Merial and Others v Cipla Vet (Pty) Ltd (96/8057) [2014] ZACCP 3; 2014 BIP 42 (CP) (24 July 2014)

IN THE COURT OF

THE COMMISSIONER OF PATENTS

FOR THE REPUBLIC

OF SOUTH AFRICA

DATE:24 July 2014

CASE NO:96/8057

In the matter between:

MERIAL................................................................................................................................First Plaintiff

MERIAL LIMITED.........................................................................................................Second Plaintiff

MERIAL

SOUTH AFRICA...............................................................................................Third Plaintiff

and

CIPLA VET (PTY) LTD...........................................................................................................Defendant

JUDGMENT

MURPHY, J

1. The plaintiffs have instituted an action against the defendant issued out of the Court of the Commissioner of Patents in which they allege that the defendant is infringing various claims of Patent No. 96/8057 of which the first plaintiff is the patentee and the second and third plaintiffs are registered licensees under the patent.

2. The first plaintiff is Merial, a company incorporated in France, the second plaintiff is Merial Ltd, a company incorporated in the UK and the third plaintiff is Merial South Africa (Pty) Ltd, a South African company.

3. The defendant is Cipla Vet (Pty) Ltd, a South African company.

4. As stated, the first plaintiff is the registered proprietor of South African patent no. 96/8057 entitled: “Anti-parasitic

composition for the treatment and protection of pets.”

5. It is common cause that the defendant has since 2008 made, used, sold, offered for sale, and imported a composition in the form of a ready-to-use solution for the treatment and protection of domestic animals which are infested with parasites or are likely to be infested with them, under the trade mark “Fiprotec”, and continues to make, use, exercise dispose or offer to dispose of and import the Fiprotec composition. The plaintiffs allege that the defendant’s conduct infringes claims 1, 2, 3, 7 to 15 and 18 to 20 of the patent and that as a result of the infringement have suffered damages in amounts which they are at present unable to quantify. In the event of their establishing infringement, the plaintiffs also seek an order that the defendant deliver up to them all infringing Fiprotec products in its possession and an order directing an inquiry into the damages suffered by the plaintiff as a consequence of the infringement.

6. Fiprotec, like the plaintiffs’ product “Frontline”, is a “spot-on” composition used in the treatment and protection of domestic animals. The term “spot-on” refers to a product which is applied locally to a limited area of the body of the animal but which is effective over the entire body of the animal.

7. The defendant has denied infringement of the various claims, and additionally pleads that the patent is invalid on various grounds. It somewhat unusually, but entirely legitimately, does not counterclaim for revocation of the patent. Section 65(4) of the Patents Act 57 of 1978 (“the Act”) provides:

“In any proceedings for infringement the defendant may counterclaim for the revocation of the patent and, by way of defence, rely upon any ground on which a patent may be revoked.” - (emphasis supplied).

Hence should it be found that the patent is invalid in one or more of the respects pleaded by the defendant then whether or not Fiprotec infringes the claims of the patent is rendered moot.

8. Given that the claims, other than claim 1, which the plaintiffs allege to have been infringed, are dependant claims, should the plaintiffs establish infringement of claim 1 there will be no answer to the case of the plaintiffs in relation to the infringement of the dependant claims.

9. Claim 1 of the patent reads:

“Composition which is useful in particular for the treatment and protection of domestic animals which are infested with parasites or are likely to be infested with them, these compositions comprising in the form of a ready-to-use solution:

(a) 1-[4CF₃ 2, 6-CI₂ phenyl] 3-cyano 4-[CF₃-SO] 5-NH₂ pyrazole (hereinafter referred to as “fipronil”);

(b) a crystallisation inhibitor which satisfies the test according to which:

0.3ml of a solution A comprising 10% (W/V) of the compound (fipronil) in the solvent defined in (c) below, and 10% of this inhibitor, are placed on a glass slide at 20⁰C for 24 hours, after which fewer than 10 crystals, preferably 0 crystals, are seen with the naked eye on the glass slide;

(c) an organic solvent having a dielectric constant of between 10 and 35, preferably of between 20 and 30;

(d) an organic co-solvent which is a drying promoter, having a boiling point below 100⁰C, preferably below 80⁰C, and a dielectric constant of between 10 and 40, preferably of between 20 and 30,

wherein fipronil is present in a proportion of from 1 to 20% W/V in the composition.”

10. The composition of the invention thus comprises four constituents: fipronil, a solvent, a co-solvent and a crystallisation inhibitor.

These constituents are described in further detail in the body of the specification.

11. It is common cause on the pleadings that Fiprotec includes:

11.1 - 9,7% fipronil (the active pharmaceutical ingredient - “API”);

11.2 - 10% ethanol;

11.3 - 0,10% butylated hydroxyanesole and 0,10% butylated hydroxytoluene;

11.4 - 1,40% polyvinylpyrrolidone - PVP K30;

11.5 - 1,00% Polysorbate 80 (Tween 80);

11.6 - 50% diethylene glycol monethyl ether –“DGME” (Transcutol P); and

11.7 - 27,7% propylene glycol- “PG”.

12. In the body of the specification of the patent ethanol, PG and DGME are all identified as solvents which can be used in the invention as integer c) of claim 1. And it is stated that “a mixture of at least two of these solvents” can be used in the invention. Likewise, in relation to integer b) of claim 1, the crystallization inhibitor, the specification mentions inter alia PVP and polysorbate 80, and preferably a mixture of two crystallization inhibitors, as fit for use in the invention.

13. As for the organic co-solvent constituting integer d), the specification mentions only: “absolute ethanol, isopropanol

(2-propanol), methanol”.

14. Butylated hydroxyanesole and butylated hydroxytoluene are anti-oxidants, which though probably adding to the efficacy of the

composition or product are not identified in Claim 1 of the patent as an essential integer - though are additional integers in claims 7, 8 and 19.

15. The plaintiffs contend that Fiprotec therefore includes all of the integers of Claim 1 of the patent, namely: fipronil within the concentration range of 1-20%; an organic solvent in the form of a mixture of PG and DGME; a co-solvent in the form of ethanol; and a crystallisation inhibitor in the form of a mixture of a film-forming agent, PVP and a surfactant Polysorbate 80, which in the ratio of 1.4 to 1 (as in Fiprotec), satisfies the test specified in integer b) of Claim 1 of the patent.

16. The dispute on the pleadings and in the evidence with regard to the question of infringement has narrowed to three issues; namely:

16.1 Whether the mixture of PVP and Polysorbate 80 in Fiprotec is a crystallisation inhibitor for the purposes of integer b), and one which satisfies the test prescribed there;

16.2 Whether the mixture of DGME and PG constitute together an organic solvent for the purposes of integer c); and

16.3 Whether the ethanol is an organic co-solvent for purposes of integer d).

17. The determination of patent infringement is a matter of the proper construction of the claims of the patent. The court must endeavour to understand what the language of the claims of the patent means by having regard to the ordinary meaning of the words used in the context of the remainder of the specification and as they would be understood by a person skilled in the art.[1] Expert evidence is permissible to place the court in the position of a person skilled in the art. The adjudication of the issue of infringement then involves a comparison between the article and/or process involved in the alleged infringement and the contextually

understood language of the claims in the patent.[2] The question of whether or not the product infringes is ultimately a question for the court and not the expert, who acts as a guide to elucidate the workings of the product, or, as in the present case, to demonstrate the results of a screening test.[3] The onus is on the plaintiff to prove infringement on a balance of probabilities.

18. The skilled addressee of the patent is a person or a team interested in the development or formulation of an anti-parasitic composition for the treatment and protection of pets. As appears clearly from the specification, the aim of the invention is to control and eliminate the parasites which infests pets, and especially cats and dogs.

