Federal Court of Australia

Boehringer Ingelheim Animal Health USA Inc. v Intervet International B.V. [2022] FCAFC 88

ORDERS

THE COURT ORDERS THAT:

1.    The application for leave to appeal be dismissed.

2.    The applicant pay the respondent’s costs of the application.

Note:    Entry of orders is dealt with in Rule 39.32 of the Federal Court Rules 2011.

REASONS FOR JUDGMENT

THE COURT:

Introduction

1    Before the Court is an application for leave to appeal from the judgment of the primary judge dismissing an appeal brought by the opponent (“Boehringer”) pursuant to s 60(4) of the Patents Act 1990 (Cth) (“the Act”) against the decision of the delegate of the Commissioner of Patents rejecting Boehringer’s opposition to Australian Patent Application No AU 2011268899 C1 (“the patent application”) entitled “Injectable formulation of a macrocyclic lactone and levamisole” filed by the respondent (“Intervet”).

2    Although Boehringer relied on various grounds of opposition before the primary judge, its proposed appeal does not challenge the correctness of the primary judge’s decision except in relation to the issue of inventive step. Boehringer contends that the primary judge’s rejection of its opposition on the basis that the invention described and claimed did not involve an inventive step was affected by a number of legal and factual errors.

3    The priority date of the patent application is 24 June 2010 (“the priority date”). Examination of the patent application was requested on 11 April 2013. It follows that the amendments made to the Act by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 (Cth) do not apply.

LEAVE TO APPEAL

4    Leave to appeal is required by s 158(2) of the Act because the proceeding heard by the primary judge involved an “appeal” from a delegate of the Commissioner of Patents. The principles guiding the exercise of the Court’s discretion to grant leave to appeal were considered by the Full Court in Genetics Institute Inc v Kirin-Amgen Inc (1999) 92 FCR 106 at [19]-[23] (Black CJ, Merkel and Goldberg JJ). Generally speaking, an application for leave to appeal in a matter of this kind should only be granted where the applicant has demonstrated a clear prima facie error which, if not corrected, would be likely to result in the grant of an invalid patent: Meat and Livestock Australia Limited v Branhaven LLC (2020) 281 FCR 640 at [6] (Kenny, Nicholas and Burley JJ). For reasons that follow we are not persuaded that the applicant has demonstrated any such error in this case and therefore leave to appeal should be refused.

The Patent Application

5    At page 1, lines 1-33 the patent application states:

The present invention relates to injectable formulations for controlling parasites and the use of such formulations in the preparation of a medicament for controlling parasites.

Endoparasites commonly cause clinical disease in especially in [sic] livestock animals and have significant adverse economic effects on farming economies when present at subclinical levels. The most frequently encountered endoparasites are the group of worms referred to as nematodes. The nematodes are found in the intestinal tract, heart, lungs, blood vessels and other body tissues of animals and are a primary cause of anemia, weight loss and malnutrition in the infected animals. The nematodes most commonly found to be the infecting agents of ruminants include Haemonchus and Ostertagia generally found in abomasum; Cooperia, Trichostrongylus and Nematodirus generally found in the intestinal tract, and Dictyocaulus found in the lungs.

Treatment of animals to prevent infestation by any of the above-mentioned parasites, or to reduce or control the proliferation of these parasites in animals is thus important.

Meanwhile the problem has arisen that some parasites develop a resistance to antiparasitic drugs like ivermectin. The resistance occurs when a strain of a parasite is able to tolerate doses of an active ingredient that is efficacious against other populations of parasites of the same species. This characteristic is inheritable.

After the use of macrocyclic lactones (ML) for almost two decades in cattle in Brazil several reports on resistant endoparasites in sheep, cattle and goats were published.

The discovery of novel anti-parasitics with equal or better qualities than macrocyclic lactones seems to be a distant reality in the veterinary pharmaceutical industry.

Therefore, the chemical groups available nowadays must be used in a rational way, with a view to achieving high percentages of efficacy against endoparasites, especially in ruminants and delaying the occurrence of resistant strains.

Therefore a stable formulation for a combination of a macrocyclic lacone ad [sic] levamisole would be desirable However, such combinations have been difficult to formulate.

Accordingly, there is a need for a stable suspension formulation capable of including macrocyclic lactone compounds together with levamisole.

6    At page 2, lines 2-5 the following appears:

Herein disclosed is a macrocyclic lactone solution formulation comprising levamisole in a particulate form in a non-aqueous solvent system.

The non-aqueous solvent system may comprise oil and an organic solvent.

The formulation may be suitable for injectable administration.

This is followed by a number of consistory statements which mirror various claims including claim 1.

7    This is then followed by a detailed description of the invention which includes at page 3, lines 2-28 the following:

The macrocyclic lactone solution formulation comprising levamisole in a particulate form in a non-aqueous solvent system is advantageous as it provides stable formulations including an avermectin or milbemycin in combination with levamisole.

The complicated nature of prior art formulations is due in part to the different formulation requirements of the actives. Avermectins and milbemycins being substantially insoluble in water, whereas levamisole is water soluble. In addition, levamisole has previously been found to require a pH of less than about 4 for stability while avermectins and milbemycin require a pH of about 6.6.

The formulations of the present invention exhibit desirable properties which are useful characteristics for the administration of relatively high concentrations of levamisole. The formulations are physically and chemically stable. In addition, as the formulation excludes water, the issue of incompatible pH requirements is alleviated. Enabling the two actives to stability co-exist in a single phase.

The formulations of the present invention must be stable to be of commercial use. In this specification, a commercially acceptable anthelmintic formulation is one which is stable at room temperature for a period of at least 6 months. In conditions of accelerated testing, at 40° C., this requires the potency of the actives within the formulation to remain within specified and acceptable limits for 3 months.

The macrocyclic lactones, i.e. the avermectin and milbemycin series of compounds are potent endo- and ectoparasitic agents. The compounds which belong to this series are either natural products or are semi-synthetic derivatives thereof. The structure of these two series of compounds are closely related and they both share a complex 1,6-membered macrocyclic lactone ring; the avermectins comprise a disaccharide substituent in the 1,3-position of the lactone ring, which the milbemycins do not. The macrocyclic lactones (avermectins and milbemycins) are products, or chemical derivatives thereof, of soil microorganisms belonging to the genus Streptomyces.

A number of preferred embodiments are then described.

8    The patent application also includes four example formulations (F1-F4) and some tables incorporating stability data (Table 2) and efficacy data (Table 3) for formulation F3. The formulation is set out at page 9 of the patent application. There is a statement on page 4 that “[g]ood results were obtained with a formulation comprising 1.6 – 4% w/v ivermectin and 15.04 – 18.8% w/v levamisole hydrochloride”. Formulation F3 is at the uppermost end of each of those ranges.

9    The efficacy data presented in Table 3 includes a control group (ie. untreated animals), a group treated with ivermectin only (3.15% concentration), a group treated with levamisole only (18.8% concentration), and two groups treated with a combination of those active ingredients. The first group of the combination treatments (Group 4) included active ingredient levamisole HCl at 15.05% concentration, and ivermectin at 3.2% concentration, while the second group (Group 5) included the same active ingredients at 18.8% and 4% respectively. The combination treatments were administered at different dosage rates (Group 4, 1 mL/40 kg v Group 5, 1 mL/50 kg). Efficacy figures expressed in percentage terms imply high levels of efficacy for the combination products that are comparable to, or slightly better than, the efficacy figures for the levamisole only treatment. The data appears to indicate that the use of levamisole in combination with ivermectin did not reduce the effectiveness of levamisole when used as a monotherapy.

10    The patent application includes 19 claims. Claim 1 is the only independent claim. It was not suggested by Intervet that, if claim 1 does not involve an inventive step, any of the dependent claims might still be found to do so.

11    Claim 1 defines the invention as follows:

An injectable formulation of a macrocyclic lactone and levamisole in a non-aqueous solvent system comprising oil and an organic solvent, wherein the macrocyclic lactone is in solution and the levamisole is a salt in a particulate form, and wherein the levamisole salt is present in the range of between 10-35% w/v.

12    According to the patent application at page 4, lines 35-37 a “non-aqueous solvent system” is a solvent or a mixture of solvents that essentially consists of liquids other than water and comprising at least one oil and at least one organic solvent. “Levamisole” is defined at page 4, lines 19-20 and includes levamisole hydrochloride and levamisole phosphate. Other terms used in claim 1 that are explained in the patent application at page 4, lines 26-34 include:

By “particulate form” it is meant mobile, un-dissolved, solid matter suspended in a liquid. The liquid may be aqueous, oily, or both.

A solution is a mixture of two or more components that form a single phase that is homogeneous down to the molecular level.

A suspension consists of insoluble solid particles dispersed in a liquid medium, with the solid particles accounting for about 0.5% to about 30% of the suspension.

By “w/v” is meant weight/volume, i.e. “1% w/v” means 1 g in 100 ml of the formulation. “v/v” means volume per volume, and 1% v/v means 1 ml, in a total of 100 ml.

The Primary Judge’s Reasons

13    The primary judge referred to the relevant principles governing an appeal against a decision of the Commissioner of Patents in an opposition to the grant of a patent. His Honour noted that, although the proceeding before him is referred to in the Act as an appeal, it is not an appeal in the strict sense, but rather a proceeding in the original jurisdiction by way of re-hearing. His Honour also noted that Boehringer bore the onus in relation to each ground of opposition and that, for an opposition to be upheld, it must be “clear” or “practically certain” that the patent, if granted, would not be valid.

14    His Honour made some observations concerning the witnesses who gave evidence including the three witnesses whose evidence was most relevant to inventive step. The first of these witnesses was Mr Lau, an expert witness called by Boehringer, who has qualifications in science and more than 30 years’ experience in the field of pharmaceutical formulation, particularly the formulation of medicaments for animals. His Honour found that Mr Lau had specialised knowledge in the field of pharmaceutical formulation, in particular, the formulation and chemical and physical analysis of veterinary products. His Honour observed that Mr Lau demonstrated deep experience in matters of chemistry and the formulation aspects of the development of pharmaceutical products and, subject to some particular matters, he generally accepted Mr Lau’s evidence.

15    The second witness relevant to inventive step was Dr Martin, also called by Boehringer, who his Honour found had specialist knowledge in the field of parasitology and the development of parasiticides for animals. Dr Martin’s work appears to have focused on animal parasitology and the development of animal parasiticide products. His Honour generally accepted Dr Martin’s evidence.

