FEDERAL COURT OF AUSTRALIA

Orion Corporation v Actavis Pty Ltd [2015] FCA 909

THE COURT ORDERS THAT:

1.    On or before 28 August 2015 the parties confer and prepare draft orders to give effect to these reasons and:

(a)    if the form of those orders is:

(i)    agreed provide them to the associate to Rares J;

(ii)    not agreed provide the respective forms of orders for which each contends together with written submissions limited to one page in support;

(b)    deal with the question of costs, if agreed.

2.    If on or before 2 September 2015 the parties cannot agree on what order for costs is appropriate, they confer as to a timetable to file and serve any evidence and written submissions limited to five pages in chief and reply so that the question of costs be ready to be heard on a date to be fixed.

3.    The proceedings stand over to 28 August 2015 at 2.15 pm for mention.

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

REASONS FOR JUDGMENT

1    This case concerns, first, the validity of Orion Corporation’s Australian patent No. 765932, that makes claims for a monopoly over compositions consisting of a combination of three known active pharmaceutical ingredients (APIs) called levodopa, carbidopa and entacapone, and methods of producing that combination and tablets comprising it, secondly, whether Actavis Pty Ltd’s compositions of those three APIs infringe any of the valid claims in the patent and thirdly, whether some of the claims are invalid on various bases. The three APIs are used in the treatment of Parkinson’s disease.

2    Parkinson’s disease affects the ability to initiate movement voluntarily. Its principal characteristics are slowness or lack of movement, rigidity of the limbs or trunk and tremor of body parts when at rest. Sufferers of this disease often have a stooped posture, shuffling gait and an expressionless face. Typically, the onset of the disease occurs between the ages of 40 and 70, and the average age for its onset is about 60.

3    In the late 1950s and early 1960s scientists discovered, first, the role of dopamine as a neurotransmitter in the brain, secondly, an association between a depletion of dopamine in the brain and symptoms of Parkinson’s disease and, thirdly, that that depletion could be reversed or reduced by administering an amino acid, the abbreviated name of which was D,L-dopa. D,L-dopa can be partially converted to dopamine in the brain by the enzyme dopa decarboxylase (DDC).

4    Importantly, dopamine cannot be administered to a patient directly, that is, orally or by injection into peripheral tissues, because it degrades rapidly in the body before it reaches the brain. And, the administration of D,L-dopa in large doses produces serious and unwanted side effects. The next discovery, in 1969, was that L-dopa, an isomer of D,L-dopa, was effective in treating the disease and could be administered in markedly lower doses. L-dopa is called “levodopa”.

5    Then, in 1974, scientists discovered that two substances, carbidopa and benserazide inhibited the action of DDC in peripheral tissues, but not in the brain. That resulted in a significant reduction in the rate of degradation of a dose of levodopa in the body and bloodstream before the dose reached the brain. In other words, the DDC inhibitors protected the dose of levodopa from degrading while it traveled through the body, but, at the blood-brain barrier, the DDC inhibitors did not cross into the brain with the levodopa. The consequence was a further reduction in the size of the necessary dose of levodopa that a patient needed. From the time of this discovery, the standard therapy for Parkinson’s disease employing levodopa invariably consisted of using that API in formulations prepared together with either carbidopa or benserazide in particular fixed ratios.

6    Even so, only 5% to 10% of the initial dose of levodopa administered with a DDC inhibitor ultimately reached the patient’s brain to produce dopamine and its beneficial effect. That was partly because of a further degrading effect as a result of the action of another enzyme present in the body, catechol O-methyl transferase, called COMT. That enzyme naturally converted levodopa into a substance called 3-O-methyldopa.

7    By at least June 1999, persons skilled in this field were aware of the desirability of using a COMT inhibitor in conjunction with the administration of levodopa in order to increase the amount of levodopa that reached the brain. Early investigations into potential COMT inhibitors had encountered problems with toxicity and a lack of selectivity. However, three COMT inhibitors had been progressed to use in experiments on animals with parkinsonian symptoms, two of those, tolcapone and entacapone, had been the subject of clinical trials and had been brought to market for use in levodopa therapy.

8    Tolcapone was first marketed in the United Kingdom in August 1997 and in Australia in 1998. It only needed to be administered three times daily. However, experience developed in 1998 that led to the appreciation that tolcapone had a rare, but potentially fatal, side effect – it could cause major liver toxicity, that had resulted in the death of some patients. This side effect led to tolcapone being withdrawn from the market very early in 1999 in some countries, including the United Kingdom and Australia. The occurrence of this side effect was unexpected, since tolcapone had previously passed regulatory scrutiny, including toxicity assessment, for use in the treatment of Parkinson’s disease.

9    One consequence of the problems with tolcapone was heightened interest in entacapone. However, entacapone had to be administered more frequently, namely with each dose of levodopa, because it had a shorter half-life in the body than tolcapone.

10    Orion’s related companies, Novartis Pharma AG (a Swiss corporation) and Novartis Pharmaceuticals (Australia) Pty Ltd, claim to be, respectively, the exclusive licensee and sub-licensee of the patent. Actavis and its related company, Medis Pharma Pty Ltd, dispute the effect of the inter-group licensing arrangements. That issue has been separated from those that I must decide in this stage of the proceedings.

11    Orion relied on the patent having the priority date of 30 June 1999 being the date, for the purposes of s 43(1) of the Patents Act 1990 (Cth), of filing in Finland of the priority document being the original patent application No. 991485. The complete specification of the patent was filed on 29 June 2000, and that is the deferred priority date for which Actavis contended in relation to whether claims 19, 20 and 21 were novel or involved an inventive step, as I will explain later in these reasons.

12    The above history helps set the scene for consideration of the first set of issues in these proceedings. Those issues are:

(1)    is any of claims 1, 2, 12, 13, 14, 17, 18 and 21 invalid because it fails to define the invention? (the definition of the invention issue);

(2)    what is the proper construction of the patent? (the construction issue);

(3)    do Actavis’ products infringe any of claims 1, 2, 12, 13, 14, 17, 18, 19, 20 or 21? (the infringement issue);

(4)    is any of claims 1, 2, 13, 14, 17, 18 and 21 invalid because it is not clear? (the clarity issue);

(5)    is any of claims 1, 2, 12, 13, 14, 17, 18, 19, 20 and 21 fairly based on the matter described in the specification? (the fair basis issue);

(6)    is any of claims 1, 2, 12, 13, 14, 17, 18, 19, 20 and 21 invalid because it lacks utility? (the utility issue);

(7)    is any of claims 19, 20 and 21 invalid because when compared with the prior art base as it existed before the asserted or deferred priority date of that claim because:

(a)    it was not novel? (the novelty issue);

(b)    it did not involve an inventive steps? (the inventive step issue).

The legislative scheme

13    Relevantly, the Act provided at 29 June 2000, being the time of filing of the complete specification, as follows:

7    Novelty and inventive step

(1)    For the purposes of this Act, an invention is to be taken to be novel when compared with the prior art base unless it is not novel in the light of any one of the following kinds of information, each of which must be considered separately:

(a)    prior art information (other than that mentioned in paragraph (c)) made publicly available in a single document or through doing a single act;

(b)    prior art information (other than that mentioned in paragraph (c)) made publicly available in 2 or more related documents, or through doing 2 or more related acts, if the relationship between the documents or acts is such that a person skilled in the relevant art in the patent area would treat them as a single source of that information;

(c)    prior art information contained in a single specification of the kind mentioned in subparagraph (b)(ii) of the definition of prior art base in Schedule 1.

(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 either of the kinds of information mentioned in subsection (3), each of which must be considered separately.

(3)    For the purposes of subsection (2), the kinds of information are:

(a)    prior art information made publicly available in a single document or through doing a single act; and

(b)    prior art information made publicly available in 2 or more related documents, or through doing 2 or more related acts, if the relationship between the documents or acts is such that a person skilled in the relevant art in the patent area would treat them as a single source of that 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 and regarded as relevant to work in the relevant art in the patent area.

[Notes:

(1)    For the meaning of document see section 25 of the Acts Interpretation Act 1901.

(2)    See also the definitions of prior art base and prior art information in Schedule 1: see also paragraph 18(1)(b) and subsection 98(1).]

Division 1—Validity

18    Patentable inventions

(1)    Subject to subsection (2), a patentable invention is an invention that, so far as claimed in any claim:

…

(b)    when compared with the prior art base as it existed before the priority date of that claim:

(i)    is novel; and

(ii)    involves an inventive step; and

(c)    is useful; and

(d)    was not secretly used in the patent area before the priority date of that claim by, or on behalf of, or with the authority of, the patentee or nominated person or the patentee’s or nominated person’s predecessor in title to the invention.

(2)    Human beings, and the biological processes for their generation, are not patentable inventions.

[Note: see also sections 7 and 9.]

40    Specifications

(1)    A provisional specification must describe the invention.

(2)    A complete specification must:

(a)    describe the invention fully, including the best method known to the applicant of performing the invention; and

(b)    where it relates to an application for a standard patent– end with a claim or claims defining the invention; and

(c)    where it relates to an application for a petty patent– end with a single claim, or a single independent claim and not more than 2 dependent claims, defining the invention.

(3)    The claim or claims must be clear and succinct and fairly based on the matter described in the specification.

(4)    The claim or claims must relate to one invention only.

43    Priority dates

(1)    Each claim of a specification must have a priority date.

(2)    The priority date of a claim is:

(a)    the date of filing of the specification; or

(b)    where the regulations provide for the determination of a different date as the priority date – the date determined under the regulations.

(3)    Where a claim defines more than one form of an invention, then, for the purposes of determining the priority date of the claim, it must be treated as if it were a separate claim for each form of the invention that is defined.

(4)    The priority date of a claim of a specification may be different from the priority date of any other claim of the specification.

138    Revocation of patents in other circumstances

(1)    The Minister or any other person may apply to a prescribed court for an order revoking a patent.

…

(3)    After hearing the application, the court may, by order, revoke the patent, either wholly or so far as it relates to a claim, on one or more of the following grounds, but on no other ground:

…

(b)    that the invention is not a patentable invention;

…

(f)     that the specification does not comply with subsection 40(2) or (3).

14    The Dictionary in Sch 1 to the Act provided:

invention means any manner of new manufacture the subject of letters patent and grant of privilege within section 6 of the Statute of Monopolies, and includes an alleged invention.

prior art base means:

(a)    in relation to deciding whether an invention does or does not involve an inventive step:

(i)    information in a document, being a document publicly available anywhere in the patent area; and

(ii)    information made publicly available through doing an act anywhere in the patent area; and

(iii)    where the invention is the subject of a standard patent or an application for a standard patent–information in a document publicly available outside the patent area; and

(b)    in relation to deciding whether an invention is or is not novel:

(i)    information of a kind mentioned in paragraph (a); and

(ii)    information contained in a published specification filed in respect of a complete application where:

(A)    if the information is, or were to be, the subject of a claim of the specification, the claim has, or would have, a priority date earlier than that of the claim under consideration; and

(B)    the specification was published after the priority date of the claim under consideration; and

(C)    the information was contained in the specification on its filing date and when it was published.

[Note: For the meaning of document see section 25 of the Acts Interpretation Act 1901.]

prior art information means:

(a)    for the purposes of subsection 7(1) – information that is part of the prior art base in relation to deciding whether an invention is or is not novel; and

(b)    for the purposes of subsection 7(3) – 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 patent

15    The patent described the field of the invention as relating to, first, new pharmaceutical compositions comprising entacapone, levodopa and carbidopa, or a pharmaceutically acceptable salt or hydrate thereof, secondly, a preparation method of the compositions, thirdly, a use of the compositions in a therapeutic method and, fourthly, the use of entacapone, levodopa and carbidopa in the manufacture of an oral solid fixed dose combination (page 1 par 1 [The patent does not have line or paragraph numbers. I will use the first full paragraph on a page to describe paragraph numbers]).

16    Throughout the patent, references to the three APIs are accompanied by references to their pharmaceutically acceptable salts or hydrates, but, for simplicity, I will omit referring to those alternatives because there is no issue that concerns whether the form of the API is pure, or a salt or hydrate.

17    The complete specification described the background of the invention by stating the chemical name of each API. It noted that entacapone had been described as a COMT inhibitor in US Patent 5,446,194 and that the US Patent had also discussed the API being administered by enteral (basically, oral) and parenteral (basically, intravenous) routes. The specification noted that Orion manufactured and marketed in Europe an oral compacted composition containing entacapone under the trademarks COMTESS® and COMTAN®. It stated that levodopa and carbidopa were the most commonly used drugs to treat Parkinson’s disease and were commercially available as combination tablets sold in Europe by Du Pont Pharma under various trademarks, including SINEMET®.

18    The background explained that patients needed to take parkinsonism medication several times daily to keep them without symptoms. It observed that patient compliance, especially for those with tremor and old age, could be improved by using a fixed dose combination of all three APIs rather than two separate tablets (namely, the combination levodopa/carbidopa tablet and a separate entacapone tablet) several times a day.

19    The patentee said that the inventors had found that the three APIs “are preferable [sic] released from the oral composition as soon as possible after ingesting it”. It said that it was very difficult to adjust the absorption of three different active agents from a single oral, solid composition and that, usually in practice, absorption of one active agent could decrease while another’s increased. It stated that numerous factors had to be considered when selecting excipients, disintegrants and other auxiliary agents for use in combination with the active agents, including the chemical and physical characteristics of those agents and the auxiliary agents, the bioavailabilities of the active agents, the stability of the composition and its method of preparation (pages 1-3).

20    The patentee stated that none of the earlier patents cited in the background section, or any other patent or publication of which it was aware, described an oral solid composition comprising the three APIs. It also said that the purpose of the discussion in the background section was to explain the context of the invention, but was not an admission that any of the material it referred to had been published, or was known or part of the common general knowledge in Australia as at the priority date of each claim (page 3).

21    Under the heading “Summary of the invention”, the specification stated (page 3 pars 3-4):

Applicants have discovered that entacapone, levodopa and carbidopa … can be combined into one oral solid composition with particularly interesting properties.

The invention thus provides an oral solid fixed dose composition comprising pharmacologically effective amounts of entacapone, levodopa, and carbidopa …, and comprising at least one pharmaceutically acceptable excipient (hereinafter referred to as a composition according to the invention), which has i.a. [scil: inter alia] preferable stability and bioavailability characteristics and which is easy to swallow. (emphasis added)

22    The patentee then asserted that the invention particularly provided an oral solid composition comprising pharmacologically effective amounts of the three APIs and, first, at least one pharmaceutically acceptable excipient being a sugar alcohol, starch or both (and preferably the former was mannitol and the latter maize starch), and secondly, one excipient other than microcrystalline cellulose (MCC) (pages 3-4).

23    Next, the background continued (page 4 pars 2-3):

Applicants have found that a particularly interesting way to increase the bioavailability of carbidopa from an oral solid composition comprising entacapone, levodopa, and carbidopa is to add carbidopa separately, for instance by granulating first levodopa and entacapone together and then adding carbidopa to these granules separately.

Accordingly, the invention further provides an oral solid composition comprising pharmacologically effective amounts of entacapone, levodopa, and carbidopa … and a pharmaceutically acceptable excipient, wherein a substantial portion of carbidopa is separated from entacapone and/or levodopa. (emphasis added)

24    The specification then discussed different techniques to accomplish the separation of carbidopa from the other two APIs, that included granulating and mixing levodopa and entacapone together and adding carbidopa separately, “as such” or in granule form. The specification recorded that, therefore, the invention also provided a method for producing an oral solid pharmaceutical composition comprising the three APIs and a pharmaceutically acceptable excipient, that involved first mixing levodopa and entacapone separately and then adding carbidopa separately (pages 4-5). It stated that the oral solid composition according to the invention included “a tablet [being the preferable form], a capsule and the like” (page 5 par 1). The specification also said that the invention provided a method for treating Parkinson’s disease (but this aspect is not in issue in these proceedings).

25    The background then stated that the invention provided a use of the three APIs in the manufacture of an oral solid composition for treating Parkinson’s disease in its different stages. The section concluded by saying that the description it contained, and that which followed in the specification, were “exemplary and explanatory only and [did] not restrict the invention, as claimed” (page 5 par 5).

26    Next, the specification gave a brief description of the drawings at the end of the document. The drawings were, in fact, six graphs that depicted two separate sets of blood plasma concentrations of each of the three APIs achieved after a single oral dose of, in each set, a reference dosage being a 200 mg COMTESS® tablet (i.e. entacapone) together with a SINEMET® PLUS 100/25 tablet (i.e. 100 mg of levodopa and 25 mg of carbidopa) and, in one set, formulations 1 and 2 as later described in the complete specification and in the second set, formulations 3 and 4 also later described there.

27    Figures 1 and 4 recorded the concentrations for entacapone, Figures 2 and 5 those for levodopa and Figures 3 and 6 those for carbidopa respectively for the three recorded dose forms, being the reference and two relevant formulations (p 6, Figures 1-6). The two reference doses produced different graphical results for each comparator API, as compared to those in the other set. The four described formulations also produced different graphical results for each API.

28    The next heading in the specification was “Detailed description of the invention” and it was followed immediately by the statements (page 7 pars 1-2):

Applicants have surprisingly discovered that an oral solid composition enabling sufficient absorption of active agents can be achieved by combining entacapone, levodopa and carbidopa … in a single formulation. This has been achieved, inter alia, by improving the bioavailability and the stability of the composition, and improving the method for preparing the composition.

Applicants have found that absorptions of levodopa, carbidopa and entacapone from the digestive tract are highly variable. The bioavailabilities of levodopa and carbidopa vary both intra- and interindividually. The bioavailability of entacapone has also been extensively studied by the Applicant to arrive at the present invention. (emphasis added)

29    The patentee then stated that it was very challenging to harmonise the absorptions of the three APIs from the one oral solid composition. It said that it had found that the method for preparing the composition had a significant effect on the bioavailability of carbidopa, and continued:

For example, the bioavailability of carbidopa from Formulation 1 (see Example 1, Table 1), wherein all the active agents are wet granulated together, is too low compared to the reference product, SINEMET® PLUS 100/25 mg tablet. On the other hand, the bioavailability of carbidopa from Formulation 2 (see Example 1, Table 1), wherein all the active agents are dry granulated together (compaction granulated) is acceptable. However, polyethylene glycol used in Formulation 2 as a compression aid found [sic] to cause stability problems as indicated below. The absorption data from the bioavailability studies of Formulations 1 and 2 are shown in Figures 1-3. (pages 7-8) (emphasis added)

30    The patentee stated that the inventors had found that a preferred way to increase the bioavailability of carbidopa from a oral solid composition comprising the three APIs was to mix, for example to granulate, levodopa and entacapone together and then to add carbidopa to that mixture, for example in granules, separately.

31    The specification then set out its first consistory clause, corresponding to claim 1, as:

The invention therefore provides an oral solid composition of entacapone, levodopa, and carbidopa … and a pharmaceutically acceptable excipient, wherein a substantial portion of carbidopa is separated from entacapone and levodopa. (emphasis added)

32    The specification then identified a preferred way of obtaining a composition of the invention “wherein a substantial portion of carbidopa is separated from entacapone and levodopa”, was to mix (e.g. granulate) entacapone and levodopa particles separately and then to add carbidopa particles separately, “as such or in the form of granules”, optionally adding one or more excipients and formulating the mixture “thus formed to an oral solid composition, e.g. tablet, of the invention” (emphasis added) (page 8 par 3).

33    The specification then stated the following consistory clause, reflecting what would be included as claims 12 and 13 (page 8 par 4):

Accordingly, a preparation process for an oral solid composition of the invention is also provided, wherein carbidopa… is added separately to the composition, e.g. entacapone and levodopa, together with (an) excipient(s), are first mixed separately, carbidopa is added separately to the mixture obtained and the mixture is formulated, optionally together with (an) excipient(s), to a plurality of dosage forms.

34    The specification said that preferably, entacapone and levodopa should be first granulated, either separately or together, and that carbidopa be separated from them by adding it to the mixture either as separate granules, or “extragranularly as such (in powder form)”. The latter alternative was reflected in claims 2 and 14. The patentee noted that both wet and dry granulation could be used. However, it stated that wet granulation was preferable, as later reflected in claim 18, and that suitable granulation methods were known in the art (page 9 par 1).

35    The specification described examples of “these kinds of formulations according to the invention” in Example 2. The specification stated that the absorption of the three APIs, from formulations 3 and 4 (being those in Example 2) had been studied and that the results in Figures 4-6 showed that the respective absorption from those formulations was comparable to commercial reference formulations (page 9 par 2).

36    The specification stated that the inventors had found that the three APIs “are as such compatible with each other” (page 9 par 3). But, it then noted that the inventors had found that many commonly used excipients were “not suitable to be used in oral solid compositions” containing the three APIs. It continued (page 9 par 4-page 10):

Most of the levodopa-carbidopa formulations available in the market contain microcrystalline cellulose as a carrier. Also, the entacapone formulations COMTESS® and COMTAN®, which recently became available in Europe, contain considerable amounts of microcrystalline cellulose. In the prior art microcrystalline cellulose appears to be an acceptable excipient. For compositions of the invention, applicants unexpectedly found that microcrystalline cellulose destabilizes the formulations on long term storage, when all three active agents are combined together. (emphasis added)

37    The specification continued with a consistory clause foreshadowing claim 11, that the invention provided an oral solid pharmaceutical composition comprising pharmacologically effective amounts of the three APIs “and at least one pharmaceutically acceptable excipient other than [MCC]” (page 10 par 1).