19. The objects of the invention are set out in the specification as follows:

“The object of the invention is to provide novel anti-parasitic compositions for the treatment and protection of animals, these compositions being of great efficacy while at the same time being easy to use.

Another object of the invention is to provide such compositions which are easy to use on any type of domestic animal, irrespective of its size and the nature of its coat.

Yet another object of the invention is to provide such compositions which are effective and do not need to be sprinkled over the animal’s entire body.

Yet another object of the invention is to provide such compositions which, when applied locally, will subsequently diffuse over the animal’s entire body and then dry, while at the same time avoiding any phenomenon of crystallisation as far as possible.

Yet another object of the invention is to provide such compositions which, after drying, do not affect the appearance of the coat and in particular do not leave crystals and do not make the coat sticky.”

20. Thus, the object of the invention is plainly to provide an efficacious anti-parasitic formulation which is easy to use and when

applied locally will be effective over the entire body, will dry and avoid crystallisation as far as possible and will not affect the appearance of the coat. I agree with the plaintiffs that the object of the invention, as evident in the object clauses of the

specification, is therefore not merely the avoidance of crystallisation, but an efficacious spot-on formulation which avoids crystallisation and an un-aesthetic appearance on the coat of the animal.

21. As alluded to earlier, the patent provides guidance on which chemicals or mixtures can be used as solvents, co-solvents and

crystallization inhibitors. The specification additionally identifies preferred constituents for integers b) and c) by stating the preferred solvents to be the glycol ethers in particular DGME and dipropylene glycol monoethyl ether, DPGME, and the preferred

crystallization inhibitor system to be a combination of a film-forming agent of polymer type (such as PVP) and a surfactant (such as Polysorbate 80). The patent teaches that the co-solvent, integer d), should serve as a drying promoter aimed at ensuring that

the formulation does not remain wet on the animal’s skin for a prolonged period.

22. The specification concludes with a significant teaching which has assumed some relevance. It states:

“The compositions according to the invention are usually prepared by simply mixing the constituents as defined above; advantageously, to begin with, the active substance (the API or fipronil) is mixed into the main solvent, and the other ingredients or adjuvants are subsequently added.”

23. Against that background, I now turn to the first issue in relation to the alleged infringement: whether the mixture of PVP and Polysorbate 80 in Fiprotec is a crystallization inhibitor for the purposes of integer b), and one which satisfies the test prescribed.

24. Paragraph (b) of the consistory clause in the body of the specification, which is repeated verbatim in integer b) of Claim 1,

provides a qualitative test to determine which constituents, or combination of constituents, will constitute a crystallization

inhibitor within the scope of the claim. The test requires that a solution be prepared containing 10% of the API and 10% of the

crystallization inhibitor found in the allegedly infringing formulation dissolved in the organic solvent in integer c). No organic co-solvent (drying promoter) as specified in integer d) is included. The solution is then placed on a glass slide at 20 degrees

Celsius for 24 hours. The crystallization inhibitor will pass the test if after 24 hours fewer than 10 crystals are seen with the naked eye on the slide.

25. The plaintiffs led the evidence of Dr Witchey-Lakshmanan (“Dr Witchey”), while the defendant led the evidence of Prof Barbour, who both performed crystallization inhibitor tests as specified in integer b). Dr Witchey found that there was no visible crystallization on the glass slide after 24 hours, while the tests performed by Prof Barbour resulted in visible crystallization. The experts thus reached opposite conclusions on their tests and the parties have predictably urged me to prefer the evidence of their respective witnesses.

26. The purpose of the integer b) test is evident from a proper contextual reading of the specification. The patent promises (as a consequence of the presence of a crystallization inhibitor) the maintenance of the cosmetic appearance of the coat of the animal “in a noteworthy manner”. The test is unrelated to the efficacy of the API or fipronil (the anti-parasitic ingredient), it relates rather to the efficacy of the constituents inhibiting the formation of crystals on the coat. Crystallization is a random process and can be affected by atmospheric and other conditions. The test postulates the formation of some crystals but with a precise threshold, namely no more than nine crystals. A test resulting in more than nine crystals will fail and the allegedly infringing product will not infringe on account of it not including integer b).

27. Neither the consistory clause (being the only part of the specification making any reference to the test) nor Claim 1 give any

instructions regarding the environment and conditions for conducting the test, other than requiring the solution to be placed on a glass slide for 24 hours at 20 degrees Celsius. Mr Puckrin SC, counsel for the defendant, has submitted, correctly in my view, that it would be desirable, as a matter of logic, in the absence of any other stipulated parameters, for the test to be conducted in normal laboratory conditions at 20°C for 24 hours. The entire purpose of the test would be thwarted if the atmosphere was so controlled as to inhibit crystallization altogether. Additional controls could make it difficult for the formulator to discern whether the lack of crystals was due to the environment or the crystallization inhibiter, especially if they impacted upon the rate of evaporation.

28. The plaintiff’s expert witness, Dr Witchey, performed a crystallization inhibitor test. A descriptive analysis of the test and the results is annexed as Annexure LCWL2 to her expert summary filed in terms of Rule 36(9)(b). Dr Witchey is a formulation chemist, trained as a chemical engineer, with 25 years of experience in pharmaceutical product development. She is a registered patent agent in the USA and works as a consultant for several pharmaceutical companies involved in the development of pharmaceutical products for human and animal use and consumption. She is indisputably a person skilled in the art and thus an addressee of the patent.

29. In her evidence Dr Witchey identified the purpose of the exercise to be a determination of whether or not a combination of PVP and Polysorbate 80 in a ratio of 1,4:1, as found in Fiprotec, satisfies the test for crystallization inhibitor in Claim 1 of the patent. She took the system representative of Fiprotec to be: 10% w/v fipronil, 10% w/v of the combination of PVP and Polysorbate 80 in the ratio of 1,4:1, and a mixture of DGME and PG as an organic solvent of which DGME was 50% w/v and the remaining volume comprising PG.

30. Dr Witchey ran the test in triplicate following the method described in integer b) of Claim 1, by placing 0,3ml of the solution on a glass slide and allowing it to rest for 24 hours at 20°C. No crystals were observed in any of the three replicates tested. Therefore Dr Witchey concluded that the relevant constituents of Fiprotec satisfied the requirements of the crystallization inhibitor test in integer b).

31. All the materials used in the test were supplied to Dr Witchey by the plaintiff. Thus, the fipronil came from Merial, and the other constituents came from other suppliers or manufacturers. Dr Witchey noted a difference between the DGME she used and that found in Fiprotec. The Fiprotec lists the DGME as Transcutol P from the supplier Gattefosse. The DGME she used in the test was Transcutol V from Gattefosse, which she described as “virtually identical” to Transcutol P. Both materials are listed with identical CAS (Chemical Abstract) numbers and are therefore chemically the same material. The impurities in the two different DGME types were at the same specification level except for 2-ethoxyethonal and ethylene glycol. The differences were deemed to be inconsequential to the experiment and the Transcutol V was deemed by Dr Witchey to be acceptable for use in the test.

32. While, as just stated, Dr Witchey in her test used fipronil supplied to her by the plaintiff, Prof Barbour, the expert who conducted the integer b) test on behalf of the defendant, used fipronil supplied by the defendant, being the actual fipronil ingredient contained in Fiprotec. The fipronil used by Dr. Witchey was not that used in the manufacture of the Fiprotec composition. The parties agreed at the pre-trial conference that the evidence of Mr Desai, an employee of Cipla Ltd of India (a company associated with the defendant),

regarding the source of the constituents used by Prof Barbour, could be admitted into the record by way of affidavit and that there would be no need for the defendant to call him for purposes of cross-examination.