16    The third witness relevant to inventive step was Mr Vickers who was called by Intervet. Although Mr Vickers has a Bachelor of Veterinary Science, his Honour noted that Mr Vickers accepted that he had never been a formulation chemist. It is apparent that Mr Vickers’ expertise was more in the area of product development and regulatory affairs management.

17    His Honour noted that he preferred Mr Lau’s evidence in relation to matters of formulation chemistry to that of Mr Vickers, but that Mr Vickers impressed him as having considerable knowledge and experience in relation to the matters of safety and efficacy in the development of veterinary pharmaceutical products.

18    His Honour referred to joint expert reports that were in evidence. The first was a joint report of Mr Lau and Mr Vickers which largely focussed on issues of pharmaceutical formulation. The second was a joint report of Dr Martin and Mr Vickers which covered issues relating to the administration of veterinary pharmaceuticals, in particular, issues relating to the safety and efficacy of parasiticides.

19    His Honour referred to the description of the invention in the body of the specification and the claims including those matters to which we have previously drawn attention. His Honour noted at [29] of his reasons that “[d]ata from efficacy testing is set out in Table 3 on page 11” but did not refer again to Table 3 in his reasons.

20    His Honour found that the person skilled in the art to which the patent application was directed consisted of a team with experience in the field of animal health including a pharmaceutical formulator and parasitology expert. His Honour observed at [88]:

In Boehringer’s outline of closing submissions, it submits that: the skilled person to whom the Patent Application is directed is a team with experience in the field of animal health, including the development of injectable dosage forms for drug delivery for use in the treatment of animals (including cattle); and the team consists of a pharmaceutical formulator, instructed by a parasitology expert or experts with knowledge of the possible modes of administration, active ingredients and their concentration and the dose volume. Intervet did not dispute that the person skilled in the art was a team comprising these persons, but also placed some emphasis in its evidence and submissions on the process of obtaining regulatory approval of new products. However, I am not persuaded that the notional team need include a person with such skills, which relate to processes after development of a product. I accept Boehringer’s description of the notional skilled team.

21    His Honour found that it was common general knowledge at the priority date that it would be desirable to develop an injectable formulation for a combination of macrocyclic lactones and levamisole. The primary judge also noted that there was no suggestion that it was inventive to seek to combine macrocyclic lactones with levamisole at the priority date.

22    The findings made by the primary judge in relation to the common general knowledge at the priority date also included the following:

(1)    Livestock including sheep and cattle were affected by endoparasites (which live inside the host) such as helminths or parasitic worms. Common parasites of this kind included Ostertagia (brown stomach worm) and Cooperia (small intestinal worm). Parasiticides is an overarching term for products that treated parasites, and parasiticides that acted on helminths were referred to as anthelmintics.

(2)    Common anthelmintics for broad spectrum use include macrocyclic lactones (such as ivermectin, abamectin, avermectin, eprinomectin, moxidectin and doramectin) and imidazothiazoles such as levamisole.

(3)    Macrocyclic lactones had been in use since the 1980s, and could be applied orally, topically and by injection. They were known to be effective against nematodes living in the stomach, small intestine and lungs of sheep and cattle. They tended to be longer acting, and to be effective for days or weeks.

(4)    Levamisole had been in use since the 1970s and could be administered orally, by injection and by pour-on. Levamisole could be administered as levamisole base, or as a salt (such as levamisole HCl and levamisole phosphate). Levamisole was effective against nematodes such as Haemonchus, Ostertagia and Trichostrongylus, as well as lungworms, and it was also known to be effective against Cooperia. Levamisole tended to be short acting and rapidly excreted.

(5)    The problem of resistance was well-known. Resistance occurs where anthelmintics become less effective after several years of usage, because ongoing use will eradicate parasites that do not have the genetic makeup to survive the anthelmintic, while parasites that do have the genetic make-up to survive become the main source of subsequent generations, and become the predominant population. The growing resistance of Cooperia populations to macrocyclic lactones was well-known.

(6)    Although one strategy for dealing with resistance was to use new active ingredients, new active ingredients are very rare. A more common strategy was to combine two or three parasiticides from different classes, either separately or in combination products. From the mid-1990s, macrocyclic lactones were co-administered with levamisole to counter Cooperia resistance to macrocyclic lactones.

(7)    There was a strong market demand to formulate combination products for ease of administration.

(8)    Levamisole and macrocyclic lactones are chemically incompatible and tend to react with each other when combined.

(9)    Levamisole and macrocyclic lactones are stable under different pH conditions (levamisole requires a pH of about 3.0-4.0 to be stable, while macrocyclic lactones require a pH of around 6.0-7.0).

(10)    Levamisole salts are soluble in water. Macrocyclic lactones are not water soluble but are soluble in organic solvents, and are commonly formulated in oils and organic solvents.

(11)    Macrocyclic lactones were routinely administered to cattle by injection at a dose of 0.2 mg per kg of cow.

(12)    A safe and effective dose of levamisole HCl routinely administered to cattle by injection was 7.5 mg per kg (equivalent to 6.35 mg of levamisole base and 9.4 mg of levamisole phosphate).

(13)    For a 500 kg cow, a preferred dose volume would be no more than 20 mL overall, and preferably 10-15 mL; this equates to a dose volume rate of 1 mL/25 kg to 1 mL/50 kg of cow; where necessary, a dose volume may be divided and injected at more than one site.

(14)    The concentration of active ingredient was calculated based on the desired dose of that active ingredient, and the desired dose volume rate. Thus, for example, for an injectable combination product with a dose volume rate of 1 mL/25 kg of cow, the required concentration of levamisole and ivermectin to ensure a safe and effective dose of each of these active ingredients would be 15.9% w/v, 18.8% w/v or 23.5% w/v of levamisole (depending on whether the base, hydrochloride or phosphate form was used), and 0.5% w/v of ivermectin.

(15)    In addition to the active ingredients, there was a range of common ingredients available for use in formulating an injectable combination product. These included organic or non-aqueous solvents such as benzyl alcohol and dimethylacetamide, and oils such as castor oil and medium chain triglycerides, as well as the other ingredients disclosed in the patent application.

23    There was also expert evidence, accepted by his Honour, as to the mode of operation of levamisole in the animal. His Honour said at [178]:

In oral evidence, Dr Martin agreed with the following propositions regarding the mode of operation of levamisole: one requires a sufficient dose level and concentration within the animal to achieve paralysis of the relevant worms; the intention of the particular mode of operation of levamisole is that the worms stay paralysed for long enough that they are excreted; one typically aims to achieve a rapid, high blood level of levamisole if levamisole is being administered by injection; the nature of levamisole is that it is rapidly metabolised by the animal; the effect of this is to rapidly reduce the concentration of levamisole within the animal; in terms of the speed of excretion, typically more than 90% is excreted within 24 hours for cattle. Mr Vickers agreed with these matters and added that levamisole usually peaks very quickly, usually about two to three hours after administration by an oral or injectable; it peaks very quickly and then it is excreted very quickly. Dr Martin agreed with this. I take these matters to form part of the common general knowledge as at the priority date.

24    There are several observations to make in relation to his Honour’s common general knowledge findings.

25    First, an injectable formulation including as active ingredients a macrocyclic lactone, ivermectin at 0.5% w/v and the levamisole salt, levamisole HCl at 18.8% w/v would be within the concentrations specified in claim 1.

26    Secondly, since macrocyclic lactones are not water soluble, they were commonly formulated in oils and organic solvents. Claim 1 requires that the macrocyclic lactone be present in solution (ie. dissolved) in such a system.

27    Thirdly, there were no known oily formulations in which levamisole was present in particulate form (or at least none that were common general knowledge). This is presumably because levamisole is water soluble and can only be dissolved in an aqueous solution.

28    Fourthly, since macrocyclic lactone and levamisole salt are chemically incompatible, requiring different pH conditions if they are to remain stable, a formulation that combined these ingredients would need to address these issues.

29    The primary judge also made a number of significant findings concerning the way in which the hypothetical team, including the formulation chemist, would develop a new formulation including, in particular, an injectable combination product with a macrocyclic lactone and levamisole as the two active ingredients. His Honour found at [196]-[199]:

[196]    There were a range of routine or conventional tests or trials available to the skilled team to evaluate and assess the stability, safety and efficacy of a formulation. These would be carried out as a matter of course. Such tests or trials included dose titration or confirmation studies to identify preferred concentrations of the active ingredients, and routine preliminary tests to assess the occurrence and extent of potential issues with injection site irritation, the blood/release profile of the active ingredient, any impact of using an oil-based formulation, and any impact of the active ingredient being in particulate form. Where appropriate, the tests or trials would be carried out in parallel on multiple variants of a proposed formulation.

[197]    More particularly, the formulation chemist would develop preliminary formulations, which would be assessed for chemical stability using [high performance liquid chromatography] under normal and accelerated testing conditions. Formulators would also assess the physical characteristics and physical stability of each formulation. The preliminary formulations would be refined until there was a lead formulation or formulations that could be progressed to preliminary efficacy trials in the field and further stability testing. Lead formulations that proved effective and stable in preliminary trials would then be submitted to full-scale efficacy and safety trials and stability testing for the purpose of obtaining regulatory approval. The formulation chemist would understand that the regulator would require full-scale efficacy and stability testing irrespective of whether or [sic] the formulation was based on a registered single-active product, or formulated as a suspension rather than another type of formulation.

[198]    A formulation chemist asked to formulate an injectable combination product as at June 2010 would seek to develop a product that was effective, stable, safe, sterile and syringeable. The formulation chemist would depend on other members of the skilled team to provide the effective dose of the product, as well as other relevant information. The formulation chemist would receive a briefing from a colleague with biological training as to issues relating to the biological properties of the active ingredients. The formulation chemist would have some knowledge of each ingredient, based on his or her experience in developing anthelmintic products, including other injectable formulations and other dosage forms.

[199]    In the case of a combination of a macrocyclic lactone and levamisole or its salts, the formulation chemist would know that levamisole HCl or levamisole phosphate were preferred over levamisole base because they are more chemically stable, with a longer shelf life. The formulation chemist would know that levamisole HCl was commonly used in anthelmintic products and readily available. The formulation chemist would prefer to use ivermectin and abamectin over other macrocyclic lactones, since these were widely available from suppliers.