38    Next, the specification stated that the inventors had found that tablets containing polyethylene glycol (being the product Macrogol 6000) as an excipient were unstable in a standard stability test, as in formulation 2. The inventors said that they believed that a reason for the stability problems was that the surface activity of polyethylene glycol might have enhanced the degradation of the active substance,s and that they had found that other surface active substances such as polysorbate and sodium lauryl sulphate were also “incompatible with the fixed dose combination e.g. as indicated by standard stability tests”. The stability tests had also revealed “incompatibilities of the drug combination with colloidal silicon oxide, copolyvidone and previously mentioned substances with surface active properties” (page 10 par 2). The specification said that a preferred embodiment of “a stable oral solid pharmaceutical composition” would be comprised of pharmacologically effective amounts of the three APIs and “at least one pharmaceutically acceptable excipient other than [MCC] and/or surface active agents and/or silica” (page 10–page 11)). It continued (page 11 par 1):

Despite the several incompatibilities found, the oral solid composition according to the invention can still surprisingly be prepared by using few compatible excipients alone or two or more together. Compatible excipients include, e.g., sugar alcohols, preferably mannitol, and starch, preferably maize starch as well as other appropriate excipients mentioned herein.

39    The specification then proceeded to recite a consistory clause for claim 4 based on the above identification of “compatible excipients” and to discuss preferable proportions of those and other excipients (page 11 par 2 – page 12).

40    The patentee then said that the amount of each API in the oral composition “is dependent on numerous factors known to one skilled in the art, such as, the severity of the condition of the patient, the desired duration of use, etc” and that “[t]he solid oral composition of the invention may also contain one or more other pharmacologically active agents”. The specification then stated that in the formulation according to the invention, the amounts of each API were, preferably, 25 to 400 mg of entacapone, 25 to 300 mg of levodopa and 5 to 75 mg of carbidopa, with especial ranges within each of the wider ones (page 12 par 3 – page 13). It said that the inventors had discovered that “the following embodiment is particularly preferred, e.g. for a wide variety of patient populations, including early and late stage Parkinson patients” namely doses of 200 mg of entacapone with 100 mg of levodopa and 25 mg of carbidopa, and then gave four other preferred embodiments, with 200 mg of entacapone in each and dosages of levodopa/carbidopa of: 50/12.5 mg, 150/37.5 mg, 100/10 mg and 250/25 mg, reflecting ratios of either 4:1 or 10:1 (page 13 par 1).

41    The specification then recited a consistory clause for claim 21 (page 13 par 2):

As a further aspect the invention provides an oral solid fixed dose composition comprising pharmacologically effective amounts of entacapone, levodopa, and carbidopa … and comprising at least one pharmaceutically acceptable excipient, whereby the therapeutic effect achieved with the said composition in the treatment of Parkinson's disease is comparable, e.g. similar, to that achieved with the known separate formulations of entacapone, levodopa and carbidopa, e.g. entacapone tablets and levodopa-carbidopa tablets referred to herein, which are administered concomitantly, at the same doses of the active agents as the combination formulation of the invention.

(the italicised portions above were not later included in claim 21; the word “therapeutic” appeared in claim 21 as “therapeutical” but it was common ground that the latter word meant therapeutic; and the final phase appeared in claim 21 as the “present combination formulation”)

42    Next, the patentee stated that one embodiment of “the said composition of the invention” was “pharmacokinetically comparable” to the known reference formulations, and another embodiment was “substantially bioequivalent with” those reference formulations (page 13 par 3 – page 14):

e.g. the bioavailability achieved with the composition of the invention is at levels comparable to that achieved with the concomitant administration of the same doses of the known separate formulations of entacapone, levodopa and carbidopa, e.g. the entacapone and levodopa-carbidopa formulations used herein as a reference. (See also Examples). (emphasis added)

43    Importantly, the specification then set out five preferred embodiments using the same dosage combinations as in [40] above, the first of which was (page 14 par ):

In preferred embodiments,

a}    the therapeutic effect, such as pharmacokinetics, e.g. bioavailability, achieved with a combination composition of the invention of the dose of 200 mg entacapone/100 mg levodopa/25 mg carbidopa is comparable to that of the known formulation of entacapone and the known formulation of levodopa-carbidopa administered concomitantly at the same doses of active agents as the present combination composition;

44    The specification stated that COMTESS and COMTAN were made using compaction granulation for which “large amounts of excipients are needed to obtain compressible granules and tablets having the desired, fast, dissolution behaviour of an immediate release formulation”. The patentee said that the compactability of entacapone was sufficient to allow a tablet with a 200 mg dose that was relatively easy to swallow. The patentee then explained that the compactability of the fixed dose combination tablets was “surprisingly worse than that of entacapone alone”. It said that using polyethylene glycol improved compactability but produced tablets “indicated to be unstable in storage”. The specification stated that the size of a 3-in-one composition prepared by compaction granulation could become too large “especially for parkinsonism patients who have difficulties in swallowing” (page 16).

45    Relevantly, the specification then set out consistory clauses for claims 16 and 17, the latter dealing with a four step process for preparing an oral solid composition “according to the invention”. That process consisted of, first, mixing pharmacologically effective amounts of entacapone and levodopa with at least one pharmaceutically acceptable excipient and, optionally, a disintegrant to obtain a first mixture, secondly, granulation of that mixture to obtain a plurality of granules, thirdly, adding a pharmacologically effective amount of carbidopa and optionally both a lubricant and one or more pharmaceutically acceptable excipients to the granules to obtain a second mixture and, last, formulating the second mixture into a plurality of dosage forms (page 17 par 1). The specification discussed different mixing techniques, including wet granulation and coating for the tablets (page 17 par 2) and then stated (page 17 par 3 – page 18):

By using the process of the invention tablet compositions of the invention may be made which are particularly small for the dosages contained therein and are convenient to administer. These may be any of a wide variety of shapes, although an oval form is preferred. The small size is particularly surprising in view of the size of the presently commercialized COMTAN®/COMTESS® entacapone tablet and in view of the fact that entacapone is difficult to compress and still give an acceptable release especially in the presence of levodopa and carbidopa. Furthermore, we have found that the composition of the invention surprisingly have [sic] especially good flowability properties. (emphasis added)

46    Next, the specification set out consistory clauses for claims 19 and 20 that said that another aspect of the invention provided “an oral pharmaceutical tablet” comprising the preferred ranges of dosages of the three APIs and preferable weights, volume and dimension ranges for the tablets (page 18 pars 1 and 2).

47    The patentee stated that “[i]nsofar as the details of the pharmaceutical excipients are not specifically described herein”, they were described in handbooks known in the art (page 18 par 5). The specification then set out details of Examples 1 and 2 that recorded the absorptions of the three APIs when tested using Formulations 1 and 2 and Formulations 3 and 4 respectively, against two sets of reference products from the known formulations. Thus, the patentee described Example 1 as follows (pages 19 par 3 – page 20 par 2):

EXAMPLE 1

The absorptions of entacapone, levodopa, and carbidopa from entacapone/levodopa/carbidopa 200/100/25 mg tablet formulations containing different excipients and prepared by different methods were tested after a single oral dose in 15 healthy volunteers. The tablets were prepared by wet granulating all the active agents at the same time (Formulation 1) and by compaction granulating all the active agents at the same time (Formulation 2). The formulations were as described in Table 1.

The absorption study was designed to assess the absorption of the active substances between two fixed dose combination tablets and an entacapone 200 mg tablet administered together with a levodopa/carbidopa 100/25 mg tablet, i.e., SINEMET PLUS® distributed in Europe by DuPont Pharmaceuticals Ltd. The study was performed according to an open randomized cross-over design. The plasma entacapone, levodopa, and carbidopa concentrations were determined by two separate reversed-phase HPLC methods, i.e., the entacapone concentrations were measured by one method and the levodopa and carbidopa concentrations by another method.

The results are shown in Figures 1-3. (emphasis added)

48    Table 1 set out three columns identifying the ingredients and, for each of formulations 1 and 2, the quantity of any ingredient added. The table culminated in giving, first, the total theoretical weights of the coated tablets as 619.5 mg and 660 mg respectively and, secondly, the methods of manufacture being, high shear granulation of all active substances together for Formulation 1 and compaction granulation of the three APIs together with Formulation 2 (pages 20-21).

49    The specification then proceeded to explain Example 2, which had adopted a similar process of recording test results using 15 healthy volunteers, a control dose and then doses of Formulations 3 and 4. The specification described these as “[e]xamples of suitable entacapone/levodopa/carbidopa 200/100/25 mg tablet formulations”. The inventors said that they added carbidopa separately as granules in Formulation 3 and in powder form in Formulation 4. They stated that otherwise they prepared both formulations 3 and 4 by, first, wet granulating entacapone and levodopa together with maize starch, mannitol, croscarmellose sodium and povidone in a conventional high shear mixer, secondly, wet granulating the respective form of carbidopa separately with the same excipients in a high shear mixer, thirdly, mixing the dry entacapone/levodopa granulates and the dry carbidopa granules with croscarmellose sodium, mannitol and magnesium stearate and then compressing the mass so obtained into tablets with an oval shape that were coated with a coloured HPMC coating (page 21 par 1 – page 22). Example 2 concluded (page 22 par 1):

According to the results shown in Figures 4-6 the absorptions of the tested two formulations are comparable to the commercial reference formulations. The dissolved amounts of entacapone, levodopa and carbidopa are at least 50 % in 30 minutes when measured with USP dissolution equipment. (emphasis added)

50    Table 2 was as follows (page 23):

The oval tablets compressed from the tablet mixtures had the following dimensions: Formulation 3 (length of 16.4 mm; width of 7.7 mm and height of 5.7 mm) and Formulation 4 (length of 16.4 mm; width of 7.7 mm and height of 5.1 mm)

51    Next, Example 3 used different dosages of levodopa and carbidopa in Formulation 5 (150/37.5 mg) and Formulation 6 (100/10 mg) that Table 3 recorded as having a core weight of 694 mg and 444 mg respectively, before a weight gain of about 2-3% from a coloured HPMC coating (page 24 par 1).

52    The specification stated that those skilled in the art would recognise that other embodidments were possible “without departing from the spirit and scope of the invention” and that the specification and examples be considered as exemplary only “with a true scope and spirit of the invention being indicated by the following claims” (page 24 par 3 – page 25). The specification next stated:

Throughout the description and claims of the specification the word “comprise” and variations of the word, such as “comprising” and “comprises”, is not intended to exclude other additives, components, integers or steps.

53    After setting out the 21 claims, the specification concluded with 6 sheets, being Figures 1-6.

The claims

54    The specification included the following claims that are in issue in these proceedings.

CLAIMS:

1.    An oral solid composition comprising pharmacologically effective amounts of entacapone, levodopa and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, and a pharmaceutically acceptable excipient, wherein a substantial portion of carbidopa is separated from entacapone and levodopa.

2.    The composition according to claim 1, wherein entacapone and levodopa are in the form of granules and carbidopa is in powder form.

…

12.    A method for preparing an oral solid composition comprising entacapone, levodopa, and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, which comprises adding carbidopa, or a pharmaceutically acceptable salt or hydrate thereof, separately to the remainder of the composition.

13.    A method for preparing an oral solid composition comprising entacapone, levodopa, and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, which comprises mixing first entacapone and levodopa separately, adding carbidopa separately and formulating the mixture into a plurality of dosage forms.

14.    A method according to claim 12 or 13, wherein carbidopa is added in powder form extragranually to granules of entacapone and levodopa.

…

17.    A method for preparing an oral solid composition comprising entacapone, levodopa, and carbidopa, or a pharmaceutically acceptable salt or hydrate thereof, wherein the method comprises

a)    mixing pharmacologically effective amounts of entacapone and levodopa, or a pharmaceutically acceptable salt or hydrate thereof, with at least one pharmaceutically acceptable excipient and a disintegrant to obtain a first mixture;

b)    granulating the first mixture to obtain a granule batch;

c)    adding a pharmacologically effective amount of carbidopa, or a pharmaceutically acceptable salt or hydrate thereof, optionally a lubricant, and optionally one or more pharmaceutically acceptable excipients to the granule batch to obtain a second mixture;

d)    formulating the second mixture into a plurality of dosage forms.

18.    The method according to claim 16 or 17, wherein the granulation method is wet granulation.

19.    An oral pharmaceutical tablet comprising 200 mg entacapone, 50-150 mg levodopa, and 10-37.5 mg carbidopa and having substantially the following characteristics:

weight 400-750 mg; and volume dimensions for tablet from 200 to 1000 mm3.

20.    An oral pharmaceutical tablet comprising 200 mg entacapone, 50-150 mg levodopa, and 10-37.5 mg carbidopa and having substantially the following characteristics:

weight 400-750 mg; and volume dimensions for tablet: length 13-18 mm; width 6-9 mm; and height 4-7 mm.

21.    An oral solid fixed dose composition comprising pharmacologically effective amounts of entacapone, levodopa and carbidopa, or pharmaceutically acceptable salts or hydrates thereof, and comprising at least one pharmaceutically acceptable excipient, whereby the therapeutical effect achieved with the said composition in the treatment of Parkinson's disease is comparable to that achieved with the known separate formulations of entacapone and levodopa and carbidopa which are administered concomitantly at the same doses of the active agents as the present combination formulation. (emphasis added)

The skilled addressee

55    The objective person through whose experience and knowledge the construction of a patent and issues about it must be approached is a person skilled in the relevant art who is aware of, or able to access, the common general knowledge as it existed at a relevant priority date. This person is a skilled addressee. Very often, in pharmaceutical or other technical patent cases, the issues arising in relation to an invention are not confined simply to one field, discipline, or art. Thus, the skilled addressee will be a legal construct whose appreciation must draw upon expertise in more than one field, discipline or art. That will reflect the likely reality that the claimed invention will have involved an inter-disciplinary team of various skilled persons, as Sachs LJ explained giving the reasons of the Court of Appeal of England and Wales in General Tire & Rubber Co v Firestone Tyre and Rubber Co Ltd [1972] RPC 457 at 485. The legal standard for the degree of expertise that the skilled addressee will bring to the problem at hand, in light of the common general knowledge, is, again, an objective one of a non-inventive skilled worker in the field: Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253 at 293 per Aickin J with whom Barwick CJ, Stephen, Mason and Wilson JJ agreed.

56    The purpose of this legal construct, like that of the reasonable person in the law of negligence, or the ordinary reasonable reader, viewer or listener in the law of defamation, is to provide an objective standard that can be applied to the resolution of the issue at hand. Here, it was common ground that the skilled addressee of the patent consists of persons skilled in the arts of clinical medicine, pharmacology, pharmacy and formulation of medicines in the treatment of Parkinson’s disease.

The expert witnesses

57    The diversity of callings of the members of the skilled composite or team to whom the patent was addressed was reflected in the expert witnesses. Orion relied on four experts, Professor Martyn Davies, Professor Peter Jenner, Dr Angelo Morella and Dr John O’Neill.

58    Professor Davies had been Professor of Biomedical Surface Chemistry in the School of Pharmacy at the University of Nottingham since 1996. He had extensive academic and practical experience in pharmaceutical technology, formulation of oral compositions, advanced drug delivery systems and consulting for pharmaceutical companies. This had included supervising detailed analysis of various combination products for medical treatments, including determining their structure and the compatibility of various APIs with one another as well as with formulation excipients. Although, as at June 1999, he was familiar with the use of levodopa and carbidopa and the SINEMET product in the treatment of Parkinson’s disease, he did not recall then (or at June 2000) being aware of entacapone. Prof Davies gave evidence principally on matters concerning the issue of the construction of the patent.

59    Professor Jenner had been Emeritus Professor of Pharmacology, Kings College, London, since 2008. Until recently he had been Director of the Neurodegenerative Diseases Research Centre at King’s College and Director of the National Parkinson Foundation Centre of Excellence. He had worked in the area of pharmacology of Parkinson’s disease for over 40 years. He had been, among other distinctions, a Fellow of the Royal Pharmaceutical Society of Great Britain since 1994, a Fellow of the British Pharmacological Society since 2005 and a Fellow of the Royal Society of Medicine since 2011. He is one of the most cited authors in Neuroscience having authored or co-authored over 700 papers, review articles and book chapters, written or edited numerous monographs and, before June 1999, over 200 of his then 319 publications related to Parkinson’s disease. He had undertaken research into Parkinson’s disease continuously from the early 1970s, during much of which time he worked in a clinical department of neurology. He had worked, written and spoken extensively in relation to clinical practice of treating Parkinson’s disease at the clinician-patient level, and on the use of drugs and treatment strategies of neurologists treating patients with the disease.

60    Prof Jenner had contributed chapters to the multi-volume book series Handbook of Clinical Neurology that Dr Richard Peppard, a clinician called by Actavis, described as being in the nature of an encyclopaedia of clinical neurology focused primarily on the pathological features, clinical manifestations and diagnoses of neurological disorders. Dr Peppard referred to that text as at June 1999 and subsequently in relation to, among others, Parkinson’s disease in the course of his clinical practice, teaching and research. Prof Jenner had also consulted extensively for pharmaceutical companies, principally in relation to the discovery and development of new therapeutic drugs for treatment of neurological disorders, including Parkinson’s disease. He gave evidence relating to pharmacological and formulatory issues, although he had not worked on drug formulation in the way a formulator would. He also had extensive experience of working with clinicians in the treatment of Parkinson’s disease.

61    Dr Morella was a consultant in the area of drug delivery and pharmaceuticals. He had about 27 years’ experience as a pharmaceutical formulator in the industry, including extensive experience in developing oral formulations, granulation techniques and pharmacology. The latter experience included using and interpreting pharmacokinetic data (i.e. data relating to drug absorption, distribution, metabolism and excretion by the human body) and pharmacodynamic data (i.e. data relating to the biochemical and physiological effect of a drug on the body). He gave evidence relating to pharmacology and formulation.

62    Dr O’Neill was a consultant neurologist at St Vincent’s General and Private Hospitals and Mater Misericordiae Private Hospital in Sydney and in private practice in Wollongong who had specialised in this field since he became a Fellow of the Royal Australasian College of Physicians in 1985. He attained a Doctorate of Medicine from the University of New South Wales in 1987 and since 2002 he has been a conjoint senior lecturer at that University. From 1981 to mid-2000 Dr O’Neill had treated many hundreds of patients with Parkinson’s disease, and that class of patients had comprised a significant proportion of his neurology practice during his career. He gave evidence as to the clinical treatment of Parkinson’s disease.

63    Actavis relied on three experts, Dr Peppard, Dr Phillip Reece and Professor Peter Stewart.

64    Dr Peppard was a senior consultant neurologist at St Vincent’s Hospital, Melbourne and the senior movement disorders specialist at Wantirna Health, a rehabilitation and palliative care hospital in Victoria at which over 80% of his patients have suffered from Parkinson’s disease. He has conducted clinics in other parts of Victoria and in Hobart and Launceston. He also practised privately, specialising in diagnosis and management of movement disorders. About 70% of patients referred to him in his private practice have suffered from Parkinson’s disease. He became a Fellow of the Royal Australian College of Physicians in 1986 after completing advanced training in neurology. He was a post-doctoral research fellow at the University of British Columbia between 1986 and 1988, researching neurodegenerative disorders, including Parkinson’s disease and providing clinical care to patients suffering Parkinson’s disease and other neurodegenerative diseases. He has continued his research interest in his career. He teaches at the St Vincent’s Clinical School, that is part of the Faculty of Medicine at the University of Melbourne. In 1993 he was awarded the degree of Doctor of Medicine by that University. Dr Peppard gave evidence as to the clinical treatment of Parkinson’s disease.

65     Dr Reece was a clinical pharmacologist with over 30 years’ experience involving extensive research and practical work on pharmacokinetic and pharmacological studies of pharmaceuticals. Early in his career he worked as a hospital scientist. Between 1986 and 1987, in addition to his work as a scientist, he worked part-time as an evaluator of pharmacokinetic properties of about six products for the Therapeutic Goods Administration (TGA). Later, he worked for a number of pharmaceutical companies in developing new pharmaceutical products, including the conduct of clinical trials, before becoming an independent consultant in pharmaceutical and biotechnology matters in 2003. Also, in late 2003 he was appointed an Honorary Senior Fellow in the Department of Pharmacology in the University of Melbourne, and has lectured there since then. He gave evidence relating to pharmacology.