33. The affidavit of Mr Desai confirms that Cipla Ltd in India supplies the defendant with the Fiprotec product which is the alleged

infringing product. Mr Desai is the person who supervises the production of Fiprotec in India. He procured samples of the raw materials used in the production of Fiprotec for the purposes of conducting tests on these ingredients. He averred that in order to provide the very same ingredients as used in the regular production of Fiprotec, a number of work orders were placed. These work orders are essentially orders for batches of Fiprotec. The raw materials and their relative quantities used in the production of Fiprotec are apparent from the orders attached to his affidavit. Mr Desai also attached certificates of analysis in respect of the materials. Considering that the raw materials were required for the integer b) test, they were not used to manufacture a composition of Fiprotec. Rather, the raw materials were dispensed from the factory stores, packaged and dispatched to the defendant. Mr Desai confirmed that the materials collected by him from the factory were “the very ingredients used in the regular production” of Fiprotec.

34. The manufacturing work orders reveal that not all of the ingredients contained in Fiprotec were sourced from the same suppliers or producers of the ingredients used by Dr Witchey when she conducted her test. The identified source of the fipronil in Fiprotec is stated to be “GSP crop science”, while that used by Dr Witchey is stated to be “Merial”, presumably one of the plaintiffs. Likewise, the PG used in Fiprotec was sourced from “Shell Chemicals”, whereas that used by Dr Witchey was sourced from “Spectrum”. The other ingredients used in the test PVP, Polysorbate 80 and DGME appear to have been sourced from the same producers namely BASF, Croda and Gattefosse respectively, though as already discussed, Dr Witchey used DGME, Transcutol V rather than DGME Transcutol P, the actual ingredient in Fiprotec.

35. No adequate explanation was tendered in evidence for why the actual ingredients of Fiprotec supplied by Mr Desai were not made available to Dr Witchey for the purpose of the plaintiff conducting the integer b) test. Prof Barbour, as mentioned, used the ingredients provided by Mr Desai for the purpose of conducting his test.

36. The certificate of analysis in relation to the fipronil supplied by Mr Desai records an impurity of 0,6%, meaning that the fipronil was considered to be 99,4% pure.

37. Thus, Dr Witchey conducted her test using materials somewhat different from the actual ingredients in Fiprotec. Her test was

conducted in a controlled laboratory setting. Temperature data was collected continuously throughout the 24 hour period.

38. Dr Witchey described the method she followed in conducting the test at pages 3-4 of her report as follows:

“The test was conducted by preparing the solution described above and then placing the solution on to each of three glass slides, following the description of claim 1 of the noted patent. In particular:

1. Approximately 1.5g of the DGME vehicle were added to a 5ml large-mouth volumetric flask.

2. The prescribed amount of PVP was added to the vehicle and mixed with the micro stir bar until visually dissolved.

3. The prescribed amount of Tween 80 (Polysorbate 80) was added to the vehicle solution and mixed with the micro stir bar until visually dissolved.

4. Approximately 0.5g of fipronil (10% w/v) was added to the vehicle solution and mixed with the micro stir bar until visually dissolved.

5. Additional DGME was added as required and mixed with the micro stir bar until homogeneous.

6. The stir bar was removed, then the flask was filled to the 5ml mark with propylene glycol (PG) and mixed with the micro stir bar till homogeneous. The resulting solution was a clear, light yellow solution.

7. Glass slides were prepared in triplicate by rinsing with methanol, then wiping with delicate task wipers and allowing to air dry.

8. The bottom of each slide was marked with an identifying symbol using an indelible marker. The slides were examined for the presence of particles and placed in the weighing chamber.

9. The surface inside the weighing cabinet was confirmed to be level and the temperature of the environment was confirmed to be 20°C. The weighing cabinet was closed on three sides, and the front sash was left open to the environment ……

10. 0.3ml of the prepared solution was placed on each of the glass slides.

11. These slides were then left within the weighing cabinet for 24 hours.

12. At just after the 24hour mark, each slide was examined visually for crystals.”

Confirmation for the fact that the steps described by Dr Witchey in her method were followed sequentially is found in her observation (under the heading “Results and Discussion”) that “the dissolution of the materials into the vehicles was complete at each step”.

39. As stated, the results of the test were that no crystals were observed on any of the three slides and there was still some solution

which had not evaporated. The results are confirmed by the photographs annexed to the test report. Dr Witchey accordingly concluded that the requirements of the integer b) test had been satisfied in relation to Fiprotec.

40. Dr Witchey confirmed her method of conducting the test during her testimony but noted that it was a laboratory technician who had put the ingredients into the flask and mixed them in the manner described in the test report.

41. The witnesses who testified on behalf of the defendant, Prof Barbour and Mr Swiegers, between them conducted four tests in support of the case for non-infringement. Prof Barbour conducted tests B1, B2 and C. The defendants abandoned reliance upon test C. Mr Swiegers conducted tests on six dogs, the purpose of which was to demonstrate that Fiprotec did not yield the promise of non-crystallization.

42. Prof Barbour holds a PhD and a DSc in chemistry with a specialist interest in crystallography. He performed the integer b) test using the actual ingredients of Fiprotec supplied by Mr Desai. He performed the test twice, and recorded his results referring to the two tests as “Test B1” and “Test B2” respectively. In the case of Test B1, Prof Barbour observed at the conclusion of the test that there was heavy crystallization, with a layer of crystallites visible on the slide. Although the slide was still damp, almost all of the solvent had evaporated. The photographic evidence depicts visible precipitation after 5 hours. In the case of Test B2, virtually all the solvent had evaporated after 24 hours leaving a crystalline residue on the slide, in which more than 10 crystals could be observed with the naked eye. Visible precipitation was noticeable after 13 minutes and “fairly heavy crystallization” apparent after 78 minutes. Prof Barbour accordingly concluded that there was a complete failure of the purported crystallization inhibitor system in the Fiprotec composition.

43. The plaintiffs made an effort in argument and cross examination to persuade me that Prof Barbour, being a crystallographer and not a formulation chemist, was not a person skilled in the art, in that the skilled addressee of the patent, they contended, was a formulation chemist or a veterinary scientist, of which Prof Barbour was neither. Their contention was however contradicted by their own witness, Dr Witchey, who conceded that the skilled addressee could constitute a team and that the integer b) test could be performed by a person with “a basic knowledge of general, physical and organic chemistry”. That concession is hardly surprising as the test quite evidently is a simple test. Hence, once it is accepted that the skilled addressee may constitute a team, one of the team will be able to speak about a limited aspect of the invention, in this case the integer b) test, provided he or she is the member of the team qualified to speak about that aspect. Prof Barbour holds two doctorates in chemistry and is thus plainly possessed of more than a basic knowledge of chemistry. It seems to me that there is no need for the person performing the integer b) test to have a detailed understanding of how the test and its results relate to the formulation of the composition. It is also wrong to suggest that Prof Barbour had no insight into what was being screened and the ultimate purpose of the test. He clearly did. The plaintiffs’ attempts to disqualify Prof Barbour are accordingly unconvincing. That is not to say that Prof Barbour’s performance of the test is beyond criticism. It is debatable whether he employed the optimal method for conducting the test; a matter to which I will return later.

44. Mr Swiegers gave factual evidence of a non-expert nature. He has relevant experience as a Quality Assurance Manager with a research organization conducting efficacy, safety and local tolerance studies and clinical trials on animals. He conducted a trial using Fiprotec on 6 black dogs all weighing above 20 kilograms. All the dogs were dosed with 2,68ml of Fiprotec, being the recommended dosage for dogs of that size. On examination of the coats of the dogs after 24 hours, all demonstrated white crystalline deposits.