30    The primary judge referred to Mr Lau’s evidence in which he was instructed to assume that, as at the priority date, he was given the task of formulating a combination injectable product containing a macrocyclic lactone and levamisole for cattle that was effective, stable, safe, sterile and syringeable. According to Mr Lau, he would have selected levamisole HCl together with ivermectin or abamectin. Due to the chemical incompatibility of these ingredients Mr Lau would have explored strategies for formulating the combination injectable which kept the levamisole and macrocyclic lactone separated.

31    The two main strategies Mr Lau would have considered involved the use of either a micellar formulation or a suspension formulation with the aim of keeping the two active ingredients physically separated.

32    Using the micellar approach proposed by Mr Lau, a micellar solution would form when the concentration of surfactant in water reached the concentration at which micelles formed. In a micellar solution, each micelle has a hydrophilic exterior, where the polar hydrophilic ends of the surfactant molecules are in contact with water molecules, and a hydrophobic interior, where the fatty ends of the surfactant are located. The abamectin or ivermectin would be dissolved in an organic co-solvent and reside in the hydrophobic environment inside the micelles. The levamisole HCl would be dissolved in the aqueous environment outside the micelles. It may be noted that in such a system both the macrocyclic lactone (ie. abamectin or ivermectin) and the levamisole HCl are dissolved in solution. Such a system would be outside claim 1.

33    If Mr Lau was to have used the suspension approach, he would have dissolved the abamectin or ivermectin in a carrier made using an oil or organic carrier as the base. He would also use a co-solvent, such as benzyl alcohol, to assist in solubilizing the abamectin or ivermectin. He might use more than two organic carriers depending on the viscosity of his preliminary formulation and whether it was suitable for holding the levamisole HCl in suspension. He would, if necessary, adjust the viscosity of his formulations through the selection of different solvents or the use of a suspending agent to increase the viscosity of the carrier. Mr Lau expected that, if he were to formulate the combination of abamectin or ivermectin and levamisole HCl as a suspension, it would be stable. A formulation such as that described by Mr Lau in which the macrocyclic lactone is in solution, and the levamisole HCl is in particulate form, would be within claim 1 subject to it meeting the relevant concentration requirements.

34    The primary judge referred to the evidence of Mr Vickers who expressed concern that the use of a suspension could affect the release profile of the levamisole in the formulation making it different from the known release profile of the drug. We note that his Honour’s reasons do not indicate what the release profile of levamisole was when used in solution or to what extent this would also be affected by the mode of administration, its concentration, or whether it was used in combination with other active ingredients. However, Mr Vickers’ evidence was that use of a suspension in which the levamisole was in particulate form could affect its release profile.

35    Mr Lau accepted that the use of a suspension in which the levamisole was in particulate form could affect its release profile. His response to Mr Vickers’ evidence on this topic was referred to by the primary judge as follows at [227]-[229]:

[227]    Mr Lau also stated in his third affidavit that he did not agree with Mr Vickers that a potential change in the release profile or absorption rate of levamisole salt was a reason not to formulate the combination injectable with the levamisole salt in suspension. Mr Lau stated that an active ingredient could be formulated so as to have a different release profile and a different absorption rate from an existing formulation and still be effective. He stated that the efficacy of the levamisole salt as part of the combination injectable would be tested in the ordinary course of product development.

[228]    In oral evidence, Mr Lau was questioned about the statement in [60] of his first affidavit (summarised in [212(a)] above) regarding the risk that an active ingredient formulated as a suspension will not be dispersed evenly throughout the formulation. Mr Lau had stated in his affidavit that this risk was greater if the active ingredient was present at a low concentration. It was put to Mr Lau that the same would be true where there was a high concentration of the active ingredient. Mr Lau accepted that, theoretically, this was the case, but said that he did not think it was an issue practically. In response to a question whether he had conducted any tests to establish that it was not an issue practically, Mr Lau said that he had not. I am not persuaded that there was a relevant difference in relation to the risk that an active ingredient may not be evenly dispersed as between a low concentration and a high concentration of the active ingredient. Accordingly, I find that this is a risk in both scenarios (and this formed part of the common general knowledge as at the priority date).

[229]    Mr Lau was asked during oral evidence about issues regarding agglomeration of particles (that is, the formation of larger particles). Mr Lau accepted that if there are more solid particles present, there is a higher chance of agglomeration; he said agglomeration was possible. Mr Lau was asked whether, all other things being equal, for an injectable formulation, it is preferable to have a solution rather than a suspension. Mr Lau responded: “If you take away the compatibility problem and you take away things like – you might want an extended release product, yes.” On the basis of this evidence, I find that, all other things being equal, for an injectable formulation, a solution is preferable to a suspension (and this formed part of the common general knowledge as at the priority date).

36    It is apparent that Mr Lau did not accept that a potential change in the release profile of levamisole was a reason not to use the suspension and the fact that the release profile might be different from an existing formulation did not mean that the drug would not be effective. He acknowledged that there was a risk that levamisole might not be evenly dispersed in a suspension, which was a risk his Honour found existed irrespective of whether the concentration used was high or low.

37    His Honour found that if levamisole was present in particulate form in a formulation, an issue requiring investigation would be whether this affected the rate of absorption of the levamisole. His Honour found that was a matter of common general knowledge at the priority date.

38    As to the risk of agglomeration, Mr Lau acknowledged that agglomeration was possible and that, all other things being equal, this risk could be avoided by using a solution rather than a suspension. His Honour found that due to the risk of agglomeration occurring in a suspension, it would be preferable to employ a solution rather than a suspension. We should say it is not clear to us whether his Honour is referring here to a single phase solution, which would not be capable of carrying two incompatible active ingredients, or a micellar solution which, as explained in Mr Lau’s evidence, would be able to provide the physical separation necessary to carry two incompatible active ingredients.

39    There was other evidence given by Mr Vickers and summarised by the primary judge which indicated that use of levamisole in particulate form and with an oil based solvent system had the potential to affect the release rate. According to Mr Vickers it would therefore be necessary to test the formulation to prove that it was effective and safe. There was other evidence given by Mr Lau, also referred to by the primary judge, which indicated that because micellar solutions contain large amounts of surfactants, they can suffer from foaming problems during manufacture and use in the field.

40    His Honour also referred to oral evidence given by Mr Vickers and Dr Martin in relation to the concentration of active ingredients to be included in an injectable formulation of macrocyclic lactone and levamisole and the impact that the use of an oil based solvent system with levamisole in particulate form might have on the release rate. His Honour referred to this evidence as follows at [237]-[238]:

[237]    During the oral evidence, Mr Vickers was taken to [21]-[24] of the Martin/Vickers Joint Report, which sets out the concentrations of macrocyclic lactone and levamisole salt that the experts would include in an injectable veterinary pharmaceutical product for cattle, comprising a combination of (a) a macrocyclic lactone; and (b) a levamisole salt. Dr Martin and Mr Vickers agreed on certain concentrations, which are summarised in [195] above. In that context, the following exchange took place:

    [COUNSEL FOR BOEHRINGER]: And so if [sic] this right? If you were considering a formulation, an injectable veterinary pharmaceutical formulation as at June 2010 that comprised those two ingredients, the macrocyclic lactone and the levamisole salt, the amounts that you’ve set out in your answers are the amounts or concentrations of those ingredients that you would include in that formulation?

    MR VICKERS: Correct.

    [COUNSEL FOR BOEHRINGER]: And you would do that based on the standard dose rates that you’ve previously referred to and the desirable dose volume rates for cattle; correct?

    MR VICKERS: Correct.

    [COUNSEL FOR BOEHRINGER]: And in adopting that approach, you would expect, based on the knowledge that you had as at June 2010, that those concentrations of those two active ingredients in that formulation may well produce an acceptable formulation in terms of its efficacy and the action of the two active ingredients.

    MR VICKERS: Yes.

    [COUNSEL FOR BOEHRINGER]: Doctor – sorry.

    MR VICKERS: My only comment about that is that we’re using desired dose rates which are actually known dose rates.

    [COUNSEL FOR BOEHRINGER]: Yes.

    MR VICKERS: So they’re not based on solutions of levamisole salt.

    [COUNSEL FOR BOEHRINGER]: Yes. But you’re using the information that was known to derive a concentration that you would use, and then seek to take it forward; correct?

    MR VICKERS: Correct, yes.

    [COUNSEL FOR BOEHRINGER]: Dr Martin, do you agree with that?

    DR MARTIN: Yes, I would agree with that.

[238]    The following exchange also occurred:

    [COUNSEL FOR BOEHRINGER]: Yes. I think I asked you this before, but just to come back to it, just based on what you knew as at June 2010, you wouldn’t know whether or not these issues that you’ve raised, having the levamisole in an oil-based organic solvent system and being in a particular [sic] form, would have an impact on the release rate ..... of it, correct?

    MR VICKERS: I actually believe I would have considered it possible and quite probable that it could change the release of the levamisole hydrochloride, but I wouldn’t know the extent or the duration.

    [COUNSEL FOR BOEHRINGER]: And in light of the fact that you wouldn’t know the extent or the duration, your expectation, if you were asked to consider a formulation of this kind, as at June 2010 would be that it may well produce an acceptable release rate of levamisole hydrochloride, but you wouldn’t know? You would have to go and test it; is that correct?

    MR VICKERS: Correct.

    [COUNSEL FOR BOEHRINGER]: And, Dr Martin, do you agree with that?

    DR MARTIN: Yes. I would agree with that.

41    His Honour also referred to other evidence by Mr Lau concerning work he undertook while he was the Head of Chemistry at Jurox relating to the formulation of a stable parasiticide composition comprising a mixture of tetramisole (a class of active ingredients that includes levamisole and levamisole salts) and macrocyclic lactone. His Honour noted that this project led to the filing on 20 December 2005 of a patent application in respect of which Mr Lau was the named inventor. His Honour referred to this patent application and oral evidence given by Mr Lau in relation to it as follows at [241]-[243]:

[241]    The title of the patent application is “Stable Parasiticide Composition” and the abstract commences: “The invention provides a stable preparation containing a mixture of tetramisole and macrocyclic lactone in an alkaline medium without the need for formation of an emulsion or micelle solution.” The “Background art” section of the application included:

    It has been difficult to formulate liquid formulations which contain a mixture of some classes of actives due to chemical incompatibility between active compounds, hydrolysis, low solubility of the active compounds and instability at alkali pH.