66    Professor Stewart was Emeritus Professor in the Faculty of Pharmacy and Pharmaceutical Sciences at Monash University. He was awarded a Doctor of Philosophy in Pharmacy by the University of Queensland in 1976, having attained his Bachelor of Pharmacy degree there in 1966. He worked in the Department of Pharmacy there from 1967 in various academic positions and was appointed Head of that Department in 1987, which he remained until 1991. In 1992 he moved to become Dean of the School of Pharmaceutics at the then Victorian College of Pharmacy, which subsequently became the Faculty of Pharmacy and Pharmaceutical Sciences at Monash University. Over the course of his career he undertook work relating to the design and manufacture of solid oral dosage forms, including work for pharmaceutical companies relating to the evaluation of both the dissolution of drugs from solid oral dosage forms and the chemical and physical stability of drugs and dosage forms, investigating mixing techniques for pharmaceutical ingredients in powder form and investigating the development of formulations for new drugs. He was made a Fellow of the Pharmaceutical Society of Australia in 1990, and between 1990 and 1995, was a member of the Pharmaceutical Sub-Committee of the Australian Drug Evaluation Committee. He has also held a number of other positions. Prof Stewart gave evidence relating to formulation.

(1)    The definition of the invention issue – Actavis’ argument

67    Actavis argued that the patentee had defined the invention in the whole passage that I have quoted (page 3 pars 3-4) of the complete specification at [21] above. The words on which Actavis relied were “which has i.a. preferable stability and bioavailability characteristics and which is easy to swallow”. That is, it contended that the words appearing after the words in brackets “hereinafter referred to as a composition according to the invention” defined essential characteristics of every such composition.

68    Actavis submitted that, read as a whole, the specification repeatedly characterised the invention by reference to the characteristics of stability, bioavailability and tablet sizes appropriate for administration to patients suffering from Parkinson’s disease, being persons who are known to have potential difficulties in swallowing. It argued that the skilled addressee would know that a tablet containing a composition of the three APIs would have to achieve at least equivalent bioavailability to the existing separate formulations of entacapone and a composition containing levodopa and carbidopa.

69    It also relied on the description on page 7 par 1, set out in [28] above, and other references in the body of the specification to bioavailability, absorption of the APIs and stability as critical indicia of the invention. Actavis argued that the specification made clear that the patentee did not consider formulations 1 and 2 to be within the invention claimed. That was because, Actavis contended, the specification taught that the bioavailability of carbidopa from formulation 1 was “too low” and the use of polyethelene glycol in formulation 2 caused stability problems, whereas the specification’s teaching on formulations 3 and 4 was not so qualified, and on formulations 5 and 6 was that these were examples of “suitable” formulations of the three APIs.

(1)    The definition of the invention issue – consideration

70    The question of what the invention described in the specification was must be decided first, before considering arguments as to the validity of the individual claims: Welch Perrin & Co Pty Ltd v Worrel (1961) 106 CLR 588 at 609 per Dixon CJ, Kitto and Windeyer JJ. The specification must be read through the eyes of a skilled addressee in light of the common general knowledge in the relevant art at the priority date. That is the familiar process of construction of any written document, by which its meaning is ascertained objectively having regard to the way in which a reasonable person, in the position of a skilled addressee at the priority date (or in a contractual setting, the parties), would understand the meaning conveyed by the document as a whole. However, because a patent is a public instrument, for any claim to be valid it must define the asserted monopoly in a way that is not reasonably capable of being misunderstood: Welch Perrin 106 CLR at 610. As with all other areas of law involving the construction of a document or other forms of expression, the proper construction of a patent is a question of law, not fact.

71    I am of opinion that the invention described in the complete specification was, first, a product, being an oral solid fixed dose composition comprising pharmacologically effective amounts of entacapone, levodopa and carbidopa and at least one pharmaceutically acceptable excipient, secondly, a process or method for preparing that product and, thirdly, a method of using it. In short, the patent identified a new three-in-one combination (tablet) that provided an oral fixed dose of pharmacologically effective amounts of the three APIs with at least one pharmaceutically acceptable excipient and methods to produce and use that combination product.

72    I reject Actavis’ wider characterisation of the invention as encompassing particular or specific characteristics relating to stability, bioavailability and ease of swallowing. Those characteristics represented consequences of preferred embodiments of the invention that the specification described. The discussion of the invention in the field, background and summary sections of the specification described the oral solid composition of the three APIs and methods for preparing it in connection with a variety of preferred and other embodiments.

73    Thus, in the background section, the inventors observed that none of the prior art had described such an oral solid composition (page 3 par 1) and later stated that the definition of “a composition according to the invention” was that the invention “provide[d] an oral solid fixed dose composition comprising pharmacologically effective” amounts of the three APIs and at least one pharmaceutically acceptable excipient (page 3 par 4). That definition was followed by the statement “which has i.a. [scil inter alia] preferable stability and bioavailability characteristics and which is easy to swallow”. The skilled addressee would have understood that this latter statement conveyed that there were preferable embodiments of the invention that achieved each of the three nominated characteristics, as indeed was borne out in the succeeding pages of the complete specification.

74    It would be unusual for a patentee to define an invention as being limited to preferable embodiments. Ordinarily, a patentee will set out in the specification a number of possible embodiments of aspects of the invention, all of which will fall within a claim and will identify, in addition, one or more embodiments that the patentee wishes to teach addressees is, or are, preferable.

75    Notably, the complete specification did not prescribe particular stability or bioavailability characteristics to limit or further define the invention beyond identifying the preferred embodiment, reflected in claim 21, that the composition could achieve the therapeutic effect of the known separate formulations of entacapone tablets and combined levodopa and carbidopa tablets (page 13 par 2). Moreover, other than claim 21, the claims, which are part of the complete specification, did not define such integers of the asserted monopoly by reference to stability, bioavailability or therapeutic criteria or results. In addition, the specification described the preferred embodiments, reflected in claims 19 and 20, of pharmaceutical tablets with dosage ranges of each API within ranges of weights, volumes and dimensions that the skilled addressee would understand as conformable with the manufacture of tablets that were sufficiently small to be easy for sufferers of Parkinson’s disease to swallow.

76    I am of opinion that Actavis’ characterisation of the invention was driven with an eye to avoiding the consequences of infringement. That is not an appropriate way in which to construe a patent: GlaxoSmithKline Australia Pty Ltd v Reckitt Benckiser Healthcare (UK) Ltd (2013) 305 ALR 363 at 379 [60] per Bennett, Jagot and Griffiths JJ.

1.    The parties’ submissions as to construction

77    Orion argued that when claim 1 required that the composition comprise pharmacologically effective amounts of the three APIs wherein “a substantial portion of carbidopa is separated from entacapone and levodopa” it envisaged a composition with two constituent parts, namely “one containing carbidopa and the other containing entacapone and levodopa together”. Orion’s submission continued that, as a consequence, the separation of carbidopa need not be absolute because the words “a substantial portion” recognised that interfacial contact could occur between different parts. Next, Orion argued, because the separation of carbidopa need not be absolute, the carbidopa constituent part of the composition could be mixed with any amount of one or both of entacapone or levodopa. Similarly, Orion argued that the requirement in the dependent claims 2 and 14, that the carbidopa be in powder form and the entacapone and levodopa be in granular form, did not preclude another API or excipient being present with carbidopa in the powder form when it is added to the composition.

78    Next, Orion argued that the integer of the method in claim 12 for “adding carbidopa … separately to the remainder of the composition” simply required that the mixture of entacapone and levodopa occur first, before the addition of carbidopa. It contended that other ingredients, including the other APIs and excipients, could be added with the carbidopa. Orion submitted that claim 12 could not be read so as to entail that no other ingredient could be added at the same time as the carbidopa. It contended that both claims 12 and 13 referred to a manufacturing principle that the specification had repeatedly referred to as a preferred way of separating carbidopa from entacapone and levodopa.

79    Orion said that claim 13 only required that the mixture of entacapone and levodopa be created separately first, before the addition of carbidopa. It submitted that there was no requirement for carbidopa to be added in the way prescribed by claim 12, namely “separately to the remainder of the composition”. Orion contended that by omitting that prescription from claim 13, the patentee intentionally left open the possibility of adding carbidopa mixed with other ingredients. Orion supported that argument by noting that claim 13 omitted the prescription in claim 1 for the composition to comprise “a substantial portion of carbidopa [that] is separated from entacapone and levodopa”.

80    Actavis argued that the words “pharmaceutically acceptable excipient” when used in any claim necessarily excluded MCC because the complete specification (at pages 9-10) identified MCC as an excipient that was not suitable to be used or, alternatively, was not “compatible”. Actavis also argued that the definition of “comprise” and its analogues (on page 25) only operated to clarify that, when used, the defined term was inclusive, not exhaustive. It submitted that the term, however, did not enable the addition of steps or integers that were otherwise excluded by the language of the claim. It also argued that steps a) and c) in claim 17, which prescribed the stage at which an API could be added, could not be read using “comprising” in a way that permitted another API to be added out of turn.

81    Actavis also contended that the expression “pharmacologically effective amount(s)”, when used in connection with one or more of the three APIs denoted the total intended dosage of the particular API, for example in steps a) and c) of claim 17.

82    Actavis argued that claims 19, 20 and 21 were not limited to tablets prepared by using the process of the invention, being the mixing of levodopa with entacapone separately and then adding carbidopa separately, and for that reason were not fairly based or lacked utility. Alternatively, it contended that if claims 19, 20 and 21 were so limited, then its products complained of did not infringe those claims.

83    In answer to the possibility that I raised, that the adjective “pharmaceutical” qualifying the word “tablet” in claims 19 and 20 conveyed a tablet that is stable and bioavailable and so suitable for oral administration as a medicine in treating Parkinson’s disease, Actavis argued that the word “pharmaceutical” was not used in that sense in the specification. It referred to the patentee’s use of that adjective elsewhere in the patent as qualifying “excipients” (such as on page 18 par 4) in the sense of them being recognised in pharmaceutical usage but not as having particular characteristics. Actavis also contended that none of the expert witnesses understood the expression “pharmaceutical tablet” in the way I had suggested. It submitted that the word “stable” had been expressly used in claim 11. Actavis also said that such a construction would leave uncertain when any particular “pharmaceutical tablet” would fall within the two claims. It also contended that if this were the proper construction of the expression “pharmaceutical tablet”, then claims 19 and 20 were not fairly based.

84    Actavis argued that claim 21 was uncertain or lacked clarity because of the imprecision of the expression “whereby the therapeutical effect achieved with the said composition in the treatment of Parkinson’s disease is comparable to that achieved with the known separate formulations”. It relied on Dr Reece’s evidence that a skilled addressee would not understand the precise criteria by reference to which the comparison had to be made.

Consideration – construction of claims 1, 2, 12, 13, 14, 17, 18, 19, 20 and 21

85    Claim 1: The critical difference between the parties on the construction of claim 1 concerned the nature of the requirement that the composition be one “wherein a substantial portion of carbidopa is separated from entacapone and levodopa”. I am of opinion that that clause should be construed as a limitation, to identify a product in which a substantial portion of carbidopa is present in a discrete or separate form from the other two APIs. Claim 1 should be construed in a way in which the invention will work in preference to one in which it will not: Pfizer Overseas Pharmaceuticals v Eli Lilly & Co (2005) 68 IPR 1 at 54 [250] per French and Lindgren JJ with whom Crennan J agreed at 83 [406].

86    The inventors had taught that where all three APIs had been wet granulated together (in Example 1) the bioavailability of carbidopa was lower than in the reference product SINEMET®, in which carbidopa and levodopa are mixed together. They taught that a preferred way to increase the bioavailability of carbidopa from an oral solid composition comprising the three APIs was to mix or granulate levodopa and entacapone together and then add, to that mixture, the carbidopa (page 7 par 3 – page 8 par 2).

87    Professors Davies and Stewart and Dr Morella all agreed that the skilled addressee would understand that some amount of interfacial contact between the three APIs within the composition defined in claim 1 was acceptable. They differed as to the degree of the interfacial contact, in that Prof Stewart considered that the clause only went that far, so as to permit only such interfacial contact, and did not allow, as Prof Davies and Dr Morella contended, any intermixing of carbidopa with either or both of the other APIs.

88    I do not consider that either of the expert views as to the construction of claim 1 is entirely correct. First, Prof Stewart’s view would deny the possibility of any amount of carbidopa being mixed with one or both of the other APIs, while a substantial portion of carbidopa was not. Secondly, Prof Davies’ and Dr Morella’s view would allow an indeterminately large amount of the carbidopa to be mixed to a point beyond mere interfacial contact with either of both levodopa and entacapone, so long as the bioavailability of the carbidopa were maintained.

89    However, I prefer Prof Davies’ and Dr Morella’s explanation that, at the priority date, a skilled addressee would have understood that interfacial contact in a composition of the three APIs would be unavoidable and that, accordingly, the requirement in claim 1 that a substantial portion of carbidopa be separated from entacapone and levodopa, would not have been necessary had it related only to permitting interfacial contact between the three APIs.

90    The requirement in claim 1 demanded that a substantial, identifiable portion of carbidopa retain its distinctness in the composition. That is because of two linguistic emphases in the relevant clause, namely that there be present in the composition an identifiable portion of carbidopa, being “a substantial portion”, and that that portion be separated from the other two APIs. The indicia of a portion and a separation ensure that a product falling within claim 1 will comprise a composition in which a substantial amount, but not necessarily all, of the carbidopa can be in interfacial contact with, but otherwise must be separate from, both the levodopa and entacapone.

91    The patent does not lack clarity because it does not directly specify what quantum of carbidopa has to be present in the “substantial portion”. A skilled addressee would readily understand that any mixing or dilution of the total dose of carbidopa should not adversely affect the overall bioavailability of carbidopa, or the other APIs. This is because, first, claim 1 requires the composition to comprise “pharmacologically effective amounts” of each API. Commonsense suggests that the doses must be bioavailable when included in the composition, so that they can be pharmacologically effective when the composition is actually administered to patients. Secondly, since claim 1 also requires that a substantial portion of carbidopa be separated from the other two APIs, the claim must be understood as defining a limit on the amount of carbidopa permitted to be used or mixed outside the separate substantial portion, by reference to pharmacological effects, principally bioavailability. Both Dr Morella and Prof Davies had expressed a similar understanding.

92    What amount of carbidopa is sufficient to meet the criterion of “substantial” in the expression “substantial portion of carbidopa” is a matter of fact and degree having regard to any particular composition of the three APIs. The ordinary and natural meaning of “substantial” is “of ample or considerable amount or size; sizable” (Oxford English Dictionary online sense 3) or “of ample or considerable amount, quantity, size, etc” (Macquarie Dictionary online sense 2).

93    In the context of the complete specification, the skilled addressee would understand that the expression related to the inventors’ discovery that the bioavailability of carbidopa is increased if it is added separately to levodopa and entacapone (page 4 par 2). Accordingly, the skilled addressee would relate the feature in claim 1 requiring there to be a substantial portion of carbidopa being added separately to the other two APIs to the achievement of the result of increasing the bioavailability of carbidopa. In that context, the portion would have to be ample, considerable or sizeable and any amount of carbidopa that was not added separately to either or both of the other two APIs could not result in a material reduction of the overall bioavailability of the total dose of carbidopa.

94    Of course, this understanding of the expression “substantial portion” in claim 1 involves matters of degree. As Dixon CJ explained in Martin v Scribal Pty Ltd (1954) 92 CLR 17 at 60, a specification can convey an idea which “involves a matter of degree and for that reason any distinction that is precise must be but an arbitrary restriction on the inherent variability of the feature”. Indeed, relative expressions that require the exercise of judgment can be used in a claim but must be understood in a practical commonsense manner: Stena Rederi Aktiebolag v Austal Ships Sales Pty Ltd (2007) 73 IPR 257 at 264 [22] per Tamberlin J, whose decision and reasoning Heerey, Finn and Dowsett JJ affirmed in Austal Ship Sales Pty Ltd v Stena Rederi Aktiebolag (2008) 77 IPR 229; see at 232-240 [12]-[36].

95    The lack of a precise definition in a claim is not fatal to its validity so long as it provides a workable standard suitable to the intended use: Minnesota Mining 144 CLR at 274 per Aickin J, with whom Barwick CJ, Stephen, Mason and Wilson JJ agreed. Aickin J approved what Stephen J had said in Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59 at 60 in dealing with a claim in a patent that used a criterion prohibiting “admixture with any heat absorbing fluid in an amount to have any substantial effect as a cooling medium to control the polymerizaiton reaction by heat absorption”. The Commissioner had argued that the word “substantial” created a lack of clarity. Stephen J held that the word had to be construed in the context of a claim to control temperature. He said (48 ALJR at 60E, G):

It will in each case be a question of fact and degree whether or not an injected admixture has a substantial effect as a cooling medium and this is the very sort of question which not only do courts have to answer daily, but which I believe that those skilled in the art would have little difficulty in resolving.

… There will, I think, in the present case be no difficulty in a third party ascertaining whether or not what he proposes to do falls within the ambit of the claim; the injection of a cooled admixed fluid in any quantity sufficient substantially to affect reactor temperatures will greatly exceed the quantities which might be required for use as modifiers or solvents. (emphasis added)

96    It follows that the elucidation of such a workable standard, for those skilled in the art who need to know both what the boundaries of the claim are, while it defines an asserted monopoly, and how to work the invention, must be part of the construction of the claim.

97    I do not accept Orion’s argument that the phrase “from entacapone and levopoda” should be construed as identifying separation of carbidopa from only a combination of those two APIs, but permitting a substantial portion of carbidopa to be mixed with one or other of them. Orion referred, in support of its argument, to the use in the summary of the invention (page 4 par 3) of the expression “from entacapone and/or levodopa” that appeared there in a description of the invention that was otherwise reflective of the language of claim 1. That was the only instance in the patent of the use of “and/or”. Had the patentee intended claim 1 to have this ambulatory qualification, it should have said so in the language which it chose to define its claimed monopoly. The expression “and/or” in that particular instance has all the appearance of a stray phrase that is not repeated or discussed elsewhere in the specification.

98    In my opinion, claim 1 requires that the substantial portion of carbidopa, first, not be intermixed with either of the other two APIs so that, other than through any interfacial contact, that portion will be separate from both of the levodopa and entacapone, and secondly, be sufficient so that bioavailability of the overall dose of each of the APIs is not adversely affected by any intermixing.

99    However, claim 1 does not exclude there being a discrete portion of carbidopa included in the overall composition, different from the substantial portion necessary to satisfy the integer in claim 1, which is an admixture with one of both of the other APIs or another ingredient. How much carbidopa must be in the requisite “substantial portion” is a matter of fact and degree.

100    Claim 2: The construction which I have given to claim 1 is consistent with the integer of different forms for entacapone and levodopa, on the one hand, and carbidopa, on the other, in claim 2. That claim made clear that the requisite separation would be achieved if the entacapone and levodopa were in the form of granules and the carbidopa was in powder, a different, and separating, form.

101    Claim 12: The controversy on the construction of claim 12 involved the meaning of its requirement that the method for preparing the composition “comprises adding carbidopa … separately to the remainder of the composition”. Orion contended that this integer should be construed in the same way as Prof Davies and Dr Morella had interpreted the separation requirement in claim 1. In other words, Orion argued that the method did not require carbidopa to be added separately to all of the entacapone and levodopa. It also submitted that the absence of both definite and indefinite articles before “carbidopa” suggested that not all the carbidopa had to be added at once or by itself.

102    I reject Orion’s argument. The ordinary and natural meaning of claim 12 is that the step for adding carbidopa in the method prescribed must occur discretely, at the conclusion of the process of adding all other ingredients that will make up the composition. The phrase “separately to the remainder of the composition” conveys the meaning that the addition of carbidopa must be, first, separate or discrete and, secondly, done to something that already exists, namely “the remainder of the composition”, or all the other ingredients. Moreover, if any amount of carbidopa could be omitted from that which was to be added separately, as Orion contended, there is nothing in claim 12 that can be used to identify what amount sufficed to meet the requirement of the integer. The consequence of Orion’s submission would be that a mere sprinkling of a fraction of the total amount of carbidopa included in the ultimate composition at the final stage of adding ingredients would suffice. That submission does not give content to the express words that prescribe a method of preparation. Nor does it reflect the teaching of the patent to which claims 12, 13 and 14 appear to relate, namely the inventors’ discovery of “a particularly interesting way to increase the bioavailability of carbidopa”, was to add it separately after first granulating levodopa and entacapone together (page 4-5 pars 2-5 page 5).

103    Unlike claim 1, claim 12 does not specify either that any particular portion or amount of carbidopa be added separately or that the composition comprise pharmacologically effective amounts of each of the three APIs. In my opinion, the method prescribed in claim 12, in its ordinary and natural meaning, requires that all of the carbidopa be added separately to, and after, all of the other ingredients.

104    Claim 13: A similar issue to that in claim 12 arises in the construction of claim 13. That claim provided that the method for preparing the composition “comprises mixing first entacapone and levodopa separately, adding carbidopa separately and formulating the mixture into a plurality of dosage forms”.

105    I reject Orion’s argument that the absence of the definite and indefinite articles before any of the three APIs’ names and the use of the word “comprises” supports a construction of claim 13 that some carbidopa can be added at a point other than the only point expressly stated in the method. The ordinary and natural meaning derived from the repetition of the word “separately” and the ordered sequential structure of claim 13 conveys the sense that all of the carbidopa is added once for all separately, and after, the mixing of all of the levodopa and entacapone.