45. Dr Witchey in her evidence was unable to offer any explanation for why the results of her test and those of Prof Barbour differed. In her view the tests were similar using the same though not identical ingredients and should have produced the same results. She could not offer any definitive or conclusive explanation for the difference in results. Although she had “been trying to figure out why we would have so much difference in our tests”, she could not explain why there was such difference.

46. During cross-examination a number of possible factors contributing to the divergent results were put to Dr Witchey. As just explained, she conceded that the test could be carried out by a person “having basic knowledge of general, physical and organic chemistry”, and essentially that it did not need to be carried out by a skilled formulator. The test could be carried out by a laboratory technician, and that Prof Barbour while not being a formulator had the skills required to carry out the test.

47. Three reasons for the divergent results were explored with Dr Witchey. The first was that she might have inhibited crystallization

by carrying out her tests in a weighing cabinet which was shielded on three sides which would have inhibited evaporation of the solvent and thus the formation of crystals. The second possibility was that Dr Witchey did not use the constituents of the defendant’s actual composition. As explained earlier, the fipronil and the PG came from different sources and the DGME used by Dr Witchey was Transcutol V and not Transcutol P. In cross-examination, Dr Witchey further admitted that she did not refer to the Chemical Abstracts (CAS) in order to ensure that the fipronil which she tested was the equivalent to the fipronil which was used in Fiprotec. Fipronil is the most important ingredient in the test because it is the active pharmaceutical ingredient which causes the problem of crystallization

and there are five different polymorphs of fipronil indicating that there are different processes for manufacturing it as a substance.

This in turn gives rise to a possible third reason for the divergent results, different processes may have inherent within them different impurities, and, as Dr Witchey conceded under cross-examination different impurities may affect crystallization. Mr Puckrin concluded his cross-examination with the following pertinent exchange, resulting in a significant concession by Dr Witchey:

“Mr Puckrin: All in all Dr Witchey, would you agree with me that it would have been preferable to have conducted this test with the very constituents of the alleged infringing product. I understand Merial did not do so, but that is their own fault, they could have asked for it. Would you agree that it would have better, save to have conducted your experiment? (sic)

Dr Witchey: Better implies a value. With regard to helping us perhaps figure our differences between my test and Dr Barbour’s test. That is an approach that one could take to help make that determination. I would agree with that as a scientist.”

48. Counsel for the plaintiffs, Mr Bowman SC, sought to counter the defendant’s postulated reasons for the divergent results. With regard to the control of the environment by use of the weighing cabinet, he argued that it was appropriate “as a formulator”,

a person skilled in the art, for Dr Witchey to use the cabinet to prevent “undue evaporation”. At first glance, there is merit though in the defendant’s suggestion that the in vitro test should approximate the in vivo conditions in which the product would be applied to the animals. However, the plaintiffs justified the use of the cabinet as legitimate as it would avoid artificial means of enhancing evaporation, such as would occur where a convective flux was allowed to push across the surface of a slide. Dr Witchey was satisfied that the cabinet was of sufficient size and sufficient configuration to allow free evaporation within the system. In her opinion, leaving the slide in the open laboratory (as Prof Barbour did) would enhance evaporation, especially if they were exposed to air handling systems. While it is true that the solution on the slides in the cabinet had not evaporated completely, the same was true of the “control” slides containing just solvent which Dr Witchey placed outside of the cabinet. This evidence was not contained in the test report, but nor was it challenged in cross-examination. She noted in relation to these that there had been “observable evaporation”, as on the test plates, and there was still liquid on the control slides. That unchallenged evidence, in my view, puts paid to the suggestion that the use of the weighing cabinet inhibited crystallization.

49. Mr Bowman was pressed in argument to explain and qualify the concession made by Dr Witchey that the different processes applied in the production of the differently sourced fipronil may have affected the rate of crystallization. Prof Barbour testified that if the synthetic process was different then it would be “highly possible” that the impurities would be different. When asked whether different impurities may result in different degrees of crystallization his response was that it would depend on what the impurities were as they could be substances which could promote or enhance crystallization. He could not say for sure, without knowing what the impurities were, but could say only that it was possible. He too was of the opinion that it would have been preferable had the tests of the two parties been done using the same ingredients, more especially the actual ingredients used in Fiprotec.

50. Mr Bowman submitted that the presence of impurities in the fipronil used in Fiprotec is insufficient reason to hold that such was the factual cause of the difference and pointed to the fact that one of Prof Barbour’s tests (in which he used DPGME) resulted in no observed crystallization. He also relied on the undisputed fact that the possible existence of a different fipronil polymorph would not directly bear upon possible crystallization because once in solution the polymorphic form is lost and is accordingly irrelevant. The significance of polymorphism, as I understand the submission of the defendant, is the fact that it is indicative of different manufacturing processes. The defendant’s case is that the different processes employed in the production of fipronil (not the different polymorphic structure) might be the cause of the different rates of crystallization and hence it was incumbent upon the plaintiff to determine the efficacy of the crystallization inhibitor system in Fiprotec, and thus the question of infringement, by testing it in relation to the actual fipronil used as the API in Fiprotec, bearing in mind that it is fipronil that produces the crystals. This Dr Witchey did not do. She used the fipronil which the plaintiff employs in its own product, Frontline.

51. Mr Bowman has trenchantly criticized the manner in which Prof Barbour conducted his tests. He suggested, in my opinion not entirely

correctly, that Prof Barbour based his evidence of the possibility of crystallization being the result of impurities on his observations

that the fipronil he used had a different solubility and that he experienced difficulties in dissolving the fipronil into the solution. His difficulty resulted, according to Mr Bowman, from his failure to follow the instructions of the patent, something a skilled addressee (which he claimed Prof Barbour was not) would know better how to do. This criticism is tenuous. In his evidence in chief, Prof Barbour testified that he weighed the fipronil and the PVP, added that to a volumetric flask, then added the Polysorbate 80 and the DGME to 50% of total volume and then made up the final volume with the PG. Dr Witchey did it differently, she added PVP and Polysorbate (the crystal inhibitor) to DGME then added the fipronil. Neither of them followed the “advantageous” method mentioned in the specification, which states that generally the compositions according to the invention “are usually prepared by simply mixing the constituents”. While the advantageous method (followed by neither expert in this case) is to first mix the API with the main solvent and then to add the other ingredients in no specified order. Hence, in my view, the order of mixing the ingredients has not been demonstrated as being the cause of an absence of crystallization. Moreover, integer b) of claim 1 offers no instruction in that regard.

52. Mr Bowman has advanced a number of legitimate criticisms indicating a measure of carelessness on the part of Prof Barbour in conducting his tests. Some relate to incorrectly recorded information and do not in the final analysis bring into question the actual results of his test, though do raise concerns about his reliability as an expert. For reasons which will become evident it is not necessary to canvass the criticisms in any detail. The principal reason for which I hesitate to accept the results of Prof Barbour’s Test B1, as scientifically establishing the failure of the crystallization inhibitor in Fiprotec, is that there is a distinct possibility, if not probability, that an etching on the slide used by Prof Barbour (caused by a microscope) contributed significantly to the formation of crystals. Instead of using a clean, new slide, Prof Barbour used a five year- old glass slide which he took from his microscope. The etching was caused by the pressure of the component of the microscope holding the slide in place. Prof Barbour conceded that any scratching on a glass slide could encourage crystallization. The photographic

evidence in relation to Test B1 reveals that the solution may have pooled against the edge of the etching. This alone makes Test B1 unreliable and the results must be disregarded.