    When formulating a preparation containing tetramisoles and macrocyclic lactones, traditional formulations require micelles or emulsions to stabilise the macrocyclic lactones at alkaline pH or the use of a salt of tetramisole in an acidic medium. Emulsions and micelle solutions contain large amounts of surfactants and tend to create foaming problems during manufacturing and use in the field. Emulsions and micelle solutions tend to foam when agitated during transport or shaking. Foaming traps air bubbles in the product and therefore a 30 ml dose may be altered to contain for example, 25 mL liquid and 5 mL air. This may cause non-uniformity in dose volume. Emulsions may also suffer from emulsion breakdown at high or low storage temperature, which causes break down of the formulation.

(Emphasis added.)

[242]    In oral evidence, Mr Lau was taken to the passage set out above and the following exchange occurred:

    [COUNSEL FOR INTERVET]: If I could then just direct your attention down to about line 16, is this the case, that – so this is from around 2005. At that time – this is reflective of your understanding, that it had been:

    … difficult to formulate liquid formulations which contain a mixture of some classes of actives, due to chemical incompatibility between active compounds, hydrolysis, low solubility of the active compounds and instability at alkali pH.

       MR LAU: Yes.

    [COUNSEL FOR INTERVET]: And that related specifically to the tetramisoles, including levamisole and to – with macrocyclic lactones?

       MR LAU: Yes.

    [COUNSEL FOR INTERVET]: And is this a document – did you help draft this or review it at the time?

      MR LAU: Yes, I helped draft and review it, yes.

    [COUNSEL FOR INTERVET]: And if you go down a few more lines, it says here:

    Emulsions and micelle solutions contain large amounts of surfactants and tend to create foaming problems during manufacturing and use in the field.

    And down a couple more lines, it states that that can cause non-uniformity in dose volume. So that was a potential issue with having a micellar formulation; is that the case?

    MR LAU: Yes.

[243]    Mr Lau accepted that the approach taken in the 2005 patent application involved a co-solvent approach, and that the patent application was an example of a co-solvent approach being used to achieve a stable formulation of a macrocyclic lactone and levamisole; in other words, the approach taken did not involve the use of a suspension. After further discussion of the patent application, the following exchange took place:

    [COUNSEL FOR INTERVET]: So what this patent shows – or patent application, rather, shows, back in 2005, you were working on the very same issue – at least at the level of achieving a stable liquid formulation of levamisole and a macrocyclic lactone; is that correct?

       MR LAU: Yes.

    [COUNSEL FOR INTERVET]: It doesn’t relate – the approach that you took doesn’t relate to either of the two approaches that you describe in your affidavit, does it?

       MR LAU: Yes, that’s right.

42    With regard to Boehringer’s case that the invention, as claimed, did not involve an inventive step, the primary judge described two available approaches to the question of inventive step. His Honour said at [257]:

[257]    If the matter is approached by reference to the modified “Cripps question”, the question is whether, in light of the common general knowledge as at June 2010, the notional skilled team would be directly led as a matter of course to try a formulation as claimed in claim 1 of the Patent Application in the expectation that it might well produce a useful alternative to or better alternative than known products. Alternatively, the matter may be approached by asking whether, in light of the common general knowledge as at June 2010, the task of formulating a composition as claimed in claim 1 involves steps of a routine character that would be tried by the skilled team as a matter of course.

We will refer to the authorities that inform these approaches to inventive step later in these reasons.

43    His Honour next referred to the submissions made by Boehringer which his Honour recorded as follows at [258]-[259]:

[258]    Boehringer submits that the evidence discloses that it would have been obvious to the notional skilled person or team to make a suspension formulation using an oil or organic carrier as a base and a co-solvent such as benzyl alcohol (an organic solvent), in which the macrocyclic lactone was in solution and the levamisole salt was in suspension. It is submitted that the skilled person would appreciate that, in such a composition, the levamisole salt would be in particulate form, and would know to use a concentration of levamisole salt of 18.8% w/v (for levamisole HCl) or 23.5% w/v (for levamisole phosphate) to achieve the desired dose in a product for cattle having a dose volume rate of 1 mL/25 kg. Boehringer submits that that results in a formulation in accordance with claim 1 of the Patent Application, and that a conclusion of obviousness similarly follows in relation to the dependent claims (for the reasons set out in a schedule to Boehringer’s closing submissions).

[259]    Boehringer relies heavily on Mr Lau’s evidence that he would have adopted either of two routine formulation approaches, namely a micellar solution approach or a suspension formulation approach. Boehringer submits that the fact that two such options were available does not undermine the conclusion that the suspension formulation approach was obvious; this is a case where there were two obvious pathways available, one of which directly led to the claimed invention.

44    His Honour then enumerated eight reasons why he considered that the lack of inventive step case was not made out. These eight reasons were the focus of Boehringer’s submissions in this Court. We now summarise his Honour’s eight reasons, and will refer to them in greater detail when considering the parties’ submissions.

45    First, his Honour referred to “the extent of departure from existing known formulations”. His Honour regarded it as important that there were no commercially available injectable formulations of levamisole in particulate form including, injectable formulations of levamisole in particulate form in an oily formulation.

46    Second, his Honour referred to his previous findings in relation to the common general knowledge which included the fact that levamisole and macrocyclic lactones are chemically incompatible and have different pH requirements, that levamisole salts are soluble in water, whereas macrocyclic lactones are not soluble in water and are commonly formulated in oils and organic solvents.

47    These first two matters were said by his Honour to be important. His Honour also said at [263]:

[263]    These matters presented, at the least, challenges in developing a satisfactory formulation for a combination injectable comprising a macrocyclic lactone and levamisole. As noted at [242] above, Mr Lau accepted that the statement in the 2005 patent application (Exhibit R6) that “[i]t has been difficult to formulate liquid formulations which contain a mixture of some classes of actives due to chemical incompatibility between active compounds, hydrolysis, low solubility of the active compounds and instability at alkali pH” reflected his understanding.

48    His Honour then referred to a statement by Dr Martin made in 2007 that “[d]ifferent classes of actives are difficult to formulate together, and some combinations are incompatible, and degrade if held in the same solvent formulation”. His Honour noted that Dr Martin accepted that statement applied to a combination of macrocyclic lactone and levamisole, with Dr Martin adding that “I’d have to be careful of combining anthelmintics to achieve the stability that’s required, and I think that’s also the case for macrocyclic lactone and levamisole.”

49    Thirdly, the primary judge referred to the fact that Mr Lau’s second approach, which broadly corresponded with claim 1 of the patent application, was proposed by Mr Lau without knowledge of the mode of action and desired release profile of levamisole. His Honour observed at [265] that “… [t]he fact that Mr Lau, a formulation chemist, came up with his two main approaches without the benefit of input from the biology team and thus without relevant knowledge regarding the mode of action and release profile of levamisole, calls into question whether his approach to the hypothetical formulation task is representative of that of the notional skilled team”.

50    In relation to Mr Lau’s evidence concerning the significance of the release profile and absorption rate of levamisole salt, and evidence given by Dr Martin concerning those matters, his Honour said at [266]-[267]:

[266]    I note for completeness that Mr Lau in [33] of his third affidavit stated that he did not agree with Mr Vickers that a potential change to the release profile or absorption rate of levamisole salt was a reason not to formulate the combination injectable with the levamisole salt in suspension. However, that needs to be read with Mr Lau’s oral evidence in relation to that paragraph. In response to questions by counsel for Intervet, Mr Lau accepted that the release profile and absorption rate of levamisole were relevant considerations. He also said that a formulation with a different release profile may nevertheless prove to be effective upon testing. The difficulty with the evidence at [33] of Mr Lau’s third affidavit is that it comes after the event, that is, after he had already developed his two main approaches without the benefit of input from the biology team and thus without relevant information.

[267]    I also note for completeness the evidence given by Dr Martin quoted at [235] above. With reference to the proposition that the fact that the levamisole salts were in particulate form could potentially affect the release rate of the levamisole, Dr Martin was asked by senior counsel for Boehringer: “Is it the case, then, that that proposition wouldn’t have dissuaded you from trying and considering a formulation that had levamisole salts in particulate form?” Dr Martin answered: “I think the answer is yes. I would think that could be tried. I didn’t at the time do that, but if it had have been suggested to me, then perhaps yes, you could undertake that process.” In relation to that evidence, and the other evidence quoted in [235] above, I note that several of Dr Martin’s answers were couched in tentative terms. Thus, I do not consider this evidence to detract substantially from the point that Mr Lau developed his two main approaches without the benefit of input from the biology team and thus without relevant information, and that this is relevant in considering whether his approach is representative of that of the notional skilled team.

51    Thus, his Honour appears to have regarded the persuasiveness of Mr Lau’s evidence on this point was diminished because Mr Lau’s two main approaches were developed without the benefit of relevant information which would have been provided to him by the biology team. As to Dr Martin’s evidence, his Honour characterised this as “tentative” and that it did not overcome the difficulty with Mr Lau’s evidence.

52    Fourth, his Honour made an important finding regarding uncertainty as to the efficacy of levamisole when delivered in a combination product as a particulate form and in an oily formulation. His Honour found at [268] that “… this uncertainty would have pointed the notional skilled team away from adopting this type of formulation with the expectation that it might well produce a useful alternative to or better alternative than the known products”.

53    His Honour developed this proposition as follows at [269]-[274]:

[269]    As set out at [178] above, one requires a sufficient dose level and concentration of levamisole within the animal to achieve paralysis of the relevant worms; the intention of the particular mode of operation of levamisole is that the worms stay paralysed for long enough that they are excreted; one typically aims to achieve a rapid, high blood level of levamisole if levamisole is being administered by injection; levamisole usually peaks very quickly, usually about two to three hours after administration by an oral or injectable; it is then excreted very quickly.

[270]    All commercially available injectable formulations of levamisole had the levamisole dissolved in an aqueous solution, which allowed for sufficiently quick absorption to achieve the above concentration peak. The effect of shifting to an oily formulation involved significant unknowns. Oily formulations were used to delay the absorption of active ingredients, for long-acting active ingredients such as macrocyclic lactones. An oily formulation for levamisole was a significant departure from known formulations, and its impact could only be known by conducting testing. There was clear potential for such a formulation to prevent the necessary peak concentration from being reached.

[271]    Further, a particulate formulation of levamisole was also a significant departure from known injectable formulations, all of which had levamisole in dissolved form. Before the particulate levamisole became effective it would need to reach the animal’s gut, where the relevant helminths are located. Dr Martin said in oral evidence that that could happen by it being dissolved, or being absorbed by some other process. He explained that one possibility was that it would “simply dissolve in the aqueous environment in the subcutaneous area of the animal”, and then said: “And I don’t know, but I would be interested to ask the question as a researched [sic] or how that did impact on its absorption and the blood levels in the animal. I don’t know the answer. I would want to explore it.”