106    Claim 14: Since claim 14 is dependent on each of claims 12 and 13, it cannot convey a wider latitude as to when, or how much, carbidopa can be added than that provided in the express sequential terms of the two claimed methods. Like claim 2, claim 14 reflects a means of achieving the separation of carbidopa and its sequential addition to the mixture. That construction flows from the integer “wherein carbidopa is added in powder form extragranually to granules to entacapone and levodopa”. That integer contemplates that the granules of entacapone and levodopa already exist at the time that the carbidopa, in powder form, is added extragranually or outside the existing granules.

107     Claim 17: The critical issue of construction is that raised in step c) in the process identified in claim 17, namely:

c)    adding a pharmacologically effective amount of carbidopa … optionally a lubricant, and optionally one or more pharmaceutical excipients to the granule batch to obtain a second mixture.

108    The granule batch is the product of steps a) and b), namely the granulation of a first mixture obtained from mixing “pharmacologically effective amounts of entacapone and levodopa … with at least one pharmaceutically acceptable excipient and a disintegrant”.

109    The non-clinician experts disagreed about the meaning of the expression “pharmacologically effective amount”. Professors Davies and Jenner, together with Dr Morella, understood the expression, as used in the patent, to refer to the “preferred”, “especially preferred” and “particularly preferred” ranges of dosages of the three APIs. In contrast, Prof Stewart and Dr Reece understood the expression in the patent to mean a specific dosage in a particular tablet. Prof Stewart said that was because of his understanding of the ordinary use of particular dosages in the treatment of patients. However, Prof Stewart acknowledged that the expression could involve a range.

110    As the clinicians’ evidence established, both Drs O’Neill and Peppard, in accordance with accepted practice, titrated the dosage prescribed for individual patients in accordance with their diagnoses of the patient’s medical condition. They agreed that there was no fixed dosage to administer in any particular class or classes of case related to a patient’s manifestation of symptoms, although there were usual dosages from which a treating doctor could choose a prescription. Moreover, at the priority dates, Dr Peppard said that he would prescribe that some patients should take a half or one and a half SINEMET® tablets, noting that those tablets were manufactured with a fracture line in their middle to enable them to be cut in half.

111    I am of opinion that the skilled addressee would understand that the expression in claim 17 “pharmacologically effective amount” conveyed the meaning of an amount of the relevant API that ordinarily is known to be capable of producing a desired beneficial effect in the treatment of patients suffering Parkinson’s disease. In other words, it is an amount within the range that a treating doctor could prescribe because it is known, ordinarily, to produce a drug plasma level useful in treatment of patients. As the two clinicians’ evidence made clear, that amount is not necessarily the same as the dosage ratios of 4:1 and 10:1 of levodopa and carbidopa referred to in the preferred embodiments in the patent (pages 13-15) and in the commercial reference formulations (pages 2 and 22) that were available at the priority date.

112    The skilled addressee would be aware of the minimum and maximum amounts of each API suitable for prescription. For example, at the priority date, 200 mg of entacapone was administered regardless of the amounts of levodopa and carbidopa that were also administered. That was because 200 mg of that COMT inhibitor was effective to ensure that, whatever combined doses of levodopa and carbidopa the patient took, a therapeutically sufficient amount of levodopa crossed the patient’s blood brain barrier to achieve the clinician’s or treating doctor’s purpose of delivering a desired dosage of dopamine to the brain.

113    The reason that an amount of one API is pharmacologically effective is because it is known to produce, in ordinary experience, a desired level or range of levels of the API in a patient’s blood plasma, bearing in mind that there is no uniquely correct amount for any stage of Parkinson’s disease or uniformity of patient conditions or metabolisms. The decision of how much levodopa should be prescribed is a matter of clinical judgment for a treating doctor. The doctor can vary the dose, even from a prefabricated tablet designed for halving, or division into smaller dosages, depending on what he or she considers will be useful in treating the patient. The patentee conveyed the flexibility of what amounts of each API should be included in any formulation of the composition by using the ambulatory expression “pharmacologically effective amount” to allow for the large range of variations in treatment dosages. Those skilled in the art knew that both levodopa and carbidopa were effective over a range of dosages, although the pharmaceutical industry had developed conventional compositions of those two APIs mixed in ratios of either 10:1 or 4:1. There is nonetheless a difference between an amount that is clinically, as opposed to pharmacologically, effective. The former is the dose that works in an individual as his or her actual treatment, the latter is an amount that ordinarily produces desired blood plasma levels in patients, that ought to achieve that successful clinical outcome.

114    That does not mean that there is any medical reason why a further or different amount of one or more of the APIs within the accepted maximum and minimum dosages could not be included in the ultimate formulation of the composition, provided that that inclusion does not compromise the pharmacological effectiveness of the overall composition. Thus, the amount of levodopa added in step a) in claim 17 could be the lowest in the particularly preferred range described in the patent (page 13), namely 50 mg. That is a pharmacologically effective dose of levopoda. That 50 mg would be added with the 200 mg of entacapone in the first mixture, but a further 50 mg of levodopa could be added later to take the total dose to 100 mg, also a pharmacologically effective amount.

115    Moreover, step a) in claim 17 does not require that the whole amount of the intended dose of entacapone and levodopa be added at that point. Rather, it requires an amount of each of those APIs that is pharmacologically effective and leaves open subsequent supplementation of that dosage.

116    Unlike claims 1, 2, 12, 13 and 14, claim 17 does not require specifically that all, or a substantial portion of, carbidopa be separate, or added separately from, the other two APIs. Clearly enough, step c) requires that carbidopa be added after the creation of the first mixture. But, the word “comprises” in the chapeau of claim 17 can be given the wide meaning of its definition in this claim that would permit the addition, at step c), of “other additives [or] components” (page 25). The word “comprises”, as used in claim 17, qualifies the whole of the balance of the claim in steps a) - d).

117    The granulation of the first mixture in step b) can impact upon the effective separation of the three APIs, in order to achieve the requirement that they will not be mixed together so as to affect the bioavailability of carbidopa against which the patent cautioned. Moreover, the prior art comprised a number of effective combinations of levodopa and carbidopa, so, for example, they might both be added in step c), provided that any extra amount of levodopa so added does not adversely affect the pharmacological efficacy of the total doses of the three APIs in the overall composition, to achieve the intended pharmacological result for which that composition will be prescribed.

118    The method in claim 17 is intended to result in a composition of the three APIs for administration to patients. It is not a recipe for particular strengths or dosages of any of the APIs or for any particular treatment. There is no reason to ignore the natural and ordinary meaning of claim 17 as teaching a method that can be adapted to produce a variety of dosages of the three APIs within their known overall pharmacologically effective dosage ranges to suit the manufacturer’s choice.

119    Claim 18: Claim 18 is dependent on claim 17 and simply provides that wet granulation be the method used in step b) to obtain the first mixture. It otherwise has the same meaning as claim 17.

120    Claims 19 and 20: Each of claims 19 and 20 has the following integers, first, an oral pharmaceutical tablet, secondly, dosages of the three APIs in each of which there is always 200 mg of entacapone, ranges of 50-150 mg for levodopa and 10-37.5 mg for carbidopa and, thirdly, characteristics for ranges of weight (400-750 mg) and, in the case of claim 19, tablet volume (200-1,000 mm3) or, in the case of claim 20, tablet dimensions (length 13-18 mm, width 6-9 mm and height 4-7 mm).

121    Clearly enough, the word “comprising” as used in each of claims 19 and 20 must have its broad defined meaning (page 25), so that excipients can be used to create a tablet from a composition that includes each of the three APIs. It is necessary and obvious that “comprising” have this meaning in order that a tablet will achieve a minimum weight of 400 mg, which is 12.5 mg more than the total of the maximum combined weights of the three APIs.

122    I reject Actavis’ submission that claims 19 and 20 are not limited to tablets prepared using the process of the invention disclosed in the specification. That argument gave no weight to the adjective “pharmaceutical” before the word “tablet” and the necessary implication in both claims that the three APIs would be in a composition with excipients. The natural and ordinary meaning of “pharmaceutical” is “of, relating to, or engaged in pharmacy”, “of the nature of a medicinal drug” (Oxford English Dictionary online). In the Macquarie Dictionary online it is defined as “relating to pharmacy” which in turn is defined as “the art or practice of preparing and dispensing drugs and medicines”.

123    The expression “an oral pharmaceutical tablet” as used in claims 19 and 20 conveys the meaning of a tablet suitable for oral administration as a medicine in the treatment of Parkinson’s disease. Such a meaning is reinforced by the integers in each claim as to the dosages of the three APIs and the weights, volumes or dimensions of the resulting tablets.

124    The skilled addressee would understand that the word “pharmaceutical” in claims 19 and 20 would convey that such a tablet must have sufficient stability and be composed of such additional ingredients that it would be of a standard and quality that is suitable to be approved by regulatory authorities for administration to patients as a treatment for Parkinson’s disease.

125    Claim 21: The significant issue in the construction of claim 21 concerned the expression “whereby the therapeutical [sic] effect achieved with the said composition … is comparable to that achieved with the known separate formulations”. The known formulations of the three APIs involved a combination of levodopa and carbidopa in dosages within the ranges specified in the patent (as in claims 19 and 20 and described earlier in the complete specification on pages 13-15) and a separate concurrent dosage of 200 mg of entacapone. The experts agreed that the word “therapeutical” would be understood by a skilled addressee to mean “therapeutic”.

126    I reject Actavis’ argument that the integer of comparability of therapeutic effect is vague or uncertain or cannot be discerned with clarity from figures 1-6 in the complete specification. I do not accept Dr Reece’s evidence that a skilled addressee would not understand the comparison required by claim 21. Indeed, Dr Reece used the same expression as in claim 21 in the joint experts’ report in his explanation of his understanding of what two pieces of prior art, an article entitled “Entacapone enhances the response to levodopa in parkinsonsian patients with motor fluctuations” by UK Rinne, JP Larsen, Å Siden, J Worm-Petersen and the Nomecomt Study Group: Neurology Vol 51 (5) at 1309 to 1314, published in November 1998 (the Nomecomt report) and an entry in Martindale: The Complete Drug Reference (32nd ed, 1999), would have conveyed to him in June 1999. There he wrote that the three APIs “could be combined in a single composition that would give a therapeutic effect comparable to that of the known, separate tablets (entacapone + levodopa/carbidopa) (without regard to stability or tablet size)”.

127    I am of opinion that the skilled addressee would understand that the comparison identified in claim 21 will be between the overall therapeutic effect achieved by each of the three APIs as a result of the two means of delivery, namely, the claimed solid oral fixed dose composition of the three APIs on the one hand and, on the other, the concurrent administration of the known means, being separate formulations of, first, entacapone and, secondly, the combination of levodopa and carbidopa.

128    A skilled addressee would understand that the comparison called for by claim 21 was of the respective efficacy of the three-in-one combination, to achieve a similar amount of levodopa crossing the blood brain barrier as occurred by use of the existing reference products with similar administered amounts of the three APIs.

129    The ordinary and natural meaning of “therapeutic” is “curative” or “healing” (Macquarie Dictionary online and cf: Oxford English Dictionary online). The curative or healing effect of levodopa is in its mitigation, or control, of the effects of Parkinson’s disease by creating dopamine after it passes the blood brain barrier. Each of the formulations existing at the priority date achieved, in the ordinary course of treatment, a therapeutic effect based on the dosages of the three APIs administered that depended ultimately on the amount of levodopa that crossed the blood brain barrier. The absence of a precise scale or measure in claim 21 does not render the claim unclear. The comparison that it calls for concerns the curative or healing effect of a three-in-one combination with the two reference tablets being products containing separate, commercially available, comparable dosages of the three APIs. That effect is, and can only be, delivered by the amount of levodopa that ultimately reaches its intended destination i.e., after it passes the blood brain barrier.

130    The assessment of comparability in respect of claim 21 in any case will involve a question of fact and degree, but, in the present context, I do not think that it gives rise to any ambiguity: Monsanto 48 ALJR at 60; Minnesota 144 CLR at 286. The skilled addressee would have little difficulty in assessing whether a particular composition of pharmacologically effective amounts of the three APIs achieves a comparable effect to that of the known formulations at the priority date of 200 mg of entacapone and any one of the combinations of levodopa and carbidopa (including fractional dosages that the manufacturers of those tablets allowed to occur and clinicians prescribed), in effecting the ultimate healing or curative purpose of delivering a sufficient amount of levodopa past the blood brain barrier. Ordinarily, such a comparison can be made by considering the respective bioavailability of each API in the two forms of administration being considered.

131    I do not accept Actavis’ argument or Dr Reece’s evidence that the comparison that claim 21 requires involves the use of figures 1-6 in the patent. Those figures illustrated, in a broad brush way, results that the inventors achieved and on which they based their own assessment of the bioavailability results reflected in two separate trials, using formulations 1 and 2, in one trial, and formulations 3 and 4 in the other, against different control groups using the existing reference products containing doses of 200 mg entacapone and a separately administered combination of levodopa and carbidopa. In the discussion of the bioavailability results of the trials on pages 7-8 and 22 of the complete specification, that were summarised in the graphs in figures 1-6, the inventors opined that the result for carbidopa’s bioavailability from formulation 1 was “too low compared to the reference product”, but that the result from formulation 2 was “acceptable”. Indeed, on page 22 of the patent the inventors said:

According to the results shown in Figures 4-6 the absorptions of the tested two formulations are comparable to the commercial reference formulations. The dissolved amounts of entacapone, levodopa and carbidopa are at least 50 % in 30 minutes when measured with USP dissolution equipment.

132    Dr Reece acknowledged that this comparison was based on a different test to that used to compare formulations 1 and 2, because of the different absorption results plotted for the reference APIs for figures 1-3 on the one hand and figures 4-6 on the other. However, Dr Reece then tried to juxtapose the results from the different trials, including the different reference product results, and draw some standard out of those results by which to make the comparison called for by claim 21.

133    I do not accept that that approach is what the patentee mandated to define the monopoly in claim 21. It is impractical and unrealistic, as unfortunately was much of Dr Reece’s evidence. It ignores what the skilled addressee would do in assessing whether a generic product had comparable pharmacokinetic properties with a patented API for regulatory purposes.

134    A skilled addressee would know, as the concurrent expert evidence demonstrated, that when a generic manufacturer seeks registration of an API in a product, standard comparative studies must be undertaken of the new product’s characteristics, including bioavailability of the API, as against those of the original invention or existing product. As Dr Morella said:

… what’s accepted is that if you achieve a Cmax and an area under the curve within certain limits for a test product and it’s shown to be bioequivalent to the reference product which, in this case, is the marketed products, then they will have an equivalent effect, an equivalent therapeutic effect. And that’s the basis under which generic products are registered. The test product, the generic, is compared to the innovator product, the reference. On making that comparison, the regulators will assess the data and decide on whether or not it’s bioequivalent, and that in itself then it’s assumed that the product will be therapeutically equivalent.

135    The standard of comparison in claim 21 is not expressed to be based on the opinion of the inventors as to the adequacy of formulations 1 or 2 or of the data in the graphs in figures 1-6. Rather, that standard, as Dr Morella, Professors Davies and Jenner said in the joint experts’ report, is one that involves an objective comparison of the pharmacokinetics, including bioavailability (tested by reference to standard methods of using maximum concentration (C max) and area under curve (AUC) measures of blood plasma levels over time), of each of the three APIs in the composition said to fall within claim 21 as against those of the reference products.

2.     The infringement issue

136    Actavis has a secret proprietary method of preparing its proposed combination product comprising the three APIs. That method has a particular distinguishing aspect that Actavis relies on to deny that any of its proposed products could be found to be infringements of any claims 1, 2, 12, 13, 14, 17, 18, 19, 20 and 21. The parties understand the nature of the distinguishing aspect is to do with whether there is a blending step in Actavis’ process. Thus, having regard to my findings on the construction of the claims in issue, they should be able to understand, without the need for more detailed confidential reasons, the conclusions that I will express below. However, I will give further reasons, if either side considers that some confidential elaboration of the basis of those conclusions is necessary, to enable them or an appellate court to understand how I reached them.

137    Actavis’ open written final submissions encapsulated the essence of the parties’ principal dispute on infringement in relation to the significance of whether Actavis’ process had a blending step (par 27) as follows:

As Dr Morella and Prof Stewart said, it [the blending step] is essential to ensure homogeneity. The proper construction of each of claims 1, 2, 12, 13, 14, 17 and 18 requires carbidopa to be separated from entacapone and levodopa, not merely “added separately (ie subsequently) to the granules”. Ensuring homogeneity in a blend of carbidopa and levodopa is the very opposite of “adding carbidopa separately”. It is directly contrary to clear teaching of the patent. (emphasis in original)

138    Claim 1: No substantial portion of carbidopa is separated from any of the entacapone and levodopa in Actavis’ products. It follows that, having regard to my construction of claim 1, the Actavis products do not infringe claim 1.

139    I reject Actavis’ argument that it cannot infringe any of the claims in issue because its method uses MCC as an excipient when the patent excluded MCC from the class of “pharmaceutically acceptable excipients”, wherever the latter expression appeared in the claims. That argument is untenable given the express words of the exclusion in claim 11. That exclusion is in the following terms:

… and comprising at least one pharmaceutically acceptable excipient other than microcrystalline cellulose. (emphasis added)

140    The patentee considered MCC to be a pharmaceutically acceptable excipient because it excluded it from the class of those substances to which claim 11 alone applied. If the patent, properly construed, had determined or defined MCC as not being a pharmaceutically acceptable excipient, its exclusion in claim 11 would have had no work to do. All that the inventors said in the complete specification (at pages 9 and 10) was that they had found unexpectedly that MCC “destabilizes the formulations on long term storage, when all three active agents are combined together.” The formulations to which this passage referred were unspecified, other than, by inference, formulation 1 in table 1. The passage did not say that this result applied to all possible formulations in which the three APIs were present as ingredients. It merely stated that MCC had the particular, identified effect when “all three active agents are combined together”. The skilled addressee would know, as the complete specification stated, that at least levodopa and carbidopa could be successfully combined in one composition administered simultaneously with entacapone, because that was a then conventional form of treatment.

141    The passage on pages 9 and 10 of the complete specification dealing with MCC immediately preceded the consistory clause that reflected claim 11. The inventors did not say anywhere in the patent that MCC was not a pharmaceutically acceptable excipient for any purpose and in any method where all three APIs were ingredients in a composition, except for one made up in accordance with claim 11. Indeed, claim 11 said that MCC was a pharmaceutically acceptable excipient but that MCC should not be an ingredient of a composition made in accordance with that claim.

142    For these reasons, I am not satisfied that the patent conveys in its natural and ordinary meaning, or that a skilled addressee would understand it to convey, that MCC was not in the class of pharmaceutically acceptable excipients in any claim other than claim 11.

143    Claim 2: There is no dispute that the determination of whether the Actavis products infringe claim 1 governs whether they do or do not infringe claim 2. Accordingly, based on my conclusion in relation to claim 1, the Actavis products do not infringe claim 2.

144    Claim 12: The distinguishing aspect is present in Actavis’ method for manufacturing its products. Accordingly, based on my construction of claim 12, Actavis’ method does not infringe that claim.

145    Claims 13 and 14: It follows from my finding as to claim 12, that because the distinguishing aspect is present in Actavis’ method, neither of claims 13 or 14 is infringed by that method.

146    Claim 17: The method the subject of claim 17 does not involve an integer requiring the absence of the distinguishing aspect from any one or more steps in making in the composition, on the construction of that claim that I have reached. Actavis’ method infringes the method in claim 17 because its method comprises all of the integers of claim 17, as I have construed that claim.

147    A person does not escape a finding of infringement by adding further integers to a product or steps to a method if the person has taken all of the essential integers of the patentee’s claim: Minnesota Mining 144 CLR at 286; Bitech Engineering Pty Ltd v Garth Living Pty Ltd (2010) 86 IPR 468 at 476 [29]-[30] per Sundberg, Bennett and Yates JJ. The additional integers in Actavis’ method do not make a new working of the combination of integers in claim 17 so as to make it non-infringing.

148    Claim 18: The interposition of the integer of wet granulation in claim 18 does not affect the fact that, because it is dependent on claim 17, Actavis’ method also infringes claim 18.

149    Claims 19 and 20: Based on the construction that I have given these two claims, Actavis accepted that five of its six products would infringe them. It was common ground that the sixth product, a combination of 200 mg of levodopa, 50 mg of carbidopa and 200 mg of entacapone could not infringe. That was because the doses of levodopa and carbidopa in that combination exceeded the maxima for those APIs in the two claims.

150    Claim 21: Actavis accepted that all its products infringed claim 21, if it were construed to have the meaning that I have found.

3.     The clarity issue – submissions

151    Claims 1 and 2: Actavis argued that these claims would lack definition if they allowed some carbidopa to be intermixed with entacapone and levodopa without defining the boundaries of that amount. Actavis contended that any limitation by reference to the bioavailability of carbidopa, such as had been suggested by Prof Davies or Dr Morella, did not form any part of claims 1 or 2.