53. Likewise, I agree with Mr Bowman that the results of Test B2, conducted by Prof Barbour, are not sufficiently credible to definitively exclude integer b). In this instance crystallization materialised after 13 minutes, whereas it took 5 hours in Test B1 despite using the same solution, in the same laboratory at the same temperature. Normally, before one would see crystallization, at least

part of the solution would have to reach the saturation point of the solute in the solvent. Dr Witchey estimated that some 45% of the solution would have to evaporate before the concentration of fipronil reaches a point where the crystallization inhibitor is even needed. To accept the results of Test B2 it must be accepted that 45% of a solvent system having boiling points of 200°C (DGME) and 185°C (PG) evaporated in 13 minutes. The probabilities point to an error of some kind, inexplicable in the evidence. Prof Barbour might have been prudent when confronted with the rapid rate of evaporation in this test to have conducted a third test.

54. The defendants, for reasons not clear to me, did not in argument place much reliance on the test performed by Mr Swiegers. I assume the criticism of the plaintiffs may have hit the mark. Firstly, there is no requirement in claim 1 of the patent that the crystallization inhibitor in the defendant’s product be proven to act as a crystallization inhibitor to any particular degree when used on a dog. It needs only to be shown that Fiprotec includes the constituents of the claim and specifically that the constituents

would pass the test in integer b) of claim 1 in an in vitro test. The test on the dogs (in vivo), strictly speaking, is accordingly irrelevant, at least as far as the question of infringement is concerned. At face value though, it points to the possibility that Fiprotec may not inhibit crystallization to the extent of the promise of the patent. The plaintiffs contend furthermore that the tests do not establish that Fiprotec lacks an effective crystallization inhibitor because one cannot draw that conclusion without a control group. Fiprotec, they argued, should have been compared against a formulation which had all the constituents of Fiprotec except the crystallization inhibitors. The whitish deposit observed by Mr Swiegers might have been more prevalent had Fiprotec not included a crystallization inhibitor. I am less persuaded by this argument. A control test of the order proposed could only have established more or less crystallization (most likely more). The failure of Fiprotec to inhibit crystallization to the extent suggested by the integer b) test (less than 10 crystals) could not be assessed differently by taking account of a composition of Fiprotec without the crystallization ingredients resulting in more or less crystallization. If there were less crystallization then that could not be attributable to any inhibitor and the test would be inconsequential to the

question of infringement. More crystallization would not alter the fact that the ingredients in Fiprotec did not have the desired result, assuming of course the in vivo test was properly performed. The plaintiffs have raised a plethora of other objections to the tests, but again, on account of the questionable relevance of the test, it is unnecessary to canvass them. The defendants made no attempt in argument to rebut them.

55. The evidence of the defendant therefore does not conclusively establish that Fiprotec does not include a crystallization inhibitor that satisfies the test in integer b). But that does not resolve the question of infringement.

The onus is on the plaintiffs to establish positively, on a balance of probabilities, that Fiprotec does indeed include a crystallization

inhibitor that satisfies the test in integer b). The weaknesses in the defence’s case is not to my mind sufficient to warrant an inference that the combination of PVP K30 and Polysorbate 80 in a ratio of 1,4:1 (mixed in a solution of DGME, PG and/or ethanol) will operate to inhibit fipronil sourced from “GSP crop science” from producing fewer than 10 crystals. There is no reliable test before me which adequately demonstrates that fact. The plaintiffs’ evidence shows that the Fiprotec crystallization inhibitor system will achieve that result in relation to fipronil produced and/or supplied by Merial. Neither that fact nor the flawed results of the tests of the defendant provide sufficient evidence to conclude on the probabilities that the crystallization inhibitor system in Fiprotec achieves the same result in relation to the fipronil used in Fiprotec supplied by GSP. A test on the constituents of the patented product does not prove the constituents of the alleged infringing product actually infringe. To my mind it is impermissible, from the perspective of logic and fairness, to infer that because the crystallization inhibitor proved successful in inhibiting the Merial fipronil from producing crystals that it has equal success in so inhibiting the fipronil in Fiprotec. The evidence is insufficient to reach that conclusion. While the different polymorphs of fipronil may be

insignificant once in solution, their existence in different polymorphic form points to different manufacturing processes that may or may not account for impurities which could impact upon the process of crystallization. Whether that is or is not so can only be established once the actual ingredients in Fiprotec have been subjected to a reliable integer b) test – something which has not happened in this case.

56. When a party carries a burden to prove its case on a balance of probabilities the evidence must carry a reasonable degree of

probability to allow the court to conclude that the alleged conduct is more probable than not. But if the evidence is not sufficient to enable the court to say that either party’s version is the more probable, then it is in a position akin to the probabilities being equal, posing the danger of conjecture. Courts should not be too ready to make findings of probability on insufficient evidence. It is a well-known principle of our law of evidence that the onus in a civil case decides which party should prevail if, at the end of the trial, the evidence is of such a nature that the court is unable to come to a definite conclusion without taking the onus into consideration.[4]

57. In the premises, I am of the view that the plaintiffs have failed to discharge the onus upon them to prove on a balance of probabilities

that the Fiprotec composition infringes claim 1 of the patent by including a crystallization inhibitor that satisfies the test in integer b).

58. That finding is dispositive of the action and the plaintiffs’ suit should be dismissed on that basis alone. However, lest another court should reach a different conclusion, I consider it desirable, and in the interests of justice between the parties, to consider the other defences pleaded by the defendant.

59. The defendant did not persist with its second pleaded defence on infringement, namely that the mixture of DGME and PG do not

constitute together an organic solvent for the purposes of integer c). It did however persist with its position that the plaintiff

failed to prove on a balance of probabilities that the ethanol in Fiprotec constitutes a co-solvent as contemplated in integer d). In the specification ethanol is listed as both an organic solvent comprising integer c) and as a co-solvent in integer d). The organic solvent in integer c) can also be comprised of “a mixture of at least two” of the specified solvents.

60. In paragraph 18 of their particulars of claim, the plaintiffs alleged that the ethanol in the Fiprotec composition is an organic

co-solvent, having a boiling point below 100°C and a dielectric constant of between 10 and 40, and which is a drying promoter. In paragraph 21 of the plea, the defendant admitted that ethanol is a drying promoter having a boiling point below 100°C and a dielectric constant of between 10 and 40 but denied the balance of the contents of the paragraph, namely that the ethanol in the Fiprotec composition is an organic co-solvent (as described in integer d)).

61. In her expert summary, Dr Witchey assumed that the ethanol in Fiprotec was a co-solvent, without any comment or observation in that regard. That assumption formed part of the basis of her conclusion that Fiprotec includes all the integers of claim 1 of the patent. She was not challenged on her statement in her expert report but the nature and function of ethanol was canvassed with her during her cross examination on the issue of clarity. Her evidence was to the effect that in the Fiprotec composition there is no other element that would serve as a potential co-solvent. The plaintiffs have also referred to an affidavit by Dr Cromarty, filed in earlier interim interdict proceedings on behalf of the defendant who stated:

“Further, as mentioned ….. ethanol is present in an amount of only 10% whilst DGME is present in an amount of 50% and PG in the amount of about 28%. Ethanol is clearly not the only, or even primary solvent in Cipla’s Fiprotec spot-on products. It is, with respect, clear that the combination of DGME and PG is the principal solvent in Cipla’s Fiprotec spot-on product. Ethanol is the low-boiling co-solvent, used to perform the drying function referred to in the specification of the patent …. When Cipla’s Fiprotec spot-on product is applied to an animal, the 10% ethanol present in the formulation would be expected to evaporate rapidly, fulfilling the drying promoter role of the low-boiling co-solvent (d) as discussed in the specification.”