[272]    In his written and oral evidence, Mr Vickers identified using levamisole as a particulate and in an oily formulation as areas of uncertainty. In particular, as noted above, in oral evidence Mr Vickers was asked about the issue of the slowing down of the release rate in the context of an approach that had the levamisole present in an oily formulation as particles. Mr Vickers stated that he thought the issue “arises even more so” in such a case. He stated that if the levamisole was present in particles, his concern was: “would that even slow it down further and slow the release rate?”

[273]    I note that Dr Martin gave evidence (quoted at [235] above) that his expectation, without more than the knowledge he had then, would be that levamisole in particulate form “would be absorbed not too differently to the aqueous solutions”. However, elsewhere in Dr Martin’s evidence he seemed to accept that this was an area of uncertainty. To the extent that there is a difference between Mr Vickers’s evidence and that of Dr Martin on this point, I prefer Mr Vickers’s evidence, which I found persuasive.

[274]    In closing submissions, Boehringer drew attention to the fact that there were commercially available products with the anthelmintic in suspension products as at the priority date. One example given was the Triton product. However, as described in [61] and [69] of Mr Vickers’s affidavit, this was an oral drench product rather than an injectable, and the anthelmintic present as suspended particles was albendazole. Further, it was a predominantly aqueous formulation in which the levamisole was dissolved in the aqueous phase.

54    His Honour concluded at [275] that the possibility of an oily formulation with levamisole present as a particulate was a substantial departure from known formulations, particularly in relation to levamisole and that the resultant “uncertainties as to efficacy” would point the notional skilled team away from the adoption of Mr Lau’s second approach.

55    Fifth, his Honour referred to the risk that an active ingredient formulated as a suspension would not be dispersed evenly throughout the formulation, which would also give rise to the risk of agglomeration. It followed, according to his Honour, that, all other things being equal, it was preferable to use a solution rather than a suspension for an injectable formulation.

56    Sixth, his Honour referred to secondary evidence that he found supported the existence of an inventive step. He found at [277] that there was a long-standing need for combination treatments of levamisole and macrocyclic lactone which could be administered as a combination in injectable form. His Honour considered that the fact that no one had suggested or made an oily injectable formulation with levamisole salt in particulate form before the priority date was some evidence that such a formulation was not obvious. In this context his Honour referred to Mr Lau’s work at Jurox aimed at developing a stable liquid formulation of levamisole and a macrocyclic lactone. Importantly, his Honour noted that the approach in the patent application did not reflect either of the two main approaches identified in Mr Lau’s first affidavit. His Honour also referred to Dr Martin’s involvement in the Virbac project which was focused on a combined treatment of macrocyclic lactone and levamisole. However, as his Honour’s reasons recognise, the Virbac project related to the use of two different formulations rather than a single combined formulation.

57    Seventh, his Honour did not regard the uncertainties associated with Mr Lau’s second approach as merely issues to be resolved by way of routine testing. His Honour reiterated that the uncertainties he had identified would point the notional research team away from the second approach proposed by Mr Lau. His Honour added (without elaboration) that “… while the uncertainties could be the subject of testing, I would not characterise such tests as routine”.

58    The eighth and final reason given by his Honour for rejecting Boehringer’s lack of inventive step case based on the common general knowledge alone concerned the evidence given by Dr Martin and Mr Vickers which concerned matters such as efficacy, release rate and absorption (rather than formulation chemistry). His Honour referred here to Dr Martin’s evidence (set out above) concerning his willingness to consider a formulation that had levamisole salts in particulate form. As to Mr Vickers’ evidence, his Honour observed that, while Mr Vickers accepted certain propositions as to his expectation of achieving an acceptable result “… this was qualified by the need for testing … not merely routine testing but testing of a more fundamental nature”. His Honour said this evidence of Dr Martin and Mr Vickers was evidence that “does not go very far”.

59    In the result, with regard to Boehringer’s case based on the common general knowledge alone, his Honour said that he was not satisfied (let alone clearly satisfied) that the notional skilled team would be directly led as a matter of course to try a formulation as claimed in claim 1 of the patent application in the expectation that it might well produce a useful alternative to or better alternative than known products or that the task of formulating a composition as claimed in claim 1 involved steps of a routine character that would be tried by the skilled team as a matter of course.

60    His Honour then turned to the lack of inventive step case which relied on both the common general knowledge and a patent application (“CN 291”) entitled “Veterinary Compound Injection Containing Levamisole or Salts thereof” published on 23 October 2002. His Honour noted that there was no issue that CN 291 is a document falling within s 7(3) of the Act and that it was prior art information that the skilled person or team could, before the priority date, be reasonably expected to have ascertained, understood and regarded as relevant.

61    It is necessary to refer to CN 291 in a little detail before explaining why it was that his Honour rejected Boehringer’s lack of inventive step case based on the common general knowledge together with the information contained in that document.

62    CN 291 states at p 1 of the specification:

The present invention relates to a veterinary anthelmintic compound injection prepared by using levamisole or salts thereof and macrolide anthelmintic.

Levamisole is a levo form of tetramisole and a broad-spectrum nematode-repelling drug, and has a repelling and killing effect for various nematodes which parasitize in animal body. However, the repelling and killing activities to nematodes of different species are different. For example, the repelling and killing activity to several nematodes which parasitize in stomach and lung tissues of animals (such as pigs, cattle and sheep) can reach 95-100% (see Table 1), while the repelling and killing activity to some nematodes which parasitize in small intestine and large intestine is lower, and levamisole does not have repelling and killing activities to trematodes, tapeworms and ectozoic parasites.

Macrolide anthelmintic includes abamectin, ivermectin, eprinomectin, moxidectin and doramectin. They are a kind of high-efficacy broad-spectrum anthelmintic and have activities to nematodes and ectozoic parasites which widely parasitize in animal body. However, the repelling and killing activities to nematodes of different species which parasitize at different parts of organisms are different (see Table 1). Recent investigation and clinical tests indicate that, since ivermectin or levamisole single-component preparation has been used for many years (approximately 20 years), some nematodes have resistance to these two kinds of drugs in different degree. For example, the repelling rate of ivermectin to haemonchus is 100% at the beginning of use but the current repelling rate is 78-85%. When the compound preparation (containing 5mg of abamectin or ivermectin and 50-60mg of levamisole) provided by the present invention is injected into castle and sheep according to a dosage of 0.5ml per 10kg of weight, the repelling rate thereof to haemonchus and other various nematodes can still reach 95-100% (see Table 1), and after abamectin or ivermectin is added into the formula, ectozoic parasites can be controlled at the same time.

Therefore, the preparation provided by the present invention has the feature that levamisole and the macrolide anthelmintic such as abamectin are combined to form a compound preparation which can be used for controlling drug-resistant nematodes. In addition, the compound injection provided by the present invention not only has a fast-acting efficacy, but also has a long-acting efficacy, therefore not only reducing both dosing times and dosing cost but also thoroughly repelling parasites.

The veterinary compound injection containing levamisole or salts thereof provided by the present invention comprises the following formula components:

(a)    1-25% (W/V) of levamisole or salts thereof;

(b)    0.1-10% (W/V) of macrolide anthelmintic (abamectin, ivermectin, eprinomectin, moxidectin and doramectin);

(c)    balance of dispersion media;

63    CN 291 includes three examples. Example 1 on p 4 of the specification is an example of what we would understand to be a micellar solution containing the surfactant Tween-80 (10% w/v) and the two active ingredients levamisole HCl (12% w/v) and abamectin (1% w/v). Example 3 on p 5 of the specification is as follows:

Example 3

This example is used for preparing an oil injection containing 0.5% of ivermectin and 5% of levamisole hydrochloride

Levamisole hydrochloride    5% (W/V)

Ivermectin    0.5% (W/V)

Benzyl alcohol    10% (V/V)

Benzyl benzoate    40% (V/V)

Soybean oil added to    100% (V/V)

64    We will return to consider evidence given in relation to CN 291 later in these reasons. For present purposes we merely note that Mr Lau gave evidence that Example 3 was a suspension formulation. We also note that Example 3 includes the two relevant active ingredients, levamisole HCl and ivermectin, but that the concentration of levamisole HCl is below that specified in claim 1 of the patent application in suit.

65    Having referred to evidence given by Mr Lau and Mr Vickers in relation to CN 291 and Boehringer’s submissions in relation to that document, his Honour provided three reasons why Boehringer’s case of lack of inventive step based on the common general knowledge and CN 291 was not made out.

66    First, his Honour observed at [292] that there was no discussion in CN 291 of stability issues or stability tests. His Honour said that the authors of CN 291 appear to have been unaware of the chemical incompatibility of levamisole and macrocyclic lactones. It followed, according to his Honour, that CN 291 did not provide any direct assistance to the notional skilled team in addressing the known chemical incompatibility of levamisole and macrocyclic lactones.

67    Secondly, his Honour noted at [293] that Example 3 of CN 291 does not set out any manufacturing steps or any description of the formulation that is intended to be made including whether it was intended that the levamisole HCl be in particulate form.

68    Thirdly, his Honour also noted at [294] that, after being taken through the detail of CN 291, Mr Lau accepted that it would not provide any additional assistance to the task of solving the relevant problem. In this regard his Honour referred to evidence he previously set out in connection with his consideration of novelty. His Honour said at [99]:

[99]    Mr Lau accepted during oral evidence that CN 291 does not state whether any of the Examples had been made or tested. Mr Lau accepted that none of the Examples sets out any manufacturing steps, or any description of what is intended to be made. The following exchange took place during the oral evidence, with reference to Mr Lau undertaking the task of formulating a combination injectable comprising a combination of a macrocyclic lactone and levamisole:

    [COUNSEL FOR INTERVET]: In practical terms, though, if you were actually undertaking this task in 2010, there is nothing in CN291 that would have provided you with any practical assistance, is there?

    MR LAU: Could you repeat your question?

    [COUNSEL FOR INTERVET]: Yes. So as a practical matter, had you actually been undertaking that task in June 2010? There’s nothing in CN291 that would have provided you with any practical assistance.

    MR LAU: Okay. I would be using my experience to make up those formulations.

