuming Schering AG did consider the 9274 report, I am also unable to accept Generic Health's proposition that the 9274 report does not provide proper scientific support for the 4mg upper limit. The submission is based on a misconception that aldosterone antagonist effect and diuresis are unrelated concepts. As the patent records, an aldosterone antagonist effect is related directly to diuresis (because it counteracts water retention which EE promotes). In other words, and again in a layperson's terms, EE acts to increase water retention and thus possibly blood pressure but DRSP acts to reduce water retention by increasing urine production. The ratio of DRSP to EE was important to Schering AG's objective of minimal side effects because the two components counteracted the tendencies of each other.
144 Thus, to submit as Generic Health does that the 9274 report says nothing about diuresis, when the report is concerned with the aldosterone antagonist effect of DRSP, is to miss the point of the report. The 9274 report reported that both dosages (2mg DRSP + 30µg EE; 4mg DRSP +30µg EE compared to Microgynon which has 0.15mg levonorgestrel + 30µg EE) were "well tolerated, subjectively and objectively", with "no adverse drug reactions" and the aldosterone antagonistic effect was clearly demonstrated for DRSP in both doses with initial increased sodium excretion being later neutralised by the body's counter regulation. No one with the expertise within Schering AG or P&V would have failed to appreciate that the report was dealing with water retention and removal by diuresis. The dosages being well tolerated must have meant that the water retention effects of EE were effectively countered by the DRSP without excessive diuresis at either dose.
145 While it is true that the 9274 report does not involve testing doses higher than 4mg of DRSP, Generic Health's submission that the "document says nothing about dosages above 4 mg, nor does it assess why 4 mg is a maximum" is based on another misconception. The submission appears to assume that rather than predicting the effect of a dose which is likely to achieve therapeutic efficacy and minimise side effects (which must include avoiding excessive diuresis) and then testing the prediction, the only way a pharmaceutical innovator, in good faith and with reasonable skill and knowledge, can decide upon a maximum dosage range to achieve these objectives is to conduct a test which will show adverse side effects and then, in effect, conduct a precise titration exercise, lowering the dose by degrees to find the highest absolute dose at which the effect is avoided. This approach has nothing to commend it. It assumes that dosages are not subject to any possible variance when this is not how a person skilled in the art approaches a dosage range. It rules out the role of sensible prediction by those skilled in the art. It would involve subjecting people to the risk of the very adverse side effects which are sought to be avoided.
146 Generic Health's other objections to the weight which might be given to the 9274 report are also without substance. The fact that the study on which it reports involved a sample of 27 women, when other Schering AG research involved more women, is immaterial. It does not mean that the 9274 report did other than demonstrate that the range of 2 to 4mg of DRSP was well tolerated which, in the context of the 9274 report, must include that the water retention effects of EE were effectively countered by the DRSP without excessive diuresis at either dose.
147 The 9274 report also said that the ovulation inhibitory effect of the formulations had not been conclusively proved but that the results indicated that ovulation was probably inhibited by both formulations. However, inhibition of ovulation was dealt with in the other reports identified in the table discussed above.
148 I also find Generic Health's approach to those other reports unpersuasive. Generic Health submitted this:
As to the selection of the lower range of 2 mg of drospirenone, the evidence indicates Bayer's own doubts about the efficacy of that dosage amount. See: (1) the 9693 Report (CB3.585), which concludes, in relation to a comparison between a tablet containing 2 and 3 mg drosprinenone, "a 3 mg-ZK 30.595-version should be developed further because an ovulation-inhibiting effect was demonstrable under the 3-mg version in all cases examined. It is to be expected that the contraceptive reliability of a 3 mg version will be greater than that of a 2 mg version on widespread use of the preparation": (2) the A892 Report (CB3.590-1), which describes trials using 0.5, 1, 2 and 3 mg drospirenone, states on page 2 (CB3.590), "The present results confirm what already been shown in earlier studies: with 2 mg, the dose of DRSP lies in the threshold range of inhibition of ovulation" and concludes on page 3 (CB3.591) that the research "demonstrates that the DRSP dosage of 3 mg DRSP provides a safety margin and can be recommended for use as an oral contraceptive in combination with an estrogen". No contemporaneous witness has been called by Bayer to explain these documents. In the circumstances, the appropriate inference to draw is that Bayer had doubts about the efficacy of a dosage of 2 mg of drospirenone.
149 This submission does not reflect the substance of the other reports.
150 The 9692 report dealt with a study of formulations of 2 and 3mg of DRSP (with 30µg EE in each formulation). It found a distinct aldosterone antagonist effect for both formulations (see the discussion above). It said that "clinically, no differences worth mentioning were observed between the two trial preparations" and that both were equally well tolerated so that other criteria would be needed to be employed to select a candidate for future development.
151 The 9693 report related to a trial for ovulation inhibition of the 2 and 3mg DRSP formulations (with 30µg EE in each formulation). The results in respect of tolerance were consistent with the 9692 report. In respect of ovulation, it was reported that follicular ripening occurred in several cases under both preparations. Further, although three ovulations were diagnosed under the 2mg preparation, one was "equivocal" and another involved "tablet-taking error", and "no differences were demonstrated statistically…between the two preparations as regards the hormones LH, FSH, estradiol and progesterone" and the parameter "ovulation during the treatment cycles". Further, "in keeping with the hormones, cervical function was greatly limited…under both trial preparations". The conclusions of the 9693 report include that:
• The present results confirm what has already been demonstrated in earlier studies: with 2 mg, ZK 30.3595 is in the threshold region of ovulation inhibition.