152    Prof Davies had said that the expression “a substantial portion of carbidopa is separated from entacapone and levodopa” in claim 1 allowed for some mixing of the three APIs so long as the bioavailability of carbidopa is acceptable by way of comparison to the reference products. Dr Morella said that such intermixing was permitted provided that the bioavailability of the APIs was maintained.

153    Claims 12, 13, 14, 17 and 18: Actavis argued that, similarly, the requirement in these claims that carbidopa be added separately was ambiguous.

154    Claims 1, 2, 13, 14, 17, 18, 19, 20 and 21: Actavis argued that the use of “comprising” and “comprises” in these claims could make them unclear or ambiguous, if they were construed as Orion had argued. Actavis contended that the words “comprising” and “comprises” in these claims could not justify a construction that did not respect the distinction or separation that each claim required for carbidopa, or a substantial portion of that API, from the other two APIs.

155    Claim 21: Actavis argued that the standard of comparability prescribed in this claim lacked clarity. It contended that what constituted a comparable therapeutic effect was unclear and an “archetype of imprecise language” because there was no precise standard against which the comparison could be evaluated. Actavis submitted that this claim required a skilled addressee to make a subjective judgment as to comparability and that this demonstrated its lack of clarity.

3.     The clarity issue – consideration

156    I have already discussed the clarity issue in dealing with the construction issues. Importantly, the definition of a monopoly sought in a claim must be expressed so that it is not reasonably capable of being misunderstood: Martin 92 CLR at 59: Welch Perrin 106 CLR at 610. Dixon CJ explained in Martin 92 CLR at 59 that if the patentee deliberately introduced an ambiguity to produce a vagueness in the boundaries of the asserted monopoly, that purposeful design would destroy the patent, or claim, regardless of how great or small be the ambiguity.

157    I reject Actavis’ arguments on the issue of clarity.

158    There is nothing to suggest that the patentee introduced any such deliberate ambiguity in any of the ways suggested by Actavis. I have found that each of claims 1, 2, 12, 13 and 14 is clear and unambiguous, for the reasons above, in respect of their requirements for separation of carbidopa from the other two APIs and the separate addition of carbidopa. And I found that claims 17 and 18 did not require carbidopa to be separated from either or both of the other two APIs.

159    Likewise, as I have construed claims 1, 2, 12, 13, 14, 17, 18, 19, 20 and 21, the words “comprising” and “comprise” in those claims do not cause any of those claims to lack clarity or become ambiguous.

160    Finally, as I have construed the expression in claim 21 “whereby the therapeutical [sic] effect achieved with the said composition in the treatment of Parkinson’s disease is comparable to that achieved with the known separate formulations”, the claim is clear and does not give rise to ambiguity.

4.    The fair basis issue – Actavis’ submissions

161    Actavis argued that claims 1, 2, 12, 13, 14, 17, 18, 19, 20 and 21 (the challenged claims) were not fairly based on the matter described in the specification. The principal basis of Actavis’ attack was its identification of the definition of the invention that I have rejected at [72]-[76] above. In essence, it argued that the body of the specification as a whole disclosed the invention as encompassing particular or specific characteristics relating to stability, bioavailability and ease of swallowing and that these characteristics were achieved by a particular process for preparing the composition. Actavis also submitted that the process described in the specification included, first, both the use of certain compatible excipients and excluded certain incompatible ones so as to achieve stability, and, secondly, the method of mixing entacapone and levodopa separately and then adding carbidopa so as to result in the separation of a substantial portion of carbidopa from the other two APIs in order to achieve bioavailability and ease of swallowing.

162    Actavis contended that each of the challenged claims was not fairly based because it did not exclude incompatible excipients, namely MCC as well as surface active agents and silica (being the three excipients excluded from the preferred embodiment described in the specification (pp 10-11)). It noted that each of claims 1, 2, 17, 18 and 21 referred to the inclusion of at least one “pharmaceutically acceptable excipient” while claims 12, 13, 14, 19 and 20 were silent as to the excipients to be used. It argued that as none of the challenged claims excluded the incompatible excipients, each travelled beyond the disclosure in the specification. Moreover, Actavis contended that the specification did not contain any real and reasonably clear disclosure of an oral solid composition, or method for preparing one, that used MCC, surface active agents or silica.

163    Next, Actavis argued that the separation integers in claims 1, 2, 12, 13, 14, 17 and 18 would not be fairly based if I accepted Orion’s construction of those claims in relation to those integers. It is not necessary to consider Actavis’ argument on claims 1, 2, 12, 13 and 14 since I have rejected Orion’s construction of those claims. But, I did not construe claims 17 and 18 to require the addition of carbidopa separately from any other ingredient, including levodopa or entacapone, at step c) (see [111]-[116] above). Actavis contended that any mixing of carbidopa with either of the other two APIs was not described in the specification and that the mere repetition of the consistory clause (at page 17) for claim 17 was insufficient.

164    Finally, Actavis argued that claims 19, 20 and 21 did not refer to the separation, or separate addition, of carbidopa requirements or to the need to exclude incompatible excipients. It contended that each of those matters was a central requirement of the invention disclosed in the specification. I have rejected that characterisation of the invention, on which Actavis relied for this argument. Accordingly, it is not necessary to consider it here. Actavis also argued that claims 19 and 20 travelled beyond the disclosure in the specification because they described tablets of a particular size or volume that could be made by any method. That is, claims 19 and 20, so Actavis contended, were not limited to tablets made by a method described in the specification. It also submitted that claim 21 was not limited to preparations made with the method described in formulations 3 and 4 and so the claim travelled beyond what was disclosed in the specification.

4.    The fair basis issue – consideration

165    Much of Actavis’ argument that the challenged claims were not fairly based on the matter described in the specification within the meaning of s 40(3) was premised on its posited characterisation of what the invention was. As I have explained above, the invention was more limited than Actavis propounded (at [71]). The invention was a product, being “an oral solid fixed dose composition comprising pharmacologically effective amounts of entacapone, levodopa and carbidopa … and comprising at least one pharmaceutically acceptable excipient” (page 3 par 4), a method of preparing that product (pages 4-5 par 5) and a method of using it (page 5 par 3).

166    The question is whether each of the challenged claims is “fairly based on the matter described in the specification” within the meaning of s 40(3) of the Act or whether the claims travel beyond that matter: Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd (2001) 207 CLR 1 at 12 [15] per Gleeson CJ, McHugh, Gummow, Hayne and Callinan JJ, approving what Barwick CJ had said in Olin Corporation v Super Cartridge Co Pty Ltd (1977) 180 CLR 236 at 240. The complete specification must not be read in the abstract. Rather, it must be construed by the Court from the vantage point of a skilled addressee in light of the common general knowledge and the art at the priority date: Kimberly-Clark 207 CLR at 16-17 [24]-[25]. I explained the principles in Apotex Pty Ltd v Les Laboratoires Servier [2013] FCA 1426 at [134]-[136] as follows:

134    A consistory clause in a specification in a patent is a general description of what the invention is said to consist of: Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (2004) 217 CLR 274 at 282 [10] per Gleeson CJ, McHugh, Gummow, Hayne and Heydon JJ (Lockwood [No 1]). The expression “the matter described in the specification” as used in s 40(3) refers to the invention as discussed in the specification (217 CLR at 293-294 [53]-[54]). The Court must evaluate whether the claims assert a monopoly over something wider than the invention as it was really and reasonably clearly disclosed in the specification in the sense in which a skilled addressee would read it (217 CLR at 300-301 [68]-[69], 306 [83]-[85]). However, a claim that is couched in the same terms as the description of the invention in the specification, is not necessarily “fairly based” on that description because, as the Court explained in Lockwood [No 1] 217 CLR at 306 [87]:

“A “coincidence of language” between a claim and part of the body of a specification does not establish fair basing if that part of the language of the specification does not reflect the description of the invention in the light of the specification as a whole.” (emphasis added)

135    Thus, if a specification described an apparatus limited to a particular use as the invention, a claim for the apparatus itself, without the limitation described, would not be fairly based on the more limited description and, so, would travel beyond the specification (217 CLR at 311 [101]). However, if the words of the claim reflect, even in the same language, what the specification discloses in real and reasonably clear words as the invention, it will be fairly based. The requirement of s 40(3) is distinct from that in s 40(2)(a) for the specification to describe the invention fully (217 CLR at 292 [49], 301 [70]). The Court held in Lockwood [No 1] 217 CLR at 310 [99] that:

“Doric submitted that Olin decided that a claim based on a consistory clause cannot be fairly based. It did not. Rather, as the Patentee submitted, the correct position is that a claim based on what has been cast in the form of a consistory clause is not fairly based if other parts of the matter in the specification show that the invention is narrower than that consistory clause. The inquiry is into what the body of the specification read as a whole discloses as the invention [Welch Perrin & Co Pty Ltd v Worrel (1961) 106 CLR 588 at 612-613]. An assertion by the inventor in a consistory clause of that of which the invention consists does not compel the conclusion by the court that the claims are fairly based nor is the assertion determinative of the identity of the invention. The consistory clause is to be considered by the court with the rest of the specification.” (emphasis added)

136    As Bennett J put it in Sigma Pharmaceuticals (Australia) Pty Ltd v Wyeth [2011] FCAFC 132 at [90] (and see too at [169] per Nicholas J, [243], [249] per Yates J):

“… it is not simply a matter of matching a consistory clause or other stray phrases with a claim. It is a question of comparing the invention claimed with the invention disclosed. Frequently, indeed most often, there is no real difference; sometimes there is.” (original emphasis)

167    Here, the skilled addressee would understand that claim 1 was based on the express description in the specification of an oral solid composition comprised of the three APIs and a pharmaceutically acceptable excipient (page 3 par 4 and repeated several times) and the express consistory clause (page 4 par 3) replicating claim 1 that followed the preceding paragraphs which discussed the separate addition of carbidopa after first granulating entacapone and levodopa together (page 4 par 2). Further, the specification also discussed methods of producing the composition in which carbidopa was expressly required to be added separately, and after, entacapone and levodopa first had been granulated together (e.g. page 8 par 1 – page 9 par 1). It follows that claim 1 was fairly based on the matter described in the specification.

168    Claim 2, which was dependant on claim 1, merely added that as discussed in the specification on page 9 par 1, carbidopa could be added “extragranularly as such (in powder form) into the mixture”. The skilled addressee would understand from this, if this were not part of the common general knowledge, that the ordinary form of carbidopa was a powder and that this was the form referred to in one technique to accomplish the desired separation described (page 4 par 4) in the sentence: “Carbidopa can be added as such or in a form of granules”. This sufficed to be a fair basis for claim 2.

169    Similarly, the methods in claims 12, 13 and 14 were fairly based on the matter described in the specification (see page 4 par 5 – page 5), the consistory clauses and elaborations for claims 12 and 13 (at page 8 par 4, page 12 par 3 – page 15) which disclosed dosage forms for the composition, and the description on which claim 14 is based (at page 9 par 1).

170    In essence, claim 12 was for a method that required the separate addition of carbidopa to the remainder of the composition, while the method in claim 13 required mixing the other two APIs separately before adding carbidopa separately and then formulating the mixture into dosage forms. Claim 14 simply referred to a method in which carbidopa was added in a powder form extragranularly to granules of entacapone and levodopa.

171    I reject Actavis’ argument that it was essential for the challenged claims to exclude MCC, surface agents and silica in order for them to be fairly based. The specification did not describe MCC as an unacceptable excipient except in the one circumstance in which all three APIs were combined together (page 9 par 4 – page 10). Hence, claim 11 reflected that exclusion. The specification did not suggest that MCC was unsuitable if carbidopa were added separately to the other two APIs, and the three APIs were not all combined together. The specification described the exclusion of MCC, surface agents and silica (at page 10 par 3 – page 11) as a preferred embodiment, as opposed to an essential feature.

172    The specification noted that tablets containing surface-active agents, such as polyethylene glycol, polysorbate and sodium lauryl sulphate, had been found to be unstable in standard stability tests. The only description of a process in which those tests considered tablets comprising MCC and polyethylene glycol was in formulation 2 in Example 1 (page 10 par 2, pages 20-21). However, formulation 2 also comprised granules in which the three APIs were compaction granulated together.

173    In Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (2004) 217 CLR 274 (Lockwood [No 1]) at 300 [68]-[69] Gleeson CJ, McHugh, Gummow, Hayne and Heydon JJ explained that s 40(3) required “a real and reasonably clear disclosure”, but this obligation did not limit the disclosure simply to preferred embodiments. Thus, what is disclosed in the specification as required for the performance of a preferred embodiment is not necessarily essential for the performance of the invention itself. Their Honours said that s 40(3) did not require over meticulous verbal analysis or the isolation in a specification of essential features or essential integers of the claim in question. They approved what Gummow J had said in Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd (1988) 81 ALR 79 at 95, namely:

The circumstance that something is a requirement for the best method of performing an invention does not make it necessarily a requirement for all claims; likewise, the circumstance that material is part of the description of the invention does not mean that it must be included as an integer of each claim. Rather, the question is whether there is a real and reasonably clear disclosure in the body of the specification of what is then claimed, so that the alleged invention as claimed is broadly, that is to say in a general sense, described in the body of the specification. (emphasis added)

174    None of the challenged claims required the exclusion of particular excipients. The fact that some excipients might cause a composition not to meet standard stability tests did not necessarily entail, and there was no evidence to suggest that it did entail, that a composition of the three APIs that included any such excipient would not work at all. The achievement of particular stability over time in standard conditions is a desirable result for commercial drug manufacture. However, the mere failure of a product to achieve that level of stability because it includes a particular ingredient does not necessarily mean that a patent claim that can include the ingredient is not fairly based on a specification that discloses the problem of achieving the desired stability.

175    Such a situation does not establish that, despite the combination’s tenuous longevity, it does not work as claimed before it deteriorates. And a preferred embodiment that excludes the ingredient, and so achieves the requisite stability, can also be within the claim. The former, less stable, embodiment merely did not work as well, or for as long, as the preferred one. Actavis did not prove, and the specification did not teach, that the inclusion of MCC, surface-active substances or silica in the combination affected anything other than the resultant product’s longer term stability.

176    During their concurrent evidence, Profs Davies, Jenner and Stewart and Dr Morella accepted that before the testing of any new drug product on human volunteers, a researcher must obtain ethical approval and demonstrate that what is proposed for testing is sufficiently stable for those tests. Prof Davies said it would be unethical for one to undertake clinical studies of a product where it was known to degrade materially while used in or before the study. And he agreed with Dr Morella’s evidence that:

It’s very common, and I would say without exception, according to my experience, that you conduct stability on products prior to putting them into humans. The Helsinki Convention requires that you put products into humans that you can reasonably expect to derive valuable information, and the way that that manifests itself in the pharmaceutical industry is that you will have conducted initial stability tests to give yourself confidence that the products will be stable in a screening pharmacokinetic study. (emphasis added)

177    Dr Morella said that products for screening studies are normally prepared shortly before they are used in the studies, and only subsequently are long term storage studies done. Thus, ordinarily, only after a screening study, such as those reported in the specification, are long term stability tests undertaken on formulations that are sufficiently promising for further research. Thus, the stability studies revealed to the inventors issues with MCC, surface-active agents and silica that had the potential to affect the stability of a 3-in-one combination in the longer term. Of course, if no other formulation can be made, a manufacturer may seek to discover whether longer term or sufficient stability can be achieved by other means such as packaging or temperature controlled storage.

178    Importantly, the inclusion of any of those excipients did not, on the evidence, preclude a composition containing it and the three APIs from delivering an intended dosage of levodopa past the blood brain barrier, if it were administered before the time that the effect of the relevant excipient’s inclusion on the longer term stability of the product had caused it to deteriorate so that it would not deliver that intended dose.

179    In other words, Actavis’ argument that the possibility of inclusion of MCC, surface–active agents or silica in a product, process or method claimed meant that the challenged claims were not fairly based on matter disclosed in the specification wrongly sought to elevate the omission of those excipients into an essential integer. The existence of that possibility does not negate the existence of a sufficient relationship between what is claimed in the challenged claims and what is described in the body of the specification: Lockwood [No 1] 217 CLR at 309 [95]. The disclosure in the specification, that inclusion of some excipients could affect adversely the stability of a composition of the three APIs, did not create a limitation or narrow the invention as described (217 CLR at 309-310 [98]-[99]).

180    I also reject Actavis’ contention that claims 19 and 20 travelled beyond the disclosure in the specification. They did not. They mirrored the corresponding earlier consistory clauses in the specification (page 18) which satisfied s 40(3): Lockwood [No 1] 217 CLR at 310 [99].

181    Actavis’ argument that claim 21 is not fairly based because it is not limited to preparations made with the method described in formulations 3 and 4 is equally flawed. The therapeutic effect that claim 21 claimed was based on a composition consisting of a combination of the three APIs and a pharmaceutically acceptable excipient. The specification discussed the reason for allowing flexibility in dosages of the three APIs as being based on what would be appropriate to treat patients at various stages of the disease (page 12 par 3 – page 15). The specification put forward formulations 3 and 4 as examples of embodiments that achieved therapeutic effects comparable to the then existing commercial separate dosages of 200 mg of entacapone in one tablet and a combined dosage of various amounts of levodopa and carbidopa in another tablet. It continued (page 24 par 2 – page 25):

Those skilled in the art will recognize that while specific embodiments have been illustrated and described, various modifications and changes may be made without departing from the spirit and scope of the invention.

Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims. (emphasis added)

182    It is not possible to discern any limitation of the kind suggested by Actavis to render claim 21 invalid as not complying with s 40(3). The invention was not limited to, or by, formulations 3 and 4. Claim 21 was fairly based because it created a limitation of the monopoly by identifying a requirement of comparability of therapeutic effect for the new 3-in-one combination tablet with that achieved by the existing products.

5.    The utility issue – consideration

183    In Ranbaxy Australia Pty Ltd v Warner-Lambert Co LLC (2008) 77 IPR 449 at 479 [141] Emmett, Weinberg and Bennett JJ said:

Under ss 138 and 18(1)(c) of the 1990 Act, it is a ground of invalidity if the claimed invention is not useful “so far as claimed in any claim”. If the claimed invention does what it is intended by the patentee to do and the end obtained is itself useful, the invention is useful within the meaning of s 18(1)(c) (see Rehm Pty Ltd v Webster’s Security Systems (International) Pty Ltd (1981) 81 ALR 79 at 96 … Welcome Real-Time SA v Catuity Inc (2001) 113 FCR 110 at 144 and Fawcett v Homan (1896) 13 RPC 398 at 405). As to the first aspect, the invention as claimed must attain the result promised by the patentee (Advanced Building Systems Pty Ltd v Ramset Fasteners (Aust) Pty Ltd (1998) 194 CLR 171 at 187). (references corrected as per [2008] FCAFC 82)

184    A patent is not invalid merely because it is commercially impractical, but as Brennan CJ, Gaudron, McHugh and Gummow JJ said in Advanced Building Systems Pty Ltd v Ramset Fasteners (Aust) Pty Ltd (1998) 194 CLR 171 at 187 [24]:

… its utility depends upon whether, by following the teaching of the complete specification, the result claimed is produced (Lane Fox v Kensington & Knightsbridge Electric Lighting Co [1892] 3 Ch 424 at 430-431).

185    The monopoly asserted in each claim must be for an invention that, as s 18(1)(c) requires, “is useful” in the sense of producing the result claimed: Ramset 194 CLR at 187 [24]. The utility of a claim depends on whether, on its proper construction, it asserts a monopoly over only something that is useful, in which case it is good, or it also extends to something that is not useful, in which case it is bad. That is, the claim for the invention must catch only useful results if it is to comply with s 18(1)(c). This construction of s 18(1)(c) flows from the language of the chapeau in s 18(1) that “a patentable invention is an invention that, so far as claimed in any claim” is useful.

186    Bennett J discussed the authorities in Austal Ships Pty Ltd v Stena Rederi Aktiebolag (2005) 66 IPR 420 at 456-457 [235]-[240]. Her Honour held that the person propounding inutility had to do so positively on evidence (66 IPR at 459 [253]), although, depending on the circumstances, the specification itself may be sufficient evidence that a claim encompasses something that is not useful: Uniline Australia Ltd v SBriggs Pty Ltd (2009) 81 IPR 42 at 72-73 [123] per Greenwood J. However, it is not appropriate to test whether a claim has utility by considering characteristics that are totally impractical or contrived: Austal 66 IPR at 456 [236], applying what Stephen J had said in Washex Machinery Corporation v Roy Burton & Co Pty Ltd (1974) 49 ALJR 12 at 19B-C.

187    Claims 1 and 2: There is no evidence that, on the construction I have given to these claims, any formulation of a composition in which a substantial portion of carbidopa is separated from entacapone and levodopa would not be useful. Accordingly, Actavis has not established that these claims do not satisfy s 18(1)(c).

188    Claims 12, 13 and 14: I construed these claims to prescribe a method of preparation that requires that all the carbidopa be added separately to, and after, all the other ingredients. There is no evidence that employment of such a process of preparation can produce something that will not be useful. Accordingly, Actavis has not established that these claims do not satisfy s 18(1)(c).