62. Prof Barbour did not contradict Dr Witchey’s view that ethanol was the co-solvent. It will be recalled that the integer b) test excludes the co-solvent from the composition. Prof Barbour stated that both sides were in agreement on what was crystallization

inhibitor and what was solvent for the purpose of carrying out the test. By using DGME and PG as the solvents, by implication Prof

Barbour arguably accepted that the ethanol in Fiprotec was in fact the co-solvent. However, in cross-examination he was at pains to point out that the teaching of the patent was confusing because ethanol was identified in the specification to be both a solvent and a co-solvent. He emphasised that he performed the test as pleaded in the plaintiffs’ pleadings. In view of the denial of ethanol being the co-solvent in the plea, his conduct, it was submitted, did not constitute an admission that Fiprotec included integer d). This is borne out by the characterisation of the issue by Prof Barbour in his expert report where he stated in relation to his use of DGME and PG in the test:

“17. The witness will state that he is advised that the plaintiffs have pleaded that:

17.1 The “organic solvent” for the purposes of the crystallization test is a mixture of DGME and PG; and

17.2 The “crystallisation inhibitor for the purposes of the crystallisation inhibitor for the purposes of the crystallisation

test is a mixture of PVP and Polysorbate 80”. (emphasis supplied)

This statement cannot be construed as an admission that ethanol is the co-solvent in Fiprotec. If Prof Barbour’s evidence is read holistically it is evident that he doubted whether ethanol should be accepted as the co-solvent in Fiprotec. He merely assumed that ethanol was integer d) for the purpose of performing the integer b) test because that was the assumption of the plaintiffs.

64. In any event, during her cross-examination in relation to the questions of validity, in particular insufficiency and lack of

clarity, Dr Witchey was unable convincingly to provide a proper basis for her characterisation of ethanol as an organic co-solvent and accepted with reference to certain hypothetical examples posed to her (Exhibit K) that ethanol could be legitimately used together with other solvents as a mixture of solvents for the purposes of integer c), conceding in effect that in such instance integer d) would not be established as present. That concession, that in one case ethanol may be regarded as a solvent and in another may be regarded as a co-solvent, raised the spectre, in the words of counsel, “that the skilled addressee is left to hazard a guess as to whether any particular composition may constitute an infringement”.

65. Once again, the determination of this issue can be resolved only with reference to the sufficiency of the admitted evidence and by taking the onus into consideration. The evidence of Dr Witchey and Prof Barbour is inconclusive giving rise to equipoised probabilities. The statements in the affidavit of Dr Cromarty provide a compelling indication that the defendant regarded ethanol as the co-solvent, but that affidavit was never admitted into evidence during the trial. The extract from it quoted above is taken from the plaintiffs’ “notes in reply” handed in during argument. Even if the affidavit formed part of the record, it remains essentially hearsay in these proceedings. As there is no basis to surmise that the defendant consented to its admission and no application before me for its admission in the interests of justice in terms of section 3(1)(c) of the Law of Evidence Amendment Act 1988, the evidence is arguably inadmissible and I should accordingly not have regard to or place any reliance upon it. But even if the affidavit is admissible, on account perhaps of a tacit agreement to admit all the affidavits of the application proceedings, notwithstanding their not actually being handed in as evidence, it remains un-examined hearsay and of insufficient weight alone to establish the presence of integer d) in the infringing product.

66. The onus is on the plaintiffs to establish that Fiprotec includes integer d) of claim 1 of the patent by proving that ethanol is the co-solvent. The mere assumption by Dr Witchey that it was and the mere reliance on that assumption by Prof Barbour to perform the test he was asked to perform with the agreed ingredients, in my opinion, provide insufficient evidence from which to infer that the inclusion of ethanol in Fiprotec conclusively establishes on a balance of probabilities the existence of integer d) in claim 1. The hearsay of Dr Cromarty, assuming it to be admissible, given its necessarily limited weight and cogency, does not take the evidence beyond the requisite standard of sufficiency. It is not possible on the evidence before me to decisively reject the proposition that ethanol, together with DGME and PG merely constituted a mixture of solvents, integer c), in Fiprotec and that integer d) is accordingly absent. The defendant is accordingly correct in its submission that the plaintiffs have failed to prove that an essential integer is present in the Fiprotec composition, namely integer d), and the plaintiffs may be non-suited on this simple basis as well.

67. That leaves the defences related to validity. The defendant challenges the validity of the patent on three grounds: lack of

clarity (ambiguity or uncertainty of claiming); insufficiency; and inutility.

68. The objection of inutility is predicated upon section 65(1)(d) of the Act which provides that a patent may be revoked on the ground that the invention as illustrated or exemplified in the complete specification concerned cannot be performed or does not lead to the results and advantages set out in the complete specification. In terms of this provision inutility is assessed with reference to the body of the specification, in particular as illustrated in drawings or as exemplified by way of example.[5] Inutility is a question of fact in respect of which expert opinion evidence is admissible.

69. The defendant’s plea of inutility is set out in paragraph 5.3 of its plea as follows:

“5.3.1 The complete specification of the patent states on page 2 that: Yet another object of the invention is to provide such compositions

which, after drying do not affect the appearance of the coat and in particular do not leave crystals and do not make the coat feel

sticky, and on page 7 that ‘After deposition, the composition diffuses, in particular over the animal’s entire body, and then dries, without crystallizing or changing the appearance (in particular absence of any whitish deposit or any dusty appearance) or the feel of the coat’; and

5.3.2 compositions manufactured following examples 1-12 of the complete specification of the patent, and most notably the plaintiffs

commercial product, do affect the appearance of the coat of the animal to which it is applied after drying, and do leaves crystals

(sic) and do make the coat sticky, contrary to the results and advantages set out in the complete specification of the patent;

5.3.3 conducting a crystallisation inhibitor test using a solution ‘A’ as defined in paragraph (b) of claim 1, prepared using the ingredients of the composition exemplified in Example No. 1 of the complete specification, does not result in fewer than 10 crystals been seen with the naked eye on the glass slide.”

70. In paragraphs 26-30 of his expert report Prof Barbour referred to various tests conducted to determine whether or not crystallization

tests in relation to the composition exemplified in the patent specification produced results indicated in the specification. In

argument, counsel for the defendant relied exclusively on Example 1, which is the composition which constitutes the plaintiffs’

commercial product, composed of fipronil 10%, PVP 5%, polysorbate 80 5%, ethanol 10%, the antioxidants, 03% and DGME qs. Prof Barbour

excluded the ethanol and antioxidants in accordance with what was required in relation to the integer b) test. In his report he

recorded that “many crystals formed around the perimeter” of the 0,3ml drop which after 24 hours had formed a glassy film and that he was able to see more than 10 crystalline particles. He confirmed his finding during his evidence in chief. In paragraph 31 of his expert report Prof Barbour stated that he had been referred to 22 documents discovered by the plaintiff each of which recorded a degree of hair modification 24 hours after application to the animal in respect of a spot-on formulation including fipronil, ethanol, a solvent listed in the patent specification as suitable and a substance listed in the specification as a suitable crystallization inhibitor or a combination of such substances. Prof Barbour accordingly concluded that not all combinations of fipronil with substances named as suitable organic solvents and crystallization inhibitors will produce a result which satisfies the crystallization test and do not affect the appearance of the coat as said in the specification.

71. The fipronil used by Prof Barbour in performing these tests was that supplied by Mr Desai and not by Merial, and hence was not the actual fipronil ingredient in Frontline. The documents in question related to experiments performed by Merial associated companies and persons in the period 1994 - 1998. They were introduced in evidence, through Prof Barbour, with the aim of showing that example 1 as at 1995 did not in fact realize the promise of the patent. The documents upon which the defendant ultimately relied were admitted into evidence as Exhibit H, consisting of five documents.