    [COUNSEL FOR INTERVET]: But you could have used your experience based on the description you have already given in your affidavit. You don’t get any additional assistance from anything that’s in CN291, do you?

    MR LAU: Sorry, I didn’t quite understand your question.

    [COUNSEL FOR INTERVET]: So you had a set of knowledge as at June - - -

    MR LAU: Yes.

    [COUNSEL FOR INTERVET]: - - - 2010, as you’ve - - -

    MR LAU: Yes.

    [COUNSEL FOR INTERVET]: - - - described previously, in earlier parts of this affidavit.

    MR LAU: Yes.

    [COUNSEL FOR INTERVET]: And what I am saying – suggesting to you that in approaching this combination [injectable] exercise at that time, there is nothing in CN291 that would provide you with any additional assistance.

    MR LAU: Correct.

    [COUNSEL FOR INTERVET]: Sorry?

    MR LAU: Yes, there is not.

69    His Honour concluded at [295] that, in light of those matters, he was not satisfied (let alone clearly satisfied) that, equipped with the common general knowledge and CN 291, the notional skilled team would be directly led as a matter of course to try a formulation as claimed in claim 1 of the patent application in the expectation that it might well produce a useful alternative to or better alternative than known products or that the task of formulating a composition as claimed in claim 1 involves steps of a routine character that would be tried by the skilled team as a matter of course. His Honour therefore rejected Boehringer’s case based on the common general knowledge and CN 291.

The Proposed Grounds of Appeal

70    Boehringer relied on the following five grounds of appeal:

1.    The primary judge erred in finding that the ground of lack of inventive step (on the basis of the common general knowledge alone or in combination with CN 291) was not made out in relation to claim 1 and dependent claims of the Application (at [283], [296]).

2.    In particular, the primary judge erred in failing to apply the principle that it is necessary to assess whether an invention involves an inventive step by reference to the invention as claimed (at [225], [232], [265]-[275]).

3.    Further or in the alternative, the primary judge erred in misapplying the principle that the skilled person had to be “directly led as a matter of course” to try the invention as claimed “in the expectation that it might well produce a useful alternative to or better alternative than known products” (at [282], [295]).

4.    Further or in the alternative, the primary judge erred in failing to find that the task of formulating a composition as claimed involved steps of a routine character that would be tried by the skilled person as a matter of course (at [282], [295]).

5.    Further or in the alternative, having found that CN 291 met the threshold requirements of s 7(3) of the Act (at [284]), the primary judge failed to give proper consideration to whether the invention as claimed was obvious in the light of common general knowledge considered together with the information in CN 291 (at [292]-[294]).

71    Each ground was accompanied by detailed particulars which we have not reproduced but which cover matters that were addressed by Boehringer in its written and oral submissions.

72    We will briefly summarise the parties’ submissions and where necessary refer to these in greater detail in our consideration of the issues raised. We note that there was no difference between the parties as to the relevant principles of law. The application for leave to appeal, and any appeal, turns on what Boehringer characterises as errors by the primary judge in fact finding, and in the application of the relevant principles to the facts as found.

Boehringer’s Submissions

73    In support of its application for leave to appeal, Boehringer submitted that the correctness of the primary judge’s decision was attended by sufficient doubt to warrant its re-consideration by the Full Court, and that his Honour made a number of clear errors of principle which, if not corrected, would allow what would be an invalid patent to proceed to grant.

74    Further, Boehringer submitted that leave to appeal should be granted in the interest of justice because the issues of principle raised were important, that there was a public interest in the integrity of the Register, and that the primary judge’s decision involved the first consideration of the evidence of Mr Lau, Dr Martin and Mr Vickers, none of which was before the delegate.

75    Boehringer’s criticisms of the primary judge’s reasons fell into three broad categories.

76    First, Boehringer submitted that the primary judge erred in failing to determine whether the invention, as claimed, involved an inventive step. In essence Boehringer contended that the primary judge’s consideration of inventive step focused on issues relating to the efficacy, release rate and rate of absorption, even though claim 1 does not require that the formulation achieve any particular degree of efficacy or exhibit a particular release rate or rate of absorption. Boehringer also contended that the primary judge erred in considering these issues in relation to Mr Lau’s micellar and suspension formulation. Rather, Boehringer submitted that the issue or “problem” addressed by the application was one of formulation chemistry: the task of combining two known active ingredients, a macrocyclic lactone and levamisole, in a single injectable formulation. Boehringer relied upon the judgment of Jagot J (with whom Besanko and Nicholas JJ agreed) in Nichia Corporation v Arrow Electronics Australia Pty Ltd [2019] FCAFC 2 (“Nichia”) at [114]-[120]. In that case her Honour found that the primary judge had, in applying the Cripps question, wrongly approached the matter on the basis that the relevant “useful result” was a device (a white light emitting device or LED) that possessed certain desirable qualities (related to durability, tone and luminance) found in embodiments described in the body of the specification, but which were not referred to in the relevant claim.

77    Secondly, Boehringer submitted that his Honour required too high a standard of expectation of success on the part of the notional skilled team and in doing so failed to give proper weight to the evidence of Mr Lau and the other experts when applying the Cripps question concerning expectation of success. Boehringer submitted that the relevant expectation of success need only relate to stability and not stability and efficacy. However, Boehringer submitted that the requisite expectation of success in relation to both stability and efficacy was established by the evidence of Dr Martin and Mr Vickers.

78    The evidence, and his Honour’s own findings, were said by Boehringer to show that the steps that would need to be taken by the notional skilled team to arrive at a formulation within claim 1 were routine and would be taken as a matter of course with the requisite expectation of success. Boehringer submitted the routine testing would only take place after the relevant formulation was created and that such testing was therefore not relevant to inventive step. Boehringer further submitted that the evidence did not disclose anything in the nature of a difficulty overcome, a barrier crossed, or something beyond the skill of the calling, in creating an injectable formulation falling within the scope of claim 1.

79    In relation to the eight reasons given by the primary judge regarding his Honour’s conclusion that the obviousness case was not made out based on common general knowledge alone, Boehringer submitted that upon analysis those reasons do not support his Honour’s conclusion and involve the errors of principle outlined above.

80    Thirdly, Boehringer submitted that the primary judge made a number of errors in relation to its case based on the common general knowledge and CN 291. An error of principle was said to arise out of his Honour’s application of ss 7(2) and 7(3) of the Act by reason of what was said to be the primary judge’s failure to have regard to the information in CN 291 in combination with the common general knowledge. Boehringer submitted that a skilled person in the art would have construed Example 3 to be a suspension and also noted that CN 291 included express statements regarding the efficacy of the formulations including in relation to Example 3. Boehringer also submitted that his Honour either misinterpreted or misapplied evidence given by Mr Lau in relation to the significance of the information contained in CN 291.

Intervet’s Submissions

81    Intervet opposed the application for leave to appeal on the basis that the correctness of the primary judge’s decision was not attended by sufficient doubt. However, it submitted that if leave to appeal was granted, the appeal should be dismissed on the basis that the primary judge was correct in concluding that it had not been shown that the patent applied for would be clearly invalid or that it was “practically certain” that it would be invalid if granted.

82    Intervet submitted that the primary judge gave proper consideration to the language of the claims when considering whether the invention, as claimed, lacked an inventive step. It drew attention to [144]-[170] of the primary judge’s reasons, in [144] his Honour refers to s 18(1)(b)(ii) of the Act which requires that the invention, so far as claimed in any claim, involves an inventive step.

83    Intervet submitted that the problem to be solved was not simply to create a stable mixture of two drugs that sits on a shelf unused, but to create a stable injectable formulation that would have some anti-parasitic effect. Intervet accepted that the claims do not include any express or specific requirement as to either the stability or efficacy of the formulations of claim 1. However, it submitted that these were considerations that were relevant to the question whether the notional skilled team would have been directly led as a matter of course to try, with the requisite expectation of success, to make an injectable formulation comprising macrocyclic lactone and levamisole as active ingredients, with the levamisole present in particulate form in an oily phase.

84    The essence of Intervet’s submission on this point was that his Honour was correct to find that neither of the tests applied by him for determining whether the invention was obvious was satisfied because uncertainty as to the efficacy of such a formulation would point the notional skilled team away from such an approach. It was submitted that, as his Honour found, the evidence did not establish that the notional skilled team would be directly led as a matter of course to try a formulation as claimed in claim 1 in the expectation that it might well produce a useful or better alternative to known products. Intervet further submitted that his Honour was correct to find that the steps involved in arriving at such a formulation were not routine in character.

85    In its submissions Intervet emphasised the following matters:

(1)    Although claim 1 did not require the formulation to exhibit any particular degree of efficacy, the notional skilled team would understand that it had to be safe and stable and also demonstrate some efficacy (ie. anti-parasitic effect).

(2)    Mr Lau did not profess to have any expertise as to the modes of operation of macrocyclic lactone or levamisole salt even though the modes of action, rates of release and absorption rates, are all matters relevant to the efficacy of a proposed formulation.

(3)    Since levamisole salt is a key component of the formulation claimed in claim 1, it would be necessary for the skilled team to understand its method of action and how it might behave in an injectable composition with macrocyclic lactone. Those are matters about which the parasitologist, as a member of the skilled team, would express his or her views.

(4)    There were at the priority date no injectable formulations combining the macrocyclic lactone and levamisole or any formulation in which solid particles of levamisole were suspended in an organic carrier. In the relevant prior art formulations that were at the priority date common general knowledge, the levamisole was dissolved in an aqueous solution. The primary judge observed the extent of the departure from past inventions was ‘significant’ and ‘substantial’, particularly regarding the use of levamisole in a particulate form in an oily solution.

(5)    A formulation that included particles of levamisole suspended in an oily phase would be likely to decrease the rate of absorption of the drug and might also lead to increased irritation at the injection site. Such a formulation would most likely be less effective than one in which the levamisole was dissolved in an aqueous solution. For those reasons, Mr Vickers (a parasitologist) would not have considered using a suspension for an injectable formulation.

(6)    The stability and efficacy of any proposed pharmaceutical formulation can be assessed through routine testing, but that does not make any and every proposed formulation obvious. A distinction was drawn between routine tests for confirmatory purposes and testing that would take place at an earlier stage of a research project.

(7)    There were secondary indicia of inventiveness including that this was a longstanding problem and Mr Lau’s and Dr Martin’s own work before the priority date which suggested that the second of Mr Lau’s proposed approaches (ie. the use of a suspension) was, in the real world, unlikely to have been tried by the notional skilled team either at all or with the requisite expectation of success.