189    Claims 17 and 18: I construed these claims to prescribe a method of preparation that has, as its first step, a), mixing amounts of entacapone and levodopa that are in themselves pharmacologically effective, together with at least one pharmaceutically acceptable excipient, then, as a second step, b), granulating that mixture to obtain a granule batch, and as a third step, c), adding a pharmacologically effective amount of carbidopa, which could be done together with other ingredients, including one or both of the other two APIs in quantities that respect the need for the overall product to be capable of being administered to patients. That is, the final dosages of each API in the finished product will be suitable for administration to patients, whether as a single oral solid composition or titrated with another dosage, as the treating doctor sees fit.

190    Once again, there is no evidence that employment of such a process can produce a result that is not useful. The highest that Actavis’ case went was to rely on the disclosure in the specification that, if all three APIs were wet granulated together, as in formulation 1, the patentee considered that the bioavailability of carbidopa was too low compared to the existing reference product (page 7 par 3, Example 1 pages 19-20).

191    The process or method of preparation that claims 17 and 18 prescribe does not replicate the method of preparation in formulation 1 in the patent. Indeed, claims 17 and 18 prescribe granulating pharmacologically effective amounts of entacapone and levodopa together first, before any carbidopa or other possible further amounts of the other two APIs with it are added.

192    Actavis has not proved that the method of preparation prescribed in either of claims 17 or 18 can produce a product that is not useful. First, there is no evidence as to what amount or proportion of either or both of entacapone or levodopa is necessary to be wet granulated with carbidopa so as to affect the bioavailability of carbidopa. Secondly, the mere fact that the patentee expressed the opinion that “the bioavailability of carbidopa from Formulation 1 (see Example 1, Table 1) wherein all the active agents are wet granulated together, is too low compared to the reference product, SINEMET® PLUS 100/25 mg tablet” (page 7 par 3), does not demonstrate that the product of formulation 1 was not useful. All that the patentee’s opinion, so expressed, establishes is that, while carbidopa was bioavailable in formulation 1, the level was not sufficiently high to meet the patentee’s unstated comparator standard. That bare expression of opinion did not establish that no useful result of any kind was obtained from formulation 1, or that that formulation could not be useful in treating Parkinson’s disease. All that the opinion revealed was the patentee’s judgment that the bioavailability of carbidopa was “too low” compared to the reference product, as opposed to being inutile.

193    I accept Prof Jenner’s evidence concerning formulation 1 and the graphical representations of its results in figures 1-3 in the patent when he said:

If you look at formulation 1, the authors describe the carbidopa levels as too low, but that doesn’t mean that the carbidopa levels aren’t effective, because you could still have perfectly adequate inhibition of decarboxylase activity in formulation 1, and that would give you something which was a viable product in that respect, and also I just go back to the point that whatever the entacapone and carbidopa are doing, its reflected in the levodopa plasma levels, because, as you pointed out, they’re the ones that protect the levodopa, and it’s what you achieve with the levodopa that’s going to give you the clinical response. (emphasis added)

194    The relevant invention the subject of claims 17 and 18, however, was a method for preparing an oral solid fixed dose composition comprising pharmacologically effective amounts of entacapone, levodopa and carbidopa together with at least one pharmaceutically acceptable excipient (see [112] above). If any amount of entacapone and or levodopa that was, or were, added at step c) with the carbidopa rendered the carbidopa pharmacologically ineffective, for example because its bioavailability was too low to be useful, then that would not be a process conformable with either the requirement of step c) in claim 17 or the teaching of the specification.

195    This is because the essential feature of step c) in claim 17 is that what is added to the granule batch of entacapone and levodopa is an amount of carbidopa that is pharmacologically effective and that amount, together with whatever else is in the newly produced mixture resulting from step c), will next be formulated into a plurality of dosage forms. That is, step c) does not allow the amount of carbidopa to be added to be other than pharmacologically effective. It must, therefore, be useful. And the specification teaches that wet granulation of the total dosages of all three APIs together may interfere with the pharmacological efficacy (i.e. bioavailability) of carbidopa. So, the addition of any amounts of entacapone and or levodopa at step c) that would render the amount of carbidopa then added other than pharmacologically effective, will not be a process within claim 17 or that follows the teaching of the patent.

196    A specification, including a claim, should not be construed in a way that to any sensible person would lead to unworkability when, by construction, it can be given a more limited meaning: Welch Perrin 106 CLR at 602 per Menzies J, whose decision on this point was not challenged on the appeal: applied in Washex 49 ALJR at 19B-C. As Prof Stewart said in evidence:

MR DIMITRIADIS: You’re not suggesting that you would, in practice, go about making a formulation that doesn’t aim to achieve good bioavailability or good stability, would you? That’s just not the way that you would approach your task as a formulator in practice as part of a development project.

PROF STEWART: No. You’re correct in that …

197    For all these reasons, I am not satisfied that Actavis has established that claims 17 and 18 lack utility.

198    Claims 19 and 20: I construed these claims to be for a tablet that is suitable for oral administration as a medicine in the treatment of Parkinson’s disease within the particular weight, volume and dimension ranges specified in the claims. There is no evidence that any formulation made in accordance with the integers of claims 19 and 20, as I have construed them, would not be useful or comply with s 18(1)(c).

199    Claim 21: Since I have construed claim 21 to have an integer that requires any composition made according to it to be objectively comparable in therapeutic effect to the then existing known formulations, any product made in accordance with the claim must be useful.

200    Accordingly, none of the challenged claims is invalid for failure to comply with s 18(1)(c).

7(a)    The novelty issue – What is the priority date for the patent? – Background

201    The issues concerning the priority date, novelty and inventive step are limited to whether each of claims 19, 20 and 21 is valid. Actavis argued that those claims should have the deferred priority date of 29 June 2000, when the complete specification was filed here. For the purposes of s 43(1), the priority document was filed in Finland on 30 June 1999.

202    Actavis contended that the deferred priority date applied to claims 19, 20 and 21 because they were not fairly based on any matter disclosed in the priority document. The critical issue is whether the priority document makes a real and reasonably clear disclosure of, or plainly foreshadows, the subject matter that is subsequently claimed in the complete specification.

203    The priority document need not disclose a claim that is later made in the complete specification for the latter to be fairly based on the former and so entitled to the priority date of the priority document: Société des Usines Chimiques Rhône-Poulenc v Commissioner of Patents (1958) 100 CLR 5 at 11 per Fullagar J; CCOM Pty Ltd v Jiejing Pty Ltd (1994) 51 FCR 260 at 281E-G per Spender, Gummow and Heerey JJ.

204    In CCOM 51 FCR at 281A-G, the Full Court adopted the approach of Buckley LJ in Re Stauffer Chemical Co’s Application [1977] RPC 33 at 42 that fair basing for the purpose of giving a claim in a complete specification a priority date earlier than its filing requires the Court to ascertain whether the earlier document affords a sufficient basis for a claim in the latter. Their Honours said that Buckley LJ’s approach eschewed an over-meticulous verbal analysis and approved what his Lordship said in the following passage ([1977] RPC at 54):

If a new feature were a development along the same line of thought which constitutes or underlies the invention described in the earlier document, it might be that that development could properly be regarded as fairly based on the matter disclosed in the earlier document, and that the new process described in the later document which incorporates that development could as a whole be regarded as fairly based upon the matter disclosed in the earlier document. If, on the other hand, the additional feature involves a new inventive step or brings something new into the combination which represents a departure from the idea of the invention described in the earlier document, it could not, I think, be properly described as fairly based upon the earlier document. (emphasis added)

205    This recognises that the later document can develop a matter disclosed in the earlier one into a new process, provided that this development is not the product of a new inventive step or an additional feature that departs from the original idea of the invention as previously described. Spender, Gummow and Heerey JJ also approved (51 FCR at 281D-E) of what Fox J had said in Coopers Animal Health Australia Ltd v Western Stock Distributors Pty Ltd (1987) 15 FCR 382 at 389, namely:

Where the holder of the provisional specification proceeds with a complete specification with a view to the grant of a patent, it is recognised that greater definition, as a result of further experimentation or otherwise, may be achieved before the later step is taken and the result expressed therein. Some generality of expression in the provisional specification is accepted.

206    Bennett J, with whom Yates J agreed, said in Sigma Pharmaceuticals (Australia) Pty Ltd v Wyeth (No 3) [2011] FCAFC 132 at [78] that:

the earlier document must in substance disclose the claimed invention. Even if that invention were further developed in the later document, it must be the same invention. Additionally, a disclaimer of the scope of the invention described in the earlier document cannot be disregarded in assessing the external fair basis of the subsequent claim on that earlier document.

Priority date for claims 19 and 20

207    Actavis argued that nothing in the priority document provided a fair basis for claims 19 and 20. It submitted that this was because there was no real and reasonably clear disclosure of tablet volume or size in the priority document or of any process or means to achieve such volumes or sizes. Actavis contended that the priority document stated a definition for “pharmaceutically acceptable excipient” in the section “Summary of the Invention” when it said (page 4 par 3):

The pharmaceutically acceptable excipient includes all pharmaceutically acceptable excipients that are compatible with entacapone, levodopa, and carbidopa, or their pharmaceutically acceptable salts or hydrates. (emphasis added)

208     Actavis observed that such a statement was not repeated in the complete specification and that the priority document had gone to some lengths to describe incompatible excipients in page 4 par 4 – page 5 par 2 and page 11 par 1 – page 12 par 3.

209    I reject that argument. The priority document stated (page 10 par 2 – page 11):

Entacapone alone is available as a tablet where the granulation method used is compaction granulation, i.e., COMTESS® and COMTAN®. When the compaction granulation is used, large amounts of excipients are needed to obtain compressible granules and tablets having the desired dissolution behaviour. The compactability of entacapone is sufficient to allow the preparation of a 200 mg tablet that is still relatively easy to swallow. However, the size of the fixed dose combination tablet comprising entacapone, levodopa, and carbidopa prepared by compaction granulation becomes too large especially for parkinsonism patients who have difficulties in swallowing. (emphasis added)

210    The priority document identified weight ranges of the dosages of each of the three APIs (page 13 par 1) and discussed means of formulating these into tablets as an oral solid composition with excipients. The priority document also described Examples 1 and 2 and set out tables 1 and 2 (pages 15-18) that were in very similar terms to those in the complete specification (pages 19-23). However, the note to table 2 in the complete specification was new and gave the tablet dimensions for formulations 3 and 4. Importantly, each of tables 1 and 2 in both documents gave the same weights of the ingredients and theoretical weights for the finished coated tablets in the four formulations.

211    As Dr Morella explained in evidence the complete specification did not suggest that the volunteers who took the tablets in formulations 1 and 2 had any difficulty swallowing them. Table 1 in both the priority document and the complete specification gave no information about the size of the tablets that were used in the trial. However, both documents dealt with all the tablets used in the trials as ones that were being tested as oral solid compositions. A person skilled in the art would understand that all the tablets used in the trials were of such sizes and volumes that they were capable of being swallowed by persons suffering from Parkinson’s disease.

212    The coated weights of the tablets disclosed in tables 1 and 2 were in the range 525 mg to 660 mg. Dr Morella said, and demonstrated in cross-examination, that he could calculate the volume of the tablets from the information in tables 1 and 2 once he knew or assumed the density, saying:

… what I what I read here is that the dimensions of formulation 2 well, one of the metrics provided are 660 milligrams, so it falls within the weight dimensions. I don’t know what the density of that tablet is, but I would expect that to be greater than 0.66, so it should have a volume dimension of less than 1 cc.

MR BURLEY: And, what, so you’re inferring a volume dimension? Are you inferring a size or a length? --- Well, from that volume dimension, one could then attempt to calculate what the size of an oval tablet would be.

I see. And could you explain what that calculation is? --- Well, if the density of the tablet is at least 0.66, then that tablet would occupy a volume of 1 cc. One could then, if one assumes that the tablet occupies 70 per cent of the volume of a rectangle, one could then take that 1 cc and see how large or small a rectangle one could produce, where you would have to divide 1 cc by 0.7, so it would be like 1.3 or 1.4 ccs for a rectangle, and look at the dimensions of that rectangle in terms of length.

And that’s a mathematical exercise that you would perform, is it? --- That’s a mathematical exercise that I would and have performed. (emphasis added)

213    I am of opinion that a person skilled in the art would understand that the priority document made a real and reasonably clear disclosure of the volume and size of tablets capable of being produced according to the invention of an oral pharmaceutical tablet comprising dosages of the three APIs with the ranges claimed in claims 19 and 20.

214    Claims 19 and 20 simply developed the matter disclosed in the priority document as to the sizes and volumes of an oral pharmaceutical tablet that could be swallowed by a person being treated for Parkinson’s disease.

215    The statement concerning what was a pharmaceutically acceptable excipient in the priority document (on page 4 par 2) did not provide any definition or information to teach a skilled addressee what was or was not compatible with each of the three APIs. Importantly, the statement did not limit the incompatible excipients to ones that were not conducive to long-term stability for compositions of the three APIs. A skilled addressee would read the priority document as a whole and would understand that each of formulations 1-6 had been assessed as suitable for use in screening trials with humans (see [192]-[196] above).

216    Thus, the level of disclosure in the priority document, dealing with pharmaceutically acceptable excipients, did not have the consequence that Actavis contended for, and so claims 19 and 20 were fairly based on the priority document.

217    Accordingly, claims 19 and 20 are entitled to the priority date of 30 June 1999.

Priority date for claim 21

218    Actavis argued that claim 21 was not limited by reference to any process by which the claimed composition was prepared. It contended that claim 21 thus travelled beyond any relevant disclosure in the priority document in the passage I have set out at [207]. This was, Actavis submitted, because it dealt (on page 10 par 2 – page 11) only with compositions made by granulating entacapone and levopoda together before adding carbidopa that had “absorptions” comparable to the commercial reference formulations. Actavis argued that the priority document said that the bioavailability of carbidopa from formulation 2 was “acceptable” but, it submitted, this was not the same as “comparable” (page 9 par 4 – page 10). It also contended that the inventors identified “severe stability problems” in formulation 2. And, Actavis submitted that, in the priority document, while claim 21 included at least one pharmaceutically acceptable excipient, it did not exclude incompatible excipients and so the claim travelled beyond, and was not fairly based on, the disclosure in the priority document.

219    I reject Actavis’ arguments that claim 21 was not fairly based on the priority document. First, claim 21 was limited by the result of a composition’s resultant pharmacokinetic properties’ comparability with the results obtained by the existing commercial reference products, as I explained in [133]-[135] above. The priority document discussed such comparability in the context of results achieved by the new 3-in-one composition in discussing the results of formulations 1-6 (at page 9 par 2 – page 10 par 1 and page 17 par 3) in very similar terms to those used in the complete specification in the patent in suit (page 7 par 3 – page 9, page 22 par 2).

220    Thus, the comparability of results achievable by the 3-in-one composition with those of the existing reference products was disclosed in substance in the priority document. When the priority document used the word “acceptable” to describe the results of the bioavailability of carbidopa from formulation 2 (page 10) it did so by referring to the results described as “too low” from formulation 1 as against those obtained from the reference product. This disclosed the concept of comparability sufficiently. But, as the inventors noted in both the priority document (page 10) and the complete specification (page 10 par 2) the use of polyethylene glycol as an excipient created “severe stability problems” (priority document p 10). Moreover, the priority document had explained earlier that one goal in designing an oral 3-in-one composition was “to achieve an absorption of the active agents from the gastrointestinal tract similar to the reference products” (page 3 par 2, emphasis added).

221    Secondly, Actavis’ argument presupposed that the invention described in the specification and claimed in the patent included each of the need for separation of carbidopa from entacapone and levodopa and the exclusion of particular excipients. I have rejected Actavis’ argument that each of those presuppositions was an essential feature of the invention, although each could be present in a preferred embodiment. Thus, I am not satisfied that claim 21 was not fairly based on the disclosure in the priority document.

222    Accordingly, claim 21 also has the priority date of 30 June 1999.

7(a)    The novelty issue – background

223    Actavis contended that only claims 19 and 20 lacked novelty. It based that contention on the publication of two papers that were delivered at the Orion Pharma symposium at the 32nd Scandinavian Congress of Neurology and 1st Congress of Neurological Nursing held on 12 June 1998 in Oulu, Finland. The papers were Need of new therapies in the treatment of Parkinson’s disease by CW Olanow (the Olanow paper) and The development of entacapone – from animal studies to clinical profile by A Gordin (the Gordin paper). They were printed in a single booklet, containing the program for the symposium and abstracts, entitled Entacapone Enhances Levodopa Therapy – The Way Forward. Against the headings for each paper in the booklet was a logo with the word “entacapone” below it. The two papers appeared sequentially in the booklet.

224    The following statements appeared in the Olanow paper:

•    “Another approach that has proven beneficial for patients with Parkinson’s disease is the use of COMT inhibitors with levodopa. Levodopa is primarily metabolized by dopa decarboxylase and COMT. COMT inhibitors block the metabolism of plasma levodopa in a manner similar to dopa decarboxylase inhibitors such as carbidopa ...” (p8).

•    “Clinically, this results in more predictable and consistent availability of levodopa to the brain.” (p9).

•    “Numerous clinical trials have now demonstrated that the addition of a COMT inhibitor to a levodopa-treated PD patients with motor fluctuations provides a significant reduction in OFF time and an increase in ON time.” (p9).

•    “This can translate into several hours of increased ON time for a patient per day and provide him/her with meaningful benefit.” (p9).

•    “Finally, there is interest in the idea of combining levodopa with a decarboxylase inhibitor and a COMT inhibitor in a single pill. This would provide levodopa in the most efficient manner for purposes of absorption and would simplify the administration of these medications for Parkinson's disease patients.” (p9)

225    Actavis contended that when the Olanow paper referred to COMT inhibitors, a skilled addressee would understand it to be referring to entacapone.

226    The following statements appeared in the Gordin paper:

•    “Entacapone was selected in the late 1980's as the lead molecule to be studied as an adjunct to levodopa in the treatment of PD” (p10).

•    In the phase II studies, levodopa/carbidopa 100/25 mg was administered in combination with 200 mg of entacapone (p12).

•    “Dose-finding studies showed that 200 mg was the most effective dose of entacapone to be combine with levodopa/DDC inhibitors” (p12).

•    “Effective COMT inhibitor” (p13).

•    “Entacapone has a quite similar profile pharmacokinetic properties as levodopa and carbidopa” (p13).

•    “Dosing with each daily levodopa dose” (p13).

•    “One strength (200 mg), no dose titration of entacapone needed” (p13).

•    “Effective from the very first dose” (p13).

•    “No clinically meaningful changes in laboratory safety parameters – no need to follow liver function” (p13).

•    “In conclusion, the new COMT inhibitor entacapone has been shown to cause a clinically relevant prolongation of the effect of levodopa in patients with PD suffering from wearing-off. It seems that the current double therapy (levodopa/DDC inhibitor) can in the future be replaced by triple therapy (levodopa/DDC inhibitor, entacapone)” (p13). (emphasis added)

227    Orion did not contend that a skilled addressee would have treated the papers as separate sources of information for the purposes of s 7(1)(b)(ii) of the Patents Act. Given that the two papers were delivered on the same day, to the same audience, about similar subject matter and were published in the same booklet one after the other, I am satisfied that a skilled addressee in the patent area (i.e. Australia) would have treated the two papers as a single source of information within the meaning of s 7(1)(b)(ii) and understood that they referred to entacapone.

7(a)    The novelty issue – Actavis’ submissions

228    Actavis argued that the Olanow and Gordin papers ought be taken together and approached having regard to the skilled addressee’s background knowledge. It contended that claims 19 and 20 involved, first, 3-in-one oral pharmaceutical tablets with dosage ranges that formed part of the skilled addressee’s background knowledge and, secondly, ranges for weights and volumes that did not form part of the invention, because the specification did not suggest that these factors were part of the invention. Actavis asserted that this was a case of “parameteritis”. It argued that, assessed against the skilled addressee’s background knowledge, the two papers taken together disclosed an oral pharmaceutical tablet comprising the three APIs. Actavis relied particularly on the fifth quotation above from the Olanow paper, that there was interest in combining the three APIs into a single pill and on the tenth quotation above from the Gordin paper, that the then current double therapy could be replaced by a triple therapy.

229    Actavis submitted that the skilled addressee would understand the two papers to disclose an oral pharmaceutical tablet comprising dosages of the three APIs that, as a matter of course, would fall within the ranges in claims 19 and 20. It argued that the two papers read together expressly referred to dosages of 200 mg of entacapone, 100 mg of levodopa and 25 mg of carbidopa that were within the ranges in claims 19 and 20 and that in any event, before June 1999 the background knowledge of movement disorder specialists and general neurologists, within the concept of a skilled addressee in Australia, included:

    the doses of SINEMET, being combinations of 100/25 mg, 100/10 mg and 250/25 mg of levodopa and carbidopa;

    the fixed dose of 200 mg of entacapone in COMTAN, that Orion had promoted since, at least 12 May 1999, when the TGA registered that drug.