72. Mr Bowman objected to this evidence in that example 1 was not concerned with a crystallization inhibitor test but was in fact a test carried out on dogs which had been infested with fleas, thus involving a composition incorporating all the ingredients including

the co-solvent and the anti-oxidants. Prof Barbour conducted the test in relation to example 1 in exactly the same way he had conducted the integer b) test, but using the proportions of ingredients of the Frontline product, and the fipronil in Fiprotec obtained from India, the impurities in which might have accounted for the failure. Such a test, in my view, is accordingly not in conformity with the requirements of example 1 and provides an insufficient basis to conclude that Frontline does not lead to the results and advantages set out in the complete specification.

73. Consequently, the defendant’s case on inutility rests in the final analysis upon the five documents in Exhibit H, which it maintained demonstrate that the Frontline product did not satisfy the promises of the specification.

74. Document 37 (Exhibit H3) describes a test on thirty-two randomly sourced cats with the compound RM 160 IE/2 which is identified in Exhibit H1, Document 50, to be “Frontline spot-on”. It concludes:

“Hair appearance at the treatment site compared to the rest of the animal was evaluated on the RM 160IE/62 treated animals. At 4 hours post treatment, most of the cats had detectable areas at the treatment sites. By 24 hours, about 30% of the cats still had detectable areas at the treatment sites.”

75. The test recorded in Document 42 (Exhibit H4) had similar poor results. Document 50 (Exhibit H7) records at the 24 hour period 20,8% of the animals treated with RM 160 IE/62 exhibited observations of crystals. The tests in the other documents produced similar results. The documentary evidence shows convincingly that Merial’s own researchers found that in various tests conducted at around the priority date there was significant residue of crystals or matting of the hair on various animals after 24 hours application of the example 1 product Frontline.

76. The plaintiffs have submitted that this evidence (hearsay admitted by consent) is insufficient to discharge the onus upon the defendant to prove inutility. The five documents selected by the defendant are taken from a bundle of 36 discovered documents comprising nearly 1500 pages. The selection does not adequately account for the context in which the test reports were written, their purpose in reporting on the development of new formulations and the circumstances in which the clinical trials were conducted. Dr Clark, a veterinary scientist called as a witness by the plaintiffs, referred in his evidence to studies conducted around about the same time which had more positive results. The defendants did not adduce evidence providing a complete picture of the number of tests performed in relation to Frontline or the number of which had positive or negative results. Presented in the way it was, the evidence is too selective to be anything but an unreliable indicator of occasional failure. This is especially the case when it is kept in mind that there is no evidence confirming that the appropriate methodology for conducting the tests was followed in the selected tests indicating failure.

77. Furthermore, the promises in the specification and the object of the invention do not equate with the requirements of the crystallization

inhibitor test in integer b) of claim 1. The promises are limited to the provision of a composition which avoids any phenomenon of crystallization “as far as possible”. It hopes to achieve in “a noteworthy manner” the absence of crystallization

on the hair and maintenance of the cosmetic appearance of the coat, that is to say without a tendency to stick together or to have a sticky appearance, despite a high concentration of active substance. I agree with the plaintiffs that the patent does not make an absolute promise in respect of the aesthetics of the coat. It does not claim that there will be no visible effect whatsoever post-application. Crystallization is promised to be reduced but not necessarily eliminated.

78. In addition, the defendant did not challenge the evidence of Dr Clark and opted not to cross-examine him. Dr Clark, a veterinary scientist with more than 30 years of experience carried out a trial to show that the claimed invention of the patent, embodied in the Frontline product, does lead to the results and advantages set out in the complete specification. His results showed no evidence of crystallization or any other change to the appearance of the coat in the form of stickiness, any whitish deposit, a dusty appearance or otherwise at either the 24 or 48 hour observation time points. He accordingly concluded that the invention delivered on the promise of the patent specification. This evidence stands unchallenged. As such, it carries more weight and cogency than the hearsay in documentary form presented by the defendants through Prof Barbour. Dr Clark’s evidence that the results of the earlier trials conducted by the plaintiff were acceptable also stands uncontroverted. As does his assertion that Frontline is the most successful anti-parasitic product on the market, which is borne out by the absence of evidence of any complaints by veterinarians or end users in relation to its efficacy.

79. The defendant has accordingly not persuaded me that it may rely upon the ground of inutility as a defence to the action for infringement.

80. The defendant’s plea in relation to clarity is set out in paragraph 5.1 of the plea as follows:

5.1 By virtue of the following Claim 1 of the patent is not clear and as such the patent is open to revocation in terms of the provisions of section 61 (1)(f)(i) of the Patents Act 57/1978 (“the Act”):

5.1.1 The meanings of the following terms are not clear in the context of the specification of the patent:

5.1.1.1 “solvent”;

5.1.1.2 “co-solvent”;

5.1.1.3 “crystallization inhibitor”; and

5.1.1.4 “fewer than 10 crystals, preferably 0 crystals, are seen with the naked eye”; and

5.1.2 The test set out in paragraph (b) of claim 1 (hereinafter referred to as “the crystallization inhibitor test”) is not clear in that:

5.1.2.1 The objective, physical results of the crystallization inhibitor test may vary depending on the conditions under which the test is conducted; and

5.1.2.2 The subjective, observed results of the crystallization inhibitor test may vary depending on each of (a) the person of the observer, and (b) the conditions under which the test results are observed.

81. Section 61(1)(f) of the Act provides that a patent may be revoked on the ground that the claims of the complete specification are not clear. The ground is directed against claims that are not clearly worded. The objection of lack of clarity differs from the objection of insufficiency in that the former is directed to the claims and not to the body of the specification, whereas in dealing with an objection based on insufficiency the whole specification must be considered. The evidence on the two issues may however overlap.[6] The requirement of clarity in the claims obliges the patentee to state clearly and distinctly the nature and limits of its claim in order to define its monopoly and so that others may understand the scope and extent of the prohibited domain.

82. The defendant did not persist in argument with its contentions that the terms “solvent”, “co-solvent” and “crystallization inhibitor” are not clear. The terms have ordinary meanings which to the extent that they have technical import would be understood by a person skilled in the act having regard to the context and the specification within which they are used.

83. The second clarity attack, which appears to be based upon a combination of the objections set out in paragraphs 5.1.1.4 and 5.1.2 relating to the integer b) test, asserts that there is ambiguity, beyond the language, in the standard by which the results of the test are measured and the unspecified variables that can affect the result of the test. It was contended in the expert report of Prof Barbour that the expression “fewer than 10 crystals … seen with the naked eye” begs the question as to whether 10 crystals must be individually visible or whether a visible collection would be fine crystalline powder. Insofar as the standard of measurement depends on whether the crystals can be seen with the naked eye certain extraneous factors like lighting, background, colour, texture, distance from the eye of the observer and the observer’s eyesight, all allegedly give rise to a lack of clarity. Likewise, it was contended that unspecified variables such as the surface condition of the slide, ventilation, humidity, seeds and impurities could result in differing observable results; and thus the test lacked clarity.

84. Prof Barbour retreated from these assertions in cross-examination during which he conceded that in his own tests he had no difficulty

in perceiving and measuring the crystallization with his naked eye, in other words with ordinary vision corrected by spectacles if necessary, and that the factors impacting on the standard of measurement were easily controllable. Similarly, the skilled formulator would know to control against the so-called unspecified variables. In the light of these concessions there is nothing left of the pleaded case of uncertainty or lack of clarity.

85. The lack of clarity attack, however, evolved somewhat during evidence and argument. A further contention was made that the claims lack clarity because the same chemical can serve different functions in the composition of claim 1 of the patent. In particular, benzyl alcohol can serve as the organic solvent in integer c) as well as being the crystallization inhibiter in integer b). Also, ethanol and isopropanol can serve as a solvent in integer c) and as the co-solvent in integer d). As mentioned earlier, this prompted counsel for the defendant to argue that the patent is unclear because “the skilled addressee is left to hazard a guess as to whether any particular composition may constitute an infringement”.