86    With regard to Boehringer’s case based on the common general knowledge and the information contained in CN 291, Intervet submitted that all the primary judge was required to do by reason of s 7(3) of the Act was to take the information in CN 291 into account, which he plainly did. Intervet submitted that even though the notional skilled team would have ascertained, understood and regarded that information as relevant, CN 291, even when read with the common general knowledge, would not have directly led the notional skilled team to try, with the requisite expectation of success, an injectable formulation in which levamisole HCl was included in particulate form in a suspension with ivermectin in solution. Intervet submitted that the contents of CN 291 suggested a lack of understanding on the part of its authors of the stability issues that arise when combining levamisole HCl and ivermectin and noted that it does not mention that any testing had been done. It further submitted, in effect, that CN 291 did not reflect any consistent or coherent approach to the problem of combining levamisole HCl and ivermectin in a single injectable formulation and that it would not be likely to provide the notional skilled team with any meaningful direction or insight beyond what would be gained from the common general knowledge.

CONSIDERATION

87    Before considering the parties’ submissions, it is useful to refer to the relevant statutory provisions and legal principles applicable to Boehringer’s opposition to the patent application on the ground that the invention as claimed did not involve an inventive step. For this purpose we have drawn on the primary judge’s detailed account of the relevant provisions and principles which, as we have mentioned, was accepted by the parties as accurate.

88    Section 18(1)(b)(ii) of the Act requires that the invention, so far as claimed in any claim, involves an inventive step when compared with the prior art base as it stood before the priority date. The concept of inventive step is dealt within ss 7(2) and (3) of the Act. At the relevant time ss 7(2) and (3) provided as follows:

(2)    For the purposes of this Act, an invention is to be taken to involve an inventive step when compared with the prior art base unless the invention would have been obvious to a person skilled in the relevant art in the light of the common general knowledge as it existed in the patent area before the priority date of the relevant claim, whether that knowledge is considered separately or together with the information mentioned in subsection (3).

(3)    The information for the purposes of subsection (2) is:

(a)    any single piece of prior art information; or

(b)    a combination of any 2 or more pieces of prior art information;

being information that the skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood, regarded as relevant and, in the case of information mentioned in paragraph (b), combined as mentioned in that paragraph.

89    For the purposes of s 7(3), the expression “prior art information” is defined in the Dictionary in Sch 1 to the Act to mean information that is part of the prior art base in relation to deciding whether an invention does or does not involve an inventive step. The expression “prior art base” is also defined. It is not in dispute that CN 291 was part of the prior art base as defined.

90    The principles relating to inventive step were considered by the High Court in Aktiebolaget Hässle v Alphapharm Pty Ltd (2002) 212 CLR 411 (“Alphapharm”); Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (No 2) (2007) 235 CLR 173 (“Lockwood No 2”); and AstraZeneca AB v Apotex Pty Ltd (2015) 257 CLR 356 (“AstraZeneca HC”).

91    Alphapharm was concerned with the provisions of the Patents Act 1952 (Cth). However, it remains a leading authority in relation to the issue of inventive step (or obviousness) more generally.

92    In Alphapharm, the majority (Gleeson CJ, Gaudron, Gummow and Hayne JJ) referred to the expression “matter of routine” at [50]-[53] and quoted from the judgment of Aickin J in Wellcome Foundation Ltd v VR Laboratories (Aust) Pty Ltd (1981) 148 CLR 262 (“Wellcome Foundation”) at 286 where his Honour discussed the relevance of research and experiments performed by an inventor leading to the invention. In Alphapharm the majority said at [50]-[53]:

[50]    In Wellcome Foundation, Aickin J referred to the taking of a series of routine steps and the making of a series of routine experiments and continued:

    “The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not.” (Emphasis added.)

    …

[51]    What Aickin J had in mind as “routine” appears from an earlier passage in his judgment in which he was discussing the question whether evidence of the steps taken by the patentee was relevant and therefore admissible in a revocation action. His Honour said:

    “Evidence of what he did by way of experiment may be another matter. It might show that the experiments devised for the purpose were part of an inventive step. Alternatively it might show that the experiments were of a routine character which the uninventive worker in the field would try as a matter of course. The latter could be relevant though not decisive in every case. It may be that the perception of the true nature of the problem was the inventive step which, once taken, revealed that straightforward experiments will provide the solution. It will always be necessary to distinguish between experiments leading to an invention and subsequent experiments for checking and testing the product or process the subject of the invention. The latter would not be material to obviousness but might be material to the question of utility.” (Emphasis added.)

[52]    There are distinct strands of thought in this passage which may now be considered in terms applicable to the issues in this ligitation [sic]. First, the working trials of which Dr Cederberg gave evidence may be (it is not necessary to determine the point) an example of the “subsequent experiments for checking and testing”, to which Aickin J referred at the end of the above passage. Secondly, the invention claimed in the Patent lay not in perceiving “the true nature of the problem” to which “straightforward experiments” then would provide the solution; the invention was in the interaction between the integers of the compound, to answer the known problem. Thirdly, in a case such as the present, the relevant question was that posed in the first part of the passage. Were the experiments “part of” that inventive step claimed in the Patent or were they “of a routine character” to be tried “as a matter of course”? If the latter be attributable to the hypothetical addressee of the Patent, such a finding would support a holding of obviousness.

[53]    That way of approaching the matter has an affinity with the reformulation of the “Cripps question” by Graham J in Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd [1970] RPC 157. This Court had been referred to Olin in the argument in Wellcome Foundation. Graham J had posed the question:

    “Would the notional research group at the relevant date, in all the circumstances, which include a knowledge of all the relevant prior art and of the facts of the nature and success of chlorpromazine, directly be led as a matter of course to try the –CF3 substitution in the ‘2’ position in place of the –C1 atom in chlorpromazine or in any other body which, apart from the –CF3 substitution, has the other characteristics of the formula of claim 1, in the expectation that it might well produce a useful alternative to or better drug than chlorpromazine or a body useful for any other purpose?” (Emphasis added.)

    That approach should be accepted.

(some footnotes omitted)

93    It may be noted that the Cripps question, or the reformulated Cripps question as it is sometimes called, as expressed in light of the facts in Alphapharm at [53], was directed to the formula of claim 1 of the patent in suit in that case and the particular characteristics of the formula as claimed.

94    The first of Boehringer’s submissions focused on the primary judge’s references to “considerable uncertainty”, “significant unknowns”, and “uncertainties” in relation to the efficacy of a formulation in which the levamisole was present as a particulate in an oily formulation. At [268] his Honour said that he considered that this uncertainty would point the notional skilled team away from adopting this type of formulation with the requisite expectation. At [270] his Honour stated that the effect of shifting to an oily formulation involved significant unknowns, that there was a clear potential for such a formulation to “prevent the necessary peak concentration being reached”, and at [280] his Honour stated that the uncertainties were not merely issues to resolve by way of routine tests. At [275] his Honour referred again to the “uncertainties as to efficacy” which he reiterated would point away from the adoption of such a formulation.

95    Boehringer says that in referring to these uncertainties and unknowns in relation to efficacy, his Honour was adopting too high a standard, in much the same way as was found to have occurred in Nichia, because claim 1 does not require that a formulation within its scope have any particular release profile or absorption rate or other measure of efficacy.

96    We think it is apparent from his Honour’s reasons that in considering the matter of efficacy in the context of the Cripps question, and whether the uncertainties to which his Honour referred would point the notional skilled team toward or away from any shift to an oily formulation, his Honour was merely recognising that a formulation within the scope of claim 1 had to be safe and efficacious. Efficacious in this context requires no more than that it have some meaningful anti-parasitic effect. The very nature of the invention, a pharmaceutical composition for use in the treatment of animals, as described and claimed requires that it be safe and efficacious for it to be useful. This distinguishes the case from Nichia which concerned desirable but non-essential qualities identified in the body of the specification but not referred to in the claims.

97    The notional skilled team looking to create an injectable composition comprising a macrocyclic lactone and levamisole would clearly be aiming to develop a product that was safe and efficacious. His Honour reasoned that the adoption of a formulation which used levamisole as a particulate in an oily formulation gave rise to considerable uncertainty as to whether such a formulation would have any anti-parasitic effect and that this is a factor that should be taken into account when addressing the Cripps question. We are not persuaded that his Honour imposed too high a standard or that he failed to have regard to the requirements of claim 1 and the absence of any express efficacy requirement.

98    Boehringer’s second submission is concerned with the oral evidence given by Mr Vickers and Dr Martin referred to by the primary judge at [237] and [238]. According to the transcript reproduced by the primary judge at [237] counsel for Boehringer put to Mr Vickers that if he were to use what were agreed to be standard concentrations of a macrocyclic lactone and a levamisole salt as the active ingredients in an injectable formulation then this “may well produce an acceptable formulation in terms of its efficacy …”. Mr Vickers agreed with that proposition subject to the use of known dose rates which were not based on levamisole salt. Dr Martin agreed with that evidence. It will be recalled that the primary judge said of this evidence that it “does not go very far”.

99    It was also put to Mr Vickers in the transcript reproduced by the primary judge at [238] that he would not know whether having the levamisole in an oil based organic solvent system in particulate form would have an impact on the release rate. Mr Vickers said that it was “quite probable” it could change the release rate of levamisole HCl. He accepted that in order to know whether the release rate for levamisole HCl was acceptable, he would need to test the formulation. Dr Martin agreed with that proposition.

100    The substance of Boehringer’s submission in relation to the evidence referred to at [237] is that the primary judge should have given it decisive, or at least greater, weight when addressing the Cripps question. So understood, Boehringer’s submission is not directed to any error of principle but is rather a complaint as to the primary judge’s evaluation of the relevant evidence.

101    It is important in this context to recognise the advantages enjoyed by the primary judge. As Gyles J observed in Azuko Pty Ltd v Old Digger Pty Ltd (2001) 52 IPR 75 at [152]:

… Apart from seeing the witnesses, including the expert witnesses, the trial judge is educated in the issues, including the technical issues, in a comprehensive and orderly fashion which is difficult, if not impossible, to recreate on appeal: see the cogent comments by Kirby J in State Rail Authority (NSW) v Earthline Constructions Pty Ltd (in liq) (1999) 160 ALR 588 at 619, [90]; 73 ALJR 306 at 330 …

102    In the present case the relevant evidence was directed to an aspect of the Cripps question which involves a hypothetical test expressed in subtle language (including “in the expectation that it might well”) that is capable of being understood in different ways. In any event, the Cripps question was ultimately for the primary judge to answer, and although his Honour was bound to consider the oral evidence of the expert witnesses in question, he was not bound by the answers given by them, and was entitled to assess the strength of that evidence in light of the evidence as a whole. It will be apparent from what we have said that the primary judge’s assessment of the oral evidence in question did not involve, and was not affected by, any error of principle.