• Although no differences were demonstrable between the two preparations (p > 0.05), a 3-mg-ZK 30.595-version should be developed further because an ovulation-inhibiting effect was demonstrable under the 3-mg-version in all cases examined. It is to be expected that the contraceptive reliability of a 3-mg-version will be greater than that of a 2mg-version on wide-spread use of the preparation.
152 Dr McCann gave this evidence which I accept:
I guess, I mean, the way I look at these reports is that they were trying to - and if you look at one of the earlier ones they're trying to work out whether to go with the two or the three milligrams because both of them had contraceptive properties and one of the earlier reports they just couldn't tell the - there was a difference between two or three whatsoever…
But subsequent reports - there were what you call equivocal results with the two, and so they thought from a commercial perspective it would be better to go with the three, but it still worked within the statistical significance with the two which, to me, as a patent attorney - the experimental results show it works. Statistically, you couldn't - they couldn't really tell the difference between the two…
As a patent attorney, I - to be honest, I would probably put two as the lower range and have a backup 2.5, if you like, as my fall-back position on the basis of that information.
153 It was not suggested to Dr McCann that selecting 2mg as the lower end of the range would lack good faith or reasonable skill and knowledge given the reports available. Nor, given those reports, could it be.
154 The 9970 and A187 reports concerned trials in which all formulations included 3mg of DRSP but the dosage of EE was varied. The A892 report concerned a comparison between formulations containing 0.5, 1, 2, and 3mg DRSP. This report includes the following:
Adequate ovulation inhibition was found only under SH T 470 C and SH T 470 N. The present results confirm what had already been shown in earlier studies: with 2 mg, the dose of DRSP lied in the threshold range of inhibition of ovulation.
…
Body weight and blood pressure were stable and the tolerance was good. No pregnancy, no unexpected and no serious adverse events occurred.
The aldosterone antagonist effect of DRSP could be demonstrated for all dose ranges investigated….
…
Conclusions
• The investigation on the ovulation inhibiting effect reported here showed adequate ovulation inhibition only under SH T 470 C and SH T 470 N. This is in agreement with earlier studies in which the threshold dose for ovulation inhibition was 2 mg. This also demonstrates that the DRSP dosage of 3 mg DRSP provides a safety margin and can be recommended for use as an oral contraceptive in combination with an estrogen.
• The aldosterone antagonistic effect of DRSP could be demonstrated for all dose ranges investigated…
155 Based on the substance of the reports I do not accept that Bayer (or Schering AG at the time) "had doubts about the efficacy of a dosage of 2 mg of drospirenone". To draw this inference would be to place excessive weight upon a layperson's approach to the notion of a "threshold dose" and to ignore the clinical and statistical analyses which demonstrated not that the 2mg dosage of DRSP was unreliable, but that it was the lowest dose at which ovulation was adequately inhibited. Given this, Generic Health's submission that "in order for Bayer to discharge its onus of proving that that lower limit was selected in good faith and with reasonable skill and knowledge, an explanation from a witness in Bayer's camp would be expected" must be rejected.
156 I also do not accept Ms Sinclair's evidence about the lower end of the range. Ms Sinclair said that "…it is questionable whether a claim is framed in good faith if it includes a range that is not efficacious, in its contraceptive reliability, in all circumstances, when this is the promise of the invention". As Bayer said in response:
(1) The patent states at p. 2, lines 25 to 26 that it has surprisingly been found that "a hitherto undisclosed minimum dosage level of drospirenone is required for reliable contraceptive activity".
(2) The statement must be read (through the eyes of the person skilled in the art) in the context of the specification as a whole.
(3) The context includes example 5 in the patent, which reproduces the conclusions drawn by Bayer in relevant experimental reports and openly repeats much of the text of the 9692 report.
(4) "There is no (nor can there be) [a] suggestion that Bayer misrepresented the performance characteristics of the 2mg dose or that it did not honestly believe that a dose of 2mg would relevantly work".
(5) As Dr McCann said, no contraceptive is 100% reliable. Nor does utility require 100% effectiveness (see Apotex Pty Ltd v Warner-Lambert Company LLC (No 2) [2016] FCA 1238 at [170]).
157 Documents referred to in the PCT application: As noted, the PCT application (and the Australian patent) referred to the disclosure in numerous Schering AG patents related to DRSP. Schering AG patent specification no. DE2652761 disclosed DRSP as a diuretic. Schering AG patent specification no. DE3022337 disclosed DRSP as involving gestagen-like activity and utility as a contraceptive agent at dosage levels of 0.5-50mg of DRSP per day, that the mechanism of action of the compound is very similar to that of the natural corpus luteum hormone progesterone, and does not give rise to increased blood pressure. Schering AG patent specification no. EP398460 (for which Dr Broesamle drafted the priority document) disclosed the use of DRSP for the treatment of androgen-induced disorders at dosage levels of 0.5-50mg, preferably 1-10mg per day. Schering AG patent specification for DE3051166 disclosed the use of DRSP for the treatment of gynaecological irregularities and for contraception at a dosage level of 0.5-50mg per day. All of these disclosures are identified in the specification for the unamended patent (and the PCT application on which it was based). Given his role, Dr Broesamle must have been involved in the preparation of all of these patents. The unamended specification also contains Example 5 which contains information from the 9693 report. As I do not accept Generic Health's submissions about that report, I also do not accept its submission that Example 5 does not provide support to Bayer's contentions.
158 It necessarily follows that the specification for the unamended patent was framed having regard to all of this information, in addition to the other documents to which I have referred.