230    Actavis also argued that the ranges for weights, volumes and dimensions in claims 19 and 20 were arbitrary, in the non-pejorative sense that they depended on the will or discretion of the patentee who had not explained why it had selected them. Actavis argued that the complete specification did not suggest that any of those ranges was a new discovery or scientific insight. Rather, it contended, the maximum size corresponded substantially to the dimensions of then existing dosage forms that could be swallowed by patients with Parkinson’s disease. Actavis relied on Prof Stewart’s evidence that a skilled addressee would understand, as a matter of course, that a tablet comprising of 200 mg of entacapone, 100 mg of levodopa and 25 mg of carbidopa, when formulated with excipients, would fall within the ranges of weight and volume in claims 19 and 20.

231    And, Actavis added, the background knowledge of a clinician withinin the concept of a skilled addressee included knowledge that the largest oral dosage forms routinely used in treating Parkinson’s disease before June 1999 was MADOPAR (18 mm) and, by at least June 2000, included COMTAN (17 mm). Actavis submitted that the skilled addressee would understand the two papers to be describing a tablet that could be swallowed by patients with Parkinson’s disease comfortably. It contended that Dr Morella had confirmed that a formulator could use routine methods of wet granulation (as in formulation 1 in the patent) and dry compaction (as in formulation 2) to mix the dosages referred to in the Gordin paper of 200 mg of entacapone, 100 mg of levodopa and 25 mg of carbidopa, together with excipients, to make a tablet within the weight and volume dimensions of claims 19 and 20.

232    Actavis submitted that, accordingly, claims 19 and 20 lacked novelty “over [the two papers] when assessed against the skilled addressee’s background knowledge”.

7(b)    The novelty issue – consideration

233    Contrary to Actavis’ argument, there is no distinction between the background state of knowledge that a skilled addressee would bring to bear in considering a piece of prior art and the common general knowledge. Actavis sought to support its use of what it termed “background knowledge” by referring to what Lee, Heerey and Lehane JJ had said in ICI Chemicals & Polymers Ltd v Lubrizol Corp Inc (2000) 106 FCR 214 at 228 [43]. But, their Honours’ remarks there did not support Actavis’ contention. In that case, the Full Court was considering whether a skilled addressee would read a piece of prior art published in 1957 in light of the common general knowledge at either the date of publication or the subsequent priority date in 1989 of the patent there in suit for the purpose of determining a lack of novelty of the latter. Their Honours held that they did not have to decide whether the prior art had to be read in light of the common general knowledge at the date of its publication and without regard to subsequent developments (see 106 FCR at 227-228 [40]-[41], 229 [45]-[46]). However, they said (106 FCR at 228 [43]):

There is, of course, ample authority (including Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253 at 292, 293; Nicaro [Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR 513] at 526, 532 et seq) for the proposition that it is not permissible, in considering novelty, to make a mosaic. Each prior publication must be looked at separately. Thus it is not permissible to supplement a prior publication by reference to some other disclosure, forming part of the common general knowledge, in order to assess whether the publication truly amounts to an anticipation. It is, on the other hand, equally clear that, though construction is a matter for the Court, a prior publication is to be assessed by reference to what it would disclose to the skilled addressee. (emphasis added)

234    Moreover, in AstraZeneca AB v Apotex Pty Ltd (2014) 226 FCR 324 at 401 [352], Besanko, Foster, Nicholas and Yates JJ, with whom Jessup J agreed on this issue (at 421 [447]), said:

Although the common general knowledge can be used in a limited way to construe a prior art document, s 7(1) does not permit the common general knowledge to be used as a resource that can be deployed complementarily to arrive at a disclosure which the document alone, properly construed, does not make. If it were otherwise, the separate requirement of an inventive step to support a patentable invention (see s 18(1)(b)(ii) of the Act) would be otiose. The test of novelty would encompass the test for inventive step, without the need to satisfy the threshold requirements of s 7(3) (as it then stood) that the information in the document be information that the person skilled in the art could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood and regarded as relevant to work in the relevant art in the patent area. All that would be required is that the information in the prior art document be publicly available. (emphasis added)

235    The Full Court then concluded that the piece of prior art in question had not itself disclosed what was part of the common general knowledge and so did not anticipate the claim for a new drug, including its dosage range (see 226 FCR at 402 [354]). In Minnesota Mining 144 CLR at 292-293, Aickin J explained that the notion of common general knowledge involves the use of that which is known or used by those in the relevant trade. He said:

It forms the background knowledge and experience which is available to all in the trade in considering the making of new products, or the making of improvements in old, and it must be treated as being used by an individual as a general body of knowledge. I do not with respect think that it is correct to describe that process as the making of a mosaic although it has often been so described, a usage which however may be misleading. The process of applying such common general knowledge to the solution of a problem is not a process of picking out individual pieces of information and combining them, including inferences from known facts and known principles, as well as the application of such principles. The making of a mosaic prohibited in the case of an allegation of want of novelty is the picking out of individual items of information from prior publications or prior objects and assembling them together so as to give them an appearance of unity and then alleging that such mosaic reveals the very thing claimed. That is an understandable, though not a permissible, process. (emphasis added)

236    Importantly, s 7 of the Act established distinct criteria for ascertaining whether an invention was novel, within the meaning of s 7(1), and whether the invention involved an inventive step within the meaning of s 7(2). Each set of criteria required the Court to place itself in the position of a skilled addressee when considering both the challenged patent and the prior art information (in s 7(1)) or the prior art base, including prior art information considered in light of the relevant common general knowledge (in s 7(2)).

237    The distinction between the criteria in s 7 was reinforced by the express provision in s 7(2) that the common general knowledge of a skilled addressee could inform the determination of the issue of obviousness. Section 7 necessarily required the Court to evaluate any disputed question from the perspective, and informed by the relevant knowledge, of a skilled addressee. But, the relevant knowledge of the skilled addressee for the purposes of s 7(1) was not, or was not used in the same way as, the common general knowledge referred to in s 7(2).

238    In essence, the role of a skilled addressee in considering the issues in s 7(1) is analogous to that of an interpreter of technical terms or concepts, in prior art information and the challenged patent, so that the Court can determine whether, as interpreted, the prior art information made the claimed invention publicly available before its priority date. The role of the skilled addressee in s 7(1) is, in effect, to translate into natural and ordinary English what the technical information conveys, regardless of other knowledge that the skilled addressee could bring to bear that might expand such an understanding. For example, if a document stated that carbidopa is a DDC inhibitor, a skilled addressee could translate the scientific term as a substance that inhibits the activity of the enzyme dopa decarboxylate in breaking down levodopa before it passes the blood brain barrier. But, for the purposes of s 7(1), that is as far as the evidence or understanding of a skilled addressee would be relevant, if nothing else in either the prior art information or the challenged patent explained what properties the substance had or what consequences flowed from its release into the bloodstream.

239    This is because s 7(1) was concerned with whether a prior publication itself had disclosed each of the essential integers of the relevant claim that the later patent claimed as an invention: i.e. s 7(1) was focused on a comparison of what was, or was not, conveyed by the two publications read in their own terms, as they would be understood by a skilled addressee. In other words, the question under s 7(1) was whether the exact integers of the claim that the patentee claimed as the invention had been expressed publicly before the relevant priority date for the claim in the patent in one (or a cognate) publication. But, s 7(1) was not concerned about whether the prior publication would have conveyed more than its own wording, if the skilled addressee also took into account other facts.

240    In the “carbidopa is a DDC inhibitor” example, the skilled addressee could not add an integer to the disclosure, such as the COMT inhibitor should not produce liver toxicity. That is because, if he or she did so, the addressee would use information that was not based on anything in the document, namely that tolcapone is another class of inhibitor of enzyme activity that operates on a different enzyme and had produced some toxic results. Such information would not be part of what the relevant document itself disclosed and could only derive from the skilled addressee’s, or reader’s, specialised or common general knowledge. The position is analogous to that in defamation, articulated in a well-known example given by Lord Devlin in Lewis v Daily Telegraph Ltd [1964] AC 234 at 278:

… a derogatory implication might be easy or difficult to detect; and, of course, it might not be detected at all, except by a person who was already in possession of some specific information. Thus, to say of a man that he was seen to enter a named house would contain a derogatory implication for anyone who knew that that house was a brothel but not for anyone who did not. (emphasis added)

241    The specific information as to the nature of the premises is like an additional integer that may have been derived from the specialised or common general knowledge – it is an additional fact that is not conveyed expressly or by implication in the words of the publication in their natural and ordinary meaning. The specific information can change the meaning of the words because the reader is given a fact, extrinsic to what the words themselves disclose, that adds new information not conveyed or disclosed in the publication and so changes the natural and ordinary meaning of the words used.

242    Given that further information, the reader can then construct a mosaic to infer a reason why the man went to the brothel. Of course, the reason might be different if the reader was told he was an electrician who was responding to a telephone request for him to fix a broken light fitting. At the end of the day, a skilled addressee or expert, or indeed, a judge or jury, could draw on his or her or their knowledge of what a house was to understand what the publication was conveying about houses in general in its natural and ordinary meaning, but he or she or they would need an extra fact, not conveyed in the publication, to arrive at some other meaning about the particular nature of the house and the purpose of the visit.

243    In my opinion, Actavis sought to build its case for lack of novelty into a mosaic out of what it characterised as “background knowledge” or information and assembled that material together with what was contained in the Olanow and Gordin papers. Thus, Actavis’ argument that a skilled addressee’s “background knowledge” of dosage ranges, the ranges of or specific weights or dimensions of other oral tablets used to treat Parkinson’s disease and how a formulator could go about preparing a tablet within those parameters relied on extrinsic facts, or what may well have been aspects of the common general knowledge. Those extrinsic facts, being the background knowledge on which Actavis relied, were not conveyed by the Olanow and Gordin papers to the skilled addressee. The extrinsic facts were akin to knowledge that the house was a brothel in Lord Devlin’s example, or to pieces being added to a mosaic around the prior art information.

244    Accordingly, the background knowledge on which Actavis relied on the novelty issue was not relevant to that issue. The relevant question is whether the Olanow and Gordin papers conveyed, and so made publicly available to a skilled addressee, the precise information claimed in either of claims 19 and 20.

245    Read together, the two papers revealed that an untitrated dose of 200 mg of entacapone that was administered simultaneously with a standard levodopa and carbidopa dose (disclosed as 100/25 mg in the Gordin paper) prolonged the beneficial effect of levodopa in patients suffering from Parkinson’s disease. This suggested a new form of “triple therapy”, involving the concurrent administration of entacapone with the existing use of levodopa and DDC inhibitors, including carbidopa, as the Gordin paper concluded. And, as the Olanow paper mused, “there is interest in the idea of combining levopoda with a decarboxylase inhibitor and a COMT inhibitor in a single pill”.

246    However, nothing in either paper revealed anything beyond that “interest in the idea” of a 3-in-one pill that could include 200 mg of entacapone, 100 mg of levodopa and 25 mg of carbidopa. Thus, even though the Gordin paper disclosed those specific dosages, neither paper discussed other dosages, or ranges of dosages of levodopa or carbidopa, or, in particular, the weight, volume or dimensions of any single pill.

247    The subject matters of claims 19 and 20 included not just an oral pharmaceutical tablet comprising a combination of the three APIs, including 200 mg of entacapone and amounts of levodopa and carbidopa within specific dosage ranges, but also specific integers comprising particular ranges of volume, weight and dimensions for the tablets. There was nothing in the two papers to anticipate, let alone identify, any of the latter integers. The two papers did not give any directions as to the various ranges in each of claims 19 and 20, or how to make such tablets within those ranges.

248    The specification had explained that the composition should be easy to swallow (page 3 par 4) and that there were larger ranges of each of the three APIs that could be included in an oral solid composition (page 12 par 3 – page 13). However, the patentee identified, as a preferred embodiment of those ranges for the APIs, what it claimed as integers for the three APIs in claims 19 and 20 (page 13 par 1). The patentee explained that it had found that preferred embodiments of a 3-in-one composition at the boundaries of each given range for combinations of levodopa and carbidopa, as well as combinations within those boundaries together with the standard dosage of 200 mg of entacapone, produced substantially bioequivalent results as those achieved by the existing known separately administered dosages of entacapone and combinations of levodopa/carbidopa tablets (page 13 par 3 – page 15).

249    The specification explained that entacapone was sufficiently compactable that a dosage of 200 mg could be prepared by compaction granulation into a tablet that was relatively easy to swallow (page 15 par 1 – page 16). However, the specification then disclosed that the compactability of fixed dose combination tablets was surprisingly worse than that of entacapone alone, and that a combination tablet prepared by compaction granulation “can become too large especially for parkinsonism patients who have difficulties in swallowing” (page 16).

250    The specification next provided consistory clauses for claims 16 and 17 and described the processes that these involved in seeking to produce composition tablets. It then stated that by using the process of the invention, composition tablets might be made particularly small for the dosages they contained and would be convenient to administer (page 16 par 1 – page 17 par 3). The specification stated immediately before the consistory clauses for claims 19 and 20 (page 17 par 3 – 18):

These may be any of a wide variety of shapes, although an oval form is preferred. The small size is particularly surprising in view of the size of the presently commercialized COMTAN®/COMTESS® entacapone tablet and in view of the fact that entacapone is difficult to compress and still give an acceptable release especially in the presence of levodopa and carbidopa. Furthermore, we have found that the composition of the invention surprisingly have especially good flowability properties. (emphasis added)

251    Accordingly, I do not accept Actavis’ argument that the specification provided no explanation for the sizes specified in claims 19 and 20, or that they were “parameteritis”. The specification identified the processes that the patentee had discovered that were capable of producing oral pharmaceutical tablets that were also easy to swallow and achieved comparable bioequivalent effects as the existing reference products, despite difficulties encountered in compacting entacapone with levodopa and carbidopa. However, claims 19 and 20 did not include any integers relating to a process by which tablets within the ranges it prescribed could be produced.

252    Moreover, there was no evidence that the ranges of dosage for any of the three APIs in claims 19 and 20 were in any sense arbitrary. Those ranges conformed with, first, what the specification stated were known dosage ranges for the APIs within which treating doctors could make therapeutic titration adjustments appropriate for the condition of each patient. Secondly, the evidence also showed that the ranges for volume, weight and dimensions in claims 19 and 20 specified a tablet size that was easy to swallow.

253    Nothing in either of the Olanow or Gordin papers anticipated either of claims 19 or 20 within the tests in the authorities: cf General Tire [1972] RPC at 485-486 where Sachs LJ stated that the prior publication had to:

contain clear and unmistakable directions to do what the patentee claims to have invented … A signpost, however clear, upon the road to the patentee’s invention will not suffice. The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentees. (emphasis added)

254    Neither paper individually, or read together, planted such a flag. They contained no directions as to how to produce tablets of any particular dimensions that would be oral solid compositions of the three APIs. In particular, they did not contain or disclose any integers of either of claims 19 and 20 as to the ranges of dosage (other than one), weight, volume or dimensions. For these reasons, I am not satisfied that either of claims 19 and 20 is not novel with the meaning of s 7(1)(b) of the Act.

7(b)    The inventive step issue – background

255    Actavis contended that each of claims 19, 20 and 21 lacked an inventive step at each of the priority dates of 30 June 1999 (which I have found is the actual priority date: see [196]-[201]) or 29 June 2000, when the complete specification was filed. It argued that this was because, as at 30 June 1999, the common general knowledge and the prior art base included the Nomecomt report (see [126] above).

256    Actavis’ subsidiary argument was that, as at 29 June 2000, both the common general knowledge and the prior art had expanded, the latter by a further article entitled “COMT Inhibition with Entacapone in the Treatment of Parkinson’s Disease” by UK Rinne, A Gordin and HT Teräväinen: Advances in Neurology Vol 80 at 491-494 (the Rinne article). I will deal briefly with the subsidiary argument after considering the inventive step issue as at the priority date to which I have found the patent is entitled.

257    In essence, Actavis’ case on the inventive step issue was that, as it put in its closing written submissions, “the aim of obtaining a tablet combining levodopa, carbidopa and entacapone was an ‘obvious goal’ to the skilled team, and that aim would have been adopted as a matter of routine”. It submitted that, for the purposes of claims 19 and 20, the goal was merely to create a tablet within the parameters of each claim, and the skilled team would have pursued this goal with high expectations of success. And, Actavis argued, if claim 21 required a composite tablet with bioequivalence to the known formulations, it was obvious to want the 3-in-one combination of APIs to be bioequivalent to the existing formulations.

7(b)    The inventive step issue – the position as at 30 June 1999

258    The following matters were common ground as being within the common general knowledge of the skilled addressee (being a hypothetical composite of a team of pharmacologists, pharmacists, clinicians and formulators) as at 30 June 1999:

    there was a class of compounds known as COMT inhibitors, that included entacapone and tolcapone;

    COMT inhibitors were one novel area of interest as a means of treating Parkinson’s disease that were being evaluated and developed, for example, as noted in a well-known text used in Australia: Harrison’s Principles of Internal Medicine (14th ed), McGraw Hill 1998 Vol 2 p 235. And, as Prof Jenner and Dr Peppard said, other novel areas of interest at this time were the use of dopamine agonists, and another class of agents called monoamine oxidase type B inhibitors, such as selegiline, that modify brain chemistry to prolong the action of dopamine delivered by levodopa. Selegiline was a treatment that was in use in June 1999;

    in June 1998, tolcapone became available in Australia and began to be prescribed as a COMT inhibitor in combination with levodopa and DDC inhibitors, such as carbidopa;

    no observations of liver toxicity occurred during clinical trials for both tolcapone and entacapone, that had taken place before the two medications entered into clinical use;

    by 1 February 1999, tolcapone had been withdrawn from the Australian market due to rare, but severe, liver toxicity issues that only became apparent after it had entered into clinical use here and in other countries;

    on 12 May 1999 the TGA registered COMTAN, that contained entacapone, thus enabling it to be prescribed by doctors, but its cost to patients was not subsidised because it had not been listed in the Pharmaceutical Benefits Scheme (PBS) before 30 June 1999. (Indeed, COMTAN was included in the PBS only on 1 February 2000.);

    clinicians in Australia were concerned that entacapone may be associated with the same toxicity issues as had occurred with tolcapone, because they were drugs of the same class;

    patients with advanced Parkinson’s disease can have difficulty in swallowing tablets or capsules;

    levopoda had been the main form of drug therapy used for Parkinson’s disease since the 1960s. From no later than the 1980s, it was accepted practice for doctors to prescribe levodopa in combination with a DDC inhibitor for treating the disease. In Australia, SINEMET was one standard brand name combination tablet that doctors prescribed. It comprised levodopa and carbidopa and was sold in three standard dosages, of 100/25 mg, 100/10 mg and 250/25 mg. In practice, doctors prescribed several doses per day;

    another such commonly prescribed fixed dose product that was available as capsules and tablets was MADOPAR. It comprised levodopa and benserazide. MADOPAR was sold in three standard dosages, in capsules and tablets, of 50/12.5 mg, 100/25 mg and 200/50 mg;

    treating doctors individually titrated the dosages of the combined levodopa/DDC combination tablets. The SINEMET tablets were scored once and some of the MADOPAR tablets were double scored so that they could be broken into half or, in the latter case, quarters as part of the titration. These features of the two brands were recorded in the 23rd edition of MIMS Annual published in June 1999, a standard medical reference work used by medical practitioners, pharmacologists and formulators;

    as Prof Stewart said, so that tablets could be comfortably swallowed, generally their maximum diameter when they had a round shape was about 12 mm and those could weigh up to 700 mg, depending on their ingredients. Larger tablets, generally, were made in an oval shape, because that shape facilitates swallowing. The maximum diameter for oval tablets that could be swallowed comfortably by most patients was about 18-19 mm and these could weigh between 500-1200 mg, depending on their ingredients;

    commonly used manufacturing methods for solid oral dosage forms included wet granulation, compaction granulation and direct compression;

    there were many well-known pharmaceutical excipients used for inclusion in manufacturing pharmaceutical tablets;

    the development of a formulation for a pharmaceutical tablet is an iterative process that involves problem solving and testing. There is no certainty that any particular recipe will inevitably result in a suitable formulation ;

    regulators, such as the TGA, required generic products to demonstrate bioequivalence of results with those of known, approved drugs and medications and if this could be done there was no need for the generic product to undergo full clinical trials.

The Nomecomt report

259    As I have noted above, the Nomecomt report was published in Neurology in November 1998. Neurology was, as Dr Peppard explained, a pre-eminent international general journal for neurology. It was common ground that, before 30 June 1999, a skilled addressee conducting research into new treatments for Parkinson’s disease, including ones using entacapone, could reasonably be expected to have ascertained, understood and regarded the Nomecomt report as relevant, for the purposes of s 7(3) of the Act.