103    As mentioned, Boehringer submitted that the evidence did not disclose anything in the nature of “some difficulty overcome, some barrier crossed” or something “beyond the skill of the calling” using language referred to with approval in Lockwood No 2 at [52]. However, having regard to the way in which the case was run, the question whether the patent application, if granted, would result in a patent that was clearly invalid, was to be addressed by reference to the Cripps question. Boehringer’s contention that there was here no difficulty overcome, or barrier crossed, is not consistent with the answer given to the Cripps question. Moreover, it is not supported by the secondary evidence referred to by the primary judge including, in particular, “… the failure of others to find a solution to the problem at hand …”; Lockwood No 2 at [115]. As the High Court observed at [116]:

An Australian court should be slow to ignore secondary evidence or to rely on its own assumed technical expertise to reach conclusions contrary to such evidence. Australian courts have long recognised that the importance of such evidence and its weight will vary from case to case; it will not necessarily be determinative.

(Footnotes omitted)

104    The secondary evidence in this case was of particular significance in that it concerned attempts made by both of Boehringer’s expert witnesses to solve the very problem to which the patent application is directed. Mr Lau’s evidence in chief focused on two approaches that he said he would have taken in 2010 to the hypothetical problem of formulating an injectable combination of the relevant active ingredients. The 2005 patent application filed by Jurox, which named Mr Lau as the sole inventor, referred to the difficulty of formulating combinations of some classes of active ingredients due to their chemical incompatibility. The compositions described in the Jurox application (at p 3) were said to be suitable for oral or topical administration “and may also be administered as an injection”. The claims were not restricted to any particular form of administration and would clearly extend to the relevant compositions for use as an injectable. The research work that culminated in the filing of Jurox’s application was not addressed in Mr Lau’s evidence in chief but in cross-examination he acknowledged that the approach he then took involved use of a co-solvent to achieve a stable formulation of macrocyclic lactone and levamisole which did not involve the use of either a micellar solution or a suspension.

105    Boehringer submitted that Mr Lau’s prior work, as reflected in the 2005 patent application, was done some years before the priority date, and that he would have taken a different approach in 2010. However, we were not directed to any evidence which would support such a conclusion. Nothing emerged in the course of Mr Lau’s re-examination which would explain why the approach he took in 2005 should have been different from the approach he said he would have taken in 2010.

106    Dr Martin’s evidence showed that his work on the Virbac project did not involve an attempt at combining the relevant active ingredients into a single injectable composition. But it did show that he recognised at the time that although there was a need for a combination treatment, the different release profiles for levamisole and macrocyclic lactones, and their chemical incompatibility, raised challenges that would need to be addressed if the two ingredients were to be combined in a single formulation.

107    Boehringer submitted that it was significant that there was no pharmaceutical formulator on the team that worked with Dr Martin on the Virbac project. That may be so, but at the very least Dr Martin’s evidence appears to confirm the existence of a long standing need (dating back to 2005 or earlier) for a combination product of the type covered by claim 1.

108    Another matter on which Boehringer placed particular reliance was the primary judge’s observation at [281] of his reasons suggesting that any testing that would need to be done to determine the efficacy of a combination formulation in which the levamisole was present in particulate form in an oil based phase would not be routine. Boehringer submitted that this was contrary to Mr Vickers’ evidence, and to his Honour’s own findings set out at [196]-[197] of his reasons.

109    Mr Vickers was asked various questions in cross-examination as to how a new pharmaceutical composition comprising a combination of known active ingredients would typically be developed. He agreed that there were a variety of tests routinely used to determine the stability, safety and efficacy of such a composition. He distinguished between preliminary testing aimed at evaluating the new composition and other testing that was required to be performed in order to obtain regulatory approval.

110    We did not understand Mr Vickers to say that the development of any new composition comprising a combination of known active ingredients involved no more than routine testing. It was necessary for Boehringer to establish that there was no inventive step involved in arriving at a composition in which the levamisole would be present in particulate form in an oil based phase and the macrocyclic lactones present in solution. In this case any inventive step resided in the selection of that system. Whether or not any testing of the system was, or would be, routine does not establish that the selection of that system would have been obvious to the notional skilled team or that it would have been directly led as a matter of course to try such a system with the requisite expectation of success. In any event, we think that the preliminary testing that Mr Vickers was referring to in his evidence would not have been routine in the sense that it was merely confirmatory, or undertaken for regulatory purposes, but that it was testing engaged in as part of a research project aimed at exploring some possibilities.

111    Boehringer’s other criticisms of the primary judge’s eight reasons for not rejecting the obviousness case based on the common general knowledge alone were essentially directed to the weight that his Honour gave to particular matters relevant to his ultimate conclusion. The criticisms overlook the fact that none of the various matters referred to by his Honour was itself determinative. Rather, each of the eight reasons referred to by his Honour, weighed collectively, led his Honour to his ultimate conclusion.

112    Further, we do not accept that the primary judge made any error in relation to CN 291.

113    Although it was established that the information in CN 291 meets the requirements of s 7(3) of the Act, it was still necessary for the primary judge to consider whether the invention as claimed was obvious in light of that information together with the common general knowledge. The extent to which the information contained in CN 291 may have assisted the notional skilled team in considering how to proceed was relevant to the question to be addressed under s 7(2) of the Act and, in particular, the Cripps question as formulated in his Honour’s reasons at [285].

114    As to Boehringer’s submission that his Honour did not consider CN 291 in combination with, or in light of, the common general knowledge, we think it clear that his Honour made no such error. The relevant section of his Honour’s reasons is headed “Common general knowledge and CN 291” and at [285] of the reasons the Cripps question is expressed by his Honour by reference to the common general knowledge and CN 291. At [291] of the reasons, his Honour indicates that the case “based on the common general knowledge and CN 291, is not made out”. There is no substance to the submission that his Honour failed to have regard to the common general knowledge in combination with CN 291.

115    It is apparent from his Honour’s reasons that the focus of his consideration was whether there was any additional information in CN 291 which would lead the notional skilled team on a course that his Honour was not persuaded it would have taken (at least not with the requisite expectation of success) based on the common general knowledge alone. It was therefore necessary for his Honour to consider what additional information CN 291 provided to the notional skilled team and whether it added anything to the common general knowledge which would have directly led that team to try, with the requisite expectation of success, an oil based organic solvent system in which the levamisole was present in particulate form.

116    In rejecting Boehringer’s case based on CN 291 in combination with the common general knowledge, the primary judge focused on the quality of the information in CN 291 and the extent to which it might have encouraged the notional skilled team to take an approach different from that which it would have taken if it possessed the common general knowledge alone.

117    His Honour observed that CN 291 does not include any discussion of stability issues nor any reference to stability testing. His Honour found that the authors did not appear to have an appreciation of the difficulties involved in combining levamisole and macrocyclic lactones due to their chemical incompatibility. These are matters which, having regard to the primary judge’s earlier findings, would be likely to have an impact on the willingness of the notional skilled team to make use of any information described in CN 291 in addressing the problem of how to combine those chemicals in a single injectable formulation.

118    Another matter to which his Honour drew attention was the absence of any explicit indication that Example 3 includes levamisole HCl in particulate form. We agree that this too may have diminished the significance of CN 291 and, in particular, the potential for it to encourage the notional skilled team to try the Example 3 formulation or any formulation like it falling within claim 1 of the patent application with the requisite expectation of success. The fact that levamisole is present in a particulate form in formulations described and claimed in the patent application is a key feature of the invention and is not something described or even alluded to in CN 291. Nor are there any manufacturing steps or processes described in the document from which the skilled reader could infer whether the levamisole was present in particulate form or in solution (although experiments conducted later by Mr Lau established that it was present in particulate form).

119    So far as Mr Lau’s oral evidence is concerned, the relevant extract is set out at [99] of his Honour’s reasons which is reproduced above. In his evidence Mr Lau in effect agreed that if he was seeking to develop an injectable formulation combining both levamisole and macrocyclic lactones, CN 291 would not have provided him with any additional assistance.

120    Boehringer submitted that the primary judge’s evaluation of this evidence overlooks the fact that Mr Lau’s position was that he would have tried an oil based organic solvent system in which the levamisole was present in particulate form in any event based on common general knowledge alone, without the need for any assistance from CN 291 and that his evidence should have been understood in that light.

121    We do not accept this submission for two reasons.

122    First, Mr Lau was clearly asked whether, in attempting to develop an injectable formulation combining levamisole and macrocyclic lactones, he would have derived any additional assistance from CN 291 and he answered this question in the negative. Boehringer would have us interpret Mr Lau’s evidence as meaning that CN 291 did not disclose to Mr Lau anything that he did not already know and that is why he did not think it provided him with any additional assistance. That is not how we read Mr Lau’s evidence. We think it is more likely that the lack of stability and efficacy data led Mr Lau to answer the relevant question in the way he did. We note that his answer was not the subject of any re-examination.

123    Secondly, Mr Lau’s evidence is significant for what he did not say. For example, he did not say in his oral evidence that CN 291 showed that a formulation similar to Example 3 had been shown to be stable or effective or that it would provide the notional skilled team with any justification or encouragement to try Example 3 in the expectation that it may well produce a stable and effective formulation. In circumstances where there is no stability or efficacy data reported it is not surprising that Mr Lau did not suggest that CN 291 was a particularly helpful or encouraging document.

124    In our opinion it was open to the primary judge to reject the obviousness case based on CN 291 when read with the common general knowledge for the reasons his Honour gave.

Disposition

125    In our opinion Boehringer has failed to establish that any of the primary judge’s findings or conclusions with respect to the issue of inventive step was affected by any relevant error. Nor do we consider that the applicant established any clear prima facie error which, if not corrected, would result in the grant of an invalid patent. In those circumstances we propose to dismiss the application for leave to appeal with costs. It is therefore not necessary for us to consider various additional factual matters raised in a proposed notice of contention upon which Intervet indicated it would rely if leave to appeal was granted.

Associate:

Dated:    18 May 2022