86. I agree with Mr Bowman that this attack goes to the issue of insufficiency not clarity in that it essentially alleges that the

specification does not sufficiently describe the manner in which the invention is to be performed in order to enable the invention to be carried out by a person skilled in the art of the invention. The attack is not directed at the wording of claim 1. And, in any event, to the extent that any clarity issue arises on this basis it was never pleaded by the defendant and hence I am disinclined to entertain it.

87. In consequence, the defendant has made out no case of lack of clarity upon which it may rely as a defence to the action for infringement.

88. Paragraph 5.4 of the plea raises the defence of insufficiency. It states:

“The patent is open to revocation in terms of section 61(1)(e) of the Act as the complete specification concerned does not sufficiently

describe, ascertain and, where necessary, illustrate or exemplify the invention and the manner in which it is to be performed in order to enable the invention to be carried out by a person skilled in the art of such invention, in particular in that the specification does not teach the person skilled in the art of such invention how to select a combination of ingredients so as to satisfy the crystallization inhibitor test and thus perform the invention.”

89. A challenge on grounds of insufficiency involves “a question of fact, namely, whether to a person skilled in the art the

specification contains proper instructions for enabling the invention to be put into use”.[7] Expert evidence is admissible in the matter of insufficiency and the expert is entitled to say whether in his opinion that which is described in the specification on a given hypothesis as to its meaning is capable of being carried into effect by a skilled worker. The specification should not be held to be insufficient if the person to whom it is addressed would be able to produce the article or carry out the process claimed without any difficulty and with the aid of simple routine experiments not requiring any prolonged research or enquiry. Whether that is so in any particular case is a pure question of fact, to be determined by the evidence of persons skilled in the relevant art. [8]

90. The defendant submitted that it is not possible to perform the invention, with regard to the specification alone. All of the

co-solvents listed in the patent could also be solvents and benzyl alcohol can serve as a crystallization inhibitor or a solvent. As counsel put it, once any particular compound is described in the patent specification as being capable of more than one identity or characterisation, in logic it would be impossible for the court as a matter of pure construction to determine whether such compound is to fall within the purview of integers b), c) or d) of the claim. As a matter of semantics the court is unable to determine in a composition containing ethanol together with other solvents whether it is to be regarded as a solvent or a co-solvent (integer c) or integer d)) or whether it is part of an integer c) mixture. Similar considerations apply to benzyl alcohol which may be used equally as a solvent or a crystallization inhibitor.

91. Prof Barbour confirmed in his evidence the confusion that arose from the dual function of certain constituents. However, he was prepared to concede under cross-examination that where, for instance, benzyl alcohol is both the solvent and the crystallisation inhibitor then, for the purposes of the crystallisation inhibitor test, one would simply add 10% benzyl alcohol as the crystallisation inhibitor and also add benzyl alcohol as the solvent. He also seemed to concede that one could add 10% fipronil with 10% of the crystallisation inhibitor to ethanol which would act as both solvent and co-solvent. If these concessions were correctly made they accept that the dual function of certain constituents pose no difficulties in performing the crystallisation inhibitor test. If such constituents make up the composition of the product it may be that the patentee will have difficulty in proving infringement, as in this case, but that does not mean that the specification does not sufficiently describe the manner in which the invention is to be performed in order to enable it to be carried out by a person skilled in the art.

92. Dr Witchey testified that lists of different types of solvents, co-solvents and crystallisation inhibitors in a patent are fairly

typical. She said that it would not bother her that a particular constituent performs a dual function and that there could be conceivable benefits in having as few constituents as possible in a formulation. When asked how she would perform the integer b) test, she replied that she might try a few ways of doing it acting as a formulator, or product developer. She later added that the knowledgeable formulator would follow an experimental method that would provide knowledge of the function of the relevant constituent.

93. During cross-examination, Dr Witchey was presented with Exhibit K, a series of formulas in which various constituents performed the different functions. As explained when discussing the question of infringement, she was forced to concede that if ethanol or

isopropanol was regarded as a solvent in any of the solutions, the Exhibit K composition would not infringe because of the absence of integer d); but if she made the value judgment that they were co-solvents then the composition would infringe. That evidence

advances the defendant’s case on infringement, and perhaps the un-pleaded case on uncertainty of claiming, but in my judgement does nothing for the case of insufficiency.

94. The plaintiffs’ submission that the selection of compounds for use in a particular composition is a matter for the formulation

chemist has merit. That some measure of experimentation may be required in assessing the functionality of the constituents does not render the specification insufficient. The fact that one constituent performs more than one function does not give rise to any difficulty in clarifying the functionality of the constituent in order for the invention to be carried out. There is no evidence that using benzyl alcohol, for instance, as both a crystallisation inhibitor and a solvent would have resulted in a failure of the integer b) test. If that would be the result there would then be no infringement, but it does not necessarily follow that there is insufficiency. The defendant has also not led evidence that the experimentation suggested by Dr Witchey went beyond permissible limits. Prevailing judicial authority dictates that a specification should not be held to be insufficient when the skilled addressee can produce the article or carry out the process with the aid of simple or routine experiments not requiring any prolonged research or enquiry, even if the formulator would only be able to determine ex post facto what role the constituents in a particular formulation were performing.[9]

95. Accordingly, the defendant has not made out a case that it may rely on the ground of insufficiency as a defence to the action for infringement.

96. In the result, while the defendant has not proven invalidity, the action stands to be dismissed on the ground that the plaintiffs

failed to discharge the onus to prove that the defendant’s product, Fiprotec, included integers b) and d) of claim 1 of the

patent and thus infringed. Costs should follow the defendant’s success, including, by reason of the nature of the claim and its complexity, the costs of two counsel. It was agreed between the parties that the expert witnesses would be entitled to their

qualifying fees. The defendant agreed that it was liable for the costs occasioned by the amendment of the plea.

97. In the premises, I make the following orders:

i) The action is dismissed with costs, such costs to include the costs of two counsel and the qualifying fees of Prof Barbour.

ii) The defendant is ordered to pay the wasted costs occasioned by its amendment of its plea.

JR

MURPHY

JUDGE OF THE

NORTH GAUTENG HIGH COURT

Heard on: 4-11 March 2014 & 29 April 2014

For the Plaintiffs : Adv. L Bowman SC

Adv G Marriott

Instructed by: DM Kisch Inc, Pretoria

For the Defendant : Adv CE Puckrin SC

Adv R Michau

Instructed by: Brian Bacon & Associates Inc. c/o Dr Samantha

Gregory Attorneys, Pretoria

[1] Monsanto Co. v MDB Animal Health (Pty) Ltd (formerly MD Biologics CC) 2001 (2) SA 887 (SCA); and RG Murray v Vodacom (Pty) Ltd and Another 2008 BP 31 (CP).

[2] Stauffer Chemical Co v Safsan Marketing and Distribution Co (Pty) Ltd 1987 (2) SA 331 (A) at 342 D-E.

[3] Johnson and Johnson (Pty) Ltd v Kimberley-Clark Corporation and Kimberley-Clark of South Africa (Pty) Ltd 1985 (11) BP 126 at 135-136.

[4] Van Aswegen v De Clerq 1960 (4) SA 875 (A) at 882.

[5] Burrell’s South African Patent and Design Law (3ed) para 4.4.

[6] Unilever Ltd v Colgate-Palmolive Co 1977 BP 200 (CP) at 202F.

[7] Cipla Medpro (Pty) Ltd v Aventis Pharma SA 2013 (4) SA 579 (SCA) para 23.

[8] De Beers Industrial Diamond Division (Pty) Ltd v Ishizuka 1980 (2) SA 191 (T) 198-199.

[9] Unilever v Colgate-Palmolive 1979 BP 110 (T) 115H-116A.