260    The Nomecomt report described a six month randomised, double blind study that evaluated the efficiency of treatment for Parkinson’s disease combining the use of entacapone with the then standard daily 4 to 10 doses of levodopa and a DDC inhibitor on 171 patients, about half of whom were in a control group that received a placebo. Patients took either a tablet with 200 mg of entacapone or an identical placebo with each of their levodopa/DDC medications and diarised resulting “on” and “off” times as well as other effects and side-effects of the treatment. The Nomecomt report stated that the study found that:

    the current use of levodopa/DDC treatment was not considered to be pharmacokinetically or pharmacodynamically ideal. Because entacapone and levodopa have similar pharmacokinetic profiles, doses of each are administered at the same time;

•    [w]hen used concomitantly with levodopa/DDC inhibitor treatment regimes, entacapone increases the area under the concentration-time curve of levodopa, prolongs its half-life of elimination, and delays the fall in plasma levodopa without influencing the peak plasma levodopa concentration (C max) or the time when the maximum concentration is reached (t max). (emphasis added; references omitted)

    entacapone treatment did not notably affect any laboratory safety parameters used in the study;

•    the results of this study demonstrated that long-term treatment with entacapone as an adjuvant to levodopa therapy resulted in a clinically significant increase in “on” time, and a corresponding reduction in “off” time, whereas no change was evident in patients taking placebo. The well-being of the patients also improved, as shown by a statistically significant improvement in activities of daily living score (UPDRS, part II) in the entacapone group. This beneficial effect of entacapone was almost completely lost during the withdrawal period, thus emphasizing the relevance of the therapeutic value of entacapone. Almost identical results were obtained in an independently conducted 6-month study of similar design. … Similar results have been obtained with tolcapone, another COMT inhibitor, in two 6-week … and in one 3-month study …. (emphasis added; references omitted)

7(b)    Actavis’ submissions – The inventive step issue at 30 June 1999

261    Actavis argued that, prior to 30 June 1999, it would have been obvious to the skilled addressee, in light of the common general knowledge together with the Nomecomt report, to combine levodopa, carbidopa and entacapone into a single tablet. That was because, so Actavis contended, the skilled addressee would recognise, first, the therapeutic benefits to patients in administering entacapone at the same time as levodopa and carbidopa (i.e. greater “on” time), secondly, the reduction of the burden in taking two pills between 4 and 10 times daily, and, thirdly, following the withdrawal of tolcapone from the market, clinicians would be concerned to close the gap in their treatment regimes by including entacapone as a replacement.

262    Actavis submitted that the use of entacapone as such a treatment was part of the common general knowledge in Australia by 30 June 1999, it having been registered as COMTAN®, and launched into the United Kingdom market in November 1998, and registered here by the TGA on 12 May 1999. It contended that Orion was promoting the use of COMTAN to Australian doctors from the time of its TGA registration, and entacapone was included in the publication Martindale: The Complete Drug Reference (32rd ed), another standard pharmaceutical reference work used by clinicians, pharmacologists and formulators which was available in Australia by, at latest, 4 June 1999.

263    Actavis also relied on evidence of experts whom it called. Dr Peppard said in his first affidavit that by 29 June 2000, based on his knowledge, which included more than the common general knowledge and also the Nomecomt report which he had read at about the time of its publication, he expected that entacapone would be made available in a single tablet with levodopa and a DCC inhibitor, just as combinations of levodopa and DDC inhibitors had been manufactured years before. He was mindful of the significant extra burden on patients having to take another tablet with each dose of levopoda/DDC medication between, 4 and 10 times daily.

264    Actavis also relied on the opinion of each of Prof Stewart and Dr Reece, that the Nomecomt report would have suggested to him that a 3-in-one combination using entacapone was obvious. Prof Stewart said in his affidavit that, having read the Nomecomt report, he believed that it would have indicated to him in 1999, as a formulator, that entacapone was “a natural candidate” for incorporation into a fixed dose combination form with levodopa and carbidopa. During his concurrent evidence he explained that, based on his training, this was logical because the pharmacokinetics of the three APIs were very similar and it was “very obvious”. But he also said that in formulating such a combination:

There would still need to be some experimentation. That wouldn’t be just a matter of routinely fitting things in to a specific system and getting the answer out the end. There would still need to be some experimentation. And there may need to be some inventiveness there, but the task is much easier than having to develop a new drug. (emphasis added)

265    Last, Actavis relied on Dr Reece’s evidence that the Nomecomt report indicated to him a “clear precedent in the sense of the use of a combination product which is a DDC inhibitor and levodopa for the idea of adding yet another inhibitor” and that there was not “a huge increment” in having two inhibitors rather than one. He said that the report taught him that the use of entacapone “certainly worked”.

7(b)     The inventive step issue – consideration

266    In concurrent evidence, Dr Peppard observed that, unlike tolcapone which was administered in a flat dose three times daily, entacapone had to be taken each time with the levodopa/DDC medication and that a combination tablet “seemed just a small extra step to me”. However Dr Peppard candidly, as he gave all of his evidence, acknowledged that he could not put a precise date on this thought. As he also acknowledged, he did not have any record made before 29 June 2000 that he had envisaged such a 3-in-one combination. And, despite his practice when attending international conferences, as he regularly did, of discussing important topics with a core group of 20 to 30 Australian colleagues, he did not discuss this subject with them before 29 June 2000.

267    While I have no doubt that Dr Peppard was giving his honest recollection, I do not consider that it is likely that he thought of a 3-in-one combination before 30 June 1999. First, he never expressed this idea to any of his colleagues, or anyone else, or recorded it, before 29 June 2000. Given that, as he said, it would relieve patients of a potentially significant extra burden of taking an additional tablet up to 10 times daily, I think that, had the idea of a combination occurred to him, he at least would have talked with colleagues about it at the time. Secondly, Dr Peppard, like all of the other experts, was dealing with long past events. He was seeking to recall his thought processes over 15 years earlier, where he had no contemporaneous record of his own to draw on and where the very idea (of a 3-in-one tablet) had been a reality in his daily practice for over a decade. The precision and dating of any recollection in those circumstances is highly likely to be a reconstruction that is inevitably affected by hindsight and experience. Indeed, as Dr Peppard said, “it’s something I didn’t give any great deal of thought to”.

268    Thirdly, entacapone was a new medicine that had been in commercial use in England for eight months and only registered in Australia for about seven weeks by 30 June 1999. There had been a very recent significant setback in confidence in the use of COMT inhibitors because of the withdrawal of tolcapone from the market. There had been no foreshadowing of the potential of the fatal liver toxicity that three patients had suffered in 1998, after tolcapone had gone to market. Prof Jenner, Drs O’Neill and Peppard agreed in their joint report that, as at both June 1999 and June 2000, experience in Australia with tolcapone had raised concerns over the toxicity of COMT inhibitors and these concerns included entacapone. As Dr Peppard commented in the joint report, during this period neurologists were concerned that there “could be group toxicity between tolcapone and entacapone” and that they were looking “keenly at the characteristics and safety of entacapone, which was the only replacement COMT inhibitor on the horizon”.

269    Having regard to all those factors, I am not satisfied that Dr Peppard’s evidence as to his having had an idea about a 3-in-one combination using entacapone before 30 June 1999 is reliable. I think that he was honestly mistaken and thought of this idea much later, and only after entacapone had been in widespread, safe use for some time. As he said, first, he had not prescribed entacapone as at June 1999 and its approval by the TGA “wasn’t enough for me” and, secondly, even on 1 February 2000, when entacapone received its PBS listing, he said “I would have been hesitant” about prescribing entacapone then. Given that this was his contemporaneous response in dealing with patients, I am not persuaded that he gave consideration before this time to a combination tablet of entacapone, levodopa and carbidopa.

270    Dr Peppard also said that his concern had been alleviated by June 2000. Even so, I am not satisfied that Dr Peppard’s recollection of when he thought of the idea of a combination is sufficiently reliable to find that this occurred at any time before 29 June 2000.

271    Prof Stewart and Dr Morella agreed in the joint report that fixed dose combination prescription products were uncommon and that development of a formulation is an interactive process involving problem solving. They also agreed that the process was not a recipe that, if followed, inevitably would result in a suitable formulation.

272    Unlike Prof Stewart, Dr Morella considered that the development process to formulate a combination tablet comprised of the three APIs (entacapone, levodopa and carbidopa), even though much was known about their properties, was complex. He explained why he considered this development process not to be straightforward even with components with known properties saying, persuasively to my mind:

You just don’t get answer A, B and C, plonk that into a development program and have it pop out the end. There are real issues that you encounter, unexpected issues that you encounter, during the development and you start to make compromises and choices. In the end, if the process was routine and simple and predictable, you should be able to come up with a formulation, very few experiments to satisfy the needs of the regulatory authorities. In my experience, unless you’re producing a product that’s … the same as what’s on the market, that’s unlikely to be the case. (emphasis added)

273    Prof Davies did not give evidence-in-chief on the obviousness of the invention. However, he had considerable experience in working with pharmaceutical companies on detailed analyses of various combination products that had included determining the structure, compatibility of each of APIs both with one another and with excipients used in a formulation, as well as the homogeneity of a drug product. I accept his evidence that, when placing one drug into a formulation with another, “you cannot predict what the release profile would be” and that:

it’s rare that you have three drugs in a single product which is a prescription medicine, like this, and it would be extremely challenging to be able to reproduce and mimic the release profiles of those individual drugs. (emphasis added)

274    Professor Davies was also asked in cross-examination about formulating a combination tablet of the three APIs within a particular size range, in the following exchange:

And those challenges are ones that would involve you using the skills that you’ve developed as a formulator, to make selections of excipients that are compatible and appropriately sized to achieve a successful formulation? --- It’s possible. It’s a challenge, though, particularly in this context, where you have three drugs and you’re trying to prepare formulations which are of a particular size for that target patient population. It can be extremely challenging. (emphasis added)

275    These difficulties in the formulation task are relevant to an overall assessment of whether a skilled addressee would have regarded the invention in each of claims 19, 20 and 21, as I have construed them, as obvious at either of the priority dates in issue.

276    Dr Reece gave evidence that:

So in terms of the logic of a triple dose regimen … if that concept is simply adding one pill to another is working, then one could think, well, [the] experiment pharmacokinetically has been done. Now, what I mean by that, pharmacokinetics is a study of the drug absorption, distribution, elimination, but … the simple experiment of putting those two pills together has been done pharmacokinetically, and so any discussion we’ve had about drugs in solution means that, putting formulation matters aside, and I don’t portray myself as a formulator, but from a pharmacologist’s perspective, we’ve learned a lot from this study about the pharmacokinetics of these two drugs and the context of the clinical effect. They’re going in a solution and they’re working. Whatever the obstacles, the outcome is there. We have a clinical effect. (emphasis added)

277    Dr Reece later asserted his perception that DDC and COMT inhibitors affected two separate enzymes and that it was “simple” science, from a pharmacological point of view, to develop a fixed dose 3-in-one combination. He again acknowledged his lack of formulation expertise. In the joint expert report he said that, as of June 1999, based on the Nomecomt report, he would reasonably expect that “without regard to stability or tablet size” the three APIs could be combined into a single composition that would provide a therapeutic effect comparable to the known separate formulations.

278    As Dr Reece acknowledged in oral evidence, his expectation was based on the unstated assumption that each of the three APIs had been released already into the gastrointestinal tract and were in solution:

I’m only considering the pharmacology component of it, and so that I’m interested in everything after the dissolution.

MR DIMITRIADIS: Yes.

DR REECE: So we’re talking just about the, you know, potential effects of the biology on the system thereafter.

MR DIMITRIADIS: And so, the assumption does apply here as well; that’s right, isn’t it?

DR REECE: Yes. I’m just making the connection that this is a yes, that’s a logical progression, so yes. (emphasis added)

279    Prof Jenner explained that while DDC inhibitors substantially blocked the enzyme activity to which they were directed, COMT inhibitors only inhibited about half of the enzyme activity for which they were introduced. As he and Dr Morella made clear, the formulation task required that any 3-in-one combination work inside the body in the way entacapone had done when administered separately (as COMTAN) with the levodopa/carbidopa dose administered (as SINEMET). Prof Jenner said that this required a triple combination to be “time locked” to achieve, as far as possible, the release into the gut of each of the three APIs in a way that enabled them to be absorbed into the bloodstream so as to act in a substantially similar way as the administration of two separate tablets had achieved.

280    Prof Jenner explained in his affidavit that carbidopa was absorbed into the blood (technically, systemic circulation) from a significant portion of the small intestine. However, because both levodopa and entacapone were only absorbed from the upper small intestine, those two APIs had a smaller window of opportunity to be absorbed into the blood. And each API used a different bodily transport mechanism to convey the API towards the blood brain barrier. Carbidopa is probably absorbed by simple passive diffusion. Levopoda is a naturally occurring amino acid and utilises what Prof Jenner described as “a capacity limited active transport mechanism that exists to take large neutral amino acids from ingested food in to the body”. Entacapone uses another active transport process the nature of which, Prof Jenner said, is not fully understood. He said that he knew, before June 1999, both levodopa and entacapone were only partially absorbed in a way that was erratic, with large inter-subject and intra-subject variations. Prof Jenner continued:

This is an important issue as small differences in the amounts of the two drugs entering the systemic circulation can have a major effect on the clinical response achieved.

Levodopa and entacapone have short half-lives in plasma, while the half-life of carbidopa is longer and the duration of inhibition of DDC is maintained. By half-life, I refer to the time over which a 50% fall in plasma concentrations of the drug will occur following the absorption phase and after peak concentrations have been achieved. The inhibition of COMT produced by entacapone is transient, reflecting its short half-life. As a result, it is essential that the plasma exposure to levodopa and entacapone is “time locked” as differences in peaks and troughs of plasma concentrations of the drugs will negate the enhanced clinical effect that is sought. By “time locked”, I refer to the need to ensure that both DDC and COMT are adequately inhibited peripherally to prevent levodopa metabolism by ensuring that both carbidopa and entacapone are absorbed and reach effective concentrations in plasma simultaneously.

I would not have expected that this could have been achieved in a combined formulation. Instead I would have expected that:

(a)    the release of drug from the combined preparation would be different from that of individual immediate release formulations; and

(b)    the subsequent absorption of one or the other of these drugs would have been altered such that the concentrations in plasma required to inhibit enzyme activity would not be achieved at the same time. (emphasis added)

281    I accept Prof Jenner’s pharmacological explanation. It is cogently reasoned. That explanation was supported by Dr Morella whose expertise included both pharmacology and formulation.

282    As both Drs O’Neill and Peppard said, few Australian doctors would have prescribed COMTAN until its PBS listing on 1 February 2000, and neither clinician thought he had done so. And, the PBS records show that only 31 prescriptions for COMTAN were filled in February 2000. I accept Dr Peppard’s evidence as reflective of the general attitude of treating doctors dealing with patients suffering from Parkinson’s disease. As I noted above he said that before 30 June 1999, he “would have been hesitant” about COMTAN in light of what had happened with tolcapone.

283    Accordingly, I am satisfied that the use of entacapone as a part of treatment for Parkinson’s disease was not part of the common general knowledge before 30 June 1999.

284    The skilled addressee, for present purposes, is a hypothetical construct of one person who has the background and skills of a non-inventive worker in each of the four presently relevant fields relating to therapy for Parkinson’s disease (clinical, pharmacological, pharmaceutical and formulatory); he or she makes an assessment of obviousness in light of the common general knowledge having regard to the interaction of each of those three fields together. Just as, in the case of a skilled addressee in one field or discipline, the hypothetical amalgam must approach the issue of obviousness through one set of eyes, not three. If an addressee in one discipline would scotch a suggestion from their discipline as impractical or not worth thinking about because of known or perceived impediments, where both disciplines had to work together to achieve a result, then the invention will not be obvious to an amalgam skilled addressee, anymore than it would be to one in a single discipline who would not see it as obvious.

285    In Otsuka Pharmaceutical Co Ltd v Generic Health Pty Ltd (No 4) (2015) 113 IPR 191 at 213 [124] Yates J adopted the following passage from General Tire [1972] RPC at 485 to explain how the Court places itself into the position of the skilled addressee, including in cases where that person is taken to have the composite skills of a team of persons namely, in the words of Sachs LJ:

The earlier publication and the patentee’s claim must each be construed as they would be at the respective relevant dates by a reader skilled in the art to which they relate having regard to the state of knowledge in such art at the relevant date. The construction of these documents is a function of the court, being a matter of law, but, since documents of this nature are almost certain to contain technical material, the court must, by evidence, be put in the position of a person of the kind to whom the document is addressed, that is to say, a person skilled in the relevant art at the relevant date. If the art is one having a highly developed technology, the notional skilled reader to whom the document is addressed may not be a single person but a team, whose combined skill would normally be employed in that art in interpreting and carrying into effect instructions such as those which are contained in the document to be construed. (emphasis added)

286    This is why, whatever characteristics the skilled addressee has in any particular case, if the prior art discloses only some, but not all, of the integers of the claimed invention, it would only be obvious, or anticipated by the prior art, if the skilled addressee would add the missing information as a matter of course and without the application of inventive ingenuity or undue experimentation.

287    I summarised the principles applicable to a consideration of obviousness in relation to a product claim, such as claims 19, 20 and 21, in Apotex Pty Ltd v Les Laboratoires Servier [2013] FCA 1426 at [83]-[90] as follows:

83    The word “obvious” in s 7(2) of the Act means “very plain”. It is a question of fact whether an invention is “obvious”. However, that assessment involves a question of degree and this often will be by no means easy: Lockwood [No 2] 235 CLR at 195 [51]. The parties agreed that no question arises under s 7(3) in these proceedings. In Aktiebolaget HÄssle v Alphapharm Pty Ltd (2002) 212 CLR 411 at 427-433 [33]-[53] Gleeson CJ, Gaudron, Gummow and Hayne JJ discussed the law in respect of obviousness and the requirement of an inventive step as it had developed up to the Patents Act 1952 (Cth) (the 1952 Act). Subsequently, the Court said that that discussion was relevant and applicable to the current Act: Lockwood [No 2] 235 CLR at 193 [46]. The Court observed that (at 195 [52]):

“obviousness and inventiveness are antitheses and the question is always “is the step taken over the prior art an ‘obvious step’ or ‘an inventive step’?” ... A “scintilla of invention” remains sufficient in Australian law to support the validity of a patent.” (citations omitted, emphasis added)

84    There is no unique approach to ascertaining whether any invention claimed involves “an inventive step” for the purposes of s 18(1)(b)(ii). Sometimes, the question of whether an invention is obvious when compared to the prior art base, in light of common general knowledge, can be approached by a “problem and solution” analysis. But, this has its limitations, as the Court explained in Lockwood [No 2] 235 CLR at 200-201 [65]-[66]. They held that such an approach could be unfair to an inventor of a simple solution adding (at [65]):

“… especially as a small amount of ingenuity can sustain a patent in Australia. Ingenuity may lie in an idea for overcoming a practical difficulty in circumstances where a difficulty with a product consisting of a known set of integers is common general knowledge. This is a narrow but critical point if, as here, the circumstances are that no skilled person in the art called to give evidence had thought of a general idea or general method of solving a known difficulty with respect to a known product, as at the priority date.” (citations omitted, emphasis added)

85    The Court cautioned against treating a specification that described a problem and solution as a conclusive admission by the patentee. That was because the patentee makes such statements from the vantage point of knowing the solution. Their Honours said that statements of this type must be weighed with any evidence given by persons skilled in the art of their perception, before the priority date, of any problem: i.e. before those witnesses had been exposed to the solution contained in, or provided by, the invention (235 CLR at 211 [105]). The concept of whether a step is inventive (235 CLR at 213-214 [111]):

“… will turn on what a person skilled in the relevant art, possessed with that person's knowledge, would have regarded, at the time, as technically possible in terms of mechanics, and also as practical. That is the sense in which an idea can involve an inventive insight about a known product. A court cannot substitute its own deduction or proposition for that objective touchstone, except in the rarest of circumstances, such as where an expressly admitted matter of common general knowledge is the precise matter in respect of which a monopoly is claimed. Even if an idea of combining integers, which individually may be considered mere design choices, is simple, its simplicity does not necessarily make it obvious. Older cases concerning simple mechanical combinations illustrate this point. Common general knowledge has negative as well as positive aspects. Practical and technical issues can affect the means by which a concept may be implemented in respect of an already known vendible product, and scepticism can inhibit recognition of the utility of applying a concept or idea to a known set of integers. These are matters within the knowledge of relevant witnesses.” (citations omitted, emphasis added)

86    Thus, the practical considerations that a person skilled in the art would take into account in seeking to address a problem may affect the characterisation of a step as inventive or not. In Alphapharm 212 CLR at 432-433 [50]-[53] Gleeson CJ, Gaudron, Gummow and Hayne JJ discussed the difference between what a person skilled in the relevant art, in light of common general knowledge, might do to lead to the alleged invention by way of a series of steps or experiments that were routine as opposed to doing something that amounted to an inventive step. They drew on what Aickin J had said, with the agreement of Gibbs ACJ, Stephen, Mason and Wilson JJ, in The Wellcome Foundation Ltd v VR Laboratories (Aust) Pty Ltd (1981) 148 CLR 262 at 280-281 and 286. Aickin J referred to evidence of what the inventor did, for example by way of experiment, as one means of establishing or negating the involvement of an inventive step. He said (212 CLR at 432-433 [51]):

“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.” (original emphasis)

Aickin J also said (148 CLR at 286):

“It is still correct to say that a valid patent may be obtained for something stumbled upon by accident, remembered from a dream or imported from abroad, if it otherwise satisfies the requirements of the legislation. What is important is that the patent itself should involve an inventive step, whether or not it was consciously taken by the patentee and whether or not it appeared obvious to the patentee himself. 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)